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Artículos originales (todos) *** Original articles (all)
Cancer Pharmacogenomics.
February - March 2013
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[1]
TÍTULO / TITLE: - ERCC1 isoform expression and DNA repair in non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - N Engl J Med. 2013 Mar 21;368(12):1101-10. doi: 10.1056/NEJMoa1214271.
●● Enlace al texto completo (gratuito o de pago) 1056/NEJMoa1214271
AUTORES / AUTHORS: - Friboulet L; Olaussen KA; Pignon JP; Shepherd FA; Tsao MS; Graziano S; Kratzke R; Douillard JY; Seymour L; Pirker R; Filipits M; Andre F; Solary E; Ponsonnailles F; Robin A; Stoclin A; Dorvault N; Commo F; Adam J; Vanhecke E; Saulnier P; Thomale J; Le Chevalier T; Dunant A; Rousseau V; Le Teuff G; Brambilla E; Soria JC
INSTITUCIÓN / INSTITUTION: - INSERM Unite 981, and Departement Hospitalo-Universitaire Thorax Innovation, Institut Gustave-Roussy, Villejuif, France.
RESUMEN / SUMMARY: - BACKGROUND: The excision repair cross-complementation group 1 (ERCC1) protein is a potential prognostic biomarker of the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer (NSCLC). Although several ongoing trials are evaluating the level of expression of ERCC1, no consensus has been reached regarding a method for evaluation. METHODS: We used the 8F1 antibody to measure the level of expression of ERCC1 protein by means of immunohistochemical analysis in a validation set of samples obtained from 494 patients in two independent phase 3 trials (the National Cancer Institute of Canada Clinical Trials Group JBR.10 and the Cancer and Leukemia Group B 9633 trial from the Lung Adjuvant Cisplatin Evaluation Biology project). We compared the results of repeated staining of the entire original set of samples obtained from 589 patients in the International Adjuvant Lung Cancer Trial Biology study, which had led to the initial correlation between the absence of ERCC1 expression and platinum response, with our previous results in the same tumors. We mapped the epitope recognized by 16 commercially available ERCC1 antibodies and investigated the capacity of the different ERCC1 isoforms to repair platinum-induced DNA damage. RESULTS: We were unable to validate the predictive effect of immunostaining for ERCC1 protein. The discordance in the results of staining for ERCC1 suggested a change in the performance of the 8F1 antibody since 2006. We found that none of the 16 antibodies could distinguish among the four ERCC1 protein isoforms, whereas only one isoform produced a protein that had full capacities for nucleotide excision repair and cisplatin resistance. CONCLUSIONS: Immunohistochemical analysis with the use of currently available ERCC1 antibodies did not specifically detect the unique functional ERCC1 isoform. As a result, its usefulness in guiding therapeutic decision making is limited. (Funded by Eli Lilly and others.).
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[2]
TÍTULO / TITLE: - Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Mar 13. pii: S0959-8049(13)00045-2. doi: 10.1016/j.ejca.2013.01.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.007
AUTORES / AUTHORS: - Harbeck N; Schmitt M; Meisner C; Friedel C; Untch M; Schmidt M; Sweep CG; Lisboa BW; Lux MP; Beck T; Hasmuller S; Kiechle M; Janicke F; Thomssen C
INSTITUCIÓN / INSTITUTION: - Brustzentrum, Frauenklinik Maistrasse, Universitaet Munchen, 80337 Munich, Germany. Electronic address: nadia.harbeck@med.uni-muenchen.de.
RESUMEN / SUMMARY: - AIM: Final 10-year analysis of the prospective randomised Chemo-N0 trial is presented. Based on the Chemo-N0 interim results and an European Organisation for Research and Treatment of Cancer (EORTC) pooled analysis (n=8377), American Society of Clinical Oncology (ASCO) and Arbeitsgemeinschaft Gynakologische Onkologie (AGO) guidelines recommend invasion and metastasis markers urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) for risk assessment and treatment decision in node-negative (N0) breast cancer (BC). METHODS: The final Chemo-N0 trial analysis (recruitment 1993-1998; n=647; 12 centres) comprises 113 (5-167) months of median follow-up. Patients with low-uPA and PAI-1 tumour tissue levels (n=283) were observed. External quality assurance guaranteed uPA/PAI-1 enzyme-linked immunosorbent assay (ELISA) standardisation. Of 364 high uPA and/or PAI-1 patients, 242 agreed to randomisation for CMF chemotherapy (n=117) versus observation (n=125). RESULTS: Actuarial 10-year recurrence rate (without any adjuvant systemic therapy) for high-uPA/PAI-1 observation group patients (randomised and non-randomised) was 23.0%, in contrast to only 12.9% for low-uPA/PAI-1 patients (plog-rank=0.011). High-risk patients randomised to cyclophosphamide-methotrexate-5-fluorouracil (CMF) therapy had a 26.0% lower estimated probability of disease recurrence than those randomised for observation (intention-to-treat (ITT)-analysis: hazard ratio (HR) 0.74 (0.44-1.27); plog-rank=0.28). Per-protocol analysis demonstrated significant treatment benefit: HR 0.48 (0.26-0.88), p=0.019, disease-free survival (DFS) Cox regression, adjusted for tumour stage and grade. CONCLUSIONS: Chemo-N0 is the first prospective biomarker-based therapy trial in early BC defining patients reaching good long-term DFS without adjuvant systemic therapy. Using a standardised uPA/PAI-1 ELISA, almost half of N0-patients could be spared chemotherapy, while high-risk patients benefit from adjuvant chemotherapy. These 10-year results validate the long-term prognostic impact of uPA/PAI-1 and the benefit from adjuvant chemotherapy in the high-uPA/PAI-1 group at highest level of evidence. They thus support the guideline-based routine use of uPA/PAI-1 for risk-adapted individualised therapy decisions in N0 breast cancer.
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[3]
TÍTULO / TITLE: - Efficacy of tamoxifen+/-aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 19. doi: 10.1038/bjc.2013.114.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.114
AUTORES / AUTHORS: - Pfeiler G; Stoger H; Dubsky P; Mlineritsch B; Singer C; Balic M; Fitzal F; Moik M; Kwasny W; Selim U; Renner K; Ploner F; Steger GG; Seifert M; Hofbauer F; Sandbichler P; Samonigg H; Jakesz R; Greil R; Fesl C; Gnant M
INSTITUCIÓN / INSTITUTION: - Division of Gynecology and Gynecological Oncology, Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
RESUMEN / SUMMARY: - Background:There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.Methods:ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m-2), overweight (BMI=25-29.9 kg m-2), and obese (30 kg m-2) according to WHO criteria.Results:Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0.018) and a worse overall survival (OS; HR: 1.49; Cox P=0.052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0.24) and OS (HR: 0.99; Cox P=0.97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0.03) and a worse OS (1.47; Cox P=0.11) compared with normal weight patients.Conclusion:BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.British Journal of Cancer advance online publication, 19 March 2013; doi:10.1038/bjc.2013.114 www.bjcancer.com.
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[4]
TÍTULO / TITLE: - Multicenter Phase I Trial of the Mitogen-Activated Protein Kinase ½ Inhibitor BAY 86-9766 in Patients with Advanced Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 1;19(5):1232-43. doi: 10.1158/1078-0432.CCR-12-3529. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3529
AUTORES / AUTHORS: - Weekes CD; Von Hoff DD; Adjei AA; Leffingwell DP; Eckhardt SG; Gore L; Lewis KD; Weiss GJ; Ramanathan RK; Dy GK; Ma WW; Sheedy B; Iverson C; Miner JN; Shen Z; Yeh LT; Dubowy RL; Jeffers M; Rajagopalan P; Clendeninn NJ
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: University of Colorado Cancer Center, Aurora, Colorado; Translational Genomics Research Institute (TGen); Virginia G. Piper Cancer Center at Scottsdale Healthcare, Scottsdale, Arizona; Roswell Park Cancer Institute, Buffalo, New York; Ardea Biosciences, Inc., San Diego, California; and Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
RESUMEN / SUMMARY: - PURPOSE: To evaluate the safety, pharmacokinetics, and pharmacodynamics of BAY 86-9766, a selective, potent, orally available, small-molecule allosteric inhibitor of mitogen-activated protein kinase ½ in patients with advanced solid tumors. EXPERIMENTAL DESIGN: BAY 86-9766 was administered orally daily in 28-day courses, with doses escalated to establish the maximum-tolerated dose (MTD). An expanded cohort was evaluated at the MTD. Pharmacokinetic and pharmacodynamic parameters were assessed, with extracellular signal-regulated kinase (ERK) phosphorylation evaluated in paired biopsies from a subset of the expanded MTD cohort. Tumor specimens were evaluated for mutations in select genes. RESULTS: Sixty-nine patients were enrolled, including 20 patients at the MTD. The MTD was 100 mg given once-daily or in two divided doses. BAY 86-9766 was well-tolerated. The most common treatment-related toxicities were acneiform rash and gastrointestinal toxicity. BAY 86-9766 was well-absorbed after oral administration (plasma half-life approximately 12 hours), and displayed dose proportional pharmacokinetics throughout the tested dose range. Continuous daily dosing resulted in moderate accumulation at most dose levels. BAY 86-9766 suppressed ERK phosphorylation in biopsied tissue and tetradecanoylphorbol acetate-stimulated peripheral blood leukocytes. Of 53 evaluable patients, one patient with colorectal cancer achieved a partial response and 11 patients had stable disease for 4 or more courses. An ocular melanoma specimen harbored a GNAQ-activating mutation and exhibited reduced ERK phosphorylation in response to therapy. CONCLUSION: This phase I study showed that BAY 86-9766 was well-tolerated, with good oral absorption, dose proportional pharmacokinetics, target inhibition at the MTD, and some evidence of clinical benefit across a range of tumor types. Clin Cancer Res; 19(5); 1232-43. ©2012 AACR.
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[5]
TÍTULO / TITLE: - Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Neurol. 2013 Jan;73(1):95-103. doi: 10.1002/ana.23758.
●● Enlace al texto completo (gratuito o de pago) 1002/ana.23758
AUTORES / AUTHORS: - Bermel RA; You X; Foulds P; Hyde R; Simon JH; Fisher E; Rudick RA
INSTITUCIÓN / INSTITUTION: - Neurological Institute, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, OH, USA. bermelr@ccf.org
RESUMEN / SUMMARY: - OBJECTIVE: To identify early predictors of long-term outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) treated with intramuscular (IM) interferon beta-1a (IFNbeta-1a). METHODS: A multicenter, observational, 15-year follow-up study of patients who completed >/=2 years in the pivotal trial of IM IFNbeta-1a for RRMS was conducted. One hundred thirty-six patients participated in the 15-year follow-up (69 originally randomized to IM IFNbeta-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: >/=2 gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 magnetic resonance imaging (MRI); >/=3 new T2 lesions on year 2 MRI compared to baseline; and >/=2 relapses over 2 years. Odds ratios were calculated for early disease activity predicting severe Expanded Disability Status Scale (EDSS) worsening (worst quartile of change, >/=4.5 EDSS points) during the 15-year interval. RESULTS: The proportion of patients experiencing early disease activity was lower in patients on IM IFNbeta-1a than placebo for all disease activity markers (range, 23.5-29.0% vs 41.0-45.5%). In the IM IFNbeta-1a group, persistent disease activity predicted severe EDSS worsening: gadolinium-enhancing lesions (odds ratio [OR], 8.96; p < 0.001); relapses (OR, 4.44; p = 0.010); and new T2 lesions (OR, 2.90; p = 0.080). In placebo patients, early disease activity was not as strongly associated with long-term outcomes (OR range, 1.53-2.62; p = 0.069-0.408). INTERPRETATION: Disease activity despite treatment with IFNbeta is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNbeta therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNbeta-treated patients with MRI, and for changing therapy in patients with active disease.
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[6]
TÍTULO / TITLE: - Prognosis of early breast cancer by immunohistochemistry defined intrinsic sub-types in patients treated with adjuvant chemotherapy in the NEAT/BR9601 trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Mar 9. doi: 10.1002/ijc.28150.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28150
AUTORES / AUTHORS: - Ali A; Provenzano E; Bartlett JM; Abraham J; Driver K; Munro AF; Twelves C; Poole CJ; Hiller L; Dunn J; Earl HM; Caldas C; Pharoah P
INSTITUCIÓN / INSTITUTION: - Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Department of Biostatistics and Cancer Epidemiology, South Egypt Cancer Institute, University of Assiut, Egypt.
RESUMEN / SUMMARY: - Breast cancer can be classified into molecular sub-types that have distinct survival patterns. We evaluated the prognostic significance of breast cancer sub-types in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing cyclophosphamide, methotrexate, and fluorouracil (CMF) with ECMF (epirubicin and CMF). Furthermore we evaluated whether the sub-types were predictive of the added benefit of epirubicin in these trials. Tumour tissue microarrays were stained and scored for ER, PR, HER2, EGFR and CK5/6. These were used to classify the tumours into six intrinsic sub-types. We used Cox regression to compare overall survival (OS), breast cancer-specific survival (BCSS) and relapse-free survival (RFS) in the different sub-groups. We also compared the effect of ECMF with CMF by sub-group. Immunohistochemistry data were available for 1,725 cases of whom 805 were luminal 1-basal negative. Median follow-up time was 7 years. The luminal 1-basal negative tumours were associated with the best prognosis in five years after surgery and the HER2-like tumours were associated with the poorest prognosis. There was little evidence for significant heterogeneity of this effect by tumour sub-type (OS P =0.40, BCSS P=0.53 RFS P=0.50) - the largest additional benefit of epirubicin was in women with tumours of the 5-negative phenotype (OS HR=0.39 95% CI:0.21-0.73) and the smallest was in Luminal 1-basal negative tumours (OS HR=0.86 95% CI:0.64-1.16). We confirmed that breast cancer sub-types show distinct behaviour with differences in short- and long-term survival. The benefit of ECMF over CMF was statistically similar in all disease sub-types. © 2013 Wiley Periodicals, Inc.
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[7]
TÍTULO / TITLE: - Progression-free Survival Is Accurately Predicted in Patients Treated with Chemotherapy for Epithelial Ovarian Cancer by the Histoculture Drug Response Assay in a Prospective Correlative Clinical Trial at a Single Institution.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1029-34.
AUTORES / AUTHORS: - Jung PS; Kim DY; Kim MB; Lee SW; Kim JH; Kim YM; Kim YT; Hoffman RM; Nam JH
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 139-736, Korea. kdyog@amc.seoul.kr.
RESUMEN / SUMMARY: - This study aimed to prospectively correlate clinical outcomes of advanced epithelial ovarian cancer (AEOC), with the results of in vitro chemosensitivity testing of taxol and carboplatin using the in vitro histoculture drug response assay (HDRA). A total of 104 patients with AEOC were treated with combination chemotherapy of taxol and carboplatin after primary cytoreductive surgery between 2007 and 2012 at the Asan Medical Center, Seoul, Korea. To compare chemosensitivity in the HDRA with clinical response, all patients were first categorized into two groups as either sensitive to both taxol and carboplatin (SS), or not sensitive to one or both drugs ® based on HDRA results. The recurrence rate was much lower in the SS group compared to the R group; 29.2% vs 69.8%, respectively (p=0.02). The SS group had a significantly longer progression-free survival compared to the R group, 34.0 months vs 16.0 months, respectively (p=0.025). These results demonstrate that the HDRA prospectively correlates to clinical outcome from chemotherapy and that treatment regimens can be individualized based on the HDRA.
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[8]
TÍTULO / TITLE: - Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.45.9453
AUTORES / AUTHORS: - Vose JM; Carter S; Burns LJ; Ayala E; Press OW; Moskowitz CH; Stadtmauer EA; Mineshi S; Ambinder R; Fenske T; Horowitz M; Fisher R; Tomblyn M
INSTITUCIÓN / INSTITUTION: - Julie M. Vose, University of Nebraska Medical Center, Omaha, NE; Shelly Carter, EMMES, Rockville; Richard Ambinder, Johns Hopkins Medical Center, Baltimore, MD; Linda J. Burns, University of Minnesota, Minneapolis, MN; Ernesto Ayala and Marcie Tomblyn, H. Lee Moffitt Cancer Center, Tampa, FL; Oliver W. Press, Fred Hutchinson Cancer Center, Seattle, WA; Craig H. Moskowitz, Memorial Sloan-Kettering Cancer Center, New York; Richard Fisher, University of Rochester, Rochester, NY; Edward A. Stadtmauer, Abramson Cancer Center, The University of Pennsylvania, Philadelphia, PA; Shin Mineshi, University of Michigan; Richard Fisher, Southwest Oncology Group, Ann Arbor, MI; Timothy Fenske and Mary Horowitz, Medical College of Wisconsin, Milwaukee, WI.
RESUMEN / SUMMARY: - PURPOSEThis clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODSPatients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day -19 and therapeutic dose of 0.75 Gy on day -12), carmustine 300 mg/m2 (day -6), etoposide 100 mg/m2 twice daily (days -5 to -2), cytarabine 100 mg/m2 twice daily (days -5 to -2), and melphalan 140 mg/m2 (day -1; B-BEAM) or rituximab 375 mg/m2 on days -19 and -12 and the same chemotherapy regimen (R-BEAM).ResultsTwo hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001). CONCLUSIONThe B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted.
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[9]
TÍTULO / TITLE: - Cytotoxic T cells induce proliferation of chronic myeloid leukemia stem cells by secreting interferon-gamma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Exp Med. 2013 Mar 11;210(3):605-21. doi: 10.1084/jem.20121229. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1084/jem.20121229
AUTORES / AUTHORS: - Schurch C; Riether C; Amrein MA; Ochsenbein AF
INSTITUCIÓN / INSTITUTION: - Tumor Immunology, Department of Clinical Research, 2 Institute of Pathology, and 3 Department of Medical Oncology, University of Bern, 3010 Bern, Switzerland.
RESUMEN / SUMMARY: - Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia arising from the oncogenic break point cluster region/Abelson murine leukemia viral oncogene homolog 1 translocation in hematopoietic stem cells (HSCs), resulting in a leukemia stem cell (LSC). Curing CML depends on the eradication of LSCs. Unfortunately, LSCs are resistant to current treatment strategies. The host’s immune system is thought to contribute to disease control, and several immunotherapy strategies are under investigation. However, the interaction of the immune system with LSCs is poorly defined. In the present study, we use a murine CML model to show that LSCs express major histocompatibility complex (MHC) and co-stimulatory molecules and are recognized and killed by leukemia-specific CD8 effector CTLs in vitro. In contrast, therapeutic infusions of effector CTLs into CML mice in vivo failed to eradicate LSCs but, paradoxically, increased LSC numbers. LSC proliferation and differentiation was induced by CTL-secreted IFN-gamma. Effector CTLs were only able to eliminate LSCs in a situation with minimal leukemia load where CTL-secreted IFN-gamma levels were low. In addition, IFN-gamma increased proliferation and colony formation of CD34 stem/progenitor cells from CML patients in vitro. Our study reveals a novel mechanism by which the immune system contributes to leukemia progression and may be important to improve T cell-based immunotherapy against leukemia.
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[10]
TÍTULO / TITLE: - Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leukemia. 2013 Mar 5. doi: 10.1038/leu.2013.69.
●● Enlace al texto completo (gratuito o de pago) 1038/leu.2013.69
AUTORES / AUTHORS: - Giles FJ; Mauro MJ; Hong F; Ortmann CE; McNeill C; Woodman RC; Hochhaus A; le Coutre PD; Saglio G
INSTITUCIÓN / INSTITUTION: - HRB Clinical Research Facility, National University of Ireland Galway and Trinity College Dublin, Dublin, Ireland.
RESUMEN / SUMMARY: - Peripheral arterial occlusive disease (PAOD) occurs in patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs). The risk of developing PAOD on TKI therapy is unknown and causality has not been established. Patients with CML-CP from three randomized phase III studies (IRIS, TOPS and ENESTnd) were divided into three cohorts: no TKI (cohort 1; n=533), nilotinib (cohort 2; n=556) and imatinib (cohort 3; n=1301). Patients with atherosclerotic risk factors were not excluded. Data were queried for terms indicative of PAOD. Overall, 3, 7 and 2 patients in cohorts 1, 2 and 3, respectively, had PAOD; 11/12 patients had baseline PAOD risk factors. Compared with that of cohort 1, exposure-adjusted risks of PAOD for cohorts 2 and 3 were 0.9 (95% CI, 0.2-3.3) and 0.1 (95% CI, 0.0-0.5), respectively. Multivariate logistic regression revealed that nilotinib had no impact on PAOD rates compared with no TKI, whereas imatinib had decreased rates of PAOD compared with no TKI. Nilotinib was associated with higher rates of PAOD versus imatinib. Baseline assessments, preferably within clinical studies, of PAOD and associated risk factors should occur when initiating TKI therapy in CML; patients should receive monitoring and treatment according to the standard of care for these comorbidities.Leukemia advance online publication, 5 April 2013; doi:10.1038/leu.2013.69.
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[11]
TÍTULO / TITLE: - Prognostic model for predicting survival of patients with metastatic urothelial cancer treated with Cisplatin-based chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Cancer Inst. 2013 Apr 3;105(7):499-503. doi: 10.1093/jnci/djt015. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djt015
AUTORES / AUTHORS: - Apolo AB; Ostrovnaya I; Halabi S; Iasonos A; Philips GK; Rosenberg JE; Riches J; Small EJ; Milowsky MI; Bajorin DF
INSTITUCIÓN / INSTITUTION: - Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065. bajorind@mskcc.org.
RESUMEN / SUMMARY: - A prognostic model that predicts overall survival (OS) for metastatic urothelial cancer (MetUC) patients treated with cisplatin-based chemotherapy was developed, validated, and compared with a commonly used Memorial Sloan-Kettering Cancer Center (MSKCC) risk-score model. Data from 7 protocols that enrolled 308 patients with MetUC were pooled. An external multi-institutional dataset was used to validate the model. The primary measurement of predictive discrimination was Harrell’s c-index, computed with 95% confidence interval (CI). The final model included four pretreatment variables to predict OS: visceral metastases, albumin, performance status, and hemoglobin. The Harrell’s c-index was 0.67 for the four-variable model and 0.64 for the MSKCC risk-score model, with a prediction improvement for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .002). In the validation cohort, the c-indices for the four-variable and the MSKCC risk-score models were 0.63 (95% CI = 0.56 to 0.69) and 0.58 (95% CI = 0.52 to 0.65), respectively, with superiority of the four-variable model compared with the MSKCC risk-score model for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .02).
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[12]
TÍTULO / TITLE: - Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2011.40.5241
AUTORES / AUTHORS: - Guan Z; Xu B; Desilvio ML; Shen Z; Arpornwirat W; Tong Z; Lorvidhaya V; Jiang Z; Yang J; Makhson A; Leung WL; Russo MW; Newstat B; Wang L; Chen G; Oliva C; Gomez H
INSTITUCIÓN / INSTITUTION: - Zhongzhen Guan, Sun Yat-Sen University Cancer Center, Guangzhou; Binghe Xu, Chinese Academy of Medical Sciences Cancer Hospital; Zefei Jiang, Military Medical Science Academy Hospital; Junlan Yang, Beijing 301 People’s Liberation Army Hospital; George Chen, BeiGene (Beijing) Company, Beijing; Zhenzhou Shen, Fudan University Cancer Hospital; Li Wang, Eli Lilly, Shanghai; Zhongsheng Tong, Tianjin Cancer Hospital, Tianjin, People’s Republic of China; Michelle L. DeSilvio, Mark W. Russo, and Beth Newstat, Medicine Development Center Oncology, GlaxoSmithKline, Collegeville, PA; Wichit Arpornwirat, National Cancer Institute, Bangkok; Vicharn Lorvidhaya, Maharaj Nakorn Chiangmai Hospital, Chiang Mai University, Chiang Mai, Thailand; Anatoly Makhson, State Healthcare Institution of Moscow, Moscow, Russian Federation; Wai Lim Leung, Queen Elizabeth Hospital, Kowloon, Hong Kong; Cristina Oliva, Takeda Pharmaceutical, London, United Kingdom; and Henry Gomez, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
RESUMEN / SUMMARY: - PURPOSELapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).Patients And methodsThis phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety.ResultsThe addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. CONCLUSIONThis trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.
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[13]
TÍTULO / TITLE: - Immune thrombocytopenia in patients with chronic lymphocytic leukemia treated with cladribine-based regiments or chlorambucil - follow-up of PALG-CLL randomized trials.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Haematol. 2013 Mar 23. doi: 10.1111/ejh.12112.
●● Enlace al texto completo (gratuito o de pago) 1111/ejh.12112
AUTORES / AUTHORS: - Blonski JZ; Robak T; Chojnowski K; Gora-Tybor J; Warzocha K; Ceglarek B; Seferynska I; Calbecka M; Kostyra A; Stella-Holowiecka B; Kloczko J; Dmoszynska A; Kowal M; Lewandowski K; Dwilewicz-Trojaczek J; Wiater E; Kuliczkowski K; Potoczek S; Hellmann A; Mital A; Skotnicki A; Nowak W; Sulek K; Zawilska K; Trelinski J
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Medical University of Lodz, Lodz.
RESUMEN / SUMMARY: - OBJECTIVES: The relationship between treatment of Chronic lymphocytic leukemia (CLL) with cladribine (2 - CdA) or chlorambucil and immune thrombocytopenia (IT) have not been yet determined. Methods:The records of 777 patients in two randomized PALG (Polish Adult Leukemia Group) CLL programs treated with these agents were retrospectively analyzed. RESULTS: Immune thrombocytopenia occurred in 55 of 777 (7.1%) patients. No significant differences in IT prevalence was seen between patients on chlorambucil or 2-CdA - based regiments (p=0.33). IT developed at a median time of 0.499 years (0,06 - 4.8) from the start of CLL therapy. This time was significantly longer in patients treated with chlorambucil (2.03 yrs, 95%CI: 0.06-4.22) in relation to patients treated with 2- CdA- based regiments (0.52 yrs, 95%CI: 0.34-0.69, p=0,049). Overall survival (OS) of patients with IT and those without IT were similar (2.65 yrs. vs. 3.2 yrs. p=0.23) but the severity of bleeding was more pronounced in the 2- CdA group. The responses to IT therapy was 35%, 54% and 75% for steroids, chemotherapy and splenectomy respectively. CONCLUSIONS: In this study, an unexpectedly high percentage of IT incidence was demonstrated in patients with CLL requiring chemotherapy. Although no marked differences were seen in IT frequency in patients treated with 2 - CdA-based regiments compared to chlorambucil regimen the clinical course of haemorrhagic diathesis was more severe in 2 - CdA group. Also the time elapsed from study screening to IT diagnosis was significantly shorter in the 2-CdA group than in the chlorambucil group suggesting a causative relationship. The appearance of IT did not influence the median time of OS. © 2013 John Wiley & Sons A/S.
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[14]
TÍTULO / TITLE: - Translational Phase I Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytarabine and Etoposide in Patients with Relapsed, Refractory, or High-Risk Acute Myeloid Leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 1;19(7):1838-1851. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3165
AUTORES / AUTHORS: - Gojo I; Tan M; Fang HB; Sadowska M; Lapidus R; Baer MR; Carrier F; Beumer JH; Anyang BN; Srivastava RK; Espinoza-Delgado I; Ross DD
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: University of Maryland Marlene and Stewart Greenebaum Cancer Center (UMGCC), Department of Medicine, Division of Biostatistics, University of Maryland School of Medicine, Translational Laboratory Shared Service, UMGCC; Department of Medicine, Division of Hematology and Oncology, Departments of Epidemiology and Public Health and Radiation Oncology, University of Maryland School of Medicine; The Baltimore Veterans Affairs Medical Center, Baltimore; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland; Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute (UPCI); Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania; and University of Kansas Medical Center, Kansas City, Kansas.
RESUMEN / SUMMARY: - PURPOSE: To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts. EXPERIMENTAL DESIGN: In this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m2) and cytarabine (1 or 2 g/m2 twice a day if >/=65 or <65 years old, respectively) were given. The study used a standard 3+3 dose escalation design. RESULTS: Eighteen of 21 patients with acute myelogenous leukemia (AML) treated on study completed planned therapy. Dose-limiting toxicities [hyperbilirubinemia/septic death (1) and anorexia/fatigue (1)] were encountered at the 200 mg three times a day level; thus, the MTD was established to be vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment. CONCLUSIONS: Vorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings. Clin Cancer Res; 19(7); 1838-51. ©2013 AACR.
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[15]
TÍTULO / TITLE: - A dual-center randomized controlled double blind trial assessing the effect of acupuncture in reducing musculoskeletal symptoms in breast cancer patients taking aromatase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Feb;138(1):167-74. doi: 10.1007/s10549-013-2427-z. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2427-z
AUTORES / AUTHORS: - Bao T; Cai L; Giles JT; Gould J; Tarpinian K; Betts K; Medeiros M; Jeter S; Tait N; Chumsri S; Armstrong DK; Tan M; Folkerd E; Dowsett M; Singh H; Tkaczuk K; Stearns V
INSTITUCIÓN / INSTITUTION: - University of Maryland Greenebaum Cancer Center, Baltimore, MD, 20201, USA, tbao@umm.edu.
RESUMEN / SUMMARY: - Up to 50 % of women receiving aromatase inhibitor (AI) complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture improves AIMSS and to explore potential mechanisms. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. We evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS) following the intervention compared to baseline. Serum estradiol, beta-endorphin, and proinflammatory cytokine concentrations were measured pre and post-intervention. We enrolled 51 women of whom 47 were evaluable, including 23 randomized to real and 24 to sham acupuncture. Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group (p = 0.047). We did not observe a statistically significant difference in reduction of HAQ-DI (p = 0.30) or VAS (p = 0.31) between the two groups. Following eight weekly treatments, we observed a statistically significant reduction of IL-17 (p </= 0.009) in both groups. No significant modulation was seen in estradiol, beta-endorphin, or other proinflammatory cytokine concentrations in either group. We did not observe a significant difference in AIMSS changes between real and sham acupuncture. As sham acupuncture used in this study may not be equivalent to placebo, further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMSS.
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[16]
TÍTULO / TITLE: - Post-transplant T cell chimerism predicts graft versus host disease but not disease relapse in patients undergoing an alemtuzumab based reduced intensity conditioned allogeneic transplant.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 5. pii: S0145-2126(13)00024-6. doi: 10.1016/j.leukres.2013.01.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.010
AUTORES / AUTHORS: - Nikolousis E; Robinson S; Nagra S; Brookes C; Kinsella F; Tauro S; Jeffries S; Griffiths M; Mahendra P; Cook M; Paneesha S; Lovell R; Kishore B; Chaganti S; Malladi R; Raghavan M; Moss P; Milligan D; Craddock C
INSTITUCIÓN / INSTITUTION: - Department of Haematology, Heart of England NHS Foundation Trust, Birmingham, UK. Electronic address: emelni@hotmail.com.
RESUMEN / SUMMARY: - In this multicentre retrospective study we have studied the impact of T cell chimerism on the outcome of 133 patients undergoing an alemtuzumab based reduced intensity conditioning allograft (RIC). The median age of the patients was 50 years (range 42-55 years). 77 patients were transplanted using an HLA identical sibling donor while 56 patients received a fully matched volunteer unrelated donor graft. 64 patients had a lymphoid malignancy and 69 were transplanted for a myeloid malignancy. 38 patients (29%) relapsed with no significant difference in risk of relapse between patients developing full donor and mixed donor chimerism in the T-cell compartment on D+90 and D+180 post transplant. Day 90 full donor T cell chimerism correlated with an increased incidence of acute GVHD according to NIH criteria (p=0.0004) and the subsequent development of chronic GVHD. Consistent with previous observations, our results confirmed a correlation between the establishment of T cell full donor chimerism and acute GVHD in T deplete RIC allografts. However our study failed to identify any correlation between T cell chimerism and relapse risk and challenge the use of pre-emptive donor lymphocyte infusions (DLI) in patients with mixed T cell chimerism transplanted using an alemtuzumab based RIC regimen.
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[17]
TÍTULO / TITLE: - A potentially neuroprotective role for erythropoietin with paclitaxel treatment in ovarian cancer patients: a prospective phase II GINECO trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Support Care Cancer. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1748-0
AUTORES / AUTHORS: - Weber B; Largillier R; Ray-Coquard I; Yazbek G; Meunier J; Alexandre J; Dauba J; Spaeth D; Delva R; Joly F; Pujade-Lauraine E; Copel L
INSTITUCIÓN / INSTITUTION: - Centre Alexis Vautrin, 6 Avenue de Bourgogne Brabois, Vandoeuvre-les-Nancy, France.
RESUMEN / SUMMARY: - PURPOSE: A prospective phase II multicenter study was performed in two steps in paclitaxel-treated ovarian cancer patients in France. A French version of the four-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was validated. This was then used to evaluate neurotoxicity in relation to erythropoietin treatment. METHODS: Patients received standard second-line paclitaxel-based chemotherapy and erythropoietin for anemia. Neurotoxicity and hemoglobin levels were evaluated every cycle with the FACT/GOG-Ntx and NCI-CTCAE. The translated questionnaire was tested in 20 patients to confirm the translation accuracy. The final questionnaire was validated in 98 patients with internal consistency (Cronbach’s coefficient) and item correlation (Pearson’s r coefficient) tests. Neurotoxicity severity was analyzed according to erythropoietin intake (first three cycles versus no or late intake) and correlated with anemia. RESULTS: Patients received a median of six paclitaxel cycles (range 1-9). Neurotoxicity was validated in 484 questionnaires. Internal consistency was excellent with Cronbach’s coefficients of >/=0.89 at inclusion, after 3 cycles and at study end. Inter-question correlation was high with Pearson’s coefficients of 0.65-0.85. FACT/GOG-Ntx and NCI-CTCAE severity scoring was similar. Globally, the incidence of severe neurotoxicity (FACT/GOG-Ntx and NCI-CTCAE) was found significantly higher in patients with severe anemia. Of 98 evaluable patients, 31 received erythropoietin during the first three cycles. Mean hemoglobin level was significantly lower in this group from baseline to cycle 4; however, these anemic patients with early EPO intake did not develop an increase rate of severe neurotoxicity. CONCLUSIONS: The French FACT/GOG-Ntx questionnaire is a reliable and valid tool for assessing chemotherapy-induced neuropathy. This study raises the possibility that erythropoietin might play a neuroprotective role when administered with paclitaxel.
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[18]
TÍTULO / TITLE: - Words of wisdom: re: prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Urol. 2013 Apr;63(4):769. doi: 10.1016/j.eururo.2012.12.055.
●● Enlace al texto completo (gratuito o de pago) 1016/j.eururo.2012.12.055
AUTORES / AUTHORS: - Karam JA; Wood CG
INSTITUCIÓN / INSTITUTION: - Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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[19]
TÍTULO / TITLE: - Long-term Follow-up of a Phase II Trial of Chemotherapy Plus Hormone Therapy for Biochemical Relapse After Definitive Local Therapy for Prostate Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urology. 2013 Mar;81(3):611-6. doi: 10.1016/j.urology.2012.12.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.12.025
AUTORES / AUTHORS: - Nakabayashi M; Xie W; Buckle G; Bubley G; Ernstoff MS; Walsh W; Morganstern DE; Kantoff PW; Taplin ME
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Department of Medicine, Lank Center for Genitourinary Oncology, Boston, MA.
RESUMEN / SUMMARY: - OBJECTIVE: To evaluate long-term follow-up of a phase II trial of chemohormonal therapy in 62 men with prostate cancer biochemical relapse (BR). METHODS: Treatment was 4 cycles of docetaxel (70 mg/m) every 3 weeks and estramustine 280 mg three times a day (days 1-5) followed by 15 months of goserelin acetate/bicalutamide. The primary endpoint was the proportion with prostate-specific antigen (PSA) <0.1 with recovered testosterone 5 years after completion of therapy. Secondary endpoints included time to progression (TTP), time to reinitiate androgen deprivation therapy (ADT), the proportion with castration-resistant prostate cancer (CRPC), and overall survival (OS). RESULTS: Median follow-up was 8.6 years (range 1.3-11.1 years). At 5 year follow-up, 7 patients (11%) had PSA <0.1 (5 undetectable); 8 (13%) had PSA >0.1 but without reinitiation of ADT (median PSA 0.37). Of the 15 (24%) men without reinitiation of ADT, and 14 have recovered testosterone to normal range. Median TTP for the complete cohort was 35.0 months (95% confidence interval [CI] 31.7-39.2). Baseline PSA <3.0 ng/dL, no prior ADT, and prostatectomy (vs radiation) were associated with longer TTP (P = .0001, P = .0055, and P = .0398, respectively). At the time of analysis, 42 men (68%) had restarted ADT, 23 men had CRPC (37%), and 11 (18%) had chemotherapy. Median time to reinitiation of ADT was 32.6 months (range 0-107.6 months). Median OS has not been reached; there were 15 deaths. CONCLUSION: Chemotherapy plus ADT for BR resulted in durable (>5 years) complete responses (<0.1 ng/mL) in 7 men (11%). Twenty-four percent of men have not re-initiated ADT 5 years from completion of protocol therapy.
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[20]
TÍTULO / TITLE: - Clinical Significance of CD33 Nonsynonymous Single-Nucleotide Polymorphisms in Pediatric Patients with Acute Myeloid Leukemia Treated with Gemtuzumab-Ozogamicin-Containing Chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 15;19(6):1620-1627. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3115
AUTORES / AUTHORS: - Mortland L; Alonzo TA; Walter RB; Gerbing RB; Mitra AK; Pollard JA; Loken MR; Hirsch B; Raimondi S; Franklin J; Pounds S; Cao X; Rubnitz JE; Ribeiro RC; Gamis A; Meshinchi S; Lamba JK
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Hematology and Oncology and Department of Lab Medicine and Pathology, PUMA-Institute of Personalized Medicine, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota; Department of Experimental and Clinical Pharmacology, Clinical Research Division, Fred Hutchinson Cancer Research Center; Department of Medicine, Division of Hematology, Department of Pediatrics, University of Washington; Hematologics, Inc, Seattle, Washington; Department of Biostatistics, University of Southern California, Los Angeles; Children’s Oncology Group, Arcadia; University of Southern California and Amgen Incorporated, Thousand Oaks, California; Departments of Pathology, Biostatistics, and Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee; and Division of Hematology/Oncology/Bone Marrow Transplantation, Children’s Mercy Hospitals & Clinics, Kansas City, Missouri.
RESUMEN / SUMMARY: - PURPOSE: The purpose of this study was to evaluate clinical implications of CD33 single-nucleotide polymorphisms (SNP) in pediatric patients with acute myeloid leukemia (AML) treated with gemtuzumab-ozogamicin (GO)-based therapy. EXPERIMENTAL DESIGN: We genotyped four CD33 SNPs: rs35112940 (G>A; Arg304Gly), rs12459419 (C>T; Ala14Val), rs2455069 (A>G; Arg69Gly), and rs1803254 (G>C; 3’UTR) in pediatric patients undergoing induction chemotherapy containing GO (COG-AAML03P1 trial; n = 242) or not containing GO (St. Jude AML02 trial; n = 172). RESULTS: CD33 SNPs were correlated significantly with clinical characteristics and treatment outcome. The coding SNPs, rs35112940 and rs12459419, were significantly associated with clinical endpoints in COG-AAML03P1 but not in the St. Jude AML02 trial. Specifically, among white patients in COG-AAML03P1, the 3-year overall survival (OS) rate from remission was 84% +/- 8% for those homozygous (GG) for rs35112940 versus 68% +/- 15% for the other genotypes (P = 0.018); these patients also had a lower relapse risk and superior disease-free survival. Likewise, patients homozygous for variant allele (TT) for rs12459419 were more likely to have favorable risk disease than CC and CT genotypes (52% vs. 31%, P = 0.034) and significantly lower diagnostic blast CD33 expression than other genotypes (P < 0.001). CONCLUSION: Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AMLs. Clin Cancer Res; 19(6); 1620-7. ©2013 AACR.
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[21]
TÍTULO / TITLE: - Geriatric Factors Predict Chemotherapy Feasibility: Ancillary Results of FFCD 2001-02 Phase III Study in First-Line Chemotherapy for Metastatic Colorectal Cancer in Elderly Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.42.9894
AUTORES / AUTHORS: - Aparicio T; Jouve JL; Teillet L; Gargot D; Subtil F; Le Brun-Ly V; Cretin J; Locher C; Bouche O; Breysacher G; Charneau J; Seitz JF; Gasmi M; Stefani L; Ramdani M; Lecomte T; Mitry E
INSTITUCIÓN / INSTITUTION: - Thomas Aparicio, Avicenne Hospital, Assistance Publique-Hopitaux de Paris (AP-HP), Universite Paris 13, Sorbonne Paris Cite, Bobigny; Laurent Teillet, Sainte Perine Hospital, AP-HP; Emmanuel Mitry, Institut Curie, Versaille Saint Quentin University, Paris; Jean-Louis Jouve, Centre Hospitalier Universitaire (CHU) Dijon; Fabien Subtil, Federation Francophone de Cancerologie Digestive, Dijon; Dany Gargot, Centre Hospitalier (CH) Blois, Blois; Valerie Le Brun-Ly, CHU Limoges, Limoges; Jacques Cretin, CH Ales, Ales; Christophe Locher, CH Meaux, Meaux; Olivier Bouche, CHU Robert Debre, Reims; Gilles Breysacher, CH Colmar Colmar; Jacky Charneau, CH Boulogne-sur-Mer, Boulogne-sur-Mer; Jean-Francois Seitz, Timone Hospital, Assistance Publique-Hopitaux de Marseille (AP-HM); Mohamed Gasmi, Hopital Nord, AP-HM, Marseille; Laetitia Stefani, CH Pringy, Pringy; Mohamed Ramdani, CH Bezier, Bezier; and Thierry Lecomte, CHU Trousseau, Universite Francois-Rabelais, Tours, France.
RESUMEN / SUMMARY: - PURPOSEElderly patients form a heterogeneous population. Evaluation of geriatric factors may help evaluate a patient’s health status to better adapt treatment. PATIENTS AND METHODSElderly patients with previously untreated metastatic colorectal cancer (mCRC) were randomly assigned to receive fluorouracil (FU) -based chemotherapy either alone or in combination with irinotecan (IRI) in the Federation Francophone de Cancerologie Digestive (FFCD) 2001-02 study. Sites participating in the geriatric substudy completed geriatric screening tools to perform prognostic factor analyses for treatment safety during the first 4 months after treatment initiation.ResultsThe geriatric score was calculated in 123 patients (44%). Median age was 80 years (range, 75 to 91 years). The Charlson comorbidity index was </= 1 in 75%, Mini-Mental State Examination (MMSE) score was </= 27/30 in 31%, and Instrumental Activities of Daily Living (IADL) showed impairment in 34% of the patients. Seventy-one patients (58%) had grade 3 to 4 toxicity, 41 (33%) had a dose-intensity reduction of more than 33%, and 54 (44%) had at least one unexpected hospitalization during the first 4 months after starting treatment. In multivariate analysis, significant predictive factors for grade 3-4 toxicity were IRI arm (odds ratio [OR], 5.03), MMSE </= 27/30 (OR, 3.84), and impaired IADL (OR, 4.67); for dose-intensity reduction of > 33%, the significant predictive factors were alkaline phosphates > 2 x upper limit of normal (OR, 4.16) and IRI arm (OR, 6.85); and for unexpected hospitalization, significant predictive factors were MMSE </= 27/30 (OR, 4.56) and Geriatric Depression Scale </= 2 (OR, 5.52). CONCLUSIONGeriatric factors (MMSE and IADL) are predictive of severe toxicity or unexpected hospitalization (MMSE) in a randomized prospective phase III study in mCRC. These results suggest that cognitive function and autonomy impairment should be taken into account when choosing a regimen for chemotherapy.
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[22]
TÍTULO / TITLE: - Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 20;31(9):1157-63. doi: 10.1200/JCO.2012.44.9694. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.9694
AUTORES / AUTHORS: - Hurvitz SA; Dirix L; Kocsis J; Bianchi GV; Lu J; Vinholes J; Guardino E; Song C; Tong B; Ng V; Chu YW; Perez EA
INSTITUCIÓN / INSTITUTION: - Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; perez.edith@mayo.edu.
RESUMEN / SUMMARY: - PURPOSE Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting. PATIENTS AND METHODS Patients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life. Results Median PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95% CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0% (95% CI, 45.5% to 69.2%) with HT and 64.2% (95% CI, 51.8% to 74.8%) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade >/= 3 adverse events (AEs; 46.4% v 90.9%), AEs leading to treatment discontinuations (7.2% v 40.9%), and serious AEs (20.3% v 25.8%). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms. CONCLUSION In this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.
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[23]
TÍTULO / TITLE: - Etoposide in combination with low-dose CAG (cytarabine, aclarubicin, G-CSF) for the treatment of relapsed or refractory acute myeloid leukemia: A multicenter, randomized control trial in southwest China.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Mar 25. pii: S0145-2126(13)00080-5. doi: 10.1016/j.leukres.2013.03.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.03.005
AUTORES / AUTHORS: - Zhang X; Li Y; Zhang Y; Chen X; Zhang C; Gao L; Kong P; Liu Y; Wen Q; Zeng Y; Wang Q; Su Y; Wang C; Wang S; Yuan Z; Gao L
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
RESUMEN / SUMMARY: - In a well-controlled multi-center randomized trial in southwestern China, 228 patients with refractory or relapsed AML were received a low-dose CAG regimen either with etoposide (E-CAG) or without etoposide (CAG). The complete remission (CR) rate, overall survival (OS) and toxicity were evaluated. Patients with E-CAG had a higher CR rate (71.1% vs. CAG 50.9%, P=0.0002). The tolerability appeared to be equivalent. Patients with CR who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) had a higher five-year OS over those without allo-HSCT (73.8% vs. 10.8%, P=0.000). The E-CAG regimen is expected to become a bridge between relapsed or refractory AML and allo-HSCT.
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[24]
TÍTULO / TITLE: - Phase Ib trial of the Toll-like receptor 9 agonist IMO-2055 in combination with 5-fluorouracil, cisplatin, and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Invest New Drugs. 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s10637-013-9933-z
AUTORES / AUTHORS: - Machiels JP; Kaminsky MC; Keller U; Brummendorf TH; Goddemeier T; Forssmann U; Delord JP
INSTITUCIÓN / INSTITUTION: - Service d’Oncologie Medicale, Centre du Cancer, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Experimentale (IREC, MIRO), Universite Catholique de Louvain, Bruxelles, Belgium, Jean-Pascal.Machiels@uclouvain.be.
RESUMEN / SUMMARY: - Background This Phase Ib trial assessed the maximum tolerated dose (MTD) and safety of the Toll-like receptor 9 agonist IMO-2055 combined with 5-fluorouracil, cisplatin, and cetuximab (PFE) as first-line palliative treatment in patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Methods A standard 3 + 3 study design was used. Patients were sequentially enrolled to be treated with IMO-2055 (0.16, 0.32, or 0.48 mg/kg/day; days 1, 8, 15), 5-fluorouracil (1,000 mg/m(2)/day; days 1-4), cisplatin (100 mg/m(2)/day; day 1) and cetuximab (400 mg/m(2)/day first dose; then 250 mg/m(2)/day; days 1, 8, 15) every 3 weeks. Results Thirteen patients received IMO-2055. Dose-limiting toxicities (DLTs; ie, any Grade [G]3/4 treatment-related adverse events [TEAEs] in cycle 1) occurred in 2/4 patients treated with IMO-2055 0.32 mg/kg (G4 hypokalemia and hypomagnesemia [n = 1]; G4 septicemia, hyperthermia, febrile neutropenia, and G3 hypotension [n = 1]). In the IMO-2055 0.16-mg/kg expansion cohort, 1 patient experienced DLTs of G3 sepsis, bacteremia, and hyperthermia. The most common G >/= 3 TEAEs were neutropenia (n = 9; not including febrile neutropenia [n = 1]), hypokalemia (n = 5), and hypomagnesemia (n = 4). Serious adverse events (SAEs) occurred in 8 patients, including 4 with SAEs considered IMO-2055 related; 1 of these patients died. Best response achieved overall was partial response in 3 patients and stable disease in 9 patients. The overall safety profile led to early trial termination; the safety monitoring committee did not confirm the MTD (formally IMO-2055 0.16 mg/kg). Conclusions Regimens combining IMO-2055 and PFE cannot be recommended for further development in R/M SCCHN patients.
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[25]
TÍTULO / TITLE: - Phase II trial of non-pegylated liposomal doxorubicin and low-dose prednisone in second-line chemotherapy for hormone-refractory prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):696-701. doi: 10.1700/1217.13491.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13491
AUTORES / AUTHORS: - Montanari M; Fabbri F; Rondini E; Frassineti GL; Mattioli R; Carloni S; Scarpi E; Zoli W; Amadori D; Cruciani G
INSTITUCIÓN / INSTITUTION: - Oncology Unit, Santa Maria delle Croci Hospital, Viale Randi 5, Ravenna, Italy. marcomontanarimail@libero.it
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: Non-pegylated liposomal doxorubicin (NPLD) (Myocet) has shown marked in vitro activity in castration-resistant prostate cancer (CRPC) and also in docetaxel-resistant cells, higher than that shown by pegylated liposomal doxorubicin. Its activity would seem to be due to a high intracellular drug concentration and induction of Golgi-dependent apoptosis. On the basis of these results, a clinical study was designed to assess the activity of NPLD and low-dose prednisone in second-line therapy. METHODS: Fifty-four patients were enrolled and evaluated. Eligibility criteria were histologically confirmed CRPC, PSA >20 ng/mL or measurable lesions according to the RECIST criteria, previous docetaxel-based chemotherapy, and adequate cardiac function. Patients were treated with weekly intravenous NPLD 25 mg/m2 and daily prednisone 10 mg until progression. RESULTS: Median patient age was 69 years (range, 52-83) and median baseline PSA concentration was 120 ng/mL (range, 5.35-4350). Sixteen (29.6%) patients had measurable lesions. Objective or PSA responses (>50% reduction) were observed in 8 (14.8%) patients. The median time to progression was 2.8 months and the median overall survival was 11.3 months. Toxicity was generally mild (grade 1-2) and infrequent, with grade 3-4 neutropenia in 12.9% of cases. Grade 3 nonhematological toxicities included nausea in 2 patients (3.7%) and fatigue and stomatitis in 1 case (1.9%). No drug-related serious adverse events were reported. CONCLUSIONS: Weekly administration of NPLD is a well tolerated treatment with proven albeit limited activity.
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[26]
TÍTULO / TITLE: - Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Toxicol Appl Pharmacol. 2013 May 1;268(3):318-30. doi: 10.1016/j.taap.2013.02.001. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1016/j.taap.2013.02.001
AUTORES / AUTHORS: - Puntel M; A K M GM; Farrokhi C; Vanderveen N; Paran C; Appelhans A; Kroeger KM; Salem A; Lacayo L; Pechnick RN; Kelson KR; Kaur S; Kennedy S; Palmer D; Ng P; Liu C; Krasinkiewicz J; Lowenstein PR; Castro MG
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
RESUMEN / SUMMARY: - Adenoviral vectors (Ads) are promising gene delivery vehicles due to their high transduction efficiency; however, their clinical usefulness has been hampered by their immunogenicity and the presence of anti-Ad immunity in humans. We reported the efficacy of a gene therapy approach for glioma consisting of intratumoral injection of Ads encoding conditionally cytotoxic herpes simplex type 1 thymidine kinase (Ad-TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Ad-Flt3L). Herein, we report the biodistribution, efficacy, and neurological and systemic effects of a bicistronic high-capacity Ad, i.e., HC-Ad-TK/TetOn-Flt3L. HC-Ads elicit sustained transgene expression, even in the presence of anti-Ad immunity, and can encode large therapeutic cassettes, including regulatory elements to enable turning gene expression “on” or “off” according to clinical need. The inclusion of two therapeutic transgenes within a single vector enables a reduction of the total vector load without adversely impacting efficacy. Because clinically the vectors will be delivered into the surgical cavity, normal regions of the brain parenchyma are likely to be transduced. Thus, we assessed any potential toxicities elicited by escalating doses of HC-Ad-TK/TetOn-Flt3L (1x10(8), 1x10(9), or 1x10(10) viral particles [vp]) delivered into the rat brain parenchyma. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points. The results indicate that doses up to 1x10(9) vp of HC-Ad-TK/TetOn-Flt3L can be safely delivered into the normal rat brain and underpin further developments for its implementation in a phase I clinical trial for glioma.
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[27]
TÍTULO / TITLE: - Frequency of ABL gene mutations in chronic myeloid leukemia patients resistant to imatinib and results of treatment switch to second-generation tyrosine kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Clin (Barc). 2013 Feb 21. pii: S0025-7753(13)00014-6. doi: 10.1016/j.medcli.2012.10.028.
●● Enlace al texto completo (gratuito o de pago) 1016/j.medcli.2012.10.028
AUTORES / AUTHORS: - Marce S; Zamora L; Cabezon M; Xicoy B; Boque C; Fernandez C; Grau J; Navarro JT; Fernandez de Sevilla A; Ribera JM; Feliu E; Milla F
INSTITUCIÓN / INSTITUTION: - Hematology Department, ICO Badalona-Hospital Germans Trias i Pujol, Instituto de Investigacion contra la Leucemia Josep Carreras, Universitat Autonoma de Barcelona, Badalona, Barcelona, España.
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVES: Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients do not achieve the optimal response or are resistant to TKI. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKI has produced high rates of hematologic and cytogenetic responses in mutated ABL patients. The aim of this study was to determine the type and frequency of ABL mutations in patients who were resistant to imatinib or had lost the response, and to analyze the effect of second-generation TKI on their outcome. PATIENTS AND METHODS: The presence of ABL mutations in 45 CML patients resistant to imatinib was evaluated by direct sequencing and was correlated with the results of the cytogenetic study (performed in 39 cases). The outcome of these patients after therapy with nilotinib or dasatinib was analyzed. RESULTS: ABL mutations were detected in 14 out of 45 resistant patients. Patients with clonal cytogenetic evolution tended to develop mutations more frequently than those without clonal evolution. Nine out of the 15 patients with ABL mutation responded to a treatment switch to nilotinib (n=4), dasatinib (n=2), interferon (n=1) or hematopoietic stem cell transplantation (n=2). CONCLUSION: The frequency of ABL mutations in CML patients resistant to imatinib is high and is more frequent among those with clonal cytogenetic evolution. The change to second-generation TKI can overcome imatinib resistance in most of the mutated patients.
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[28]
TÍTULO / TITLE: - A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 19;108(5):1061-70. doi: 10.1038/bjc.2013.74. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.74
AUTORES / AUTHORS: - Warso MA; Richards JM; Mehta D; Christov K; Schaeffer C; Rae Bressler L; Yamada T; Majumdar D; Kennedy SA; Beattie CW; Das Gupta TK
INSTITUCIÓN / INSTITUTION: - UIC Department of Surgery, Division of Surgical Oncology, 840 South Wood Street, #618, MC 820, Chicago, IL 60612, USA.
RESUMEN / SUMMARY: - Background:This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53(+) metastatic solid tumours.Methods:A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival.Results:No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7-61 weeks, three a partial response for 44-125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion.Conclusion:p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.
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[29]
TÍTULO / TITLE: - Safety analysis of weekly paclitaxel plus S-1 versus paclitaxel plus 5-fluorouracil/calcium folinate as first-line therapy in advanced gastric cancer: a multicenter open random phase II trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Chemother. 2013 Feb;25(1):56-9. doi: 10.1179/1973947812Y.0000000057.
●● Enlace al texto completo (gratuito o de pago) 1179/1973947812Y.0000000057
AUTORES / AUTHORS: - Deng T; Xu N; Xiong JP; Yan Z; Zhuang ZX; Yu Z; Wan HP; Zhang Y; Huang DZ; Zheng RS; Guo ZQ; Hu CH; Wang ML; Yu ZH; Yao Y; Meng JC; Ba Y
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Medical Oncology,Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Cancer Prevention and Therapy of Tianjin, China.
RESUMEN / SUMMARY: - PURPOSE: To report the results of a safety analysis from a phase II trial comparing administration of weekly paclitaxel plus S-1 (TS) versus paclitaxel plus 5-fluorouracil (5-FU)/calcium folinate (LV) (TLF) as first-line therapy for advanced gastric cancer. METHODS: Patients (n = 240) with previously untreated advanced gastric cancer were randomly assigned to receive either TS or TLF in a 28-day cycle for six cycles. RESULTS: The clinical features of both sets of patients were similar, with the exception of the incidence of prior chemotherapy (P>0.05). Most treatment-related adverse events occurred at similar rates in both treatment arms. However, patients receiving TS experienced an increase in all-grade especially grade ¾ neutropenia, with an incidence of 43.7% in the TS arm and 16.3% in the TLF arm, respectively (P<0.05). Other severe adverse events were infrequent and not significantly different between the groups. CONCLUSION: The safety and tolerance of weekly paclitaxel plus S-1 or 5-FU/LV is well in untreated advanced gastric cancer patients.
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[30]
TÍTULO / TITLE: - Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American co-operative group trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Blood. 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1182/blood-2012-09-454694
AUTORES / AUTHORS: - Kanakry JA; Li H; Gellert LL; Lemas MV; Hsieh WS; Hong F; Tan KL; Gascoyne RD; Gordon LI; Fisher RI; Bartlett NL; Stiff P; Cheson BD; Advani R; Miller TP; Kahl BS; Horning SJ; Ambinder RF
INSTITUCIÓN / INSTITUTION: - Johns Hopkins University, School of Medicine, Baltimore, MD, United States;
RESUMEN / SUMMARY: - Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from a Cancer Cooperative Intergroup Trial (E2496/Stanford V versus ABVD for HL) were used to compare pre-treatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cut-off of >60 viral copies/100 microL plasma yielded 96% concordance with EBER-ISH. Pre-treatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cut-off. Patients with pre-treatment EBV(+) plasma (n=54) had inferior failure-free survival (FFS) compared to those with pre-treatment EBV(-) plasma (n=274), log-rank p=0.009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pre-treatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n=7) had inferior FFS compared to plasma EBV(-) patients (n=125), log-rank p=0.007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility at baseline and after 6 months of therapy for HL. (Clinical trial information: NCT00003389).
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[31]
TÍTULO / TITLE: - Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.45.9636
AUTORES / AUTHORS: - Ong CA; Shapiro J; Nason KS; Davison JM; Liu X; Ross-Innes C; O’Donovan M; Dinjens WN; Biermann K; Shannon N; Worster S; Schulz LK; Luketich JD; Wijnhoven BP; Hardwick RH; Fitzgerald RC
INSTITUCIÓN / INSTITUTION: - Chin-Ann J. Ong, Xinxue Liu, Caryn Ross-Innes, Maria O’Donovan, Susannah Worster, Laura K.E. Schulz, and Rebecca C. Fitzgerald, Hutchison/MRC Research Centre; Nicholas Shannon, Cambridge Research Institute; Richard H. Hardwick, Addenbrooke’s Hospital, Cambridge, United Kingdom; Joel Shapiro, Winand N.M. Dinjens, Katharina Biermann, and Bas P.L. Wijnhoven, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands; and Katie S. Nason, Jon M. Davison, and James D. Luketich, University of Pittsburgh, Pittsburgh, PA.
RESUMEN / SUMMARY: - PURPOSEEsophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. PATIENTS AND METHODSWe recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666).ResultsThree of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). CONCLUSIONWe identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage.
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[32]
TÍTULO / TITLE: - Predictors for the 5-year risk of serious infections in patients with rheumatoid arthritis treated with anti-tumor necrosis factor therapy: a cohort study in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Rheumatology (Oxford). 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1093/rheumatology/kes413
AUTORES / AUTHORS: - van Dartel SA; Fransen J; Kievit W; Dutmer EA; Brus HL; Houtman NM; van de Laar MA; van Riel PL
INSTITUCIÓN / INSTITUTION: - Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Department of Rheumatology, Gelderse Vallei Hospital, Ede, Department of Rheumatology, TweeSteden Hospital, Tilburg, Department of Rheumatology, Medical Centre Leeuwarden, Leeuwarden and Department of Rheumatology, Arthritis Centre Twente, Enschede, The Netherlands.
RESUMEN / SUMMARY: - Objective. The use of TNF inhibitors leads to an increased risk of serious infections in RA. Predicting this risk would facilitate the prevention of serious infections. The objective of this study was to identify which factors are predictive of the increased risk of serious infections in RA patients treated with TNF inhibiting therapy.Methods. Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry of 2044 patients with RA were used for the analyses. Data were censored at stopping TNF inhibitors or end of observation time up to 5 years. Univariate and multivariate analysis of baseline variables was performed using Cox regression with time to the first serious infection as dependent variable.Results. During a follow-up time of 5 years, 128 of 2044 (6.3%) patients developed a first serious infection with a total of 141 serious infections. The incidence rate in the first year after start of TNF inhibiting therapy was 4.57 first serious infections per 100 patient-years and 2.91 per 100 patient-years over 5 years. Age, corticosteroid use, visual analogue scale (VAS) pain, HAQ, tender joint count 28 joints (TJC28) and the presence of comorbidities were significant predictors for developing a serious infection during TNF inhibiting therapy in the multivariate model.Conclusion. Age, corticosteroid use, VAS pain, HAQ, TJC28 and the presence of comorbidities all at baseline were significant predictors for developing a serious infection during TNF inhibiting therapy in RA patients.
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[33]
TÍTULO / TITLE: - High-Grade KIT-Negative Sarcoma of the Small Bowel in a Patient With Chronic Myeloid Leukemia Receiving Long-Term Tyrosine Kinase Inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.42.7989
AUTORES / AUTHORS: - Martz J; Jain S; Vahdat LT; Qin L; Mosquera JM; Antonescu CR; Popa EC
INSTITUCIÓN / INSTITUTION: - Ludwig-Maximilians Universitat Munich, Munich, Germany.
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[34]
TÍTULO / TITLE: - Neoadjuvant epirubicin, gemcitabine and docetaxel for primary breast cancer: Long-term survival data and major prognostic factors based on two consecutive neoadjuvant phase I/II trials.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28094.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28094
AUTORES / AUTHORS: - Marme F; Aigner J; Lorenzo Bermejo J; Sinn P; Sohn C; Jager D; Schneeweiss A
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, University Hospital Heidelberg, Heidelberg, Germany; National Centre for Tumour Diseases, University Hospital, Heidelberg, Germany.
RESUMEN / SUMMARY: - We previously reported primary endpoints of two consecutive phase I/II trials, evaluating different schedules of neoadjuvant epirubicin (E), gemcitabine (G) and docetaxel (Doc) for primary breast cancer (PBC). Here, we report mature survival data and prognostic factors. One hundred fifty-one patients were recruited into two consecutive phase I/II trials of neoadjuvant chemotherapy for T2-4 N0-2 M0 PBC. Patients received six cycles of G/E/Doc every 3 weeks with G repeated on d8 (GEDoc, n = 84) or five cycles of G/E followed by four cycles of Doc all given every two weeks (GEsDoc, n = 67). Prognostic factors were investigated using univariate and multivariate analyses. No survival differences by treatment were found. Among reported predictive factors for pathologic complete response (pCR), oestrogen receptor (ER) status was the only relevant factor in the multivariate analysis. Unexpectedly, pCR resulted in poorer survival (univariate HR for overall survival [OS] 3.11, p = 0.007). Multivariate analyses identified molecular subtype and tumour size as the most relevant prognostic factors for OS. HER2-receptor status and the CPS-EG score (Mittendorf et al., J Clin Oncol 2011;29:1956-62), based on clinical and pathological stage, ER-status and tumour grade, were particularly relevant in disease-free survival. Our findings cast doubt on the reliability of pCR as single marker for prognosis of this unselected breast cancer cohort, with an abundance of luminal subtypes. These results underline the significance of additional molecular characteristics for breast cancer survival.
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[35]
TÍTULO / TITLE: - The clinical characteristics and prognostic significance of MN1 gene and MN1-associated microRNA expression in adult patients with de novo acute myeloid leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hematol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s00277-013-1729-x
AUTORES / AUTHORS: - Xiang L; Li M; Liu Y; Cen J; Chen Z; Zhen X; Xie X; Cao X; Gu W
INSTITUCIÓN / INSTITUTION: - Department of Hematology, The First People’s Hospital of Changzhou, Third Affiliated Hospital of Suzhou University, No.185, Juqian Street, Tianning District, Changzhou, 213003, Jiangsu, China.
RESUMEN / SUMMARY: - This study aimed to determine the clinical characteristics and prognostic significance of the meningioma 1 (MN1) gene and MN1-associated microRNA expression in Chinese adult de novo acute myeloid leukemia (AML) patients. The expression level of MN1, microRNA-20 (miR-20a), and microRNA-181b (miR-181b) in bone marrow mononuclear cells was measured in 158 newly diagnosed AML patients and 20 cases of normal healthy donors by real-time quantitative reverse transcriptase polymerase chain reaction. All AML patients significantly overexpressed MN1 at the level of 0.01983 (P < 0.001) compared with normal controls. High MN1 expression was associated with spleen involvement (P = 0.037), NPM1 wild type (P = 0.001), lower miR-20a expression levels (P = 0.015), and higher miR-181b expression levels (P = 0.035). MiR-20a (P = 0.029) and miR-181b (P = 0.017) overexpressed in the bone marrow cells of patients with certain subtypes of AML compared with healthy donors. High MN1 expressers had lower complete remission (CR) rates and shorter overall survival (OS) within the Southwest Oncology Group classification. In multivariable models, high MN1 expression was associated with worse CR rates (P = 0.01), relapse-free survival (RFS; P = 0.02), and OS (P = 0.02); high miR-20a expression was associated with higher CR rates (P = 0.008) and longer OS (P = 0.04), whereas high miR-181b expression was associated with lower CR rates (P = 0.03), and shorter RFS (P = 0.045) and OS (P = 0.017). High MN1 expression confers worse prognosis in Chinese adult patients with de novo AML. MN1 gene and MN1-associated microRNAs provide clinical prognosis of AML patients and may refine their molecular risk classification.
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[36]
TÍTULO / TITLE: - Validation of serum C-reactive protein (CRP) as an independent prognostic factor for disease-free survival in patients with localised renal cell carcinoma (RCC).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BJU Int. 2013 Mar 15. doi: 10.1111/bju.12067.
●● Enlace al texto completo (gratuito o de pago) 1111/bju.12067
AUTORES / AUTHORS: - de Martino M; Klatte T; Seemann C; Waldert M; Haitel A; Schatzl G; Remzi M; Weibl P
INSTITUCIÓN / INSTITUTION: - Department of Urology, Medical University of Vienna, Vienna.
RESUMEN / SUMMARY: - OBJECTIVE: To validate high-sensitivity C-reactive protein (hs-CRP) serum levels as an independent marker for disease-free survival (DFS) in clinically localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 403 consecutive patients with clinically localised (T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled. Preoperative serum levels of hs-CRP were evaluated as both a continuous and categorical variables. Associations with clinical (age, gender) and pathological variables (T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal-Wallis tests. Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy (PA) was assessed with Harrell’s C-index. RESULTS: The mean hs-CRP level was 1.32 mg/dL. The hs-CRP levels were associated with T classification (P = 0.05), high-grade disease (P < 0.001) and tumour necrosis (P = 0.003). After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs-CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015). The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence. These categorically coded hs-CRP levels were identified as independent prognostic factors in multivariable analyses (P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the ‘Stage, Size, Grade and Necrosis’ (SSIGN) score. CONCLUSIONS: This study validates preoperative serum hs-CRP levels as independent prognostic factor after surgery for localised ccRCC. Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials.
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[37]
TÍTULO / TITLE: - Immunohistochemically Detected Expression of 3 Major Genes (CDKN2A/p16, TP53, and SMAD4/DPC4) Strongly Predicts Survival in Patients With Resectable Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e3182827a65
AUTORES / AUTHORS: - Oshima M; Okano K; Muraki S; Haba R; Maeba T; Suzuki Y; Yachida S
INSTITUCIÓN / INSTITUTION: - *Departments of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan daggerDepartment of Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan double daggerDepartment of Laboratory Medicine, Social Insurance Ritsurin Hospital, Takamatsu, Kagawa, Japan section signDepartment of Surgery, Social Insurance Ritsurin Hospital, Takamatsu, Kagawa, Japan paragraph signDivision of Refractory Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
RESUMEN / SUMMARY: - OBJECTIVE:: The goal of this retrospective study was to clarify the clinical implications of the status of the 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4). BACKGROUND:: Recent whole-exome sequencing had shown that the landscape of the pancreatic ductal adenocarcinoma (PDAC) genome is notable for 4 frequently mutated genes (KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4). METHODS:: We determined immunohistochemically the status of TP53, CDKN2A/p16, and SMAD4/DPC4 among the 4 genes because the KRAS gene is mutated in virtually all PDAC patients, and analyzed relationships with clinicopathological findings, including survival and patterns of disease progression, in 106 patients with PDAC undergoing radical surgery. RESULTS:: Abnormal immunolabeling of p53 was detected in 81.1% of PDACs and was significantly associated with tumor dedifferentiation (P = 0.022) and the presence of locoregional recurrence (P = 0.020). Loss of p16 and Smad4/Dpc4 immunolabeling was identified in 67.0% and 60.4%, respectively. Loss of p16 immunolabeling was associated with lymphatic invasion (P = 0.012) and postoperative widespread metastases (P < 0.001). A significant correlation was found between Smad4/Dpc4 immunolabeling and tumor size (P = 0.006), lymphatic invasion (P = 0.033), and lymph node metastasis (P = 0.006). Interestingly, all of the 6 patients demonstrating 5-year survival had intact SMAD4/DPC4. Kaplan-Meier survival analysis showed that lymph node metastasis (P = 0.001), lymphatic invasion (P = 0.008), the tumor (T) factor (T3 vs. T1/T2, P = 0.004), loss of p16 immunolabeling (P = 0.029), and loss of Smad4/Dpc4 immunolabeling (P < 0.001) were significantly associated with shorter overall survival. Multivariate analysis revealed that loss of Smad4/Dpc4 immunolabeling was an independent and significant poor prognostic factor for overall and disease-free survival. On analysis of combinations of the status of these 3 genes, increasing number of alterations reflected poorer survival. CONCLUSIONS:: Genetic alterations of these 3 genes and their accumulation are strongly associated with malignant behavior of PDAC. Their immunohistochemical assessment at the time of diagnosis may provide a new prognostic tool, assisting in deciding optimal therapeutic strategies for patients.
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[38]
TÍTULO / TITLE: - Homozygosity for killer immunoglobin-like receptor haplotype a predicts complete molecular response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Hematol. 2013 Feb 1. pii: S0301-472X(13)00011-8. doi: 10.1016/j.exphem.2013.01.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.exphem.2013.01.008
AUTORES / AUTHORS: - La Nasa G; Caocci G; Littera R; Atzeni S; Vacca A; Mulas O; Langiu M; Greco M; Orru S; Orru N; Floris A; Carcassi C
INSTITUCIÓN / INSTITUTION: - Bone Marrow Transplant Center, R. Binaghi Hospital - ASL 8, Cagliari, Italy; Hematology Unit, Department of Medical Sciences, University of Cagliari, Italy. Electronic address: lanasa@tiscali.it.
RESUMEN / SUMMARY: - Several recent reports suggest a possible role for killer immunoglobulin-like receptors (KIR) in the onset of chronic myeloid leukemia (CML) and response to therapy with tyrosine kinase inhibitors (TKIs). To explore this hypothesis, we studied KIRs and their human leukocyte antigen class I ligands in 59 consecutive patients with chronic-phase CML (mean age, 53 years; range, 23-81 years) and a group of 121 healthy control participants belonging to the same ethnic group as the patients. The 2-year cumulative incidence of complete molecular response, obtained after a median of 27 months (range, 4-52 months), was 51.2%. An increased frequency of the activating receptor KIR2DS1 (pm = 0.05) and a reduced frequency of the KIR-ligand combination KIR2DS2/2DL2 absent/C1 present (pm = 0.001) were significantly associated with CML. Moreover, KIR repertoires in patients appeared to influence response to TKI therapy. Homozygosity for KIR haplotype A (pm = 0.01), a decreased frequency of the inhibitory KIR gene KIR2DL2 (pm = 0.02), and low numbers of inhibitory KIR genes (pm = 0.05) were all significantly associated with achievement of complete molecular remission. These data suggest that a decrease in properly stimulated and activated NK cells might contribute to the occurrence of CML and indicate homozygosity for KIR haplotype A as a promising immunogenetic marker of complete molecular response that could help clinicians decide whether to withdraw treatment in patients with CML.
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[39]
TÍTULO / TITLE: - Association between serum levels of C-reactive protein and response to treatment of chemotherapy-induced anemia in patients with solid tumors: a multicenter, prospective, observational study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Mar;30(1):417. doi: 10.1007/s12032-012-0417-3. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-012-0417-3
AUTORES / AUTHORS: - Esquerdo Galiana G; Cervera JM; Barrajon E; Juarez A; Llorca C; Diaz N; Lopez A; Peiro R
INSTITUCIÓN / INSTITUTION: - Medical Oncology Service, Hospital Clinica Benidorm, Avda Alfonso Puchades 8, 03501 Benidorm, Alicante, España. gasparesquerdo@yahoo.es
RESUMEN / SUMMARY: - Our objective was to determine the association between C-reactive protein (CRP) levels at initiation of anemia treatment and response in solid tumor patients with chemotherapy (CT)-induced anemia. This was a multicenter, prospective, observational study which included adult patients with solid tumor initiating treatment for CT-induced anemia. Data were collected up to 16 weeks, or until premature discontinuation. We included 98 patients (median age 62.5 years, 64 % males, 57 % with ECOG 0-1, 85.7 % at stages III-IV and 54.1 % undergoing palliative CT). Mean (SD) Hb levels at baseline were 10.3 (0.9) g/dL (85.7 % < 11 g/dL) and median (Q1; Q3) CRP was 16.4 mg/L (3.9; 77.8) (68 % >/= 5 mg/L). A total of 96 % of patients initiated erythropoiesis-stimulating agents (ESA) and iron supplementation; 4 % initiated iron monotherapy. After a median of 85 days, 65 % of patients had Hb >/= 11 g/dL (in absence of transfusion) (mean change: +0.86 g/dL, 95 % confidence interval (CI) 0.53-1.19). A total of 8 patients required transfusion. A significant correlation (r = -0.39, p = 0.003) was observed between baseline CRP and final Hb levels. In the multivariate linear regression analysis, the independent predictors of higher final Hb levels were a high baseline Hb (adjusted ss = +0.69 g/dL for each g/dL of baseline Hb, 95 % CI 0.17-1.21) and a low log baseline CRP (-0.62 for each log mg/L, 95 %CI -1.22 to -0.02). Our results suggest that, in patients with solid tumors and CT-induced anemia, high CRP levels at treatment initiation predict a poor response to treatment with ESA and iron, independently from anemia severity at therapy initiation and from other patient and disease characteristics.
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[40]
TÍTULO / TITLE: - Combination of Rituximab, Bendamustine, and Cytarabine for Patients With Mantle-Cell Non-Hodgkin Lymphoma Ineligible for Intensive Regimens or Autologous Transplantation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.45.9842
AUTORES / AUTHORS: - Visco C; Finotto S; Zambello R; Paolini R; Menin A; Zanotti R; Zaja F; Semenzato G; Pizzolo G; D’Amore ES; Rodeghiero F
INSTITUCIÓN / INSTITUTION: - Carlo Visco, Silvia Finotto, Andrea Menin, Emanuele S.G. D’Amore, and Francesco Rodeghiero, San Bortolo Hospital, Vicenza; Renato Zambello and Gianpietro Semenzato, Padua University School of Medicine, Padova; Rossella Paolini, Santa Maria della Misericordia Hospital, Rovigo; Roberta Zanotti and Giovanni Pizzolo, University of Verona, Verona; and Francesco Zaja, Azienda Ospedaliera Universitaria Santa Maria Misericordia, Udine, Italy.
RESUMEN / SUMMARY: - PURPOSEThe combination of bendamustine (B) and rituximab ® is efficacious, with favorable toxicity in mantle-cell lymphoma (MCL). In this phase II study, we combined cytarabine with R and B (R-BAC) in patients with MCL age >/= 65 years who were previously untreated or relapsed or refractory (R/R) after one prior immunochemotherapy treatment. PATIENTS AND METHODSIn stage one, we established the maximum-tolerated dose (MTD) of cytarabine in R-BAC. In stage two, patients received R (375 mg/m(2) intravenously [IV] on day 1), B (70 mg/m(2) IV on days 2 and 3), and cytarabine (MTD IV on days 2 to 4) every 28 days for four to six cycles. The primary end point (overall response rate [ORR]) was evaluated by positron emission tomography. Secondary end points included safety, progression-free survival (PFS), response duration, and overall survival.ResultsForty patients (median age, 70 years; 20 previously untreated patients) were enrolled; 93% had Ann Arbor stage III/IV disease; 49% had high Mantle Cell International Prognostic Index scores, with 15% blastoid histology. All R/R patients (35% refractory) had previously received R-containing regimens. The cytarabine MTD used in stage two was 800 mg/m(2), and R-BAC was well tolerated, with an 85% treatment completion rate. The major toxicity was transient grades 3 to 4 thrombocytopenia (87% of patients); febrile neutropenia occurred in 12%. The ORR was 100% (95% complete response [CR]) for previously untreated and 80% (70% CR) for R/R patients. The 2-year PFS rate (+/- standard deviation) was 95% +/- 5% for untreated and 70% +/- 10% for R/R patients. CONCLUSIONR-BAC is well tolerated and active against MCL.
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[41]
TÍTULO / TITLE: - Preferential eradication of acute myelogenous leukemia stem cells by fenretinide.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5606-11. doi: 10.1073/pnas.1302352110. Epub 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1302352110
AUTORES / AUTHORS: - Zhang H; Mi JQ; Fang H; Wang Z; Wang C; Wu L; Zhang B; Minden M; Yang WT; Wang HW; Li JM; Xi XD; Chen SJ; Zhang J; Chen Z; Wang KK
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
RESUMEN / SUMMARY: - Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34(+) cells, especially the LSC-enriched CD34(+)CD38(-) subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34(+) cells but not those from normal CD34(+) cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-kappaB and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide-down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML.
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[42]
TÍTULO / TITLE: - Predictors of depression in breast cancer patients treated with radiation: Role of prior chemotherapy and nuclear factor kappa B.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Mar 19. doi: 10.1002/cncr.28003.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.28003
AUTORES / AUTHORS: - Torres MA; Pace TW; Liu T; Felger JC; Mister D; Doho GH; Kohn JN; Barsevick AM; Long Q; Miller AH
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Emory University, Atlanta, Georgia. matorre@emory.edu.
RESUMEN / SUMMARY: - BACKGROUND: Depression is common during and after breast cancer treatment. However, the role of specific therapeutic modalities and related biologic mechanisms remains unclear. Radiation is an essential component of breast-conserving therapy and may contribute to depression in patients with breast cancer through the activation of inflammatory pathways. METHODS: Depressive symptoms and inflammatory mediators, including nuclear factor kappa B (NF-kappaB), were assessed at baseline (before radiation), during radiation, and 6 weeks after radiation in 64 women who had stage 0 through IIIA breast cancer. RESULTS: No significant increases in depressive symptoms occurred during or after radiation, although a number of patients exhibited moderate-to-severe depression throughout the study. Multivariate analyses of baseline factors predictive of depression revealed that educational status, perceived stress, prior chemotherapy, and peripheral blood NF-kappaB DNA binding all were independent predictors of persistent depressive symptoms after radiation (all P < .05). Of these factors, only prior chemotherapy was associated with inflammatory mediators, including NF-kappaB DNA binding, soluble tumor necrosis factor-alpha receptor 2, and interleukin-6, which, in univariate analyses predicted depressive symptoms after radiation (all P < .05). Chemotherapy-treated patients also exhibited an over-representation of gene transcripts regulated by NF-kappaB. CONCLUSIONS: Radiation was not associated with increased depressive symptoms in the current study, but of disease and treatment-related factors, prior chemotherapy predicted significant depression after radiation. Longitudinal studies are warranted to investigate the relationship among prior chemotherapy, inflammation, and persistent depression after breast cancer treatment. Cancer 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 American Cancer Society.
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[43]
TÍTULO / TITLE: - Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Mar;30(1):482. doi: 10.1007/s12032-013-0482-2. Epub 2013 Feb 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0482-2
AUTORES / AUTHORS: - Zhen ZJ; Ling JY; Cai Y; Luo WB; He YJ
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China. zhenzj@sysucc.org.cn
RESUMEN / SUMMARY: - Human leukocyte antigen (HLA)-E can contribute to the escape of cancer cells from host immune mechanisms. However, it is unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. This study aimed to evaluate the correlation between HLA-E gene polymorphisms and HLA-E expression in tumor tissue and determine the effects on clinical outcome of patients with stage III colorectal cancer. Two hundred thirty patients with stage III colorectal cancer were enrolled. HLA-E expression was detected in patient-derived tumor tissues with immunohistochemistry. HLA-E gene alleles in tumor tissues were detected with the polymerase chain reaction-sequence-specific primer method. In colorectal cancer tissue and in the normal tissue adjacent to the tumor, the HLA-E expression rates were 72.2 and 15.1 %, respectively (P < 0.05). Patients with overexpression, low expression, and no expression of HLA-E exhibited disease-free survival of 55.3, 72.9, and 72.1 %, respectively. Patients with HLA-E overexpression exhibited the lowest long-term survival rate. No relationship was observed between the type of HLA-E gene polymorphism and its expression level in tumor tissues; moreover, no polymorphisms appeared to affect the long-term survival of patients with colorectal cancer. The type of HLA-E polymorphism did not have an impact on HLA-E expression in tumors or the prognosis in patients with stage III colorectal cancer. However, the level of HLA-E expression in tumor tissue strongly predicted long-term survival in these patients.
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[44]
TÍTULO / TITLE: - Metformin—an adjunct antineoplastic therapy—divergently modulates tumor metabolism and proliferation, interfering with early response prediction by 18F-FDG PET imaging.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Nucl Med. 2013 Feb;54(2):252-8. doi: 10.2967/jnumed.112.107011.
●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.107011
AUTORES / AUTHORS: - Habibollahi P; van den Berg NS; Kuruppu D; Loda M; Mahmood U
INSTITUCIÓN / INSTITUTION: - Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
RESUMEN / SUMMARY: - Over the last several years, epidemiologic data have suggested that the antidiabetes drug metformin (MET), an adenosine monophosphate-activated protein kinase (AMPK) activator, improves progression-free survival of patients with multiple cancers; more than 30 clinical trials are under way to confirm this finding. We postulated that the role of AMPK as a central cellular energy sensor would result in opposite effects on glucose uptake and proliferation, suggesting different roles for (18)F-FDG and 3’-deoxy-3’-(18)F-fluorothymidine ((18)F-FLT) in assessing its effectiveness as an antineoplastic agent. METHODS: Colon cancer cell lines HT29 (human) and MC26 (murine) were treated for 24 or 72 h with a range of MET concentrations (0-10 mM). Western blotting was used to study the activation of AMPK after MET treatment. Glucose uptake and cell proliferation were measured by cell retention studies with either (18)F-FDG or (18)F-FLT. EdU (ethynyl deoxyuridine, a thymidine analog) and annexin-propidium iodide flow cytometry was performed to determine cell cycle S-phase and apoptotic changes. In vivo (18)F-FDG and (18)F-FLT PET images were acquired before and 24 h after MET treatment of HT29 tumor-bearing mice. RESULTS: After 24 h of MET incubation, phosphorylated AMPK levels increased severalfold in both cell lines, whereas total AMPK levels remained unchanged. In cell retention studies, (18)F-FDG uptake increased but (18)F-FLT retention decreased significantly in both cell lines. The numbers of HT29 and MC26 cells in the S phase decreased 36% and 33%, respectively, after MET therapy. Apoptosis increased 10.5-fold and 5.8-fold in HT29 and MC26 cells, respectively, after 72 h of incubation with MET. PET imaging revealed increased (18)F-FDG uptake (mean +/- SEM standardized uptake values were 0.71 +/- 0.03 before and 1.29 +/- 0.11 after MET therapy) (P < 0.05) and decreased (18)F-FLT uptake (mean +/- SEM standardized uptake values were 1.18 +/- 0.05 before and 0.89 +/- 0.01 after MET therapy) (P < 0.05) in HT29 tumor-bearing mice. CONCLUSION: MET, through activation of the AMPK pathway, produces a dose-dependent increase in tumor glucose uptake while decreasing cell proliferation in human and murine colon cancer cells. Thus, changes in (18)F-FDG uptake after MET treatment may be misleading. (18)F-FLT imaging is a promising alternative that correlates with the tumor response.
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[45]
TÍTULO / TITLE: - Identification of a 24-Gene Prognostic Signature That Improves the European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: An International Collaborative Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 20;31(9):1172-81. doi: 10.1200/JCO.2012.44.3184. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.3184
AUTORES / AUTHORS: - Li Z; Herold T; He C; Valk PJ; Chen P; Jurinovic V; Mansmann U; Radmacher MD; Maharry KS; Sun M; Yang X; Huang H; Jiang X; Sauerland MC; Buchner T; Hiddemann W; Elkahloun A; Neilly MB; Zhang Y; Larson RA; Le Beau MM; Caligiuri MA; Dohner K; Bullinger L; Liu PP; Delwel R; Marcucci G; Lowenberg B; Bloomfield CD; Rowley JD; Bohlander SK; Chen J
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University of Chicago, 900 E. 57th St, Room 7134, Chicago, IL 60637; jchen@medicine.bsd.uchicago.edu.
RESUMEN / SUMMARY: - PURPOSE To identify a robust prognostic gene expression signature as an independent predictor of survival of patients with acute myeloid leukemia (AML) and use it to improve established risk classification. PATIENTS AND METHODS Four independent sets totaling 499 patients with AML carrying various cytogenetic and molecular abnormalities were used as training sets. Two independent patient sets composed of 825 patients were used as validation sets. Notably, patients from different sets were treated with different protocols, and their gene expression profiles were derived using different microarray platforms. Cox regression and Kaplan-Meier methods were used for survival analyses. Results A prognostic signature composed of 24 genes was derived from a meta-analysis of Cox regression values of each gene across the four training sets. In multivariable models, a higher sum value of the 24-gene signature was an independent predictor of shorter overall (OS) and event-free survival (EFS) in both training and validation sets (P < .01). Moreover, this signature could substantially improve the European LeukemiaNet (ELN) risk classification of AML, and patients in three new risk groups classified by the integrated risk classification showed significantly (P < .001) distinct OS and EFS. CONCLUSION Despite different treatment protocols applied to patients and use of different microarray platforms for expression profiling, a common prognostic gene signature was identified as an independent predictor of survival of patients with AML. The integrated risk classification incorporating this gene signature provides a better framework for risk stratification and outcome prediction than the ELN classification.
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[46]
TÍTULO / TITLE: - Influence of polymorphisms in genes encoding immunoregulatory proteins and metabolizing enzymes on susceptibility and outcome in patients with diffuse large B-cell lymphoma treated with rituximab.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Apr 2.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.774392
AUTORES / AUTHORS: - Yri OE; Ekstrom PO; Hilden V; Gaudernack G; Liestol K; Smeland EB; Holte H
INSTITUCIÓN / INSTITUTION: - Division for Surgery and Cancer Medicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital , Oslo , Norway.
RESUMEN / SUMMARY: - We analyzed the allelic distribution of 12 candidate polymorphisms in a large retrospective study of 486 patients with diffuse large B-cell lymphoma (DLBCL) treated at Oslo University Hospital with 1056 blood donors serving as controls. Variants in TNFalpha (rs1800629) (GG vs. AG/AA, p < 0.001) and LTA (rs909253) (AA vs. AG/GG, p = 0.02) and deletions in GSTM1 and GSTT1 (undeleted vs. deleted, p = 0.01 and p = 0.01, respectively) were associated with increased susceptibility of developing DLBCL. IL-10 (rs1800896) variants (GG vs. AG/AA, p = 0.03) were associated with decreased susceptibility. In line with several previous reports, patients carrying the TNFalpha (rs1800629) A allele treated in the pre-rituximab era had inferior outcome compared to patients carrying the homozygous GG genotype (p = 0.004, n = 33). However, patients receiving at least one dose of rituximab had equal outcome regardless of their TNFalpha genotype (HR = 0.94, p = 0.79, n = 307). Deletion in GSTM1 was associated with inferior outcome for patients with low International Prognostic Index (IPI) score (p = 0.04). Our findings support the suggestions that polymorphisms in genes encoding immunoregulatory proteins and enzymes that metabolize carcinogens and chemotherapeutic drugs influence DLBCL susceptibility and possibly treatment outcome. The influence of polymorphisms in immunoregulatory genes on outcome in DLBCL should be reevaluated in the rituximab era.
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[47]
TÍTULO / TITLE: - Genetic variability in the multidrug resistance associated protein-1 (ABCC1/MRP1) predicts hematological toxicity in breast cancer patients receiving (neo-)adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt008
AUTORES / AUTHORS: - Vulsteke C; Lambrechts D; Dieudonne A; Hatse S; Brouwers B; van Brussel T; Neven P; Belmans A; Schoffski P; Paridaens R; Wildiers H
INSTITUCIÓN / INSTITUTION: - Department of General Medical Oncology and Laboratory of Experimental Oncology, University Hospitals Leuven, Leuven.
RESUMEN / SUMMARY: - BackgroundTo assess the impact of single-nucleotide polymorphisms (SNPs) on predefined severe adverse events in breast cancer (BC) patients receiving (neo-)adjuvant 5-fluorouracil (FU), epirubicin and cyclophosphamide (FEC) chemotherapy.Patients and methodsTwenty-six SNPs in 16 genes of interest, including the drug transporter gene ABCC1/MRP1, were selected based on a literature survey. An additional 33 SNPs were selected in these genes, as well as in 12 other genes known to be involved in the metabolism of the studied chemotherapeutics. One thousand and twelve female patients treated between 2000 and 2010 with 3-6 cycles of (neo-)adjuvant FEC were genotyped for these SNPs using Sequenom MassARRAY. Severe adverse events were evaluated through an electronic chart review for febrile neutropenia (FN, primary end point), FN first cycle, prolonged grade 4 or deep (<100/microl) neutropenia, anemia grade 3-4, thrombocytopenia grade 3-4 and non-hematological grade 3-4 events (secondary end points).ResultsCarriers of the rs4148350 variant T-allele in ABCC1/MRP1 were associated with FN relative to homozygous carriers of the G-allele [P = 0.0006; false discovery rate (FDR) = 0.026]. Strong correlations with secondary end points such as prolonged grade 4 neutropenia (P = 0.002, FDR = 0.046) were also observed. Additionally, two other SNPs in ABCC1/MRP1 (rs45511401 and rs246221) correlated with FN (P = 0.007 and P = 0.01, respectively; FDR = 0.16 and 0.19), as well as two SNPs in UGT2B7 and FGFR4 (P = 0.024 and P = 0.04; FDR = 0.28 and 0.38).ConclusionGenetic variability in ABCC1/MRP1 was associated with severe hematological toxicity of FEC.
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[48]
TÍTULO / TITLE: - Whole blood interferon-gamma levels predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 19. doi: 10.1002/ijc.28117.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28117
AUTORES / AUTHORS: - Ishikawa T; Kokura S; Sakamoto N; Okayama T; Endo M; Tsuchiya R; Okajima M; Matsuyama T; Adachi S; Kamada K; Katada K; Uchiyama K; Handa O; Takagi T; Yagi N; Ando T; Uno K; Naito Y; Yoshikawa T
INSTITUCIÓN / INSTITUTION: - Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
RESUMEN / SUMMARY: - A core challenge in administering immune-based treatments for cancer is the establishment of easily accessible immunological assays that can predict patients’ clinical responses to immunotherapy. In this study, our aim was to predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer. To do this, we evaluated whole blood cytokine levels and peripheral regulatory T cells (Tregs) in 46 patients with unresectable or recurrent pancreatic cancer who received adoptive T-cell therapy at 2-week intervals. To test immune function, venous blood was obtained from patients before the start of therapy and 2 weeks after the 4th treatment. Whole blood interferon (IFN)-alpha levels (after stimulation with the Sendai virus) were evaluated, as well as the levels of 9 cytokines stimulated with phytohemagglutinin [interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, tumor necrosis factor-alpha, IFN-gamma, and granulocyte-monocyte colony-stimulating factor]. Peripheral Tregs were analyzed by flow cytometry. Using the obtained data, we then observed the relationship between these immunological parameters and clinical outcome of patients. We found that the whole blood production of IFN-gamma, IL-2, IL-4, IL-5 and IL-13 significantly increased after adoptive T-cell therapy, whereas the number of peripheral Tregs did not change. Multivariate Cox proportional hazards analyses indicated that the number of peripheral Tregs before receiving adoptive T-cell therapy and the change in IFN-gamma levels after adoptive T-cell therapy were independent variables predicting overall survival. The findings of this study indicate that the assay of whole blood IFN-gamma production offers promise for evaluating the clinical response of patients to cancer immunotherapy.
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[49]
TÍTULO / TITLE: - Survival in patients with newly diagnosed conventional glioblastoma: a modified prognostic score based on a single-institution series.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):756-61. doi: 10.1700/1217.13500.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13500
AUTORES / AUTHORS: - Bertolini F; Zunarelli E; Baraldi C; Valentini A; Del Giovane C; Depenni R; Falasca A; Giacobazzi P; Malagoli M; Meletti S; Fontana A; Conte P
INSTITUCIÓN / INSTITUTION: - Division of Oncology, University Hospital, Via del Pozzo 71, Modena, Italy. bertolini.federica@policlinico.mo.it
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: Recursive partioning analysis (RPA) is commonly used to define the stratification of patients with glioblastoma. Epigenetic silencing of the O6-methylguanine methyltransferase (MGMT) gene by promoter methylation plays an important role in regulating MGMT expression in gliomas and this is an established independent prognostic factor. We tested a prognostic scoring system including all clinical variables used by RPA classification (age, ECOG performance status and type of surgery) and MGMT gene promoter methylation status. METHODS: Seventy-eight consecutive patients with newly diagnosed, histopathologically confirmed conventional glioblastoma were included. Information about MGMT promoter methylation status was available for all of them. Based on the patients’ age (<50 vs >/=50 years), ECOG performance status (0 vs >/=1), type of surgery (gross tumor resection versus partial resection/biopsy) and MGMT promoter methylation status (methylated versus unmethylated), three classes of risk were generated where the prognostic score was defined assigning 1 point to every favorable parameter (Class I: >/=3; Class II: 2; Class III: 0-1). All classes were correlated with overall survival. RESULTS: The median survival times were 32.4, 8.6 and 8.8 months for Class I, II and III, respectively, corresponding to 2-year survival rates of 69%, 13.5% and <1%. The same analysis was performed on 54 patients treated with postoperative concomitant chemoradiotherapy. The median survival times were 32.5, 13.4 and 8.9 months for Class I, II and III, respectively, corresponding to 2-year survival rates of 68.6%, 26.9% and <1%. In both groups of 78 and 54 patients the differences in survival between Class I and III were statistically significant ( P <0.0001). CONCLUSIONS: The proposed prognostic scoring system including clinical variables and MGMT promoter methylation status proved valuable in patients with primary conventional glioblastoma, especially those treated with postoperative chemoradiotherapy.
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[50]
TÍTULO / TITLE: - Re: safety and treatment patterns of angiogenesis inhibitors in patients with metastatic renal cell carcinoma: evidence from US community oncology clinics.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Urol. 2013 Mar;189(3):842. doi: 10.1016/j.juro.2012.11.127. Epub 2012 Nov 21.
●● Enlace al texto completo (gratuito o de pago) 1016/j.juro.2012.11.127
AUTORES / AUTHORS: - Penson DF
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[51]
TÍTULO / TITLE: - MYC/BCL2 protein co-expression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Blood. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1182/blood-2012-10-460063
AUTORES / AUTHORS: - Hu S; Xu-Monette ZY; Tzankov A; Green T; Wu L; Balasubramanyam A; Liu WM; Visco C; Li Y; Miranda RN; Montes-Moreno S; Dybkaer K; Chiu A; Orazi A; Zu Y; Bhagat G; Richards KL; Hsi ED; Choi WW; Zhao X; van Krieken JH; Huang Q; Huh J; Ai W; Ponzoni M; Ferreri AJ; Zhou F; Slack GW; Gascoyne RD; Tu M; Variakojis D; Chen W; Go RS; Piris MA; Moller MB; Medeiros LJ; Young KH
INSTITUCIÓN / INSTITUTION: - Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States;
RESUMEN / SUMMARY: - Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes according to their gene-expression signatures. In this study, we assessed a cohort of 893 de novo DLBCL patients treated with R-CHOP therapy. We show that MYC/BCL2 protein co-expression occurred significantly more commonly in the ABC subtype. The ABC and GCB subtypes had similar prognoses in DLBCL with MYC/BCL2 co-expression as well as in DLBCL without MYC/BCL2 co-expression. Consistent with the notion that the prognostic difference between the two subtypes was attributable to MYC/BCL2 co-expression, the difference in gene-expression signatures between the two subtypes was dramatically diminished in the absence of MYC/BCL2 co-expression. Furthermore, DLBCL with MYC/BCL2 co-expression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 co-expression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. Furthermore, the data suggest that MYC/BCL2 co-expression, rather than cell of origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP therapy.
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[52]
TÍTULO / TITLE: - Azacitidine in the treatment of therapy related myelodysplastic syndrome and acute myeloid leukemia (tMDS/AML): A report on 54 patients by the Groupe Francophone Des Myelodysplasies (GFM).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Mar 14. pii: S0145-2126(13)00068-4. doi: 10.1016/j.leukres.2013.02.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.02.014
AUTORES / AUTHORS: - Bally C; Thepot S; Quesnel B; Vey N; Dreyfus F; Fadlallah J; Turlure P; de Botton S; Dartigeas C; de Renzis B; Itzykson R; Fenaux P; Ades L
INSTITUCIÓN / INSTITUTION: - Groupe Francophone des Myelodysplasies, France; Hopital Avicenne et universite Paris 13, APHP, Bobigny, France.
RESUMEN / SUMMARY: - The effect of azacitidine (AZA) in therapy related MDS and AML (t-MDS/AML) is not well established. 54 patients (42 t-MDS and 12 t-AML), 71% of whom had complex karyotype, received AZA for at least one cycle (median 4 cycles). The overall response rate (ORR) was 39% in the whole cohort and 62% in patients who received >/=4 cycles. One, 2 and 3 year OS was 36%, 14% and 8% respectively. Female gender (p=0.01) and ECOG 0-1 (p=0.04) were associated with significantly better OS, while karyotype and marrow blast percentage had no significant impact. By comparison with de novo MDS/AML treated in the same program, t-MDS/AML had a similar response rate (38% vs 45% in de novo MDS/AML, p=0.53), but significantly shorter OS (2 year OS of 14% vs 33.9%, p=0.0005). However, in a multivariate analysis performed in all patients (de novo and therapy related cases), only complex karyotype and high IPSS, and not etiology (i.e. de novo versus therapy related), had a significant impact on OS. Nine (15%) patients received allogeneic stem cell transplantation, 4 of whom were still alive.
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[53]
TÍTULO / TITLE: - Postoperative-stimulated serum thyroglobulin measured at the time of I ablation is useful for the prediction of disease status in patients with differentiated thyroid carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surgery. 2013 Mar 8. pii: S0039-6060(12)00756-8. doi: 10.1016/j.surg.2012.12.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.12.008
AUTORES / AUTHORS: - Lee JI; Chung YJ; Cho BY; Chong S; Seok JW; Park SJ
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUND: This study was conducted to identify the relevant cutoff value and to evaluate the usefulness of postoperative-stimulated serum thyroglobulin (Tg) at the time of 131I ablation for the prediction of disease status in patients with differentiated thyroid carcinoma (DTC) who received high-dose 131I ablation therapy after total thyroidectomy. METHODS: We analyzed 218 consecutively enrolled patients who were diagnosed with DTC and underwent total thyroidectomy. All patients underwent 131I ablation at doses of 100-200 mCi, and stimulated serum Tg was measured at the time of 131I ablation therapy. To assess disease-free status after 131I ablation therapy, stimulated serum Tg levels, diagnostic whole-body scan (DxWBS) and neck ultrasonography (US) were performed 6-12 months after 131I ablation. RESULTS: The relevant cutoff value of postoperative stimulated Tg for the prediction of disease-free status was 2 ng/mL. A total of 138 patients (63.3%) showed values of <2 ng/mL. Postoperative-stimulated Tg < 2 ng/mL had a negative predictive value of 94.9%, which increased to 97.7% when low Tg was combined with negative neck US findings. CONCLUSIONS: Postoperative-stimulated Tg at the time of 131I remnant ablation is a useful biochemical marker for the prediction of disease status in patients with DTC. When high-dose 131I remnant ablation is performed after total thyroidectomy, the stimulated Tg measurement and DxWBS that are usually performed 6-12 months after 131I ablation therapy may be skipped, at least in low- and intermediate-risk patients with postoperative stimulated Tg of < 2 ng/mL and negative neck US findings.
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[54]
TÍTULO / TITLE: - Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Mar 21. pii: S0959-8049(13)00163-9. doi: 10.1016/j.ejca.2013.02.031.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.02.031
AUTORES / AUTHORS: - Blamey RW; Bates T; Chetty U; Duffy SW; Ellis IO; George D; Mallon E; Mitchell MJ; Monypenny I; Morgan DA; Macmillan RD; Patnick J; Pinder SE
INSTITUCIÓN / INSTITUTION: - Nottingham City Hospital, Hucknall Rd., Nottingham NG5 1PB, United Kingdom.
RESUMEN / SUMMARY: - BACKGROUND: The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features. METHODS: Patients with primary invasive breast cancer <2cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2x2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both. FINDINGS: The actuarial breast cancer specific survival in 1135 randomised patients at 10years was 96%. Analysis by intention to treat showed that LR after WLE was reduced in patients randomised to radiotherapy (RT) (HR 0.37, CI 0.22-0.61 p<0.001) and to tamoxifen (HR 0.33, CI 0.15 - 0.70 p<0.004). Actuarial analysis of patients entered into the four-way randomisation showed that LR after WLE alone was 1.9% per annum (PA) versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomised to both adjuvant treatments developed LR. Analysis by treatment received showed LR at 2.2%PA for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments. CONCLUSIONS: Even in these patients with tumours of excellent prognosis, LR after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments.
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[55]
TÍTULO / TITLE: - Differential Contributions of STAT5A and STAT5B to Stress Protection and Tyrosine Kinase Inhibitor Resistance of Chronic Myeloid Leukemia Stem/Progenitor Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Apr 1;73(7):2052-8. doi: 10.1158/0008-5472.CAN-12-3955. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3955
AUTORES / AUTHORS: - Casetti L; Martin-Lanneree S; Najjar I; Plo I; Auge S; Roy L; Chomel JC; Lauret E; Turhan AG; Dusanter-Fourt I
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Inserm U1016, Institut Cochin; Universite Paris Descartes, Sorbonne Paris Cite, Paris; Inserm U1009, Villejuif; Inserm CIC0802, CHU; and Inserm U935, Universite and CHU, Poitiers, France.
RESUMEN / SUMMARY: - STAT5 fulfills essential roles in hematopoietic stem cell (HSC) self-renewal and chronic myeloid leukemia (CML), a prototypical stem cell malignancy. However, the specific contributions of the two related genes STAT5A and STAT5B have not been determined. In this study, we used a RNAi-based strategy to establish participation of these genes to CML disease and persistence following targeted therapy. We showed that STAT5A/STAT5B double-knockdown triggers CML cell apoptosis and suppresses both normal and CML HSC long-term clonogenic potential. STAT5A and STAT5B exhibited similar prosurvival activity, but STAT5A attenuation alone was ineffective at impairing growth of normal and CML CD34(+) cells isolated at diagnosis. In contrast, STAT5A attenuation was sufficient to enhance basal oxidative stress and DNA damage of normal CD34(+) and CML cells. Furthermore, it weakened the ability to manage exogenous oxidative stress, increased p53 (TRP53)/CHK-2 (CHEK2) stress pathway activation, and enhanced prolyl hydroxylase domain (PHD)-3 (EGLN3) mRNA expression. Only STAT5A and its transactivation domain-deficient mutant STAT5ADelta749 specifically rescued these activities. STAT5A attenuation was also active at inhibiting growth of CML CD34(+) cells from patients with acquired resistance to imatinib. Our findings show that STAT5A has a selective role in contributing to stress resistance through unconventional mechanisms, offering new opportunities to eradicate the most primitive and tyrosine kinase inhibitor-resistant CML cells with an additional potential to eradicate persistent stem cell populations. Cancer Res; 73(7); 2052-8. ©2013 AACR.
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[56]
TÍTULO / TITLE: - Large genomic aberrations detected by SNP array are independent prognosticators of a shorter time to first treatment in chronic lymphocytic leukemia patients with normal FISH.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds646
AUTORES / AUTHORS: - Mian M; Rinaldi A; Mensah AA; Rossi D; Ladetto M; Forconi F; Marasca R; Uhr M; Stussi G; Kwee I; Cavalli F; Gaidano G; Zucca E; Bertoni F
INSTITUCIÓN / INSTITUTION: - Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
RESUMEN / SUMMARY: - BackgroundGenomic complexity can predict the clinical course of patients affected by chronic lymphocytic leukemia (CLL) with a normal FISH. However, large studies are still lacking. Here, we analyzed a large series of CLL patients and also carried out the so far largest comparison of FISH versus single-nucleotide polymorphism (SNP) array in this disease.Patients and methodsSNP-array data were derived from a previously reported dataset.ResultsSeventy-seven of 329 CLL patients (23%) presented with a normal FISH. At least one large (>5 Mb) genomic aberration was detected by SNP array in 17 of 77 patients (22%); this finding significantly affected TTT. There was no correlation with the presence of TP53 mutations. In multivariate analysis, including age, Binet stage, IGHV genes mutational status and large genomic lesion, the latter three factors emerged as independent prognosticators. The concordance between FISH and SNP array varied between 84 and 97%, depending on the specific genomic locus investigated.ConclusionsSNP array detected additional large genomic aberrations not covered by the standard FISH panel predicting the outcome of CLL patients.
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[57]
TÍTULO / TITLE: - Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 21. doi: 10.1038/bjc.2013.115.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.115
AUTORES / AUTHORS: - El Hajj P; Journe F; Wiedig M; Laios I; Sales F; Galibert MD; Van Kempen LC; Spatz A; Badran B; Larsimont D; Awada A; Ghanem G
INSTITUCIÓN / INSTITUTION: - Laboratoire d’Oncologie et de Chirurgie Experimentale, Institut Jules Bordet, Universite Libre de Bruxelles, B1000 Brussels, Belgium.
RESUMEN / SUMMARY: - Background:Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients.Methods:TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion.Results:A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P=0.005 and 0.01, respectively), increased Breslow thickness (Spearman’s rho test, P<0.001) and the presence of ulceration (Mann-Whitney test, P=0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P-value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups.Conclusion:High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients.British Journal of Cancer advance online publication, 21 March 2013; doi:10.1038/bjc.2013.115 www.bjcancer.com.
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[58]
TÍTULO / TITLE: - Androgen receptor expression is a predictive marker in chemotherapy-treated patients with endocrine receptor-positive primary breast cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cancer Res Clin Oncol. 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s00432-013-1382-8
AUTORES / AUTHORS: - Witzel I; Graeser M; Karn T; Schmidt M; Wirtz R; Schutze D; Rausch A; Janicke F; Milde-Langosch K; Muller V
INSTITUCIÓN / INSTITUTION: - Department of Gynecology, University Medical Center, Martinistrasse 52, 20246, Hamburg, Germany, iwitzel@uke.de.
RESUMEN / SUMMARY: - PURPOSE: The androgen receptor (AR) is intensively discussed as a prognostic and/or predictive marker in breast cancer patients. METHODS: We evaluated the value of AR mRNA expression with the Affymetrix HG-U 133A array in 3 different cohorts: a cohort of breast cancer patients who received adjuvant treatment (cohort A; n = 165), a cohort of untreated breast cancer patients (cohort B; n = 200) and a cohort of chemotherapy-treated breast cancer patients with estrogen receptor (ER)-positive tumors (cohort C; n = 223). RESULTS: AR mRNA expression was associated with lower grading (Grades 1 and 2) as well as ER and progesterone receptor (PgR) positivity in all cohorts. In the treated cohort (cohort A), low androgen receptor expression was associated with shorter event-free survival (OR 2,34, 95 % CI 1.01-5.43, p = 0.047) which was not seen in the untreated cohort B. Subgroup analysis revealed that shorter survival of patients with low AR mRNA expression was observed mainly in the ER-positive subgroup of patients treated with adjuvant chemotherapy. In the validation cohort C we could confirm a benefit of chemotherapy for the group of tumors with high AR mRNA expression (5-year event-free survival (EFS) 74 % versus 57 %, p = 0.013). In this cohort, low AR mRNA expression was associated with shorter event-free survival also in multivariate analysis (OR 2.86, 95 % CI 1.29-6.35, p = 0.010) adjusted for HER2, ki-67, tumor size, age and tumor grade. CONCLUSIONS: We provide evidence that AR expression is associated with chemotherapy responsiveness in ER-positive patients.
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[59]
TÍTULO / TITLE: - Increased expression of metadherin protein predicts worse disease-free and overall survival in laryngeal squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Jan 30. doi: 10.1002/ijc.28071.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28071
AUTORES / AUTHORS: - Liu Y; Su Z; Li G; Yu C; Ren S; Huang D; Fan S; Tian Y; Zhang X; Qiu Y
INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China.
RESUMEN / SUMMARY: - Metadherin (MTDH) is involved in tumourigenesis and cancer progression in multiple human malignancies. However, the MTDH protein has rarely been reported in laryngeal squamous cell carcinoma (LSCC). The expression pattern of the MTDH protein in 176 primary archival LSCC and 27 corresponding adjacent noncarcinoma specimens was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results demonstrated that 161 (91.48%) primary LSCC samples stained positive for MTDH; however, staining was barely detectable in all adjacent noncarcinoma samples. Moreover, the expression of the MTDH protein was significantly associated with the primary tumour site (p = 0.021), T classification (p = 0.002), clinical stage (I + II/III + IV; p < 0.001), lymph node metastasis (p < 0.001) and postoperational recurrence (p < 0.001). Kaplan-Meier analysis revealed that MTDH expression was significantly associated with worse disease-free survival (DFS) and overall survival (OS) rates in patients with LSCC (both p < 0.001). When lymph node metastasis and MTDH expression were considered together, patients with lymph node metastasis and high MTDH expression had both poorer DFS and OS rates than others (both p < 0.001). Finally, multivariate analysis demonstrated that MTDH expression was an independent prognostic factor for both DFS and OS rates in patients with LSCC. Strong MTDH expression was negatively correlated with a canonical epithelial-mesenchymal transition molecule E-cadherin (p < 0.001) and positively associated with proangiogenic protein vascular endothelial growth factor (p < 0.001). MTDH overexpression was tightly associated with more aggressive tumour behaviour and a poor prognosis, indicating that MTDH is a valuable molecular biomarker for LSCC progression.
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[60]
TÍTULO / TITLE: - Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Causes Control. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s10552-013-0169-1
AUTORES / AUTHORS: - Simonsson M; Soderlind V; Henningson M; Hjertberg M; Rose C; Ingvar C; Jernstrom H
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Clinical Sciences, Lund, Lund University, Barngatan 2B, 22185, Lund, Sweden.
RESUMEN / SUMMARY: - PURPOSE: Whether coffee modulates response to endocrine therapy in breast cancer patients is currently unknown. The CYP1A2 and CYP2C8 enzymes contribute to tamoxifen and caffeine metabolism. The purpose was to investigate the impact of coffee consumption on tumor characteristics and risk for early events in relation to breast cancer treatment and CYP1A2 and CYP2C8 genotypes. METHODS: Questionnaires regarding lifestyle were completed preoperatively by 634 patients in southern Sweden. CYP1A2*1F and CYP2C8*3 were genotyped. Clinical data and tumor characteristics were obtained from patients’ charts, population registries, and pathology reports. Coffee consumption was categorized as low (0-1 cups/day), moderate (2-4 cups/day), or high (5+ cups/day). RESULTS: The proportion of estrogen receptor negative (ER-) tumors increased with increasing coffee consumption (p (trend) = 0.042). Moderate to high consumption was associated with lower frequency of discordant receptor status (ER + PgR-) OR 0.38 (0.23-0.63) compared to low consumption. Median follow-up time was 4.92 (IQR 3.01-6.42) years. Tamoxifen-treated patients with ER+ tumors (n = 310) who consumed two or more cups/day had significantly decreased risk for early events compared to patients with low consumption, adjusted HR 0.40 (0.19-0.83). Low consumption combined with at least one CYP1A2*1F C-allele (n = 35) or CYP2C8*3 (n = 13) was associated with a high risk for early events in tamoxifen-treated patients compared to other tamoxifen-treated patients, adjusted HRs 3.49 (1.54-7.91) and 6.15 (2.46-15.36), respectively. CONCLUSION: Moderate to high coffee consumption was associated with significantly decreased risk for early events in tamoxifen-treated patients and modified hormone receptor status. If confirmed, new recommendations regarding coffee consumption during tamoxifen treatment may be warranted.
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[61]
TÍTULO / TITLE: - Lenalidomide in International Prognostic Scoring System Low and Intermediate-1 risk myelodysplastic syndromes with del(5q): an Italian phase II trial of health-related quality of life, safety and efficacy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.778406
AUTORES / AUTHORS: - Oliva EN; Latagliata R; Lagana C; Breccia M; Galimberti S; Morabito F; Poloni A; Balleari E; Cortelezzi A; Palumbo G; Sanpaolo G; Volpe A; Specchia G; Finelli C; D’Errigo MG; Roda F; Alati C; Alimena G; Nobile F; Aloe Spiriti MA
INSTITUCIÓN / INSTITUTION: - “Bianchi-Melacrino-Morelli” Hospital , Reggio Calabria , Italy.
RESUMEN / SUMMARY: - In lower-risk myelodysplastic syndromes (MDS) with del(5q), lenalidomide induces erythroid responses associated with better survival. In a phase II, single-arm trial, 45 patients with anemia and lower-risk del(5q) MDS received lenalidomide 10 mg/day to evaluate quality of life (QoL) changes, measured by QOL-E, safety, responses and survival. Lenalidomide was well tolerated, with 80% completing >/= 24 weeks of treatment. Earlier study discontinuation was related to disease progression (n = 5), death (n = 1) and withdrawal of consent (n = 3). Within 24 weeks, 82% obtained erythroid responses, durable in 69% at 52 weeks. Cytogenetic responses occurred in 29 patients (64%), with 10 patients achieving a complete cytogenetic response. QoL-E scores correlated with hemoglobin levels and improved in erythroid responders. Erythroid responders had an 86% reduced risk of disease progression and an 80% reduction in mortality risk compared with non-responders. These findings corroborate earlier studies and give further support to the use of lenalidomide in lower-risk MDS and del(5q).
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[62]
TÍTULO / TITLE: - Phase II Trial Assessing Granulocyte-macrophage-Colony Stimulating Factor, Ketoconazole Plus Mitoxantrone in Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel Treatments.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Invest. 2013 Mar;31(3):177-82. doi: 10.3109/07357907.2013.764564. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2013.764564
AUTORES / AUTHORS: - Amato RJ; Saxena S; Stepankiw M
INSTITUCIÓN / INSTITUTION: - The University of Texas Health Science Center at Houston, Department of Internal Medicine, Division of Oncology , Houston, Texas , USA,1.
RESUMEN / SUMMARY: - Introduction: This study evaluated objective response and safety for the combination of granulocyte macrophage-colony stimulating factor (GM-CSF), ketoconazole, and mitoxantrone in castration-resistant prostate cancer (CRPC) patients who previously failed docetaxel-based chemotherapy. Methods: Treatment consisted of 400 mg TID ketoconazole, 12 mg/m mitoxantrone every 3 weeks, and 250 mug/m GM-CSF. Results: Twenty-nine patients were evaluable for response. Median overall survival (OS) for all patients was 18.03 months. Patients with a higher PSA decrease experienced an increased OS and progression-free survival (PFS). Conclusion: This combination demonstrated significant antitumor activity with reversible toxicity in CRPC patients who previously failed docetaxel-based therapy.
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[63]
TÍTULO / TITLE: - Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 12. pii: S0145-2126(13)00018-0. doi: 10.1016/j.leukres.2013.01.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.004
AUTORES / AUTHORS: - Ades L; Sekeres MA; Wolfromm A; Teichman ML; Tiu RV; Itzykson R; Maciejewski JP; Dreyfus F; List AF; Fenaux P; Komrokji RS
INSTITUCIÓN / INSTITUTION: - Groupe Francophone des Myelodysplasies, France. Electronic address: lionel.ades@avc.aphp.fr.
RESUMEN / SUMMARY: - Treatment of CMML remains a clinical challenge, with no drug demonstrating clear clinical benefit. Even if azacitidine is approved in the treatment of CMML, its role remains disputed. We report a cohort of 76 CMML patients (according to WHO classification) treated with azacitidine in 3 programs (French AZA compassionate program, Cleveland Clinic Foundation and H. Lee Moffitt Cancer Center). 45% had CMML2, and 55% had splenomegaly and/or WBC counts >13G/L, which are known to be poor prognostic factors in CMML. All patients received AZA for at least one cycle, and the median number of cycles administered was 6. Thirty-three patients (43%) achieved a response according to IWG 2006 criteria, including 13 complete remissions (%). Median survival was 29 months. Increased bone marrow blast percentage and proliferative features of the disease, including splenomegaly and high WBC counts, were significantly associated with shorter survival. By multivariate analysis, only marrow blasts >10% and palpable splenomegaly had prognostic impact on survival. Although promising, the efficacy of azacitidine in advanced CMML needs to be confirmed in a randomized prospective study.
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[64]
TÍTULO / TITLE: - Cetuximab-activated natural killer and dendritic cells collaborate to trigger tumor antigen-specific T-cell immunity in head and neck cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 1;19(7):1858-72. doi: 10.1158/1078-0432.CCR-12-2426. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2426
AUTORES / AUTHORS: - Srivastava RM; Lee SC; Andrade Filho PA; Lord CA; Jie HB; Davidson HC; Lopez-Albaitero A; Gibson SP; Gooding WE; Ferrone S; Ferris RL
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Otolaryngology, Surgery, Pathology, and Immunology, University of Pittsburgh; Biostatistics Facility and Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
RESUMEN / SUMMARY: - PURPOSE: Tumor antigen-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcgamma receptor (FcgammaR)-mediated cytotoxicity. However, the role of CD8(+) CTL and FcgammaR in initiating innate and adaptive immune responses in mAb-treated human patients with cancer is still emerging. EXPERIMENTAL DESIGN: FcgammaRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated patients with head and neck cancer (HNC). Flow cytometry was carried out to quantify EGF receptor (EGFR)-specific T cells in cetuximab-treated patients with HNC. The effect of cetuximab on natural killer (NK) cell, dendritic cell (DC), and T-cell activation was measured using IFN-gamma release assays and flow cytometry. RESULTS: FcgammaRIIIa polymorphism did not predict clinical outcome in cetuximab-treated patients with HNC; however, elevated circulating EGFR853-861-specific CD8(+) T cells were found in cetuximab-treated patients with HNC (P < 0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR(+) tumor cells and FcgammaRIIIa on NK cells but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-gamma-dependent expression of DC maturation markers, antigen processing machinery components such as TAP-1/2 and T-helper cell (TH1) chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK cell-induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another tumor antigen, MAGE-3. CONCLUSION: Cetuximab-activated NK cells promote DC maturation and CD8(+) T-cell priming, leading to tumor antigen spreading and TH1 cytokine release through “NK-DC cross-talk.” FcgammaRIIIa polymorphism did not predict clinical response to cetuximab but was necessary for NK-DC interaction and mAb-induced cross-presentation. EGFR-specific T cells in cetuximab-treated patients with HNC may contribute to clinical response. Clin Cancer Res; 19(7); 1858-72. ©2013 AACR.
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[65]
TÍTULO / TITLE: - A dose finding, safety and pharmacokinetic study of AVE1642, an anti-insulin-like growth factor-1 receptor (IGF-1R/CD221) monoclonal antibody, administered as a single agent and in combination with docetaxel in patients with advanced solid tumours.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Feb 26. pii: S0959-8049(13)00030-0. doi: 10.1016/j.ejca.2013.01.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.003
AUTORES / AUTHORS: - Soria JC; Massard C; Lazar V; Ozoux ML; Mery-Mignard D; Deslandes A; Tolcher AW
INSTITUCIÓN / INSTITUTION: - Universite Paris XI, SITEP (Service des Innovations Therapeutiques Precoces), Departement de Medecine, Institut Gustave Roussy, Villejuif, France. Electronic address: soria@igr.fr.
RESUMEN / SUMMARY: - PURPOSE: AVE1642, a humanised mAb, binds the human IGF-1R specifically and with high affinity. This study aimed to select the dose of AVE1642 alone and then combined with docetaxel 75mg/m2 (D). MATERIAL AND METHODS: AVE1642 was administered alone at cycle (cy) 1 and then combined with D from cy2, q3w. RESULTS: A total of 27 patients received a median number of 5 cy (range, 1-10). The most common tumour types were sarcoma (18.5%), osseous tumours (11.1%) and colon cancer (11.1%). Two DLTs were reported in cy1 at dose level (DL) 18mg/kg and dose escalation was stopped. No major safety issue was observed. No anti-drug antibodies were detected. The Maximal Tolerated Dose of AVE1642 was 12mg/kg. The dose selected for further combinations is 6mg/kg, based on PK/PD data. Three objective responses, (two in sarcoma and one breast cancer) were observed but only one was confirmed. Eleven patients appeared to benefit from treatment with prolonged disease stabilisation 4months. CONCLUSION: AVE1642 is well tolerated as a single agent and combined with D. The selected dose of AVE1642 combined with D is 6mg/kg. Promising activity was seen in sarcoma and breast cancer patients.
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[66]
TÍTULO / TITLE: - Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Proc Natl Acad Sci U S A. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1219232110
AUTORES / AUTHORS: - Sievert AJ; Lang SS; Boucher KL; Madsen PJ; Slaunwhite E; Choudhari N; Kellet M; Storm PB; Resnick AC
INSTITUCIÓN / INSTITUTION: - Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104.
RESUMEN / SUMMARY: - Astrocytomas are the most common type of brain tumors in children. Activated BRAF protein kinase mutations are characteristic of pediatric astrocytomas with KIAA1549-BRAF fusion genes typifying low-grade astrocytomas and V600EBRAF alterations characterizing distinct or higher-grade tumors. Recently, BRAF-targeted therapies, such as vemurafenib, have shown great promise in treating V600E-dependent melanomas. Like V600EBRAF, BRAF fusion kinases activate MAPK signaling and are sufficient for malignant transformation; however, here we characterized the distinct mechanisms of action of KIAA1549-BRAF and its differential responsiveness to PLX4720, a first-generation BRAF inhibitor and research analog of vemurafenib. We found that in cells expressing KIAA1549-BRAF, the fusion kinase functions as a homodimer that is resistant to PLX4720 and accordingly is associated with CRAF-independent paradoxical activation of MAPK signaling. Mutagenesis studies demonstrated that KIAA1549-BRAF fusion-mediated signaling is diminished with disruption of the BRAF kinase dimer interface. In addition, the KIAA1549-BRAF fusion displays increased binding affinity to kinase suppressor of RAS (KSR), an RAF relative recently demonstrated to facilitate MEK phosphorylation by BRAF. Despite its resistance to PLX4720, the KIAA1549-BRAF fusion is responsive to a second-generation selective BRAF inhibitor that, unlike vemurafenib, does not induce activation of wild-type BRAF. Our data support the development of targeted treatment paradigms for BRAF-altered pediatric astrocytomas and also demonstrate that therapies must be tailored to the specific mutational context and distinct mechanisms of action of the mutant kinase.
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[67]
TÍTULO / TITLE: - Efficacy of goserelin plus anastrozole in premenopausal women with advanced or recurrent breast cancer refractory to an LH-RH analogue with tamoxifen: Results of the JMTO BC08-01 phase II trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 27. doi: 10.3892/or.2013.2312.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2312
AUTORES / AUTHORS: - Nishimura R; Anan K; Yamamoto Y; Higaki K; Tanaka M; Shibuta K; Sagara Y; Ohno S; Tsuyuki S; Mase T; Teramukai S
INSTITUCIÓN / INSTITUTION: - Department of Breast and Endocrine Surgery, Kumamoto City Hospital, Kumamoto 862-8505, Japan.
RESUMEN / SUMMARY: - The aim of the present study was to assess the efficacy and tolerability of a luteinizing hormone-releasing hormone (LH-RH) analogue plus an aromatase inhibitor following failure to respond to standard LH-RH analogue plus tamoxifen (TAM) in premenopausal patients. Premenopausal women with estrogen receptor (ER)-positive and/or progesterone-receptor positive, advanced or recurrent breast cancer refractory to an LH-RH analogue plus TAM received goserelin (GOS) in conjunction with anastrozole (ANA). The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and safety. Between September 2008 and November 2010, 37 patients were enrolled. Thirty-five patients (94.6%) had ER-positive tumors, and 36 (97.3%) had human epidermal growth factor receptor (HER) 2-negative tumors. Thirty-six (97.3%) had measurable lesions and 1 (2.7%) had only bone metastasis. The ORR was 18.9% [95% confidence interval (CI), 8.0-35.2%], the CBR was 62.2% (95% CI, 44.8-77.5%) and the median PFS was 7.3 months. Eight patients had adverse drug reactions but none resulted in discontinuation of treatment. GOS plus ANA is a safe effective treatment for premenopausal women with hormone receptor-positive, recurrent or advanced breast cancer. The treatment may become viable treatment in the future, particularly when TAM is ineffective or contraindicated. Further studies and discussion are warranted.
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[68]
TÍTULO / TITLE: - High levels of bcl-2 protein expression do not correlate with genetic abnormalities but predict worse prognosis in patients with lymphoblastic lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0647-9
AUTORES / AUTHORS: - Gu Y; Pan Y; Meng B; Guan B; Fu K; Sun B; Zheng F
INSTITUCIÓN / INSTITUTION: - Department of Clinical Immunology, School of Medical Laboratory, Tianjin Medical University, Tianjin, 300203, China.
RESUMEN / SUMMARY: - We aimed to investigate bcl-2, bcl-6, and c-myc rearrangements in patients with lymphoblastic lymphoma (LBL), especially focus on the correlation of protein expression with genetic abnormalities. Moreover, their prognostic significance was further analyzed in LBL. Protein expression and genetic abnormalities of bcl-2, bcl-6, and c-myc were investigated in microarrayed tumors from 33 cases of T cell LBL and eight cases of B cell lineage. Immunohistochemical (IHC) staining was performed to evaluate protein expression, including bcl-2, bcl-6, c-myc, TdT, CD1alpha, CD34, Ki-67, PAX-5, CD2, CD3, CD4, CD8, and CD20. Genetic abnormalities of bcl-2, bcl-6, and c-myc were detected by dual color fluorescence in situ hybridization (FISH). Bcl-2 protein was positive in 51.2 % (21/41) of the patients, bcl-6 protein in 7.3 % (three out of 41), and c-myc protein in 78.0 % (32/41). Bcl-2 breakpoint was found in two cases by FISH analysis. There was no evidence of bcl-6 or c-myc rearrangement in patients with LBL. However, both gene gain and loss events occurred in bcl-2, bcl-6, and c-myc. A univariate analysis showed that stage III or IV, elevated lactate dehydrogenase (LDH), and positivity for bcl-2 protein were associated with shorter survival (p < 0.05). Enhanced protein expression and detectable genetic abnormalities of bcl-2, bcl-6, and c-myc were observed in patients with LBL. No statistical correlation was found between IHC results and cytogenetic findings. Stage III or IV, elevated LDH, and positivity for bcl-2 protein were identified as adverse prognostic factors. The patients with more adverse factors would have increasingly worse prognosis.
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[69]
TÍTULO / TITLE: - The Influence of MTHFR Gene Polymorphisms on the Outcome of Pediatric Non-Hodgkin Lymphoma Patients Treated with High-Dose Methotrexate.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.784758
AUTORES / AUTHORS: - D’Angelo V; Ramaglia M; Iannotta A; Francese M; Pota E; Affinita MC; Pecoraro G; Indolfi C; Di Martino M; Di Pinto D; Buffardi S; Poggi V; Indolfi P; Casale F
RESUMEN / SUMMARY: - Abstract High-dose Methotrexate (MTX) is a key component of most treatment protocols for childhood and adolescent NHL. Recent studies have suggested that the toxicity of antifolate drugs, such as MTX, is affected by inherited single nucleotide polymorphisms (SNPs) in folate metabolising genes. The aim of our study was to investigate the potential influence of the C677T and A1298C genetic variants of MTHFR on the clinical toxicity and efficacy of MTX in paediatric NHL patients (n=95) treated with therapeutic protocols AIEOP NHL 97 and EURO LB-02. We demonstrated that patients with the 677T genotype had an approximately 6-fold greater risk of developing haematological toxicity compared with wild-type carriers, especially in the 1 g/sq m treatment group (p=0.01). Moreover, we identified a correlation between the risk of relapse and the T genotype; T carriers have a reduced DFS compared with wild-type patients (67% vs. 100%). Our data suggest a pharmacogenetic influence on the adverse effects of high-dose MTX in the 1 g/sq m treatment group.
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[70]
TÍTULO / TITLE: - Azacitidine as salvage therapy in elderly patients with relapsed acute myeloid leukemia after autologous transplantation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hematol. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s00277-013-1732-2
AUTORES / AUTHORS: - Breccia M; Salaroli A; Serrao A; Alimena G
INSTITUCIÓN / INSTITUTION: - Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy, breccia@bce.uniroma1.it.
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[71]
TÍTULO / TITLE: - Effect of the BCL2 Gene Polymorphism on Survival in Advanced-Stage Non-Small Cell Lung Cancer Patients Who Received Chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncology. 2013;84(4):214-8. doi: 10.1159/000342854. Epub 2013 Jan 24.
●● Enlace al texto completo (gratuito o de pago) 1159/000342854
AUTORES / AUTHORS: - Masago K; Togashi Y; Fujita S; Nagai H; Sakamori Y; Okuda C; Kim YH; Mishima M
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
RESUMEN / SUMMARY: - Introduction: This study aimed to evaluate the association between BCL2 single-nucleotide polymorphisms and survival outcome in advanced non-small cell lung cancer (NSCLC). Methods: One hundred and sixty-eight patients with advanced NSCLC who were treated with anti-cancer drugs and could be evaluated for therapeutic response between April 2005 and March 2010 at Kyoto University Hospital were enrolled. DNA was extracted from peripheral blood samples. The BCL2 polymorphisms -938 C-->A (rs2279115) and +21 A-->G (rs1801018) were genotyped using the 5’-nuclease assay. The univariate relationship between each independent clinicopathologic variable and BCL2 genotype was examined using Fisher’s exact test. To evaluate risk factors associated with prognosis, a Cox proportional hazards regression model with a step-down procedure was used. Results: The median survival time of patients with the -938 AA and AC genotypes were significantly shorter than those with the -938 CC genotype (p = 0.027 by log-rank test). Based on multivariate analysis, poor performance status [hazard ratio (HR) 2.424, 95% confidence interval (CI) 1.727-3.262; p < 0.0001], non-adenocarcinoma histology (HR 1.512, 95% CI 1.167-1.938; p = 0.0048) and the BCL2 -938 AA + AC genotype (HR 1.219, 95% CI, 1.024-1.456; p = 0.0256) were significant independent prognostic factors for survival. Conclusions: Polymorphisms in BCL2 may be associated with survival in advanced-stage NSCLC patients who received chemotherapy.
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[72]
TÍTULO / TITLE: - Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Mar 9. pii: S0360-3016(12)03914-4. doi: 10.1016/j.ijrobp.2012.12.018.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.12.018
AUTORES / AUTHORS: - Kim JC; Ha YJ; Roh SA; Cho DH; Choi EY; Kim TW; Kim JH; Kang TW; Kim SY; Kim YS
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Ulsan College of Medicine, Seoul, Korea; Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea. Electronic address: jckim@amc.seoul.kr.
RESUMEN / SUMMARY: - PURPOSE: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. METHODS AND MATERIALS: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. RESULTS: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele © of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). CONCLUSION: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts.
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[73]
TÍTULO / TITLE: - Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cardiology. 2013;124(3):190-8. doi: 10.1159/000346621. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1159/000346621
AUTORES / AUTHORS: - Osmancik P; Herman D; Stros P; Linkova H; Vondrak K; Paskova E
INSTITUCIÓN / INSTITUTION: - Cardiocenter, Department of Cardiology, Third Medical School, Charles University and University Hospital Kralovske Vinohrady Prague, Prague, Czech Republic.
RESUMEN / SUMMARY: - Objectives: In patients with heart failure, increased apoptosis, inflammation and activation of the transforming growth factor (TGF)-beta cytokine system have been documented. The aim of the present study was to establish (i) whether cytokine concentrations decrease in patients who respond to cardiac resynchronization therapy (CRT), and (ii) whether pre-implant values have any prognostic value. Methods: Eighty-one CRT candidates were prospectively studied. The success of CRT was assessed based on clinical and echocardiographic improvement 6 months after implantation. Mortality was assessed 2 years after implantation. Blood samples were drawn before and 6 months after implantation. Serum concentrations of Fas, TNF-related apoptosis-inducing ligand, tumor necrosis factor (TNF)-alpha, TNF-receptor 1, TGF-beta1 and interleukin (IL)-6 were measured using ELISA. Results: At 6 months, 46 (56.8%) patients were classified as responders and 35 (43.2%) as nonresponders. Neither group differed with respect to baseline characteristics. In responders, the concentrations of IL-6, TNF-alpha and TGF-beta1 decreased significantly. In nonresponders, the concentration of TGF-beta1 even increased significantly. In multivariate analysis, the concentration of TGF-beta1 was a significant predictor of death during follow-up. Conclusions: The response to CRT implantation was associated with a decrease of TGF-beta1, IL-6 and TNF-alpha. Higher pre-implant concentrations of TGF-1beta were independently associated with a poor prognosis in CRT patients.
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[74]
TÍTULO / TITLE: - The predictive value of BRCA1 and RAP80 mRNA expression in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Apr;24(4):1130-2. doi: 10.1093/annonc/mdt063. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt063
AUTORES / AUTHORS: - Bonanno L; Costa C; Majem M; Favaretto A; Rugge M; Rosell R
INSTITUCIÓN / INSTITUTION: - Second Medical Oncology Unit, Istituto Oncologico Veneto IOV-I.R.C.C.S, Padova, Italy.
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[75]
TÍTULO / TITLE: - Early increase in alpha-fetoprotein for predicting unfavorable clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Gastroenterol Hepatol. 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1097/MEG.0b013e32835d913b
AUTORES / AUTHORS: - Nakazawa T; Hidaka H; Takada J; Okuwaki Y; Tanaka Y; Watanabe M; Shibuya A; Minamino T; Kokubu S; Koizumi W
INSTITUCIÓN / INSTITUTION: - aDepartment of Gastroenterology, Internal Medicine, Kitasato University School of Medicine bNakazawa Medical Clinic, Sagamihara cDepartment of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan.
RESUMEN / SUMMARY: - BACKGROUND: To determine the value of early alterations of the tumor markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) for predicting the outcomes of patients with advanced hepatocellular carcinoma (HCC) who receive sorafenib. MATERIALS AND METHODS: Tumor response, overall survival (OS), and progression-free survival (PFS) were retrospectively analyzed in 59 patients with advanced HCC. Serum AFP and DCP were examined for early elevation within 4 weeks after the initiation of sorafenib. An increase in AFP was defined as AFP of more than 20%, and an increase in DCP was defined as more than two-fold higher level than the baseline. The relationship of the clinical characteristics, laboratory data at baseline, and early elevations of AFP and DCP with disease progression was analyzed. RESULTS: The median OS and PFS were 11 and 3.3 months, respectively. The rate of progressive disease (PD) was 54%, and an early increase in AFP was significantly related to PD (P=0.006) and was a significant independent predictor of both poorer OS and PFS (P<0.001, hazard ratio, 4.14; 95% confidence interval, 1.946-8.811; and P=0.001, hazard ratio, 2.852; 95% confidence interval, 1.524-5.337, respectively). There was no association between early increase in DCP and clinical outcomes. CONCLUSION: Early increase in AFP predicted PD and poorer survival and may thus be a useful biomarker in patients with advanced HCC who receive sorafenib.
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[76]
TÍTULO / TITLE: - Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 19;108(5):1052-60. doi: 10.1038/bjc.2013.69. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.69
AUTORES / AUTHORS: - Miles DW; de Haas SL; Dirix LY; Romieu G; Chan A; Pivot X; Tomczak P; Provencher L; Cortes J; Delmar PR; Scherer SJ
INSTITUCIÓN / INSTITUTION: - Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, London, HA6 2RN, UK.
RESUMEN / SUMMARY: - Background:Combining bevacizumab with first-line chemotherapy significantly improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC). However, identification of patients benefitting most from bevacizumab remains elusive. The AVADO trial included an extensive optional exploratory biomarker programme.Methods:Patients with HER2-negative mBC were randomised to receive docetaxel with placebo or bevacizumab. The primary end point was PFS. Plasma samples were analysed using a multiplex ELISA. Blood mRNA expression was assessed using quantitative PCR. Tumour tissue samples were analysed by immunohistochemistry. Single-nucleotide polymorphisms (SNPs) involved in the VEGF pathway were analysed in germline DNA.Results:Samples for biomarker analysis were available from 24-54% of the 736 treated patients (depending on specimen type). The most consistent potential predictive effect was observed with plasma VEGF-A and VEGFR-2; high baseline concentrations were associated with greater treatment effect. Blood mRNA analyses suggested a greater bevacizumab effect in patients with high VEGF121. No consistent predictive effect was seen for tumour neuropilin or other candidate tumour markers by immunohistochemistry, or for any of the SNPs investigated.Conclusion:Plasma VEGF-A and VEGFR-2 are potential predictive markers for bevacizumab efficacy, supporting findings in gastric and pancreatic cancers. Plasma VEGF-A is being evaluated prospectively in mBC in the MERiDiAN trial.
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[77]
TÍTULO / TITLE: - Clinical response, drug survival and predictors thereof among 548 switchers of tumor necrosis factor alpha inhibitor therapy in psoriatic arthritis. Results from the Danish nationwide DANBIO registry.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arthritis Rheum. 2013 Mar 4. doi: 10.1002/art.37876.
●● Enlace al texto completo (gratuito o de pago) 1002/art.37876
AUTORES / AUTHORS: - Glintborg B; Ostergaard M; Krogh NS; Andersen MD; Tarp U; Loft AG; Lindegaard HM; Holland-Fischer M; Nordin H; Jensen DV; Olsen CH; Hetland ML
INSTITUCIÓN / INSTITUTION: - Department of Rheumatology, Gentofte University Hospital, Copenhagen, Denmark; The Danish Rheumatologic Database (DANBIO, Denmark. glintborg@dadlnet.dk.
RESUMEN / SUMMARY: - OBJECTIVE: To describe switch frequencies and outcomes among patients with psoriatic arthritis switching tumor-necrosis-factor-alpha inhibitor (TNFi) treatment in routine care. METHODS: Observational cohort study based on the Danish nationwide DANBIO registry. Treatment outcomes were evaluated by ACR20/50/70-responses, EULAR-good-response and 28-joint Disease Activity Score (DAS28)-remission. Kaplan-Meier and regression analyses were used for drug survival analyses and to identify predictors of outcome after switching. RESULTS: Of 1,422 patients starting TNFi, 548 patients (39%) switched to a second biological drug during up to 10 years’ follow-up. Median follow-up was 2.3 years (interquartile-range, IQR 1.0-4.3 years). Switchers were more frequently women (56%/45%), had shorter disease duration (3 years/4 years), higher Health Assessment Questionnaire (HAQ) (1.1(0.6-1.6)/0.9(0.5-1.4) (median(IQR))), DAS28 (4.8(4.0-5.7)/4.4(3.6-5.2)), visual-analogue-scale (VAS) pain (65(46-77)/62(40-75)mm) and fatigue scores (67(50-83)/64(42-80)mm) (all p<0.05 at start of first TNFi). During the first and second treatment HAQ, DAS28, CRP and VAS-scores had decreased after 6 months’ (all p<0.05), median drug survivals were 2.2 vs. 1.3 years (p<0.001). Lower fatigue score increased survival of the second TNFi. After switching, the proportions of patients achieving sustained ACR20/ACR50/ACR70/EULAR-good-response/DAS28-remission after 3-6 months were 22% (number-needed-to-treat, NNT 4.5)/13%(7.9)/5%(20)/19%(5.3)/34%(2.9) respectively. Response rates were lower during the second treatment (compared to first TNFi, all p<0.01). At the 2-year visit, 47% of switchers had achieved ACR20 response. No differences between drug-drug combinations were found. CONCLUSION: 39% of psoriatic arthritis patients switched TNFi. Response rates and drug survivals were lower after switching, however, half of switchers had ACR20 response 2 years after starting the first TNFi.
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[78]
TÍTULO / TITLE: - Insulin-like growth factor 1 and musculoskeletal pain among breast cancer patients on aromatase inhibitor therapy and women without a history of cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cancer Res Clin Oncol. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s00432-013-1391-7
AUTORES / AUTHORS: - Gallicchio L; Macdonald R; Helzlsouer KJ
INSTITUCIÓN / INSTITUTION: - The Prevention and Research Center, The Weinberg Center for Women’s Health and Medicine, Mercy Medical Center, 227 St. Paul Place, 6th Floor, Baltimore, MD, 21202, USA, lgallic@mdmercy.com.
RESUMEN / SUMMARY: - PURPOSE: Musculoskeletal pain is a common side effect of aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen-receptor-positive breast cancer. Although the pain is usually attributed to the estrogen depletion associated with AIs, not all women on AIs experience these symptoms. Thus, the goal of this study was to examine whether changes in the insulin-like growth factor (IGF) axis were associated with pain among women initiating AI therapy or a comparison group of women without a history of cancer. METHODS: Data were analyzed from a cohort study of 52 breast cancer patients for whom AI therapy was planned and 88 women without a history of cancer. Questionnaire data on pain symptoms were collected, and blood was drawn at baseline (prior to AI therapy for patients) and 6 months after baseline. The blood samples were assayed for IGF-1 and IGF-binding protein-3 (IGFBP-3). RESULTS: While results showed no statistically significant changes in any of the measures across time for either the breast cancer or the comparison group, increases in both IGF-1 concentrations and the IGF-1/IGFBP-3 ratio over the first 6 months of AI treatment were significantly associated with the onset or increase in musculoskeletal pain among the breast cancer patients. Associations between IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio and pain were not observed in the comparison group. CONCLUSIONS: Although preliminary, findings from this study implicate the IGF axis in the development of AI-associated musculoskeletal pain and represent a first step in developing effective interventions to alleviate this side effect.
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[79]
TÍTULO / TITLE: - Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dose-finding trial with pharmacokinetic and biomarker correlates.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt109
AUTORES / AUTHORS: - Kelley RK; Nimeiri HS; Munster PN; Vergo MT; Huang Y; Li CM; Hwang J; Mulcahy MF; Yeh BM; Kuhn P; Luttgen MS; Grabowsky JA; Stucky-Marshall L; Korn WM; Ko AH; Bergsland EK; Benson AB 3rd; Venook AP
INSTITUCIÓN / INSTITUTION: - Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco.
RESUMEN / SUMMARY: - BackgroundBased upon preclinical evidence for improved antitumor activity in combination, this phase I study investigated the maximum-tolerated dose (MTD), safety, activity, pharmacokinetics (PK), and biomarkers of the mammalian target of rapamycin inhibitor, temsirolimus, combined with sorafenib in hepatocellular carcinoma (HCC).Patients and methodsPatients with incurable HCC and Child Pugh score </=B7 were treated with sorafenib plus temsirolimus by 3 + 3 design. The dose-limiting toxicity (DLT) interval was 28 days. The response was assessed every two cycles. PK of temsirolimus was measured in a cohort at MTD.ResultsTwenty-five patients were enrolled. The MTD was temsirolimus 10 mg weekly plus sorafenib 200 mg twice daily. Among 18 patients at MTD, DLT included grade 3 hand-foot skin reaction (HFSR) and grade 3 thrombocytopenia. Grade 3 or 4 related adverse events at MTD included hypophosphatemia (33%), infection (22%), thrombocytopenia (17%), HFSR (11%), and fatigue (11%). With sorafenib, temsirolimus clearance was more rapid (P < 0.05). Two patients (8%) had a confirmed partial response (PR); 15 (60%) had stable disease (SD). Alpha-fetoprotein (AFP) declined >/=50% in 60% assessable patients.ConclusionThe MTD of sorafenib plus temsirolimus in HCC was lower than in other tumor types. HCC-specific phase I studies are necessary. The observed efficacy warrants further study.
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[80]
TÍTULO / TITLE: - Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis: A study of 176 patients with prognostic implications.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Feb 19. doi: 10.1002/cncr.27930.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27930
AUTORES / AUTHORS: - Tadmor T; Shvidel L; Aviv A; Ruchlemer R; Bairey O; Yuklea M; Herishanu Y; Braester A; Levene N; Vernea F; Ben-Ezra J; Bejar J; Polliack A
INSTITUCIÓN / INSTITUTION: - Hematology Unit, Bnai-Zion Medical Center, Haifa, Israel; The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. tamar.tadmor@b-zion.org.il.
RESUMEN / SUMMARY: - BACKGROUND: Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL. METHODS: Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0-3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well-recognized prognostic factors for CLL. RESULTS: The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32-86 years) and the 5-year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2-3) was associated with thrombocytopenia (platelet counts of < 100,000/mm(3) ) (P = .025), anemia (P = .018), elevated beta2-microglobulin < 4000 mug/mL (P = .048), and the presence of 11q deletion (P = .0015). CONCLUSIONS: There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications. Cancer 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 American Cancer Society.
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[81]
TÍTULO / TITLE: - Genetic basis for the increased expression of vacuolar H(+) translocating ATPase genes upon imatinib treatment in human lymphoblastoid cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):1095-100. doi: 10.1007/s00280-013-2110-4. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2110-4
AUTORES / AUTHORS: - Kulkarni H; Goring HH; Curran JE; Diego V; Dyer TD; Cole S; Walder KR; Collier GR; Blangero J; Carless MA
INSTITUCIÓN / INSTITUTION: - Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA, hkulkarn@txbiomedgenetics.org.
RESUMEN / SUMMARY: - PURPOSE: The role of v-ATPases in cancer biology is being increasingly recognized. Yeast studies indicate that the tyrosine kinase inhibitor imatinib may interact with the v-ATPase genes and alter the course of cancer progression. Data from humans in this regard are lacking. METHODS: We constructed 55 lymphoblastoid cell lines from pedigreed, cancer-free human subjects and treated them with IC20 concentration of imatinib mesylate. Using these cell lines, we (i) estimated the heritability and differential expression of 19 genes encoding several subunits of the v-ATPase protein in response to imatinib treatment; (ii) estimated the genetic similarity among these genes; and (iii) conducted a high-density scan to find cis-regulating genetic variation associated with differential expression of these genes. RESULTS: We found that the imatinib response of the genes encoding v-ATPase subunits is significantly heritable and can be clustered to identify novel drug targets in imatinib therapy. Further, five of these genes were significantly cis-regulated and together represented nearly half-log fold change in response to imatinib (p = 0.0107) that was homogenous (p = 0.2598). CONCLUSIONS: Our results proffer support to the growing view that personalized regimens using proton pump inhibitors or v-ATPase inhibitors may improve outcomes of imatinib therapy in various cancers.
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[82]
TÍTULO / TITLE: - Occurrence and current management of side effects in chronic myeloid leukemia patients treated frontline with tyrosine kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Mar 6. pii: S0145-2126(13)00037-4. doi: 10.1016/j.leukres.2013.01.021.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.021
AUTORES / AUTHORS: - Breccia M; Alimena G
INSTITUCIÓN / INSTITUTION: - Department of Cellular Biotechnology and Hematology, Sapienza University, Rome, Italy. Electronic address: breccia@bce.uniroma1.it.
RESUMEN / SUMMARY: - Tyrosine kinase inhibitors (TKIs) represent the gold standard therapy of chronic myeloid leukemia and, after being used in imatinib resistant patients, dasatinib and nilotinib are now also used in frontline. In this article, we review data about occurrence of side effects in several trials testing imatinib or second-generation tyrosine kinase inhibitors first line. Literature data about high-dose imatinib used front-line as single treatment or with different combinations is also examined. A literature search for relevant studies was undertaken mainly in PubMed. This review is aimed to summarize the safety of different treatments and to discuss the current management of most common side effects. Literature evidence supports the fact that side effects associated to TKIs seem to differ between agents, but most of side effects reported occur early within the treatment course. Second generation frontline TKIs reduce the incidence of most of side effects reported with imatinib and peculiar events observed are typically manageable through drug dose reduction or treatment interruption.
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[83]
TÍTULO / TITLE: - Raf kinase inhibitor protein expression combined with peritoneal involvement and lymphovascular invasion predicts prognosis in Dukes’ B colorectal cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Histopathology. 2013 Feb;62(3):505-10.
AUTORES / AUTHORS: - Doyle B; Hagan S; Al-Mulla F; Scott L; Harden S; Paul J; Mulcahy H; Murray GI; Sheahan K; O’Sullivan J; Kolch W
INSTITUCIÓN / INSTITUTION: - Beatson Institute for Cancer Research, Glasgow, UK.
RESUMEN / SUMMARY: - AIMS: There is controversy regarding the use of adjuvant therapy in patients with Dukes’ B colorectal cancer (CRC). New markers, identifying high-risk Dukes’ B patients, are needed. Here, we examine the utility of Raf kinase inhibitor protein (RKIP) as such a marker and promoter methylation as a mechanism of RKIP down-regulation. METHODS AND RESULTS: We used a tissue microarray of 220 patients with Dukes’ B CRC to examine the effect of RKIP expression on survival. Pyrosequencing was used to assess RKIP promoter methylation status.RKIP expression correlated inversely with disease-specific survival in this cohort. In multivariate analysis, RKIP was found to be an independent prognostic indicator, along with peritoneal invasion and lymphovascular invasion (LVI). RKIP promoter hypermethylation was seen in only one of 29 tumours analysed by pyrosequencing. CONCLUSIONS: Raf kinase inhibitor protein, peritoneal invasion and LVI provide independent prognostic information in this cohort of Dukes’ B CRC patients.This demonstrates the potential utility of RKIP in identifying ‘high-risk’ Dukes’ B patients. It is this high-risk group which is most likely to benefit from close postoperative monitoring and may derive the most benefit from adjuvant therapy.
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[84]
TÍTULO / TITLE: - Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormone-receptor-positive breast cancer: a randomised, controlled, double-blind, phase 2 trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lancet Oncol. 2013 Mar;14(3):228-35. doi: 10.1016/S1470-2045(13)70026-3. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(13)70026-3
AUTORES / AUTHORS: - Robertson JF; Ferrero JM; Bourgeois H; Kennecke H; de Boer RH; Jacot W; McGreivy J; Suzuki S; Zhu M; McCaffery I; Loh E; Gansert JL; Kaufman PA
INSTITUCIÓN / INSTITUTION: - Royal Derby Hospital, Derby, UK. Electronic address: john.robertson@nottingham.ac.uk.
RESUMEN / SUMMARY: - BACKGROUND: Insulin-like growth factors (IGF-1 and IGF-2) bind to the IGF-1 receptor (IGF-1R), increasing cell proliferation and survival. Ganitumab is a monoclonal IgG1 antibody that blocks IGF-1R. We tested the efficacy and safety of adding ganitumab to endocrine treatment for patients with hormone-receptor-positive breast cancer. METHODS: We did this phase 2 trial in outpatient clinics and hospitals. We enrolled postmenopausal women with hormone-receptor-positive, locally advanced or metastatic breast cancer previously treated with endocrine treatment. They were randomly assigned (2:1) with a central randomisation schedule to receive intravenous ganitumab 12 mg per kg bodyweight or placebo in combination with open-label intramuscular fulvestrant (500 mg on day 1, then 250 mg on days 15, 29, and every 28 days) or oral exemestane (25 mg once daily) on a 28-day cycle. Patients, investigators, study monitors, and the sponsor staff were masked to treatment allocation. Response was assessed every 8 weeks. The primary endpoint was median progression-free survival in the intention-to-treat population. We analysed overall survival as one of our secondary endpoints. The study is registered at ClinicalTrials.gov, number NCT00626106. FINDINGS: We screened 189 patients and enrolled 156 (106 in the ganitumab group and 50 in the placebo group). Median progression-free survival did not differ significantly between the ganitumab and placebo groups (3.9 months, 80% CI 3.6-5.3 vs 5.7 months, 4.4-7.4; hazard ratio [HR] 1.17, 80% CI 0.91-1.50; p=0.44). However, overall survival was worse in the the ganitumab group than in the placebo group (HR 1.78, 80% CI 1.27-2.50; p=0.025). With the exception of hyperglycaemia, adverse events were generally similar between groups. The most common grade 3 or higher adverse event was neutropenia-reported by six of 106 (6%) patients in the ganitumab group and one of 49 (2%) in the placebo group. Hyperglycaemia was reported by 12 of 106 (11%) patients in the ganitumab group (with six patients having grade 3 or 4 hyperglycaemia) and none of 49 in the placebo group. Serious adverse events were reported by 27 of 106 (25%) patients in the ganitumab group and nine of 49 (18%) patients in the placebo group. INTERPRETATION: Addition of ganitumab to endocrine treatment in women with previously treated hormone-receptor-positive locally advanced or metastatic breast cancer did not improve outcomes. Our results do not support further study of ganitumab in this subgroup of patients. FUNDING: Amgen.
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[85]
TÍTULO / TITLE: - Preoperative Carcinoembryonic Antigen Level Predicts Prognosis in Patients with Pseudomyxoma Peritonei Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg. 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-1988-7
AUTORES / AUTHORS: - Canbay E; Ishibashi H; Sako S; Mizumoto A; Hirano M; Ichinose M; Takao N; Yonemura Y
INSTITUCIÓN / INSTITUTION: - NPO Organization to Support Peritoneal Dissemination Treatment, 1-26, Harukimotomachi, Kishiwada City, Osaka, 596-0032, Japan, drecanbay@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: Even though management of pseudomyxoma peritonei (PMP) was improved with cytoreductive surgery (CRS) and hyperthermic chemotherapy (HIPEC), several aspects of PMP still need to be optimized, including patient selection for surgery and prognostic factors. We assessed the role of preoperative carcinoembryonic antigen (CEA) levels in PMP patients treated with CRS and HIPEC. METHODS: A total of 449 PMP patients with documented preoperative CEA levels referred to our center between 2005 and 2011 underwent CRS and HIPEC. The association between CEA levels and characteristics of patients with PMP was assessed with chi 2 test, linear correlation, and logistic regression analyses. Survival analysis was performed with Cox proportional hazard model. RESULTS: Median age was 55 (range 19-84) years. There were 245 (54.5 %) females and 204 (45.5 %) males. Preoperative CEA levels were elevated in 328 (73 %, sensitivity) patients with PMP. Preoperative CEA levels were also related to peritoneal cancer index (P < 0.0001), cytoreductive surgery scores (P < 0.0001), progress free survival (P < 0.001) and overall survival (P < 0.001) in patients with PMP. CONCLUSIONS: Our results indicated that preoperative CEA levels are useful in predicting the extent of disease and surgical success as well as progress-free and overall survival in patients with PMP treated with cytoreductive surgery and HIPEC.
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[86]
TÍTULO / TITLE: - Androgen receptor-induced tumor suppressor, KLLN, inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Mol Genet. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1093/hmg/ddt077
AUTORES / AUTHORS: - Wang Y; He X; Yu Q; Eng C
INSTITUCIÓN / INSTITUTION: - Genomic Medicine Institute.
RESUMEN / SUMMARY: - Androgen receptor (AR) expression by immunohistochemistry correlates with better prognosis and survival among breast cancer patients. We and others have shown that AR inhibits proliferation and induces apoptosis in breast cancer cells. However, the mechanism of AR’s anti-tumor effect in breast cancer is still not fully understood. Our recent study indicates that AR upregulates expression of tumor suppressor gene PTEN by promoter activation in breast cancer. KLLN, encoding KLLN protein, is a newly identified gene, which shares a bidirectional promoter with PTEN and is transcribed in the opposite direction. So far, the function of KLLN has never been studied in tumorigenesis. Here, we define KLLN as a tumor suppressor in breast carcinomas, which inhibits tumor growth and invasiveness. After analyzing 188 normal breast and 1247 malignant breast cancer tissues, we observed the loss of KLLN in multiple breast cancer subtypes and this decreased KLLN expression associates with tumor progression and increasing histological grade in invasive carcinomas. We characterize KLLN, for the first time, as a transcription factor, directly promoting the expression of TP53 and TP73, with consequent elevated apoptosis and cell cycle arrest in breast cancer cells. We demonstrate, in vitro and in murine xenograph models, that both KLLN and PTEN are AR-target genes, mediating androgen-induced growth inhibition and apoptosis in breast cancer cells. Our observations suggest that KLLN might be used as a potential prognostic marker and novel therapy target for breast carcinomas.
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[87]
TÍTULO / TITLE: - Risk factors for recurrence after curative resection of hepatitis C-related hepatocellular carcinoma in patients without postoperative interferon therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatol Res. 2013 Mar 27. doi: 10.1111/hepr.12091.
●● Enlace al texto completo (gratuito o de pago) 1111/hepr.12091
AUTORES / AUTHORS: - Yamashita YI; Shirabe K; Toshima T; Tsuijita E; Takeishi K; Harimoto N; Ikegami T; Yoshizumi T; Ikeda T; Soejima Y; Maehara Y
INSTITUCIÓN / INSTITUTION: - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan.
RESUMEN / SUMMARY: - AIM: Hepatitis C (HC)-related hepatocellular carcinoma (HCC; HC-HCC) is highly recurrent. METHODS: From 1995-2007, 183 curative hepatic resections for primary solitary HC-HCC without postoperative interferon therapy were included in this study. The patients were divided into three groups: (i) 2 cm or less (n = 56); (ii) more than 2 cm to less than 5 cm (n = 79); and (iii) 5 cm or more (n = 48). Independent risk factors for HC-HCC recurrence for each group were determined. RESULTS: Independent risk factors for recurrence were aspartate aminotransferase or alanine aminotransferase (AST/ALT) of 80 IU/L or more (hazard ratio [HR], 2.1; P = 0.02) in patients with HCC of 2 cm or less, des-gamma-carboxy prothrombin of 100 mAU/mL or more (HR, 2.5; P = 0.02) and AST/ALT of 80 IU/L or more (HR, 2.1; P = 0.04) in patients with HCC of more than 2 cm to less than 5 cm, and the presence of macroscopic portal vein tumor thrombus (HR, 2.8; P = 0.02) and AST/ALT of 80 IU/L or more (HR, 2.1; P = 0.04) in patients with HCC of 5 cm or more. All 13 late recurrences of 1 year or more after hepatic resection (27.1%) in patients with HCC of 5 cm or more were accompanied by AST/ALT of 80 IU/L or more. CONCLUSION: AST/ALT of 80 IU/L or more is an independent risk factor for the recurrence of primary solitary HC-HCC after curative resection irrespective of the primary HC-HCC size.
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[88]
TÍTULO / TITLE: - Impact of global and gene-specific DNA methylation pattern in relapsed multiple myeloma patients treated with bortezomib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 7. pii: S0145-2126(13)00027-1. doi: 10.1016/j.leukres.2013.01.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.013
AUTORES / AUTHORS: - Fernandez de Larrea C; Martin-Antonio B; Cibeira MT; Navarro A; Tovar N; Diaz T; Rosinol L; Monzo M; Urbano-Ispizua A; Blade J
INSTITUCIÓN / INSTITUTION: - Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clinic, Barcelona, Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Jose Carreras Leukaemia Research Institute, University of Barcelona, Barcelona, España.
RESUMEN / SUMMARY: - We studied seventy-five patients with relapsed MM treated with bortezomib-based regimens. DNA was isolated from bone marrow samples at the time of relapse. Global methylation was determined by ELISA, and CpG island DNA methylation profile of 30 genes by a DNA methylation PCR system. Patients with more than 3.95% of total DNA methylated achieved better overall survival (OS) (p=0.004). A relatively low methylation percentage (<1.07%) of NFKB1 was also associated with longer OS after bortezomib treatment (p=0.015). The combination of highly methylated global genome with low NFKB1 methylation status defined a specific subset of patients with better prognosis.
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[89]
TÍTULO / TITLE: - IgG4 subclass antibodies impair antitumor immunity in melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Invest. 2013 Mar 1. pii: 65579. doi: 10.1172/JCI65579.
●● Enlace al texto completo (gratuito o de pago) 1172/JCI65579
AUTORES / AUTHORS: - Karagiannis P; Gilbert AE; Josephs DH; Ali N; Dodev T; Saul L; Correa I; Roberts L; Beddowes E; Koers A; Hobbs C; Ferreira S; Geh JL; Healy C; Harries M; Acland KM; Blower PJ; Mitchell T; Fear DJ; Spicer JF; Lacy KE; Nestle FO; Karagiannis SN
RESUMEN / SUMMARY: - Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10-driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell-mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcgammaRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches.
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[90]
TÍTULO / TITLE: - Impact of hyperthermic intraperitoneal chemotherapy on Hsp27 protein expression in serum of patients with peritoneal carcinomatosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Stress Chaperones. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s12192-013-0415-1
AUTORES / AUTHORS: - Kepenekian V; Aloy MT; Magne N; Passot G; Armandy E; Decullier E; Sayag-Beaujard A; Gilly FN; Glehen O; Rodriguez-Lafrasse C
INSTITUCIÓN / INSTITUTION: - EMR3738, Faculte de Medecine Lyon-Sud, Universite Lyon 1, BP12 69921, Oullins Cedex, France.
RESUMEN / SUMMARY: - Despite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial.
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[91]
TÍTULO / TITLE: - Arf/p53 module, which induces apoptosis, downregulates histone H2AX to allow normal cells to survive in the presence of anti-cancer drugs.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.402560
AUTORES / AUTHORS: - Atsumi Y; Inase A; Osawa T; Sugihara E; Sakasai R; Fujimori H; Teraoka H; Saya H; Kanno M; Tashiro F; Nakagama H; Masutani M; Yoshioka KI
INSTITUCIÓN / INSTITUTION: - National Cancer Center, Japan;
RESUMEN / SUMMARY: - Anti-cancer drugs generally target cancer cells rather than normal somatic cells. However, the factors that determine this differential sensitivity are poorly understood. Here, we show that Arf/p53-dependent downregulation of H2AX induced the selective survival of normal cells after drug treatment, resulting in the preferential targeting of cancer cells. Treatment with camptothecin, a topoisomerase I inhibitor, caused normal cells to downregulate H2AX and become quiescent, a process mediated by both Arf and p53. By contrast, transformed cells that harbor mutations in either Arf or p53 do not downregulate H2AX and are more sensitive to drugs unless they have developed drug resistance. Such transformation-associated changes in H2AX expression rendered cancer cells more susceptible to drug-induced damage (by two orders of magnitude); thus, the expression of H2AX and gammaH2AX (phosphorylated form of H2AX at S139) is a critical factor that determines drug sensitivity, and should be considered when administering chemotherapy.
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[92]
TÍTULO / TITLE: - ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Apr 2;108(6):1238-44. doi: 10.1038/bjc.2013.83. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.83
AUTORES / AUTHORS: - Li P; Fang YJ; Li F; Ou QJ; Chen G; Ma G
INSTITUCIÓN / INSTITUTION: - Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
RESUMEN / SUMMARY: - Background:Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy.Methods:Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression.Results:Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group.Conclusion:Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.
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[93]
TÍTULO / TITLE: - Refining the UGT1A Haplotype Associated with Irinotecan-Induced Hematological Toxicity in Metastatic Colorectal Cancer Patients Treated with 5-Fluorouracil/Irinotecan-Based Regimens.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pharmacol Exp Ther. 2013 Apr;345(1):95-101. doi: 10.1124/jpet.112.202242. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1124/jpet.112.202242
AUTORES / AUTHORS: - Levesque E; Belanger AS; Harvey M; Couture F; Jonker D; Innocenti F; Cecchin E; Toffoli G; Guillemette C
INSTITUCIÓN / INSTITUTION: - Canada Research Chair in Pharmacogenomics, Pharmacogenomics Laboratory, CHU de Quebec Research Center, T3-48, 2705 Boul. Laurier, Quebec, Canada, G1V 4G2. Chantal.Guillemette@crchul.ulaval.ca.
RESUMEN / SUMMARY: - Despite the importance of UDP-glucuronosyltransferase (UGT) 1A1*28 in irinotecan pharmacogenetics, our capability to predict drug-induced severe toxicity remains limited. We aimed at identifying novel genetic markers that would improve prediction of irinotecan toxicity and response in advanced colorectal cancer patients treated with folic acid (leucovorin), fluorouracil (5-FU), and irinotecan (camptosar)-based regimens. The relationships between UGT1A candidate markers across the gene (n = 21) and toxicity were prospectively evaluated in 167 patients. We included variants in the 3’untranscribed region (3’UTR) of the UGT1A locus, not studied in this context yet. These genetic markers were further investigated in 250 Italian FOLFIRI-treated patients. Several functional UGT1A variants, including UGT1A1*28, significantly influenced risk of severe hematologic toxicity. As previously reported in the Italian cohort, a 5-marker risk haplotype [haplotype II (HII); UGTs 1A9/1A7/1A1] was associated with severe neutropenia in our cohort [odds ratio (OR) = 2.43; P = 0.004]. The inclusion of a 3’UTR single-nucleotide polymorphism (SNP) permitted refinement of the previously defined HI, in which HIa was associated with the absence of severe neutropenia in combined cohorts (OR = 0.55; P = 0.038). Among all tested UGT1A variations and upon multivariate analyses, no UGT1A1 SNPs remained significant, whereas three SNPs located in the central region of UGT1A were linked to neutropenia grade 3-4. Haplotype analyses of these markers with the 3’UTR SNP allowed the identification of a protective HI (OR = 0.50; P = 0.048) and two risk haplotypes, HII and HIII, characterized by 2 and 3 unfavorable alleles, respectively, revealing a dosage effect (ORs of 2.15 and 5.28; P </= 0.030). Our results suggest that specific SNPs in UGT1A, other than UGT1A1*28, may influence irinotecan toxicity and should be considered to refine pharmacogenetic testing.
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[94]
TÍTULO / TITLE: - Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biochem Funct. 2013 Feb 11. doi: 10.1002/cbf.2954.
●● Enlace al texto completo (gratuito o de pago) 1002/cbf.2954
AUTORES / AUTHORS: - Shaker O; El-Shehaby A; Fayez S; Zahra A; Marzouk S; Raziky ME
INSTITUCIÓN / INSTITUTION: - Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
RESUMEN / SUMMARY: - This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon-based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa-2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real-time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide -155, -443 and -1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at -443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide -443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment. Copyright © 2013 John Wiley & Sons, Ltd.
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[95]
TÍTULO / TITLE: - HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Feb 25. doi: 10.1038/onc.2013.30.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.30
AUTORES / AUTHORS: - Wardwell-Ozgo J; Dogruluk T; Gifford A; Zhang Y; Heffernan TP; van Doorn R; Creighton CJ; Chin L; Scott KL
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
RESUMEN / SUMMARY: - Melanoma is a highly lethal malignancy notorious for its aggressive clinical course and eventual resistance to existing therapies. Currently, we possess a limited understanding of the genetic events driving melanoma progression, and much effort is focused on identifying pro-metastatic aberrations or perturbed signaling networks that constitute new therapeutic targets. In this study, we validate and assess the mechanism by which homeobox transcription factor A1 (HOXA1), a pro-invasion oncogene previously identified in a metastasis screen by our group, contributes to melanoma progression. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveals upregulation of factors involved in diverse cytokine pathways that include the transforming growth factor beta (TGFbeta) signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion in melanoma cells. Transcriptome profiling also shows HOXA1’s ability to potently downregulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive cell state concomitant with TGFbeta activation. Our analysis of publicly available data sets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors. Together, these validation data and mechanistic insights suggest that patients whose primary tumors express HOXA1 are among a high-risk metastasis subgroup that should be considered for anti-TGFbeta therapy in adjuvant settings. Moreover, further analysis of HOXA1 target genes in melanoma may reveal new pathways or targets amenable to therapeutic intervention.Oncogene advance online publication, 25 February 2013; doi:10.1038/onc.2013.30.
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[96]
TÍTULO / TITLE: - Quality of life (QoL) analyses from OPTIMAL (CTONG-0802), a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt012
AUTORES / AUTHORS: - Chen G; Feng J; Zhou C; Wu YL; Liu XQ; Wang C; Zhang S; Wang J; Zhou S; Ren S; Lu S; Zhang L; Hu CP; Hu C; Luo Y; Chen L; Ye M; Huang J; Zhi X; Zhang Y; Xiu Q; Ma J; Zhang L; You C
INSTITUCIÓN / INSTITUTION: - Tumor Medicine, The Cancer Hospital of Harbin Medical University, Harbin.
RESUMEN / SUMMARY: - BackgroundThe OPTIMAL study found that erlotinib improved progression-free survival (PFS) versus standard chemotherapy in Chinese patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). This report describes the quality of life (QoL) and updated PFS analyses from this study.Patients and methodsChinese patients >/=18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received erlotinib (150 mg/day; n = 82) or gemcitabine-carboplatin (n = 72). The primary efficacy end point was PFS; QoL was assessed using the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, Trial Outcome Index (TOI) and Lung Cancer Subscale (LCS).ResultsPatients receiving erlotinib experienced clinically relevant improvements in QoL compared with the chemotherapy group in total FACT-L, TOI and LCS (P < 0.0001 for all scales). Erlotinib scored better than chemotherapy for all FACT-L subscales from baseline to cycles 2 and 4 (non-significant). In the updated analysis, PFS was significantly longer for erlotinib than chemotherapy (median PFS 13.7 versus 4.6 months; HR = 0.164, 95% CI = 0.105-0.256; P < 0.0001), which was similar to the previously reported primary analysis.ConclusionErlotinib improves QoL compared with standard chemotherapy in the first-line treatment of patients with EGFR mutation-positive advanced NSCLC.
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[97]
TÍTULO / TITLE: - Indirubin-3’-monoxime promotes autophagic and apoptotic death in JM1 human acute lymphoblastic leukemia cells and K562 human chronic myelogenous leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 6. doi: 10.3892/or.2013.2334.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2334
AUTORES / AUTHORS: - Lee MY; Liu YW; Chen MH; Wu JY; Ho HY; Wang QF; Chuang JJ
INSTITUCIÓN / INSTITUTION: - Department of Hematology and Oncology, Ditmanson Medical Foundation ChiaYi Christian Hospital, Chiayi, Taiwan, R.O.C.
RESUMEN / SUMMARY: - Indirubin is the active component of Dang gui Long hui Wan, a traditional Chinese herbal medicine used as therapy for chronic myelogenous leukemia (CML). In clinical studies, indirubin seldom caused major side-effects. However, the functional effect of indirubin on acute lymphoblastic leukemia (ALL) is unclear. Therefore, we investigated the effects of indirubin-3’-monoxime (I3M) on the ALL cell line JM1 and the CML cell line K562 (control). The anti-leukemia effects and mechanisms of I3M were similar on ALL and CML cells. I3M significantly and dose-dependently decreased cell viability. The G2/M cell cycle phase was arrested and the sub-G1 proportion was relatively increased. In addition, caspase-3 activation led to poly(ADP-ribose) polymerase (PARP)-1 cleavage and the progression of apoptosis. Notably, I3M induced autophagy. However, I3M had no effect on necrosis in either cell line. We specifically found that I3M only marginally affected the survival of primary mature lymphocytes, and was not cytotoxic to granulocytes. Since I3M induced apoptosis and autophagy in human lymphocytic leukemia cells and caused few side-effects in healthy lymphocytes and granulocytes, I3M may be useful for clinical anti-ALL therapy.
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[98]
TÍTULO / TITLE: - In vivo RAF signal transduction as a potential biomarker for sorafenib efficacy in patients with neuroendocrine tumours.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Apr 2;108(6):1298-305. doi: 10.1038/bjc.2013.64. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.64
AUTORES / AUTHORS: - Quintela-Fandino M; Krzyzanowska M; Duncan G; Young A; Moore MJ; Chen EX; Stathis A; Colomer R; Petronis J; Grewal M; Webster S; Wang L; Siu LL
INSTITUCIÓN / INSTITUTION: - 1] Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, 610 University Avenue, Suite 5-718, Toronto, Ontario, Canada M5G2M9 [2] CNIO - Spanish National Cancer Research Center Clinical Program, Melchor Fernandez Almagro 3, Madrid 28029, España.
RESUMEN / SUMMARY: - Background:Targeted therapies elicit anticancer activity by exerting pharmacodynamic effects on specific molecular targets. Currently, there is limited use of pharmacodynamic assessment to guide drug administration in the routine oncology setting.Methods:We developed a phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells, and evaluated it in a phase II clinical trial of oral sorafenib plus low-dose cyclophosphamide in patients with advanced neuroendocrine tumours (NETs), in order to predict clinical course and/or guide individual dose-titration.Results:Twenty-two patients were enrolled. Median progression-free survival (PFS) was 3 months (95% CI 2-10.7), and one patient had a partial response. PFS was longer among five patients who demonstrated an increase in pShift after 7 days of sorafenib compared with those who did not (14.9 months vs 2.8 months; P=0.047). However, pShift did not add value to toxicity-based dose-titration.Conclusion:The pharmacodynamic assessment of RAF transduction may identify selected patients with advanced NETs most likely to benefit from the combination of sorafenib plus cyclophosphamide. Further investigation of this test as a potential biomarker is warranted.
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[99]
TÍTULO / TITLE: - Prognosis factors for recurrence in patients with locally advanced rectal cancer preoperatively treated with chemoradiotherapy and adjuvant chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dis Colon Rectum. 2013 Apr;56(4):416-21. doi: 10.1097/DCR.0b013e318274d9c6.
●● Enlace al texto completo (gratuito o de pago) 1097/DCR.0b013e318274d9c6
AUTORES / AUTHORS: - Arredondo J; Baixauli J; Beorlegui C; Arbea L; Rodriguez J; Sola JJ; Chopitea A; Hernandez-Lizoain JL
INSTITUCIÓN / INSTITUTION: - 1 Department of General Surgery, Clinica Universidad de Navarra, Pamplona, España 2 Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, España 3 Department of Radiation Oncology, Clinica Universidad de Navarra, Pamplona, España 4 Department of Medical Oncology, Clinica Universidad de Navarra, Pamplona, España 5 Department of Pathology, Clinica Universidad de Navarra, Pamplona, España.
RESUMEN / SUMMARY: - BACKGROUND: : Neoadjuvant chemoradiotherapy followed by total mesorectal excision has improved the outcome of locally advanced rectal carcinoma. OBJECTIVE: : The aim of this study was to identify independent prognosis factors of disease recurrence in a group of patients treated with this approach. DESIGN AND PATIENTS: : This study was retrospective in design. Data from patients with locally advanced rectal cancer who had completed treatment from 2000 to 2010 were reviewed. SETTINGS: : The analysis was performed in a tertiary referral center. MAIN OUTCOME MEASURES: : The primary outcomes measured were the recurrence risk factors. RESULTS: : The cohort consisted of 228 patients; 69.3% of them were men, and median age was 59 years. Stage III rectal cancer was found in 64.9% of patients. The most frequently administered therapy was concurrent capecitabine, oxaliplatin, and 7-field radiotherapy, followed by 3-field radiotherapy and fluoropyrimidines. After a median follow-up of 49 months, 23.7% of the patients experienced disease recurrence: 2.6% had local recurrence, 21.1% had distant metastases, and 0.5% had both. Factors significantly correlated with recurrence risk in multivariate logistic regression were y-pathological stage (III vs I/II: OR = 2.51), tumor regression grade (1/2 vs 3+/4: OR = 3.34; 3 vs 3+/4: OR = 1.20), and low rectal location (OR = 2.36). The only independent prognosis factor for liver metastases was tumor regression grade (1/2 vs 3+/4: OR = 4.67; 3 vs 3+/4: OR = 1.41), whereas tumor regression grade (1-2 vs 3+/4: OR = 5.5; 3 vs 3+/4: OR = 1.84), low rectal location (OR = 3.23), and previous liver metastasis (OR = 7.73) predicted lung recurrence. LIMITATIONS: : This is a single institutional experience, neoadjuvant combined therapy is not homogeneous, and the analysis has been performed in a retrospective manner. CONCLUSIONS: : Patients with low third locally advanced rectal cancer with a poor response to neoadjuvant chemoradiotherapy (high y-pathological stage or low tumor regression grade) are at high risk of recurrence. Intense surveillance and the design of alternative therapeutic approaches aimed to lower the distant failure rate seem warranted.
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[100]
TÍTULO / TITLE: - Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Hematol. 2013 Feb 26. doi: 10.1002/ajh.23427.
●● Enlace al texto completo (gratuito o de pago) 1002/ajh.23427
AUTORES / AUTHORS: - Lee SE; Choi SY; Bang JH; Kim SH; Jang EJ; Byeun JY; Park JE; Jeon HR; Oh YJ; Kim HJ; Kim YK; Park JS; Jeong SH; Kim SH; Zang DY; Oh S; Koo DH; Kim H; Do YR; Kwak JY; Kim JA; Kim DY; Mun YC; Mauro MJ; Kim DW
INSTITUCIÓN / INSTITUTION: - Cancer Research Institute, The Catholic University of Korea, Seoul, Korea.
RESUMEN / SUMMARY: - Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR-ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19-74 years) were enrolled. Twenty patients received IM for post-transplant relapse. After a median follow-up of 15.8 months (1.4-28.2 months) after IM discontinuation, nine of the non-transplant group lost undetectable molecular residual disease (UMRD) and major molecular response (MMR), whereas none of the 20 patients in the transplant group experienced UMRD loss. Probabilities for sustained MMR and UMRD were 64.4% and 66.3% in the non-transplant group, respectively. Of nine patients re-treated with IM, eight patients re-achieved MMR at a median of 1.7 months (0.9-2.8 months). Seven of these patients re-achieved UMRD at a median of 5.6 months (2.8-12.1 months). Previous transplantation, IM duration, and UMRD duration were significantly associated with sustained molecular responses. Our data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post-transplant relapse. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
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[101]
TÍTULO / TITLE: - Hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis: role of heat shock proteins and dissecting effects of hyperthermia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Apr;20(4):1105-13. doi: 10.1245/s10434-012-2784-6. Epub 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2784-6
AUTORES / AUTHORS: - Pelz JO; Vetterlein M; Grimmig T; Kerscher AG; Moll E; Lazariotou M; Matthes N; Faber M; Germer CT; Waaga-Gasser AM; Gasser M
INSTITUCIÓN / INSTITUTION: - Department of Surgery I, University of Wuerzburg, Wuerzburg, Germany.
RESUMEN / SUMMARY: - BACKGROUND: In patients with isolated peritoneal carcinomatosis (PC) of gastrointestinal cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) seem to play a major role in cellular stress during HIPEC therapy. We analyzed differentially hyperthermic conditions and HSPs responsible for cell stress-mediated repair mechanisms in tumor tissues from patients who underwent HIPEC therapy and in an in vitro hyperthermic model. METHODS: Tumor tissues from our patient cohort with isolated PC were selected for further analysis when representative material was available before and after HIPEC therapy. To further dissect the role of HSPs under conditions of hyperthermia, gene and protein expression was additionally determined, together with cellular apoptosis and proliferation in human HT-29 colon cancer cells. RESULTS: Differently up-regulated HSP70/72 and HSP90 gene and protein expression was found in all investigated patient tumors. In vitro studies confirmed observations from clinical tumor analysis as underlying HSP-mediated cell stress mechanisms. Moreover, results from proliferation and apoptosis assays combined with differentiated HSP expression analysis demonstrated the relevance of preselecting specific target temperatures to achieve optimal toxic effects on remaining tumor cells in vivo. CONCLUSIONS: Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis-inducing cellular effects in patients with PC are negatively influenced by highly conserved HSP mechanisms in tumor cells. This study shows for the first time that specific hyperthermic conditions are necessary to be established to achieve optimal toxic effects on tumor cells during HIPEC therapy, a finding that opens potentially new therapeutic strategies.
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[102]
TÍTULO / TITLE: - Phase I Trial of Intravesical Recombinant Adenovirus-Mediated Interferon-alpha2b Formulated in Syn3 for BCG failures in Non-Muscle-Invasive Bladder Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Urol. 2013 Mar 15. pii: S0022-5347(13)03676-8. doi: 10.1016/j.juro.2013.03.030.
●● Enlace al texto completo (gratuito o de pago) 1016/j.juro.2013.03.030
AUTORES / AUTHORS: - Dinney CP; Fisher MB; Navai N; O’Donnell MA; Cutler D; Abraham A; Young S; Hutchins B; Caceres M; Kishnani N; Soder G; Cullen C; Zhang G; Grossman HB; Kamat AM; Gonzales M; Kincaid M; Ainslie N; Maneval DC; Wszolek MF; Benedict WF
INSTITUCIÓN / INSTITUTION: - Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030. Electronic address: cdinney@mdanderson.org.
RESUMEN / SUMMARY: - PURPOSE: A Phase l trial of intravesical recombinant adenovirus-mediated interferon-alpha2b gene therapy (rAd-IFNalpha) formulated with the excipient SCH Syn3 was conducted in patients with non-muscle invasive bladder cancer (NMIBC) who recurred after Bacillus Calmette-Guerin (BCG). The primary objective was to determine the safety of rAd-IFNalpha/Syn3; secondary endpoints were to demonstrate effective rAd-IFNalpha gene expression and preliminary evidence of clinical activity at three months. PATIENTS AND METHODS: Seventeen patients with recurrent NMIBC after BCG were enrolled. A single treatment of rAd-IFNalpha (3x109 to 3x1011 particles/mL) formulated with the excipient Syn3 was administered. Patient safety was evaluated for >/=12 weeks. Efficacy of gene transfer was determined by urine IFNalpha protein concentrations. Preliminary drug efficacy was determined at 3 months. RESULTS: Intravesical rAd-IFNalpha/Syn3 was well tolerated as no dose limiting toxicity (DLT) was encountered. Urgency was the most common adverse event and all were grade 1 or 2. rAd-IFNalpha DNA was not detected in the blood, however, transient low serum IFNalpha and Syn3 levels were measured. High and prolonged dose-related urine IFNalpha levels were achieved with the initial treatment. Of the 14 patients treated at doses >/= 1010 particles/mL with detectable urine IFNalpha, 6 (43%) experienced a complete response at 3 months and 2 remained disease free at 29.0 and 39.2 months respectively. CONCLUSION: Intravesical rAd-IFNalpha/Syn3 was well tolerated with no DLT encountered. Dose dependent urinary IFNalpha concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNalpha/Syn3 demonstrated clinical activity in NMIBC recurring after BCG.
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[103]
TÍTULO / TITLE: - PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3559
AUTORES / AUTHORS: - Shigaki H; Baba Y; Watanabe M; Murata A; Ishimoto T; Iwatsuki M; Iwagami S; Nosho K; Baba H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University.
RESUMEN / SUMMARY: - PURPOSE: PIK3CA encodes the catalytic subunit of PI3K, p110alpha. Mutant PIK3CA stimulates the AKT pathway and promotes cancer cell proliferation. PIK3CA mutations have been associated with poor prognosis in patients with colorectal or lung cancer. In contrast, the relationship between PIK3CA mutations and favorable prognoses has been shown in breast cancer. However, the influence of PIK3CA mutations on the prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. EXPERIMENTAL DESIGN: Using a non-biased database of 219 curatively resected ESCCs and eight esophageal cancer cell lines, we evaluated PIK3CA mutational status by pyrosequencing. The expression of p53 and phosphorylated AKT (i.e., AKT activation) was evaluated by immunohistochemistry. RESULTS: PIK3CA mutations in exon 9 and/or 20 were detected in 46 cases (21%). No ESCC cell line harbored PIK3CA mutations. PIK3CA mutations were significantly associated with phosphorylated AKT expression, but not with p53 expression, sex, age at surgery, tobacco use, alcohol use, or histological grade. Compared with wild-type PIK3CA cases, patients with PIK3CA mutations in exons 9 and/or 20 experienced significantly better disease-free survival [log-rank P=0.0089; univariate HR= 0.37, 95% confidence interval (CI) 0.15-0.75, P=0.0042; multivariate HR=0.34, 95% CI 0.10-0.86, P=0.021] and overall survival (log-rank P=0.012; univariate HR=0.38, 95% CI 0.16-0.78, P=0.0060; multivariate HR=0.35, 95% CI 0.10-0.90, P=0.028]. CONCLUSIONS: PIK3CA mutations in ESCC are associated with longer survival, suggesting its role as a prognostic biomarker. Future studies are needed to confirm this association and to elucidate the exact mechanisms by which PIK3CA mutations affect tumor behavior.
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[104]
TÍTULO / TITLE: - Successful treatment by azacitidine therapy of intestinal Behcet’s disease associated with myelodysplastic syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Hematol. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s12185-013-1316-x
AUTORES / AUTHORS: - Tanaka H; Shimizu N; Tougasaki E; Kawajiri C; Hashimoto S; Takeda Y; Sakai S; Takeuchi M; Ohwada C; Sakaida E; Takagi T; Nakaseko C
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Oami Municipal Hospital, 884-1 Tomita, Oamishirasato, Chiba, 299-3221, Japan, hiroakitanaka@oami-hp.jp.
RESUMEN / SUMMARY: - Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell diseases. It has been reported that several autoimmune diseases are associated with MDS. Recently, the co-occurrence of MDS with trisomy 8 and rare disorders of the immune system, such as Behcet’s disease (BD), has been described. Prognosis in the older-onset group of MDS-associated BD is unfavorable. Here, we report a case of MDS-associated intestinal BD treated successfully by azacitidine therapy. A 59-year-old Japanese male suffering from recurrent high fever, melena, and oral and genital ulcerations was diagnosed with MDS with trisomy 8 and intestinal BD by endoscopic and bone marrow examinations. Immunosuppressive therapies, including infliximab, were ineffective. Due to his severe emphysema, the patient was considered ineligible for stem cell transplantation, and azacitidine therapy was initiated. With the exception of fever, the symptoms of intestinal BD improved, and severe malnutrition and anemia were ameliorated. Fluorescence in situ hybridization analyses of the bone marrow before the eighth cycle revealed that the trisomy 8 had not decreased. To our knowledge, this is the first report of azacitidine therapy for MDS-associated BD. We suggest that azacitidine may control intestinal BD by mechanisms other than those responsible for its effect in MDS.
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[105]
TÍTULO / TITLE: - Hepatic interferon-gamma-induced protein-10 expression is more strongly associated with liver fibrosis than interleukin-28B single nucleotide polymorphisms in hepatocellular carcinoma resected patients with chronic hepatitis C.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatol Res. 2013 Jan 14. doi: 10.1111/hepr.12070.
●● Enlace al texto completo (gratuito o de pago) 1111/hepr.12070
AUTORES / AUTHORS: - Konishi H; Shirabe K; Yoshiya S; Ikeda T; Ikegami T; Yoshizumi T; Ikawa-Yoshida A; Motomura T; Fukuhara T; Maehara Y
INSTITUCIÓN / INSTITUTION: - Departments of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - AIM: Single nucleotide polymorphisms (SNP) around IL-28B and interferon (IFN)-stimulated gene (ISG) expression are predictors of response to standard therapy involving IFN for chronic hepatitis C virus (HCV) infection. We analyzed the association between these predictors to improve the prediction of the response to IFN therapy after liver resection for hepatocellular carcinoma (HCC). METHODS: Data were collected from 74 patients with HCV-induced HCC. The IL-28B genotype and hepatic ISG mRNA levels were analyzed to clarify their association, focusing on the progression of liver fibrosis. RESULTS: Fifty patients were identified as having major alleles (rs8099917 TT) and the remaining 24 patients had minor alleles (rs8099917 TG or GG). Hepatic ISG15 expression was lower in the IL-28B major group than that in the IL-28B minor group (P < 0.005). IP-10 expression was similar between the IL-28B major and minor groups (P = 0.44). IP-10 expression was elevated with advancing stages of liver fibrosis in HCV infected patients (P = 0.005). In patients with mild or no fibrosis, the IL-28B major group had lower IP-10 expression than the IL-28B minor group (P = 0.02). However, in patients with advanced fibrosis, IP-10 expression was not different between the IL-28B major and minor groups (P = 0.66). CONCLUSION: Hepatic ISG15 expression is associated with IL-28B polymorphisms, while IP-10 is strongly affected by liver fibrosis.
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[106]
TÍTULO / TITLE: - Role of epidermal growth factor receptor inhibitors in epidermal growth factor receptor wild-type non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1061-9. doi: 10.1200/JCO.2012.43.4522. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.4522
AUTORES / AUTHORS: - Laurie SA; Goss GD
INSTITUCIÓN / INSTITUTION: - FRCPC, Division of Medical Oncology, Ottawa Hospital Cancer Centre, University of Ottawa, 501 Smyth Rd, Ottawa, Ontario, K1H 8L6, Canada; slaurie@toh.on.ca.
RESUMEN / SUMMARY: - Worldwide, the majority of patients with advanced non-small-cell lung cancer (NSCLC) do not have activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). These wild-type patients comprise a significant proportion of those treated with inhibitors of this pathway, and data from randomized trials suggest that some of these wild-type patients will derive a modest benefit from these agents. Although the detection of an activating mutation predicts for a greater likelihood of response and longer progression-free survival from an EGFR tyrosine kinase inhibitor, currently there are no biomarkers that consistently and reproducibly predict for lack of benefit in wild-type patients. Several strategies to increase the efficacy of these inhibitors in wild-type NSCLC are the subject of ongoing investigations.
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[107]
TÍTULO / TITLE: - A Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome after Radiation Therapy for Localized Prostate Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 15;19(6):1612-9. doi: 10.1158/1078-0432.CCR-12-2718. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2718
AUTORES / AUTHORS: - Schoenfeld JD; Margalit DN; Kasperzyk JL; Shui IM; Rider JR; Epstein MM; Meisner A; Kenfield SA; Martin NE; Nguyen PL; Kantoff PW; Giovannucci EL; Stampfer MJ; Mucci LA
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Harvard Radiation Oncology Program; Brigham and Women’s Hospital; Dana-Farber Cancer Institute; and Harvard School of Public Health, Boston, Massachusetts.
RESUMEN / SUMMARY: - PURPOSE: To study associations between single nucleotide polymorphisms (SNP) in Ribonuclease L (RNASEL), a gene implicated in inflammation and prostate cancer risk, and outcomes after radiation therapy. EXPERIMENTAL DESIGN: We followed participants in the prospective US Health Professionals Follow-Up Study treated with radiation therapy for early-stage prostate cancer. Three SNPs were genotyped based on previously determined functional and biological significance. We used multivariable Cox proportional hazards models to assess per-allele associations with the primary outcome defined as time to a composite endpoint including development of lethal prostate cancer or biochemical recurrence. RESULTS: We followed 434 patients treated with radiation therapy for a median of 9 years. On multivariate analysis, the rs12757998 variant allele was associated with significantly decreased risk of the composite endpoint [HR: 0.65; 95% confidence interval (CI), 0.45-0.94%; P = 0.02] driven by decreased biochemical recurrence (HR: 0.60; 95% CI, 0.40-0.89%; P = 0.01) and men treated with external beam (HR: 0.58; 95% CI, 0.36-0.93%; P = 0.02). In contrast, in 516 men from the same cohort treated with radical prostatectomy, we found no significant impact of this variant on outcome. Furthermore, the rs12757998 variant allele significantly modified the association between androgen deprivation therapy and outcomes after radiation therapy (p-interaction = 0.02). CONCLUSION: We show an association between RNASEL SNP rs12757998 and outcome after radiation therapy for prostate cancer. This SNP is associated with increased circulating C-reactive protein and interleukin-6, suggesting a potential role for inflammation in the response to radiation. If validated, genetic predictors of outcome may help inform prostate cancer management. Clin Cancer Res; 19(6); 1612-9. ©2013 AACR.
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[108]
TÍTULO / TITLE: - Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Pharmacol. 2013 Mar 13. pii: S0006-2952(13)00187-1. doi: 10.1016/j.bcp.2013.03.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.03.006
AUTORES / AUTHORS: - Shanmugam MK; Dai X; Kumar AP; Tan BK; Sethi G; Bishayee A
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
RESUMEN / SUMMARY: - Discovery of bioactive molecules and elucidation of their molecular mechanisms open up an enormous opportunity for the development of improved therapy for different inflammatory diseases, including cancer. Triterpenoids isolated several decades ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments and some have already entered Phase I clinical trials. One such important and highly investigated pentacyclic triterpenoid, ursolic acid has attracted great attention of late for its potential as a chemopreventive and chemotherapeutic agent in various types of cancer. Ursolic acid has been shown to target multiple proinflammatory transcription factors, cell cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of ursolic acid by inhibiting the initiation, promotion and metastasis of cancer. This review not only summarizes the diverse molecular targets of ursolic acid, but also provides an insight into the various preclinical and clinical studies that have been performed in the last decade with this promising triterpenoid.
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[109]
TÍTULO / TITLE: - MYC rearrangements are useful for predicting outcomes following rituximab and chemotherapy: multicenter analysis of Japanese patients with diffuse large B-cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.771398
AUTORES / AUTHORS: - Kojima M; Nishikii H; Takizawa J; Aoki S; Noguchi M; Chiba S; Ando K; Nakamura N
INSTITUCIÓN / INSTITUTION: - Division of Hematology/Oncology, Department of Internal Medicine.
RESUMEN / SUMMARY: - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and it has several morphologic and clinicopathologic variants. The prognosis of DLBCL can vary according to specific genetic and immunophenotypic abnormalities. The aim of this study was to investigate the prognostic impact of previously identified prognostic factors, such as activated B cell-like immunophenotype, CD5, BCL2 and MYC rearrangement (MYC-R), in patients treated with rituximab. We retrospectively analyzed the prognosis of 100 patients with DLBCL (median age, 66.5 years) treated with rituximab-containing chemotherapy. The 3-year overall survival (OS) and progression-free survival (PFS) were 66% and 62%. Outcomes were significantly worse in patients with MYC-R in 3-year OS (50% vs. 67.8%, p = 0.043) and PFS (30% vs. 57.8%, p = 0.003), and multivariate analysis showed that this finding was independent of the International Prognostic Index (IPI). Immunostaining by Muris algorithm had the highest predictive power among the three algorithms. However, other previously reported prognostic factors, such as BCL2 and CD5, were not good predictors of outcomes in these patients. In conclusion, our data suggest that fluorescence in situ hybridization (FISH) analysis for MYC-R can predict outcomes in response to rituximab-containing chemotherapy in Japanese patients with DLBCL.
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[110]
TÍTULO / TITLE: - Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):1073-82. doi: 10.1007/s00280-013-2103-3. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2103-3
AUTORES / AUTHORS: - Wang S; Chen L; Zhao Q; Rong H; Wang M; Gong W; Zhou J; Wu D; Zhang Z
INSTITUCIÓN / INSTITUTION: - Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, 211166, China.
RESUMEN / SUMMARY: - PURPOSE: Several studies have examined the prognostic value of the TP53 Arg72Pro polymorphism (rs1042522) and/or MDM2 SNP309 (rs2279744) in multiple tumors. Our aim was to determine whether these two genetic variants were correlated with clinical outcome of gastric cancer. METHODS: We genotyped the two SNPs, TP53 codon 72 polymorphism and MDM2 SNP309, in 940 gastric cancer patients with complete follow-up information and analyzed the correlation between the SNPs and gastric cancer survival. RESULTS: The two SNPs were not significantly associated with gastric cancer survival. However, the TP53 codon 72 polymorphism had a prominent correlation with clinical outcome of patients receiving 5-fluorouracil (5-Fu)-based postoperative chemotherapy [Arg/Arg + Arg/Pro vs. Pro/Pro, adjusted hazard ratio (HR) = 1.63, 95 % confidence interval (CI) = 1.08-2.44]. Moreover, the unfavorable effect of Arg allele on survival outcome was more predominant for subgroups of older (age >60 years), male, intestinal histology type, advanced stage (T3/T4), and none metastasis of lymph node (N0) or distant (M0) (adjusted HR = 2.34, 95 % CI = 1.24-4.44 for age >60 years; 1.72, 1.10-2.69 for male; 2.30, 1.10-4.80 for intestinal; 1.62, 1.01-2.59 for T3/T4; 3.42, 1.26-9.24 for N0; and 1.62, 1.06-2.47 for M0). Among multiple chemotherapy regimens, the association was only significant in the subgroup of 5-Fu/calcium folinate plus oxaliplatin (FOLFOX) chemotherapy regimen (adjusted HR = 4.47, 95 % CI = 1.21-16.55). CONCLUSIONS: Our findings showed that TP53 codon 72 polymorphism was associated with survival of gastric cancer patients treated with 5-Fu-based postoperative chemotherapy. The codon 72 polymorphism may be a potential prognostic factor.
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[111]
TÍTULO / TITLE: - Histone deacetylase inhibitors and pancreatic cancer: Are there any promising clinical trials?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Feb 28;19(8):1173-81. doi: 10.3748/wjg.v19.i8.1173.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i8.1173
AUTORES / AUTHORS: - Koutsounas I; Giaginis C; Theocharis S
INSTITUCIÓN / INSTITUTION: - Ioannis Koutsounas, Constantinos Giaginis, Stamatios Theocharis, Department of Forensic Medicine and Toxicology, Medical School, University of Athens, GR-11527 Athens, Greece.
RESUMEN / SUMMARY: - Pancreatic cancer, although not very frequent, has an exceptionally high mortality rate, making it one of the most common causes of cancer mortality in developed countries. Pancreatic cancer is difficult to diagnose, allowing few patients to have the necessary treatment at a relatively early stage. Despite a marginal benefit in survival, the overall response of pancreatic cancer to current systemic therapy continues to be poor, and new therapies are desperately needed. Histone deacetylase (HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors (HDACIs) have been shown to induce differentiation and cell cycle arrest, activate the extrinsic or intrinsic pathways of apoptosis, and inhibit invasion, migration and angiogenesis in different cancer cell lines. As a result of promising preclinical data, various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies. Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma. The use of HDACIs in clinical trials, in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed. Unfortunately, clinical data for HDACIs in patients with pancreatic cancer are inadequate, because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase II/III trials, among others with advanced solid tumors, is very limited. More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.
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[112]
TÍTULO / TITLE: - Development and validation of a 32-gene prognostic index for prostate cancer progression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Proc Natl Acad Sci U S A. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1215870110
AUTORES / AUTHORS: - Wu CL; Schroeder BE; Ma XJ; Cutie CJ; Wu S; Salunga R; Zhang Y; Kattan MW; Schnabel CA; Erlander MG; McDougal WS
INSTITUCIÓN / INSTITUTION: - Departments of Pathology and Urology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
RESUMEN / SUMMARY: - The accurate determination of the risk of cancer recurrence is an important unmet need in the management of prostate cancer. Patients and physicians must weigh the benefits of currently available therapies against the potential morbidity of these treatments. Herein we describe the development of a gene expression-based continuous risk index and a validation of this test in an independent, blinded cohort of post-radical prostatectomy (RP) patients. A gene expression signature, prognostic for prostate-specific antigen (PSA) recurrence, was identified through a bioinformatic analysis of the expression of 1,536 genes in malignant prostate tissue from a training cohort of consecutive patients treated with RP. The assay was transferred to a real-time RT-PCR platform, and a continuous risk index model was constructed based on the expression of 32 genes. This 32-gene risk index model was validated in an independent, blinded cohort of 270 RP patients. In multivariate analyses, the risk index was prognostic for risk of PSA recurrence and had added value over standard prognostic markers such as Gleason score, pathologic tumor stage, surgical margin status, and presurgery PSA (hazard ratio, 4.05; 95% confidence interval, 1.50-10.94; P = 0.0057). Furthermore, RP patients could be stratified based on the risk of PSA recurrence and the development of metastatic disease. The 32-gene signature identified here is a robust prognostic marker for disease recurrence. This assay may aid in postoperative treatment selection and has the potential to impact decision making at the biopsy stage.
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[113]
TÍTULO / TITLE: - Everolimus in Combination with Exemestane: A Review of its Use in the Treatment of Patients with Postmenopausal Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Drugs. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s40265-013-0034-2
AUTORES / AUTHORS: - Dhillon S
INSTITUCIÓN / INSTITUTION: - Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
RESUMEN / SUMMARY: - Oral everolimus (Afinitor®) in combination with exemestane is indicated for the treatment of hormone receptor-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer in postmenopausal women after failure of treatment with letrozole or anastrozole (in the USA) or after recurrence of progression following a nonsteroidal aromatase inhibitor (AI) in women without symptomatic visceral disease (in the EU). Everolimus, a selective inhibitor of mammalian target of rapamycin (mTOR), inhibits the downstream signalling events of the mTOR pathway. This review summarizes the pharmacology of everolimus and reviews its efficacy and tolerability when administered in combination with exemestane in postmenopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer refractory to nonsteroidal AIs. In the well-designed BOLERO-2 study, the addition of everolimus to exemestane was shown to significantly prolong progression-free survival in this patient population. However, treatment-emergent adverse events and treatment discontinuations occurred more frequently with combination therapy than with exemestane alone, suggesting a need for careful benefit/risk assessment prior to initiating therapy. Mature survival data from this study are awaited and additional studies would help to further demonstrate the benefit of combination therapy. Nevertheless, current evidence suggests that everolimus plus exemestane combination therapy may be a useful treatment option in patients with postmenopausal hormone receptor-positive, HER2-negative, advanced breast cancer refractory to nonsteroidal AIs.
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[114]
TÍTULO / TITLE: - “NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora A inhibitors: implications for treatment of metastatic solid tumors.”
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4008
AUTORES / AUTHORS: - Ice RJ; McLaughlin SL; Livengood RH; Culp MV; Eddy ER; Ivanov AV; Pugacheva EN
INSTITUCIÓN / INSTITUTION: - Mary Babb Randolph Cancer Center, West Virginia University School of Medicine.
RESUMEN / SUMMARY: - Aurora A Kinase (AURKA) is overexpressed in 96% of human cancers and is considered an independent marker of poor prognosis. While the majority of tumors have elevated levels of AURKA protein, few have AURKA gene amplification, implying that posttranscriptional mechanism regulating AURKA protein levels are significant. Here we show that NEDD9, a known activator of AURKA, is directly involved in AURKA stability. Analysis of a comprehensive breast cancer tissue microarray revealed a tight correlation between the expression of both proteins, significantly corresponding with increased prognostic value. A decrease in AURKA, concomitant with increased ubiquitination and proteasome-dependent degradation, occurs due to depletion or knockout of NEDD9. Re-expression of wild type NEDD9 was sufficient to rescue the observed phenomenon. Binding of NEDD9 to AURKA is critical for AURKA stabilization, as mutation of S296E was sufficient to disrupt binding and led to reduced AURKA protein levels. NEDD9 confers AURKA stability by limiting the binding of the cdh1-substrate recognition subunit of APC/C ubiquitin ligase to AURKA. Depletion of NEDD9 in tumor cells increases sensitivity to AURKA inhibitors. Combination therapy with NEDD9 shRNAs and AURKA inhibitors impairs tumor growth and distant metastasis in mice harboring xenografts of breast tumors. Collectively, our findings provide rationale for the use of AURKA inhibitors in treatment of metastatic tumors and predict the sensitivity of the patients to AURKA inhibitors based on NEDD9 expression.
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[115]
TÍTULO / TITLE: - The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cytokine. 2013 Apr;62(1):34-7. doi: 10.1016/j.cyto.2013.02.030. Epub 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cyto.2013.02.030
AUTORES / AUTHORS: - Urbonas V; Eidukaite A; Tamuliene I
INSTITUCIÓN / INSTITUTION: - National Research Institute, Center for Innovative Medicine, Department of Immunology, Moletu pl. 29, LT-08409 Vilnius, Lithuania; Klaipeda University Hospital, Diagnostic Department, Molecular Diagnostic Laboratory, Lithuania. Electronic address: v.urbonas@kul.lt.
RESUMEN / SUMMARY: - BACKGROUND: Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients. METHODS: A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups. RESULTS: Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently. CONCLUSIONS: PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia.
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[116]
TÍTULO / TITLE: - Restoration of Mannose-Binding Lectin Complement Activity Is Associated With Improved Outcome in Patients With Advanced Pancreatic Cancer Treated With Gemcitabine and Intravenous omega-3 Fish Oil.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JPEN J Parenter Enteral Nutr. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1177/0148607113476304
AUTORES / AUTHORS: - Arshad A; Chung W; Isherwood J; Steward W; Metcalfe M; Dennison A
INSTITUCIÓN / INSTITUTION: - Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.
RESUMEN / SUMMARY: - Background: Pancreatic cancer has an extremely poor clinical outcome. Surrogate biomarkers for outcome are scarce. There is mixed evidence for the association of high mannose-binding lectin (MBL) complement activity with cancer outcomes, including reduced survival and increased infectious complications. omega-3-rich fatty acids (omega-3FA) attenuate production of proinflammatory cytokines and potentially manipulate complement activity. Materials and Methods: As part of a single-arm phase II trial in a university hospital, patients with advanced pancreatic adenocarcinoma were treated with weekly omega-3FA-rich intravenous infusion (Lipidem [B. Braun Melsungen AG, Melsungen, Germany]: up to 100 g/wk) plus gemcitabine chemotherapy until withdrawal or tumor progression. Primary outcome measure was objective response rate. Changes in complement activity, which were a secondary outcome measure, were analyzed and relation to clinical outcome determined. Results: Twenty-three patients were assessable for time to progression (TTP), overall survival (OS), and complement activity. No hypoactivity in alternative and classical pathways was demonstrated. Baseline MBL was low in 10 of 23 patients (43.5%). There was no difference in OS or TTP between low- and high-baseline MBL patients. Of these 10 patients, 5 were classified as MBL responders. MBL responders had a tendency toward improved OS over nonresponders (8.9 vs 4.4 months, P = .07). MBL responders had significantly improved TTP over nonresponders (10.6 vs 5.3 months, P = .03). Conclusion: MBL restoration had an association with improved outcome in the cohort of patients with low MBL activity at baseline. The independent contribution of omega-3FA to this effect warrants further investigation in the form of randomized clinical trials.
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[117]
TÍTULO / TITLE: - A neuropharmacokinetic assessment of bafetinib, a second generation dual BCR-Abl/Lyn tyrosine kinase inhibitor, in patients with recurrent high-grade gliomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Feb 4. pii: S0959-8049(13)00005-1. doi: 10.1016/j.ejca.2013.01.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.001
AUTORES / AUTHORS: - Portnow J; Badie B; Markel S; Liu A; D’Apuzzo M; Frankel P; Jandial R; Synold TW
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, City of Hope/Beckman Research Institute, 1500 East Duarte Road, Duarte, CA 91010, United States. Electronic address: jportnow@coh.org.
RESUMEN / SUMMARY: - PURPOSE: The primary objective of this study was to use intracerebral microdialysis (ICMD) to determine the neuropharmacokinetics of bafetinib, a dual BCR-Abl/Lyn tyrosine kinase inhibitor that may have activity against gliomas. METHODS: A microdialysis catheter was placed into either peritumoural or enhancing brain tissue of seven patients at the time of tumour resection or biopsy. Twenty-four hours later, bafetinib was administered, 240 or 360mg po, repeating the same dose 12h later. Dialysate samples were continuously collected for 24h, with plasma samples obtained in parallel. One to two weeks after finishing ICMD, patients were allowed to resume taking bafetinib continuously while being observed for toxicity and tumour response. RESULTS: Twenty-six dialysate samples per patient were collected (n=6) and analysed for bafetinib by tandem mass spectrometry. Bafetinib concentrations in the brain were below the lower limit of detection of the assay (0.1ng/ml) in all samples except one from a single subject that was 0.52ng/ml. The mean plasma bafetinib maximum concentrations after dose 1 and 2 were 143+/-99 and 247+/-73ng/ml, respectively. Only one patient remained on treatment past two cycles, and no radiographic responses were seen. CONCLUSIONS: Bafetinib does not sufficiently cross intact or disrupted blood-brain barrier, and therefore, systemic administration of bafetinib is not recommended when investigating this drug as a treatment for brain tumours. ICMD can be a valuable research tool in early drug development. Lead-in ICMD studies can be performed relatively quickly, requiring only a small number of patients, and without significantly disrupting standard cancer care.
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[118]
TÍTULO / TITLE: - Transcription factor Nuclear Factor Erythroid-2 mediates expression of the cytokine Interleukin 8, a known predictor of inferior outcome in patients with myeloproliferative neoplasms.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Haematologica. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 3324/haematol.2012.071183
AUTORES / AUTHORS: - Wehrle J; Seeger TS; Schwemmers S; Pfeiffer D; Bullashevska A; Pahl HL
INSTITUCIÓN / INSTITUTION: - Germany.
RESUMEN / SUMMARY: - The transcription factor nuclear factor erythroid-2 (NF-E2) is overexpressed in patients with myeloproliferative neoplasms irrespective of the presence of the JAK2V617F mutation. Our NF-E2 transgenic mouse model, which recapitulates many features of myeloproliferative neoplasms including transformation to acute myeloid leukemia, clearly implicates this transcription factor in the pathophysiology of myeloproliferative neoplasms. Because the targets mediating NF-E2 effects are not well characterized, we conducted microarray analysis of CD34+ cells lentivirally transduced to overexpress NF-E2 or to silence NF-E2 via shRNA, in order to identify novel NF-E2 target genes. Here, we report that the cytokine Interleukin 8 (IL-8) is a novel NF-E2 target gene. NF-E2 directly binds the IL-8 promoter in vivo, and these binding sites are required for promoter activity. Serum levels of IL-8 are known to be elevated in both polycythemia vera and primary myelofibrosis patients. Recently, increased IL-8 levels have been shown to be predictive of inferior survival in primary myelofibrosis patients in multivariate analysis. Therefore, one of the mechanisms by which NF-E2 contributes to myeloproliferative neoplasm pathology may constitute increased IL-8 expression.
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[119]
TÍTULO / TITLE: - Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5052-7. doi: 10.1073/pnas.1202653110. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1202653110
AUTORES / AUTHORS: - Guha P; Kaptan E; Bandyopadhyaya G; Kaczanowska S; Davila E; Thompson K; Martin SS; Kalvakolanu DV; Vasta GR; Ahmed H
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, Department of Otorhinolaryngology, University of Maryland Greenebaum Cancer Center, and Departments of Physiology and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.
RESUMEN / SUMMARY: - Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a beta-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galbeta1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising antimetastatic agent for the treatment of various cancers, including prostate adenocarcinoma.
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[120]
TÍTULO / TITLE: - Clinicians Versus Nomogram: Predicting Future Technetium-99m Bone Scan Positivity in Patients With Rising Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urology. 2013 Jan 30. pii: S0090-4295(12)01497-5. doi: 10.1016/j.urology.2012.12.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.12.010
AUTORES / AUTHORS: - Kattan MW; Yu C; Stephenson AJ; Sartor O; Tombal B
INSTITUCIÓN / INSTITUTION: - Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address: kattanm@ccf.org.
RESUMEN / SUMMARY: - OBJECTIVE: To compare the ability of clinicians vs a nomogram at predicting future bone scan positivity in patients with prostate cancer. MATERIALS AND METHODS: This investigation was conducted during an advisory board meeting in June 2011. Details of 25 androgen deprivation therapy-naive prostate cancer patients were given to 24 prostate cancer experts, including urologists and oncologists. The clinicians were asked to predict the probability that the patients would have a positive bone scan if left untreated for 1 year. These predictions and those of the Slovin nomogram were compared with the actual occurrence of metastatic disease, and the discrimination ability was quantified using the concordance index (C index). RESULTS: A higher C index value was obtained with the Slovin nomogram (0.812) than with the clinicians (0.628). The nomogram outperformed all of the clinicians; individual clinician C index values varied between 0.47 and 0.75. The urologists provided superior predictions compared with the oncologists. CONCLUSION: Future bone scan positivity can be predicted more accurately using a nomogram than by expert clinicians. Nomograms should, therefore, become an integral part of the clinical decision-making process in the prostate cancer setting for patients with a rising prostate-specific antigen level after radical prostatectomy.
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[121]
TÍTULO / TITLE: - Insulin growth factor receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic adrenocortical carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 5;108(4):826-30. doi: 10.1038/bjc.2013.46. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.46
AUTORES / AUTHORS: - Naing A; Lorusso P; Fu S; Hong D; Chen HX; Doyle LA; Phan AT; Habra MA; Kurzrock R
INSTITUCIÓN / INSTITUTION: - Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
RESUMEN / SUMMARY: - Background:Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy without an available effective systemic chemotherapy. Insulin growth factor 2 (IGF-2) overexpression leading to the activation of the IGF-1 receptor (IGF-1R)/mammalian target of rapamycin (mTOR) pathway is well described in ACC. Cixutumumab, a fully human IgG1 monoclonal antibody directed at IGF-1R was combined with temsirolimus on the basis of preclinical data.Methods:Patients received cixutumumab, 3-6 mg kg intravenously (IV) weekly, and temsirolimus, 25-37.5 mg IV weekly (4-week cycles), with restaging after 8 weeks.Results:Twenty-six patients were enrolled (13 (50%) men); median age, 47 years; median number of prior therapies, 4. Five patients previously received an IGF-1R inhibitor and one, temsirolimus. The most frequent toxicities, at least possibly drug related, were grade 1-2 thrombocytopenia (38%), mucositis (58%), hypercholesterolaemia (31%), hypertriglyceridemia (35%), and hyperglycaemia (31%). In all, 11 of 26 patients (42%) achieved stable disease (SD) >6 months (duration range=6-21 months) with 3 of the 11 having received a prior IGF-1R inhibitor.Conclusion:Cixutumumab combined with temsirolimus was well tolerated and >40% of patients achieved prolonged SD.
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[122]
TÍTULO / TITLE: - Activation of Triggering Receptor Expressed on Myeloid Cells-1 Protects Monocyte from Apoptosis through Regulation of Myeloid Cell Leukemia-1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anesthesiology. 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1097/ALN.0b013e31828744a5
AUTORES / AUTHORS: - Cai M; Chen Q; Chen C; Liu X; Hou J; Zeng C; Shu Q; Fang X
INSTITUCIÓN / INSTITUTION: - * Research Assistant, double dagger Resident, vertical line Professor, Department of Thoracic and Cardiovascular Surgery, Children’s Hospital, School of Medicine, Zhejiang University, and Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People’s Republic of China. dagger Senior Research Assistant, section sign Research Assistant, # Professor, Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND:: Triggering receptor expressed on myeloid cells-1 (TREM-1) can amplify the proinflammatory response and may contribute to the pathogenesis of inflammatory disease such as sepsis. However, the role of TREM-1 in monocyte fate and the detailed molecular mechanisms evoked by TREM-1 are unknown. METHODS:: Adenoviruses overexpressing TREM-1 were constructed and transfected into a monocytic cell line. After activation of TREM-1 by agonist antibody with or without lipopolysaccharide, apoptosis was induced and assayed using flow cytometry. The signaling pathways downstream of TREM-1 were illustrated by inhibitory experiments. Proapoptotic/antiapoptotic protein levels were measured using immunoblot. In addition, the relationship between the expression levels of TREM-1 in monocytes and the magnitude of monocyte apoptosis were analyzed in septic patients. RESULTS:: Activation of TREM-1 protected monocytes from staurosporine-induced apoptosis. This characteristic was also obtained under lipopolysaccharide stimulation. The protection of TREM-1 against monocyte apoptosis was abrogated after inhibition of extracellular signal-regulated kinase or v-akt murine thymoma viral oncogene homologue signaling. Cross-linking of TREM-1 remarkably up-regulated myeloid cell leukemia-1 protein level, and inhibition of extracellular signal-regulated kinase or v-akt murine thymoma viral oncogene homologue resulted in the reduction of myeloid cell leukemia-1 expression. Inhibition of myeloid cell leukemia-1 abolished the antiapoptotic effect of TREM-1. Furthermore, in septic patients, TREM-1 levels were inversely correlated to the magnitude of apoptosis in monocyte. CONCLUSIONS:: TREM-1 played an important role in apoptosis in monocytes. Activation of TREM-1 protected monocytic cells from apoptosis through activation of both extracellular signal-regulated kinase and v-akt murine thymoma viral oncogene homologue pathways and increased expression of myeloid cell leukemia-1 protein. These findings provide a novel additional mechanism for TREM-1-mediated hyperinflammatory response in monocytes.
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[123]
TÍTULO / TITLE: - Infliximab-associated psoriasis in children with Crohn’s disease may require withdrawal of anti-tumor necrosis factor therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Inflamm Bowel Dis. 2013 Apr;19(5):E75-7. doi: 10.1097/MIB.0b013e3182802c93.
●● Enlace al texto completo (gratuito o de pago) 1097/MIB.0b013e3182802c93
AUTORES / AUTHORS: - Broge T; Nguyen N; Sacks A; Davis M
INSTITUCIÓN / INSTITUTION: - *Florida State University Pediatric Residency Program Sacred Heart Hospital Pensacola, Florida daggerGastroenterology Nemours Children’s Clinic Pensacola, Florida.
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[124]
TÍTULO / TITLE: - Sorafenib induces apoptosis in endometrial carcinoma cells by inhibiting Elk-1-dependent Mcl-1 gene expression and by inducing Akt/GSK3beta-dependent Mcl-1 protein degradation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Biochem. 2013 Mar 5. doi: 10.1002/jcb.24530.
●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24530
AUTORES / AUTHORS: - Sun NK; Huang SL; Chang TC; Chao CC
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, Chang Gung University College of Medicine, Taoyuan 333, Taiwan, Republic of China; Division of Biomedical Sciences, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan, Republic of China.
RESUMEN / SUMMARY: - Endometrial carcinoma (EC) is one of the main gynecologic malignancies affecting women, but effective treatments are currently lacking. In the present study, we investigated the effect of sorafenib, a general kinase inhibitor, on several EC cell lines (HEC1A, HEC1B, and RL95-2). Sorafenib induced cell death in EC cells with the following order of sensitivity: HEC1A > HEC1B > RL95-2. Sorafenib suppressed several anti-apoptotic proteins in HEC1A cells, including myeloid cell leukemia 1 (Mcl-1). Ectopic overexpression of Mcl-1 prevented the cell killing effect of sorafenib. Sorafenib suppressed Mcl-1 at the gene transactivation level by inactivating the ERK/Elk-1 pathway. Accordingly, the inhibitory effect of sorafenib on Mcl-1 expression decreased following knockdown of Elk-1 using short-hairpin RNA (shRNA). Elk-1 overexpression rescued both the inhibitory effect of sorafenib on Mcl-1 expression and the cell killing effect of sorafenib. Furthermore, sorafenib reduced the stability of the Mcl-1 protein by enhancing its ubiquitination and degradation by the proteasome via the AKT/GSK3beta and the ERK pathways. Similar results were detected in other EC cell lines. These results indicate that sorafenib induces apoptosis in EC cells by down-regulating the anti-apoptotic protein Mcl-1 via transcriptional inhibition and protein degradation. Our results thus support the notion that sorafenib may be used in endometrial cancer therapy. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
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[125]
TÍTULO / TITLE: - Acute lymphoblastic leukaemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lancet. 2013 Mar 21. pii: S0140-6736(12)62187-4. doi: 10.1016/S0140-6736(12)62187-4.
●● Enlace al texto completo (gratuito o de pago) 1016/S0140-6736(12)62187-4
AUTORES / AUTHORS: - Inaba H; Greaves M; Mullighan CG
INSTITUCIÓN / INSTITUTION: - Department of Oncology, St Jude Children’s Research Hospital and University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: hiroto.inaba@stjude.org.
RESUMEN / SUMMARY: - Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in paediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients’ pharmacodynamics and pharmacogenomics, and improved supportive care. However, innovative approaches are needed to further improve survival while reducing adverse effects. Prognosis remains poor in infants and adults. Genome-wide profiling of germline and leukaemic cell DNA has identified novel submicroscopic structural genetic changes and sequence mutations that contribute to leukaemogenesis, define new disease subtypes, affect responsiveness to treatment, and might provide novel prognostic markers and therapeutic targets for personalised medicine.
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[126]
TÍTULO / TITLE: - CHFR Protein Expression Predicts Outcomes to Taxane-Based First Line Therapy in Metastatic NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 15;19(6):1603-11. doi: 10.1158/1078-0432.CCR-12-2995. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2995
AUTORES / AUTHORS: - Pillai RN; Brodie SA; Sica GL; Shaojin Y; Li G; Nickleach DC; Yuan L; Varma VA; Bonta D; Herman JG; Brock MV; Ribeiro MJ; Ramalingam SS; Owonikoko TK; Khuri FR; Brandes JC
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Hematology and Oncology, Pathology, Biostatistics, and Radiology, and Winship Cancer Institute, Emory University; Atlanta VA Medical Center, Atlanta, Georgia; and Sidney Kimmel Comprehensive Cancer Institute, Johns Hopkins University, Baltimore, Maryland.
RESUMEN / SUMMARY: - PURPOSE: Currently, there is no clinically validated test for the prediction of response to tubulin-targeting agents in non-small cell lung cancer (NSCLC). Here, we investigated the significance of nuclear expression of the mitotic checkpoint gene checkpoint with forkhead and ringfinger domains (CHFR) as predictor of response and overall survival with taxane-based first-line chemotherapy in advanced stage NSCLC. Methods: We studied a cohort of 41 patients (median age 63 years) with advanced NSCLC treated at the Atlanta VAMC between 1999 and 2010. CHFR expression by immunohistochemistry (score 0-4) was correlated with clinical outcome using chi-square test and Cox proportional models. A cutoff score of “3” was determined by receiver operator characteristics analysis for “low” CHFR expression. Results were validated in an additional 20 patients who received taxane-based chemotherapy at Emory University Hospital and the Atlanta VAMC. RESULTS: High expression (score = 4) of CHFR is strongly associated with adverse outcomes: the risk for progressive disease after first-line chemotherapy with carboplatin-paclitaxel was 52% in patients with CHFR-high versus only 19% in those with CHFR-low tumors (P = 0.033). Median overall survival was strongly correlated with CHFR expression status (CHFR low: 9.9 months; CHFR high: 6.2 months; P = 0.002). After multivariate adjustment, reduced CHFR expression remained a powerful predictor of improved overall survival (HR = 0.24; 95% CI, 0.1-0.58%; P = 0.002). In the validation set, low CHFR expression was associated with higher likelihood of clinical benefit (P = 0.03) and improved overall survival (P = 0.038). CONCLUSIONS: CHFR expression is a novel predictive marker of response and overall survival in NSCLC patients treated with taxane-containing chemotherapy. Clin Cancer Res; 19(6); 1603-11. ©2013 AACR.
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[127]
TÍTULO / TITLE: - Low RPS14 expression in MDS without 5q- aberration confers higher apoptosis rate of nucleated erythrocytes and predicts prolonged survival and possible response to lenalidomide in lower-risk non-5q- patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Haematol. 2013 Mar 18. doi: 10.1111/ejh.12105.
●● Enlace al texto completo (gratuito o de pago) 1111/ejh.12105
AUTORES / AUTHORS: - Wu L; Li X; Xu F; Zhang Z; Chang C; He Q
INSTITUCIÓN / INSTITUTION: - Hematology Division, the Sixth Hospital Affiliated to Shanghai Jiaotong University.
RESUMEN / SUMMARY: - OBJECTIVES: Haploinsufficiency of the ribosomal protein S14 (RPS14) has been identified as a causal factor in myelodysplastic syndrome (MDS) with isolated del (5q). This study was carried out to investigate RPS14 expression in MDS without 5q deletion and the role of lower-expressed RPS14 plays in pathogenesis and the prognosis and lenalidomide-response predicting of non-5q-MDS. PATIENTS AND METHODS: The expression level of RPS14 transcription was detected in 156 MDS patients without 5q-. The apoptosis of bone marrow (BM) nucleated erythrocytes was also analyzed. Furthermore, patient prognosis with lower or normal RPS14 expression was analyzed and the role of RPS14 expression in lenalidomide-response prediction was evaluated. RESULTS: The reduced RPS14 expression occurred in 83 of 156 (53.2%) non- 5q- patients. Patients with RPS14 lower-expression presented higher platelet counts in the peripheral blood compared to RPS14 normal patients (p=0.012). The lower RPS14 expression status was inversely correlated with increased apoptosis ratio in nucleated erythrocytes from BM (r=-0.54, p=0.013). Patients with lower RPS14 expression have a higher two-year survival probability than normal RPS14 cases in the international prognosis scoring system (IPSS) lower-risk group (90.8% vs. 71.7%; p = 0.018). A multivariate analysis showed RPS14 expression status was an independent predictor for survival in lower-risk MDS patients without 5q deletion. Twelve patients were treated with lenalidomide. Five of seven patients achieved an erythroid response in the lower RPS14 expression group (5/7, 71.4%), compared to zero responses in the five normal RPS14 patients (p=0.018). CONCLUSION: Lower RPS14 expression in MDS patients without 5q deletion is associated with increased apoptosis of nucleated erythrocytes in lower-risk MDS. Additionally, lower RPS14 predicts prolonged survival and possible response to lenalidomide in lower-risk MDS patients. © 2013 John Wiley & Sons A/S.
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[128]
TÍTULO / TITLE: - The Oncolytic Activity of Newcastle Disease Virus in Clear Cell Renal Carcinoma Cells in Normoxic and Hypoxic Conditions: The Interplay Between VHL and Interferon-beta Signaling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Interferon Cytokine Res. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1089/jir.2012.0095
AUTORES / AUTHORS: - Ch’ng WC; Stanbridge EJ; Yusoff K; Shafee N
INSTITUCIÓN / INSTITUTION: - 1 Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia , UPM Serdang, Malaysia .
RESUMEN / SUMMARY: - Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2alpha, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-beta, but not IFN-alpha, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-beta production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells’ HIF-2alpha levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells.
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[129]
TÍTULO / TITLE: - KRAS Mutation as the Biomarker of Response to Chemotherapy and EGFR-TKIs in Patients With Advanced Non-Small Cell Lung Cancer: Clues For Its Potential Use in Second-Line Therapy Decision Making.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Clin Oncol. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e318287bb23
AUTORES / AUTHORS: - Campos-Parra AD; Zuloaga C; Manriquez ME; Aviles A; Borbolla-Escoboza J; Cardona A; Meneses A; Arrieta O
INSTITUCIÓN / INSTITUTION: - *Laboratory of Experimental Oncology daggerThoracic Oncology Clinic section signDepartment of Pathology #Laboratory of Translational Medicine, Instituto Nacional de Cancerologia (INCan) double daggerDepartment of Pathology, Instituto Nacional de Enfermedades Respiratorias (INER), Tlalpan, Mexico, D.F parallelBoehringer Ingelheim, Barrio Xaltocan, Xochimilco, Mexico City, Mexico paragraph signClinical and Translational Oncology Group, Institute of Oncology, Fundacion Santa Fe de Bogota, Bogota, Colombia.
RESUMEN / SUMMARY: - OBJETIVE:: In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation. METHODS:: From 2007 to 2010, 353 patients with NSCLC were treated with first-line CT, EGFR-TKIs were used in the second or third line of treatment. Tests were performed for EGFR and KRAS mutation and the results of the mutations were obtained 3 to 4 months after the start of the treatment. We analyzed clinical characteristics, mutation profile, response and PFS to CT and EGFR-TKIs, and overall survival. The protocol is registered with ClinicalTrials.gov, number NCT01023828. RESULTS:: Presence of the wild-type (WT) KRAS was independently associated with increased response rate to first-line CT when compared with KRAS mutation (41.4% vs. 14.7%; P=0.001). The EGFR mutation (57.8% vs. 11.7%; P<0.001) and WT-KRAS (39.6% vs. 3.3%; P=0.001) were associated with the EGFR-TKIs response. PFS of patients with WT-EGFR and KRAS mutation treated with EGFR-TKIs was shorter when compared with patients with WT-EGFR and WT-KRAS (P<0.001). CONCLUSIONS:: KRAS mutation status is a good biomarker for response to EGFR-TKIs in patients with NSCLC. KRAS mutational status could impact the decision to give CT or EGFR-TKIs as a second line of treatment to patients with NSCLC, particularly in patients with WT-EGFR.
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[130]
TÍTULO / TITLE: - The Investigational Aurora Kinase A Inhibitor MLN8237 Induces Defects in Cell Viability and Cell-Cycle Progression in Malignant Bladder Cancer Cells In Vitro and In Vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 1;19(7):1717-28. doi: 10.1158/1078-0432.CCR-12-2383. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2383
AUTORES / AUTHORS: - Zhou N; Singh K; Mir MC; Parker Y; Lindner D; Dreicer R; Ecsedy JA; Zhang Z; Teh BT; Almasan A; Hansel DE
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Pathology and Laboratory Medicine Institute; Lerner Research Institute; Glickman Urological and Kidney Institute; Genomic Medicine Institute; Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio; Millennium Pharmaceuticals, Cambridge, Massachusetts; Van Andel Research Institute, Grand Rapids, Michigan; and NCCS-VARI Translational Research Laboratory, National Cancer Center, Singapore, Singapore.
RESUMEN / SUMMARY: - PURPOSE: Despite more than 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule in bladder cancer, as a potential therapeutic target. EXPERIMENTAL DESIGN: Gene expression in human bladder cancer samples was evaluated using RNA microarray and quantitative reverse transcriptase PCR. Effects of the Aurora kinase A inhibitor MLN8237 (Millennium) on cell dynamics in malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells were evaluated in vitro and in vivo in a mouse xenograft model. RESULTS: A set of 13 genes involved in the mitotic spindle checkpoint, including Aurora kinases A and B, were upregulated in human urothelial carcinoma compared with normal urothelium. The Aurora kinase A inhibitor MLN8237 induced cell-cycle arrest, aneuploidy, mitotic spindle failure, and apoptosis in the human bladder cancer cell lines T24 and UM-UC-3. MLN8237 also arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model. Finally, in vitro sequential administration of MLN8237 with either paclitaxel or gemcitabine resulted in synergistic cytotoxic effects in T24 cells. CONCLUSIONS: Mitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma and can be exploited with pharmacologic Aurora A inhibition. Given our demonstration of the ability of the Aurora A inhibitor MLN8237 to inhibit growth of bladder cancer in vitro and in vivo, we conclude that Aurora kinase inhibitors warrant further therapeutic investigation in bladder cancer. Clin Cancer Res; 19(7); 1717-28. ©2013 AACR.
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[131]
TÍTULO / TITLE: - Prognostic Value of High Thymidine Kinase Activity in Previously Untreated Diffuse Large B-Cell Lymphoma Patients Treated by R-CHOP.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.779690
AUTORES / AUTHORS: - Suzuki K; Terui Y; Yokoyama M; Ueda K; Nishimura N; Mishima Y; Sakajiri S; Tsuyama N; Takeuchi K; Hatake K
RESUMEN / SUMMARY: - ABSTRACT The purpose of this study was to investigate prognostic factors for overall survival (OS) among previously untreated diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. We evaluated four biological parameters including thymidine kinase activity (TK). This study looked at 183 patients. The median level of TK was 14.0 IU/L, which we chose as the cut-off. After a median follow-up time of 53.0 months, OS rate at 4 years in the high TK arm and low TK arm were 46.7% and 66.7% (p = .001). By multivariate analysis, OS was significantly worse in high-TK arm (hazard ratio 2.705; p = .045). Complete response (CR) rate among high TK arm was significantly worse than low TK arm. OS was significantly better in patients who had achieved CR than partial response or less. In conclusion, high TK activity was a strong predictor for short OS and poor response among patients with previously untreated DLBCL treated with R-CHOP.
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[132]
TÍTULO / TITLE: - Does Timing of Cytoreductive Nephrectomy Impact Patient Survival With Metastatic Renal Cell Carcinoma in the Tyrosine Kinase Inhibitor Era? A Multi-institutional Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urology. 2013 Apr;81(4):805-12. doi: 10.1016/j.urology.2012.10.054. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.10.054
AUTORES / AUTHORS: - Stroup SP; Raheem OA; Palazzi KL; Liss MA; Mehrazin R; Kopp RP; Patel N; Cohen SA; Park SK; Patterson AL; Kane CJ; Millard F; Derweesh IH
INSTITUCIÓN / INSTITUTION: - Division of Urology, Department of Surgery, University of California San Diego School of Medicine, La Jolla, CA.
RESUMEN / SUMMARY: - OBJECTIVE: To compare outcomes of metastatic renal cell carcinoma (mRCC) patients who underwent primary cytoreductive nephrectomy (CRN), followed by adjuvant sunitinib therapy, vs those who underwent primary sunitinib therapy before planned CRN. METHODS: This was a multi-institutional retrospective analysis of 35 mRCC patients from June 2005 to August 2009 (median follow-up, 28.5 months): 17 underwent primary CRN, followed by adjuvant sunitinib (group 1); 18 underwent primary sunitinib therapy, followed by planned CRN (group 2). Response to therapy was determined using Response Evaluation Criteria in Solid Tumors. Group 2 patients who had partial response (PR)/stable disease (SD) proceeded to CRN (group 2 +CRN). Group 2 patients who progressed were treated with salvage systemic therapy (group 2 no-CRN). Primary and secondary outcomes were disease-specific survival (DSS) and overall survival (OS). RESULTS: Patient demographic and tumor characteristics were similar. The groups had similar rates of DSS and OS on univariate analysis (P = .318 and P = .181). In group 2, 11 (61%) had PR/DS; 7 (39%) progressed. Mean times to disease-specific death in group 1, group 2 (+CRN), and group 2 (no-CRN) were 29.2, 4.6, and 28.7 months, respectively (P = .025). Kaplan-Meier analysis of DSS and OS demonstrated significant improvement in group 2 (+CRN) vs group 1 vs group 2 (no-CRN; P <.001), which remained significant on multivariate regression. CONCLUSION: Nonresponders to primary sunitinib therapy had a poor prognosis. Offering CRN, if safely feasible, combined with sunitinib, was associated with improved disease-specific outcome in mRCC. Responders to primary sunitinib who underwent CRN had better DSS and OS than patients who underwent primary CRN, followed by sunitinib. Further investigation is required to assess the role, timing, and sequencing of targeted therapy and CRN in treatment of mRCC.
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[133]
TÍTULO / TITLE: - A phase I study of arsenic trioxide (trisenox), ascorbic Acid, and bortezomib (velcade) combination therapy in patients with relapsed/refractory multiple myeloma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Invest. 2013 Mar;31(3):172-6. doi: 10.3109/07357907.2012.756109. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2012.756109
AUTORES / AUTHORS: - Held LA; Rizzieri D; Long GD; Gockerman JP; Diehl LF; Castro CM; Moore JO; Horwitz ME; Chao NJ; Gasparetto C
INSTITUCIÓN / INSTITUTION: - Division of Cellular Therapy1.
RESUMEN / SUMMARY: - Purpose: This Phase I study assessed the feasibility of concomitant arsenic trioxide (ATO), ascorbic acid (AA), and bortezomib (Velcade) (AAV) for patients with relapsed/refractory multiple myeloma. Experimental Design: ATO (0.25 mg/kg) and AA (1 g) were given with an escalating dose of bortezomib (1 mg/m or 1.3 mg/m IV bolus on days 1 and 8 of a 21-day cycle). Results: Ten patients (median age 62 years), with a median of 3 prior regimens, were enrolled. Four (40%) patients achieved clinical benefit, with one patient achieving a durable partial response. No formal DLTs were encountered. Conclusion: AAV combination was feasible and demonstrated some benefits in this heavily pretreated population.
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[134]
TÍTULO / TITLE: - Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Chem. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.
●● Enlace a la Editora de la Revista journals.uchicago.edu/
●● Cita: Clinical Infectious Diseases: <> Lab Med. 2013 Feb 13:1-6. doi: 10.1515/cclm-2012-0320.
●● Enlace al texto completo (gratuito o de pago) 1515/cclm-2012-0320
AUTORES / AUTHORS: - Balgkouranidou I; Karayiannakis A; Matthaios D; Bolanaki H; Tripsianis G; Tentes AA; Lianidou E; Chatzaki E; Fiska A; Lambropoulou M; Kolios G; Kakolyris S
RESUMEN / SUMMARY: - Abstract Background: DNA methylation represents one of the most common epigenetic changes in human cancer providing important information regarding carcinogenesis. A possible role as a prognostic indicator has also been proposed. The aim of our study was to evaluate the prognostic significance of SOX17 promoter methylation status in patients with operable gastric cancer. Methods: Using methylation-specific PCR (MSP) we examined the incidence and prognostic significance of SOX17 methylation status in cell free circulating DNA in the serum of 73 patients with operable gastric cancer. Fifty-one patients were male (69.9%), their median age was 65 years, 43 patients (58.9%) had regional lymph node involvement and all had a Performance Status (WHO) of 0-1. Results: SOX17 promoter was found to be methylated in 43 out of 73 gastric cancer serum samples examined (58.9%). All 20 control serum samples from healthy individuals were negative. Overall survival (OS) was found to be significantly associated with SOX17 methylation (p=0.049). A significant correlation between methylation status and differentiation (p=0.031) was also observed. No other significant associations between different tumor parameters examined and SOX17 methylation status were observed. Conclusions: SOX17 promoter methylation in cell free DNA of patients with operable gastric cancer is a frequent event and may provide important information regarding prognosis in this group of patients.
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[135]
TÍTULO / TITLE: - beta-catenin/POU5F1/SOX2 transcription factor complex mediates IGF-1 receptor signaling and predicts poor prognosis in lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4403
AUTORES / AUTHORS: - Xu C; Xie D; Yu SC; Yang XJ; He LR; Yang J; Ping YF; Wang B; Yang L; Xu SL; Cui W; Wang QL; Fu WJ; Liu Q; Qian C; Cui YH; Rich JN; Kung HF; Zhang X; Bian XW
INSTITUCIÓN / INSTITUTION: - Southwest Hospital,Third Military Medical University, Institute of Pathology and Southwest Cancer Center.
RESUMEN / SUMMARY: - Cancer stem-like cells (CSLCs) are crucial in tumor initiation and progression, however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma (LAC) showed that high expression of insulin-like growth factor 1 receptor (IGF-1R) in LAC cells was positively correlated with the expressions of cancer stem cell markers, CD133 and ALDH1A1. IGF-1R activation enhanced POU5F1 expression on human lung adenocarcinoma stem-like cells (LACSLCs) through PI3K/AKT/GSK3beta/beta-catenin cascade. POU5F1 could form a novel complex with beta-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-1R. Genetic and pharmacological inhibition of IGF-1R abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-1R or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathological specimens excised from 200 patients with lung adenocarcinoma, we found that co-localization of highly expressed IGF-1R with beta-catenin and POU5F1 predicted poor prognosis. Taken together, we demonstrate that IGF-1R-mediated POU5F1 expression to form a complex with beta-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-1R, beta-catenin and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma.
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[136]
TÍTULO / TITLE: - Clinical and MRI predictors of response to interferon-beta and glatiramer acetate in relapsing-remitting multiple sclerosis patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Neurol. 2013 Feb 20. doi: 10.1111/ene.12119.
●● Enlace al texto completo (gratuito o de pago) 1111/ene.12119
AUTORES / AUTHORS: - Romeo M; Martinelli-Boneschi F; Rodegher M; Esposito F; Martinelli V; Comi G
INSTITUCIÓN / INSTITUTION: - Department of Neurology, Division of Neuroscience, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: It is still unclear which patients benefit more from available disease-modifying treatments (DMTs) in multiple sclerosis (MS). Our objective is to identify the baseline clinical and magnetic resonance imaging (MRI) predictors of response to first-line DMTs in a cohort of relapsing-remitting (RR) MS patients in a real-world clinical setting. METHODS: Consecutive naive RRMS patients treated with interferon-beta or glatiramer acetate have been included and followed for 2 years. Patients were grouped into responders ® in case of absence of clinical and MRI activity, and non-responders (NR) if the on-treatment annualized relapse rate (ARR) reduction was < 50% of the ARR in the 2 years before treatment or in the presence of MRI activity (>/= 2 active lesions at 1-year MRI or >/= 4 active lesions at 1 + 2-year MRI). RESULTS: At 2-year follow-up, 272 patients were R (34.6%) and 322 NR (40.9%), and multivariate analysis revealed that a later age at onset of the disease (P < 0.0001), a lower disability (P < 0.0001) and a lower number of gadolinium-enhancing lesions at baseline MRI (P = 0.002) were predictors of efficacy of DMTs. Moreover, the first year response had a good predictive power on the second year, as 73.7% of 1-year R had no evidence of clinical and MRI activity within the ensuing year. CONCLUSION: A lower baseline MRI and clinical activity have been identified as predictors of DMT efficacy in patients with RRMS in routine clinical practice. Evaluation of clinical and MRI activity at 1 year is recommended to monitor patients over time.
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[137]
TÍTULO / TITLE: - Millepachine, a novel chalcone, induces G2/M arrest by inhibiting CDK1 activity and causing apoptosis via ROS-mitochondrial apoptotic pathway in human hepatocarcinoma cells in vitro and in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Apr 1.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt087
AUTORES / AUTHORS: - Wu W; Ye H; Wan L; Han X; Wang G; Hu J; Tang M; Duan X; Fan Y; He S; Huang L; Pei H; Wang X; Li X; Xie C; Zhang R; Yuan Z; Mao Y; Wei Y; Chen L
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
RESUMEN / SUMMARY: - In this study, we reported millepachine (MIL), a novel chalcone compound for the first time isolated from Millettia pachycarpa Benth (Leguminosae), induced cell cycle arrest and apoptosis in human hepatocarcinoma cells in vitro and in vivo. In in vitro screening experiments, MIL showed strong antiproliferation activity in several human cancer cell lines, especially in HepG2 cells with an IC50 of 1.51 microM. Therefore, we chose HepG2 and SK-HEP-1 cells to study MIL’s antitumor mechanism. Flow cytometry showed that MIL induced a G2/M arrest and apoptosis in a dose-dependent manner. Western blot demonstrated that MIL-induced G2/M arrest was correlated with the inhibition of cyclin-dependent kinase 1 activity, including a remarkable decrease in cell division cycle (cdc) 2 synthesis, the accumulation of phosphorylated-Thr14 and decrease of phosphorylation at Thr161 of cdc2. This effect was associated with the downregulation of cdc25C and upmodulation of checkpoint kinase 2 in response to DNA damage. MIL also activated caspase 9 and caspase 3, and significantly increased the ratio of Bax/Bcl-2 and stimulated the release of cytochrome c into cytosol, suggesting MIL induced apoptosis via mitochondrial apoptotic pathway. Associated with those effects, MIL also induced the generation of reactive oxygen species. In HepG2 tumor-bearing mice models, MIL remarkably and dose dependently inhibited tumor growth. Treatment of mice with MIL (20mg/kg intravenous [i.v.]) caused more than 65% tumor inhibition without cardiac damage compared with 47.57% tumor reduction by 5mg/kg i.v. doxorubicin with significant cardiac damage. These effects suggested that MIL and its easily modified structural derivative might be a potential lead compound for antitumor drug.
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[138]
TÍTULO / TITLE: - Genetic inhibition of vascular endothelial growth factor receptor1 significantly inhibits the migration and proliferation of leukemia cells and increases their sensitivity to chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 13. doi: 10.3892/or.2013.2348.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2348
AUTORES / AUTHORS: - Xiu B; Zhang W; Huang B; Chen J; Lu H; Fu J; Xiong H; Liang A
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Tongji Hospital of Tongji University, Putuo, Shanghai 200065, P.R. China.
RESUMEN / SUMMARY: - Little is known about the role of vascular endothelial growth factor (VEGF) receptor1 (VEGFR-1) in acute leukemia. In this study, using real-time PCR and ELISA, we found that VEGF and VEGFR-1 are highly expressed in U937 leukemia cells and primary leukemia cells (M4/M5 subtypes), which are associated with an increased migration rate and extramedullary disease. In order to elucidate the role of VEGFR-1 in acute leukemia, we used a lentivirus-mediated shRNA expression system to specifically inhibit VEGFR-1 expression in the U937 cell line. In addition, a series of in vitro experiments were conducted, including cell proliferation and migration assays and drug treatments. Our results showed that shRNA reduced the proliferation and migration of U937 cells. RNA interference targeting VEGFR-1 in combination with bevacizumab did not exert synergistic antitumor effects. However, shRNA enhanced the sensitivity of the U937 cells to cytarabine by decreasing the IC50 of cytarabine, reducing the number of cells in the S phase and suppressing the expression of the survivin gene. Taken together, these results suggest that VEGFR-1 interference may serve as a novel antitumor therapeutic strategy for the treatment of leukemia.
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[139]
TÍTULO / TITLE: - Markers of cell division cycle in glioblastoma: significance in prediction of treatment response and patient prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Neurosurg. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.773287
AUTORES / AUTHORS: - Yousaf J; Hills C; Dixit S; Achawal S; O’Brien D; Greenman J; Scott IS
INSTITUCIÓN / INSTITUTION: - Departments of Neurosurgery, Hull & East Yorkshire Hospitals NHS Trust , Hull Royal Infirmary, Hull , UK.
RESUMEN / SUMMARY: - Objective. To investigate whether expression of regulatory components of the cell division cycle can be used independently to predict survival and response to adjuvant therapy in glioblastomas. Method. A tissue micro-array, constructed using glioblastomas (n = 66), was stained using antibodies against minichromosome maintenance protein-2 (Mcm-2), expressed throughout the cell-division cycle; geminin, a protein that prevents re-initiation of DNA replication; and cyclin A, an S-phase cyclin. A semi-quantitative labelling index (LI) was calculated using an average of 18 high-power fields (hpf) in three replicate cores. The patients were divided into two groups: Group 1 (n = 50) underwent surgery and radiotherapy with 24 patients receiving temozolomide, and Group 2 (n = 16) received surgical treatment only. Results. The LIs (median +/- IQR) for Group 1 were as follows: Mcm-2, 36.7% (22.9%-51.8%); geminin, 7.8% (5.8%-10.5%); and cyclin A, 4.2% (2.4%-6.9%). Elevated LIs, higher than the median, for geminin and cyclin A correlated with prolonged survival when the tumours received adjuvant therapy (Kaplan-Meier curves, p = 0.0046 and p = 0.0063 for geminin and cyclin A, respectively). Linear regression analysis revealed positive correlations with survival for Mcm-2 (p = 0.0376), geminin (p = 0.0006) and cyclin A (p = 0.004). In Group 2, there was no relationship between the patient survival and the LI for any marker. Conclusions. Geminin and cyclin A, each show potential as independent prognostic markers in glioblastomas receiving adjuvant therapy. This may reflect the fact that both geminin and cyclin A estimate proliferating tumour cell subpopulations sensitive to radio/chemotherapy. These markers could provide valuable prognostic information, even in small biopsies, especially if combined with O6MGMT expression and 1p;19q deletion status.
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[140]
TÍTULO / TITLE: - Tumor-derived Mutations in the Gene Associated with Retinoid Interferon-induced Mortality (GRIM-19) Disrupt Its Anti-signal Transducer and Activator of Transcription 3 (STAT3) Activity and Promote Oncogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Mar 15;288(11):7930-41. doi: 10.1074/jbc.M112.440610. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.440610
AUTORES / AUTHORS: - Nallar SC; Kalakonda S; Lindner DJ; Lorenz RR; Lamarre E; Weihua X; Kalvakolanu DV
INSTITUCIÓN / INSTITUTION: - From the Department of Microbiology and Immunology, Program in Oncology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201.
RESUMEN / SUMMARY: - The signal transducer and activator of transcription 3 (STAT3) protein is critical for multiple cytokine and growth factor-induced biological responses in vivo. Its transcriptional activity is controlled by a transient phosphorylation of a critical tyrosine. Constitutive activation of STAT3 imparts resistance to apoptosis, promotes cell proliferation, and induces de novo micro-angiogenesis, three of the six cardinal hallmarks of a typical cancer cell. Earlier we reported the isolation of GRIM-19 as a growth suppressor using a genome-wide expression knockdown strategy. GRIM-19 binds to STAT3 and suppresses its transcriptional activity. To understand the pathological relevance of GRIM-19, we screened a set of primary head and neck tumors and identified three somatic mutations in GRIM-19. Wild-type GRIM-19 suppressed cellular transformation by a constitutively active form of STAT3, whereas tumor-derived mutants L71P, L91P and A95T significantly lost their ability to associate with STAT3, block gene expression, and suppress cellular transformation and tumor growth in vivo. Additionally, these mutants lost their capacity to prevent metastasis. These mutations define a mechanism by which STAT3 activity is deregulated in certain human head and neck tumors.
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[141]
TÍTULO / TITLE: - Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 21. pii: S0169-5002(13)00107-4. doi: 10.1016/j.lungcan.2013.03.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.03.002
AUTORES / AUTHORS: - Lee SH; Noh KB; Lee JS; Lee EJ; Min KH; Hur GY; Lee SH; Lee SY; Kim JH; Lee SY; Shin C; Shim JJ; Kim CH; Kang KH; In KH
INSTITUCIÓN / INSTITUTION: - Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Republic of Korea. Electronic address: humanmd04@hanmail.net.
RESUMEN / SUMMARY: - Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed. Excision repair cross-complementation group 1 (ERCC1) is a predictive marker for platinum-based chemotherapy. This study evaluated whether the expression of TS and ERCC1 proteins is associated with clinical outcomes of the patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. The expressions of TS and ERCC1 were evaluated by immunohistochemistry in biopsy specimens obtained from patients with pulmonary adenocarcinoma who had received pemetrexed/cisplatin as first-line treatment. Patients were categorized according to median H-score. Response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively. Both low TS and ERCC1 expressions were significantly associated with better RR (p=0.037 and p=0.015, respectively) and longer PFS (p<0.001 and p=0.004, respectively). Low ERCC1 expression was also associated with longer OS (p=0.003) while TS only showed a trend (p=0.105). TS expression was independent predictor for the better PFS in multivariate analysis (hazard ratio [HR]=0.32, 95% confidence interval [CI]: 0.14-0.76). Combining the two markers, the low TS/low ERCC1 group showed significantly longer PFS (HR=0.48, 95% CI: 0.26-0.75) and OS (HR=0.57, 95% CI: 0.36-0.89) compared with high TS/high ERCC1 group. Protein expressions of TS and ERCC1 were associated with clinical outcomes in patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. TS and ERCC1 protein expressions can be potential predictive markers in this setting.
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[142]
TÍTULO / TITLE: - Inactivation of 9q22.3 tumor suppressor genes predict outcome for patients with head and neck squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1215-20.
AUTORES / AUTHORS: - Ghosh A; Maiti GP; Bandopadhyay MN; Chakraborty J; Biswas J; Roychoudhury S; Panda CK
INSTITUCIÓN / INSTITUTION: - Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India. ckpanda@vsnl.net, ckpanda.cnci@gmail.com.
RESUMEN / SUMMARY: - Aim: This study examined the prognostic significance of candidate tumor suppressor genes (TSGs) PHD finger protein-2 (PHF2), Fanconi anaemia complementation group C (FANCC) and human homologue of Drosophila patched gene (PTCH1), in head and neck squamous cell carcinoma (HNSCC) treated primarily with surgery, or surgery followed by adjuvant radiotherapy. PATIENTS AND METHODS: Eighty-four patients with HNSCC were followed-up for recurrence/death for up to five years after diagnosis. Molecular alterations (deletion/methylation) of TSGs and human papilloma virus (HPV) status were determined in previous studies of our group. Statistical analyses of correlation of genetic alterations with treatment response and survival were carried out. RESULTS: Alterations of FANCC and PTCH1 were significantly associated with locoregional recurrence/death. In the surgery with adjuvant radiotherapy-group (n=56), patients showing alterations in FANCC and in PTCH1 were seven- and six-times, respectively, more likely to have locoregional recurrence compared to those with no alterations. In addition, the presence of alterations of both FANCC and PTCH1 had remarkable prognostic significance. CONCLUSION: FANCC and PTCH1 alterations might be used as molecular markers for prognosis and to develop strategies for effective treatment planning.
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[143]
TÍTULO / TITLE: - Prognostic impact of atypical chemokine receptor expression in patients with gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Res. 2013 Feb 4. pii: S0022-4804(13)00021-8. doi: 10.1016/j.jss.2013.01.023.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jss.2013.01.023
AUTORES / AUTHORS: - Zhu Z; Sun Z; Wang Z; Guo P; Zheng X; Xu H
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, China.
RESUMEN / SUMMARY: - BACKGROUND: Atypical chemokine receptors (ACRs), which serve as a decoy receptor to attract chemokines, including DARC, D6, and CCX-CKR, have an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in gastric cancer has not been characterized. The purpose of this study was to determine the predictive value of ACRs for overall survival in gastric cancer. METHODS: We performed immunohistochemical analysis on formalin-fixed, paraffin-embedded cancer tissue and used Western blot analysis on cell lines with an antibody against ACR protein. We investigated tumor material from total of 282 consecutive gastric specimens, composed of 101 normal gastric tissues, 181 peri-carcinoma tissues (2 cm away from the carcinoma), and their relationships to clinicopathologic features and survival, using a tissue micro-array. RESULTS: We found the expression of ACRs to be lower in gastric cancer cell lines or tissues than in normal cell line, peri-carcinoma, or normal tissues, respectively (P < 0.05). In univariate analysis, the three proteins and their co-expression were significantly associated with higher overall survival. In multivariate analysis, each of these molecules was not favorable for overall survival; however, their co-expression was an independently prognostic factor for overall survival (hazard ratio, 0.276; 95% confidence interval, 0.173-0.444; P < 0.001). CONCLUSIONS: These findings highlight the possibility that the multiple loss of ACRs may occur during the development of tumorigenesis, and their co-expression in gastric cancer may be predictive of favorable outcomes.
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[144]
TÍTULO / TITLE: - Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 28. doi: 10.3892/or.2013.2315.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2315
AUTORES / AUTHORS: - Wang YF; Kunda PE; Lin JW; Wang H; Chen XM; Liu QL; Liu T
INSTITUCIÓN / INSTITUTION: - Graduate Division, Xinxiang Medical University, Xinxiang, He’nan 453003, P.R. China.
RESUMEN / SUMMARY: - Retinoblastoma (RB) is a challenging disease that affects mostly young children. Chemical therapy has been shown to have limitations during clinical practice, principally because of the ability of RB to become resistant to the treatment. Nevertheless, chemotherapy is still the main treatment for RB, and immunotherapy has become a promising treatment for most solid tumors with fewer side effects than traditional therapies. In this study, we explored the antitumor effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) pulsed with complete tumor antigens (DC-Ag). Cytotoxicity and specificity were evaluated on an RB cell line (RB-Y79), on a human normal retina cell line (hTERT-RPE1) and a carboplatin-resistant RB cell line. Our results showed that CIK differentiation and cytotoxicity were enhanced by co-culturing CIKs with DC-Ag. Moreover, the co-culture improved the CIK proliferation rate by increasing IL-6 and decreasing IL-10 levels in the culture medium. Furthermore, the use of DC-Ag-CIK cells had little effect on normal retinal cells but high cytotoxicity on RB cells even on carboplatin-resistant retinoblastoma cells. This is the first study showing that DC cells pulsed with the complete tumor antigen improve proliferation, differentiation and cytotoxic activity of CIKs specific not only for RB but also for the chemotherapy-resistant form of the malady. Thus highly efficient immunotherapy based on DC-Ag-CIK cells may be a potential effective and safe mean of treating RB especially to patients where traditional chemical therapy has failed.
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[145]
TÍTULO / TITLE: - Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin: Molecular mechanisms unveiled by gene expression profiling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Pharmacol. 2013 Apr 15;85(8):1077-90. doi: 10.1016/j.bcp.2013.01.028. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.01.028
AUTORES / AUTHORS: - Koch M; Krieger ML; Stolting D; Brenner N; Beier M; Jaehde U; Wiese M; Royer HD; Bendas G
INSTITUCIÓN / INSTITUTION: - Pharmaceutical Institute, Rheinische Friedrich Wilhelms University Bonn, An der Immenburg 4, 53121 Bonn, Germany.
RESUMEN / SUMMARY: - Previously we reported that liposomal cisplatin (CDDP) overcomes CDDP resistance of ovarian A2780cis cancer cells (Krieger et al., Int. J. Pharm. 389, 2010, 10-17). Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells. This suggests that the mode of action of liposomal CDDP is different from the free drug. To gain insight into mechanisms of liposomal CDDP activity, we performed a transcriptome analysis of untreated A2780cis cells, and A2780cis cells in response to exposure with IC50 values of free or liposomal CDDP. A process network analysis of upregulated genes showed that liposomal CDDP induced a highly different gene expression profile in comparison to the free drug. p53 was identified as a key player directing transcriptional responses to free or liposomal CDDP. The free drug induced expression of essential genes of the intrinsic (mitochondrial) apoptosis pathway (BAX, BID, CASP9) most likely through p38MAPK activation. In contrast, liposomal CDDP induced expression of genes from DNA damage pathways and several genes of the extrinsic pathway of apoptosis (TNFRSF10B-DR5, CD70-TNFSF7). It thus appears that liposomal CDDP overcomes CDDP resistance by inducing DNA damage and in consequence programmed cell death by the extrinsic pathway. Predictions from gene expression data with respect to apoptosis activation were confirmed at the protein level by an apoptosis antibody array. This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal CDDP as promising strategy for the treatment of CDDP resistant ovarian carcinomas.
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[146]
TÍTULO / TITLE: - Mechanisms of the Antitumor Activity of Human Vgamma9Vdelta2 T Cells in Combination With Zoledronic Acid in a Preclinical Model of Neuroblastoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Ther. 2013 Mar 12. doi: 10.1038/mt.2013.38.
●● Enlace al texto completo (gratuito o de pago) 1038/mt.2013.38
AUTORES / AUTHORS: - Di Carlo E; Bocca P; Emionite L; Cilli M; Cipollone G; Morandi F; Raffaghello L; Pistoia V; Prigione I
INSTITUCIÓN / INSTITUTION: - 1] Anatomic Pathology and Molecular Medicine, Department of Medicine and Sciences of Aging, “G. d’Annunzio” University, Chieti, Italy [2] Ce.S.I. Aging Research Center, “G. d’Annunzio” University Foundation, Chieti, Italy.
RESUMEN / SUMMARY: - Low expression of surface major histocompatibility complex (MHC) class I molecules and defects in antigen processing machinery make human neuroblastoma (NB) cells appropriate targets for MHC unrestricted immunotherapeutic approaches. Human T-cell receptor (TCR) Vgamma9Vdelta2 lymphocytes exert MHC-unrestricted antitumor activity and are activated by phosphoantigens, whose expression in cancer cells is increased by aminobisphosphonates. With this background, we have investigated the in vivo anti-NB activity of human Vgamma9Vdelta2 lymphocytes and zoledronic acid (ZOL). SH-SY-5Y human NB cells were injected in the adrenal gland of immunodeficient mice. After 3 days, mice received ZOL or human Vgamma9Vdelta2 T cells or both agents by intravenous administration once a week for 4 weeks. A significantly improved overall survival was observed in mice receiving Vgamma9Vdelta2 T cells in combination with ZOL. Inhibition of tumor cell proliferation, angiogenesis and lymphangiogenesis, and increased tumor cell apoptosis were detected. Vgamma9Vdelta2 T lymphocytes were attracted to NB-tumor masses of mice receiving ZOL where they actively modified tumor microenvironment by producing interferon-gamma (IFN-gamma), that in turn induced CXCL10 expression in NB cells. This study shows that human Vgamma9Vdelta2 T cells and ZOL in combination inhibit NB growth in vivo and may provide the rationale for a phase I clinical trial in patients with high-risk NB.Molecular Therapy (2013); doi:10.1038/mt.2013.38.
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[147]
TÍTULO / TITLE: - Keratin 8 and 18 loss in epithelial cancer cells increases collective cell migration and cisplatin sensitivity through claudin1 up-regulation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.428920
AUTORES / AUTHORS: - Fortier AM; Asselin E; Cadrin M
INSTITUCIÓN / INSTITUTION: - Universite du Quebec a Trois-Rivieres, Canada.
RESUMEN / SUMMARY: - Keratins 8 and 18 (K8/18) are simple epithelial-specific intermediate filament proteins. Keratins are essential for tissues integrity and are involved in intracellular signaling pathways which regulate cell response to injuries, cell growth and death. K8/18 expression are maintained during tumorigenesis, hence their use as diagnostic marker in tumor pathology. In recent years, studies provided evidence that keratins should not be considered only as markers but also as regulators of cancer cell signaling. The loss of K8/18 expression during epithelial-mesenchymal transition (EMT) is associated with metastasis and chemoresistance. In the present study, we investigated whether K8/18 expression play an active role in EMT. We show that K8/18 stable knockdown using shRNA increases collective migration and invasiveness of epithelial cancer cells without modulating EMT markers. K8/18-depleted cells show PI3K/Akt/NF-kappaB hyperactivation and increased MMP2 and MMP9 expression. K8/18 deletion also increases cisplatin-induced apoptosis. Increased FasR membrane targeting suggest that apoptosis is enhanced via the extrinsic pathway. Interestingly, we identified the tight junction protein claudin1 as a regulator of these processes. This is the first indication that modulation of K8/18 expression can influence the phenotype of epithelial cancer cells at a transcriptional level and support the hypothesis that keratins play an active role in cancer progression.
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[148]
TÍTULO / TITLE: - Angiopoietin-2: an attractive target for improved antiangiogenic tumor therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 15;73(6):1649-57. doi: 10.1158/0008-5472.CAN-12-4697. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4697
AUTORES / AUTHORS: - Gerald D; Chintharlapalli S; Augustin HG; Benjamin LE
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, New York, New York; Eli Lilly and Company, Indianapolis, Indiana; Department of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg University; and Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ-ZMBH Alliance), Heidelberg, Germany.
RESUMEN / SUMMARY: - Anti-VEGF pathway therapies primarily target immature blood vessels in tumors. However, emerging approaches to combine with targeted therapies impacting the later stages of remodeling and vessel maturation are expected to improve clinical efficacy by expanding the target vessel population. The angiopoietin/Tie ligand/receptor system is a prototypic regulator of vessel remodeling and maturation. Angiopoietin-2 (Ang2) appears to be a particularly attractive therapeutic target. In fact, the experimental proof-of-concept showing improved efficacy when VEGF and Ang2-targeting therapies are combined has been solidly established in preclinical models, and several Ang2-targeting drugs are in clinical trials. However, rational development of these second-generation combination therapies is hampered by a limited understanding of the biological complexity that is generated from agonistic and antagonistic Ang/Tie signaling. This review discusses recent mechanistic advances in angiopoietin signaling, particularly in light of the recent study published on REGN910 and summarizes the status quo of Ang2-targeting therapies. In light of the clarified partial agonist function of Ang2, we propose that clarity on the expression profile of the angiopoietin ligands and Tie1 and Tie2 receptors in subsets of cancer vessels and cancer cells will provide clearer hypotheses for more focused rational clinical trials to exploit this seminal pathway and improve current antiangiogenic therapies. Cancer Res; 73(6); 1649-57. ©2013 AACR.
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[149]
TÍTULO / TITLE: - Hyaluronic Acid as a Marker of Hepatic Sinusoidal Obstruction Syndrome Secondary to Oxaliplatin-Based Chemotherapy in Patients with Colorectal Liver Metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2915-8
AUTORES / AUTHORS: - van den Broek MA; Vreuls CP; Winstanley A; Jansen RL; van Bijnen AA; Dello SA; Bemelmans MH; Dejong CH; Driessen A; Olde Damink SW
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands, m.vandenbroek@maastrichtuniversity.nl.
RESUMEN / SUMMARY: - BACKGROUND: A considerable number of patients develop sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy for colorectal liver metastases (CLMs). SOS is associated with adverse outcomes after major hepatectomy. Hyaluronic acid (HA) is a marker of hepatic sinusoidal endothelial cell function and may serve as an accurate marker of SOS. This study aimed to assess the value of systemic HA levels and fractional extraction (FE) of HA by the splanchnic area and liver as markers of SOS after oxaliplatin-based chemotherapy for CLMs. METHODS: Forty patients were studied. The presence of SOS was assessed histopathologically. Blood samples from the radial artery and portal and hepatic veins were collected. HA levels were determined by ELISA and the FE of HA was estimated. RESULTS: SOS was present in 23 patients, 11 of whom demonstrated moderate or severe SOS. Preoperative HA levels were significantly higher in patients with moderate or severe SOS (group B, n = 11) compared to patients with no or mild SOS (group A, n = 29) (51.6 +/- 10.2 ng/mL vs. 32.1 +/- 3.5 ng/mL, p = 0.030). A cutoff HA level of 44.1 ng/mL yielded a sensitivity of 67 % and specificity of 83 % for detection of SOS. The positive predictive value was 50 % and the negative predictive value 91 %. Both groups exhibited a similar FE of HA by the splanchnic area (-7.9 +/- 8.5 % in Group A vs. 7.3 +/- 3.6 % in Group B, p = 0.422) and liver (-10.7 +/- 6.2 % in Group A vs. 4.6 +/- 2.3 % in Group B, p = 0.265). CONCLUSIONS: Systemic HA levels can be used to detect patients at risk of SOS after oxaliplatin-based chemotherapy for CLMs. Additional investigations into the presence of SOS are indicated in patients with elevated HA levels.
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[150]
TÍTULO / TITLE: - Wwox expression may predict benefit from adjuvant tamoxifen in randomized breast cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1467-74. doi: 10.3892/or.2013.2261. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2261
AUTORES / AUTHORS: - Gothlin Eremo A; Wegman P; Stal O; Nordenskjold B; Fornander T; Wingren S
INSTITUCIÓN / INSTITUTION: - School of Health and Medical Sciences, Orebro University, SE-70182 Orebro, Sweden. anna.gothlin-eremo@oru.se
RESUMEN / SUMMARY: - Reduced or absent Wwox expression has recently been associated with tamoxifen resistance in breast cancer and has also been proposed as a candidate predictive marker for treatment. We aimed to investigate the correlation of Wwox expression with the outcome of tamoxifen treatment by examining tissues from 912 randomized breast cancer patients. Paraffin-embedded tissues from patient tumors were arranged on tissue microarray, and Wwox protein was stained using immunohistochemistry. After microscopic examination, the results were analyzed with Cox regression, Kaplan-Meier survival curves and the log-rank test. In the group of cases having a tumor absent for Wwox expression, there was no difference in recurrence-free survival between treated and untreated patients (P=0.81). For treated cases with a tumor expressing moderate or strong Wwox protein, recurrence-free survival was improved (P=0.001 and P=0.003, respectively). The test for interaction between Wwox and treatment response demonstrated a decreased risk of recurrence for treated patients with a moderate or strong Wwox expression (HR=0.31, 95% CI 0.10-0.98 and HR=0.28, 95% CI 0.08-0.97, respectively). Our results indicate that patients with high expression of Wwox may gain more benefit from treatment with tamoxifen.
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[151]
TÍTULO / TITLE: - KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastroenterol. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s00535-013-0767-4
AUTORES / AUTHORS: - Boeck S; Jung A; Laubender RP; Neumann J; Egg R; Goritschan C; Ormanns S; Haas M; Modest DP; Kirchner T; Heinemann V
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany, stefan.boeck@med.uni-muenchen.de.
RESUMEN / SUMMARY: - BACKGROUND: It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer (PC). METHODS: AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc). RESULTS: KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc. CONCLUSION: This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.
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[152]
TÍTULO / TITLE: - Interaction with Cyclin H/Cyclin-dependent Kinase 7 (CCNH/CDK7) Stabilizes C-terminal Binding Protein 2 (CtBP2) and Promotes Cancer Cell Migration.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Mar 29;288(13):9028-34. doi: 10.1074/jbc.M112.432005. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.432005
AUTORES / AUTHORS: - Wang Y; Liu F; Mao F; Hang Q; Huang X; He S; Wang Y; Cheng C; Wang H; Xu G; Zhang T; Shen A
INSTITUCIÓN / INSTITUTION: - From the Department of Pathogen and Immunology, Medical College, Nantong University, Nantong 226001, China.
RESUMEN / SUMMARY: - CtBP2 has been demonstrated to possess tumor-promoting capacities by virtue of up-regulating epithelial-mesenchymal transition (EMT) and down-regulating apoptosis in cancer cells. As a result, cellular CtBP2 levels are considered a key factor determining the outcome of oncogenic transformation. How pro-tumorigenic and anti-tumorigenic factors compete for fine-tuning CtBP2 levels is incompletely understood. Here we report that the cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) complex interacted with CtBP2 in vivo and in vitro. Depletion of either CCNH or CDK7 decreased CtBP2 protein levels by accelerating proteasome-dependent CtBP2 clearance. Further analysis revealed that CCNH/CDK7 competed with the tumor repressor HIPK2 for CtBP2 binding and consequently inhibited phosphorylation and dimerization of CtBP2. Phosphorylation-defective CtBP2 interacted more strongly with CCNH/CDK7 and was more resistant to degradation. Finally, overexpression of CtBP2 increased whereas depletion of CtBP2 dampened the invasive and migratory potential of breast cancer cells. CtBP2 promoted the invasion and migration of breast cancer cells in a CCNH-dependent manner. Taken together, our data have delineated a novel pathway that regulates CtBP2 stability, suggesting that targeting the CCNH/CDK7-CtBP2 axis may yield a viable anti-tumor strategy.
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[153]
TÍTULO / TITLE: - Inclusion of hemoglobin level in prognostic score provides better prognostic stratification in patients with acute promyelocytic leukemia (APL).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Hematol. 2013 Mar;97(3):388-96. doi: 10.1007/s12185-013-1276-1. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s12185-013-1276-1
AUTORES / AUTHORS: - Park S; Lee SJ; Kim K; Jang JH; Kim DH; Lee KH; Lee JH; Lee JH; Kim DY; Jang DY; Kim H; Park JH; Ryoo HM; Bae SH; Kim MK; Hyun MS; Joo YD; Lee WS; Lee SM; Jung CW
INSTITUCIÓN / INSTITUTION: - Division of Hematology-Oncology, Department of Medicine, Samsung Meidical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.
RESUMEN / SUMMARY: - The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC >/=10 x 109/L, platelet <40 x 109/L, hemoglobin <8.0 g/dL) was considered as a risk factor; the sum of each was designated as the CBC-score. With a median follow-up of 8.4 years, the complete remission (CR) rate was 81.4 % (127/156), while 24 (15.4 %) were considered as treatment failures due to early death (ED). The 5-year overall survival (OS), leukemia-free survival, and cumulative incidence of relapse were 73.8, 82.8, and 13.5 %, respectively. Compared to the individual CBC parameters, combined prognostic systems such as PETHEMA or CBC-score provided better prognostic stratification. Compared to PETHEMA stratification, the proposed prognostic CBC-score system showed better stratification of APL patients in terms of CR rates (p = 0.004), OS (p = 0.004), and ED (p = 0.008). This retrospective study suggests that the proposed CBC-score may provide better prognostic stratification of APL patients.
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[154]
TÍTULO / TITLE: - Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt081
AUTORES / AUTHORS: - Kaur M; Deep G; Jain AK; Raina K; Agarwal C; Wempe MF; Agarwal R
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences and.
RESUMEN / SUMMARY: - Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2-5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase ½ and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 microl water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness.
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[155]
TÍTULO / TITLE: - Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR-ABL kinase inhibition.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Hematol. 2013 Feb 18. doi: 10.1002/ajh.23419.
●● Enlace al texto completo (gratuito o de pago) 1002/ajh.23419
AUTORES / AUTHORS: - Simara P; Stejskal S; Koutna I; Potesil D; Tesarova L; Potesilova M; Zdrahal Z; Mayer J
INSTITUCIÓN / INSTITUTION: - CBIA-Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University, Brno, Czech Republic.
RESUMEN / SUMMARY: - Transient, potent BCR-ABL inhibition with tyrosine kinase inhibitors (TKIs) was recently demonstrated to be sufficient to commit chronic myeloid leukemia (CML) cells to apoptosis irreversibly. This mechanism explains the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. However, our in vitro data suggest that apoptosis induction after transient TKI treatment, observed in the BCR-ABL-positive cell lines K562, KYO-1, and LAMA-84 and progenitor cells from chronic phase CML patients, is instead caused by a residual kinase inhibition that persists in the cells as a consequence of intracellular drug retention. High intracellular concentrations of imatinib and dasatinib residues were measured in transiently treated cells. Furthermore, the apoptosis induced by residual imatinib or dasatinib from transient treatment could be rescued by washing out the intracellularly retained drugs. The residual kinase inhibition was also undetectable by the phospho-CRKL assay. These findings confirm that continuous target inhibition is required for the optimal efficacy of kinase inhibitors. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
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[156]
TÍTULO / TITLE: - Inhibition of NF-kappaB-mediated signaling by the CDK inhibitor CR8 overcomes pro-survival stimuli to induce apoptosis in chronic lymphocytic leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2170
AUTORES / AUTHORS: - Cosimo E; McCaig AM; Carter-Brzezinski LJ; Wheadon H; Leach MT; Le Ster K; Berthou C; Durieu E; Oumata N; Galons H; Meijer L; Michie AM
INSTITUCIÓN / INSTITUTION: - Experimental Haematology, University of Glasgow.
RESUMEN / SUMMARY: - Background: Chronic lymphocytic leukemia (CLL) is currently incurable with standard chemotherapeutic agents, highlighting the need for novel therapies. Overcoming proliferative and cytoprotective signals generated within the microenvironment of lymphoid organs is essential for limiting CLL progression and ultimately developing a cure. EXPERIMENTAL DESIGN: We assessed the potency of cyclin-dependent kinase (CDK) inhibitor CR8, a roscovitine analog, to induce apoptosis in primary CLL from distinct prognostic subsets using flow cytometry based assays. CLL cells were cultured in in vitro pro-survival and pro-proliferative conditions to mimic microenvironmental signals in the lymphoid organs, to elucidate the mechanism of action of CR8 in quiescent and proliferating CLL cells utilising flow cytometry, western blotting, and quantitative real-time PCR. RESULTS: CR8 was 100-fold more potent at inducing apoptosis in primary CLL cells than roscovitine, both in isolated culture and stromal-co-culture conditions. Importantly, CR8 induced apoptosis in CD40-ligated CLL cells and preferentially targeted actively proliferating cells within these cultures. CR8 treatment induced downregulation of the anti-apoptotic proteins Mcl-1 and XIAP, through inhibition of RNA polymerase II, and inhibition of NF-kappaB signaling at the transcriptional level and through inhibition of the IKK complex, resulting in stabilisation of IkappaBalpha expression. CONCLUSIONS: CR8 is a potent CDK inhibitor that subverts pivotal pro-survival and pro-proliferative signals present in the tumor microenvironment of CLL patient lymphoid organs. Our data support the clinical development of selective CDK inhibitors as novel therapies for CLL.
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[157]
TÍTULO / TITLE: - Lung Resistance-Related Protein (LRP) Expression in Malignant Ascitic Cells as a Prognostic Marker for Advanced Ovarian Serous Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 24.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2878-9
AUTORES / AUTHORS: - Kerr EH; Frederick PJ; Egger ME; Stockard CR; Sellers J; Dellamanna D; Oelschlager DK; Amm HM; Eltoum IE; Michael Straughn J; Buchsbaum DJ; Grizzle WE; McNally LR
INSTITUCIÓN / INSTITUTION: - Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
RESUMEN / SUMMARY: - PURPOSE: Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence. METHODS: We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naive and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers. RESULTS: Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p = 0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p = 0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p = 0.001) by in vitro assay and recurrence at 1 year (p = 0.0125). CONCLUSIONS: LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.
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[158]
TÍTULO / TITLE: - Protein kinase Cdelta is required for ErbB2-driven mammary gland tumorigenesis and negatively correlates with prognosis in human breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Mar 11. doi: 10.1038/onc.2013.59.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.59
AUTORES / AUTHORS: - Allen-Petersen BL; Carter CJ; Ohm AM; Reyland ME
INSTITUCIÓN / INSTITUTION: - Program in Cell Biology, Stem Cells and Development, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
RESUMEN / SUMMARY: - Protein kinase C delta (PKCdelta) regulates apoptosis in the mammary gland, however, the functional contribution of PKCdelta to the development or progression of breast cancer has yet to be determined. Meta-analysis of ErbB2-positive breast cancers shows increased PKCdelta expression, and a negative correlation between PKCdelta expression and prognosis. Here, we present in-vivo evidence that PKCdelta is essential for the development of mammary gland tumors in a ErbB2-overexpressing transgenic mouse model, and in-vitro evidence that PKCdelta is required for proliferative signaling downstream of the ErbB2 receptor. Mouse mammary tumor virus (MMTV)-ErbB2 mice lacking PKCdelta (deltaKO) have increased tumor latency compared with MMTV-ErbB2 wild-type (deltaWT) mice, and the tumors show a dramatic decrease in Ki-67 staining. To explore the relationship between PKCdelta and ErbB2-driven proliferation more directly, we used MCF-10A cells engineered to express a synthetic ligand-inducible form of the ErbB2 receptor. Depletion of PKCdelta with short hairpin RNA inhibited ligand-induced growth in both two-dimensional (2D) (plastic) and three-dimensional (3D) (Matrigel) culture, and correlated with decreased phosphorylation of the ErbB2 receptor and reduced activation of Src and MAPK/ERK pathways. Similarly, in human breast cancer cell lines in which ErbB2 is overexpressed, depletion of PKCdelta suppresses proliferation, Src and ERK activation. PKCdelta appears to drive proliferation through the formation of an active ErbB2/PKCdelta/Src signaling complex, as depletion of PKCdelta disrupts association of Src with the ErbB2 receptor. Taken together, our studies present the first evidence that PKCdelta is a critical regulator of ErbB2-mediated tumorigenesis, and suggest further investigation of PKCdelta as a target in ErbB2-positive breast cancer.Oncogene advance online publication, 11 March 2013; doi:10.1038/onc.2013.59.
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[159]
TÍTULO / TITLE: - Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 19;108(5):1034-41. doi: 10.1038/bjc.2013.58. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.58
AUTORES / AUTHORS: - Huillard O; Mir O; Peyromaure M; Tlemsani C; Giroux J; Boudou-Rouquette P; Ropert S; Delongchamps NB; Zerbib M; Goldwasser F
INSTITUCIÓN / INSTITUTION: - CERIA (Centre for Research on Angiogenesis Inhibitors), Department of Medical Oncology, Teaching Hospital Cochin, AP-HP, University Paris Descartes, 27, rue du Faubourg Saint Jacques, Paris F75014, France.
RESUMEN / SUMMARY: - Background:Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib.Methods:Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation.Results:Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25 kg m(-2). Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25 kg m(-2) experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3-13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009).Conclusion:Patients with sarcopenia and a BMI<25 kg m(-2) experienced significantly more DLTs during the first cycle of treatment.
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[160]
TÍTULO / TITLE: - Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Hematol. 2013 Feb 8. doi: 10.1002/ajh.23408.
●● Enlace al texto completo (gratuito o de pago) 1002/ajh.23408
AUTORES / AUTHORS: - Cortes J; Digumarti R; Parikh PM; Wetzler M; Lipton JH; Hochhaus A; Craig AR; Benichou AC; Nicolini FE; Kantarjian HM
INSTITUCIÓN / INSTITUTION: - Department of Leukemia, UT MD Anderson Cancer Center, Houston, Texas.
RESUMEN / SUMMARY: - Omacetaxine mepesuccinate (omacetaxine) is a first-in-class cephalotaxine with a unique mode of action, independent of BCR-ABL, that has shown promising activity in patients with chronic myeloid leukemia (CML). This multicenter, noncomparative, open-label phase 2 study evaluated the efficacy and safety of subcutaneous omacetaxine in CML patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs); results in patients in chronic phase are reported here. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily days 1-14 every 28 days until hematologic response (up to a maximum of six cycles), then days 1-7 every 28 days as maintenance. Primary endpoints were rates of hematologic response lasting >8 weeks and major cytogenetic response (MCyR). Forty-six patients were enrolled: all had received imatinib, 83% had received dasatinib, and 57% nilotinib. A median 4.5 cycles of omacetaxine were administered (range, 1-36). Hematologic response was achieved or maintained in 31 patients (67%); median response duration was 7.0 months. Ten patients (22%) achieved MCyR, including 2 (4%) complete cytogenetic responses. Median progression-free survival was 7.0 months [95% confidence interval (CI), 5.9-8.9 months], and overall survival was 30.1 months (95% CI, 20.3 months-not reached). Grade ¾ hematologic toxicity included thrombocytopenia (54%), neutropenia (48%), and anemia (33%). Nonhematologic adverse events were predominantly grade ½ and included diarrhea (44%), nausea (30%), fatigue (24%), pyrexia (20%), headache (20%), and asthenia (20%). Subcutaneous omacetaxine may offer clinical benefit to patients with chronic-phase CML with resistance or intolerance to multiple TKI therapies. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
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[161]
TÍTULO / TITLE: - KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Immunogenetics. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1007/s00251-013-0682-0
AUTORES / AUTHORS: - Campillo JA; Legaz I; Lopez-Alvarez MR; Bolarin JM; Las Heras B; Muro M; Minguela A; Moya-Quiles MR; Blanco-Garcia R; Martinez-Banaclocha H; Garcia-Alonso AM; Alvarez-Lopez MR; Martinez-Escribano JA
INSTITUCIÓN / INSTITUTION: - Immunology Department, Virgen de la Arrixaca University Hospital, Ctra. Madrid-Cartagena, 30120, El Palmar, Murcia, España, jcampillo68@hotmail.com.
RESUMEN / SUMMARY: - Natural killer and CD8(+) T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P < 0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (P © = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (P © = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(-)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(-)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis.
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[162]
TÍTULO / TITLE: - BRAF(V600E) protein expression and outcome from BRAF inhibitor treatment in BRAF(V600E) metastatic melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 5;108(4):924-31. doi: 10.1038/bjc.2013.29. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.29
AUTORES / AUTHORS: - Wilmott JS; Menzies AM; Haydu LE; Capper D; Preusser M; Zhang YE; Thompson JF; Kefford RF; von Deimling A; Scolyer RA; Long GV
INSTITUCIÓN / INSTITUTION: - 1] Melanoma Institute Australia, Sydney, New South Wales, Australia [2] Discipline of Pathology, The University of Sydney, Sydney, New South Wales, Australia.
RESUMEN / SUMMARY: - Background:To examine the association between level and patterns of baseline intra-tumoural BRAF protein expression and clinical outcome of BRAF melanoma patients treated with selective BRAF inhibitors.Methods:Fifty-eight BRAF metastatic melanoma patients treated with dabrafenib or vemurafenib on clinical trials had pre-treatment tumour BRAF protein expression immunohistochemically (IHC) assessed using the BRAF V600E mutant-specific antibody VE1. Sections were examined for staining intensity (score 1-3) and percentage of immunoreactive tumour cells, and from this an immunoreactive score (IRS) was derived (intensity x per cent positive/10). The presence of intra-tumoural heterogeneity for BRAF protein expression was also assessed. BRAF expression was correlated with RECIST response, time to best response (TTBR), progression-free survival (PFS) and overall survival (OS).Results:Expression was generally high (median IRS 28 (range 5-30)) and homogeneous (78%). Expression of mutated protein BRAF as measured by intensity, per cent immunoreactive cells, or IRS did not correlate with RECIST response, TTBR, PFS or OS, including on multivariate analysis. Heterogeneity of staining was seen in 22% of cases and did not correlate with outcome.Conclusion:In the current study population, IHC-measured pre-treatment BRAF protein expression does not predict response or outcome to BRAF inhibitor therapy in BRAF metastatic melanoma patients.
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[163]
TÍTULO / TITLE: - Phase II Open Label Study of the oral VEGF-Receptor inhibitor PTK787/ZK222584 (Vatalanib) in Adult Patients with Refractory or Relapsed Diffuse Large B Cell Lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.784969
AUTORES / AUTHORS: - Brander D; Rizzieri D; Gockerman J; Diehl L; Shea TC; Decastro C; Moore JO; Beaven A
RESUMEN / SUMMARY: - ABSTRACT PTK787/ZK222584 (Vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGF-Rs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once daily PTK787/ZK222584 at a target dose of 1250mg. Eighteen patients were evaluable for response: 1 patient had a complete response (CR), 6 patients had stable disease but subsequently progressed, 10 patients had progressive disease by 3 cycles, and 1 subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplantation and remains disease free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of DLBCL patients, though its therapeutic potential as a single agent in DLBCL appears limited.
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[164]
TÍTULO / TITLE: - FGF-2 Prevents Cancer Cells from ER Stress-Mediated Apoptosis via Enhancing Proteasome-mediated Nck Degradation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem J. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1042/BJ20121671
AUTORES / AUTHORS: - Li B; Pi Z; Liu L; Zhang B; Huang X; Hu P; Chevet E; Yi P; Liu J
RESUMEN / SUMMARY: - Induction of Endoplasmic Reticulum (ER) stress-mediated apoptosis in cancer cells represents an alternative approach for cancer therapy. Whether fibroblast growth factor 2 (FGF-2)-induced survival signals may interact with ER stress signalling in cancer cells remains elusive. In this work, we showed that pretreatment with FGF-2 decreased the inhibition of DNA synthesis and induction of apoptosis by two different ER stress inducers, tunicamycin ™ and thapsigargin (TG), in both human hepatoblastoma HepG2 cells and breast cancer MCF-7 cells. Pretreatment with FGF-2 prevented ER stress-mediated apoptosis by decreasing ER stress-induced CCAAT/-enhancer-binding protein homologous protein (CHOP) expression. We further demonstrated that pretreatment with FGF-2 mediated decrease of TM-induced CHOP expression and apoptosis through extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. Finally, we demonstrated that FGF-2 promoted proteasome-mediated degradation of Non-catalytic region of tyrosine kinase adaptor protein (Nck), a SH2/SH3-containing adaptor protein. Whereas overexpression of Nck1 decreased FGF-2-induced ERK1/2 phosphorylation to inhibit the effect of FGF-2 on TM-induced CHOP expression and apoptosis, and decrease of Nck expression prevented TM-induced CHOP expression and apoptosis. In all, our findings provide the first evidence that Nck plays a pivotal role in integrating FGF-2 and ER stress signals to counteract ER stress deleterious impact on cancer cell survival.
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[165]
TÍTULO / TITLE: - Combined inhibition of PI3K-related DNA-damage response kinases and mTORC1 induces apoptosis in MYC-driven B-cell lymphomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Blood. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1182/blood-2012-08-446096
AUTORES / AUTHORS: - Shortt J; Martin BP; Newbold A; Hannan KM; Devlin JR; Baker AJ; Ralli R; Cullinane C; Schmitt CA; Reimann M; Hall MN; Wall M; Hannan RD; Pearson RB; McArthur GA; Johnstone RW
INSTITUCIÓN / INSTITUTION: - Gene Regulation Laboratory, Cancer Therapeutics Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;
RESUMEN / SUMMARY: - Pharmacological strategies capable of directly targeting MYC are elusive. Previous studies have shown that MYC-driven lymphomagenesis is associated with mammalian target of rapamycin (mTOR) activation and a MYC-evoked DNA damage response (DDR), transduced by phosphatidylinositol-3-kinase (PI3K)-related kinases (DNA-PK, ATM and ATR). Here we report that BEZ235, a multi-targeted pan-PI3K/dual-mTOR inhibitor, potently killed primary Myc-driven B-cell lymphomas and human cell lines bearing IG-cMYC translocations. Using pharmacological and genetic dissection of PI3K/mTOR signaling, dual DDR/mTORC1 inhibition was identified as a key mediator of apoptosis. Moreover, apoptosis was initiated at drug concentrations insufficient to antagonize PI3K/mTORC2-regulated AKT phosphorylation. p53-independent induction of the pro-apoptotic BH3-only protein, BMF, was identified as a mechanism by which dual DDR/mTORC1 inhibition caused lymphoma cell death. BEZ235 treatment induced apoptotic tumor regressions in vivo that correlated with suppression of mTORC1-regulated substrates and reduced H2AX phosphorylation and also with feedback phosphorylation of AKT. These mechanistic studies hold important implications for the use of multi-targeted PI3K inhibitors in the treatment of hematological malignancies. In particular the newly elucidated role of PI3K-related DDR-kinases in the response to PI3K inhibitors offers a novel therapeutic opportunity for the treatment of hematological malignancies with a MYC-driven DDR.
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[166]
TÍTULO / TITLE: - The Chromatin Remodeling Gene ARID1A Is a New Prognostic Marker in Clear Cell Renal Cell Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Pathol. 2013 Apr;182(4):1163-70. doi: 10.1016/j.ajpath.2013.01.007. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2013.01.007
AUTORES / AUTHORS: - Lichner Z; Scorilas A; White NM; Girgis AH; Rotstein L; Wiegand KC; Latif A; Chow C; Huntsman D; Yousef GM
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
RESUMEN / SUMMARY: - Clear cell renal cell carcinoma (ccRCC) is the most common tumor of the adult kidney, with an increasing rate of incidence. Recently, exome sequencing studies have revealed that the SWI/SNF (switch/sucrose nonfermentable) members PBRM1 and ARID1A are mutated in ccRCC, and it has also been suggested that aberrant chromatin regulation is a key step in kidney cancer pathogenesis. Herein, we show that down-regulation of another SW/SNF component, ARID1A, occurs frequently in ccRCC. We detected copy number loss of ARID1A in 16% of patients with ccRCC. Immunohistochemistry indicated that 67% of ccRCC (53 of 79) had significantly lower expression of BAF250a, the protein product of ARID1A, than did the matched normal kidney cortex. In parallel, we conducted in silico mRNA expression analysis on 404 ccRCC tumors and 167 normal kidney cortex samples using publicly available databases and confirmed significant down-regulation of ARID1A in 68.8% of patients. We also show that decreased BAF250a protein and ARID1A mRNA expression correlate with tumor stage and grade. Our results indicate that both the protein and mRNA levels of ARID1A are statistically significant prognostic markers for ccRCC. Even after controlling for other confounders in the multivariate analysis, BAF250 retained its prognostic significance. BAF250a IHC is easy to perform and represents a potential biomarker that could be incorporated in laboratory practice to enhance the accuracy of the existing prognostic models.
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[167]
TÍTULO / TITLE: - Predictive Value of Intratumoral 99mTc-Macroaggregated Albumin Uptake in Patients with Colorectal Liver Metastases Scheduled for Radioembolization with 90Y-Microspheres.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Nucl Med. 2013 Apr;54(4):516-22. doi: 10.2967/jnumed.112.112508. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 2967/jnumed.112.112508
AUTORES / AUTHORS: - Ulrich G; Dudeck O; Furth C; Ruf J; Grosser OS; Adolf D; Stiebler M; Ricke J; Amthauer H
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany; and.
RESUMEN / SUMMARY: - (90)Y radioembolization is a promising therapy for patients with primary and secondary liver malignancies. Pretherapeutic assessment consists of hepatic angiography and (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) perfusion scintigraphy to estimate the liver-to-lung shunt and exclude extrahepatic (99m)Tc-MAA deposition. However, the predictive value of intratumoral (99m)Tc-MAA uptake remains unclear. METHODS: One hundred four patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer were treated with (90)Y radioembolization between December 2006 and December 2010. All of the patients underwent angiographic assessment and perfusion scintigraphy with (99m)Tc-MAA before lobar (90)Y radioembolization. For inclusion, patients must have undergone pretherapeutic and follow-up MR imaging (6 wk and 3 mo after radioembolization, respectively). The degree of intratumoral (99m)Tc-MAA uptake was rated, and liver metastases were classified according to changes in tumor diameter on both an individual and a patient basis using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response at both time points, MAA uptake, and catheter position were then statistically analyzed in a linear and generalized linear mixed model at a significance level of 0.05 (P value). RESULTS: Sixty-six patients with a total of 435 colorectal liver metastases (mean number of lesions +/- SD, 6.6 +/- 2.8; mean lesion size +/- SD, 33.8 +/- 21.2 mm; lesion size range, 10-154 mm) were included in this analysis. According to the patient-based analysis, 3 patients had partial response, 49 stable disease, and 6 progressive disease after 6 wk. After 3 mo, 5 patients showed partial response, 26 stable disease, and 17 progressive disease. There was no association of patient-based tumor response with overall (99m)Tc-MAA uptake (P = 0.172) or with catheter position (P = 0.6456). Furthermore, an interaction effect of (99m)Tc-MAA uptake and catheter position in relation to tumor response was not found (P = 0.512). Moreover, in lesion-based analysis according to RECIST 1.1 there was no association of tumor response with degree of (99m)Tc-MAA uptake, catheter position, or interaction of (99m)Tc-MAA uptake and catheter position (P = 0.339, 0.593, and 0.658, respectively). CONCLUSION: Response to (90)Y radioembolization was found to be independent of the degree of (99m)Tc-MAA uptake. Therefore, therapy should not be withheld from patients with colorectal liver metastases lacking intratumoral (99m)Tc-MAA accumulation.
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[168]
TÍTULO / TITLE: - Phase I-IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Mar 8. pii: S0959-8049(13)00120-2. doi: 10.1016/j.ejca.2013.02.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.02.012
AUTORES / AUTHORS: - Soria JC; Baselga J; Hanna N; Laurie SA; Bahleda R; Felip E; Calvo E; Armand JP; Shepherd FA; Harbison CT; Berman D; Park JS; Zhang S; Vakkalagadda B; Kurland JF; Pathak AK; Herbst RS
INSTITUCIÓN / INSTITUTION: - SITEP, Institut Gustave Roussy, South-Paris University, Villejuif, France. Electronic address: soria@igr.fr.
RESUMEN / SUMMARY: - PURPOSE: BMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. This phase I-IIa study was designed to identify the maximum tolerated dose (MTD) and assess safety, antitumour activity, pharmacokinetics and pharmacodynamics of BMS-690514. PATIENTS AND METHODS: In phase I, patients with advanced solid tumours received escalating doses of once-daily BMS-690514. In phase IIa, erlotinib-naive (cohort A) or erlotinib-resistant (cohort B) patients with advanced non-small-cell lung cancer (NSCLC) received BMS-690514 once-daily at the MTD. RESULTS: In phase I (n=28), the MTD was determined to be 200mg daily. BMS-690514 was rapidly absorbed and highly metabolised after repeated oral administration with minimum drug accumulation. In phase IIa (n=62), the most frequent treatment-related adverse events were diarrhoea and acneiform rash. Adverse events that led to >1 discontinuation were diarrhoea (n=4; 4%) and rash (n=2; 2%). Disease control (4months) and objective response rates, respectively, were 43.3% and 3.3% (cohort A) and 22.6% and 3.2% (cohort B). Six of 21 (29%) NSCLC patients with wild-type EGFR achieved disease control versus seven of 10 (70%) patients with EGFR mutations (including T790M). At MTD, BMS-690514 modulated pharmacodynamic biomarkers associated with inhibition of VEGFR- and EGFR-signalling pathways. CONCLUSION: This phase I-IIa study suggests that BMS-690514 has manageable safety profile and antitumour activity in patients with NSCLC at 200mg/d, including those with EGFR mutations conferring resistance to erlotinib.
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[169]
TÍTULO / TITLE: - Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):346-51. doi: 10.1097/JTO.0b013e31827e1f83.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827e1f83
AUTORES / AUTHORS: - Yu HA; Sima CS; Huang J; Solomon SB; Rimner A; Paik P; Pietanza MC; Azzoli CG; Rizvi NA; Krug LM; Miller VA; Kris MG; Riely GJ
INSTITUCIÓN / INSTITUTION: - Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, NY 10065, USA.
RESUMEN / SUMMARY: - BACKGROUND: Development of acquired resistance limits the utility of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for the treatment of EGFR-mutant lung cancers. There are no accepted targeted therapies for use after acquired resistance develops. Metastasectomy is used in other cancers to manage oligometastatic disease. We hypothesized that local therapy is associated with improved outcomes in patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI. METHODS: Patients who received non-central nervous system local therapy were identified by a review of data from a prospective biopsy protocol for patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy and other institutional biospecimen registry protocols. RESULTS: Eighteen patients were identified, who received elective local therapy (surgical resection, radiofrequency ablation, or radiation). Local therapy was well tolerated, with 85% of patients restarting TKI therapy within 1 month of local therapy. The median time to progression after local therapy was 10 months (95% confidence interval [CI]: 2-27 months). The median time until a subsequent change in systemic therapy was 22 months (95% CI: 6-30 months). The median overall survival from local therapy was 41 months (95% CI: 26-not reached). CONCLUSIONS: EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy are amenable to local therapy to treat oligometastatic disease when used in conjunction with continued EGFR inhibition. Local therapy followed by continued treatment with an EGFR TKI is well tolerated and associated with long PFS and OS. Further study in selected individuals in the context of other systemic options is required.
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[170]
TÍTULO / TITLE: - Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Electrophoresis. 2013 Feb 18. doi: 10.1002/elps.201200583.
●● Enlace al texto completo (gratuito o de pago) 1002/elps.201200583
AUTORES / AUTHORS: - Jayapalan JJ; Ng KL; Shuib AS; Razack AH; Hashim OH
INSTITUCIÓN / INSTITUTION: - University of Malaya Centre for Proteomics Research, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
RESUMEN / SUMMARY: - The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of two-dimensional gel electrophoresis and tandem mass spectrometry, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto nitrocellulose membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.
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[171]
TÍTULO / TITLE: - Cytarabine, aclarubicin and granulocyte colony-stimulating factor regimen represents an effective and safe salvage regimen for patients with acute myeloid leukemia refractory to first course of induction chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Apr 2.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.776679
AUTORES / AUTHORS: - Zhu HH; Jiang H; Jiang B; Lu J; Jiang Q; Bao L; Zhang XH; Qin YZ; Huang XJ
INSTITUCIÓN / INSTITUTION: - Peking University People’s Hospital, Peking University Institute of Hematology , Beijing , China.
RESUMEN / SUMMARY: - There is no consensus regarding the optimal second induction course regimen for patients with acute myeloid leukemia (AML) refractory to an initial course of front-line induction. The CAG regimen (cytarabine, aclarubicin and granulocyte colony-stimulating factor) has shown promise for relapsed/refractory AML. We retrospectively compared the efficacy and toxicity of the CAG regimen (n = 44) with a non-CAG regimen (n = 31) in 75 patients with AML refractory to an initial induction chemotherapy. The complete remission (CR) rate was higher for the CAG than the non-CAG regimen (63.5% vs. 38.7%, p = 0.038), and this was more pronounced in the subgroup of patients with a lower white blood cell (WBC) count before first/second induction, better- and intermediate-risk patients, and non-AML-M4/5 (p = 0.019). Although the CAG group demonstrated a higher disease-free survival than the non-CAG group among the intermediate- and poor-risk patients (p = 0.019), no differences in overall survival were observed. The CAG regimen produced hematological and non-hematological side effects similar to those of the non-CAG regimen. The most frequent CAG regimen side effects were infection (45.5%), fever (50%) and elevated transaminase levels (31.8%). No patients died within 4 weeks after initiating the second induction course in the CAG regimen. Thus, CAG represents a highly effective and safe salvage regimen for patients with AML who are refractory to the first induction chemotherapy. This regimen may be of specific benefit for CR in patients with low WBC count, better- and intermediate-risk, and non-M4/5 disease.
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[172]
TÍTULO / TITLE: - Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar 8. doi: 10.1038/cgt.2013.9.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.9
AUTORES / AUTHORS: - Camp ER; Wang C; Little EC; Watson PM; Pirollo KF; Rait A; Cole DJ; Chang EH; Watson DK
INSTITUCIÓN / INSTITUTION: - 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Ralph H Johnson VA Medical Center, Charleston, SC, USA.
RESUMEN / SUMMARY: - To overcome gene therapy barriers such as low transfection efficiency and nonspecific delivery, liposomal nanoparticles targeted by a single-chain antibody fragment to the transferrin receptor (TfRscFv) delivering wild-type (wt) human p53 (SGT-53) were developed for tumor-specific targeting. We hypothesize that SGT-53 in combination with gemcitabine will demonstrate enhanced therapeutic benefit in an in vivo metastatic pancreatic cancer model. Intrasplenic injection of 1 x 106 Panc02 murine pancreatic cancer cells was used to generate in vivo hepatic metastatic tumors. Nanoparticle localization was assessed by tail vein injection of TfRscFv with fluorescently labeled oligonucleotides (6-carboxyfluorescein phosphoramidite (6FAM) ODN) imaged by Xenogen IVIS 200 scan. SGT-53 (equivalent to 30 mug of p53 intravenously) and gemcitabine (20 mg/kg intraperitoneally) alone and in combination were administered biweekly and compared with untreated mice. Survival was determined by blinded daily assessment of morbidity. Human wtp53 expression and transferrin levels in the tumors were assessed by western blot analysis. Tumor burden was quantified by liver weight. Xenogen imaging demonstrated tumor-specific uptake of TfRscFv-6FAM ODN. Exogenous human wtp53 protein was detected in the SGT-53-treated tumors compared with control. Compared with untreated mice with metastatic tumors demonstrating median survival of 20 days, SGT-53, gemcitabine and the combination demonstrated improved median survival of 29, 30 and 37 days, respectively. The combination treatment prolonged median survival when compared with single drug treatment and decreased tumor burden. The tumor targeting liposomal-based SGT-53 nanoparticle is capable of sensitizing pancreatic cancer to conventional chemotherapy in pancreatic cancer models. This approach has the potential to be translated into a new, more effective therapy for pancreatic cancer. Further optimization is ongoing, moving towards a Phase 1B/2 clinical trial.Cancer Gene Therapy advance online publication, 8 March 2013; doi:10.1038/cgt.2013.9.
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[173]
TÍTULO / TITLE: - Pharmacogenomics in Alzheimer’s disease: a genome-wide association study of response to cholinesterase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neurobiol Aging. 2013 Jun;34(6):1711.e7-1711.e13. doi: 10.1016/j.neurobiolaging.2012.12.008. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.neurobiolaging.2012.12.008
AUTORES / AUTHORS: - Martinelli-Boneschi F; Giacalone G; Magnani G; Biella G; Coppi E; Santangelo R; Brambilla P; Esposito F; Lupoli S; Clerici F; Benussi L; Ghidoni R; Galimberti D; Squitti R; Confaloni A; Bruno G; Pichler S; Mayhaus M; Riemenschneider M; Mariani C; Comi G; Scarpini E; Binetti G; Forloni G; Franceschi M; Albani D
INSTITUCIÓN / INSTITUTION: - San Raffaele Scientific Institute, Division of Neuroscience, Laboratory of Genetics of Complex Neurological Disorders, Institute of Experimental Neurology (INSPE), Milan, Italy; Memory Clinic, Department of Neurology, and Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. Electronic address: martinelli.filippo@hsr.it.
RESUMEN / SUMMARY: - We conducted a genome-wide association study in a cohort of 176 Italian Alzheimer’s disease (AD) patients with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders in case of positive, stable, or </=1 worsening of mini-mental state examination score and into nonresponders if >3 points worsening during a median follow-up of 0.85 years of treatment. Forty-eight single-nucleotide polymorphisms were selected for replication in 198 additional AD-treated patients. By using the dichotomous response trait and a quantitative trait approach (change of mini-mental state examination), a nominal replication and evidence of association when combining data were achieved for 2 single-nucleotide polymorphisms associated with response to treatment: rs6720975 (p = 2.9 x 10, beta regression coefficient: 1.61) and rs17798800 (p = 6.8 x 10, odds ratio = 0.38, 95% confidence interval = 0.25-0.58). Rs6720975 maps in the intronic region of PRKCE, a protein kinase involved in several cellular functions, whereas rs17798800 is intergenic and, according to expression quantitative trait locus (eQTL) analysis, it acts as a cis-regulator of NBEA, an A kinase-anchoring protein playing a substantial role in the maturation of the nervous system. Despite its limitations, this project paves the way for the application of personalized medicine in AD patients and for collaborative efforts in this field.
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[174]
TÍTULO / TITLE: - Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Invest New Drugs. 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s10637-013-9935-x
AUTORES / AUTHORS: - Erba HP; Sayar H; Juckett M; Lahn M; Andre V; Callies S; Schmidt S; Kadam S; Brandt JT; Van Bockstaele D; Andreeff M
INSTITUCIÓN / INSTITUTION: - University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA, herba@uabmc.edu.
RESUMEN / SUMMARY: - Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n = 8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n = 16). LY2181308 was administered with a loading dosage of three consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m(2) was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m(2) was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials.
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[175]
TÍTULO / TITLE: - Transcriptome profiling and genome-wide DNA binding define the differential role of fenretinide and all-trans RA in regulating the death and survival of human hepatocellular carcinoma Huh7 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Pharmacol. 2013 Apr 1;85(7):1007-17. doi: 10.1016/j.bcp.2013.01.023. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.01.023
AUTORES / AUTHORS: - Hu Y; Liu HX; He Y; Fang Y; Fang J; Wan YJ
INSTITUCIÓN / INSTITUTION: - Department of Medical Pathology and Laboratory Medicine, 4645 2nd Ave, Research Building III, University of California, Davis Health Systems, Sacramento, CA 95817,United States. Electronic address: yinghu0821@gmail.com.
RESUMEN / SUMMARY: - Fenretinide is significantly more effective in inducing apoptosis in cancer cells than all-trans retinoic acid (ATRA). The current study uses a genome-wide approach to understand the differential role fenretinide and ATRA have in inducing apoptosis in Huh7 cells. Fenretinide and ATRA-induced gene expressions and DNA bindings were profiled using microarray and chromatin immunoprecipitation with anti-RXRalpha antibody. The data showed that fenretinide was not a strong transcription regulator. Fenretinide only changed the expressions of 1 093 genes, approximately three times less than the number of genes regulated by ATRA (2 811). Biological function annotation demonstrated that both fenretinide and ATRA participated in pathways that determine cell fate and metabolic processes. However, fenretinide specifically induced Fas/TNFalpha-mediated apoptosis by increasing the expression of pro-apoptotic genes i.e., DEDD2, CASP8, CASP4, and HSPA1A/B; whereas, ATRA induced the expression of BIRC3 and TNFAIP3, which inhibit apoptosis by interacting with TRAF2. In addition, fenretinide inhibited the expression of the genes involved in RAS/RAF/ERK-mediated survival pathway. In contrast, ATRA increased the expression of SOSC2, BRAF, MEK, and ERK genes. Most genes regulated by fenretinide and ATRA were bound by RXRalpha, suggesting a direct effect. This study revealed that by regulating fewer genes, the effects of fenretinide become more specific and thus has fewer side effects than ATRA. The data also suggested that fenretinide induces apoptosis via death receptor effector and by inhibiting the RAS/RAF/ERK pathway. It provides insight on how retinoid efficacy can be improved and how side effects in cancer therapy can be reduced.
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[176]
TÍTULO / TITLE: - Interaction between Interferon-Stimulated Gene 56 and Melanoma Differentiation-Associated Gene 5 in Toll-Like Receptor 3 Signaling in Normal Human Mesangial Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Nephrol. 2013;37(2):118-25. doi: 10.1159/000346415. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1159/000346415
AUTORES / AUTHORS: - Imaizumi T; Aizawa-Yashiro T; Matsumiya T; Yoshida H; Watanabe S; Tsuruga K; Tatsuta T; Xing F; Hayakari R; Meng P; Tanaka H
INSTITUCIÓN / INSTITUTION: - Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
RESUMEN / SUMMARY: - Background/Aims: Toll-like receptor 3 (TLR3) is a pathogen recognition receptor against viral double-stranded RNA. TLR3 signaling is important in antiviral responses, but inappropriate TLR3 signaling may be related with inflammatory renal diseases. Interferon (IFN)-stimulated gene 56 (ISG56) is an IFN-inducible gene that encodes a multifunctional protein with 6 tetratricopeptide motifs and is thought to be involved in antiviral reactions, but the role of ISG56 in TLR3 signaling in mesangial cells is not known well. Methods: Normal human mesangial cells were cultured and treated with a synthetic TLR3 ligand polyinosinic-polycytidylic acid, and the expression of ISG56 was analyzed using real-time RT-PCR and Western blot analyses. Using an RNA-interfering technique, involvement of TLR3, IFN-beta, melanoma differentiation-associated gene 5 (MDA5) or retinoic acid-inducible gene-I (RIG-I) in ISG56 expression, and of ISG56 in the expression of MDA5, RIG-I, CXCL10 and CCL5 was examined. Results: Treatment of cells with polyinosinic-polycytidylic acid induced ISG56. ISG56 induction was inhibited by knockdown of TLR3 or IFN-beta, and knockdown of ISG56 resulted in the decreased expression of MDA5, RIG-I, CXCL10 and CCL5. RNA interference against MDA5 decreased ISG56 expression. Conclusion: ISG56 was induced by TLR3 signaling via newly synthesized IFN-beta. ISG56 is involved in the expression of MDA5, RIG-I, CXCL10 and CCL5, and ISG56 and MDA5 may constitute a positive-feedback loop. ISG56 may play a role in immune and inflammatory reactions induced by TLR3 signaling in human mesangial cells.
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[177]
TÍTULO / TITLE: - Presence of the JAK2 V617F Mutation in a Patient with Chronic Neutrophilic Leukemia and Effective Response to Interferon Alfa-2b.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Haematol. 2013 Feb 7;130(1):44-46.
●● Enlace al texto completo (gratuito o de pago) 1159/000345851
AUTORES / AUTHORS: - Zhang X; Pan J; Guo J
INSTITUCIÓN / INSTITUTION: - Department of Hematology, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, PR China.
RESUMEN / SUMMARY: - Chronic neutrophilic leukemia (CNL) is a rare type of leukemia characterized by a proliferation mainly of mature neutrophils, elevated neutrophil-alkaline phosphatase activity, and no presence of the Philadelphia chromosome. The prognosis is generally poor and there is no consensus therapeutic strategy for the treatment of this disease. The JAK2 V617F mutation has been detected in patients with classical myeloproliferative disorders (MPD) including polycythemia vera and essential thrombocythemia and idiopathic myelofibrosis. In contrast, this same mutation has been detected in only 4 patients with CNL to date, suggesting that the JAK2 V617F mutation is a rare event in patients with atypical MPD. Here, we report a case of CNL with presence of the JAK2 V617F mutation. After treatment with interferon alfa-2b with 3 million units every other day for 1 month, the patient’s white blood cell count was well controlled below 10.0 x10(9)/l. At present, our patient remains symptomatically well and is maintained on interferon alfa-2b (3 million units twice a week), and his neutrophil count now averages around 8.0-10.0 x10(9)/l.
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[178]
TÍTULO / TITLE: - Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FASEB J. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1096/fj.12-226803
AUTORES / AUTHORS: - Jin L; Sturgis EM; Cao X; Song X; Salahuddin T; Wei Q; Li G
INSTITUCIÓN / INSTITUTION: - *Department of Head and Neck Surgery and daggerDepartment of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA;
RESUMEN / SUMMARY: - Interleukin-10 (IL-10) plays an important role in a host’s defense against human papillomavirus (HPV) infection. IL-10 promoter variants may affect its expression level or functional efficiency and, subsequently, susceptibility to and survival of HPV16-associated squamous cell carcinoma of oropharynx (SCCOP). We determined tumor HPV16 DNA and genotyped three IL-10 promoter polymorphisms in 309 incident patients with SCCOP. Compared with the patients with corresponding common homozygous genotypes, patients carrying variant genotypes of IL-10 rs1800871 and rs1800872 were approximately 2.5 times more likely to have HPV16(+) tumors among patients with SCCOP. Among HPV16(+) patients with SCCOP only, compared to those with the corresponding variant genotypes, the patients with IL-10 rs1800871 and rs1800872 CC genotypes had significantly better survival and approximately 70-80% reduced risk of death/recurrence after multivariable adjustment. Additionally, functional relevance of these variants was characterized to explore the genotype-phenotype correlation. Our findings indicate that IL-10 genetic variants may be associated with tumor HPV16(+) SCCOP and predict survival of HPV16(+) patients with SCCOP. Larger studies are needed to validate our findings.-Jin, L., Sturgis, E. M., Cao, X., Song, X., Salahuddin, T., Wei, Q., Li, G. Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx.
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[179]
TÍTULO / TITLE: - Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Feb 28;19(8):1318-21. doi: 10.3748/wjg.v19.i8.1318.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i8.1318
AUTORES / AUTHORS: - Lai GM; Yan SL; Chang CS; Tsai CY
INSTITUCIÓN / INSTITUTION: - Guan-Min Lai, Cheng-Shyong Chang, Chien-Yu Tsai, Division of Hemato-Oncology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan.
RESUMEN / SUMMARY: - Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients with chronic HBV infection receiving cytotoxic or immunosuppressive chemotherapy. Imatinib mesylate and nilotinib are selective Bcr/Abl tyrosine kinase inhibitors, which are now widely used in the treatment of patients with chronic myeloid leukemia. Although HBV reactivation induced by imatinib mesylate has been reported, nilotinib-related HBV reactivation has not been reported in the English literature. We report here 2 cases of HBV reactivation in chronic myeloid leukemia patients receiving imatinib mesylate and a novel case of nilotinib related HBV reactivation.
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[180]
TÍTULO / TITLE: - Verifying Hellstrom-Lindberg score as predictive tool for response to erythropoietin therapy according to the “International Working Group” criteria, in anemic patients affected by myelodysplastic syndrome: a monocentric experience.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Hematol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s12185-013-1305-0
AUTORES / AUTHORS: - Molteni A; Riva M; Greco R; Nichelatti M; Ravano E; Marbello L; Nosari A; Morra E
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Niguarda Ca’ Granda Hospital, Milan, Italy, alfredo.molteni@ospedaleniguarda.it.
RESUMEN / SUMMARY: - The Hellstrom-Lindberg score (HLS) (1997) is designed to predict erythroid response to erythropoietin treatment in myelodysplastic patients. In order to test the validity of this scoring system, 58 patients affected by myelodysplastic syndrome, treated with a “standard dose” approach between 2001 and 2010, were analyzed. The response to erythropoietin treatment was evaluated in accordance with the “international working group” (IWG) criteria. Among the patients only two were scored “poor,” 12 “intermediate,” and 44 “good” (15 of whom were scored “3” and 29 “4”). Although the system was verified as a predictive tool for response to erythropoietin therapy, we noted that of patients scored as “good,” those with a numerical score of “4” responded more frequently than did those scored “3”, as evaluated under both the 2006- and 2000-IWG (“major response”) criteria. The modest response rate in patients scoring “3” did not show a difference in response rate in comparison to the “intermediate” group. The present data suggest that only patients scoring “4” on the scale may show an adequate response to the standard dose erythropoietin therapy, while frontline high-dose therapy should be offered to other patients. A further analysis considering endogenous erythropoietin as a possible determinant of response revealed the optimal cut-off value of 80 mIU/mL, instead of the value of 100 mIU/mL utilized by the HLS.
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[181]
TÍTULO / TITLE: - CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1570-8. doi: 10.3892/or.2013.2273. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2273
AUTORES / AUTHORS: - Saito S; Okabe H; Watanabe M; Ishimoto T; Iwatsuki M; Baba Y; Tanaka Y; Kurashige J; Miyamoto Y; Baba H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
RESUMEN / SUMMARY: - CD44 standard isoform (CD44s) is a cancer stem cell marker in many tumors, and is one of the CD44 isoforms.CD44v6 has been reported to correlate with tumor progression and poor prognosis in colorectal cancer. However, the relevance of CD44s and CD44v6 to epithelial-mesenchymal transition (EMT) remains unclear. Immunohistochemistry was performed to investigate the clinical importance of CD44s and CD44v6 and their relevance to EMT in 113 patients with stage II/III colorectal cancer treated by curative resection. The relevance of CD44v6 knockdown to the phenotype of colon cancer cells was examined using small interfering RNA (siRNA) specific for CD44v6 in vitro. CD44v6 expression showed a significant inverse correlation with E-cadherin expression (P=0.0007) and a positive correlation with vimentin expression (P=0.0096). A multivariate analysis showed that high CD44v6 expression was an independent poor prognostic factor for disease-free survival (P=0.01, HR=3.05) and overall survival (P=0.025, HR=3.16). The clinical significance and the relevance of CD44s expression to EMT markers was noted to a lesser extent compared to CD44v6 expression. The knockdown of CD44v6 decreased vimentin expression, cell invasion and HGF-induced cell migration, but conferred only a slight effect on E-cadherin expression in colon cancer cells (HCT116 and LoVo). CD44v6 is related to poor outcome of patients with colorectal cancer via upregulation of the mesenchymal phenotype.
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[182]
TÍTULO / TITLE: - A Health-Care System Perspective on Implementing Genomic Medicine: Pediatric Acute Lymphoblastic Leukemia as a Paradigm.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Pharmacol Ther. 2013 Jan 17. doi: 10.1038/clpt.2013.9.
●● Enlace al texto completo (gratuito o de pago) 1038/clpt.2013.9
AUTORES / AUTHORS: - Evans WE; Crews KR; Pui CH
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.
RESUMEN / SUMMARY: - The promise of genomic medicine has received great attention over the past decade, projecting how genomics will soon guide the prevention, diagnosis, and treatment of human diseases. However, this evolution has been slower than forecast, even where evidence is often strong (e.g., pharmacogenomics). Reasons include the requirement for institutional resources and the need for the will to push beyond barriers impeding health-care changes. Here, we illustrate how genomics has been deployed to advance the treatment of childhood leukemia.Clinical Pharmacology & Therapeutics (2013); advance online publication 6 March 2013. doi:10.1038/clpt.2013.9.
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[183]
TÍTULO / TITLE: - Inhibition of ATP Citrate Lyase Induces an Anticancer Effect via Reactive Oxygen Species: AMPK as a Predictive Biomarker for Therapeutic Impact.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Pathol. 2013 Mar 15. pii: S0002-9440(13)00136-3. doi: 10.1016/j.ajpath.2013.01.048.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2013.01.048
AUTORES / AUTHORS: - Migita T; Okabe S; Ikeda K; Igarashi S; Sugawara S; Tomida A; Taguchi R; Soga T; Seimiya H
INSTITUCIÓN / INSTITUTION: - Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo.
RESUMEN / SUMMARY: - De novo lipogenesis is activated in most cancers. Inhibition of ATP citrate lyase (ACLY), the enzyme that catalyzes the first step of de novo lipogenesis, leads to growth suppression and apoptosis in a subset of human cancer cells. Herein, we found that ACLY depletion increases the level of intracellular reactive oxygen species (ROS), whereas addition of an antioxidant reduced ROS and attenuated the anticancer effect. ACLY depletion or exogenous hydrogen peroxide induces phosphorylation of AMP-activated protein kinase (p-AMPK), a crucial regulator of lipid metabolism, independently of energy status. Analysis of various cancer cell lines revealed that cancer cells with a higher susceptibility to ACLY depletion have lower levels of basal ROS and p-AMPK. Mitochondrial-deficient rho0 cells retained high levels of ROS and p-AMPK and were resistant to ACLY depletion, whereas the replenishment of normal mitochondrial DNA reduced the levels of ROS and p-AMPK and restored the sensitivity to ACLY depletion, indicating that low basal levels of mitochondrial ROS are critical for the anticancer effect of ACLY depletion. Finally, p-AMPK levels were significantly correlated to the levels of oxidative DNA damage in colon cancer tissues, suggesting that p-AMPK reflects cellular ROS levels in vitro and in vivo. Together, these data suggest that ACLY inhibition exerts an anticancer effect via increased ROS, and p-AMPK could be a predictive biomarker for its therapeutic outcome.
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[184]
TÍTULO / TITLE: - Human epidermal growth factor receptor 2 (Her-2) and S-1 adjuvant chemotherapy in stage 2/3 gastric cancer patients who underwent D2 gastrectomy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Today. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0544-2
AUTORES / AUTHORS: - Aoyama T; Yoshikawa T; Miyagi Y; Kameda Y; Shirai J; Hayashi T; Cho H; Oshima T; Yukawa N; Rino Y; Masuda M; Tsuburaya A
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
RESUMEN / SUMMARY: - PURPOSES: The trastuzumab for Gastric Cancer study newly defined tumors that were positive for human epidermal receptor-2 (Her-2) and created a Her-2-oriented treatment strategy that is also applicable in the adjuvant setting for stage 2/3 cancers. However, there is currently no information available on the rate of Her-2 positivity and the relapse-free survival (RFS) stratified by Her-2 status in stage 2/3 patients. METHODS: The Her-2 status, defined by the current standard method, was examined in 100 gastric cancer patients who underwent curative D2 surgery, who were pathologically diagnosed with stage 2/3 cancer, and received adjuvant S-1 chemotherapy between June 2002 and December 2011. RESULTS: Ten of the 100 patients were Her-2 positive. Her-2-positive status was more frequently seen in tumors with a differentiated histology. The 5-year RFS rate was 56.3 % in Her-2-positive cases, and 48.8 % in Her-2 negative cases, which was not significantly different (P = 0.786). CONCLUSIONS: The Her-2-positive rate for stage 2/3 gastric cancer patients was low, at only 10 %. Although the RFS was not significantly different based on the Her-2 status, the low positive rate made interpretation difficult. A multi-center study with a large sample size is necessary to clarify the prognostic impact of Her-2 in stage 2/3 gastric cancer patients.
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[185]
TÍTULO / TITLE: - XBP1 promoter polymorphism modulates platinum-based chemotherapy gastrointestinal toxicity for advanced non-small cell lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 16. pii: S0169-5002(13)00071-8. doi: 10.1016/j.lungcan.2013.02.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.012
AUTORES / AUTHORS: - Peng J; Chen YY; Yang LX; Zhao XY; Gao ZQ; Yang J; Wu WT; Wang HJ; Wang JC; Qian J; Chen HY; Jin L; Bai CX; Han BH; Lu DR
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - BACKGROUND: The X-box binding protein 1 (XBP1) is a critical transcription factor in the endoplasmic reticulum stress response, which is essential for the maintenance of cellular homeostasis. Here, we investigated whether the regulatory variant rs2269577 of the XBP1 gene influences clinical outcome in advanced non-small cell lung cancer (NSCLC) patients undergoing platinum-based chemotherapy. PATIENTS AND METHODS: We recruited 663 Chinese patients with advanced NSCLC treated with platinum-based regimens and assessed the association between rs2269577 and clinical outcome. Subsequent functional analyses, including real-time quantitative PCR and dual-luciferase assays, were performed to explore possible molecular mechanisms. RESULTS: The G/G genotype of rs2269577 was significantly associated with severe gastrointestinal toxicity compared with the homozygous C/C genotype (P=0.012, odds ratio=2.755), particularly in the female, performance status 0-1, and adenocarcinoma subgroups. No significant relevance was found between rs2269577 and treatment efficacy. In gastric epithelial cells, in vitro molecular analyses demonstrated that XBP1 mRNA expression levels decreased after treatment with cisplatin and the G allele of rs2269577 weakened the transcriptional activity of the XBP1 promoter. CONCLUSION: This is the first study to evaluate the effect of XBP1 polymorphism on severe chemotherapy-related adverse outcomes in platinum-treated advanced NSCLC patients using both pharmacogenomics and functional molecular analyses.
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[186]
TÍTULO / TITLE: - Prognostic significance of CD44 and c-erb-B2 protein overexpression in patients with gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatogastroenterology. 2012 Oct;59(119):2196-201. doi: 10.5754/hge10498.
●● Enlace al texto completo (gratuito o de pago) 5754/hge10498
AUTORES / AUTHORS: - Doventas A; Bilici A; Demirell F; Ersoy G; Turna H; Doventas Y
INSTITUCIÓN / INSTITUTION: - Department of Geriatrics, Istanbul Education and Research Hospital, Istanbul, Turkey.
RESUMEN / SUMMARY: - BACKGROUND/AIMS: The aim of the study is to evaluate the correlation between c-erb-B2 and CD44 overexpression and survival of patients with gastric cancer. METHODOLOGY: The paraffin blocks of 48 patients with gastric carcinoma were retrospectively analyzed. The pathological specimens were stained with CD44 and c-erb-B2 by immunohistochemical methods. RESULTS: The positivity of c-erb-B2 was detected in 9 patients. In six of them, predominantly strong cytoplasmic staining was observed. The remaining three tumors were predominantly membranous stained. No correlation was found between the c-erb-B2 positivity and overall survival (OS). Seventeen specimens (35.4%) were CD44 positive, all localized in cell membrane. The median OS time of CD44 positive patients was worse than that of patients with CD44 negative (11 vs. 17 months, respectively). This difference was statistically significant (p=0.03). In 5 patients both CD44 and c-erb-B2 were detected as positive. However, there were 23 patients with both CD44 negative and c-erb-B2 negative. The median OS time for patients with both CD44 and cerb- B2 negative was better than those of patients with both CD44 and c-erb-B2 positive (37 vs. 11 months, respectively, p=0.03). The relationship between CD44 and c-erb-B2 positivities and clinicopathological factors (p>0.05). CONCLUSIONS: Our results showed that there was no correlation between c-erb-B2 positivity and OS, except for CD44. In addition, we found significant association of simultaneous positivities of c-erb-B2 and CD44 with OS of patients with gastric cancer. CD44 alone can be taken as a prognostic factor and also simultaneous overexpression of CD44 and c-erb-B2 may be used as a marker of poor prognosis.
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[187]
TÍTULO / TITLE: - Inhibition of S6K1 enhances glucose deprivation-induced cell death via downregulation of anti-apoptotic proteins in MCF-7 breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 1;432(1):123-8. doi: 10.1016/j.bbrc.2013.01.074. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.01.074
AUTORES / AUTHORS: - Choi HN; Jin HO; Kim JH; Hong SE; Kim HA; Kim EK; Lee JK; Park IC; Noh WC
INSTITUCIÓN / INSTITUTION: - Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Republic of Korea.
RESUMEN / SUMMARY: - Nutrient-limiting conditions are frequently encountered by tumor cells in poorly vascularized microenvironments. These stress conditions may facilitate the selection of tumor cells with an inherent ability to decrease apoptotic potential. Therefore, selective targeting of tumor cells under glucose deprivation conditions may provide an effective alternative strategy for cancer therapy. In the present study, we investigated the effects of S6 kinase 1 (S6K1) inhibition on glucose deprivation-induced cell death and the underlying mechanisms in MCF-7 breast cancer cells. PF4708671, a selective inhibitor of S6K1, and knockdown of S6K1 with specific siRNA enhanced cell death induced under glucose deprivation conditions. Moreover, inhibition of S6K1 led to apoptosis in glucose-starved MCF-7 cells via downregulation of the anti-apoptotic proteins, Mcl-1 and survivin. Further experiments revealed that sorafenib, shown to be involved in Mcl-1 and survivin downregulation via mTOR/S6K1 inhibition significantly promotes cell death under glucose deprivation conditions. These findings collectively suggest that S6K1 plays an important role in tumor cell survival under stress conditions, and thus inhibition of S6K1 may be an effective strategy for sensitizing cells to glucose deprivation.
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[188]
TÍTULO / TITLE: - Pharmacodynamic stimulation of thrombogenesis by angiotensin (1-7) in recurrent ovarian cancer patients receiving gemcitabine and platinum-based chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):965-72. doi: 10.1007/s00280-013-2089-x. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2089-x
AUTORES / AUTHORS: - Pham H; Schwartz BM; Delmore JE; Reed E; Cruickshank S; Drummond L; Rodgers KE; Peterson KJ; Dizerega GS
INSTITUCIÓN / INSTITUTION: - Livingston Laboratory, Keck School of Medicine at USC, 1321 N. Mission Rd., Los Angeles, CA, 90033, USA.
RESUMEN / SUMMARY: - PURPOSE: This randomized, double-blind, placebo-controlled Phase 2 study evaluated safety and efficacy of A(1-7) for reduction in Grade 3-4 thrombocytopenia in patients receiving myelosuppressive chemotherapy. Pharmacodynamic activity of A(1-7) in platelet production and retention of scheduled dose intensity were also determined. METHODS: Thirty-four patients with ovarian, Fallopian tube, or peritoneal carcinoma receiving gemcitabine and carboplatin or cisplatin were evaluated. Patients were randomized to receive study drug subcutaneously at 100 mcg/kg (n = 11), 300 mcg/kg (n = 13), or placebo (n = 10) following chemotherapy for up to six cycles. Hematologic variables were obtained throughout each treatment cycle. RESULTS: There were no drug-related safety issues. There were no instances of Grade 4 thrombocytopenia in patients who received 100 mcg/kg treatment compared to 6 % of chemotherapy cycles for patients receiving placebo (p = 0.07). The maximal percentage increase in platelet concentration from baseline was higher for patients who received 100 mcg/kg A(1-7) compared to placebo (p = 0.02). This increase was accompanied by a reduction in the nadir absolute neutrophil count (p = 0.04). Relative dose intensity for the combination chemotherapy was higher for patients who received 100 mcg/kg A(1-7) compared to placebo (p = 0.04). There were no differences in outcomes for patients receiving 300 mcg/kg dose compared to placebo. CONCLUSIONS: A 100 mcg/kg dose of A(1-7) was shown to produce pharmacodynamic effects on peripheral blood platelet counts, preserve planned dose intensity, and reduce Grade 3-4 thrombocytopenia following gemcitabine and platinum chemotherapy. These findings are consistent with A(1-7)-induced stimulation of thrombogenesis in the bone marrow following marrow-toxic chemotherapy.
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[189]
TÍTULO / TITLE: - Upregulation of Adhesion Molecules on Leukemia Targets Improves the Efficacy of Cytotoxic T Cells Transduced With Chimeric Anti-CD19 Receptor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Immunother. 2013 Apr;36(3):181-9. doi: 10.1097/CJI.0b013e318288f8c1.
●● Enlace al texto completo (gratuito o de pago) 1097/CJI.0b013e318288f8c1
AUTORES / AUTHORS: - Laurin D; Marin V; Biagi E; Pizzitola I; Agostoni V; Gallot G; Vie H; Christine Jacob M; Chaperot L; Aspord C; Plumas J
INSTITUCIÓN / INSTITUTION: - *EFS Rhone-Alpes daggerINSERM U823, Immunobiologie et Immunotherapie des cancers double daggerUMR 5525 CNRS UJF, TIMC-IMAG/TheREx section signUniversite Joseph Fourier paragraph signLaboratoire d’Immunologie CHU, Grenoble daggerdaggerINSERM U892 parallelCHU Hotel Dieu-UTCG, Nantes, France #Department of Paediatrics, Centro di Ricerca Matilde Tettamanti **University of Milano-Bicocca, San Gerardo Hospital, Monza, Milan, Italy.
RESUMEN / SUMMARY: - T lymphocytes engineered to express chimeric antigen receptors (CARs) interact directly with cell surface molecules, bypassing MHC antigen presentation dependence. We generated human anti-CD19zeta CAR cytotoxic T lymphocytes and cytokine-induced killer cells and studied their sensitivity to the expression of adhesion molecules for the killing of primary B-lineage acute lymphoblastic leukemia (B-ALL) targets. Despite a very low basal expression of surface adhesion molecules, B-ALL blasts were lysed by the anti-CD19zeta-CAR transduced effectors as expected. We next investigated the regulatory role of adhesion molecules during CAR-mediated cytolysis. The blocking of these accessory molecules strongly limited the chimeric effector’s cytotoxicity. Thereafter, B-ALL cells surface adhesion molecule level expression was induced by IFN-gamma or by the combined use of CD40L and IL-4 and the cells were submitted to anti-CD19zeta-CAR transduced effectors lysis. Upregulation of adhesion molecules expression by blasts potentiated their killing. The improved cytotoxicity observed was dependent on target surface expression of adhesion molecules, particularly CD54. Taken together, these results indicate that adhesion molecules, and principally CD54, are involved in the efficiency of recognition by effector chimeric zeta. These observations have potential implications for the design of immunotherapy treatment approaches for hematological malignancies and tumors based on the adoption of CAR effector cells.
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[190]
TÍTULO / TITLE: - Economic Evaluation of Fulvestrant 500 mg Versus Generic Nonsteroidal Aromatase Inhibitors in Patients With Advanced Breast Cancer in the United Kingdom.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Ther. 2013 Mar;35(3):246-260.e5. doi: 10.1016/j.clinthera.2013.01.011. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinthera.2013.01.011
AUTORES / AUTHORS: - Das R; Cope S; Ouwens M; Turner P; Howlett M
INSTITUCIÓN / INSTITUTION: - AstraZeneca, Luton, Bedfordshire, United Kingdom. Electronic address: health.economicsuk@astrazeneca.com.
RESUMEN / SUMMARY: - OBJECTIVE: The goal of this study was to examine the cost-effectiveness of fulvestrant 500 mg for the treatment of first progression or recurrence of advanced breast cancer in postmenopausal patients compared with generic nonsteroidal aromatase inhibitors (anastrozole and letrozole) in the United Kingdom. METHODS: A cost-utility model based on a time-in-state approach was used. Clinical effectiveness estimates used in the model were derived from a network meta-analysis for overall survival and serious adverse events. Overall survival was extrapolated by using a Weibull distribution, and progression-free survival (PFS) estimates were derived from a simultaneous network meta-analysis and extrapolation of PFS curves by using the log-normal distribution. Data on resource use, costs, and utilities were based on various sources, including expert opinion and published data. To explore uncertainty, 1-way and probability sensitivity analyses were conducted. The study was conducted from the perspective of the UK National Health Service, and costs are reported in 2010/2011 British pounds. RESULTS: The base case incremental cost-effectiveness ratio (ICER) for fulvestrant 500 mg versus letrozole was pound34,528, with incremental costs of pound14,383 and an incremental quality-adjusted life-year (QALY) of 0.417. Extended dominance occurred for anastrozole because the ICER for anastrozole versus letrozole was higher than the ICER for fulvestrant 500 mg versus anastrozole. Based on the probability sensitivity analyses, the probability that fulvestrant 500 mg was the most cost-effective treatment option was 3%, 20%, and 53% at a willingness-to-pay threshold of pound20,000, pound30,000, and pound40,000 per QALY, respectively. According to the 1-way sensitivity analyses, the PFS estimates were the key drivers of the model results. CONCLUSIONS: Although fulvestrant 500 mg was found not to be a cost-effective option at a standard UK threshold of pound20,000 to pound30,000 per QALY, it may be relevant to apply a higher threshold due to the poor prognosis of patients with advanced breast cancer and the limited number of hormonal treatment options available for this stage of treatment. Certain subgroups may also benefit from fulvestrant as a treatment option; however, limited data are currently available to identify these subgroups.
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[191]
TÍTULO / TITLE: - Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 14. doi: 10.1038/bjc.2013.108.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.108
AUTORES / AUTHORS: - Eto K; Kawakami H; Kuwatani M; Kudo T; Abe Y; Kawahata S; Takasawa A; Fukuoka M; Matsuno Y; Asaka M; Sakamoto N
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
RESUMEN / SUMMARY: - Background:Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC.Methods:The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription-polymerase chain reactions and examined for correlations with GEM sensitivity.Results:The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively).Conclusion:hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.British Journal of Cancer advance online publication, 14 March 2013; doi:10.1038/bjc.2013.108 www.bjcancer.com.
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[192]
TÍTULO / TITLE: - The Proteasome Inhibitor Carfilzomib Functions Independently of p53 To Induce Cytotoxicity and an Atypical NF-kappaB Response in Chronic Lymphocytic Leukemia Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2754
AUTORES / AUTHORS: - Gupta SV; Hertlein E; Lu Y; Sass EJ; Lapalombella RT; Chen TL; Davis M; Woyach JA; Lehman A; Jarjoura D; Byrd JC; Lucas DM
INSTITUCIÓN / INSTITUTION: - Internal Medicine, Ohio State University.
RESUMEN / SUMMARY: - PURPOSE: The proteasome consists of chymotrypsin-like (CT-L), trypsin-like, and caspase-like subunits that cleave substrates preferentially by amino acid sequence. Proteasomes mediate degradation of regulatory proteins of the p53, Bcl-2 and nuclear factor-kappaB (NF-kappaB) families that are aberrantly active in chronic lymphocytic leukemia (CLL). CLL remains an incurable disease, and new treatments are especially needed in the relapsed/refractory setting. We therefore investigated the effects of the proteasome inhibitor carfilzomib (CFZ) in CLL cells. EXPERIMENTAL DESIGN: Tumor cells from CLL patients were assayed in vitro using immunoblotting, real-time polymerase chain reaction and electrophoretic mobility shift assays. Additionally, a p53 dominant-negative construct was generated in a human B-cell line. RESULTS: Unlike bortezomib, CFZ potently induces apoptosis in CLL patient cells in the presence of human serum. CLL cells have significantly lower basal CT-L activity compared to normal B and T cells, although activity is inhibited similarly in T cells vs. CLL. Co-culture of CLL cells on stroma protected from CFZ-mediated cytotoxicity; however, PI3K inhibition significantly diminished this stromal protection. CFZ-mediated cytotoxicity in leukemic B-cells is caspase-dependent and occurs irrespective of p53 status. In CLL cells, CFZ promotes atypical activation of NF-kappaB evidenced by loss of cytoplasmic IkBalpha, phosphorylation of IkappaBalpha and increased p50/p65 DNA binding, without subsequent increases in canonical NF-kappaB target gene transcription. CONCLUSIONS: Together, these data provide new mechanistic insights into the activity of CFZ in CLL and support Phase I investigation of CFZ in this disease.
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[193]
TÍTULO / TITLE: - Polymeric delivery of siRNA for dual silencing of Mcl-1 and P-glycoprotein and apoptosis induction in drug-resistant breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar;20(3):169-77. doi: 10.1038/cgt.2013.8. Epub 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.8
AUTORES / AUTHORS: - Aliabadi HM; Mahdipoor P; Uludag H
INSTITUCIÓN / INSTITUTION: - Department of Chemical and Material Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada.
RESUMEN / SUMMARY: - Enhanced survival mechanisms of malignant cells in combination with elevated levels of drug transporters can sustain an undesirable resistance against drug therapy. Short interfering RNA (siRNA) delivery against targets involved in aberrant mechanisms is a promising approach and we hypothesize that simultaneous silencing of multiple targets could prove more advantageous than common approach to silence individual targets. To explore this approach, we targeted anti-apoptotic proteins myeloid cell leukemia 1 (Mcl-1) and survivin along with the efflux pump P-glycoprotein (P-gp) in drug-resistant breast cancer cells. Polymeric siRNA delivery was employed for this purpose by using small polyethylenimine (PEI) substituted with lipids. While silencing Mcl-1 caused approximately 90% cell death in wild-type cells, this effect was less significant in P-gp over-expressing cells. An additive effect for Mcl-1 and P-gp silencing was evident in the latter cells, where simultaneous silencing of these targets created a significantly higher effect compared with silencing each individual target. Prolonged exposure of wild-type cells to doxorubicin (DOX) resulted in upregulation of P-gp, breast cancer resistance protein, survivin and Mcl-1. Dual silencing of P-gp and Mcl-1 again resulted in an additive effect in resistance-induced cells, which displayed an increased dependency on Mcl-1 for survival. Cytotoxic effect of DOX was also enhanced in resistance-induced cells after silencing Mcl-1. We conclude that polymer-mediated siRNA delivery can silence multiple targets simultaneously and reverse drug resistance.
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[194]
TÍTULO / TITLE: - Obesity rather than neoadjuvant chemotherapy predicts steatohepatitis in patients with colorectal metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Surg. 2013 Feb 3. pii: S0002-9610(13)00021-4. doi: 10.1016/j.amjsurg.2012.07.034.
●● Enlace al texto completo (gratuito o de pago) 1016/j.amjsurg.2012.07.034
AUTORES / AUTHORS: - Bower M; Wunderlich C; Brown R; Scoggins CR; McMasters KM; Martin RC
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer University of Louisville School of Medicine, 315 E. Broadway #311, Louisville, KY 40202, USA.
RESUMEN / SUMMARY: - INTRODUCTION: Neoadjuvant chemotherapy has been associated with an increased risk of surgery because of chemotherapy-associated steatohepatitis and sinusoidal obstruction. The aim of the current study was to assess for other predictors of steatohepatitis and sinusoidal obstruction and to determine the role of obesity as a risk factor in patients with colorectal liver metastasis (CLM). METHODS: An institutional review board-approved prospectively maintained database of 1,605 patients who underwent hepatic procedures for CLM from 2001 to 2009 was reviewed. RESULTS: In a review of 208 resected patients, body mass index was the only predictor of liver injury according to multivariate analysis (P < .001, odds ratio = 3.88). Diabetes, neoadjuvant chemotherapy, sleep apnea, alcohol use, tobacco use, age, and sex were not significant predictors. Among preoperative chemotherapy patients, BMI was a predictor of chemotherapy liver injury according to multivariate analysis (P < .0001). The rate of obesity (BMI >30) was 36%, and among obese patients (BMI >30) the rate of steatosis or steatohepatitis was 39%. CONCLUSIONS: Obesity is the strongest predictor of steatosis and steatohepatitis in patients with CLM, and this risk is independent of the use of preoperative chemotherapy.
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[195]
TÍTULO / TITLE: - The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Hematol. 2013 Apr;88(4):289-93. doi: 10.1002/ajh.23391. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1002/ajh.23391
AUTORES / AUTHORS: - Visco C; Finotto S; Pomponi F; Sartori R; Laveder F; Trentin L; Paolini R; Di Bona E; Ruggeri M; Rodeghiero F
INSTITUCIÓN / INSTITUTION: - Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy.
RESUMEN / SUMMARY: - Treatment of patients with B-cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B-cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m(2) , Day 1), plus bendamustine (70 mg/m(2) , days 1-2), and cytarabine (800 mg/m(2) , Day 1-3; R-BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with very selected high-risk R/R CLL. All patients (median age 60 years, range 53-74) had symptomatic Binet stage B or C active disease requiring treatment, were characterized by adverse cytogenetics (17p deletion, 11q deletion, or both), unmutated immunoglobulin heavy-chain variable region, and were heavily pretreated (1-5, median three previous lines). Overall, R-BAC was well tolerated with limited non-hematological toxicity. Major toxicities were transient Grade ¾ neutropenia and thrombocytopenia in 84% and 85% of patients, respectively. Overall response rate (OR) was 84%, including complete and partial response in 38% and 46% of patients, respectively. Patients with 17p deletion had an OR of 78%. After a median follow-up of 17 months, median progression-free survival was 16 months while median overall survival (OS) was not reached (1-year OS: 75 +/- 13%). R-BAC is an active regimen in R/R heavily pretreated high-risk patients with CLL, representing an option for the treatment of patients that are usually refractory to standard therapy. Am. J. Hematol. 88:289-293, 2013. © 2013 Wiley Periodicals, Inc.
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[196]
TÍTULO / TITLE: - Growth inhibition of pancreatic cancer cells by Histone Deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NFkB, and mTOR signaling in vitro and in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Carcinog. 2013 Mar 8. doi: 10.1002/mc.22024.
●● Enlace al texto completo (gratuito o de pago) 1002/mc.22024
AUTORES / AUTHORS: - Chien W; Lee DH; Zheng Y; Wuensche P; Alvarez R; Wen DL; Aribi AM; Thean SM; Doan NB; Said JW; Koeffler HP
INSTITUCIÓN / INSTITUTION: - Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403, Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1alpha at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P = 0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. © 2013 Wiley Periodicals, Inc.
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[197]
TÍTULO / TITLE: - HDAC inhibitors induce transcriptional repression of high copy number genes in breast cancer through elongation blockade.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Feb 25. doi: 10.1038/onc.2013.32.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.32
AUTORES / AUTHORS: - Kim YJ; Greer CB; Cecchini KR; Harris LN; Tuck DP; Kim TH
INSTITUCIÓN / INSTITUTION: - Department of Genetics, Yale University, School of Medicine, New Haven, CT, USA.
RESUMEN / SUMMARY: - Treatment with histone deacetylase inhibitors (HDACI) results in potent cytotoxicity of a variety of cancer cell types, and these drugs are used clinically to treat hematological tumors. They are known to repress the transcription of ERBB2 and many other oncogenes, but little is known about this mechanism. Using global run-on sequencing (GRO-seq) to measure nascent transcription, we find that HDACI cause transcriptional repression by blocking RNA polymerase II elongation. Our data show that HDACI preferentially repress the transcription of highly expressed genes as well as high copy number genes in HER2+ breast cancer genomes. In contrast, genes that are activated by HDACI are moderately expressed. We analyzed gene copy number in combination with microarray and GRO-seq analysis of expression level, in normal and breast cancer cells to show that high copy number genes are more likely to be repressed by HDACI than non-amplified genes. The inhibition of transcription of amplified oncogenes, which promote survival and proliferation of cancer cells, might explain the cancer-specific lethality of HDACI, and may represent a general therapeutic strategy for cancer.Oncogene advance online publication, 25 February 2013; doi:10.1038/onc.2013.32.
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[198]
TÍTULO / TITLE: - Enhanced tumor suppression by adenoviral PTEN gene therapy combined with cisplatin chemotherapy in small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar 8. doi: 10.1038/cgt.2013.14.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.14
AUTORES / AUTHORS: - Li D; Zhang Y; Xie Y; Xiang J; Zhu Y; Yang J
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, China.
RESUMEN / SUMMARY: - DNA-damaging anticancer drug cisplatin (cis-diamminedichloroplatinum) (DDP)-based chemotherapy is the mainstay and standard treatment for small-cell lung cancer (SCLC). However, frequent relapse and chemoresistance of SCLC remains a significant therapeutic hurdle. Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) as a negative regulator of phosphoinositide 3-kinase/AKT survival pathway exhibits strong tumor-suppressive activities. A combination of chemotherapy and gene therapy (chemogene therapy) is a promising practice in cancer therapy. In this report, we examined the combined antitumor effect of adenovirus-mediated PTEN (AdVPTEN) gene therapy and DDP chemotherapy on PTEN-null NCI-H446 human SCLC cells in vitro and in vivo in athymic BALB/c nude mice. We demonstrated that AdVPTEN plus DDP enhanced growth suppression, cell-cycle G1 phase arrest and apoptosis in in vitro NCI-H446 tumor cells and in vivo NCI-H446 xenografted tumors subcutaneously inoculated in nude mice. Mechanistically, AdVPTEN plus DDP exerted an overlapping effect on upregulation of P53, P21, P27, Bax and Cleaved Caspase-3 as well as downregulation of Bcl-2 and survivin in in vitro and in vivo NCI-H446 tumor cells. Moreover, AdVPTEN plus DDP additively reduced tumor vessel CD34 expression and microvessel density in vivo. The enhanced therapeutic efficacy elicited by AdVPTEN plus DDP was closely associated with additive induction of G1 phase arrest and apoptosis via substantially modulating cell-cycle regulation molecules and activating intrinsic apoptotic pathway through P53 restoration, and overlapping inhibition of tumor angiogenesis. Thus, our results indicated that AdVPTEN combined with DDP may be a novel and effective chemogene therapy modality for human SCLC.Cancer Gene Therapy advance online publication, 8 March 2013; doi:10.1038/cgt.2013.14.
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[199]
TÍTULO / TITLE: - EGFR and TTF-1 Gene Amplification in Surgically Resected Lung Adenocarcinomas: Clinicopathologic Significance and Effect on Response to EGFR-Tyrosine Kinase Inhibitors in Recurred Cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 23.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2937-2
AUTORES / AUTHORS: - Lee JS; Kim HR; Lee CY; Shin M; Shim HS
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUND: Gene amplifications are implicated in cancer development and progression. In this study we investigated the clinicopathologic characteristics associated with EGFR or TTF-1 amplification in lung adenocarcinomas and its prognostic significance. METHODS: We analyzed 118 cases of surgically resected primary lung adenocarcinomas. Amplification of the EGFR or TTF-1 gene was evaluated by fluorescence in situ hybridization and correlated with patients’ clinicopathologic features, including disease-free survival (DFS) and overall survival (OS), in all patients and a subset that were TTF-1 positive or had EGFR mutation. Progression-free survival (PFS) also was analyzed among patients with EGFR mutation who had recurred cancer that was treated with EGFR tyrosine kinase inhibitors. RESULTS: EGFR or TTF-1 gene amplification was an independent poor prognostic factor for DFS in all patients (p = 0.001), in patients with TTF-1 positivity (p = 0.010), and in patients with EGFR mutation (p < 0.001) and for OS in patients with TTF-1 positivity (p = 0.021) and patients with EGFR mutation (p < 0.001). Patients with TTF-1 amplification had a shorter PFS following EGFR TKI treatment (p = 0.040). CONCLUSIONS: EGFR or TTF-1 gene amplification was a predictive factor for poor prognosis in terms of DFS and OS, especially in patients with TTF-1 positivity or EGFR mutation. Our results also suggested that TTF-1 amplification might be a predictive marker of poor response to EGFR-TKI therapy in patients with recurrent tumor after surgical resection.
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[200]
TÍTULO / TITLE: - Promoter CpG Island Hypermethylation of the DNA Repair Enzyme MGMT Predicts Clinical Response to Dacarbazine in a Phase II Study for Metastatic Colorectal Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 3.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3518
AUTORES / AUTHORS: - Amatu A; Sartore-Bianchi A; Moutinho C; Belotti A; Bencardino K; Chirico G; Cassingena A; Rusconi F; Esposito A; Nichelatti M; Esteller M; Siena S
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Department of Hematology and Oncology, Radiology, Pharmacy, and Service of Biostatistics, Ospedale Niguarda Ca’ Granda, Milan, Italy; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL); Department of Physiological Sciences II, School of Medicine, University of Barcelona; and Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Catalonia, España.
RESUMEN / SUMMARY: - PURPOSE: O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O6-guanine in DNA. Approximately 40% of colorectal cancers (CRC) display MGMT deficiency due to the promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O6-guanine site, inducing base pair mismatch; therefore, activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild-type).EXPERIMENTAL DESIGN: All patients had tumor tissue assessed for MGMT as promoter hypermethylation in double-blind for treatment outcome. Patients received dacarbazine 250 mg/m2 intravenously every day for four consecutive days, every 21 days, until progressive disease or intolerable toxicity. We used a Simon two-stage design to determine whether the overall response rate would be 10% or more. Secondary endpoints included association of response, progression-free survival, and disease control rate with MGMT status.RESULTS: Sixty-eight patients were enrolled from May 2011 to March 2012. Patients received a median of three cycles of dacarbazine (range 1-12). Grades 3 and 4 toxicities included: fatigue (41%), nausea/vomiting (29%), constipation (25%), platelet count decrease (19%), and anemia (18%). Overall, two patients (3%) achieved partial response and eight patients (12%) had stable disease. Disease control rate (partial response + stable disease) was significantly associated with MGMT promoter hypermethylation in the corresponding tumors.CONCLUSION: Objective clinical responses to dacarbazine in patients with metastatic CRC are confined to those tumors harboring epigenetic inactivation of the DNA repair enzyme MGMT. Clin Cancer Res; 19(8); 1-8. ©2013 AACR.
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[201]
TÍTULO / TITLE: - An endogenous inhibitor of angiogenesis inversely correlates with side population phenotype and function in human lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Mar 11. doi: 10.1038/onc.2013.61.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.61
AUTORES / AUTHORS: - Han H; Bourboulia D; Jensen-Taubman S; Isaac B; Wei B; Stetler-Stevenson WG
INSTITUCIÓN / INSTITUTION: - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, the National Institutes of Health, Advanced Technology Center, Bethesda, MD, USA.
RESUMEN / SUMMARY: - The side population (SP) in human lung cancer cell lines and tumors is enriched with cancer stem cells. An endogenous inhibitor of angiogenesis known as tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), characterized for its ability to inhibit matrix metalloproteinases (MMPs), has been shown by several laboratories to impede tumor progression through MMP-dependent or -independent mechanisms. We recently reported that forced expression of TIMP-2, as well as the modified form Ala+TIMP-2 (that lacks MMP inhibitory activity) significantly blocks growth of A549 human lung cancer cells in vivo. However, the mechanisms underlying TIMP-2 antitumor effects are not fully characterized. Here, we examine the hypothesis that the TIMP-2 antitumor activity may involve regulation of the SP in human lung cancer cells. Indeed, using Hoechst dye efflux assay and flow cytometry, as well as quantitative reverse transcriptase-PCR analysis, we found that endogenous TIMP-2 mRNA levels showed a significant inverse correlation with SP fraction size in six non-small cell lung cancer cell lines. In A549 cells expressing increased levels of TIMP-2, a significant decrease in SP was observed, and this decrease was associated with lowered gene expression of ABCG2, ABCB1 and AKR1C1. Functional analysis of A549 cells showed that TIMP-2 overexpression increased chemosensitivity to cytotoxic drugs. The SP isolated from TIMP-2-overexpressing A549 cells also demonstrated impaired migratory capacity compared with the SP from empty vector control. More importantly, our data provide strong evidence that these TIMP-2 functions occur independent of MMP inhibition, as A549 cells overexpressing Ala+TIMP-2 exhibited identical behavior to those overexpressing TIMP-2 alone. Our findings provide the first indication that TIMP-2 modulates SP phenotype and function, and suggests that TIMP-2 may act as an endogenous suppressor of the SP in human lung cancer cells.Oncogene advance online publication, 11 March 2013; doi:10.1038/onc.2013.61.
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[202]
TÍTULO / TITLE: - Chemotherapy and Radiotherapy Downregulate the Activity and Expression of DNA Methyltransferase and Enhance Bcl-2/E1B-19-kDa Interacting Protein-3-Induced Apoptosis in Human Colorectal Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chemotherapy. 2013 Jan 29;58(6):445-453.
●● Enlace al texto completo (gratuito o de pago) 1159/000345916
AUTORES / AUTHORS: - Deng Q; Huang CM; Chen N; Li L; Wang XD; Zhang W; Bi F; Tang QL; Li ZP; Wang W
INSTITUCIÓN / INSTITUTION: - Department of Abdomen Oncology, Cancer Center of West China Hospital, West China Medical School, Sichuan University, Chengdu, PR China.
RESUMEN / SUMMARY: - Bcl-2/E1B 19-kDa interacting protein 3 (BNIP3) is a proapoptotic protein whose expression level is often low in colorectal cancer (CRC) cells due to the BNIP3 gene promoter DNA methylation by DNA methyltransferase (DNMT). It is known that chemotherapy and radiotherapy suppress CRC through inducing tumor apoptosis. However, the molecular mechanisms underlying chemotherapy and radiotherapy-induced apoptosis of CRC cells are not well defined. In this study, we observed that the expression level of BNIP3 in colon cancer cells was significantly increased by treatment with therapeutic agents and radiation in vitro. The BNIP3 protein level in CRC tissues from patients who received preoperative concurrent chemotherapy was significantly higher than in those who received surgery alone. Furthermore, treatment with chemotherapeutic agents and radiation significantly decreased the DNMT1 expression level and enzymatic activity. Both expression level and activity of DNMT1 were inversely correlated with the expression level of BNIP3 in colon carcinoma cells after treatment with chemotherapeutic agents and radiation. Consistent with increased BNIP3 expression, chemotherapeutic agents and radiation induced colon carcinoma cell apoptosis in a dose-dependent manner. Based on these observations, we conclude that chemotherapy and radiotherapy inhibit DNMT1 expression to upregulate BNIP3 expression to promote CRC cell apoptosis. And, BNIP3 may play a role in the caspase-dependent apoptosis pathways, mainly during treatment with chemotherapy and radiotherapy.
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[203]
TÍTULO / TITLE: - Vaccination for Invasive Canine Meningioma Induces in Situ Production of Antibodies Capable of Antibody-Dependent Cell-Mediated Cytotoxicity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3366
AUTORES / AUTHORS: - Andersen BM; Pluhar GE; Seiler C; Goulart MR; Santacruz KS; Schutten MM; Meints JP; O’Sullivan G; Bentley RT; Packer RA; Thomovsky SA; Chen AV; Faissler D; Chen W; Hunt MA; Olin MR; Ohlfest JR
INSTITUCIÓN / INSTITUTION: - Pediatrics, University of Minnesota.
RESUMEN / SUMMARY: - Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. Interferon gamma elaborating T cells were detected in the peripheral blood of two cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and heat shock protein 60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, demonstrating common antigens across breed and species. Histological analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in post-treatment compared to pre-treatment samples. Tumor-reactive antibodies were capable of inducing antibody dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data demonstrate the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development towards human trials.
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[204]
TÍTULO / TITLE: - Targeting the EP1 receptor reduces Fas ligand expression and increases the antitumor immune response in an in vivo model of colon cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28076.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28076
AUTORES / AUTHORS: - O’Callaghan G; Ryan A; Neary P; O’Mahony C; Shanahan F; Houston A
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University College Cork, Cork, Ireland.
RESUMEN / SUMMARY: - Despite studies demonstrating that inhibition of cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2 ) has significant chemotherapeutic benefits in vitro and in vivo, inhibition of COX enzymes is associated with serious gastrointestinal and cardiovascular side effects, limiting the clinical utility of these drugs. PGE2 signals through four different receptors (EP1-EP4) and targeting individual receptor(s) may avoid these side effects, while retaining significant anticancer benefits. Here, we show that targeted inhibition of the EP1 receptor in the tumor cells and the tumor microenvironment resulted in the significant inhibition of tumor growth in vivo. Both dietary administration and direct injection of the EP1 receptor-specific antagonist, ONO-8713, effectively reduced the growth of established CT26 tumors in BALB/c mice, with suppression of the EP1 receptor in the tumor cells alone less effective in reducing tumor growth. This antitumor effect was associated with reduced Fas ligand expression and attenuated tumor-induced immune suppression. In particular, tumor infiltration by CD4+ CD25+ Foxp3+ regulatory T cells was decreased, whereas the cytotoxic activity of isolated splenocytes against CT26 cells was increased. F4/80+ macrophage infiltration was also decreased; however, there was no change in macrophage phenotype. These findings suggest that the EP1 receptor represents a potential target for the treatment of colon cancer.
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[205]
TÍTULO / TITLE: - Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Feb 27. pii: S0960-894X(13)00265-5. doi: 10.1016/j.bmcl.2013.02.080.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.02.080
AUTORES / AUTHORS: - You OH; Kim SH; Kim B; Sohn EJ; Lee HJ; Shim BS; Yun M; Kwon BM; Kim SH
INSTITUCIÓN / INSTITUTION: - College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
RESUMEN / SUMMARY: - Ginkgetin is a natural biflavonoid isolated from leaves of Ginkgo biloba L. Though it was known to have anti-inflammatory, anti-influenza virus, anti-fungal activity, osteoblast differentiation stimulating activity and neuro-protective effects, the underlying antitumor mechanism of ginkgetin still remains unclear. Thus, in the present study, anti-cancer mechanism of ginkgetin was elucidated in human prostate cancer PC-3 cells. Ginkgetin suppressed the viability of PC-3 cells in a concentration-dependent manner and also significantly increased the sub-G1 DNA contents of cell cycle in PC-3 cells. Ginkgetin activated caspase-3 and attenuated the expression of survival genes such as Bcl-2, Bcl-xL, survivin and Cyclin D1 at protein and mRNA levels. Consistently, pan-caspase inhibitor Z-DEVD-fmk blocked sub G1 accumulation and cleavages of PRAP and caspase 3 induced by ginkgetin in PC-3 cells. Overall, these findings suggest that ginkgetin induces apoptosis in PC-3 cells via activation of caspase 3 and inhibition of survival genes as a potent chemotherapeutic agent for prostate cancer treatment.
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[206]
TÍTULO / TITLE: - Targeting heat shock proteins by phenethyl isothiocyanate results in cell-cycle arrest and apoptosis of human breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Apr;65(3):480-93. doi: 10.1080/01635581.2013.767366.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.767366
AUTORES / AUTHORS: - Sarkars R; Mukherjee S; Roy M
INSTITUCIÓN / INSTITUTION: - a Department of Environmental Carcinogenesis & Toxicology , Chittaranjan National Cancer Institute , Kolkata , India.
RESUMEN / SUMMARY: - Heat shock proteins (HSPs) are chaperones for several client proteins involved in transcriptional regulation, signal transduction, and cell cycle control. HSPs (27, 70, and 90) are abundantly expressed in a wide range of cancers and are transcriptionally regulated by heat shock factor (HSF1). Most of the synthetic HSP inhibitors exhibit toxicity, therefore, searching for inhibitors with limited or no toxicity will be of help. The objective of the present study was to determine the effect of natural isothiocyanate (phenethyl isothiocyanate; PEITC) on different HSPs (27, 70, and 90) and HSF1 in 2 breast cancer cell lines, namely breast adenocarcinoma MCF-7 (with wild type p53) and highly metastatic breast cancer cell MDA-MB-231 (with mutated p53). PEITC significantly inhibited the expression of HSPs (particularly HSP 90) and HSF1. Molecular consequences due to HSP inhibition were downregulation of cell-cycle regulatory proteins like Cyclin B1, CDK1, Cdc25C, PLK-1, and upregulation of p21 irrespective of p53 status. These modulations were accompanied by cell-cycle arrest at G2/M phase and apoptosis by activation of caspases 3 and 9. PEITC therefore may be regarded as a potent HSP inhibitor and an antitumor agent in the treatment of breast cancer.
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[207]
TÍTULO / TITLE: - Molecular Mechanism of Action of Bisphenol and Bisphenol-A Mediated by Estrogen Receptor alpha in Growth and Apoptosis of Breast Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Pharmacol. 2013 Feb 4. doi: 10.1111/bph.12122.
●● Enlace al texto completo (gratuito o de pago) 1111/bph.12122
AUTORES / AUTHORS: - Sengupta S; Obiorah I; Maximov PY; Curpan R; Jordan VC
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: Estrogen receptor alpha (ERalpha) binds to different ligand which can function as complete / partial estrogen-agonist or antagonist. This depends on the chemical structure of the ligands which modulates the transcriptional activity of the estrogen-responsive genes by altering the conformation of the liganded-ERalpha complex. This study determined the molecular mechanism of estrogen-agonistic / antagonistic action of structurally similar ligands, bisphenol (BP) and bisphenol-A (BPA) on cell proliferation and apoptosis of ERalpha+ve breast cancer cells. EXPERIMENTAL APPROACH: DNA was measured to assess the proliferation and apoptosis of breast cancer cells. RT- PCR and ChIP assays were performed to quantify the transcripts of TFF1 gene and recruitment of ERalpha and SRC3 at the promoter of TFF1 gene, respectively. Molecular docking was used to delineate the binding modes of BP and BPA with the ERalpha. PCR-based arrays were used study the regulation of the apoptotic genes. KEY RESULTS: BP and BPA induced the proliferation of breast cancer cells, however, unlike BPA, BP failed to induce apoptosis. BPA consistently acted as an agonist in our studies but BP exhibited mixed agonistic/antagonistic properties. Molecular docking revealed agonistic and antagonistic mode of binding for BPA and BP respectively. BPA treatment resembled E2 treatment in terms of PCR-based regulation of apoptotic genes whereas BP was similar to 4OHT treatment. CONCLUSIONS AND IMPLICATIONS: The chemical structure of ERalpha ligand determines the agonistic or antagonistic biological responses by the virtue of their binding mode, conformation of the liganded-ERalpha complex and the context of the cellular function. ABBREVIATIONS: 4OHT, 4-hydroxy tamoxifen; BP, bisphenol; BPA, bisphenol-A; ChIP, chromatin-immuno precipitation assay; DES, di-ethyl stilbestrol; E2, 17beta-estradiol; ERalpha, estrogen receptor alpha; LBD, ligand binding domain; RAL, raloxifene; RT-PCR, real time polymerase chain reaction; SRC3, steroid co-activator 3; TFF1, trefoil factor 1;
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[208]
TÍTULO / TITLE: - DNA damage-independent apoptosis induced by curcumin in normal resting human T cells and leukaemic Jurkat cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mutagenesis. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1093/mutage/get017
AUTORES / AUTHORS: - Korwek Z; Bielak-Zmijewska A; Mosieniak G; Alster O; Moreno-Villanueva M; Burkle A; Sikora E
INSTITUCIÓN / INSTITUTION: - Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur street, 02-093 Warsaw, Poland.
RESUMEN / SUMMARY: - Curcumin, a phytochemical derived from the rhizome of Curcuma longa, is a very potent inducer of cancer cell death. It is believed that cancer cells are more sensitive to curcumin treatment than normal cells. Curcumin has been shown to act as a prooxidant and induce DNA lesions in normal cells. We were interested in whether curcumin induces DNA damage and the DNA damage response (DDR) signalling pathway leading to apoptosis in normal resting human T cells. To this end, we analysed DNA damage after curcumin treatment of resting human T cells (CD3+) and of proliferating leukaemic Jurkat cells by the fluorimetric detection of alkaline DNA unwinding (FADU) assay and immunocytochemical detection of gamma-H2AX foci. We showed that curcumin-treated Jurkat cells and resting T cells showed neither DNA lesions nor did they activate key proteins in the DDR signalling pathway, such as phospho-ATM and phospho-p53. However, both types of cell were equally sensitive to curcumin-induced apoptosis and displayed activation of caspase-8 but not of DNA damage-dependent caspase-2. Altogether, our results revealed that curcumin can induce apoptosis of normal resting human T cells that is not connected with DNA damage.
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[209]
TÍTULO / TITLE: - Neoadjuvant chemotherapy with or without zoledronic acid in early breast cancer - a randomised biomarker pilot study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3235
AUTORES / AUTHORS: - Winter MC; Wilson C; Syddall SP; Cross SS; Evans A; Ingram CE; Jolley IJ; Hatton MQ; Freeman JV; Mori S; Holen I; Coleman RE
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Sheffield Teaching Hospitals NHS Foundation Trust.
RESUMEN / SUMMARY: - PURPOSE: To investigate the short-term biological effects of neoadjuvant chemotherapy +/- zoledronic acid (ZOL) in invasive breast cancer Experimental design: Forty patients were randomised to receive a single 4mg infusion of ZOL 24 hours after the first cycle of FE100C chemotherapy, or chemotherapy alone. Randomisation was stratified for tumour stage, ER, HER2, and menopausal status. All patients had repeat breast core-biopsy at Day 5 (D5) +/- Day 21 (D21). Effects on apoptotic index, proliferation (Ki67), growth index, surrogate serum markers of angiogenesis (VEGF) and serum reproductive hormones within the TGFbeta family (activin-A, TGFbeta1, inhibin-A and follistatin) were evaluated and compared. RESULTS: Baseline clinico-pathological characteristics were well balanced. Cell growth index (increased apoptosis and reduced proliferation) fell at D5 in both groups but recovered more rapidly with chemotherapy+ZOL than chemotherapy alone by D21 (p=0.006). At D5, a greater reduction in serum VEGF occurred with chemotherapy+ZOL compared to chemotherapy: median percentage change -23.8% (IQR -32.9, -15.8) vs. -8.4% (IQR -27.3, +8.9; p=0.02), but these effects were lost by D21. Postmenopausal women demonstrated a decrease in follistatin levels from baseline in the chemotherapy+ZOL group at D5 and D21, compared to chemotherapy alone (interaction p=0.051). CONCLUSIONS: In this pilot study, short-term changes in biomarkers suggest potentially relevant interactions between tumour biology, chemotherapy, modification of the bone microenvironment and the endocrine status of the host. Larger studies with more frequent dosing of zoledronic acid are needed to assess these complex interactions more thoroughly.
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[210]
TÍTULO / TITLE: - Antiproliferative, Antiinvasive, and Proapoptotic Activity of Folate Receptor alpha-Targeted Liposomal Doxorubicin in Nonfunctional Pituitary Adenoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocrinology. 2013 Apr;154(4):1414-23. doi: 10.1210/en.2012-2128. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1210/en.2012-2128
AUTORES / AUTHORS: - Liu X; Ma S; Dai C; Cai F; Yao Y; Yang Y; Feng M; Deng K; Li G; Ma W; Xin B; Lian W; Xiang G; Zhang B; Wang R
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People’s Republic of China. liuxiaohai09@yahoo.com.cn.
RESUMEN / SUMMARY: - There is an urgent need for novel therapeutic strategies for the treatment of nonfunctional pituitary adenomas (NFPAs), especially those that are invasive. The folate receptor (FR)alpha is overexpressed in several cancers, including NFPA. The aim of this study was to determine the efficacy of FRalpha-targeted liposomes loaded with doxorubicin (F-L-DOX) in the treatment of NFPA. We evaluated targeting, cytotoxicity, antiinvasive, and proapoptotic activity of F-L-DOX in 25 primary cell lines derived from patients with NFPAs. We found that these liposomes effectively targeted NFPA cells through FRalpha and that endocytosis of the liposomes was blocked by 1mM free folic acid. F-L-DOX inhibited proliferation of NFPA cells and promoted apoptosis through activation of caspase-8, caspase-9, and caspase-3/7 more effectively than L-DOX. Furthermore, F-L-DOX also exerted greater antiinvasive ability in NFPA cells than L-DOX through suppression of the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9. Addition of 1mM free folic acid significantly reduced the pleotropic effects of F-L-DOX in NFPA cells, suggesting that FRalpha plays a critical role in mediating the antitumor effect of F-L-DOX. Our findings warrant further investigation of F-L-DOX as an alternative therapeutic strategy for the treatment of NFPAs that express FRalpha.
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[211]
TÍTULO / TITLE: - Phosphorylation of AKT pathway proteins is not predictive of benefit of taxane therapy in early breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2489-y
AUTORES / AUTHORS: - Bartlett JM; A’hern R; Piper T; Ellis IO; Dowsett M; Mallon EA; Cameron DA; Johnston S; Bliss JM; Ellis P; Barrett-Lee PJ
INSTITUCIÓN / INSTITUTION: - Ontario Institute for Cancer Research, MaRS Centre, South Tower, 101 College Street, Suite 800, Toronto, ON, M5G 0A3, Canada, John.Bartlett@oicr.on.ca.
RESUMEN / SUMMARY: - Results from the NSABP B-28 trial suggest AKT activation may predict reduced benefit from taxanes following standard anthracycline therapy. Pre-clinical data support a link between PI3 K/AKT signalling and taxane resistance. Using the UK taxotere as adjuvant chemotherapy trial (TACT), we tested the hypothesis that activation of AKT or downstream markers, p70S6K or p90RSK, identifies patients with reduced benefit from taxane chemotherapy. TACT is a multi-centre open-label phase III trial comparing four cycles of standard FEC (fluorouracil, epirubicin, cyclophosphamide) followed by four cycles of docetaxel versus eight cycles of anthracycline-based chemotherapy. Samples from 3,596 patients were available for the current study. We performed immunohistochemical analysis of activation of AKT, p70S6 K and p90RSK. Using a training set with multiple cut-offs for predictive values (10 % increments in expression), we found no evidence for a treatment by marker interaction for pAKT473, pS6 or p90RSK. pAKT473, pS6 and p90RSK expression levels were weakly correlated. A robust, preplanned statistical analysis in the TACT trial found no evidence that pAKT473, pS6 or p90RSK identifies patients deriving reduced benefit from adjuvant docetaxel. This result is consistent with the recent NASBP B28 study where the pAKT473 effect is not statistically significant for the treatment interaction test. Therefore, neither TACT nor NASBP-B28 provides statistically robust evidence of a treatment by marker interaction between pAKT473 and taxane treatment. Alternative methods for selecting patients benefitting from taxanes should be explored.
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[212]
TÍTULO / TITLE: - Structure-Activity Relationship Studies of Pyrazolo[3,4-d]pyrimidine Derivatives Leading to the Discovery of a Novel Multikinase Inhibitor That Potently Inhibits FLT3 and VEGFR2 and Evaluation of Its Activity against Acute Myeloid Leukemia in Vitro and in Vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Chem. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1021/jm301537p
AUTORES / AUTHORS: - Yang LL; Li GB; Ma S; Zou C; Zhou S; Sun QZ; Cheng C; Chen X; Wang LJ; Feng S; Li LL; Yang SY
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, and double daggerCollege of Chemical Engineering, Sichuan University , Sichuan 610041, China.
RESUMEN / SUMMARY: - We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish-based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin -4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti-AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once-daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.
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[213]
TÍTULO / TITLE: - Breast cancer-derived transforming growth factor-beta and tumor necrosis factor-alpha compromise interferon-alpha production by tumor-associated plasmacytoid dendritic cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28072.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28072
AUTORES / AUTHORS: - Sisirak V; Vey N; Goutagny N; Renaudineau S; Malfroy M; Thys S; Treilleux I; Labidi-Galy SI; Bachelot T; Dezutter-Dambuyant C; Menetrier-Caux C; Blay JY; Caux C; Bendriss-Vermare N
INSTITUCIÓN / INSTITUTION: - Universite de Lyon, Lyon, France; Universite Lyon 1, ISPB, Lyon, France; INSERM U1052, Centre de Recherche en Cancerologie de Lyon, Department of Immunity, Virus, and Microenvironment, Lyon, France; CNRS UMR5286, Centre de Recherche en Cancerologie de Lyon, Department of Immunity, Virus, and Microenvironment, Lyon, France; LabEx DEVweCAN, Lyon, France.
RESUMEN / SUMMARY: - We previously reported that plasmacytoid dendritic cells (pDCs) infiltrating breast tumors are impaired for their interferon-alpha (IFN-alpha) production, resulting in local regulatory T cells amplification. We designed our study to decipher molecular mechanisms of such functional defect of tumor-associated pDC (TApDC) in breast cancer. We demonstrate that besides IFN-alpha, the production by Toll-like receptor (TLR)-activated healthy pDC of IFN-beta and TNF-alpha but not IP-10/CXCL10 nor MIP1-alpha/CCL3 is impaired by the breast tumor environment. Importantly, we identified TGF-beta and TNF-alpha as major soluble factors involved in TApDC functional alteration. Indeed, recombinant TGF-beta1 and TNF-alpha synergistically blocked IFN-alpha production of TLR-activated pDC, and neutralization of TGF-beta and TNF-alpha in tumor-derived supernatants restored pDCs’ IFN-alpha production. The involvment of tumor-derived TGF-beta was further confirmed in situ by the detection of phosphorylated Smad2 in the nuclei of TApDC in breast tumor tissues. Mechanisms of type I IFN inhibition did not involve TLR downregulation but the inhibition of IRF-7 expression and nuclear translocation in pDC after their exposure to tumor-derived supernatants or recombinant TGF-beta1 and TNF-alpha. Our findings indicate that targeting TApDC to restore their IFN-alpha production might be an achievable strategy to induce antitumor immunity in breast cancer by combining TLR7/9-based immunotherapy with TGF-beta and TNF-alpha antagonists.
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[214]
TÍTULO / TITLE: - Bortezomib enhances antigen-specific cytotoxic T cell responses against immune-resistant cancer cells generated by STAT3-ablated dendritic cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacol Res. 2013 Feb 18;71C:23-33. doi: 10.1016/j.phrs.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.phrs.2013.02.001
AUTORES / AUTHORS: - Kim JE; Jin DH; Lee WJ; Hur D; Wu TC; Kim D
INSTITUCIÓN / INSTITUTION: - Department of Anatomy, Chung-Ang University, College of Medicine, Seoul, Republic of Korea; Institute for Innovate Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University, College of Medicine, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - Dendritic cell (DC)-based vaccines have received attention as a new therapeutic modality against cancer. However, increased STAT3 activity in the tumor microenvironment makes DCs tolerogenic and suppresses their antitumor activity. In this study, we explored the effects of a combination treatment consisting of a proteasome inhibitor, bortezomib, and an antigen specific STAT3-ablated (STAT3-/-) DC-based vaccine on the control of TC-1(P3) tumors, a p53-degraded immune resistant cancer cells. We found that E7-antigen expressing STAT3-/- DC (E7-DC-1STAT3-/-) vaccination enhanced generation of E7-specific CD8+ T cells, but was not enough to control TC-1(P3) cancer cells. Therefore, we investigated whether bortezomib could create a synergistic effect with E7-DC-1STAT3-/- vaccination. We found that apoptosis via down-regulation of STAT3 and NF-kappaB and up-regulation of Fas and death receptor 5 (DR5) expression in TC-1(P3) induced by bortezomib was independent of p53 status. We also observed that TC-1(P3) cells pretreated with bortezomib had markedly enhanced anti-tumor effects on E7-specific CD8+ T cells through a Fas/DR5-mediated mechanism. In addition, TC-1(P3) tumor-bearing mice treated with bortezomib prior to vaccination with E7-DC-1STAT3-/- demonstrated enhanced generation of E7-specific CD8+ T cells and prolonged survival compared to those treated with monotherapy. These results suggest that the anti-tumor effects against a p53-degraded immune resistant variant generated by antigen-expressing STAT3-ablated mature DCs may be enhanced by bortezomib via death receptor-mediated apoptosis.
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[215]
TÍTULO / TITLE: - Modulation of drug-resistant membrane and apoptosis proteins of breast cancer stem cells by targeting berberine liposomes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Jun;34(18):4452-65. doi: 10.1016/j.biomaterials.2013.02.066. Epub 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.02.066
AUTORES / AUTHORS: - Ma X; Zhou J; Zhang CX; Li XY; Li N; Ju RJ; Shi JF; Sun MG; Zhao WY; Mu LM; Yan Y; Lu WL
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
RESUMEN / SUMMARY: - The recurrence of breast cancer is associated with drug-resistance of cancer stem cells (CSCs), while overexpression of cell membrane ATP-binding cassette (ABC) transporters and resistance of mitochondrial apoptosis-related proteins are responsible for the drug-resistance of CSCs. The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs for the treatment and prevention of breast cancer relapse. Evaluations were performed on human breast CSCs and CSC xenografts in nude mice. The targeting berberine liposomes were shown to cross the CSC membrane, inhibit ABC transporters (ABCC1, ABCC2, ABCC3, ABCG2) and selectively accumulate in the mitochondria. Furthermore, the pro-apoptotic protein Bax was activated while the anti-apoptotic protein Bcl-2 was inhibited resulting in opening of the mitochondrial permeability transition pores, release of cytochrome c, and activation of caspase-9/caspase-3 enzymes. Significant efficacy of the administrations in mice was observed, indicating that the targeting berberine liposomes are a potential therapy for the treatment and prevention of breast cancer relapse arising from CSCs.
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[216]
TÍTULO / TITLE: - CCL18 as an independent favorable prognostic biomarker in patients with colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Res. 2013 Jan 31. pii: S0022-4804(13)00015-2. doi: 10.1016/j.jss.2013.01.017.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jss.2013.01.017
AUTORES / AUTHORS: - Yuan R; Chen Y; He X; Wu X; Ke J; Zou Y; Cai Z; Zeng Y; Wang L; Wang J; Fan X; Wu X; Lan P
INSTITUCIÓN / INSTITUTION: - Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou City, Guangdong Province, PR China.
RESUMEN / SUMMARY: - BACKGROUND: CCL18 has been shown to have an important role in the progression of gastric and breast cancers. However, the prognostic value of CCL18 in colorectal cancer (CRC) remains unknown. MATERIALS AND METHODS: We used immunohistochemistry to examine the expression of CCL18 in CRC patients. We applied both univariate and multivariate analysis to evaluate the prognostic value of CCL18 on CRC patients’ survival. We used double staining to investigate the relationship between CCL18 and macrophages. RESULTS: A total 371 CRC patient samples were enrolled in immunohistochemical analysis. According to our criteria, 118 samples (31.8%) showed a high CCL18 expression level. Clinicopathologic analysis revealed an association between the expression level of CCL18 and the preoperative carcino embryonic antigen level (P = 0.001), and the preoperative carbohydrate antigen 19-9 level (P = 0.003). Survival analysis and multivariate analysis revealed that CCL18 was an independent favorable prognostic factor in patients with CRC (P = 0.033). Double staining implied that CCL18 was expressed by macrophages. CONCLUSIONS: A high CCL18 level might be an independent biomarker for predicting better survival of patients with CRC.
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[217]
TÍTULO / TITLE: - EGFR-tyrosine kinase inhibitor treatment beyond progression in long-term Caucasian responders to erlotinib in advanced non-small cell lung cancer: A case-control study of overall survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 11. pii: S0169-5002(13)00069-X. doi: 10.1016/j.lungcan.2013.02.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.010
AUTORES / AUTHORS: - Faehling M; Eckert R; Kamp T; Kuom S; Griese U; Strater J; Ott G; Spengler W
INSTITUCIÓN / INSTITUTION: - Klinik fur Kardiologie und Pneumologie, Klinikum Esslingen, Hirschlandstr. 97, 73730 Esslingen, Germany. Electronic address: m.faehling@klinikum-es.de.
RESUMEN / SUMMARY: - INTRODUCTION: Some patients with advanced NSCLC show prolonged disease stabilization on treatment with an EGFR-tyrosine kinase inhibitor (TKI) such as erlotinib. It is not clear how to treat patients who progress after prolonged response to erlotinib. We hypothesized that TKI therapy beyond progression with added chemotherapy, radiotherapy or best supportive care may improve survival. PATIENTS AND METHODS: We retrospectively analyzed all NSCLC patients treated with erlotinib at our institutions since 2004who progressed after at least stable disease on erlotinib for at least 6 months. The first 16 patients did not receive further TKI treatment after progression (controls). The following 25 patients were treated with TKI beyond progression (TKI patients). Overall survival (OS) was analyzed for the whole population, a case-control analysis of pairs matched for gender, smoking status, and histology (n=28), and for patients with known EGFR mutation status (n=23). RESULTS: Treatment with TKI and chemotherapy was well tolerated. TKI-patients had a significantly longer OS from progression on TKI (case-control: median 14.5 vs. 2.0 months, HR 0.154) and longer OS from diagnosis of lung cancer (case-control: median 54.5 vs. 28.3 months, HR 0.474). An activating EGFR mutation was detected in 13 of the 23 patient tested (57%). Both among patients with and without detection of an activating EGFR mutation, those treated with erlotinib beyond progression had a longer survival. CONCLUSIONS: In our case-control analysis in long-term erlotinib responders, treatment with TKI beyond progression in addition to chemotherapy or radiotherapy was feasible and lead to prolonged overall survival.
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[218]
TÍTULO / TITLE: - Phase I/II study of albumin-bound nab-paclitaxel plus gemcitabine administered to Chinese patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):1065-72. doi: 10.1007/s00280-013-2102-4. Epub 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2102-4
AUTORES / AUTHORS: - Zhang DS; Wang DS; Wang ZQ; Wang FH; Luo HY; Qiu MZ; Wang F; Li YH; Xu RH
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.
RESUMEN / SUMMARY: - PURPOSE: The primary objective of this study was to evaluate the dose-limiting toxicities (DLTs) and identify the maximum-tolerated dose (MTD) and recommended dose of nab-paclitaxel plus gemcitabine as a first-line treatment in Chinese patients with advanced pancreatic ductal adenocarcinoma (PDA). METHODS: Patients with previously untreated advanced PDA were treated with nab-paclitaxel followed by gemcitabine (1,000 mg/m(2)) administered intravenously for 30 min on days 1 and 8 and repeated every 21 days. RESULTS: Patients received nab-paclitaxel at the following dose levels: 80 mg/m(2) (n = 3), 100 mg/m(2) (n = 6), and 120 mg/m(2) (n = 12). The DLTs evaluated were elevated alanine aminotransferase and febrile neutropenia. However, there had no two out of three to six patients experienced DLTs, the MTD was not met. A total of 93 cycles were administered. The most common grade ¾ toxicities were neutropenia (9.52 %), thrombocytopenia (4.76 %), and sensory neuropathy (4.76 %). For 12 patients receiving 120 mg/m(2), the overall response rate and disease control rate were 41.67 and 83.33 %, respectively, and the median progression-free survival and overall survival were 5.23 and 12.17 months, respectively. CONCLUSIONS: Treatment with albumin-bound nab-paclitaxel (120 mg/m(2)) plus gemcitabine has a favorable safety profile with an encouraging antitumor effect in Chinese patients.
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[219]
TÍTULO / TITLE: - Polymorphisms of Nucleotide Excision Repair Genes Predict Melanoma Survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Invest Dermatol. 2013 Feb 14. doi: 10.1038/jid.2012.498.
●● Enlace al texto completo (gratuito o de pago) 1038/jid.2012.498
AUTORES / AUTHORS: - Li C; Yin M; Wang LE; Amos CI; Zhu D; Lee JE; Gershenwald JE; Grimm EA; Wei Q
INSTITUCIÓN / INSTITUTION: - 1] Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China [2] Department of Epidemiology, Unit 1365, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
RESUMEN / SUMMARY: - Melanoma is the most highly malignant skin cancer, and nucleotide excision repair (NER) is involved in melanoma susceptibility. In this analysis of 1,042 melanoma patients, we evaluated whether genetic variants of NER genes may predict survival outcome of melanoma patients. We used genotyping data of 74 tagging single-nucleotide polymorphisms (tagSNPs) in eight core NER genes from our genome-wide association study (including two in XPA, 14 in XPC, three in XPE, four in ERCC1, 10 in ERCC2, eight in ERCC3, 14 in ERCC4, and 19 in ERCC5) and evaluated their associations with prognosis of melanoma patients. Using the Cox proportional hazards model and Kaplan-Meier analysis, we found a predictive role of XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871 SNPs in the prognosis of melanoma patients (rs28720291: AG vs. GG, adjusted hazard ratio (adjHR)=11.2, 95% confidence interval (CI) 3.04-40.9, P=0.0003; rs4150314: AG vs. GG, adjHR=4.76, 95% CI 1.09-20.8, P=0.038; rs2470458: AA vs. AG/GG, adjHR=2.11, 95% CI 1.03-4.33, P=0.040; and rs50871: AA vs. AC/CC adjHR=2.27, 95% CI 1.18-4.35, P=0.015). Patients with an increasing number of unfavorable genotypes had markedly increased death risk. Genetic variants of NER genes, particularly XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871, may independently or jointly modulate survival outcome of melanoma patients. Because our results were based on a median follow-up of 3 years without multiple test corrections, additional large prospective studies are needed to confirm our findings.Journal of Investigative Dermatology advance online publication, 14 February 2013; doi:10.1038/jid.2012.498.
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[220]
TÍTULO / TITLE: - Prognostic impact of RAS mutations in patients with myelodysplastic syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Hematol. 2013 Feb 8. doi: 10.1002/ajh.23410.
●● Enlace al texto completo (gratuito o de pago) 1002/ajh.23410
AUTORES / AUTHORS: - Al-Kali A; Quintas-Cardama A; Luthra R; Bueso-Ramos C; Pierce S; Kadia T; Borthakur G; Estrov Z; Jabbour E; Faderl S; Ravandi F; Cortes J; Tefferi A; Kantarjian H; Garcia-Manero G
INSTITUCIÓN / INSTITUTION: - Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Hematology, Mayo Clinic, Rochester, Minnesota.
RESUMEN / SUMMARY: - RAS is an oncogene frequently mutated in human cancer. RAS mutations have been reported in 10-15% of cases of acute myeloid leukemia (AML) but they appear to be less frequent among patients with myelodysplastic syndrome (MDS). The impact of RAS mutations in patients with MDS is unclear. We conducted a retrospective study in 1,067 patients with newly diagnosed MDS for whom RAS mutational analysis was available. Overall, 4% of patients carried mutant RAS alleles. Notably, FLT3 mutations, which were found in 2% of patients, were mutually exclusive with RAS mutations. Patients with RAS mutations had a higher white blood cell count as well as bone marrow blasts compared with patients carrying wild-type RAS. However, no differences were observed between both groups regarding the risk of AML transformation (9% vs. 7%) and overall survival (395 days vs. 500 days, P = 0.057). In summary, RAS mutations are infrequent in patients with MDS and do not appear to negatively impact their outcome. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
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[221]
TÍTULO / TITLE: - Downregulation of phosphatidylethanolamine binding protein 1 associates with clinical risk factors in gastrointestinal stromal tumors, but not with activation of the RAF-1-MEK-ETV1 pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Jan 31. pii: S0304-3835(13)00090-6. doi: 10.1016/j.canlet.2013.01.044.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.044
AUTORES / AUTHORS: - Schoppmann SF; Beer A; Nirtl N; Ba-Ssalamah A; Brodowicz T; Streubel B; Birner P
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Medical University of Vienna, Austria.
RESUMEN / SUMMARY: - Aim of this study was to investigate phosphatidylethanolamine binding protein 1 (PEBP1) in GIST and its relations with MEK1/2 activation and ETV1 by immunohistochemistry. Loss of PEBP1 was found in 22/161 (13.7%) GIST, was associated with clinical risk factors and with a trend towards shorter disease free survival, but not with pMEK1/2 and ETV1 expression. So downregulation of PEBP1 does not activate the Ras-Raf-1-MEK1/2-ERK1/2 pathway by phosphorylation of MEK1/2 and does not influence ETV1 expression in GIST. Loss of PEBP1 associates with clinical risk factors, but since no significant influence on survival was found, further studies are required.
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[222]
TÍTULO / TITLE: - Optimized S-Trityl-l-cysteine-Based Inhibitors of Kinesin Spindle Protein with Potent in Vivo Antitumor Activity in Lung Cancer Xenograft Models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Chem. 2013 Mar 14;56(5):1878-93. doi: 10.1021/jm3014597. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1021/jm3014597
AUTORES / AUTHORS: - Good JA; Wang F; Rath O; Kaan HY; Talapatra SK; Podgorski D; Mackay SP; Kozielski F
INSTITUCIÓN / INSTITUTION: - Molecular Motors Laboratory, The Beatson Institute for Cancer Research , Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland, U.K.
RESUMEN / SUMMARY: - The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-l-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activity. We report here their further optimization to produce extremely potent inhibitors of Eg5 (Ki(app) < 10 nM) with broad-spectrum activity against cancer cell lines comparable to the Phase II drug candidates ispinesib and SB-743921. They have good oral bioavailability and pharmacokinetics and induced complete tumor regression in nude mice explanted with lung cancer patient xenografts. Furthermore, they display fewer liabilities with CYP-metabolizing enzymes and hERG compared with ispinesib and SB-743921, which is important given the likely application of Eg5 inhibitors in combination therapies. We present the case for this preclinical series to be investigated in single and combination chemotherapies, especially targeting hematological malignancies.
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[223]
TÍTULO / TITLE: - ApoG2 induces ER stress-dependent apoptosis in gastric cancer cells in vitro and its real-time evaluation by bioluminescence imaging in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Mar 21. pii: S0304-3835(13)00247-4. doi: 10.1016/j.canlet.2013.03.019.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.019
AUTORES / AUTHORS: - Xin J; Zhan Y; Liu M; Hu H; Xia L; Nie Y; Wu K; Liang J; Tian J
INSTITUCIÓN / INSTITUTION: - School of Life Sciences and Technology, Xidian University, Xi’an 710071, China.
RESUMEN / SUMMARY: - Apogossypolone (ApoG2), a potent small molecular inhibitor of Bcl-2 family proteins, is reported to have a significant anti-cancer effect in several types of cancers, but it has not been investigated in gastric cancer. In this study, we demonstrate in vitro and in vivo that ApoG2 inhibits human gastric cancer. Gastric carcinoma cell growth and proliferation was significantly hampered in vitro, as measured by MTT and colony formation assays. Real-time, bioluminescence imaging indicated that ApoG2 causes tumor growth delay in a murine xenograft model. Further studies revealed that the ApoG2 induced apoptosis in gastric cancer cells was associated with the endoplasmic reticulum stress-induced apoptosis pathway. Conclusively, our results indicate that ApoG2 may be a promising agent for gastric cancer therapy.
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[224]
TÍTULO / TITLE: - Downregulation of serine/arginine-rich splicing factor 3 induces G1 cell cycle arrest and apoptosis in colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Mar 18. doi: 10.1038/onc.2013.86.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.86
AUTORES / AUTHORS: - Kurokawa K; Akaike Y; Masuda K; Kuwano Y; Nishida K; Yamagishi N; Kajita K; Tanahashi T; Rokutan K
INSTITUCIÓN / INSTITUTION: - Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
RESUMEN / SUMMARY: - Serine/arginine-rich splicing factor 3 (SRSF3) likely has wide-ranging roles in gene expression and facilitation of tumor cell growth. SRSF3 knockdown induced G1 arrest and apoptosis in colon cancer cells (HCT116) in association with altered expression of 833 genes. Pathway analysis revealed ‘G1/S Checkpoint Regulation’ as the most highly enriched category in the affected genes. SRSF3 knockdown did not induce p53 or stimulate phosphorylation of p53 or histone H2A.X in wild-type HCT116 cells. Furthermore, the knockdown induced G1 arrest in p53-null HCT116 cells, suggesting that p53-dependent DNA damage responses did not mediate the G1 arrest. Real-time reverse transcription-polymerase chain reaction and western blotting confirmed that SRSF3 knockdown reduced mRNA and protein levels of cyclins (D1, D3 and E1), E2F1 and E2F7. The decreased expression of cyclin D and E2F1 likely impaired the G1-to-S-phase progression. Consequently, retinoblastoma protein remained hypophosphorylated in SRSF3 knockdown cells. The knockdown also induced apoptosis in association with reduction of BCL2 protein levels. We also found that SRSF3 knockdown facilitated skipping of 81 5’-nucleotides (27 amino acids) from exon 8 of homeodomain-interacting protein kinase-2 (HIPK2) and produced a HIPK2 Deltae8 isoform. Full-length HIPK2 (HIPK2 FL) is constantly degraded through association with an E3 ubiquitin ligase (Siah-1), whereas HIPK2 Deltae8, lacking the 27 amino acids, lost Siah-1-binding ability and became resistant to proteasome digestion. Interestingly, selective knockdown of HIPK2 FL induced apoptosis in various colon cancer cells expressing wild-type or mutated p53. Thus, these findings disclose an important role of SRSF3 in the regulation of the G1-to-S-phase progression and alternative splicing of HIPK2 in tumor growth.Oncogene advance online publication, 18 March 2013; doi:10.1038/onc.2013.86.
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[225]
TÍTULO / TITLE: - Sensitisation of c-MYC-induced B-lymphoma cells to apoptosis by ATF2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Feb 18. doi: 10.1038/onc.2013.28.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.28
AUTORES / AUTHORS: - Walczynski J; Lyons S; Jones N; Breitwieser W
INSTITUCIÓN / INSTITUTION: - Department of Cell Regulation, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
RESUMEN / SUMMARY: - Transcription factors ATF2 (activating transcription factor 2) and ATF7 (activating transcription factor 7) are highly homologous members of the activator protein 1 (AP-1) family. Their activities are growth factor and stress stimulated and they strictly require phosphorylation by mitogen-activated protein (MAP) kinases for their transcriptional functions. In samples of human B-cell lymphomas as well as Emu-Myc-driven mouse B-cell lymphomas, we find that ATF2 as well as MAP kinase c-Jun N-terminal kinase (JNK) are significantly up-regulated compared with normal human B-cell lines and mouse B cells, respectively. The B cell-specific deletion of ATF2 and ATF7 in mice results in significantly accelerated onset of Emu-Myc-induced lymphoma. In addition, loss of ATF2/7 desensitises Emu-Myc lymphoma cells to spontaneous as well as stress-induced apoptosis. Our results therefore suggest that c-MYC induces stress-mediated activation of ATF2 and ATF7 and that these transcription factors regulate apoptosis in response to oncogenic transformation of B cells.Oncogene advance online publication, 18 February 2013; doi:10.1038/onc.2013.28.
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[226]
TÍTULO / TITLE: - Isatin inhibits proliferation and induces apoptosis of SH-SY5Y neuroblastoma cells in vitro and in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Pharmacol. 2013 Feb 28;702(1-3):235-41. doi: 10.1016/j.ejphar.2013.01.017. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejphar.2013.01.017
AUTORES / AUTHORS: - Song J; Hou L; Ju C; Zhang J; Ge Y; Yue W
INSTITUCIÓN / INSTITUTION: - Department of Laboratory, Women and Children’s Hospital of Qingdao, Shandong 266011, China.
RESUMEN / SUMMARY: - The purpose of this study was to investigate the anti-tumor effects of the isatin in vitro and in vivo. Human neuroblastoma cells (SH-SY5Y) were exposed to isatin at various concentrations (0, 50, 100, 200mumol/l) for 48h. Bcl-2 and Bax mRNA were analyzed via RT-PCR. Bcl-2, Bax, the inhibitor of caspase-activated DNase (ICAD) and cytochrome c protein were analyzed via western blot. Apoptosis, caspase-9, 3 activation and mitochondrial depolarization were assayed by flow cytometry. SH-SY5Y cells were injected into the right side of the mouse armpit. When the neoplasm was detected, the nude mice were randomly divided into four groups and received an injection of DMEM (negative control), 25 or 50mg/kg isatin, or cyclophosphamide (positive control). The inhibitory effects of isatin on the murine xenograft were determined using a growth curve and Bcl-2 and Bax mRNA and protein were studied using RT-PCR and western blot, respectively. The results showed that apoptosis of SH-SY5Y cells was induced by isatin. Furthermore, Bcl-2 expression was decreased and the ratio of Bcl-2 to Bax was significantly decreased by isatin. The mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c into the cytosol was increased after treatment with isatin. Simultaneously, caspase-9, 3 was activated, followed by degradation of ICAD, a caspase-3 substrate. Finally, tumor xenograft growth was markedly suppressed and a decrease was found in Bcl-2 and Bax expression in vivo. These results suggest that isatin can induce apoptosis and inhibit the growth of neuroblastoma cells via the mitochondrial pathway.
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[227]
TÍTULO / TITLE: - Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1390-8. doi: 10.3892/ijo.2013.1810. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1810
AUTORES / AUTHORS: - Zhang MH; Hu YD; Xu Y; Xiao Y; Luo Y; Song ZC; Zhou J
INSTITUCIÓN / INSTITUTION: - The Third Department of Oncology, PLA Cancer Research Institute of the Second Affiliated Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
RESUMEN / SUMMARY: - Currently, some evidence suggests that human multipotential mesenchymal stems cells (hMSCs) aid tumor growth and metastasis. Nutrient deprivation and oxygen deficiency are representative characteristics of solid tumor microenvironment during the cancer development. Because the effects of hMSCs on tumors under stressful conditions have not been determined, we investigated the survival mechanisms used by stressed stromal cells on A549 and SPC-1 lung carcinoma cell lines in vitro and in vivo. An indirect culture system was used to investigate the effects of hMSCs on viability and apoptosis in starved carcinoma cells and focused on the role of autophagy in regulating the survival of carcinoma cells. The results showed that A549 and SPC-1 cells had higher viability when co-cultured with hMSCs and that this was mainly attributed to decreased apoptosis. Autophagosomes were analyzed using GFP-LC3 and electron microscopy, which showed that autophagy was significantly activated in the starved co-culture groups. However, the inhibition of autophagy by the autophagic inhibitor 3-MA significantly abrogated the apoptosis reduction in either single groups or co-culture groups under serum deprivation, which implied that the hMSCs protected against apoptosis by enhancing autophagy in lung carcinoma cells in vitro. We also observed that hMSCs promoted tumor initiation and growth in vivo. In conclusion, our study demonstrates that hMSCs can protect carcinoma cells from nutrient deprivation-induced apoptosis and promote tumor initiation and growth, and, interestingly, autophagy plays an important role in the survival of cancer cells.
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[228]
TÍTULO / TITLE: - A Novel Tankyrase Small-molecule Inhibitor Suppresses APC Mutation-driven Colorectal Tumor Growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4562
AUTORES / AUTHORS: - Lau T; Chan E; Callow M; Waaler J; Boggs J; Blake RA; Magnuson S; Sambrone A; Schutten M; Firestein R; Machon O; Korinek V; Choo E; Diaz D; Merchant M; Polakis P; Holsworth DD; Krauss S; Costa M
INSTITUCIÓN / INSTITUTION: - Cancer Targets, Genentech, Inc.
RESUMEN / SUMMARY: - Most colorectal cancers (CRC) are initiated by mutations of APC, leading to increased beta-catenin-mediated signaling. However continued requirement of Wnt/beta-catenin signaling for tumor progression in the context of acquired KRAS and other mutations is less well established. To attenuate Wnt/beta-catenin signaling in tumors, we have developed potent and specific small-molecule tankyrase inhibitors, G007-LK and G244-LM, that reduce Wnt/beta-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby promoting beta-catenin destabilization. We show that novel tankyrase inhibitors completely block ligand-driven Wnt/beta-catenin signaling in cell culture and display approximately 50% inhibition of APC-mutation-driven signaling in most CRC cell lines. It was previously unknown whether the level of AXIN protein stabilization by tankyrase inhibition is sufficient to impact tumor growth in the absence of normal APC activity. Compound G007-LK displays favorable pharmacokinetic properties and inhibits in vivo tumor growth in a subset of APC-mutant CRC xenograft models. In the xenograft model most sensitive to tankyrase inhibitor, COLO-320DM, G007-LK inhibits cell cycle progression, reduces colony formation, and induces differentiation, suggesting that beta-catenin-dependent maintenance of an undifferentiated state may be blocked by tankyrase inhibition. The full potential of G007-LK’s anti-tumor activity may be limited by intestinal toxicity associated with inhibition of Wnt/beta-catenin signaling and cell proliferation in intestinal crypts. These results establish proof-of-concept anti-tumor efficacy for tankyrase inhibitors in APC-mutant CRC models, and uncover potential diagnostic and safety concerns to be overcome as tankyrase inhibitors are advanced into the clinic.
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[229]
TÍTULO / TITLE: - Fatty Acid synthase inhibition induces differential expression of genes involved in apoptosis and cell proliferation in ocular cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Feb;65(2):311-6. doi: 10.1080/01635581.2013.748923.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.748923
AUTORES / AUTHORS: - Deepa PR; Vandhana S; Krishnakumar S
INSTITUCIÓN / INSTITUTION: - a Department of Biological Sciences , Birla Institute of Technology & Science (BITS) , Pilani , Rajasthan , India.
RESUMEN / SUMMARY: - Fatty acid synthase (FASN), a lipogenic multienzyme complex, is overexpressed in the ocular cancer, retinoblastoma, and is strongly correlated with tumor invasion. Dietary nutrients are reported to exert anticancer effects through inhibition of lipid metabolism. Differential gene expression in cultured retinoblastoma cells induced by cerulenin, a chemical inhibitor of FASN, was evaluated by cDNA microarray analysis. Cerulenin treatment resulted in significant upregulation of cytochrome c (CYCS) by 1.2-fold, whereas S-phase kinase-associated protein-2 (SKP2), a negative regulator of cell cycle, and the lipid metabolic genes (PPARA, RXRA, and ACACB) were significantly downregulated by -1.59-, -1.8-, -1.83-, and -1.5-fold, respectively, in comparison with untreated cancer cells. The expressions of key differentially expressed genes were confirmed by quantitative real-time PCR. The altered expression of genes involved in cell proliferation, cell signaling, apoptosis, and cell cycle, correlated with the anticancer effects of cerulenin. FASN inhibition may thus be a potential strategy in retinoblastoma management.
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[230]
TÍTULO / TITLE: - The MYB oncogene can suppress apoptosis in acute myeloid leukemia cells by transcriptional repression of DRAK2 expression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 8. pii: S0145-2126(13)00026-X. doi: 10.1016/j.leukres.2013.01.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.012
AUTORES / AUTHORS: - Ye P; Zhao L; Gonda TJ
INSTITUCIÓN / INSTITUTION: - School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia; The University of Queensland, Diamantina Institute, Brisbane, Queensland, Australia.
RESUMEN / SUMMARY: - RNA interference-mediated suppression of MYB expression promoted apoptosis in the AML cell line U937, without affecting expression of the anti-apoptotic MYB target BCL2. This was accompanied by up-regulation of the pro-apoptotic gene DRAK2 and stimulation of caspase-9 activity. Moreover, RNA interference-mediated suppression of DRAK2 in U937 cells alleviated apoptosis induced by MYB down-regulation. Finally ChIP assays showed that in U937 cells MYB binds to a conserved element upstream of the DRAK2 transcription start site. Together, these findings identify a novel mechanism by which MYB suppresses apoptosis in an AML model cell line.
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[231]
TÍTULO / TITLE: - A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in combination with gemcitabine in patients with solid tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Invest New Drugs. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1007/s10637-013-9950-y
AUTORES / AUTHORS: - Raymond E; Alexandre J; Faivre S; Goldwasser F; Besse-Hammer T; Gianella-Borradori A; Jego V; Trandafir L; Rejeb N; Awada A
INSTITUCIÓN / INSTITUTION: - Service Inter-Hospitalier de Cancerologie Beaujon-Bichat, Hopital Beaujon, Clichy, France, eric.raymond@bjn.aphp.fr.
RESUMEN / SUMMARY: - Introduction MSC1992371A is an aurora kinase inhibitor with potential antitumor activity. Methods This trial established the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral MSC1992371A given before or after gemcitabine (1,000 mg/m2) in a 21-day cycle in patients with advanced malignancies. In schedule 1 (n = 31), gemcitabine was administered on days 1 and 8 followed by escalating doses of MSC1992371A on days 2 and 9. In schedule 2 (n = 35), MSC1992371A was given on days 1 and 8 followed by gemcitabine on days 2 and 9. Patients had a range of solid tumors, the most frequent of which was colorectal (n = 19). Results In both schedules, the 37 mg/m2 dose level was defined as the MTD. The main DLT was grade 4 neutropenia. Adverse events consisted of neutropenia, thrombocytopenia, asthenia, fatigue, nausea, vomiting, anorexia, and diarrhea. Administration of MSC1992371A prior to gemcitabine had no effect on the metabolism or elimination of gemcitabine. Time to reach maximum plasma concentration and area under the plasma concentration-time curve for MSC1992371A increased proportionally with dose. Exploration of drug-target-related and tumor biomarkers did not identify predictors of biologic activity or response. Two patients (1 with lung carcinoma and 1 with hepatocellular carcinoma) had durable partial responses in schedule 2, and 5 patients had stable disease (SD) lasting 6 - 14 months. Conclusion Oral MSC1992371A can be administered at a MTD of 37 mg/m2 in combination with the standard 1,000 mg/m2 dose of gemcitabine, but hematologic toxicity requires careful monitoring. Preliminary signs of efficacy were indicated by durable responses and SD.
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[232]
TÍTULO / TITLE: - Increased cytotoxic capacity of tumor antigen specific human T cells after in vitro stimulation with IL21 producing dendritic cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Immunol. 2013 Jan 29. pii: S0198-8859(13)00025-6. doi: 10.1016/j.humimm.2013.01.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humimm.2013.01.014
AUTORES / AUTHORS: - Turksma AW; Bontkes HJ; Ruizendaal JJ; van den Heuvel H; Scholten KB; Santegoets SJ; de Gruijl TD; Meijer CJ; Hooijberg E
INSTITUCIÓN / INSTITUTION: - VU University Medical Center - Cancer Center Amsterdam, Department of Pathology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - Monocyte derived dendritic cells (moDC) electroporated with tumor associated antigen derived mRNA can elicit specific T cells against tumor cells in vivo. IL21 has been shown to enhance activation and cytotoxicity in CD8+ T cells. We therefore investigated in vitro effects on human CD8+ T-cells after stimulation with IL21 mRNA electroporated moDC. Codon modification of the IL21 gene significantly enhanced IL21 production upon electroporation of moDC. Tumor associated antigen specific CTL induction efficiency was significantly enhanced when codon modified IL21 mRNA was co-electroporated with tumor associated antigen mRNA. Tumor associated antigen specific T cells induced by codon modified IL21-DC demonstrated increased cytotoxic capacity and killing compared to control cultures. In conclusion, ectopic expression of codon modified IL21 by moDC enhances the priming efficiency of the DC as well as the cytotoxic potential of the induced CTL.
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[233]
TÍTULO / TITLE: - The prognostic importance of changing serum M30 and M65 values after chemotherapy in patients with advanced-stage non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):551. doi: 10.1007/s12032-013-0551-6. Epub 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0551-6
AUTORES / AUTHORS: - Ustaalioglu BB; Bilici A; Ercan S; Seker M; Orcun A; Gumus M
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey. basakoven@yahoo.com
RESUMEN / SUMMARY: - Although oncological treatments are improving, the prognosis of non-small-cell lung cancer (NSCLC) patients has not. Several biomarkers related to prognosis have been evaluated, and M30 and M65 have been reported to be higher in patients with NSCLC than in healthy people. In the current study, we evaluated the clinical importance of the change in serum M30 and M65 values after chemotherapy in patients with NSCLC. Serum M30 and M65 values were measured before and 48 h after chemotherapy in thirty-two patients with advanced NSCLC. The importance of the change in the levels of these markers after chemotherapy was analyzed by univariate analysis. The median serum M65 and M30 values increased significantly after chemotherapy (p < 0.001). The median M30 value after chemotherapy was an important prognostic factor for both overall survival (OS) (p = 0.002) and progression-free survival (PFS) (p = 0.002). Stage and histopathological type were significant both for PFS and OS. Multivariate analysis showed that the median M30 value after chemotherapy was the only independent prognostic factor for PFS (p = 0.04, HR 5.4) and OS (p = 0.02, HR 11.49). Our results indicated that both serum M30 and M65 values increased after chemotherapy in patients with advanced NSCLC, and an elevated serum M30 value was an independent prognostic factor for both PFS and OS.
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[234]
TÍTULO / TITLE: - Controversies in antiepidermal growth factor receptor therapy in metastatic colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Mar 15. doi: 10.1002/cncr.27994.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27994
AUTORES / AUTHORS: - Woo J; Palmisiano N; Tester W; Leighton JC Jr
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania. woojangh@einstein.edu.
RESUMEN / SUMMARY: - The randomized first-line trials, including the CRYSTAL trial, the OPUS trial, and the PRIME trial, have demonstrated the significant efficacy of cetuximab or panitumumab in patients with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type tumors. The addition of an antiepidermal growth factor receptor (anti-EGFR)-directed monoclonal antibody to chemotherapy for these patients significantly improved progression-free survival, response rates, and R0 resection rates to a greater extent than overall survival compared with patients who received chemotherapy alone. However, 2 recent randomized phase 3 trials, the MRC COIN trial and the Nordic VII trial, reported an unexpected lack of benefit from the addition of cetuximab to chemotherapy in the first-line setting. In addition, recent retrospective analyses performed on a pooled data set from major clinical trials added more complexity, reporting an unexpected association of KRAS G13D mutation with a better clinical outcome compared with patients who had other KRAS mutations in the first-line and salvage settings, whereas the other independent analysis failed to demonstrate a benefit from panitumumab in patients with the same KRAS G13D mutation. The anti-EGFR monoclonal antibody-associated skin toxicity and the controversial strategies of management also are discussed. In this review, the authors analyze the previous randomized clinical trials and more critically re-evaluate recent trials and subgroup analyses to derive 3 factors that need to be taken into consideration regarding the addition of EGFR-directed monoclonal antibodies to chemotherapy: the preclinical data on mechanisms of action between chemotherapy and anti-EGFR antibodies along with mechanisms of resistance to anti-EGFR antibodies, the role of cross-over events in overall survival data, and the significant dose reductions of chemotherapeutic agents when combined with anti-EGFR agents. Cancer 2013. © 2013 American Cancer Society.
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[235]
TÍTULO / TITLE: - Androgen deprivation and androgen receptor competition by bicalutamide induce autophagy of hormone-resistant prostate cancer cells and confer resistance to apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prostate. 2013 Mar 26. doi: 10.1002/pros.22658.
●● Enlace al texto completo (gratuito o de pago) 1002/pros.22658
AUTORES / AUTHORS: - Boutin B; Tajeddine N; Vandersmissen P; Zanou N; Van Schoor M; Mondin L; Courtoy PJ; Tombal B; Gailly P
INSTITUCIÓN / INSTITUTION: - Laboratory of Cell Physiology, Universite catholique de Louvain, Brussels, Belgium.
RESUMEN / SUMMARY: - BACKGROUND: Treatment of advanced prostate cancer (PCa) relies on pharmacological or surgical androgen deprivation. However, it is only temporarily efficient. After a few months or years, the tumor relapses despite the absence of androgenic stimulation: a state referred to as hormone-refractory prostate cancer (HRPCa). Although autophagy confers chemoresistance in some cancers, its role in the development of HRPCa remains unknown. METHODS: Autophagic flux was assayed by GFP-LC3 clustering, by LC3-I to LC3-II conversion and transmission electron microscopy. Cell death was detected by sub-G1 quantification and concomitant measurement of transmembrane mitochondrial potential and plasma membrane permeabilization. Inhibition of autophagy was achieved by siRNAs and pharmacological inhibitors. RESULTS: Androgen deprivation or treatment with the anti-androgen bicalutamide promoted autophagy in HRPCa-derived LNCaP cells. This effect was dramatically reduced after depletion of Atg5 and Beclin-1, two canonical autophagy genes, and was associated with an inhibition of the androgen-induced mTOR pathway. The depletion of Atg5 and Beclin-1 significantly increased the level of cell death induced by androgen deprivation or bicalutamide. Finally, the safe anti-malarial drug chloroquine, an inhibitor of autophagy, dramatically increased cell death after androgen deprivation or bicalutamide treatment. CONCLUSION: Taken together, our data suggest that autophagy is a protective mechanism against androgen deprivation in HRPCa cells and that chloroquine could restore hormone dependence. This set of data could lead to the development of new therapeutic strategy against HRPCa. Prostate © 2013 Wiley Periodicals, Inc.
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[236]
TÍTULO / TITLE: - Estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast tumors: Early prediction of chemosensitivity with F-fluorodeoxyglucose positron emission tomography/computed tomography during neoadjuvant chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Mar 15. doi: 10.1002/cncr.28020.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.28020
AUTORES / AUTHORS: - Groheux D; Hatt M; Hindie E; Giacchetti S; de Cremoux P; Lehmann-Che J; Martineau A; Marty M; Cuvier C; Cheze-Le Rest C; de Roquancourt A; Visvikis D; Espie M
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, St. Louis Hospital, Paris, France; Doctoral School of Biology and Biotechnology, University Institute of Hematology, University of Paris VII, Paris, France. dgroheux@yahoo.fr.
RESUMEN / SUMMARY: - BACKGROUND: The objective of this prospective study was to evaluate the ability of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) to predict chemosensitivity in patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: Sixty-four consecutive patients underwent 18 F-FDG PET/CT scanning at baseline and after the second course of neoadjuvant chemotherapy (NAC). The evolution (Delta) between the 2 scans of image parameters (maximum standardized uptake value [SUVmax ], SUVmean , metabolic tumor volume, and total lesion glycolysis [TLG]) was measured. Correlations between early changes in PET-derived parameters and pathologic response observed in surgical specimens after the completion of 8 courses of NAC were estimated with Mann-Whitney U tests. Response prediction on the basis of clinical data, histologic type, or molecular markers also was assessed (Fisher exact test). Receiver operating characteristic (ROC) analysis was used to compare the area under the curve (AUC) of each parameter. RESULTS: The best prediction of chemosensitivity was obtained with DeltaTLG (-49% +/- 31% in nonresponders vs -73% +/- 25% in responders; P < .0001). Among the biologic parameters, only negative progesterone receptor status (57% responders vs 31% nonresponders; P = .04) and luminal B subtype (63% responders vs 22% nonresponders; P = .02) were predictive of a pathologic response. ROC analysis resulted in an AUC of 0.81, 0.73, 0.71, and 0.63 for DeltaTLG, DeltaSUVmax , luminal subtype, and progesterone receptor status, respectively. CONCLUSIONS: When patients responded to NAC, the majority of ER-positive/HER2 negative tumors exhibited partial tumor shrinkage; and the PET parameters that combined volume and activity measurements, such as TLG, offered better accuracy for early prediction than the SUVmax . Negative progesterone receptor status and luminal B subtype had weaker predictive power than PET-derived parameters. Cancer 2013. © 2013 American Cancer Society.
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[237]
TÍTULO / TITLE: - Outcome evaluation in pre-trastuzumab era between different breast cancer phenotypes: a population-based study on Italian women.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):743-50. doi: 10.1700/1217.13498.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13498
AUTORES / AUTHORS: - Cortesi L; De Matteis E; Cirilli C; Marcheselli L; Proietto M; Federico M
INSTITUCIÓN / INSTITUTION: - Department of Oncology and Hematology, University of Modena and Reggio Emilia, Via del Pozzo 71, Modena, Italy. hbc@unimore.it
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2-, Ki67 <14%), luminal B (ER and/or PgR/HER2-, Ki67 >/=14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2-), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women. METHODS AND STUDY DESIGN: We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated. RESULTS: A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups. CONCLUSIONS: In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.
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[238]
TÍTULO / TITLE: - Interferon alpha and ribavirin collaboratively regulate p38 mitogen-activated protein kinase signaling in hepatoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cytokine. 2013 Mar;61(3):801-7. doi: 10.1016/j.cyto.2013.01.007. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cyto.2013.01.007
AUTORES / AUTHORS: - He SF; Wang W; Ren H; Zhao LJ; Qi ZT
INSTITUCIÓN / INSTITUTION: - Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai 200433, China.
RESUMEN / SUMMARY: - Signaling events triggered by interferon alpha (IFN-alpha) and ribavirin are involved in anti-hepatitis C virus (HCV) action. The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in HCV pathogenesis. Effects of IFN-alpha and ribavirin on p38 MAPK signaling were investigated in human hepatoma cells. Type I IFN receptor 2 (IFNAR2) mediated IFN-alpha-induced p38 MAPK phosphorylation. Also, p38 MAPK phosphorylation was enhanced by ribavirin. Treatment for 48h with a combination of IFN-alpha and ribavirin increased p38 MAPK phosphorylation, whereas the treatment for 72h reduced p38 MAPK phosphorylation. Cell culture-derived HCV (HCVcc) infection dramatically increased p38 MAPK phosphorylation and such phosphorylation was inhibited by IFN-alpha or ribavirin. Moreover, siRNA-mediated knockdown of p38 MAPK resulted in enhancement of ribavirin-dependent HCV RNA replication. These results suggest that regulation of p38 MAPK signaling by IFN-alpha and ribavirin might contribute to anti-HCV action.
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[239]
TÍTULO / TITLE: - Hepatitis B virus X protein protects hepatoma and hepatic cells from complement-dependent cytotoxicity by up-regulation of CD46.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS Lett. 2013 Mar 18;587(6):645-51. doi: 10.1016/j.febslet.2013.01.019. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.febslet.2013.01.019
AUTORES / AUTHORS: - Zhang S; Shan C; Cui W; You X; Du Y; Kong G; Gao F; Ye L; Zhang X
INSTITUCIÓN / INSTITUTION: - Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology and Biochemistry, College of Life Sciences, Nankai University, PR China.
RESUMEN / SUMMARY: - The involvement of hepatitis B virus X protein (HBx) in anti-complement-dependent cytotoxicity (CDC) activity during hepatocarcinogenesis is poorly understood. Here, we report that HBx is able to up-regulate membrane-bound complement regulatory protein CD46 in hepatoma cells and human immortalized liver cells through activating the promoter activity involving cAMP response element-binding protein (CREB)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. In contrast, the down-regulation of CD46 abolishes the resistance capability of hepatoma cells to CDC. Thus, we conclude that HBx contributes to the protection of hepatoma and hepatic cells from CDC by up-regulation of CD46.
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[240]
TÍTULO / TITLE: - Population Pharmacokinetics/Pharmacodynamics of Erlotinib and Pharmacogenomic Analysis of Plasma and Cerebrospinal Fluid Drug Concentrations in Japanese Patients with Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Pharmacokinet. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s40262-013-0058-5
AUTORES / AUTHORS: - Fukudo M; Ikemi Y; Togashi Y; Masago K; Kim YH; Mio T; Terada T; Teramukai S; Mishima M; Inui KI; Katsura T
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan, mfukudo@kuhp.kyoto-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: Erlotinib shows large inter-patient pharmacokinetic variability, but the impact of early drug exposure and genetic variations on the clinical outcomes of erlotinib remains fully investigated. The primary objective of this study was to clarify the population pharmacokinetics/pharmacodynamics of erlotinib in Japanese patients with non-small cell lung cancer (NSCLC). The secondary objective was to identify genetic determinant(s) for the cerebrospinal fluid (CSF) permeability of erlotinib and its active metabolite OSI-420. METHODS: A total of 88 patients treated with erlotinib (150 mg/day) were enrolled, and CSF samples were available from 23 of these patients with leptomeningeal metastases. Plasma and CSF concentrations of erlotinib and OSI-420 were measured by high-performance liquid chromatography with UV detection. Population pharmacokinetic analysis was performed with the nonlinear mixed-effects modelling program NONMEM. Germline mutations including ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A), and CYP3A5 (6986A>G) polymorphisms, as well as somatic EGFR activating mutations if available, were examined. Early exposure to erlotinib and its safety/efficacy relationship were evaluated. RESULTS: The apparent clearance of erlotinib and OSI-420 were significantly decreased by 24 and 35 % in patients with the ABCG2 421A allele, respectively (p < 0.001), while ABCB1 and CYP3A5 polymorphisms did not affect their apparent clearance. The ABCG2 421A allele was significantly associated with increased CSF penetration for both erlotinib and OSI-420 (p < 0.05). Furthermore, the incidence of grade >/=2 diarrhea was significantly higher in patients harboring this mutant allele (p = 0.035). A multivariate logistic regression model showed that erlotinib trough (C0) levels on day 8 were an independent risk factor for the development of grade >/=2 diarrhea (p = 0.037) and skin rash (p = 0.031). Interstitial lung disease (ILD)-like events occurred in 3 patients (3.4 %), and the median value of erlotinib C0 levels adjacent to these events was approximately 3 times higher than that in patients who did not develop ILD (3253 versus 1107 ng/mL; p = 0.014). The objective response rate in the EGFR wild-type group was marginally higher in patients achieving higher erlotinib C0 levels (>/=1711 ng/mL) than that in patients having lower erlotinib C0 levels (38 versus 5 %; p = 0.058), whereas no greater response was observed in the higher group (67 %) versus the lower group (77 %) within EGFR mutation-positive patients (p = 0.62). CONCLUSIONS: ABCG2 can influence the apparent clearance of erlotinib and OSI-420, and their CSF permeabilities in patients with NSCLC. Our preliminary findings indicate that early exposure to erlotinib may be associated with the development of adverse events and that increased erlotinib exposure may be relevant to the antitumor effects in EGFR wild-type patients while having less of an impact on the tumor response in EGFR mutation-positive patients.
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[241]
TÍTULO / TITLE: - Chloroquine Promotes Apoptosis in Melanoma Cells by Inhibiting BH3 Domain-Mediated PUMA Degradation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Invest Dermatol. 2013 Jan 31. doi: 10.1038/jid.2013.56.
●● Enlace al texto completo (gratuito o de pago) 1038/jid.2013.56
AUTORES / AUTHORS: - Lakhter AJ; Sahu RP; Sun Y; Kaufmann WK; Androphy EJ; Travers JB; Naidu SR
INSTITUCIÓN / INSTITUTION: - Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
RESUMEN / SUMMARY: - The Bcl homology-3 (BH3)-only protein p53 upregulated modulator of apoptosis (PUMA) counters Bcl-2 family anti-apoptotic proteins and promotes apoptosis. Although PUMA is a key regulator of apoptosis, the post-transcriptional mechanisms that control PUMA protein stability are not understood. We show that a lysosome-independent activity of chloroquine (CQ) prevents degradation of PUMA protein, promotes apoptosis, and reduces the growth of melanoma xenografts in mice. Compared with wild-type PUMA, a BH3 domain-deleted PUMA protein showed impaired decay in melanoma cells. Fusion of the BH3 domain to a heterologous protein led to its rapid turnover that was inhibited by CQ. Although both CQ and inhibitors of lysosomal proteases stalled autophagy, only CQ stabilized PUMA protein and promoted apoptosis. Our results reveal a lysosomal protease-independent activity of CQ that selectively promotes apoptosis in melanoma cells.Journal of Investigative Dermatology advance online publication, 14 March 2013; doi:10.1038/jid.2013.56.
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[242]
TÍTULO / TITLE: - Generation of reactive oxygen species by a novel berberine-bile acid analog mediates apoptosis in hepatocarcinoma SMMC-7721 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 19. pii: S0006-291X(13)00414-2. doi: 10.1016/j.bbrc.2013.02.104.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.104
AUTORES / AUTHORS: - Li Q; Zhang L; Zu Y; Liu T; Zhang B; He W
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, China. Electronic address: li_qingyong@126.com.
RESUMEN / SUMMARY: - 2,3-Methenedioxy-9-O-(3’alpha,7’alpha-dihydroxy-5’beta-cholan-24’-propy-lester)be rberine (B4) is a novel berberine-bile acid analog synthesized in our laboratory. Previously, we showed that B4 exerted greater cytotoxicity than berberine in several human cancer cell lines. Therefore, we further evaluated the mechanism governing its anticancer actions in hepatocellular carcinoma SMMC-7721 cells. B4 inhibited the proliferation of SMMC-7721 cells, and stimulated reactive oxygen species (ROS) production and mitochondrial membrane depolarization; anti-oxidant capacity was reduced. B4 also induced the release of cytochrome c from the mitochondria to the cytosol and an increase in poly ADP-ribose polymerase (PARP) cleavage products, reflective of caspase-3 activation. Moreover, B4 induced the nuclear translocation of apoptosis-inducing factor (AIF) and a rise in DNA fragmentation. Pretreatment with the anti-oxidant N-acetylcysteine (NAC) inhibited B4-mediated effects, including cytotoxicity, ROS production, mitochondrial membrane depolarization increase in intracellular Ca2+, cytochrome c release, PARP cleavage, and AIF translocation. Our data suggest that B4 induces ROS-triggered caspase-dependent and caspase-independent apoptosis pathways in SMMC-7721 cells and that ROS production may be a specific potential strategy for treating hepatic carcinoma.
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[243]
TÍTULO / TITLE: - The Oncogene Metadherin Modulates the Apoptotic Pathway Based on the Tumor Necrosis Factor Superfamily Member TRAIL (Tumor Necrosis Factor-related Apoptosis-inducing Ligand) in Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Mar 29;288(13):9396-407. doi: 10.1074/jbc.M112.395913. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.395913
AUTORES / AUTHORS: - Zhang N; Wang X; Huo Q; Li X; Wang H; Schneider P; Hu G; Yang Q
INSTITUCIÓN / INSTITUTION: - From the Department of Breast Surgery, Qilu Hospital, Shandong University, Wenhua Xi Road 107, Jinan 250012, Shandong Province, China.
RESUMEN / SUMMARY: - Metadherin (MTDH), the newly discovered gene, is overexpressed in more than 40% of breast cancers. Recent studies have revealed that MTDH favors an oncogenic course and chemoresistance. With a number of breast cancer cell lines and breast tumor samples, we found that the relative expression of MTDH correlated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in breast cancer. In this study, we found that knockdown of endogenous MTDH cells sensitized the MDA-MB-231 cells to TRAIL-induced apoptosis both in vitro and in vivo. Conversely, stable overexpression of MTDH in MCF-7 cells enhanced cell survival with TRAIL treatment. Mechanically, MTDH down-regulated caspase-8, decreased caspase-8 recruitment into the TRAIL death-inducing signaling complex, decreased caspase-3 and poly(ADP-ribose) polymerase-2 processing, increased Bcl-2 expression, and stimulated TRAIL-induced Akt phosphorylation, without altering death receptor status. In MDA-MB-231 breast cancer cells, sensitization to TRAIL upon MTDH down-regulation was inhibited by the caspase inhibitor Z-VAD-fmk (benzyloxycarbonyl-VAD-fluoromethyl ketone), suggesting that MTDH depletion stimulates activation of caspases. In MCF-7 breast cancer cells, resistance to TRAIL upon MTDH overexpression was abrogated by depletion of Bcl-2, suggesting that MTDH-induced Bcl-2 expression contributes to TRAIL resistance. We further confirmed that MTDH may control Bcl-2 expression partly by suppressing miR-16. Collectively, our results point to a protective function of MTDH against TRAIL-induced death, whereby it inhibits the intrinsic apoptosis pathway through miR-16-mediated Bcl-2 up-regulation and the extrinsic apoptosis pathway through caspase-8 down-regulation.
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[244]
TÍTULO / TITLE: - Criteria for and outcomes of allogeneic haematopoietic stem cell transplant in children, adolescents and young adults with acute lymphoblastic leukaemia in first complete remission.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Haematol. 2013 Apr;161(1):27-42. doi: 10.1111/bjh.12239. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1111/bjh.12239
AUTORES / AUTHORS: - Hochberg J; Khaled S; Forman SJ; Cairo MS
INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
RESUMEN / SUMMARY: - Most children, adolescents and young adults with acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) have an excellent prognosis with multi-agent chemotherapy in induction, consolidation, re-induction and maintenance therapy. However, there is a subset of patients with a more guarded prognosis using this approach, who may benefit from haematopoietic allogeneic stem cell transplantation (alloHSCT). Commonly used criteria for alloHSCT in children, adolescents and young adults with ALL in CR1 include: induction failure, poor cytogenetics, persistent minimal residual disease (MRD), age, immunophenotype, white blood cell count at diagnosis and rapidity of induction response. Two-year event-free survival following alloHSCT in patients with ALL in CR1 ranges from 50 to 80% depending on disease status, donor source, conditioning therapy, age and other risk factors. Future studies should focus on more precisely identifying poor-risk features, such as disease genomics and host pharmacogenomics, refining MRD measurements, improving unrelated donor matching, reducing MRD prior to alloHSCT, and developing post-alloHSCT humoral and cellular therapy approaches.
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[245]
TÍTULO / TITLE: - Prognostic value of single nucleotide polymorphisms of candidate genes associated with inflammation in early stage breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2445-x
AUTORES / AUTHORS: - Murray JL; Thompson P; Yoo SY; Do KA; Pande M; Zhou R; Liu Y; Sahin AA; Bondy ML; Brewster AM
INSTITUCIÓN / INSTITUTION: - The University of Texas MD Anderson Cancer Center, Houston, TX, USA, jmurray@mdanderson.org.
RESUMEN / SUMMARY: - To examine the role of germline genetic variations in inflammatory pathways as modifiers of time to recurrence (TTR) in patients with early stage breast cancer (BC), DNA from 997 early stage BC patients was genotyped for 53 tagging single nucleotide polymorphisms (SNPs) in 12 genes involved in inflammation. SNPs were analyzed separately for Caucasians versus African-Americans and Hispanics. Cox proportional hazards models were used to evaluate the association between SNPs in the inflammatory genes and TTR, adjusted for clinical and pathologic covariates. In univariable analyses of Caucasian women, the homozygous genotype of 12 SNPs, including 6 NFKB1 SNPs, 4 IL4 SNPs, and 2 IL13 SNPs, were significantly associated with a decrease in TTR compared with the heterozygous and/or corresponding homozygous genotype (P < 0.05). The significant NFKB1 and IL4 SNPs were in an area of high linkage disequilibrium (D’ > 0.8). After adjusting for stage, age, and treatment, carriage of the homozygous genotypes for NFKB1 rs230532 and IL13rs1800925 were independently associated with a shorter TTR (P = 0.001 and P = 0.034, respectively). In African-American and Hispanic patients, expression of NFKB1 rs3774932, TNFrs1799964, and IL4rs3024543 SNPs were associated with a shorter TTR in univariable model. Only NFKB1 rs3774932 (P = 0.02) and IL4Rrs3024543 (P = 0.03) had independent prognostic value in the multivariable model These data support the existence of host genetic susceptibility as a component in recurrence risk mediated by pro-inflammatory and immune factors, and suggest the potential for drugs which modify immune responses and inflammatory genes to improve prognosis in early stage BC.
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[246]
TÍTULO / TITLE: - Hepatocyte growth factor activator inhibitor type 1 (Hai-1/Spint1) is a suppressor of intestinal tumorigenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3337
AUTORES / AUTHORS: - Hoshiko S; Kawaguchi M; Fukushima T; Haruyama Y; Yorita K; Tanaka H; Seiki M; Inatsu H; Kitamura K; Kataoka H
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Faculty of Medicine, University of Miyazaki.
RESUMEN / SUMMARY: - Hepatocyte growth factor activator inhibitor type 1 (HAI-1/SPINT1) is a membrane-bound serine protease inhibitor expressed on the surface of epithelial cells. Although HAI-1/SPINT1 is abundantly expressed in the intestinal epithelium, its role in intestinal tumorigenesis is not known. In this study, we investigated the role of Hai-1/Spint1 in intestinal tumorigenesis using mouse models. The membranous Hai-1/Spint1 immunoreactivity was decreased in murine ApcMin/+ tumors and also in carcinogen (azoxymethane treatment followed by dextran sodium sulfate administration)-induced colon tumors compared to the adjacent non-neoplastic epithelium. The decreased immunoreactivity appeared to be due to sheddase activity of membrane-type 1 matrix metalloprotease. Then, we examined the effect of intestine-specific deletion of Spint1 gene on ApcMin/+ mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods. Activation of hepatocyte growth factor was enhanced in Hai-1/Spint1-deficient ApcMin/+ intestine. Gene expression profiling revealed upregulation of the Wnt/beta-catenin-signaling circuit, claudin-2 expression, and angiogenesis not only in tumor tissue but also in the background mucosa without macroscopic tumors in Hai-1/Spint1-deficient ApcMin/+ intestine. Intestinal deletion of Spint1 also enhanced the susceptibility to carcinogen-induced colon tumorigenicity of wild-type Apc mice. Our findings suggest that HAI-1/SPINT1 has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli.
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[247]
TÍTULO / TITLE: - Cleavage of BCR-ABL transcripts at the T315I point mutation by DNAzyme promotes apoptotic cell death in imatinib-resistant BCR-ABL leukemic cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leukemia. 2013 Feb 25. doi: 10.1038/leu.2013.60.
●● Enlace al texto completo (gratuito o de pago) 1038/leu.2013.60
AUTORES / AUTHORS: - Kim JE; Yoon S; Choi BR; Kim KP; Cho YH; Jung W; Kim DW; Oh S; Kim DE
INSTITUCIÓN / INSTITUTION: - Department of Bioscience and Biotechnology, Konkuk University, Seoul Republic of Korea.
RESUMEN / SUMMARY: - The BCR-ABL fusion transcript encodes the BCR-ABL tyrosine kinase (TK), which causes chronic myelogenous leukemia (CML). Although the TK inhibitor imatinib mesylate, which targets the BCR-ABL protein, has been proven to be effective in controlling leukemic growth, imatinib resistance has been observed with disease relapse because of point mutations in the ABL gene that inhibit imatinib efficacy. In this study, we designed oligodeoxyribozymes (DNAzymes) that specifically target and cleave both the junction sequence and the site of the point mutation (T315I), conferring imatinib resistance in BCR-ABL mRNA. DNAzymes significantly induced apoptosis and inhibited proliferation in wild-type and T315I-mutant BCR-ABL-positive cells. Selective cleavage of T315I-mutant ABL mRNA by DNAzyme (T315I Dz) led to cell cycle arrest in G0/G1 phase, with induction of caspase-3/-7 in imatinib-resistant BCR-ABL-positive cells harboring the T315I mutation. Moreover, cotreatment with the DNAzyme targeting the T315I mutation and imatinib resulted in enhanced inhibition of proliferation and induction of apoptosis in T315I leukemic cells as compared with imatinib alone, thereby antagonizing imatinib resistance in CML cells bearing T315I-mutant BCR-ABL. Therefore, cleavage of T315I-mutant ABL mRNA by DNAzyme combined with imatinib treatment may be an alternative approach to overcoming imatinib resistance in leukemic cells.Leukemia advance online publication, 19 March 2013; doi:10.1038/leu.2013.60.
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[248]
TÍTULO / TITLE: - The BH3-only protein Puma plays an essential role in p53-mediated apoptosis of chronic lymphocytic leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.787613
AUTORES / AUTHORS: - Zhu HJ; Liu L; Fan L; Zhang LN; Fang C; Zou ZJ; Jianyong L; Xu W
RESUMEN / SUMMARY: - Abstract The purpose of this study was to explore the characteristics and functions of BH3-only proteins Puma, Noxa and Bim in the prognosis, therapy and drug resistance of chronic lymphocytic leukemia (CLL). Puma, Noxa and Bim mRNAs were evaluated by qPCR, and the correlations between the expression levels and CLL prognostic markers were analyzed. The primary CLL samples were treated in vitro with fludarabine to investigate the role of Puma, Noxa and Bim in the response to chemotherapeutic drugs, which acted through activating p53 pathway. We found that the low expression level of Puma was associated with some markers of poor prognosis. However, the level of Noxa or Bim was not different in CLL patients with variant clinical features and prognostic factors. Puma expression was upregulated after fludarabine treatment in the primary CLL cells, but there is no significant difference for Noxa and Bim. The upregulated Puma was only occurred in CLL cells with functional p53. CLL cells with p53 abnormalities are deficient in the activation of Puma by chemotherapeutics. These results suggest that the lack of Puma induction may contribute to the development of resistance to anticancer agents in CLL.
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[249]
TÍTULO / TITLE: - Silibinin Synergizes with Histone Deacetylase and DNA Methyltransferase Inhibitors in Up-regulating E-cadherin Expression Together with Inhibition of Migration and Invasion of Human Non-small Cell Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pharmacol Exp Ther. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1124/jpet.113.203471
AUTORES / AUTHORS: - Mateen S; Raina K; Agarwal C; Chan D; Agarwal R
INSTITUCIÓN / INSTITUTION: - 1 University of Colorado;
RESUMEN / SUMMARY: - Aggressive cancers in the epithelial-to-mesenchymal transition (EMT) phase are characterized by loss of cell adhesion, repression of E-cadherin and increased cell mobility. Non-small cell lung cancer (NSCLC) differs in basal level of E-cadherin; predominantly exhibiting silenced expression due to epigenetic-related modifications. Accordingly, effective treatments are needed to modulate these epigenetic events that in turn can positively regulate E-cadherin levels. Herein, we investigated silibinin, a natural flavonolignan with anti-cancer efficacy against lung cancer, either alone or in combination with epigenetic therapies to modulate E-cadherin expression in a panel of NSCLC cell lines. Silibinin combined with HDAC inhibitor Trichostatin A (TSA) or DNMT inhibitor 5’-Aza-deoxycytidine (Aza) significantly restored E-cadherin levels in NSCLC cells harboring epigenetically silenced E-cadherin expression. These combination treatments also strongly decreased the invasion/migration of these cells, which further emphasized the biological significance of E-cadherin restoration. Treatment of NSCLC cells, with basal E-cadherin levels, by silibinin further increased the E-cadherin expression and inhibited their migratory and invasive potential. Additional studies showed that silibinin alone as well as in combination with TSA or Aza down modulate the expression of Zeb1, which is a major transcriptional repressor of E-cadherin. Overall these findings demonstrate the potential of combinatorial treatments of silibinin with HDAC or DNMT inhibitor to modulate EMT events in NSCLC cell lines, leading to a significant inhibition in their migratory and invasive potentials. These results are highly significant, since loss of E-cadherin and metastatic spread of the disease via EMT is associated with poor prognosis and high mortalities in NSCLC.
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[250]
TÍTULO / TITLE: - Cancer Protection Elicited by a Single Nucleotide Polymorphism Close to the Adrenomedullin Gene.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Endocrinol Metab. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-4193
AUTORES / AUTHORS: - Martinez-Herrero S; Martinez A
INSTITUCIÓN / INSTITUTION: - Oncology Area, Center for Biomedical Research of La Rioja, 26006 Logrono, España.
RESUMEN / SUMMARY: - Context:The risk of developing cancer is regulated by genetic variants, including polymorphisms. Characterizing such variants may help in developing protocols for personalized medicine.Objective:Adrenomedullin is a regulatory peptide involved in cancer promotion and progression. Carriers of a single nucleotide polymorphism (SNP) in the proximity of the adrenomedullin gene have lower levels of circulating peptide. The aim of the present work was to investigate whether carriers of this SNP (rs4910118) are protected against cancer.Design:This was a retrospective study. DNA samples were obtained from the Carlos III DNA National Bank (University of Salamanca, Salamanca, España).Setting:Samples represent a variety of donors and patients from España.Patients or Other Participants:DNA from patients with breast cancer (n = 238), patients with lung cancer (n = 348), patients with cardiac insufficiency (n = 474), and healthy donors of advanced age (n = 500) was used.Interventions:All samples were genotyped using double-mismatch PCR, and confirmation was achieved by direct sequencing.Main Outcome Measures:The minor allele frequency was calculated in all groups. The Pearson chi2 was used to compare SNP frequencies.Results:Of 1560 samples, 14 had the minor allele, with a minor allele frequency in healthy donors of 0.90%. Patients with cancer had a statistically significantly lower frequency than healthy donors (odds ratio = 0.216, 95% confidence interval = 0.048-0.967, P = .028).Conclusions:Carriers of the minor allele have a 4.6-fold lower risk of developing cancer than homozygotes for the major allele. Knowledge of the rs4910118 genotype may be useful for stratifying patients in clinical trials and for designing prevention strategies.
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[251]
TÍTULO / TITLE: - Association between polymorphisms in apoptotic genes and susceptibility for developing breast cancer in Syrian women.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Apr;138(2):611-9. doi: 10.1007/s10549-013-2467-4. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2467-4
AUTORES / AUTHORS: - Lajin B; Alhaj Sakur A; Alachkar A
INSTITUCIÓN / INSTITUTION: - Department of Analytical Chemistry, Faculty of Pharmacy, University of Aleppo, Aleppo, Syria, BassamL7@yahoo.co.uk.
RESUMEN / SUMMARY: - Apoptosis is a major protective mechanism against cancer. The tumor suppressor protein p53 is the central protein in the apoptotic pathway and was shown to harbor mutations in a considerable fraction of breast cancer tumors. The NQO1 was shown to act as a p53 stabilizer and was suggested to play an important role in the protection against carcinogenic catechol estrogens. Functional polymorphisms in TP53 and NQO1 were investigated in relation to breast cancer susceptibility in several studies, primarily involving Asian and Caucasian populations. The aim of the present study was to investigate TP53 and NQO1 polymorphisms and their combined effects with respect to breast cancer susceptibility in a Syrian study cohort. The study cohort consisted of 122 cases and 139 controls. The tetra-primer ARMS-PCR method was used to genotype three TP53 polymorphisms; namely, exon 4 G>C Arg72Pro, IVS3 16 bp Del/Ins, and MspI IVS6+62A>G, and NQO1 C609T (Pro187Ser) polymorphism. Association was tested under six genetic models. We found a significant association for the heterozygous Arg/Pro genotype when combined with heterozygosity for IVS3 16 bp Del/Ins and MspI IVS6+62A>G (OR = 2.05 (1.22-3.47), P = 0.006). No significant association was found for NQO1 C609T or its combinations with TP53 polymorphisms. Our results support an association for TP53 polymorphisms with breast cancer susceptibility in the Syrian population.
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[252]
TÍTULO / TITLE: - Paclitaxel attenuates Bcl-2 resistance to apoptosis in breast cancer cells through an endoplasmic reticulum-mediated calcium release in a dosage dependent manner.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 15;432(3):431-7. doi: 10.1016/j.bbrc.2013.01.130. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.01.130
AUTORES / AUTHORS: - Pan Z; Gollahon L
INSTITUCIÓN / INSTITUTION: - Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409-3131, United States. Electronic address: zhi_pan@yahoo.com.
RESUMEN / SUMMARY: - To address the controversy regarding efficacy of paclitaxel in the presence of the anti-apoptotic protein Bcl-2, we investigated calcium stored in the endoplasmic reticulum as a potential factor. Our results showed that the ER calcium store is a common target for both paclitaxel and Bcl-2 protein. Paclitaxel directly associates with the endoplasmic reticulum to stimulate the release of calcium into the cytosol, contributing to the induction of apoptosis. However, Bcl-2 expression suppresses the cell’s pro-apoptotic response of endoplasmic reticulum calcium release, thus inhibiting susceptibility of cancer cells to undergo apoptosis. Depending upon dosage, a paclitaxel-induced stimulatory effect can overcome the Bcl-2-mediated inhibitory effect on endoplasmic reticulum calcium release, thus attenuating the resistance of Bcl-2 to apoptosis. Our finding is the first to demonstrate that endoplasmic reticulum calcium plays a key role in the efficacy of paclitaxel in the presence of Bcl-2, thus providing insight into the complex but crucial paclitaxel-calcium-Bcl-2 relationship, which may impact breast cancer treatment.
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[253]
TÍTULO / TITLE: - Toll-like receptor 4 genetic variants and prognosis of breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tissue Antigens. 2013 Apr;81(4):221-6. doi: 10.1111/tan.12096.
●● Enlace al texto completo (gratuito o de pago) 1111/tan.12096
AUTORES / AUTHORS: - Yang CX; Li CY; Feng W
INSTITUCIÓN / INSTITUTION: - Department of Oncology, The Lianyungang No.1 Hospital, The Lianyungang Hospital Affiliated to Xuzhou Medical College, Lianyungang, Jiangsu, China.
RESUMEN / SUMMARY: - Despite the knowledge of many genetic alterations present in breast cancer, the complexity of this disease precludes placing its biology into a simple conceptual framework. Toll-like receptor 4 (TLR4) plays important roles in regulating innate immunity and may affect the development of cancers. Polymorphisms in TLR4 gene have been shown to be associated with impaired immune responses. Here, we investigated the association of TLR4 polymorphisms with breast cancer. Four functional TLR4 polymorphisms (-2242T/C, Asp299Gly, Thr399Ile, and +3725G/C) were genotyped in a total of 665 breast cancer patients and 768 healthy controls. Data were analyzed using the chi-squared test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in breast cancer cases when compared with controls [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.08-1.73, P = 0.008 and OR = 2.34, 95% CI = 1.66-3.35, P < 0.0001, respectively]. Also, the frequency of TLR4 +3725C allele was significantly higher in breast cancer patients (P < 0.0001). The -2242T/C polymorphism did not show any significant differences between cases and controls. In addition, when analyzing the survival time of breast cancer patients with TLR4 +3725G/C polymorphism, cases with +3725C allele had significantly shorter survival time overall (P = 0.006). These results suggested that polymorphism in TLR4 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.
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[254]
TÍTULO / TITLE: - The prognostic value of platelet endothelial cell adhesion molecule-1 in non-small-cell lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):536. doi: 10.1007/s12032-013-0536-5. Epub 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0536-5
AUTORES / AUTHORS: - Kuang BH; Wen XZ; Ding Y; Peng RQ; Cai PQ; Zhang MQ; Jiang F; Zhang XS; Zhang X
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 East Dongfeng Road, Guangzhou 510060, China.
RESUMEN / SUMMARY: - Our previous studies have shown that platelet endothelial cell adhesion molecule-1 (PECAM-1), a member of the immunoglobulin superfamily, is a critical mediator of anchorage-independent growth and anoikis resistance in lung carcinoma cells. The purpose of this study was to analyze the protein expression of PECAM-1 in non-small-cell lung carcinoma (NSCLC) tissues and its clinical significance in NSCLC patients. By immunohistochemical analysis, high microvessel density (MVD) of PECAM-1 was detected in the stromal tissues of NSCLC. The MVD of PECAM-1 was strongly correlated with the N stage (p = 0.029), M stage (p = 0.001) and clinical stage (p = 0.001) of NSCLC patients. Survival analysis revealed high MVD of PECAM-1 in both primary NSCLC lesions and metastatic lymph node tissues, and these results were found to be significantly correlated with poor overall survival in NSCLC patients (p < 0.001 and p = 0.021, respectively). Moreover, patients with high PECAM-1 MVD had worse overall survival in either adenocarcinoma or EGFR mutation subgroups. Multivariate analysis revealed that the MVD of PECAM-1 was an independent prognostic factor for NSCLC patients. The MVD of PECAM-1 is also a potential predictor for NSCLC patients treated with first-line platinum-based doublet chemotherapy, as high PECAM-1 MVD correlated with worse overall survival. Our results demonstrated that MVD of PECAM-1 could be a potential prognostic factor and therapeutic target in NSCLC.
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[255]
TÍTULO / TITLE: - Sequential hTERT Knockdown and Apigenin Treatment Inhibited Invasion and Proliferation and Induced Apoptosis in Human Malignant Neuroblastoma SK-N-DZ and SK-N-BE2 Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Mol Neurosci. 2013 Feb 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s12031-013-9975-x
AUTORES / AUTHORS: - Chakrabarti M; Banik NL; Ray SK
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, 29209, USA.
RESUMEN / SUMMARY: - Human telomerase reverse transcriptase (hTERT) plays a key role in conferring immortality to human malignant neuroblastomas. We first determined differential expression of hTERT in four human malignant neuroblastoma SH-SY5Y, SK-N-DZ, SK-N-BE2, and IMR-32 cell lines. We then used SK-N-DZ and SK-N-BE2 cell lines, which showed the highest expression of hTERT, to investigate the therapeutic effects of sequential hTERT knockdown and apigenin (APG) treatment. We performed cell invasion assay and studied alterations in expression of matrix metalloproteinases and cell cycle regulatory molecules after this combination therapy. We also investigated induction of apoptosis by using in situ Wright staining, Annexin V staining, and Western blotting. Sequential hTERT knockdown and APG treatment significantly downregulated expression of hTERT so as to cause over 90 % inhibition of cell invasion and 70 % induction of apoptosis in both SK-N-DZ and SK-N-BE2 cell lines. Western blotting demonstrated downregulation of the molecules involved in cell invasion and proliferation, but upregulation of the cell cycle inhibitor and apoptosis-inducing molecules. In conclusion, our current results clearly showed that sequential hTERT knockdown and APG treatment could be a promising therapeutic strategy for effective inhibition of invasion and proliferation and induction of apoptosis in hTERT overexpressing malignant neuroblastoma cells.
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[256]
TÍTULO / TITLE: - Enzyme-responsive copper sulphide nanoparticles for combined photoacoustic imaging, tumor-selective chemotherapy and photothermal therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chem Commun (Camb). 2013 Mar 28;49(33):3455-7. doi: 10.1039/c3cc40608c.
●● Enlace al texto completo (gratuito o de pago) 1039/c3cc40608c
AUTORES / AUTHORS: - Zha Z; Zhang S; Deng Z; Li Y; Li C; Dai Z
INSTITUCIÓN / INSTITUTION: - Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China. zhifei.dai@pku.edu.cn.
RESUMEN / SUMMARY: - Gelatin-stabilized copper sulphide nanoparticles with conjugated doxorubicin have been developed for combined photoacoustic imaging, enzyme-responsive drug release and photothermal therapy.
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[257]
TÍTULO / TITLE: - Enhanced anti-cancer activity of human dendritic cells sensitized with gamma-irradiation-induced apoptotic colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 26. pii: S0304-3835(13)00164-X. doi: 10.1016/j.canlet.2013.02.038.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.038
AUTORES / AUTHORS: - Kim SK; Yun CH; Han SH
INSTITUCIÓN / INSTITUTION: - Department of Oral Microbiology and Immunology, DRI, and BK21 Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - Properly sensitized dendritic cells (DCs) can be an effective immunotherapeutic against cancers. We investigated the phenotypic and functional changes in human DCs sensitized with gamma-irradiated colon cancer cell-line HT-29 (GIH). GIH induced maturation and activation of DCs. GIH-sensitized DCs showed increased cytotoxic activity against HT-29 through higher expression of perforin and granzyme B. They further induced expression of effector cytokines, cytotoxic molecules, and mucosal-homing receptor in autologous T-cells. Conclusively, these results suggest that effective anti-cancer activity is induced when DCs are sensitized with gamma-irradiated cancer cells via both direct augmentation of the cytotoxicity and indirect activation of T cells.
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[258]
TÍTULO / TITLE: - The response to neoadjuvant chemotherapy predicts clinical outcome and increases breast conservation in advanced breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Surg. 2013 Jan 30. pii: S0002-9610(13)00013-5. doi: 10.1016/j.amjsurg.2012.10.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.amjsurg.2012.10.025
AUTORES / AUTHORS: - Spanheimer PM; Carr JC; Thomas A; Sugg SL; Scott-Conner CE; Liao J; Weigel RJ
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242-1086, USA.
RESUMEN / SUMMARY: - BACKGROUND: The aim of this study was to determine outcomes in patients with breast cancer treated with neoadjuvant chemotherapy. METHODS: Seventy-two consecutive patients receiving neoadjuvant chemotherapy for breast cancer were enrolled. RESULTS: Mastectomy was avoided in 46% of patients, and 42% converted to negative nodes after neoadjuvant chemotherapy. Thirteen patients (18%) achieved a pathologic complete response, which was associated with the estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (Her2)-negative subtype (58%) and was significantly less likely to occur in the ER+/Her2- subtype (2%) (P < .01). Patients with the ER+/Her2+ subtype were most likely to have no response or progression during chemotherapy, compared with those with the ER-/Her2- subtype (50% vs 0%, P = .01). Five-year survival for patients achieving a pathologic complete response was 100%, compared with 74% in the group with partial response and 48% in the group with no response or progression (P = .01). CONCLUSIONS: Neoadjuvant chemotherapy for patients with advanced breast cancer provided prognostic information, allowed evaluation of response to chemotherapy, decreased the mastectomy rate, and potentially reduced the need for axillary lymph node dissection.
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[259]
TÍTULO / TITLE: - Rare somatic mutation of pro-apoptotic BAX and BAK genes in common human cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):149e-51e. doi: 10.1700/1217.13509.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13509
AUTORES / AUTHORS: - Kim MS; Kim SS; Yoo NJ; Lee SH
INSTITUCIÓN / INSTITUTION: - Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, Korea.
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: BAX and BAK are both pro-apoptotic Bcl-2 proteins and are essential for the pathway of intrinsic apoptosis. Apoptosis in cancer cells is frequently inactivated by somatic mutations. The aim of the study was to see whether somatic mutations of BAX and BAK genes are characteristics of common human cancers. METHODS: We analyzed somatic mutation of BAX and BAK genes in 47 gastric, 47 colorectal, 47 breast, 47 lung and 47 prostate carcinomas, and 47 acute leukemias by a polymerase chain reaction and single-strand conformation polymorphism assay. RESULTS: We identified BAX gene mutations in one colon (2.1%) and three gastric (6.4%) cancers. All of the mutations were frameshift mutations in the G8 repeat sequences and were detected in cancers with high microsatellite instability (36.4%). There was no evidence of BAX mutation in the other cancers, nor was somatic mutation of the BAK gene detected in the cancers. CONCLUSIONS: Our data indicate that somatic mutation of BAX and BAK genes are rare in the common cancers (besides the cancers with high microsatellite instability) and suggest that neither BAX nor BAK mutation may causally be implicated in their tumorigenesis.
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[260]
TÍTULO / TITLE: - Therapeutic Agents Triggering Non-Apoptotic Cancer Cell Death.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Chem. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1021/jm400136m
AUTORES / AUTHORS: - Kornienko A; Mathieu V; Rastogi SK; Lefranc F; Kiss R
RESUMEN / SUMMARY: - It is widely recognized that the evasion of apoptotic cell death is one of the hallmarks of cancer. For many years cytotoxic agents have been developed to target apoptotic cell death as a main method of treating cancer. However, the occurrence of cellular defects involving the apoptotic machinery in many cancers has resulted in an acquired resistance to apoptotic cell death, undermining the effectiveness of chemotherapeutic agents. Over the past decade, research has revealed a growing number of cell death pathways that are not dependent on apoptosis. In addition, compounds specifically triggering these alternative cell death pathways have been identified and explored as novel cancer treatment options. These novel anticancer agents are critically discussed by the authors and, therefore, the current Perspective represents a resource for a practicing medicinal chemist looking for new opportunities to combat cancers resistant to the established pro-apoptotic therapeutic agents.
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[261]
TÍTULO / TITLE: - mTOR Inhibitors Block Kaposi Sarcoma Growth by Inhibiting Essential Autocrine Growth Factors and Tumor Angiogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Apr 1;73(7):2235-46. doi: 10.1158/0008-5472.CAN-12-1851. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1851
AUTORES / AUTHORS: - Roy D; Sin SH; Lucas A; Venkataramanan R; Wang L; Eason A; Chavakula V; Hilton IB; Tamburro KM; Damania B; Dittmer DP
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Curriculum in Genetics and Molecular Biology; Department of Microbiology and Immunology; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
RESUMEN / SUMMARY: - Kaposi sarcoma originates from endothelial cells and it is one of the most overt angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi sarcoma-associated herpesvirus (KSHV) are endemic, Kaposi sarcoma is the most common cancer overall, but model systems for disease study are insufficient. Here, we report the development of a novel mouse model of Kaposi sarcoma, where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, and RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results show that mTOR inhibitors exert a direct anti-Kaposi sarcoma effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for Kaposi sarcoma and other cancers of endothelial origin. Cancer Res; 73(7); 2235-46. ©2012 AACR.
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[262]
TÍTULO / TITLE: - Prediction of efficacy to pegylated interferon-alpha-2b plus ribavirin in patients with genotype 2 hepatitis C virus using viral response within 2 weeks.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatol Res. 2013 Feb 25. doi: 10.1111/hepr.12101.
●● Enlace al texto completo (gratuito o de pago) 1111/hepr.12101
AUTORES / AUTHORS: - Wada Y; Tamai H; Uno A; Kawashima A; Shingaki N; Mori Y; Moribata K; Miyata K; Higashi K; Deguchi H; Ueda K; Inoue I; Maekita T; Iguchi M; Kato J; Ichinose M
INSTITUCIÓN / INSTITUTION: - Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
RESUMEN / SUMMARY: - AIM: Rapid virological response (RVR), defined as serum hepatitis C virus (HCV) RNA negativity at 4 weeks, is the most useful predictor of sustained virological response (SVR) to standard pegylated interferon (PEG IFN) plus ribavirin therapy for patients infected with genotype 2 HCV. The aim of the present study was to predict SVR using viral response within 2 weeks of therapy initiation. METHODS: Of 64 HCV genotype 2 patients with a high viral load treated with standard PEG IFN-alpha-2b plus weight-based ribavirin for 24 weeks, 58 patients whose adherence was more than 67% were analyzed. RNA and core antigen levels were measured at four time points: the day of therapy initiation, the following day, and at 1 and 2 weeks. RESULTS: SVR was achieved in 73% (47/64) of patients. Univariate analysis of SVR contributing factors showed significant differences with age, bodyweight, white blood cell count, platelet count, fibrosis marker levels, baseline core antigen level and viral response. The area under the receiver-operator curve (AUC) of the core antigen level at 1 week (AUC, 0.940) was the highest among the significant SVR predicting factors. Setting 100 fmol/L as the cut-off value for core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for predicting SVR were 100%, 86%, 96%, 100% and 97%, respectively, and for predicting RVR were 66%, 93%, 97%, 46% and 72%, respectively. CONCLUSION: The HCV core antigen level at 1 week after therapy initiation is the most useful predictor for SVR.
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[263]
TÍTULO / TITLE: - IL-24 sensitizes tumor cells to TLR3-mediated apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Differ. 2013 Mar 1. doi: 10.1038/cdd.2013.15.
●● Enlace al texto completo (gratuito o de pago) 1038/cdd.2013.15
AUTORES / AUTHORS: - Weiss R; Sachet M; Zinngrebe J; Aschacher T; Krainer M; Hegedus B; Walczak H; Bergmann M
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
RESUMEN / SUMMARY: - Interleukin-24 (IL-24), a member of the IL-10 cytokine family whose physiological function remains largely unknown, has been shown to induce apoptosis when expressed in an adenoviral background. It is yet little understood, why IL-24 alone induced apoptosis only in a limited number of tumor cell lines. Analyzing an influenza A virus vector expressing IL-24 for its oncolytic potential revealed enhanced pro-apoptotic activity of the chimeric virus compared with virus or IL-24 alone. Interestingly, IL-24-mediated enhancement of influenza-A-induced apoptosis did not require viral replication but critically depended on toll-like receptor 3 (TLR3) and caspase-8. Immunoprecipitation of TLR3 showed that infection by influenza A virus induced formation of a TLR3-associated signaling complex containing TRIF, RIP1, FADD, cFLIP and pro-caspase-8. Co-administration of IL-24 decreased the presence of cFLIP in the TLR3-associated complex, converting it into an atypical, TLR3-associated death-inducing signaling complex (TLR3 DISC) that induced apoptosis by enabling caspase-8 activation at this complex. The sensitizing effect of IL-24 on TLR3-induced apoptosis, mediated by influenza A virus or the TLR3-specific agonist poly(I:C), was also evident on tumor spheroids. In conclusion, rather than acting as an apoptosis inducer itself, IL-24 sensitizes cancer cells to TLR-mediated apoptosis by enabling the formation of an atypical DISC which, in the case of influenza A virus or poly(I:C), is associated with TLR3.Cell Death and Differentiation advance online publication, 1 March 2013; doi:10.1038/cdd.2013.15.
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[264]
TÍTULO / TITLE: - The impact of V30A mutation on transthyretin protein structural stability and cytotoxicity against neuroblastoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Biochem Biophys. 2013 Mar 22. pii: S0003-9861(13)00093-3. doi: 10.1016/j.abb.2013.03.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.abb.2013.03.005
AUTORES / AUTHORS: - Zhang F; Hu C; Dong Y; Lin MS; Liu J; Jiang X; Ge Y; Guo Y
INSTITUCIÓN / INSTITUTION: - The State Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun, China.
RESUMEN / SUMMARY: - Single point mutations in the transthyretin (TTR) gene may cause a hereditary neurodegenerative disease termed familial amyloidotic polyneuropathy (FAP) due to accelerated deposition of amyloid fibrils, resulting in peripheral and autonomic nervous system dysfunction. Recently, we found a Chinese FAP family involving a TTR V30A mutation. To understand the pathogenic mechanisms of this V30A TTR, we investigated the effects of this mutation on TTR quaternary and tertiary structural stabilities and cytotoxicities against neuroblastoma cells along with the most common variant V30M TTR and the wild-type (WT) TTR. Our results showed that the V30A mutation impaired the thermodynamic and kinetic stabilities of the TTR protein by increasing the extent and rate of tetramer dissociation and unfolded monomer and amyloid fibril formation, even to a greater extent than the V30M mutation under several experimental conditions. Further, an obviously cytotoxic effect of the V30A TTR on the human neuroblastoma cell line, IMR-32, was observed. The V30A TTR induced apoptosis and autophagy concomitant with the accumulation of reactive oxygen species (ROS) and DNA double-strand breaks, reflected in the induction of phosphor-H2A.X. These results suggest that the V30A mutation in the TTR gene promotes the formation of unfolded monomers and amyloid fibrils, which potentially contribute to the increased neurotoxicity and the pathology associated with this FAP family.
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[265]
TÍTULO / TITLE: - AMP-activated protein kinase (AMPK)/Ulk1-dependent autophagic pathway contributes to C6 ceramide-induced cytotoxic effects in cultured colorectal cancer HT-29 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1608-8
AUTORES / AUTHORS: - Huo HZ; Wang B; Qin J; Guo SY; Liu WY; Gu Y
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, The Ninth People’s Hospital Affiliated to Shanghai Jiao-tong University School of Medicine, 639 Zhizhaoju Road, Shanghai, 200011, China.
RESUMEN / SUMMARY: - Colorectal cancer is the second leading cause of cancer-related deaths. Drug resistance and/or off-target toxicity against normal cells limit the effectiveness of current chemotherapies for the treatment of colorectal cancer. In the current study, we studied the potential cytotoxic effects of short-chain and cell-permeable C6 ceramide in cultured colorectal cancer HT-29 cells and focused on the underlying mechanisms. We observed that C6 ceramide-induced HT-29 cell death and growth inhibition in a dose- and time-dependent manner. However, no significant apoptosis was observed in C6 ceramide-treated HT-29 cells. Our data support that autophagy contributed to C6 ceramide-induced cytotoxic effects, as autophagy inhibitors, 3-methyladenine (3-MA) and hydroxychloroquine, inhibited C6 ceramide’s effect; however, autophagy activators, everolimus (RAD001) and temsirolimus, mimicked C6 ceramide effects and induced HT-29 cell death. Further, we indentified that AMP-activated protein kinase (AMPK)/Ulk1 signaling was required for autophagy induction by C6 ceramide, and AMPK silencing by a specific short hairpin RNA suppressed C6 ceramide-induced autophagy and cytotoxic effects. Reversely, forced activation of AMPK by its activator AICAR or by genetic manipulation caused autophagic death in HT-29 cells, which was inhibited by 3-MA. Our results suggest that autophagy, but not apoptosis, is a major contributor for C6 ceramide-induced cytotoxic effects in HT-29 cells, and activation of AMPK/Ulk1 is required for the process.
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[266]
TÍTULO / TITLE: - Pentoxifylline and the proteasome inhibitor MG132 induce apoptosis in human leukemia U937 cells through a decrease in the expression of Bcl-2 and Bcl-XL and phosphorylation of p65.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biomed Sci. 2013 Feb 28;20(1):13.
●● Enlace al texto completo (gratuito o de pago) 1186/1423-0127-20-13
AUTORES / AUTHORS: - Bravo-Cuellar A; Hernandez-Flores G; Lerma-Diaz JM; Dominguez-Rodriguez JR; Jave-Suarez LF; De Celis-Carrillo R; Aguilar-Lemarroy A; Gomez-Lomeli P; Ortiz-Lazareno PC
RESUMEN / SUMMARY: - BACKGROUND: In Oncology, the resistance of the cancerous cells to chemotherapy continues to be the principal limitation. The nuclear factor-kappa B (NF-kappaB) transcription factor plays an important role in tumor escape and resistance to chemotherapy and this factor regulates several pathways that promote tumor survival including some antiapoptotic proteins such as Bcl-2 and Bcl-XL. In this study, we investigated, in U937 human leukemia cells, the effects of Pentoxifylline (PTX) and the MG132 proteasome inhibitor, drugs that can disrupt the NF-kappaB pathway. For this, we evaluated viability, apoptosis, cell cycle, caspases-3, -8, -9, cytochrome c release, mitochondrial membrane potential loss, p65 phosphorylation, and the modification in the expression of pro- and antiapoptotic genes, and the Bcl-2 and Bcl-XL antiapoptotic proteins. RESULTS: The two drugs affect the viability of the leukemia cells in a time-dependent manner. The greatest percentage of apoptosis was obtained with a combination of the drugs; likewise, PTX and MG132 induce G1 phase cell cycle arrest and cleavage of caspases -3,-8, -9 and cytochrome c release and mitochondrial membrane potential loss in U937 human leukemia cells. In these cells, PTX and the MG132 proteasome inhibitor decrease p65 (NF-kappaB subunit) phosphorylation and the antiapoptotic proteins Bcl-2 and Bcl-XL. We also observed, with a combination of these drugs overexpression of a group of the proapoptotic genes BAX, DIABLO, and FAS while the genes BCL-XL, MCL-1, Survivin, IkappaB, and P65 were downregulated. CONCLUSIONS: The two drugs used induce apoptosis per se, this cytotoxicity was greater with combination of both drugs. These observations are related with the caspases -9, -3 cleavage and G1 phase cell cycle arrest, and a decrease in p65 phosphorylation and Bcl-2 and Bcl-XL proteins. As well as this combination of drugs promotes the upregulation of the proapoptotic genes and downregulation of antiapoptotic genes. These observations strongly confirm antileukemic potential.
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[267]
TÍTULO / TITLE: - Polymorphisms in genes of APE1, PARP1, and XRCC1: risk and prognosis of colorectal cancer in a Northeast Chinese population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):505. doi: 10.1007/s12032-013-0505-z. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0505-z
AUTORES / AUTHORS: - Li Y; Li S; Wu Z; Hu F; Zhu L; Zhao X; Cui B; Dong X; Tian S; Wang F; Zhao Y
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, People’s Republic of China.
RESUMEN / SUMMARY: - Base excision repair (BER) pathway plays critical role in maintaining genome integrity. Polymorphisms in BER genes which modulate the DNA repair capacity may affect the susceptibility and prognosis of cancer. We conducted a case-control study and followed up the cases to explore the associations between BER genes polymorphisms and the risk and prognosis of colorectal cancer (CRC). This study included 451 CRC patients and 631 controls. Four single-nucleotide polymorphisms (SNPs) in genes of apurinic/apyrimidinic endonuclease-1 (APE1), ADP-ribosyltransferase (ADPRT, also known as PARP1), and X-ray repair cross-complementing groups 1 (XRCC1) were tested by PCR-RFLP. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence intervals (CIs) were calculated by unconditional logistic regression and Cox proportional hazard model. PARP1 762 recessive model (OR = 1.57, 95 % CI 1.12-2.20) and XRCC1 194 dominant model (OR = 1.45, 95 % CI 1.12-1.88) were associated with increased CRC risk. A significant increasing trend for the risk of CRC was detected with the increasing number of putative risk genotypes (P (trend) = 0.00). However, no association was found between these four SNPs and the prognosis of CRC. In conclusion, APE1 (Asp148Glu), PARP1 (Ala762Val), and XRCC1 (Arg399Gln, Arg194Trp) were associated with the susceptibility to CRC, but were not associated with the prognosis of CRC.
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[268]
TÍTULO / TITLE: - Reduced Folate Carrier and Folylpolyglutamate Synthetase, but not Thymidylate Synthase Predict Survival in Pemetrexed-Treated Patients Suffering from Malignant Pleural Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318287c224
AUTORES / AUTHORS: - Mairinger F; Vollbrecht C; Halbwedl I; Hatz M; Stacher E; Gully C; Quehenberger F; Stephan-Falkenau S; Kollmeier J; Roth A; Mairinger T; Popper H
INSTITUCIÓN / INSTITUTION: - *Department of Pathology and Neuropathology, University Hospital Essen, University of Duisberg-Essen, Essen, Germany; daggerInstitute of Pathology, University Hospital Cologne, Cologne, Germany; double daggerDepartment of Pathology, Division of Molecular Lung and Pleurapathology, Medical University Graz, Graz, Austria; section signCenter for Medical Research, ||Department of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria; Departments of paragraph signPathology, and #Pneumology Helios Klinikum Emil von Behring, Berlin, Germany.
RESUMEN / SUMMARY: - BACKGROUND:: Malignant mesothelioma is a highly aggressive tumor arising from mesothelial-lined surfaces, most often in the pleura cavities. Antifolates belong to the most effective cytotoxic drugs for malignant pleural mesothelioma (MPM) treatment. Pemetrexed is an antifolate inhibiting different folate pathway genes (thymidylate synthase [TS], dihydrofolate reductase, glycinamide ribonucleotide formyltransferase [GARFT], and aminoimidazole carboxamide ribonucleotide formyltransferase, [AICARFT]). Increased activity of pemetrexed occurs by folylpolyglutamate synthetase (FPGS), intracellular transport by reduced folate carrier (RFC). The aim of the study was to explore potential correlations between TS, GARFT, AICARFT, RFC, and FPGS levels in MPM and associations with clinical benefit from pemetrexed treatment. METHODS:: Samples from 63 patients were tested using immunohistochemistry (IHC) and quantitative polymerase chain reaction(qPCR) for expression levels of TS, GARFT, AICARFT, RFC, and FPGS. Clinical data were evaluated to determine associations between efficacy of pemetrexed and enzyme expression levels. Evaluation of expression levels was done through TaqMan-based qPCR, and IHC was evaluated semiquantitatively by using the H-score. RESULTS:: qPCR analysis showed no difference in expression pattern of GARFT and AICARFT. IHC analysis revealed a heterogeneous staining pattern for all the enzymes. No significant association was found between TS expression and survival or objective response of the tumors after pemetrexed treatment. FPGS (p = 0.0111) and RFC (p = 0.0088) mRNA expression levels were strongly associated with overall survival in these patients. CONCLUSIONS:: Our results reveal that in pemetrexed-treated MPMs TS expression levels have no influence on patient outcome. Furthermore, GARFT and AICARFT were homogenously expressed in the patient samples. Folate uptake mechanisms by RFC and activation by FPGS were associated with clinical benefit from pemetrexed treatment.
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[269]
TÍTULO / TITLE: - BRCA1, LMO4, and CtIP mRNA expression in erlotinib-treated non-small-cell lung cancer patients with EGFR mutations.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):295-300. doi: 10.1097/JTO.0b013e31827db621.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827db621
AUTORES / AUTHORS: - Karachaliou N; Costa C; Gimenez-Capitan A; Molina-Vila MA; Bertran-Alamillo J; Mayo C; Massuti B; Majem M; Carcereny E; Moran T; Sanchez JJ; Viteri S; Gasco A; Wannesson L; Souglakos J; Jimeno J; Rosell R
INSTITUCIÓN / INSTITUTION: - Pangaea Biotech, Dexeus University Institute, Barcelona, España.
RESUMEN / SUMMARY: - INTRODUCTION: Lung adenocarcinoma patients harboring EGFR activating mutations attain improved progression-free survival (PFS) with treatment with epidermal growth factor receptor tyrosine kinase inhibitors. However, patients ultimately relapse, indicating that other genetic factors could influence outcome in such patients. We hypothesized that PFS could be influenced by the expression of genes in DNA repair pathways. METHODS: We examined the mRNA expression of C terminus-binding protein-interacting protein and Lin11, Isl-1, and Mec-3 domain only 4 (LMO4) in pretreatment tumor samples from 91 erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations in whom breast cancer gene 1 (BRCA1) expression and the concomitant presence of the EGFR T790M mutation had previously been assessed. Gene expression was analyzed by polymerase chain reaction, using beta-actin as endogenous gene. Results were correlated with PFS and overall survival. RESULTS: In patients with low LMO4 levels, PFS was 13 months, whereas it was not reached for those with high LMO4 levels (p = 0.03). In patients with low levels of both BRCA1 and LMO4, PFS was 19 months whereas it was not reached in those with low BRCA1 and high LMO4 mRNA levels (p = 0.04). In patients with high BRCA1 and low LMO4 levels, PFS was 8 months, whereas it was 18 months in those with high levels of both genes (p = 0.03). CONCLUSIONS: Low BRCA1 and high LMO4 levels were associated with longer PFS to erlotinib. Baseline assessment of BRCA1 and LMO4 mRNA expression can help predict outcome to erlotinib.
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[270]
TÍTULO / TITLE: - Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt060
AUTORES / AUTHORS: - Zhang DM; Liu JS; Deng LJ; Chen MF; Yiu A; Cao HH; Tian HY; Fung KP; Kurihara H; Pan JX; Ye WC
INSTITUCIÓN / INSTITUTION: - Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China.
RESUMEN / SUMMARY: - Hepatocellular carcinoma (HCC) is a deadly form of cancer without effective chemotherapy so far. Currently, only sorafenib, a multitargeted tyrosine kinase inhibitor, slightly improves survival in HCC patients. In searching for natural anti-HCC components from toad venom, which is frequently used in the treatment of liver cancer in traditional Chinese medicine, we discovered that arenobufagin, a bufadienolide from toad venom, had potent antineoplastic activity against HCC HepG2 cells as well as corresponding multidrug-resistant HepG2/ADM cells. We found that arenobufagin induced mitochondria-mediated apoptosis in HCC cells, with decreasing mitochondrial potential, as well as increasing Bax/Bcl-2 expression ratio, Bax translocation from cytosol to mitochondria. Arenobufagin also induced autophagy in HepG2/ADM cells. Autophagy-specific inhibitors (3-methyladenine, chloroquine and bafilomycin A1) or Beclin1 and Atg 5 small interfering RNAs (siRNAs) enhanced arenobufagin-induced apoptosis, indicating that arenobufagin-mediated autophagy may protect HepG2/ADM cells from undergoing apoptotic cell death. In addition, we observed the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway by arenobufagin. Interestingly, inhibition of mTOR by rapamycin or siRNA duplexes augmented arenobufagin-induced apoptosis and autophagy. Finally, arenobufagin inhibited the growth of HepG2/ADM xenograft tumors, which were associated with poly (ADP-ribose) polymerase cleavage, light chain 3-II activation and mTOR inhibition. In summary, we first demonstrated the antineoplastic effect of arenobufagin on HCC cells both in vitro and in vivo. We elucidated the underlying antineoplastic mechanisms of arenobufagin that involve cross talk between apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway. This study may provide a rationale for future clinical application using arenobufagin as a chemotherapeutic agent for HCC.
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[271]
TÍTULO / TITLE: - Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leukemia. 2013 Feb 21. doi: 10.1038/leu.2013.56.
●● Enlace al texto completo (gratuito o de pago) 1038/leu.2013.56
AUTORES / AUTHORS: - Leanza L; Trentin L; Becker KA; Frezzato F; Zoratti M; Semenzato G; Gulbins E; Szabo I
INSTITUCIÓN / INSTITUTION: - Department of Biology, University of Padua, Padua, Italy.
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[272]
TÍTULO / TITLE: - Overexpression of DICER1 induced by the upregulation of GATA1 contributes to the proliferation and apoptosis of leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1317-24. doi: 10.3892/ijo.2013.1831. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1831
AUTORES / AUTHORS: - Bai Y; Qiu GR; Zhou F; Gong LY; Gao F; Sun KL
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Shenyang General Military Hospital, Shenyang, P.R. China.
RESUMEN / SUMMARY: - Dicer, a member of the RNase III family, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs. Recent evidence indicates that DICER1 expression levels vary among different solid tumors and decreased or increased DICER1 expression has been associated with aggressive cancers. In this study, we assessed DICER1 expression levels in acute myeloid leukemia (AML) and investigated its biological effects and transcriptional regulation in leukemia cell lines. We demonstrated that DICER1 was overexpressed in AML patients and leukemia cell lines by real-time quantitative PCR and western blot analysis. A functional assay demonstrated that the silencing of DICER1 inhibited cell proliferation and promoted apoptosis in leukemia cell lines. We also demonstrated that DICER1 was upregulated by the hematopoietic transcription factor, GATA1, through luciferase, electrophoretic mobility shift and chromatin immunoprecipitation assays. These data suggest that DICER1 plays an important role in AML and the finding that the upregulation of DICER1 is induced by GATA1 may provide a framework for the understanding of differential DICER1 expression levels in multiple types of cancer.
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[273]
TÍTULO / TITLE: - Does lifetime exposure to hormones predict pretreatment cognitive function in women before adjuvant therapy for breast cancer?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Menopause. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1097/GME.0b013e3182843eff
AUTORES / AUTHORS: - Bender CM; Sereika SM; Ryan CM; Brufsky AM; Puhalla S; Berga SL
INSTITUCIÓN / INSTITUTION: - From the 1University of Pittsburgh School of Nursing, Pittsburgh, PA; 2University of Pittsburgh School of Medicine, Pittsburgh, PA; and 3Wake Forest University School of Medicine, Winston-Salem, NC.
RESUMEN / SUMMARY: - OBJECTIVE: Women with breast cancer have been found to have poorer cognitive function before the initiation of systemic adjuvant therapy than their age- and education-matched counterparts. The basis for this may partly include hormone exposure during the course of a woman’s life. METHODS: We compared cognitive function between postmenopausal women with breast cancer before the initiation of systemic adjuvant therapy and healthy age- and education-matched postmenopausal women and examined whether factors related to lifetime exposure to hormones predicted cognitive function before therapy. RESULTS: We found that, compared with healthy women, women with breast cancer had poorer memory (P = 0.05) and attention (P = 0.006). Controlling for the covariates age and estimated verbal intelligence, we found that factors related to greater lifetime hormone exposure (oral contraceptive use, greater years since menopause, and longer duration of hormone therapy) predicted cognitive function (executive function, verbal learning and memory, attention, psychomotor efficiency, and visual sustained attention) in women with and without breast cancer but did not explain the differences in cognitive function observed at pretreatment in women with breast cancer. CONCLUSIONS: Other factors may explain the poorer pretreatment cognitive function in women with breast cancer, including persistent effects of surgical operation and anesthesia, sleep problems, and tumor-related factors. Additional studies are needed to explicate the basis of poorer pretherapy cognitive function in this population.
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[274]
TÍTULO / TITLE: - Selective Induction of Tumor Cell Apoptosis by a Novel P450-mediated Reactive Oxygen Species (ROS) Inducer Methyl 3-(4-Nitrophenyl) Propiolate.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Mar 29;288(13):8826-37. doi: 10.1074/jbc.M112.429316. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.429316
AUTORES / AUTHORS: - Sun X; Ai M; Wang Y; Shen S; Gu Y; Jin Y; Zhou Z; Long Y; Yu Q
INSTITUCIÓN / INSTITUTION: - From the Departments of Pharmacology.
RESUMEN / SUMMARY: - Induction of tumor cell apoptosis has been recognized as a valid anticancer strategy. However, therapeutic selectivity between tumor and normal cells has always been a challenge. Here, we report a novel anti-cancer compound methyl 3-(4-nitrophenyl) propiolate (NPP) preferentially induces apoptosis in tumor cells through P450-catalyzed reactive oxygen species (ROS) production. A compound sensitivity study on multiple cell lines shows that tumor cells with high basal ROS levels, low antioxidant capacities, and p53 mutations are especially sensitive to NPP. Knockdown of p53 sensitized non-transformed cells to NPP-induced cell death. Additionally, by comparing NPP with other ROS inducers, we show that the susceptibility of tumor cells to the ROS-induced cell death is influenced by the mode, amount, duration, and perhaps location of ROS production. Our studies not only discovered a unique anticancer drug candidate but also shed new light on the understanding of ROS generation and function and the potential application of a ROS-promoting strategy in cancer treatment.
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[275]
TÍTULO / TITLE: - Blockade of DNA methylation enhances the therapeutic effect of gefitinib in non-small cell lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 21. doi: 10.3892/or.2013.2298.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2298
AUTORES / AUTHORS: - Li XY; Wu JZ; Cao HX; Ma R; Wu JQ; Zhong YJ; Feng JF
INSTITUCIÓN / INSTITUTION: - Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu 210009, P.R. China.
RESUMEN / SUMMARY: - The sensitivity of lung cancer to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has been found to be associated with mutations in the tyrosine kinase domain of EGFR. However, not all mutations are sensitive to gefitinib. While CpG island methylation in the promoter region of the EGFR gene and transcriptional silencing are common in solid tumors, the role of the EGFR gene promoter methylation in affecting resistance to TKIs in non-small cell lung cancer (NSCLC) remains unknown. In this study, we examined the correlation between EGFR gene promoter methylation and the therapeutic effect of gefitinib in NSCLC cells. Three NSCLC cell lines with different EGFR mutation statuses and levels of sensitivity to EGFR-TKIs were used in this study: H1650 (del E746-A750), H1299 (wild-type EGFR) and PC-9 (del E746-A750). Cells were treated with gefitinib or 5-aza-2’-deoxy cytidine (5-aza-CdR), a methylation inhibitor, alone or in combination. Subsequently, the methylation status of the EGFR gene promoter was examined by methylation-specific PCR (MSP). Cell survival and apoptosis assays were performed using the Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, western blot analysis and quantitative real-time PCR were used to examine the expression levels of EGFR protein and mRNA. Our study showed that the promoter region of the EGFR gene in PC-9 cells was unmethylated, and that the cells were sensitive to gefitinib. By contrast, the promoter region of the EGFR gene in the H1650 and H1299 cells was methylated, and the cells were resistant to gefitinib. Of note, the combination treatment with 5-aza-CdR and gefitinib further enhanced the growth inhibitory effects and led to the induction of apoptosis, while a significant reduction in the expression of EGFR protein and mRNA was observed in the H1650 and H1299 cells. These results suggest that blockade of DNA methylation may enhance the antitumor effects of EGFR-TKIs and gefitinib in NSCLC cells. Thus, EGFR gene promoter methylation may be a potential mechanism for acquired resistance to gefitinib.
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[276]
TÍTULO / TITLE: - Cadmium modulates H-ras expression and caspase-3 apoptotic cell death in breast cancer epithelial MCF-7 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Inorg Biochem. 2013 Apr;121:100-7. doi: 10.1016/j.jinorgbio.2012.12.015. Epub 2013 Jan 7.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jinorgbio.2012.12.015
AUTORES / AUTHORS: - Petanidis S; Hadzopoulou-Cladaras M; Salifoglou A
INSTITUCIÓN / INSTITUTION: - Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
RESUMEN / SUMMARY: - Cadmium (Cd) is a well-known metal carcinogen associated with tumor formation and carcinogenesis. It has been shown to induce cancer through various cellular mechanisms involving inhibition of DNA repair, abnormal gene expression, induction of oxidative stress, and triggering apoptosis. It is well-established that the H-ras oncogene is involved in the process of carcinogenesis with direct effects on cellular proliferation and tumorigenesis. Given the biotoxicity of cadmium and its association with carcinogenesis, the effect of that metal ion (Cd(II)) was investigated, in a concentration-dependent fashion, on cell viability, cell proliferation, caspase-3 mediated apoptosis and H-ras gene expression in human breast cancer epithelial MCF-7 cells transfected with the H-ras oncogene (wild type and G12V mutation). The findings show a significant modulation effect of cadmium on H-ras gene expression accompanied by up-regulation of caspase-3-related apoptosis in the concentration range of 100-1000nMu cadmium. Concurrently, there is a decrease in MCF-7 proliferation. Collectively, the results a) indicate an interplay of cadmium with H-ras(wt and G12V), with cadmium exhibiting a significant concentration-dependent effect on the modulation of H-ras expression, cell viability and proliferation, and b) project distinctly interwoven roles for both cadmium and H-ras in aberrant physiologies in cancer cells.
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[277]
TÍTULO / TITLE: - DNA Mismatch Repair Protein (MSH6) Correlated With the Responses of Atypical Pituitary Adenomas and Pituitary Carcinomas to Temozolomide: The National Cooperative Study by the Japan Society for Hypothalamic and Pituitary Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Endocrinol Metab. 2013 Mar;98(3):1130-6. doi: 10.1210/jc.2012-2924. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-2924
AUTORES / AUTHORS: - Hirohata T; Asano K; Ogawa Y; Takano S; Amano K; Isozaki O; Iwai Y; Sakata K; Fukuhara N; Nishioka H; Yamada S; Fujio S; Arita K; Takano K; Tominaga A; Hizuka N; Ikeda H; Osamura RY; Tahara S; Ishii Y; Kawamata T; Shimatsu A; Teramoto A; Matsuno A
INSTITUCIÓN / INSTITUTION: - MD, Department of Neurosurgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. hirohata-tky@umin.ac.jp.
RESUMEN / SUMMARY: - Context: Temozolomide (TMZ) is an alkylating agent and was a first-line chemotherapeutic agent for malignant gliomas. Recently, TMZ has been documented to be effective against atypical pituitary adenomas (APAs) and pituitary carcinomas (PCs). Objective: The clinical and pathological characteristics of APAs and PCs treated with TMZ in Japan were surveyed and analyzed retrospectively. Design: Members of the Japan Society of Hypothalamic and Pituitary Tumors were surveyed regarding the clinical characteristics of APAs and PCs treated with TMZ. Stored tumor samples were gathered from the responders and were assessed by the immunohistochemistry of Ki-67, O-methyl-guanine-DNA methyltransferase, p53, MSH6, and anterior pituitary hormones. Responses to TMZ treatment were defined as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 2.0. Subjects: Three samples from 3 subjects with APA and 11 samples from 10 subjects with PC were available. Results: The 13 subjects had APAs and PCs consisting of 5 prolactin-producing tumors, 5 ACTH-producing tumors, and 3 null cell adenomas. The clinical response to TMZ treatment was as follows: 4 cases of CR and PR (31%), 2 cases of SD (15%), 6 cases of recurrence after CR and PR (46%), and 1 case of PD (8%). However, considerable subjects had recurrent disease after a response to TMZ. The immunohistochemical findings of Ki-67, O-methyl-guanine-DNA methyltransferase, and p53 did not show any significant correlation with the efficacy of TMZ. However, the immunopositivity of MSH6 was positively correlated with TMZ response (P = .015, Fisher’s exact test). Conclusions: This study showed that preserving MSH6 function was contributory to the effectiveness of TMZ in malignant pituitary neoplasms. It is necessary to survey more cases and evaluate multifactor analyses.
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[278]
TÍTULO / TITLE: - Concordant hypermethylation of intergenic microRNA genes in human hepatocellular carcinoma as new diagnostic and prognostic marker.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Jan 30. doi: 10.1002/ijc.28068.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28068
AUTORES / AUTHORS: - Anwar SL; Albat C; Krech T; Hasemeier B; Schipper E; Schweitzer N; Vogel A; Kreipe H; Lehmann U
INSTITUCIÓN / INSTITUTION: - Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany.
RESUMEN / SUMMARY: - Epigenetic inactivation by aberrant DNA methylation has been reported for many microRNA genes in various human malignancies. However, relatively little is known about microRNA gene methylation in hepatocellular carcinoma (HCC). Therefore, a systematic screen for identification of aberrantly hypermethylated microRNA genes in HCC was initiated. The methylation status of 39 intergenic CpG island associated microRNA genes was analyzed in HCC cell lines (n = 7), immortalized hepatocytes (n = 2) and normal liver samples (n = 5). Subsequently, 13 differentially methylated microRNA genes were analyzed in primary human HCC samples (n = 40), benign liver tumors (n = 15) and the adjacent liver tissues employing pyrosequencing. Expression of microRNA genes was measured using quantitative real-time polymerase chain reaction (RT-PCR). In addition, DNA methylation and expression of microRNA genes were measured after DNMT1 knockdown or DNMT inhibition. Aberrant hypermethylation and concomitant reduction in expression of intergenic microRNA genes is a frequent event in human HCC: hsa-mir-9-2 (23%), hsa-mir-9-3 (50 %), hsa-mir-124-1 (20%), hsa-mir-124-2 (13%), hsa-mir-124-3 (43%), hsa-mir-129-2 (58%), hsa-mir-596 (28%) and hsa-mir-1247 (38%). Altogether, it affects 90% of the HCC specimens under study. MicroRNA gene methylation is not found in hepatocellular adenoma (n = 10) and focal nodular hyperplasia (n = 5). DNMT1 knockdown or DNMT inhibition reduced microRNA gene methylation and stimulated expression. In primary human HCC specimens hypermethylation and expression of microRNA genes showed an inverse correlation. Concordant hypermethylation of three or more microRNA genes is a highly specific marker for the detection of HCC and for poor prognosis.
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[279]
TÍTULO / TITLE: - Bevacizumab in breast cancer: fundamental questions remain.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lancet Oncol. 2013 Feb;14(2):99-101. doi: 10.1016/S1470-2045(13)70012-3.
●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(13)70012-3
AUTORES / AUTHORS: - Miles DW
INSTITUCIÓN / INSTITUTION: - Mount Vernon Cancer Centre, Northwood, Middlesex HA6 2RN, UK. david.miles@doctors.org.uk
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[280]
TÍTULO / TITLE: - Upregulation of DR5 receptor by the diaminothiazole DAT1 [4-amino-5-benzoyl-2-(4-methoxy phenyl amino) thiazole] triggers an independent extrinsic pathway of apoptosis in colon cancer cells with compromised pro and antiapoptotic proteins.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Feb 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0826-6
AUTORES / AUTHORS: - Thomas SA; Vasudevan S; Thamkachy R; Lekshmi SU; Santhoshkumar TR; Rajasekharan KN; Sengupta S
INSTITUCIÓN / INSTITUTION: - Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Trivandrum, 695014, India.
RESUMEN / SUMMARY: - Mitochondria mediated signalling is the more common way of apoptosis induction exhibited by many chemotherapeutic agents in cancer cells. Death receptor mediated signalling for apoptosis in many cells also requires further amplification from the mitochondrial pathway activation through tBid. Thus the potential of most chemotherapeutic agents in tumours with intrinsic apoptosis resistance due to changes in molecules involved in the mitochondrial pathway is limited. Diaminothiazoles were shown earlier to bind to tubulin thereby exhibiting cytotoxicity towards different cancer cells. We observed that the lead diaminothiazole, DAT1 [4-amino-5-benzoyl-2-(4-methoxy phenyl amino) thiazole] could induce apoptosis in the colon cancer cell line HCT116 by both pathways. However, in contrast to many other chemotherapeutic agents, DAT1 triggered apoptosis where the intrinsic pathway was blocked by changing the pro and antiapoptotic proteins. An independent extrinsic pathway activation triggered by the upregulation of DR5 receptor accounted for that. The induction of DR5 occurred in the transcriptional level and the essential role of DR5 was confirmed by the fact that siRNA downregulation of DR5 significantly reduced DAT1 induced apoptosis. HCT116 cells were earlier shown to have a type II response for apoptosis induction where extrinsic pathway was connected to the intrinsic pathway via the mediator protein tBid. Our finding thus indicates that the signalling events in the manifestation of apoptosis depend not only on the cancer cell type, but also on the inducer. Our results also place diaminothiazoles in a promising position in the treatment of tumours with compromised apoptotic factors.
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[281]
TÍTULO / TITLE: - Glucose starvation induces apoptosis in a model of acute T leukemia dependent on caspase-3 and apoptosis-inducing factor: a therapeutic strategy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013;65(1):99-109. doi: 10.1080/01635581.2013.741751.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.741751
AUTORES / AUTHORS: - Mendivil-Perez M; Jimenez-Del-Rio M; Velez-Pardo C
INSTITUCIÓN / INSTITUTION: - School of Medicine, Medical Research Institute, University of Antioquia, Medellin, Colombia.
RESUMEN / SUMMARY: - Reactivation of apoptosis appears as an ultimate goal to eliminate cancer cells. By using light and fluorescent microscopy, flow cytometry, immunohistochemistry staining, DNA fragmentation analysis, and pharmacological inhibition, we provide evidence that 2 pathways of cell death induced by glucose-starvation (GS)/oxidative stress (OS) run in parallel: apoptosis-inducing factor (AIF)-dependent and caspase-3 dependent mechanisms. However, the supremacy of 1 pathway over the other one relies on the availability of glucose, which is essential for the proper functioning of antioxidant cellular systems. It is shown that GS generates superoxide anion radical (O(2)(-))/hydrogen peroxide (H(2)O(2)), which are linked to the death ~45%-70% cells by AIF/mitochondria depolarization/chromatin condensation pathway and ~15%-30% death by nuclear factor-kappa B/p53/c-Jun/c-Jun N-terminal kinase /mitochondria depolarization/caspase-3 activation/DNA fragmentation mechanism at 24-48 h. Remarkably, chromatin condensation/nuclei fragmentation appeared to occur partially independent of the loss of the mitochondrial transmembrane potential (DeltaPsi(m)) and plasma membrane damage. Interestingly, signaling inhibitors, antioxidants, or glucose protected cells if added immediately to culture devoid of glucose (P < 0.001), but only vitamin E and glucose significantly rescued cells at 3 h of GS compared to control. Taken together these data suggest that glucose deprivation might efficiently eliminate leukemia cells via apoptosis.
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[282]
TÍTULO / TITLE: - Genistein induces apoptotic cell death associated with inhibition of the NF-kappaB pathway in adult T-cell leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biol Int. 2013 Mar 22. doi: 10.1002/cbin.10101.
●● Enlace al texto completo (gratuito o de pago) 1002/cbin.10101
AUTORES / AUTHORS: - Yamasaki M; Mine Y; Nishimura M; Fujita S; Sakakibara Y; Suiko M; Morishita K; Nishiyama K
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki 1-1 Gakuenkibanadai-nishi Miyazaki 889-2192, Japan.
RESUMEN / SUMMARY: - We have shown that genistein inhibits the growth of adult-T cell leukemia (ATL) cells in vitro and in vivo, and this leads to pronounced G2/M arrest. This report shows that genistein induces apoptotic death in ATL cells. Although the pan-caspase inhibitor, Z-VAD-fmk, did not inhibit genistein-induced apoptosis, release of apoptosis inducing factor (AIF) into the cytosol occurred. Poly-ADP ribose polymerase inhibition also abrogated genistein-induced apoptosis. Genistein decreased nuclear p65 translocation and IkappaBalpha phosphorylation, and downregulated the anti-apoptotic proteins, XIAP, cIAP and survivin, NF-kappaB-responsive gene products. Thus, genistein is a promising agent for ATL that induces caspase-independent apoptosis through inhibition of the NF-kappaB pathway.
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[283]
TÍTULO / TITLE: - Preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen level predicts postoperative distant metastasis in patients with non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cardiothorac Surg. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt076
AUTORES / AUTHORS: - Tanaka Y; Yoshimasu T; Oura S; Hirai Y; Kawago M; Ikeda M; Okamura Y
INSTITUCIÓN / INSTITUTION: - Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 +/- 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded. RESULTS: The mean preoperative serum I-CTP level was 4.1 +/- 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 +/- 18 (range 1-79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (</=4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001). CONCLUSIONS: An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC.
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[284]
TÍTULO / TITLE: - Combination of albumin-bound paclitaxel and pegylated liposomal doxorubicin is effective in treatment of heavily treated relapsed/refractory diffuse large B-cell lymphoma: a case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.776166
AUTORES / AUTHORS: - Wang L; Xia ZJ
INSTITUCIÓN / INSTITUTION: - Department of Hematological Oncology, Sun Yat-Sen University Cancer Center , Guangzhou , People’s Republic of China.
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[285]
TÍTULO / TITLE: - Statistical Identification of Predictors for Paclitaxel-induced Peripheral Neuropathy in Patients with Breast or Gynaecological Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1153-6.
AUTORES / AUTHORS: - Kanbayashi Y; Hosokawa T; Kitawaki J; Taguchi T
INSTITUCIÓN / INSTITUTION: - Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. ykokanba@koto.kpu-m.ac.jp.
RESUMEN / SUMMARY: - Aim: The aim of this study was to identify predictors for paclitaxel-induced peripheral neuropathy (PIPN). PATIENTS AND METHODS: We conducted a retrospective analysis of 227 patients who had been treated with paclitaxel at a single institution between January 2008 and July 2011. At the time of chemotherapy completion, the severity of PIPN was graded on a scale of 0-5, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Multivariate-ordered logistic regression analysis was employed to examine the relationship between various predictive factors and the occurrence of PIPN. RESULTS: Diabetes mellitus [odds ratio (OR)=0.070], age (OR=1.991), co-administration of neurotropin (OR=3.654), co-administration of opioids (OR=0.312), co-administration of vitamin B12 (OR=2.554), co-administration of antidepressant (OR=4.754) and co-administration of gabapentinoids (OR=14.620), were significantly associated with reduction of or less serious PIPN. CONCLUSION: Our study indicates that PIPN may be alleviated by co-administration of opioids.
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[286]
TÍTULO / TITLE: - Anticancer activity of pristimerin in epidermal growth factor receptor 2-positive SKBR3 human breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biol Pharm Bull. 2013;36(2):316-25.
AUTORES / AUTHORS: - Lee JS; Yoon IS; Lee MS; Cha EY; Thuong PT; Diep TT; Kim JR
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Chungnam National University Hospital, Daejeon 301-721, Korea.
RESUMEN / SUMMARY: - Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in several cancer cell lines. However, the mechanism of action for the cytotoxic effect of pristimerin has not been unexplored. The purpose of this study was to investigate the effect of pristimerin on cytotoxicity using the epidermal growth factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line. Pristimerin inhibited proliferation in dose- and time-dependent manners in cells. We found it to be effective for suppressing HER2 protein and mRNA expression. Fatty acid synthase (FASN) expression and FASN activity were downregulated by pristimerin. Adding of exogenous palmitate, the end product of de novo fatty acid synthesis, reduced the proliferation activity of pristimerin. The changes in HER2 and FASN expression induced by pristimerin altered the levels of Akt and mitogen-activated protein kinase (MAPK) phosphorylation (Erk1/2, p38, and c-Jun N-terminal kinase (JNK)). Pristimerin lowered the levels of phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets such as phosphoprotein 70 ribosomal protein S6 kinase and 4E binding protein1. Pristimerin inhibited migration and invasion of cells, and co-treatment with the mTOR inhibitor rapamycin additionally suppressed these activities. Pristimerin-induced apoptosis was evaluated using Western blotting for caspase-3, -8, -9, and poly (ADP-ribose) polymerase expression and flow cytometric analysis for propidium iodide labeling. These results suggest that pristimerin is a novel HER2-downregulated compound that is able to decrease fatty acid synthase and modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and apoptosis. Pristimerin may be further evaluated as a chemotherapeutic agent for HER2-positive breast cancers.
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[287]
TÍTULO / TITLE: - Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Jun;24(5):494-503. doi: 10.1097/CAD.0b013e328360093b.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e328360093b
AUTORES / AUTHORS: - Liu K; Guo L; Miao L; Bao W; Yang J; Li X; Xi T; Zhao W
INSTITUCIÓN / INSTITUTION: - aState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing bNingxia Key Laboratory of Cerebrocranial Diseases, School of Laboratory Medicine, Ningxia Medical University, Yinchuan cDepartment of Biomedicine, Biochemical Engineering College, Beijing Union University, Beijing, People’s Republic of China.
RESUMEN / SUMMARY: - Lung cancer is one of the most death-related cancers worldwide. Ursolic acid (UA), a pentacyclic triterpene acid, has a wide range of anticancer functions such as proapoptosis, antiangiogenesis, and antimetastasis. This study was carried out to explore the inhibition mechanism of UA on metastasis of lung cancer A549 cells. First, we found that UA inhibited the metastasis of lung cancer cells in a concentration-dependent manner through an adhesion assay, a cell wound healing assay, and a transwell migration assay in vitro. In addition, after treatment with UA, the A549 cells showed decreased expression of astrocyte-elevated gene-1 (AEG-1) accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin, which have been reported to characterize the epithelial-mesenchymal transition (EMT). Further results also confirmed that the expression of vimentin was decreased by the siRNA technique to directly knock down AEG-1 expression, indicating that AEG-1 was involved in UA-mediated EMT inhibition. Furthermore, our results showed that UA suppressed the expression level of AEG-1 by repressing nuclear factor-kappaB signaling. Altogether, UA inhibited the EMT by suppressing the expression of AEG-1, correlating with inhibition of nuclear factor-kappaB in A549 cells. These findings suggested that UA was a potent anti-lung cancer agent, and it may be able to prevent invasion and metastasis of lung cancer cells.
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[288]
TÍTULO / TITLE: - Down-regulation of RIP1 by 2-deoxy-D-glucose sensitizes breast cancer cells to TRAIL-induced apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Pharmacol. 2013 Mar 7;705(1-3):26-34. doi: 10.1016/j.ejphar.2013.02.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejphar.2013.02.005
AUTORES / AUTHORS: - Huang YY; Liu H; Li Y; Pu LJ; Jiang CC; Xu JC; Jiang ZW
INSTITUCIÓN / INSTITUTION: - Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui, PR China.
RESUMEN / SUMMARY: - TNF-related apoptosis-inducing ligand (TRAIL) appears to be a promising anticancer agent as it specifically kills a wide variety of cancer cells. However, resistance of subpopulations of cancer cells to TRAIL-induced cell death remains a major obstacle for successful treatment of cancer using TRAIL-based therapy. In this report we show that the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) efficiently enhances TRAIL-induced apoptosis through downregulation of receptor-interacting protein kinase 1 (RIP1) in breast cancer cells. Although 2-DG alone did not kill breast cancer cells, it sensitized the cells to TRAIL-induced cell death. This could be efficiently inhibited by blockage of the caspase cascade, suggesting 2-DG augments TRAIL-mediated apoptotic signaling. Indeed, treatment with 2-DG resulted in upregulation of TRAIL receptor 2 (TRAIL-R2), downregulation of cIAP1 and XIAP, and reduction in RIP1. The latter appeared to play an important role in regulating sensitivity of breast cancer cells to TRAIL, in that knockdown of RIP1 recapitulated, at least in part, the effect of 2-DG on TRAIL-induced apoptosis. Taken together, these results indicate that 2-DG enhances TRAIL-induced apoptosis in breast cancer cells by multiple mechanisms including suppression of RIP1, and highlight the potential therapeutic benefit of combinations of 2-DG and TRAIL in the treatment of breast cancer.
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[289]
TÍTULO / TITLE: - Progesterone and Estrogen Prevent Cisplatin-induced Apoptosis of Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):791-800.
AUTORES / AUTHORS: - Grott M; Karakaya S; Mayer F; Baertling F; Beyer C; Kipp M; Kopp HG
INSTITUCIÓN / INSTITUTION: - Otfried-Mueller Str. 10, D-72076 Tuebingen, Germany. hans-georg.kopp@med.uni-tuebingen.de.
RESUMEN / SUMMARY: - Metastatic non-small cell lung cancer (NSCLC) remains the most common cause of tumor mortality despite the introduction of novel agents. Female sex hormones play a role in NSCLC pathogenesis and negatively influence the course of this disease. Herein, we present data on possible underlying mechanisms. Both estrogen and progesterone pre-treatment led to chemoresistance of A549 NSCLC cells in vitro by attenuating cisplatin-induced apoptosis. These effects were not antagonized by the estrogen or progesterone receptor antagonists ICI 182,780 and RU486 (mifepristone). Cisplatin induced apoptosis via activation of caspases -3/7, -8 and -9. Estrogen and progesterone attenuated levels of caspase activation. Interestingly, copper-transporter-1, which is responsible for the intracellular accumulation of cisplatin, was not modulated by sex hormones and the effects of estrogen and progesterone were neither additive nor synergistic. Our results suggest that estrogen and progesterone contribute to the development of chemotherapy resistance in NSCLC via non-classical sex hormone signaling pathways.
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[290]
TÍTULO / TITLE: - Doxorubicin sensitizes human tumor cells to NK and T cell-mediated killing by augmented TRAIL-receptor signaling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Mar 18. doi: 10.1002/ijc.28163.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28163
AUTORES / AUTHORS: - Wennerberg E; Sarhan D; Carlsten M; Kaminskyy VO; D’arcy P; Zhivotovsky B; Childs R; Lundqvist A
INSTITUCIÓN / INSTITUTION: - Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
RESUMEN / SUMMARY: - Doxorubicin is an anthracycline antibiotic that is widely used to treat different types of malignancy. Here we studied whether doxorubicin could be used to render tumor cells susceptible to apoptosis by NK and T cells. Pretreatment with sub-apoptotic doses of doxorubicin sensitized tumor cell lines of various histotypes to both NK and T cells resulting in a 3.7 to 32.7 % increase in lysis (2.5 mean fold increase, p<0.0001) and 2.9 to 14.2 % increase in lysis (3.0 mean fold increase, p<0.05) respectively. The sensitizing effect of the drug was primarily dependent on TRAIL/TRAILR signaling, but not on Fas-ligand (FasL), perforin, NKG2D or DNAM-1. The central role of the TRAIL signaling pathway was further supported by an increased expression of TRAIL-R2 on doxorubicin-treated tumor cells and by down-regulation of cFLIP, the inhibitors of death receptor-mediated apoptosis. Compared to untreated cells, pretreatment of tumor cells with doxorubicin showed increased processing and activation of caspase-8 upon co-culture with NK or T cells. The significance of this treatment strategy was confirmed using a xenogeneic tumor-bearing mouse model. Tumor progression was delayed in mice that received either NK cells (p<0.05) or T cells (p<0.0001) following doxorubicin treatment compared to mice receiving either cell type alone. Moreover, combined infusion of both NK and T cells following doxorubicin treatment not only delayed tumor progression, but significantly improved the long-term survival (p<0.01). Based on these findings we propose that doxorubicin can be used to improve the efficacy of adoptive cell therapy in patients with cancer. © 2013 Wiley Periodicals, Inc.
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[291]
TÍTULO / TITLE: - Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Viral Hepat. 2013 Apr;20(4):e82-9. doi: 10.1111/jvh.12014. Epub 2012 Oct 16.
●● Enlace al texto completo (gratuito o de pago) 1111/jvh.12014
AUTORES / AUTHORS: - Lindh M; Arnholm B; Bjorkman P; Hellstrand K; Lagging M; Nilsson S; Wahlberg T; Wallmark E; Weiland O; Wejstal R; Westin J; Widell A; Norkrans G
INSTITUCIÓN / INSTITUTION: - Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
RESUMEN / SUMMARY: - The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24-72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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[292]
TÍTULO / TITLE: - Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth after administration of an anti-angiogenic agent, bevacizumab, as single-agent and combination therapy in tumor xenografts.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2107-z
AUTORES / AUTHORS: - Rocchetti M; Germani M; Del Bene F; Poggesi I; Magni P; Pesenti E; De Nicolao G
INSTITUCIÓN / INSTITUTION: - , Via Tommaso Grossi 13, 20017, Rho, MI, Italy.
RESUMEN / SUMMARY: - PURPOSE: Pharmacokinetic-pharmacodynamic (PK-PD) models able to predict the action of anticancer compounds in tumor xenografts have an important impact on drug development. In case of anti-angiogenic compounds, many of the available models show difficulties in their applications, as they are based on a cell kill hypothesis, while these drugs act on the tumor vascularization, without a direct tumor cell kill effect. For this reason, a PK-PD model able to describe the tumor growth modulation following treatment with a cytostatic therapy, as opposed to a cytotoxic treatment, is proposed here. METHODS: Untreated tumor growth was described using an exponential growth phase followed by a linear one. The effect of anti-angiogenic compounds was implemented using an inhibitory effect on the growth function. The model was tested on a number of experiments in tumor-bearing mice given the anti-angiogenic drug bevacizumab either alone or in combination with another investigational compound. Nonlinear regression techniques were used for estimating the model parameters. RESULTS: The model successfully captured the tumor growth data following different bevacizumab dosing regimens, allowing to estimate experiment-independent parameters. A combination model was also developed under a ‘no-interaction’ assumption to assess the effect of the combination of bevacizumab with a target-oriented agent. The observation of a significant difference between model-predicted and observed tumor growth curves was suggestive of the presence of a pharmacological interaction that was further accommodated into the model. CONCLUSIONS: This approach can be used for optimizing the design of preclinical experiments. With all the inherent limitations, the estimated experiment-independent model parameters can be used to provide useful indications for the single-agent and combination regimens to be explored in the subsequent development phases.
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[293]
TÍTULO / TITLE: - Cell cycle arrest, extracellular matrix changes and intrinsic apoptosis in human melanoma cells are induced by Boron Neutron Capture Therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Toxicol In Vitro. 2013 Feb 24;27(4):1196-1204. doi: 10.1016/j.tiv.2013.02.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.tiv.2013.02.006
AUTORES / AUTHORS: - Faiao-Flores F; Coelho PR; Arruda-Neto JD; Maria-Engler SS; Maria DA
INSTITUCIÓN / INSTITUTION: - Laboratory of Biochemistry and Biophysics, Butantan Institute, Sao Paulo, Brazil; Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: fernandafaiao@yahoo.com.br.
RESUMEN / SUMMARY: - Boron Neutron Capture Therapy (BNCT) involves the selective accumulation of boron carriers in tumor tissue followed by irradiation with a thermal or epithermal neutron beam. This therapy is therefore a cellular irradiation suited to treat tumors that have infiltrated into healthy tissues. BNCT has been used clinically to treat patients with cutaneous melanomas which have a high mortality. Human normal melanocytes and melanoma cells were treated with BNCT at different boronophenylalanine concentrations for signaling pathways analysis. BNCT induced few morphological alterations in normal melanocytes, with a negligible increase in free radical production. Melanoma cells treated with BNCT showed significant extracellular matrix (ECM) changes and a significant cyclin D1 decrease, suggesting cell death by necrosis and apoptosis and cell cycle arrest, respectively. BNCT also induced a significant increase in cleaved caspase-3 and a decrease in the mitochondrial electrical potential with selectivity for melanoma cells. Normal melanocytes had no significant differences due to BNCT treatment, confirming the data from the literature regarding the selectivity of BNCT. The results from this study suggest that some signaling pathways are involved in human melanoma treatment by BNCT, such as cell cycle arrest, ECM changes and intrinsic apoptosis.
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[294]
TÍTULO / TITLE: - Activation of c-Jun N-terminal kinase mediates tanshinone IIA-induced apoptosis in KBM-5 chronic myeloid leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biol Pharm Bull. 2013;36(2):208-14.
AUTORES / AUTHORS: - Yun SM; Jeong SJ; Kim JH; Jung JH; Lee HJ; Sohn EJ; Lee MH; Kim SH
INSTITUCIÓN / INSTITUTION: - College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
RESUMEN / SUMMARY: - Aim of this study was to identify the molecular mechanisms of tanshinone IIA-induced apoptosis in chronic myelogenous leukemia (CML) cells. Cytotoxicity of tanshinone IIA was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Our data demonstrate that tanshinone IIA induced apoptosis by increasing the sub-G1 DNA contents and DNA fragmentation in KBM-5 CML cell line. In addition, tanshinone IIA significantly reduced mitochondrial membrane potential (MMP), mediated cytochrome c release from mitochondria and activated caspase-3 and 9, indicating mitochondria-dependent apoptosis by tanshinone IIA. Tanshinone IIA attenuated expression of several apoptosis-related proteins such as c-inhibitor of apoptosis protein (IAP) 2, Mcl-1(L) and Bcl-2. Interestingly, although tanshinone IIA notably enhanced the phosphorylation of both c-Jun N-terminal protein kinase (JNK) and p38, JNK inhibitor, but not p38 inhibitor, reversed tanshinone IIA-induced apoptosis. Our findings suggest that tanshinone IIA induces mitochondria-dependent apoptosis via activation of JNK in KBM 5 cells as a potent anti-cancer agent for CML therapy.
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[295]
TÍTULO / TITLE: - Icariside II induces apoptosis of melanoma cells through the downregulation of survival pathways.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013;65(1):110-7. doi: 10.1080/01635581.2013.741745.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.741745
AUTORES / AUTHORS: - Wu J; Xu J; Eksioglu EA; Chen X; Zhou J; Fortenbery N; Wei S; Dong J
INSTITUCIÓN / INSTITUTION: - Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - This study evaluated the antitumor effects of icariside II (IS), isolated from Herba Epimedii, on in vitro and in vivo models of melanoma and determined its mechanism of apoptosis. Mouse (B16) and human (A375, SK-MEL-5) melanoma cell lines were treated with IS at different concentrations (0-100 muM). Cell viability and proliferation was detected by WST-1 assay and with the xCELLigence system, respectively. Apoptosis was measured by the annexin-V/PI flow cytometric assay. Western blot was used to measure cleaved caspase 3, survivin, P-STAT3, P-ERK and P-AKT. B16 and A375 cells were injected subcutaneously into C57BL/6J and BALB/c-nu mice, respectively. After 1 wk, IS solution at (50 mg/kg, 100 mg/kg) was administered by intraperitoneal injection 3 times for a week. Tumor size was measured with an electronic digital caliper. IS inhibited the proliferation of melanoma cells in a dose- and time-dependent manner. Treatment of A375 cells with IS resulted in an increased number of apoptotic cells ranging from 5.6% to 26.3% mirrored by increases in cleaved caspase-3 and a decrease in survivin expression. IS significantly inhibited the activation of the JAK-STAT3 and MAPK pathways but promoted an unsustained activation peak of the PI3K-AKT pathway. IS administration (50 mg/kg) resulted in a 47.5% decreased tumor volume in A375 bearing mice. Furthermore, IS administration (50 mg/kg, 100 mg/kg) resulted in 41% and 49% decreased tumor volume in B16 bearing mice, respectively. IS dramatically inhibited the proliferation of melanoma cells in vivo and in vitro through the regulation of apoptosis. These effects demonstrate the ability of IS to effectively overcome the survival signals of tumor cells, which support further preclinical evaluation of IS in cancer as a new potential chemotherapeutic agent.
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[296]
TÍTULO / TITLE: - MicroRNA-195 chemosensitizes colon cancer cells to the chemotherapeutic drug doxorubicin by targeting the first binding site of BCL2L2 mRNA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Physiol. 2013 Mar 22. doi: 10.1002/jcp.24366.
●● Enlace al texto completo (gratuito o de pago) 1002/jcp.24366
AUTORES / AUTHORS: - Qu J; Zhao L; Zhang P; Wang J; Xu N; Mi W; Jiang X; Zhang C; Qu J
INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China.
RESUMEN / SUMMARY: - The mechanisms underlying doxorubicin (Dox) resistance in colon cancer cells are not fully understood. MicroRNA (miRNA) has emerged to play important roles in tumorigenesis and drug resistance. However, the relationship between miRNA and doxorubicin resistance in colon cancer cells has not been previously explored. In this study, we utilized microRNA array and real-time PCR to verify that some microRNAs including miR-127, miR-195, miR-22, miR-137 were significantly down-regulated, while miR-21, miR-592 were up-regulated in both HT29/DOX and LOVO/DOX cell lines. In vitro cell viability assay showed that knockdown of miR-195 in HT29 and LOVO cells caused a marked inhibition of Dox-induced cytotoxicity. Moreover, we explored that miR-195 is involved in repression of BCL2L2 expression through targeting its 3’-untranslated region, especially the first binding site within its mRNA. Furthermore, down-regulation of miR-195 conferred DOX resistance in parental cells and reduced cell apoptosis activity, while over-expression of miR-195 sensitized resistant cells to DOX and enhanced cell apoptosis activity, all of which can be partly rescued by BCL2L2 siRNA and cDNA expression. These results may have implications for therapeutic strategies aiming to overcome colon cancer cells resistance to doxorubicin. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
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[297]
TÍTULO / TITLE: - Postoperative peg-interferon plus ribavirin associated with reduced recurrence of hepatitis C virus-related hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatology. 2013 Feb 6. doi: 10.1002/hep.26300.
●● Enlace al texto completo (gratuito o de pago) 1002/hep.26300
AUTORES / AUTHORS: - Hsu YC; Ho HJ; Wu MS; Lin JT; Wu CY
INSTITUCIÓN / INSTITUTION: - Graduate Institute of Clinical Medicine, China Medical University, Taichung; Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung.
RESUMEN / SUMMARY: - Hepatocellular carcinoma (HCC( frequently recurs after surgical resection. This population-based research aimed to investigate the association between postoperative antiviral treatment and risk of recurrent HCC in patients with hepatitis C virus (HCV( infection. By analyzing the Taiwan National Health Insurance Research Database, we initially screened a total of 100,938 patients diagnosed with HCC for the first time between October 2003 and December 2010. Among 2,237 antiviral-naive HCV-infected patients who curatively resected HCC, there were 213 patients receiving antiviral treatment with pegylated interferon plus ribavirin for 16 weeks or more after surgery (treated cohort(. These treated patients were matched 1:4 with 852 controls who never treated HCV infection (untreated cohort(, in age, gender, cirrhosis, and the elapsed time between surgery and antiviral therapy. Cumulative incidences of and hazard ratios for recurrent HCC were calculated after adjusting for competing mortality. The recurrence rate of HCC was significantly lower in the treated than untreated cohort, with 52.1% (95% confidence interval [CI], 42.0-62.2%( and 63.9% (95% CI, 58.9-68.8%( after 5 years of follow-up, respectively (p=0.001(. The number needed to treat for one fewer recurrent HCC at 5 years was 8. The association between postoperative antiviral treatment and risk of recurrent HCC was independent to adjustment for multiple covariates, with an adjusted hazard ratio of 0.64 (95% CI, 0.50-0.83(. Stratified analyses revealed that the attenuation in recurrence risk was greater in patients younger than 60 years and those without cirrhosis or diabetes. Conclusion: Postoperative pegylated interferon plus ribavirin is associated with reduced recurrence of HCC in patients with HCV infection. Age, liver cirrhosis, and diabetes mellitus appear to modify this association. (HEPATOLOGY 2013.).
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[298]
TÍTULO / TITLE: - Induction of apoptosis of leukemic cells by TRUE gene silencing using small guide RNAs targeting the WT1 mRNA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 9. pii: S0145-2126(13)00031-3. doi: 10.1016/j.leukres.2013.01.015.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.015
AUTORES / AUTHORS: - Watanabe N; Narita M; Yamahira A; Taniguchi T; Furukawa T; Yoshida T; Miyazawa T; Nashimoto M; Takahashi M
INSTITUCIÓN / INSTITUTION: - Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, 746-2 Asahimachi-dori, Chuo-ku, Niigata 951-8518, Japan; Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata, Niigata 956-8603, Japan.
RESUMEN / SUMMARY: - TRUE gene silencing is a technology to eliminate specific cellular RNAs by using tRNase Z(L) and small guide RNA (sgRNA). Here we investigated how WT1-mRNA-targeting sgRNAs affect leukemic cells. We showed that sgRNA can be easily taken up by cells without any transfection reagents, and that the naked sgRNAs targeting the WT1 mRNA can reduce its mRNA levels and WT1 protein amounts in the WT1-expressing leukemic cells. Concomitantly, these sgRNAs efficiently induced apoptosis in these cells but not in WT1-nonexpressing cells. We also demonstrated that the reduction in the WT1 mRNA level is caused by its cleavage by tRNase Z(L).
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[299]
TÍTULO / TITLE: - Donor lymphocyte infusion followed by pentostatin, cyclophosphamide, and rituximab therapy is effective for relapsed chronic lymphocytic leukemia after allogeneic stem cell transplantation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.788698
AUTORES / AUTHORS: - Watanabe M; Nakamura C; Fujii S; Kaneko H; Hirata H; Tsudo M
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[300]
TÍTULO / TITLE: - p73 participates in WWOX-mediated apoptosis in leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Med. 2013 Apr;31(4):849-54. doi: 10.3892/ijmm.2013.1289. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1289
AUTORES / AUTHORS: - Lin D; Cui Z; Kong L; Cheng F; Xu J; Lan F
INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratory, Fujian Medical University, Fuzhou 35004, P.R. China.
RESUMEN / SUMMARY: - The WWOX gene is considered to be a tumor-suppressor gene which encodes a protein (Wwox) implicated in various types of solid human cancers. It has been shown that overexpression of WWOX in human tumors promotes apoptosis in vitro and suppresses tumor growth in vivo. Recently, we investigated the effects of WWOX overexpression in vitro and observed marked growth arrest in human leukemia cells; however, the underlying mechanism(s) for this effect is unknown. The present study aimed to elucidate the primary mechanism(s) underlying WWOX-mediated apoptosis in human leukemia. We traced the interactions between WWOX and its associated factors p73 and p53 after WWOX overexpression was induced in Jurkat and K562 cells. Our data revealed that p73 participates in WWOX-mediated apoptosis in Jurkat and K562 cells through binding with Wwox in the cytoplasm without a nuclear-cytoplasmic translocation.
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[301]
TÍTULO / TITLE: - BTG2 inhibits the proliferation, invasion, and apoptosis of MDA-MB-231 triple-negative breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0691-5
AUTORES / AUTHORS: - Zhang YJ; Wei L; Liu M; Li J; Zheng YQ; Gao Y; Li XR
INSTITUCIÓN / INSTITUTION: - Division of Breast Surgery, Department of General Surgery, General Hospital of Chinese People’s Liberation Army (301 Hospital), No. 28, Fuxing Rd, Beijing, 100853, People’s Republic of China.
RESUMEN / SUMMARY: - The purposes of this study were to investigate the effects of B cell translocation gene 2 (BTG2) on the proliferation, apoptosis, and invasion of triple-negative breast cancer and to provide an experimental basis for the future treatment of human triple-negative breast cancer. A pcDNA3.1-BTG2 eukaryotic expression vector was constructed and transfected into the MDA-MB-231 human triple-negative breast cancer cell line using lipofection. Then, relevant changes in the biological characteristics of the BTG2-expressing cell line were analyzed using MTT (tetrazolium blue), flow cytometry, and Transwell invasion chamber assays. Additionally, the effects of BTG2 expression on cyclin D1, caspase 3, and matrix metalloproteinases ½ (MMP-1/-2) expression were analyzed. Cell proliferation was significantly lower in the pcDNA3.1-BTG2-transfected group compared to the empty vector and blank control groups (p < 0.05). There was no significant difference between the empty vector and blank control groups. FCM results demonstrated that there were significantly more cells in the G1 phase of the cell cycle and fewer S phase cells in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p < 0.05). Additionally, the proportion of cells that migrated across the membrane was significantly lower in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p < 0.05). Cyclin D1 and MMP-1/-2 expression were significantly lower in MDA-MB-231 cells transfected with pcDNA3.1-BTG2 as compared to the empty vector and blank control groups (p < 0.05). Caspase 3 expression was significantly higher in MDA-MB-231 cells from the pcDNA3.1-BTG2 group compared to the empty vector and blank control groups (p < 0.05). In conclusion, BTG2 may inhibit MDA-MB-231 proliferation and promote apoptosis. Additionally, BTG2 may also inhibit the invasion of MDA-MB-231 human triple-negative breast cancer cells.
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[302]
TÍTULO / TITLE: - The BH3-only protein Bim overrides Bcl-2-mediated apoptosis resistance in melanoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 9. pii: S0304-3835(13)00116-X. doi: 10.1016/j.canlet.2013.02.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.005
AUTORES / AUTHORS: - Plotz M; Gillissen B; Quast SA; Berger A; Daniel PT; Eberle J
INSTITUCIÓN / INSTITUTION: - Department of Dermatology and Allergy, Skin Cancer Center Charite, Chariteplatz 1, 10117 Berlin, Germany.
RESUMEN / SUMMARY: - Melanoma cells are characterized by apoptosis deficiency coinciding with reduced expression of the proapoptotic Bcl-2 protein Bim. An adenoviral vector was constructed with the BimL cDNA controlled by an inducible promoter. Highly efficient apoptosis induction and abrogated cell proliferation was seen in melanoma cells upon BimL overexpression. Loss of mitochondrial membrane potential, release of mitochondrial apoptogenic factors and caspase-9 processing indicated the activation of mitochondrial apoptosis pathways. BimL activated both Bax and Bak, as shown by siRNA knockdown and activation-specific antibodies. Of note, BimL overrode the apoptosis blockade by Bcl-2 overexpression or by Bax/Bak single knockdown. The high efficacy correlated to BimL interaction with all antiapoptotic Bcl-2 family members in melanoma cells, shown by co-immunoprecipitation analyses for Bcl-2, Bcl-xL, Mcl-1 and Bcl-w. Thus, BimL reveals an outstanding proapoptotic potential in melanoma cells, and strategies for its re-expression appear of interest. These have been reported for B-Raf inhibitors, and their efficacy may be partly attributed to BimL.
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[303]
TÍTULO / TITLE: - Individualized treatment of HBeAg-negative CHB using peg-interferon alfa-2a as first-line and week 12 HBV-DNA\HBsAg stopping rule. A cost-effectiveness analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Antivir Ther. 2013 Mar 13. doi: 10.3851/IMP2555.
●● Enlace al texto completo (gratuito o de pago) 3851/IMP2555
AUTORES / AUTHORS: - Iannazzo S; Coco B; Brunetto MR; Rossetti F; Caputo A; Latour A; Espinos B; Bonino F
INSTITUCIÓN / INSTITUTION: - IMS Health Economics & Outcomes Research, Milan, Italy. siannazzo@it.imshealth.com.
RESUMEN / SUMMARY: - BACKGROUND: HBeAg-negative chronic hepatitis B (CHB) is the most frequent and difficult to treat viral hepatitis worldwide. HBV-DNA and HBsAg serum levels, which help the early identification of non-responders to peg-interferon (PEG-IFN), prompt more flexible individualized therapeutic strategies exploiting the benefits of both PEG-IFN and nucleos(t)ide analogs (NAs). We assessed the cost-effectiveness of week-12 HBV-DNA\HBsAg stopping rule for early interruption and switch to currently most effective NAs treatments (entecavir-ETV or tenofovir-TDF). METHODS: A decision-analytic Markov model was developed in health-related states: CHB, compensated and decompensated cirrhosis, hepatocarcinoma, liver transplant, post-liver transplant, death and virologic response, relapse, HBsAg clearance. Simulated strategies were: 1) ETV/TDF in CHB; 2) ETV/TDF delayed until compensated cirrhosis (CC); 3) first-line-PEG-IFN followed by switch to ETV/TDF for either patients meeting week-12 stopping rule or week-48 null-responders/relapsers ; 4) first-line PEG-IFN followed by switch to ETV/TDF delayed until CC. ETV and TDF were considered alternatively for a total of 8 strategies. A lifetime simulation horizon was applied. RESULTS: Early treatment strategies using NAs with or without first-line PEG-IFN provided the highest results (about 22-life-years and 15-QALYs). Delayed treatments until cirrhosis development resulted in poorer outcomes. The average per-patient lifetime costs ranged from euro33,500 (TDF in CC) to euro68,900 (TDF in CHB). Costs using ETV were 20-50% higher. First-line-PEG-IFN strategies resulted ranging from dominant (i.e. more effective and less costly) to highly cost-effective, even though differences in QALY were always very narrow. CONCLUSIONS: The cost-effectiveness of antiviral therapy of HBeAg-negative CHB could be improved significantly using first-line PEG-IFN followed by a switch to NAs in either patients meeting week-12 HBV-DNA/HBsAg stopping rule or week-48 non responders/relapsers.
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[304]
TÍTULO / TITLE: - alpha-Lipoic acid ameliorates mitochondrial impairment and reverses apoptosis in FABP3-overexpressing embryonic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Bioenerg Biomembr. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s10863-013-9506-z
AUTORES / AUTHORS: - Zhou L; Jin J; Song G; Liu H; Liu M; Shi C; Qian L
INSTITUCIÓN / INSTITUTION: - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China.
RESUMEN / SUMMARY: - Fatty acid-binding protein 3 (FABP3) is a low molecular weight protein with distinct tissue distribution, which may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. We have previously shown FABP3 was more highly expressed in myocardium with ventricular septal defects than in normal myocardium and furthermore, that overexpression of FABP3 causes mitochondrial dysfunction and induces apoptosis in the P19 mouse teratocarcinoma cell line (P19), which is a suitable model for the investigation of cardiac differentiation at the molecular and functional levels. alpha-Lipoic acid (alpha-LA), a natural dithiol compound with antioxidant properties, has been reported to protect mitochondrial function in cells. In this study, we established an FABP3-overexpressing P19 cell line for the investigation of the impact of alpha-LA on mitochondrial impairment and apoptosis in these cells. Mitochondrial morphology was evaluated by transmission electron microscopy, while the effects of alpha-LA on reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), intracellular ATP content and the amount of mitochondrial DNA were analyzed by flow cytometry, a commercially available assay and quantitative real-time PCR, respectively. The results revealed that alpha-LA ameliorated mitochondrial deformation and decreased intracellular ROS production. Furthermore, the MMP, intracellular ATP synthesis and the amount of mitochondrial DNA were also increased. Most significantly, alpha-LA was shown to reverse apoptosis. Collectively, our results indicate that abnormalities in FABP3 expression contribute to mitochondrial dysfunction and apoptosis, and that alpha-LA represents a suitable candidate for development as a treatment for apoptosis-related congenital cardiac malformations.
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[305]
TÍTULO / TITLE: - A functional polymorphism in MIR196A2 is associated with risk and prognosis of gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Carcinog. 2013 Feb 19. doi: 10.1002/mc.22017.
●● Enlace al texto completo (gratuito o de pago) 1002/mc.22017
AUTORES / AUTHORS: - Wang S; Tao G; Wu D; Zhu H; Gao Y; Tan Y; Wang M; Gong W; Zhou Y; Zhou J; Zhang Z
INSTITUCIÓN / INSTITUTION: - Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
RESUMEN / SUMMARY: - Genetic variations in miRNAs have been demonstrated to be capable of altering miRNA expression, consequently affecting many cancer-related biological processes. The MIR196A2 rs11614913 (T > C) polymorphism has been reported to be associated with various cancers development and progression. In our study, we aim to explore whether this polymorphism is relevant to the genetic susceptibility and prognosis of gastric cancer in a Chinese population. We analyzed the correlations of rs11614913 polymorphism with gastric cancer susceptibility in test and validation sets. The test set comprised 749 cases and 900 controls, while the validation set enrolled 940 cases and 1046 controls. Moreover, we evaluated the association between the polymorphism and gastric cancer prognosis in the validation set with follow-up information. The variant rs11614913 CC genotype was associated with a significantly reduced risk of gastric cancer in both sets (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62-0.99 for the test set and 0.64, 0.52-0.80 for the validation set) compared with the CT/TT genotypes. Furthermore, the CC genotype was associated with a significantly increased survival of gastric cancer compared with the CT/TT genotypes (adjusted hazard ratio [HR] = 0.72, 95% CI = 0.55-0.95), and the association was more prominent among patients with non-cardia gastric cancer than those with cardia gastric cancer (adjusted HR = 0.57, 95% CI = 0.40-0.83 for NCGC and 1.00, 0.65-1.53 for CGC). Our results suggested that the genetic variation of MIR196A2 may play a role in gastric cancer tumorigenesis. © 2013 Wiley Periodicals, Inc.
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[306]
TÍTULO / TITLE: - Diallyl Sulfide Promotes Cell-Cycle Arrest Through the p53 Expression and Triggers Induction of Apoptosis Via Caspase- and Mitochondria-Dependent Signaling Pathways in Human Cervical Cancer Ca Ski Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Apr;65(3):505-14. doi: 10.1080/01635581.2012.725503.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2012.725503
AUTORES / AUTHORS: - Chiu TH; Lan KY; Yang MD; Lin JJ; Hsia TC; Wu CT; Yang JS; Chueh FS; Chung JG
INSTITUCIÓN / INSTITUTION: - a Department of Obstetrics and Gynecology , China Medical University Hospital , Taichung , Taiwan.
RESUMEN / SUMMARY: - Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 muM decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 muM) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 muM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer.
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[307]
TÍTULO / TITLE: - Antitumor activity of HM781-36B, a pan-HER tyrosine kinase inhibitor, in HER2-amplified breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2012 Mar;23(3):288-97. doi: 10.1097/CAD.0b013e32834e7d9b.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32834e7d9b
AUTORES / AUTHORS: - Kim HJ; Kim HP; Yoon YK; Kim MS; Lee GS; Han SW; Im SA; Kim TY; Oh DY; Bang YJ
INSTITUCIÓN / INSTITUTION: - Cancer Research Institute, Seoul, Korea.
RESUMEN / SUMMARY: - HM781-36B is an orally administered pan-human epidermal growth factor receptor (HER) inhibitor. To explore the role of pan-HER inhibitor in breast cancer, we investigated the antitumor effect and mechanisms of HM781-36B in breast cancer cell lines. Six breast cancer cell lines (BT474, MDA-MB-453, SK-BR-3, T47D, MCF-7, and MDA-MB-231) were tested. The growth inhibitory effect was assessed using the tetrazolium bromide [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide] assay. The cell cycle at various concentrations of HM781-36B was analyzed by flow cytometry, and analysis of downstream molecules was performed by western blot analysis. Interaction of HM781-36B with cytotoxic chemotherapeutic agents was analyzed by combination index using CalcuSyn. The HER2-amplified cells (SK-BR-3, BT474, and MDA-MB-453) were sensitive to HM781-36B (IC50=0.001 mumol/l, 0.0012 mumol/l, and 0.0095 mumol/l, respectively). HM781-36B induced G1 arrest and resulted in apoptosis. It reduced the level of p-HER2, p-AKT, p-ERK, and p-STAT3. HM781-36B combined with 5-fluorouracil, cisplatin, paclitaxel, or gemcitabine showed a synergistic inhibitory effect on the HER2-amplified and on some of the HER2-nonamplified breast cancer cells. HM781-36B could be a promising treatment for HER2-amplified breast cancer as a single agent or in combination with cytotoxic agents and can be a candidate for treatment of HER2-nonamplified breast cancer in combination with cytotoxic agents.
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[308]
TÍTULO / TITLE: - Methylation of a Novel Panel of Tumor Suppressor Genes in Urine Moves Forward Non-Invasive Diagnosis and Prognosis in Bladder Cancer: A Two Center Prospective Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Urol. 2013 Feb 25. pii: S0022-5347(13)00346-7. doi: 10.1016/j.juro.2013.01.105.
●● Enlace al texto completo (gratuito o de pago) 1016/j.juro.2013.01.105
AUTORES / AUTHORS: - Garcia-Baquero R; Puerta P; Beltran M; Alvarez M; Sacristan R; Alvarez-Ossorio JL; Sanchez-Carbayo M
INSTITUCIÓN / INSTITUTION: - Tumor Markers Group, Molecular Pathology Program, Spanish National Cancer Center, Madrid, España; Urology Department, Hospital Puerta del Mar, Cadiz, España.
RESUMEN / SUMMARY: - PURPOSE: Changes in DNA methylation of tumor suppressor genes (TSGs) occurring early in carcinogenesis, represent potential indicators for cancer detection and disease evolution. Our aim was to examine the diagnostic, stratification and prognostic biomarker role of urinary methylation of a novel panel of TSGs in bladder cancer. MATERIAL AND METHODS: Methylation of 18 TSGs was evaluated in two prospective independent sets of urinary samples (training, n=120; and validation, n=128) from bladder cancer patients (n=170) and controls (n=78) using methylation-specific multiplex ligation-dependent probe amplification assays (MS-MLPA). Diagnostic performance was evaluated using Receiver Operating Curves. Recurrence, progression, and disease-specific survival were analyzed using univariate and multivariate Cox models. RESULTS: PRDM2, HLTF, ID4, DLC1, BNIP3, H2AFX, CACNA1G, TGIF, and CACNA1A were discovered methylated in bladder cancer. CCND2, SCGB3A1, BNIP3, ID4 and RUNX3 were the most frequently methylated TSGs in both urinary sets. Methylation of several TSGs correlated to clinico-pathologic variables such as stage, tumor grade, focality or age. ROC analyses revealed significant diagnostic accuracies for RUNX3 and CACNA1A in the training set and for RUNX3 and ID4 in the validation set. Using univariate and multivariate analyses, CACNA1A methylation correlated to recurrence in the training set, while in the validation set, PRDM2 significantly associated with recurrence and BNIP3 with disease-specific survival, respectively. CONCLUSIONS: TSGs methylation allowed histopathologic and clinical stratification. Urinary methylation offered non-invasive utility not only for diagnostic assessment but also as independent prognosticators in bladder cancer.
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[309]
TÍTULO / TITLE: - Mechanisms of G1 cell cycle arrest and apoptosis in myeloma cells induced by hybrid-compound histone deacetylase inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 26. pii: S0006-291X(13)00459-2. doi: 10.1016/j.bbrc.2013.03.043.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.03.043
AUTORES / AUTHORS: - Fujii S; Okinaga T; Ariyoshi W; Takahashi O; Iwanaga K; Nishino N; Tominaga K; Nishihara T
INSTITUCIÓN / INSTITUTION: - Division of Infections and Molecular Biology, Kyushu Dental University, Japan; Department of Science of Physical Functions, Division of Maxillofacial Surgery, Kyushu Dental University, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: Histone deacetylase (HDAC) inhibitors are new therapeutic agents, used to treat various types of malignant cancers. In the present study, we investigated the effects of Ky-2, a hybrid-compound HDAC inhibitor, on the growth of mouse myeloma cells. MATERIALS AND METHODS: Myeloma cells, HS-72, P3U1, and mouse normal cells were used in this study. Effect of HDAC inhibitors on cell viability was determined by WST-assay and trypan blue assay. Cell cycle was analyzed using flow cytometer. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis. Hoechst’s staining was used to detect apoptotic cells. RESULTS: Our findings showed that Ky-2 decreased the levels of HDACs, while it enhanced acetylation of histone H3. Myeloma cell proliferation was inhibited by Ky-2 treatment. Interestingly, Ky-2 had no cytotoxic effects on mouse normal cells. Ky-2 treatment induced G1-phase cell cycle arrest and accumulation of a sub-G1 phase population, while Western blotting analysis revealed that expressions of the cell cycle-associated proteins were up-regulated. Also, Ky-2 enhanced the cleavage of caspase-9 and -3 in myeloma cells, followed by DNA fragmentation. In addition, Ky-2 was not found to induce apoptosis in bcl-2 overexpressing myeloma cells. CONCLUSION: These findings suggest that Ky-2 induces apoptosis via a caspase-dependent cascade and Bcl-2-inhibitable mechanism in myeloma cells.
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[310]
TÍTULO / TITLE: - HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: Array-based DNA methylation and expression profiling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 22. doi: 10.1002/ijc.28121.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28121
AUTORES / AUTHORS: - Kim YJ; Yoon HY; Kim JS; Kang HW; Min BD; Kim SK; Ha YS; Kim IY; Ryu KH; Lee SC; Kim WJ
INSTITUCIÓN / INSTITUTION: - Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
RESUMEN / SUMMARY: - DNA methylation patterns are associated with the development and prognosis of cancer. The aim of this study was to identify novel methylation markers for the prediction of patient outcomes using microarray analysis of DNA methylation and RNA expression patterns in samples from long-term follow-up patients with nonmuscle invasive bladder cancer (NMIBC). A total of 187 human bladder specimens were used for microarray array or pyrosequencing (PSQ) analyses: 6 normal controls (NC) and 181 NMIBC. Tumor-specific hypermethylated genes were selected from a data set comprising 24 matched microarray-based DNA methylation and gene expression profiles (6 controls and 18 NMIBC), and their clinical relevance was verified by quantitative PSQ analysis. The methylation status of Homeobox A9 (HOXA9), ISL LIM homeobox 1 (ISL1) and Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) was significantly associated with decreased gene expression levels and aggressive clinicopathological characteristics. Multivariate regression analyses showed that hypermethylation of these genes was an independent predictor of disease recurrence (HOXA9, ISL1 and ALDH1A3, either alone or in combination) and progression (ISL1 and ALDH1A3, either alone or in combination) (each p < 0.05). The results of this study suggest that these novel methylation markers are independent prognostic indicators in NMIBC patients, which may facilitate the assessment of disease recurrence and progression in NMIBC patients and inform clinical decision making regarding treatment.
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[311]
TÍTULO / TITLE: - Protein kinase Calpha inhibitor protects against downregulation of claudin-1 during epithelial-mesenchymal transition of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt057
AUTORES / AUTHORS: - Kyuno D; Kojima T; Yamaguchi H; Ito T; Kimura Y; Imamura M; Takasawa A; Murata M; Tanaka S; Hirata K; Sawada N
INSTITUCIÓN / INSTITUTION: - Department of Surgery and.
RESUMEN / SUMMARY: - Protein kinase Calpha (PKCalpha) is highly expressed in pancreatic cancer. However, the effects of PKCalpha on Snail and claudin-1, which play crucial roles in epithelial cell polarity during epithelial-mesenchymal transition (EMT), remain unclear. In this study, we investigated the mechanisms of regulation of Snail and claudin-1 via a PKCalpha signal pathway during EMT in pancreatic cancer cells and in normal human pancreatic duct epithelial cells (HPDEs). By immunostaining, overexpression of PKCalpha and downregulation of claudin-1 were observed in poorly differentiated human pancreatic cancer tissues and the pancreatic cancer cell line PANC-1. Treatment with the PKCalpha inhibitor Go6976 transcriptionally decreased Snail and increased claudin-1 in PANC-1 cells. The PKCalpha inhibitor prevented upregulation of Snail and downregulation of claudin-1 during EMT induced by transforming growth factor-beta1 (TGF-beta1) treatment and under hypoxia in PANC-1 cells. The effects of the PKCalpha inhibitor were in part regulated via an extracellular signal-regulated kinase (ERK) signaling pathway. The PKCalpha inhibitor also prevented downregulation of the barrier function and fence function during EMT in well-differentiated pancreatic cancer cell line HPAC. In normal HPDEs, the PKCalpha inhibitor transcriptionally induced not only claudin-1 but also claudin-4, -7 and occludin without a change of Snail. Treatment with the PKCalpha inhibitor in normal HPDEs prevented downregulation of claudin-1 and occludin by TGF-beta1 treatment and enhanced upregulation of claudin-1, -4, -7 and occludin under hypoxia. These findings suggest that PKCalpha regulates claudin-1 via Snail- and mitogen-activated protein kinase/ERK-dependent pathways during EMT in pancreatic cancer. Thus, PKCalpha inhibitors may be potential therapeutic agents against the malignancy of human pancreatic cancer cells.
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[312]
TÍTULO / TITLE: - Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 2. pii: S0169-5002(13)00015-9. doi: 10.1016/j.lungcan.2012.12.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.025
AUTORES / AUTHORS: - Pallis AG; Syrigos KN
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece. Electronic address: agpallis@gmail.com.
RESUMEN / SUMMARY: - Improvements in our understanding of the molecular biology of cancer have shifted management of lung cancer toward molecular-guided, individualized treatment. Development of epidermal growth factor receptor tyrosine kinase inhibitors, erlotinib and gefitinib, represent the best example of this approach. Erlotinib was tested as second/third line treatment in unselected population of patients and demonstrated a statistically significant prolongation of overall survival, while gefitinib was shown to be non-inferior to docetaxel as second line treatment. The discovery of EGFR activating mutations facilitated the selection of patients most likely to benefit from erlotinib/gefitinib. These drugs in patients with EGFR activating mutations offer an increased progression free survival and significantly higher response rates compared to chemotherapy. The purpose of this paper is to present the relevant clinical data, describe the predictive markers available for TKIs treatment in NSCLC, and describe the mechanisms associated with resistance to treatment with these agents.
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[313]
TÍTULO / TITLE: - Expression of Brachyury Gene Is a Significant Prognostic Factor for Primary Lung Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2914-9
AUTORES / AUTHORS: - Haro A; Yano T; Kohno M; Yoshida T; Koga T; Okamoto T; Takenoyama M; Maehara Y
INSTITUCIÓN / INSTITUTION: - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan, aharo@surg2.med.kyushu-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: The clinical significance of Brachyury expression and its relationship to epithelial-mesenchymal transition in primary lung carcinoma is unclear. METHODS: Expression of Brachyury mRNA was investigated in 104 surgically resected primary lung carcinoma tissues. Immunohistochemical analysis of Brachyury transcription factor, Slug, E-cadherin, IL-8, N-cadherin, and Ki67 was performed in 67 of 104 cases, and their expression was correlated to prognoses and clinicopathological factors. RESULTS: Brachyury mRNA expression in primary lung carcinoma tissues was a significant predictor of poor prognosis for 5-year disease-free survival and overall survival rates and was significantly correlated to vascular invasion, lymphatic permeation, histological grade, pathologic T stage, and pathologic N stage (P < 0.05). Brachyury mRNA expression was significantly inversely correlated to E-cadherin expression (P = 0.0252) and positively correlated to IL-8 protein (P = 0.0241) and to Slug protein (P = 0.0243) in adenocarcinoma tissues. CONCLUSIONS: A positive association between Brachyury and Slug and IL-8, and a negative association with E-cadherin may lead to invasiveness and metastasis in primary lung carcinoma. Brachyury mRNA expression is a significant predictor of poor prognosis in primary lung carcinoma.
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[314]
TÍTULO / TITLE: - Adherence to Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia: A Brazilian Single-Center Cohort.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Haematol. 2013 Jan 25;130(1):16-22.
●● Enlace al texto completo (gratuito o de pago) 1159/000345722
AUTORES / AUTHORS: - de Almeida MH; Pagnano KB; Vigorito AC; Lorand-Metze I; de Souza CA
INSTITUCIÓN / INSTITUTION: - Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil.
RESUMEN / SUMMARY: - The introduction of oral tyrosine kinase inhibitors (TKIs) has dramatically improved outcomes in chronic myeloid leukemia (CML) patients. However, treatment success is directly related to good long-term adherence. Adherence to TKI therapy was evaluated in 137 CML patients over a period of 1 year. Three different methods were used to evaluate adherence: the Morisky questionnaire, a medication diary and the medication possession ratio (MPR). MPR was the most effective method of assessing adherence (median adherence 96.5%; p = 0.0001), duration of TKI treatment was the variable that most impacted adherence (p = 0.03), and the MPR was inversely correlated to the duration of therapy. Additionally, participation in clinical trials, better quality of life as reported by patients and higher socioeconomic status were all related to better compliance (p = 0.02, 0.007 and 0.01, respectively). For patients treated with imatinib for 24-48 months (n = 22), individuals with major molecular response (MMR) had a significantly better MPR than those who failed to achieve MMR (p = 0.04). In this group, the mean MPR was 87% for the population without apparent molecular response and 96% for those achieving MMR; however, only 24% of the patients were completely adherent to TKI treatment.
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[315]
TÍTULO / TITLE: - Longitudinal expression analysis of alphav integrins in human gliomas reveals upregulation of integrin alphavbeta3 as a negative prognostic factor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Neuropathol Exp Neurol. 2013 Mar;72(3):194-210. doi: 10.1097/NEN.0b013e3182851019.
●● Enlace al texto completo (gratuito o de pago) 1097/NEN.0b013e3182851019
AUTORES / AUTHORS: - Schittenhelm J; Schwab EI; Sperveslage J; Tatagiba M; Meyermann R; Fend F; Goodman SL; Sipos B
INSTITUCIÓN / INSTITUTION: - Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tubingen, Tubingen, Germany. jens.schittenhelm@med.uni-tuebingen.de
RESUMEN / SUMMARY: - Integrin inhibitors targeting alphav series integrins are being tested for their therapeutic potential in patients with brain tumors, but pathologic studies have been limited by lack of antibodies suitable for immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded specimens. We compared the expression of alphav integrins by IHC in brain tumor and normal human brain samples with gene expression data in a public database using new rabbit monoclonal antibodies against alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 complexes using both manual and automated microscopy analyses. Glial tumors usually shared an alphavbeta3-positive/alphavbeta5-positive/alphavbeta8-positive/alphavbeta6-negati ve phenotype. In 94 WHO (World Health Organization) grade II astrocytomas, 85 anaplastic astrocytomas WHO grade III, and 324 glioblastomas from archival sources, expression of integrins generally increased with grade of malignancy. Integrins alphavbeta3 and alphavbeta5 were expressed in many glioma vessels; the intensity of vascular expression of alphavbeta3 increased with grade of malignancy, whereas alphavbeta8 was absent. Analysis of gene expression in an independent cohort showed a similar increase in integrin expression with tumor grade, particularly of ITGB3 and ITGB8; ITGB6 was not expressed, consistent with the IHC data. Parenchymal alphavbeta3 expression and ITGB3 gene overexpression in glioblastomas were associated with a poor prognosis, as revealed by survival analysis (Kaplan-Meier logrank, p = 0.016). Together, these data strengthen the rationale for anti-integrin treatment of glial tumors.
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[316]
TÍTULO / TITLE: - Single Nucleotide Polymorphisms of IL-10 and IL- 28B as predictors to the response of interferon therapy in HCV genotype 4 infected children.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pediatr Gastroenterol Nutr. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/MPG.0b013e31828febf0
AUTORES / AUTHORS: - Shaker OG; Nassar YH; Nour ZA; El-Razki M
INSTITUCIÓN / INSTITUTION: - *Medical Biochemistry and Molecular Biology daggerPediatrics Faculty of Medicine, Cairo University.
RESUMEN / SUMMARY: - BACKGROUND & AIMS:: SNPs in IL-10 gene (-1082 (rs1800896), -819 (rs3021097), and -592 (rs1800872)) and IL28B gene (rs12979860) in adults were shown to be associated with HCV clearance. The present study aimed to investigate possible association of SNPs of IL-10 and IL-28B in predicting treatment response of HCV-4 in pediatric patients. PATIENTS AND METHODS:: A RFLP-PCR and Real time PCR techniques were used to genotype 34 pediatric patients with HCV-4 for IL-10 SNPs and IL-28B SNP respectively. Patients received Peg-IFN-alpha/ RBV for 48 weeks subdivided according to their response to treatment into responders and non-responders, also 20 healthy subjects were served as control. RESULTS:: A significant difference (p < 0.005) was observed in SNP of IL-28B rs12979860 frequencies between responders and non-responders. In responders, CC genotype had greater frequency than CT and TT genotypes (60%, 30%, 10%) respectively with C allele in its homozygous (CC) genotype more likely to respond to treatment than in its homozygous (TT) genotypes. SNP of IL-10 at-819 (rs3021097) showed significant difference in its genotype frequencies between responders and non-responders to therapy, where TT genotype had greater frequency in responders that CT and CC (55%, 20%, 25%) respectively. Genotypes with T allele (CT/TT) showed higher rates of response than those with no T allele (CC). CONCLUSION:: SNP of IL28B gene at (rs12979860) CC genotype as well as the IL-10 gene SNP at- 819 (rs3021097)TT genotype can be used for predicting response to treatment before patient is prescribed to the expensive Peg-IFN/RBV therapy.
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[317]
TÍTULO / TITLE: - A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Apr;34(2):1263-71. doi: 10.1007/s13277-013-0701-7. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0701-7
AUTORES / AUTHORS: - Jiang G; Jiang AJ; Cheng Q; Tian H; Li LT; Zheng JN
INSTITUCIÓN / INSTITUTION: - Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, 221002, China.
RESUMEN / SUMMARY: - Malignant melanoma is one of the most lethal and aggressive human malignancies. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to malignant melanoma. The alkylating agent temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and with high frequency. We constructed a dual-regulated oncolytic adenovirus expressing interleukin 24 (IL-24) gene (Ki67-ZD55-IL-24) by utilizing the Ki67 promoter to replace the native viral promoter of E1A gene. We investigated whether a combination of Ki67-ZD55-IL-24-mediated gene virotherapy and chemotherapy using TMZ produces increased cytotoxicity against human melanoma cells via the induction of apoptosis. Our data indicate that this novel strategy thus holds promising potentials for further developing an effective approach to treat malignant melanoma.
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[318]
TÍTULO / TITLE: - A Targeted RNAi Screen of the Breast Cancer Genome Identifies KIF14 and TLN1 as Genes That Modulate Docetaxel Chemosensitivity in Triple-Negative Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 4.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-13-0082
AUTORES / AUTHORS: - Singel SM; Cornelius C; Batten K; Fasciani G; Wright WE; Lum L; Shay JW
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Cell Biology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
RESUMEN / SUMMARY: - PURPOSE: To identify biomarkers within the breast cancer genome that may predict chemosensitivity in breast cancer.EXPERIMENTAL DESIGN: We conducted an RNA interference (RNAi) screen within the breast cancer genome for genes whose loss-of-function enhanced docetaxel chemosensitivity in an estrogen receptor-negative, progesterone receptor-negative, and Her2-negative (ER-, PR-, and Her2-, respectively) breast cancer cell line, MDA-MB-231. Top candidates were tested for their ability to modulate chemosensitivity in 8 breast cancer cell lines and to show in vivo chemosensitivity in a mouse xenograft model.RESULTS: From ranking chemosensitivity of 328 short hairpin RNA (shRNA) MDA-MB-231 cell lines (targeting 133 genes with known somatic mutations in breast cancer), we focused on the top two genes, kinesin family member 14 (KIF14) and talin 1 (TLN1). KIF14 and TLN1 loss-of-function significantly enhanced chemosensitivity in four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, HCC38, HCC1937, and Hs478T) but not in three hormone receptor-positive cell lines (MCF7, T47D, and HCC1428) or normal human mammary epithelial cells (HMEC). Decreased expression of KIF14, but not TLN1, also enhanced docetaxel sensitivity in a Her2-amplified breast cancer cell line, SUM190PT. Higher KIF14 and TLN1 expressions are found in TNBCs compared with the other clinical subtypes. Mammary fat pad xenografts of KIF14- and TLN1-deficient MDA-MB-231 cells revealed reduced tumor mass compared with control MDA-MB-231 cells after chemotherapy. KIF14 expression is also prognostic of relapse-free and overall survival in representative breast cancer expression arrays.CONCLUSION: KIF14 and TLN1 are modulators of response to docetaxel and potential therapeutic targets in TNBC. Clin Cancer Res; 19(8); 1-10. ©2013 AACR.
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[319]
TÍTULO / TITLE: - High expressions of histone methylation- and phosphorylation-related proteins are associated with prognosis of oral squamous cell carcinoma in male population of Taiwan.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):513. doi: 10.1007/s12032-013-0513-z. Epub 2013 Mar 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0513-z
AUTORES / AUTHORS: - Chen JH; Yeh KT; Yang YM; Chang JG; Lee HE; Hung SY
INSTITUCIÓN / INSTITUTION: - Faculty of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
RESUMEN / SUMMARY: - Since 2008, oral squamous cell carcinoma (OSCC) has climbed to the fourth place in cancer mortality in the male population of Taiwan. Epigenetic regulations including DNA methylation and histone modification control gene expression and play important roles during cancer progression. Since the relationship between histone modification and prognosis of OSCC is inconclusive, we collected 215 formalin-fixed and paraffin-embedded tissues from male patients having OSCC and surveyed them by tissue microarray-based immunohistochemical staining. The association between five histone modification-related genes, clinicopathological parameters, and prognosis of OSCC was examined. From tissue microarray immunohistochemistry staining results, we found that the nuclear staining intensity of ARK2 (Aurora kinase B-a serine/threonine-protein kinase of H3S10) was associated with poor clinical outcomes (</=3-year survival, p = 0.005). The cytosolic staining intensity of the ARK2 protein was associated with tumor stage (p = 0.006) and tumor size (T) of TNM staging system (p = 0.026). Cytoplasmic staining intensity of G9a (H3K9 methyltransferase) was associated with histological grade of differentiation (p = 0.026). EZH2 (H3K27 methyltransferase) and SUV39H1 (H3K9 methyltransferase) overexpressions in nuclei were, respectively, associated with lymph node metastasis (N, p = 0.016) and stage (p = 0.009). Our result suggests that overexpressions of histone modification-related proteins-ARK2, G9a, EZH2, and SUV39H1 but not SUV39H2 are associated with prognosis of OSCC in the male population of Taiwan. These proteins, especially ARK2, may serve as effective prognostic factors and can also be used as biomarkers for predicting various clinical outcomes of OSCCs in the Taiwanese population.
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[320]
TÍTULO / TITLE: - Regulation of carboxylesterase-2 expression by p53 family proteins and enhanced anti-cancer activities among 5-fluorouracil, irinotecan and doxazolidine prodrug.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Pharmacol. 2013 Apr;168(8):1989-99. doi: 10.1111/bph.12125.
●● Enlace al texto completo (gratuito o de pago) 1111/bph.12125
AUTORES / AUTHORS: - Xiao D; Yang D; Guo L; Lu W; Charpentier M; Yan B
INSTITUCIÓN / INSTITUTION: - Department of Biomedical and Pharmaceutical Sciences, Center for Pharmacogenomics and Molecular Therapy, University of Rhode Island, Kingston, RI, USA.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: For four decades, 5-fluorouracil (5-FU) has been a major anti-cancer medicine. This drug is increasingly used with other anti-cancer agents such as irinotecan. Irinotecan and many others such as PPD (pentyl carbamate of p-aminobenzyl carbamate of doxazolidine) require activation by carboxylesterase-2 (CES2). 5-FU, on the other hand, reportedly induces CES2 in colorectal tumour lines. The aims of this study were to determine the molecular basis for the induction and to ascertain interactive cell-killing activity between 5-FU and ester prodrugs. EXPERIMENTAL APPROACH: Colorectal and non-colorectal lines and xenografts were treated with 5-FU and the expression of CES2 was determined. Cell-killing activity of irinotecan and PPD were determined in the presence or absence of CES2 inhibitor. Several molecular experiments were used to determine the molecular basis for the induction. KEY RESULTS: Without exceptions, robust induction was detected in cell lines expressing functional p53. High-level induction was also detected in xenografts. 5-FU pretreatment significantly increased cell-killing activity of irinotecan and PPD. Molecular experiments established that the induction was achieved by both transactivation and increased mRNA stability through p53. Either p63 or p73, functionally related to p53, did not support the transactivation. CONCLUSIONS AND IMPLICATIONS: The results in this study suggest that FOLFIRI, a common regimen combining irinotecan and 5-FU, should switch the dosing sequence, namely from 5-FU to irinotecan, to enhance hydrolytic activation of irinotecan. This modified order likely reduces the dose of anti-cancer agents, thus minimizing overall toxicity. The results also conclude that p53 family members act differently in regulating gene expression.
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[321]
TÍTULO / TITLE: - Ceramide induces COX-2-dependent induction of apoptosis in human ovarian cancer OVCAR-3 cells by mechanisms that partially overlap with actions of resveratrol.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Biochem. 2013 Mar 13. doi: 10.1002/jcb.24539.
●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24539
AUTORES / AUTHORS: - Lin HY; Delmas D; Vang O; Hsieh TC; Lin S; Cheng GY; Chiang HL; Chen CE; Tang HY; Crawford DR; Whang-Peng J; Hwang J; Liu LF; Wu JM
INSTITUCIÓN / INSTITUTION: - Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan. linhy@tmu.edu.tw.
RESUMEN / SUMMARY: - Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular-signal-regulated kinases (ERK)1/2- and p38 kinase-dependent apoptosis in human ovarian cancer OVCAR-3 cells, concomitant with an increase in the expression of COX-2 and p53 phosphorylation. Blockade of cyclooxygenase-2 (COX-2) activity by siRNA or NS398 correspondingly inhibited ceramide-induced p53 Ser-15 phosphorylation and apoptosis; thus COX-2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells. Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
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[322]
TÍTULO / TITLE: - Organic cadmium complexes as proteasome inhibitors and apoptosis inducers in human breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Inorg Biochem. 2013 Feb 21;123C:1-10. doi: 10.1016/j.jinorgbio.2013.02.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jinorgbio.2013.02.004
AUTORES / AUTHORS: - Zhang Z; Bi C; Buac D; Fan Y; Zhang X; Zuo J; Zhang P; Zhang N; Dong L; Dou QP
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, 266100, PR China; The Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, 48201, USA; Department of Oncology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA; Department of Pathology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA.
RESUMEN / SUMMARY: - Although cadmium (Cd) is a widespread environmental contaminant and human carcinogen, our studies indicate an organic Cd complex to be a potent inhibitor of proteasomal chymotrypsin-like (CT-like) activity, further capable of inducing apoptosis in a cancer cell-specific manner. It has been reported that the ligands indole-3-butyric acid (L1) and indole-3-propionic acid (L2) have cancer-fighting effects when tested in a rat carcinoma model. In addition, 3, 5-diaminobenzoic acid o-vanillin Schiff bases (L3) have high antimicrobial activity and a large number of Schiff base complexes have been reported to have proteasome-inhibitory activity. We therefore hypothesized that synthetic forms of Cd in combination with L1, L2 and L3 may have proteasome-inhibitory and apoptosis-inducing activities, which would be cancer cell-specific. To test this hypothesis, we have synthesized three novel Cd-containing complexes: [Cd2(C12H12O2N)4(H2O)2].2H2O (Cd1), [Cd2(C11H10O2N)4(H2O)2].2H2O (Cd2) and [Cd(C7H4N2O2)(C8H6O2)2].2H2O (Cd3), by using these three ligands. We sought out to characterize and assess the proteasome-inhibitory and anti-proliferative properties of these three Cd complexes in human breast cancer cells. Cd1, Cd2 and Cd3 were found to effectively inhibit the chymotrypsin-like activity of purified 20S proteasome with IC50 values of 2.6, 3.0 and 3.3muMu, respectively. Moreover, inhibition of cancer cell proliferation also correlated with this effect. As a result of proteasomal shutdown, the accumulation of ubiquitinated proteins and the proteasome target IkappaB-alpha protein as well as induction of apoptosis were observed. To account for the cancer specificity of this effect, immortalized, non-tumorigenic breast MCF10A cells were used under the same experimental conditions. Our results indicate that MCF10A cells are much less sensitive to the Cd1, Cd2 and Cd3 complexes when compared to MDA MB 231 breast cancer cells. Therefore, our study suggests that these Cd organic complexes are capable of inhibiting tumor cellular proteasome activity and consequently induce cancer cell-specific apoptotic death.
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[323]
TÍTULO / TITLE: - MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1533-9. doi: 10.3892/or.2013.2258. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2258
AUTORES / AUTHORS: - Bi W; Wei Y; Wu J; Sun G; Guo Y; Zhang Q; Dong L
INSTITUCIÓN / INSTITUTION: - Institute of Biochemistry and Molecular Biology, School of Medicine, Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
RESUMEN / SUMMARY: - MAPK-activating death domain protein (MADD) binds to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor and acts as a key downstream mediator in the TRAIL-induced apoptosis pathway. The aim of this study was to evaluate the expression of MADD in normal human and adenocarcinoma tissues of the lungs and its influence on proliferation and apoptosis of A549 human lung adenocarcinoma cells. Immunohistochemistry was carried out to detect the expression of MADD in normal and tumor tissues of the lungs. Expression of the MADD gene in A549 cells was measured by reverse transcription-polymerase chain reaction. A549 cells were transfected with plasmids carrying the DNA fragment encoding MADD and lentiviral vectors used for RNA interference, respectively. MADD expression in the transfected A549 cells was determined by western blotting. Proliferation and apoptosis were detected using MTT assay and flow cytometry, respectively. It was found that non-small cell lung cancer tissues expressed MADD at higher levels compared to normal lung tissues, and the level of MADD in lung adenocarcinoma was higher compared to that in lung squamous cell carcinoma. MADD was expressed in A549 cells. Both introduction of the DNA fragment encoding MADD and RNA interference targeting MADD effectively altered levels of MADD in the A549 cells. Overexpression of MADD in the A549 cells inhibited apoptosis and increased survival whereas abrogation of MADD promoted apoptosis and reduced cell proliferation. These results suggest that MADD may be a potential therapeutic target for lung adenocarcinoma therapy involving the TRAIL-induced apoptosis pathway.
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[324]
TÍTULO / TITLE: - Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Haematologica. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 3324/haematol.2012.067983
AUTORES / AUTHORS: - Driessen EM; van Roon EH; Spijkers-Hagelstein JA; Schneider P; de Lorenzo P; Valsecchi MG; Pieters R; Stam RW
INSTITUCIÓN / INSTITUTION: - The Neherlands;
RESUMEN / SUMMARY: - Abstract Background Acute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence(~80%) translocations involving the Mixed Lineage Leukemia(MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question whether these fusion proteins require secondary hits. RAS mutations are suggested as candidates. Earlier results on the incidence of RAS mutations in Mixed Lineage Leukemia-rearranged acute lymphoblastic leukemia are inconclusive. Therefore, we studied frequencies and relation with clinical parameters of RAS mutations in a large cohort of infant acute lymphoblastic leukemia patients. Design and methods Using conventional sequencing analysis, we screened neuroblastoma RAS viral (v-ras) oncogene homolog gene(NRAS), v-Ki-ras Kirsten rat sarcoma viral oncogene homolog gene(KRAS), and v-raf murine sarcoma viral oncogene homolog B1 gene(BRAF) for mutations in a large cohort(n=109) of infant acute lymphoblastic leukemia patients and studied the mutations in relation to several clinical parameters, and in relation to Homeobox gene A9 expression and the presence of ALL1 fused gene 4-Mixed Lineage Leukemia(AF4-MLL). Results Mutations were detected in ~14% of all cases, with a higher frequency of ~24% in t(4;11)-positive patients(p=0.04). Furthermore, we identified RAS mutations as an independent predictor(p=0.019) for poor outcome in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia, with a hazard ratio of 3.194(95% confidence interval:1.211-8.429). Also, RAS-mutated infants have higher white blood cell counts at diagnosis(p=0.013), and are more resistant to glucocorticoids in vitro(p<0.05). Finally, we demonstrate that RAS mutations, neither the lack of Homeobox gene A9 expression nor the expression of ALL1 fused gene 4-Mixed Lineage Leukemia are associated with poor outcome in t(4;11)-rearranged infants. Conclusions We conclude that the presence of a RAS mutations in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia is an independent predictor for a poor outcome. Therefore, future risk-stratification based on abnormal RAS-pathway activation and RAS-pathway inhibition could be beneficial in RAS-mutated infant acute lymphoblastic leukemia patients.
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[325]
TÍTULO / TITLE: - Simultaneous integrated boost-intensity modulated radiation therapy with concomitant capecitabine and mitomycin C for locally advanced anal carcinoma: a phase 1 study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):e201-7. doi: 10.1016/j.ijrobp.2012.12.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.12.008
AUTORES / AUTHORS: - Deenen MJ; Dewit L; Boot H; Beijnen JH; Schellens JH; Cats A
INSTITUCIÓN / INSTITUTION: - Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - PURPOSE: Newer radiation techniques, and the application of continuous 5-FU exposure during radiation therapy using oral capecitabine may improve the treatment of anal cancer. This phase 1, dose-finding study assessed the feasibility and efficacy of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with concomitant capecitabine and mitomycin C in locally advanced anal cancer, including pharmacokinetic and pharmacogenetic analyses. METHODS AND MATERIALS: Patients with locally advanced anal carcinoma were treated with SIB-IMRT in 33 daily fractions of 1.8 Gy to the primary tumor and macroscopically involved lymph nodes and 33 fractions of 1.5 Gy electively to the bilateral iliac and inguinal lymph node areas. Patients received a sequential radiation boost dose of 3 x 1.8 Gy on macroscopic residual tumor if this was still present in week 5 of treatment. Mitomycin C 10 mg/m(2) (maximum 15 mg) was administered intravenously on day 1, and capecitabine was given orally in a dose-escalated fashion (500-825 mg/m(2) b.i.d.) on irradiation days, until dose-limiting toxicity emerged in >/=2 of maximally 6 patients. An additional 8 patients were treated at the maximum tolerated dose (MTD). RESULTS: A total of 18 patients were included. The MTD of capecitabine was determined to be 825 mg/m(2) b.i.d. The predominant acute grade >/=3 toxicities included radiation dermatitis (50%), fatigue (22%), and pain (6%). Fifteen patients (83% [95%-CI: 66%-101%]) achieved a complete response, and 3 (17%) patients a partial response. With a median follow-up of 28 months, none of the complete responders, and 2 partial responders had relapsed. CONCLUSIONS: SIB-IMRT with concomitant single dose mitomycin C and capecitabine 825 mg/m(2) b.i.d. on irradiation days resulted in an acceptable safety profile, and proved to be a tolerable and effective treatment regimen for locally advanced anal cancer.
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[326]
TÍTULO / TITLE: - Transcription Factor KLLN Inhibits Tumor Growth by AR Suppression, Induces Apoptosis by TP53/TP73 Stimulation in Prostate Carcinomas, and Correlates With Cellular Differentiation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Endocrinol Metab. 2013 Mar;98(3):E586-94. doi: 10.1210/jc.2012-3490. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3490
AUTORES / AUTHORS: - Wang Y; Radhakrishnan D; He X; Peehl DM; Eng C
INSTITUCIÓN / INSTITUTION: - MD, PhD, Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio 44195. engc@ccf.org.
RESUMEN / SUMMARY: - Context: KLLN is a newly identified gene with unknown function and shares a bidirectional promoter with PTEN. Objective: The objective of the study was to analyze the relationship between KILLIN (KLLN) expression and prostate cancer and the potential tumor suppressive effect. Design: We conducted an in silico analysis to compare KLLN expression in normal prostate and matched primary carcinoma tissues. We subsequently used immunohistochemistry to examine KLLN expression and association with Gleason grade and score in 109 prostatectomy samples. KLLN’s tumor-suppressive effect was studied in androgen-dependent and androgen-independent cell models. Patients: Patients were diagnosed with peripheral zone prostate carcinomas without metastasis at the time of prostatectomy. Each patient’s primary tumor comprised at least 2 tumoral regions with different Gleason grades. Results: KLLN expression decreased from normal prostate tissue to primary carcinomas (P < .0001). The loss of epithelial and stromal KLLN expression is associated with poor differentiation and high Gleason scores (P < .0001), consistent with our in vitro observation that KLLN inhibits tumor cell proliferation and invasiveness. KLLN decreases prostate-specific antigen levels and suppresses androgen-mediated cell growth by inhibiting androgen receptor (AR) transcription. As an androgen receptor-regulated target, KLLN also functions as a transcriptional activator, directly promoting the expression of TP53 and TP73, with consequent elevated apoptosis, regardless of AR status. Conclusions: Our observations suggest that KLLN is a transcription factor directly regulating AR, TP53, and TP73 expression, with a role in prostate carcinogenesis. Loss of KLLN associates with high Gleason scores, suggesting that KLLN might be used as a potential prognostic marker for risk management and as a novel therapy target for advanced prostate carcinomas.
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[327]
TÍTULO / TITLE: - Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 8;432(2):314-9. doi: 10.1016/j.bbrc.2013.01.109. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.01.109
AUTORES / AUTHORS: - Liu W; Otkur W; Li L; Wang Q; He H; Zang L; Hayashi T; Tashiro S; Onodera S; Xia M; Ikejima T
INSTITUCIÓN / INSTITUTION: - China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
RESUMEN / SUMMARY: - Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases ½ (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis.
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[328]
TÍTULO / TITLE: - Cytotoxicity of chemotherapeutic agents in glyceraldehyde-3-phosphate dehydrogenase-depleted human lung carcinoma A549 cells with the accelerated senescence phenotype.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Apr;24(4):366-74. doi: 10.1097/CAD.0b013e32835e3378.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835e3378
AUTORES / AUTHORS: - Phadke M; Krynetskaia N; Krynetskiy E
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
RESUMEN / SUMMARY: - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a central role in glycolysis. Because cancer cells rely on aerobic glycolysis rather than oxidative phosphorylation, GAPDH-depleting agents have a therapeutic potential to impede cancer cell proliferation. Knockdown of GAPDH by RNA interference induced the accelerated senescent phenotype in A549 cells, suggesting that GAPDH is a potential molecular target for combination chemotherapy. The cytotoxic effects of a panel of anticancer drugs, 5-fluorouracil, 5-fluorouridine, 5-fluorodeoxyuridine, 6-thioguanine, cytarabine, fludarabine, cladribine, clofarabine, 2-chloroadenosine, and doxorubicin, were assessed in GAPDH-depleted A549 cells using a cell proliferation assay. GAPDH-depleted A549 cells, when compared with control cells, exhibited increased chemoresistance to several antimetabolite agents including cytarabine [inhibitory concentration 50 (IC50) 1.7+/-0.3 vs. 0.03+/-0.02 mumol/l], 2-chloroadenosine (IC50 7.1+/-1.8 vs. 1.5+/-0.6 mumol/l), 6-thioguanine (IC50 7.5+/-1.6 vs. 1.4+/-0.5 mumol/l), 5-fluorouracil (IC50 13.2+/-2.5 vs. 3.0+/-0.7 mumol/l), and 5-fluorodeoxyuridine (IC50 >100 vs. 3.7+/-0.9 mumol/l), which we designated as group A agents. In contrast, GAPDH-deficient and GAPDH-proficient cells were equally sensitive to group B agents including doxorubicin (IC50 0.05+/-0.02 vs. 0.04+/-0.02 mumol/l), fludarabine (IC50 18.5+/-2.3 vs. 15.7+/-2.8 mumol/l), 5-fluorouridine (IC50 0.1+/-0.03 vs. 0.1+/-0.03 mumol/l), clofarabine (IC50 0.7+/-0.3 vs. 0.5+/-0.3 mumol/l), and cladribine (IC50 0.5+/-0.1 vs. 0.5+/-0.2 mumol/l). After treatment with group B agents at concentrations equivalent to 7-10-fold the IC50 value, the fraction of apoptotic cells in GAPDH-depleted, senescent A549 cells was similar to that in GAPDH-proficient cells. Our study identified the antimetabolite drugs active in senescent cells that can be used in combination with GAPDH inhibitors in cancer treatment. GAPDH-targeted combination therapy is a novel strategy to control the proliferation of tumor cells.
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[329]
TÍTULO / TITLE: - Bortezomib influences the expression of malignant plasma cells membrane antigens.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Pharmacol. 2013 Feb 28;706(1-3):11-16. doi: 10.1016/j.ejphar.2013.02.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejphar.2013.02.002
AUTORES / AUTHORS: - Tagoug I; Plesa A; Dumontet C
INSTITUCIÓN / INSTITUTION: - Universite de Lyon, F-69008, Lyon, France; INSERM U1052/CNRS UMR 5286, Centre de Recherche en Cancerologie de Lyon, F-69008 Lyon, France; Hospices Civils de Lyon, Lyon, F-69003, France.
RESUMEN / SUMMARY: - Multiple myeloma cells can be characterized immunophenotypically as the expression levels of several membrane antigens differ from those of normal plasma cells. These antigens are important for making a diagnostic of multiple myeloma; they have a significant role in survival and proliferation of multiple myeloma cells. Analyzing the effect of bortezomib on the expression of surface antigens CD138, CD56, CD27, CD28, CD45 and CD221 and xenograft models, we have found that bortezomib increases the level of CD45 and decreases all other antigens. Bortezomib induces the reduction of IGF-1R (CD221) and syndecan 1 (CD138). This effect was associated with the reduced activation of Ras/MAPK, mTOR/p70S6K and JAK/STAT pathways in response to IGF-1 and IL-6. These results suggest that bortezomib may influence the sensitivity of myeloma cells to soluble growth factors by down-regulation of membrane receptors.
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[330]
TÍTULO / TITLE: - FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3898
AUTORES / AUTHORS: - Xie L; Su X; Zhang L; Yin X; Tang L; Zhang X; Xu Y; Gao Z; Liu K; Zhou M; Gao B; Shen D; Zhang LH; Ji JF; Gavine PR; Zhang J; Kilgour E; Zhang X; Ji Q
INSTITUCIÓN / INSTITUTION: - Innovation Center China, AstraZeneca Global R&D, Zhangjiang Hi-Tech Park, Innovation Center China, AstraZeneca Global R&D, Zhangjiang Hi-Tech Park.
RESUMEN / SUMMARY: - FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer (GC) and the therapeutic potential of AZD4547, a potent and selective ATP competitive receptor tyrosine kinase inhibitor of FGFR1-3, in patients with FGFR2-amplified GC. Array comparative genomic hybridization and FISH were used to identify FGFR2 amplification in GC patient tumor samples. The effects of FGFR2 modulation were investigated in GC cells with FGFR2 amplification and in patient-derived GC xenograft models using two approaches; inhibition with AZD4547 and shRNA knockdown of FGFR2. Amplification of FGFR2 was identified in a subset of Chinese and Caucasian patients with GC. GC cell lines SNU-16 and KATOIII, carrying the amplified FGFR2 gene, were extremely sensitive to AZD4547 in vitro with GI50 values of 3nM and 5nM, respectively. AZD4547 effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules and induced apoptosis in SNU-16 cells. Furthermore, inhibition of FGFR2 signaling by AZD4547 resulted in significant dose-dependent tumor growth inhibition in FGFR2-amplified xenograft (SNU-16) and PDGCX models (SGC083), but not in non-amplified models. ShRNA knockdown of FGFR2 similarly inhibited tumor growth in vitro and in vivo. Finally, compared to monotherapy, we demonstrated enhancement of in vivo antitumor efficacy using AZD4547 in combination with chemotherapeutic agents. FGFR2 pathway activation is required for driving growth and survival of GC carrying FGFR2 gene amplification both in vitro and in vivo. Our data support therapeutic intervention with FGFR inhibitors, such as AZD4547, in patients with GC carrying FGFR2 gene amplification.
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[331]
TÍTULO / TITLE: - Grape seed extract triggers apoptosis in Caco-2 human colon cancer cells through reactive oxygen species and calcium increase: extracellular signal-regulated kinase involvement.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Nutr. 2013 Feb 25:1-13.
●● Enlace al texto completo (gratuito o de pago) 1017/S0007114512006095
AUTORES / AUTHORS: - Dinicola S; Mariggio MA; Morabito C; Guarnieri S; Cucina A; Pasqualato A; D’Anselmi F; Proietti S; Coluccia P; Bizzarri M
INSTITUCIÓN / INSTITUTION: - Department of Clinical and Molecular Medicine, Piazza Sassari 3, La Sapienza University, 00161 Rome, Italy.
RESUMEN / SUMMARY: - Grape seed extract (GSE) from Italia, Palieri and Red Globe cultivars inhibits cell growth and induces apoptosis in Caco-2 human colon cancer cells in a dose-dependent manner. In order to investigate the mechanism(s) supporting the apoptotic process, we analysed reactive oxygen species (ROS) production, intracellular Ca2+ handling and extracellular signal-regulated kinase (ERK) activation. Upon exposure to GSE, ROS and intracellular Ca2+ levels increased in Caco-2 cells, concomitantly with ERK inactivation. As ERK activity is thought to be essential for promoting survival pathways, inhibition of this kinase is likely to play a relevant role in GSE-mediated anticancer effects. Indeed, pretreatment with N-acetyl cysteine, a ROS scavenger, reversed GSE-induced apoptosis, and promoted ERK phosphorylation. This effect was strengthened by ethylene glycol tetraacetic acid-mediated inhibition of extracellular Ca2+ influx. ROS and Ca2+ influx inhibition, in turn, increased ERK phosphorylation, and hence almost entirely suppressed GSE-mediated apoptosis. These data suggested that GSE triggers a previously unrecognised ERK-based mechanism, involving both ROS production and intracellular Ca2+ increase, eventually leading to apoptosis in cancer cells.
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[332]
TÍTULO / TITLE: - Combined inhibition of the phosphoinosityl-3-kinase (PI3Kinase) P110d subunit and mitogen-extracellular activated protein kinase (MEKinase) shows synergistic cytotoxicity against human acute myeloid leukemia progenitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Mar 20. pii: S0145-2126(13)00078-7. doi: 10.1016/j.leukres.2013.03.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.03.003
AUTORES / AUTHORS: - Xing Y; Hogge DE
INSTITUCIÓN / INSTITUTION: - Terry Fox Lab, British Columbia Cancer Agency, Vancouver, BC, Canada. Electronic address: yxing@bccrc.ca.
RESUMEN / SUMMARY: - Treatment of 32 acute myeloid leukemia (AML) blast samples showing activation of the PI3K and RAS/RAF/MEK/ERK pathways with the PI3K p110d isoform and MEKinase selective inhibitors, PCN5603 and U0126 produced dose dependent progenitor kill and inhibition of p-Akt Ser473 and p-Erk Tyr204 expression. Normal marrow or blood progenitors were less sensitive to these inhibitors (median PCN5603 IC50s for AML and normal cells 1.5 and 5.8microM and for U0126 9.6 and 25.8microM, respectively). U0126 synergized with PCN5603 for killing of both AML and normal progenitors. However, the synergy was less for normal than for AML cells and the median IC50 of each drug in the combination 7- to 10-fold higher than for AML cells.
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[333]
TÍTULO / TITLE: - Combination of Celecoxib and Doxorubicin Increases the Growth Inhibition and Apoptosis in Acute Myeloid Leukemia Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.781170
AUTORES / AUTHORS: - Chen C; Xu W; Wang CM
RESUMEN / SUMMARY: - Abstract Cyclooxygenase-2 (COX-2) inhibitors have been shown to enhance antitumor activity of therapeutic agents in a variety of solid tumor cells. However, which has not been well established in hematopoietic tumors, especially in acute myeloid leukemia (AML). This study was designed to investigate the effects of combination of celecoxib, a specific COX-2 inhibitor, and doxorubicin on the cell growth and apoptosis in human leukemia cells. Co-treatment with celecoxib and doxorubicin significantly inhibited the cell growth and induced cell apoptosis in acute leukemia cell line, HL60 and primary AML cells. The effect of growth inhibition was accompanied by down-regulating the expression of cyclinE and cyclin-dependent kinase 2 (CDK2), the key regulators of cell cycle progression, which were associated with arresting cells at G0/G1 phase. The pro-apoptotic effect was accompanied by down-regulating the expression of survivin, an inhibitor protein of apoptosis, which mediated anti-apoptosis in AML cells. These results provided the first evidence that the growth inhibitary and pro-apoptotic effects of celecoxib and doxorubicin on AML cells were synergistic.
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[334]
TÍTULO / TITLE: - Should all BRCA1 mutation carriers with stage I breast cancer receive chemotherapy?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Feb;138(1):273-9. doi: 10.1007/s10549-013-2429-x. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2429-x
AUTORES / AUTHORS: - Narod SA; Metcalfe K; Lynch HT; Ghadirian P; Robidoux A; Tung N; Gaughan E; Kim-Sing C; Olopade OI; Foulkes WD; Robson M; Offit K; Jakubowska A; Byrski T; Huzarski T; Sun P; Lubinski J
INSTITUCIÓN / INSTITUTION: - Women’s College Research Institute, 790 Bay Street, Room 750, Toronto, M5G 1N8, Canada, steven.narod@wchospital.ca.
RESUMEN / SUMMARY: - To estimate the 15-year survival following a diagnosis of stage I breast cancer among women who carry a BRCA1 mutation and to determine predictors of mortality, including the use of chemotherapy. Patients were 379 women with stage I breast cancer for whom a BRCA1 mutation had been identified, in herself or in a close family member. Patients were followed for up to 15 years from the initial diagnosis of breast cancer. Survival rates were estimated for women by age, tumor size (</=1 cm; >1 cm), ER status (+/-), and by chemotherapy (yes/no). 42 women died of breast cancer in the follow-up period (11.2 %). Survival rates were similar for women with cancers of size 0-1.0 cm and size 1.1-2.0 cm. Of the 267 women in the study who used chemotherapy, 21 had died (7.9 %) compared to 21 deaths among 112 women who did not receive chemotherapy (18.8 %; p = 0.002). The 15-year survival was 89.4 % for women who received chemotherapy and was 73.1 % for women who did not receive chemotherapy (p = 0.08; log rank). The adjusted hazard ratio for death following a diagnosis of stage I breast cancer associated with chemotherapy was 0.53 (95 % CI 0.28-1.07; p value 0.06) after adjusting for age of diagnosis, tumor size, and estrogen receptor status. This was statistically significant only among women with ER-negative breast cancers (HR = 0.28; 95 % CI 0.10-0.79; p = 0.02). BRCA1 positive women who are treated for stage I breast cancer with chemotherapy have better survival than those who do not receive chemotherapy. The difference cannot be explained by other prognostic factors. All women with invasive breast cancer and a BRCA1 mutation should be considered to be candidates for chemotherapy.
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[335]
TÍTULO / TITLE: - The Association of Glutathione S-transferase Gene Mutations (including GSTT1 and GSTM1) with the Prognostic Factors and Relapse in Acute Lymphoblastic Leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pediatr Hematol Oncol. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 3109/08880018.2013.773474
AUTORES / AUTHORS: - Zareifar S; Monabati A; Saeed A; Fakhraee F; Cohan N
INSTITUCIÓN / INSTITUTION: - Department of Pediatric Hematology/Oncology, Shiraz University of Medical Sciences , Shiraz , Iran.
RESUMEN / SUMMARY: - Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. It accounts for one fourth of all childhood cancers and approximately 75% of all childhood leukemias. Some prognostic factors determine the outcome of therapy [e.g. age, sex, initial white blood cell count (WBC), etc.]; however, it is believed that other mechanisms such as glutathione S-transferase (GST) gene mutation, the expression of lung resistance protein (LRP), and multidrug resistance-associated protein (MRP) also plays a role in treatment failure. In this study, GST gene mutations including GSTM1 and GSTT1 were evaluated in patients with leukemia. Thirty newly diagnosed ALL patients younger than 15 years of age participated in the present study. Bone marrow aspiration and biopsy were evaluated for immune phenotyping and DNA was extracted for GST genotyping. All data plus sex, age, initial WBC count, central nervous system (CNS) or testicular involvement, immune phenotype, and outcome (relapse or not) were analyzed statistically. Genotyping showed that 46% were double null, 50% were M1 null and 93.3% were T1 null for GST mutations. There was no statistically significant relationship between GSTT1 and GSTM1 mutations, or between double null status, prognostic factors and relapse (P > .05). So, although the results of GST mutations were consistent, it seems that these mutations are not statistically significant.
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[336]
TÍTULO / TITLE: - Effect of histone deacetylase and DNA methyltransferase inhibitors on the expression of the androgen receptor gene in androgen-independent prostate cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 13. doi: 10.3892/or.2013.2344.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2344
AUTORES / AUTHORS: - Fialova B; Smesny Trtkova K; Paskova L; Langova K; Kolar Z
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular Pathology, Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, 775 15 Olomouc, Czech Republic.
RESUMEN / SUMMARY: - Androgen receptor (AR) expression in prostate cancer (CaP) cells varies due to the multiple changes including epigenetic modifications such as DNA methylation and histone deacetylation. DNA methyltransferase and histone deacetylase inhibitors are promising for the treatment of CaP. The aim of our study was to analyze the 5-aza-2’-deoxycytidine (AzadC) and sodium butyrate (NaB) effects on CaP cells with modified AR gene expression. The androgen-independent human prostate cancer cell lines PC3 (lacking a functional AR) and DU145 (strongly limited expression due to methylations in the AR gene) were used. PCR of bisulfite-modified DNA and RT-PCR with bisulfite-sequencing were used for AR gene analysis of DU145 and PC3 cells following their treatment with Aza-dC and/or NaB. Re-acetylated histones around the AR gene were detected by conventional PCR of immunoprecipitated DNA obtained from treated cells. In both cell lines without the AR expression, the combined treatment was followed with significant decrease of cell viability. The co-treatment of DU145 cells caused site-specific demethylation in the AR promoter region followed by gene re-expression and increased acetylation in histones H3 and H4. The co-treatment with Aza-dC and NaB was the most effective in demethylation and re-expression of the AR gene. In the AR gene promoter, the location and density of deme-thylated CpGs indicated the existence of distinct promoter hot spot that could be a target of AR gene inactivation therapy of CaP patients during androgen deprivation.
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[337]
TÍTULO / TITLE: - Induction of apoptosis by low-molecular-weight fucoidan through calcium- and caspase-dependent mitochondrial pathways in MDA-MB-231 breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biosci Biotechnol Biochem. 2013;77(2):235-42. Epub 2013 Feb 7.
AUTORES / AUTHORS: - Zhang Z; Teruya K; Eto H; Shirahata S
INSTITUCIÓN / INSTITUTION: - Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Hakozaki, Fukuoka, Japan.
RESUMEN / SUMMARY: - Fucoidan, a fucose-rich polysaccharide extracted from brown seaweed, has antitumor, anticoagulant, antiviral, anti-inflammatory, and antibacterial activities. Several studies have shown that a fucoidan treatment of cancer cells induced cytotoxicity and apoptosis and inhibited angiogenesis and invasion. We investigated in the present study the effect of low-molecular-weight fucoidan (LMWF) on apoptosis in estrogen receptor-negative MDA-MB-231 human breast cancer cells. The LMWF treatment of MDA-MB-231 cells was associated with the activation of caspases and mitochondrial dysfunction, including dissipation of the mitochondrial membrane potential (DeltaPsim), alteration of Ca(2+) homeostasis, cytochrome c release, and decreased expression of antiapoptotic Bcl-2 family proteins. Understanding the molecular events that mediated LMWF-induced MDA-MB-231 cell death will contribute to a more rational approach to cancer chemotherapy.
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[338]
TÍTULO / TITLE: - The automated monocyte count is independently predictive of overall survival from diagnosis in chronic lymphocytic leukaemia and of survival following first-line chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Mar 19. pii: S0145-2126(13)00074-X. doi: 10.1016/j.leukres.2013.02.020.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.02.020
AUTORES / AUTHORS: - Mazumdar R; Evans P; Culpin R; Bailey J; Allsup D
INSTITUCIÓN / INSTITUTION: - Department of Haematology, Queen’s Centre for Oncology and Haematology, Castle Hill Hospital, Castle Road, Cottingham, East Yorkshire HU16 5JQ, UK.
RESUMEN / SUMMARY: - We conducted an analysis of the effect of monocytosis at diagnosis of CLL on subsequent overall (OS) and treatment-free survival (TFS). Monocyte counts were performed using the Sysmex XE2100 analyser. A monocyte count >0.91x109L-1 at the time of diagnosis was associated with a shortened OS and TFS. Monocytosis at diagnosis was associated with lymphocyte count, deletions of chromosomes 17p and 11q, the extent of IgVH somatic hypermutation and Binet stage. A multivariate analysis model which excluded somatic hypermutation found only monocyte count and age to be independently predictive of OS. The automated monocyte count is predictive of OS and TFS in newly diagnosed CLL.
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[339]
TÍTULO / TITLE: - CASQ1 gene is an unlikely candidate for malignant hyperthermia susceptibility in the North American population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anesthesiology. 2013 Feb;118(2):344-9.
●● Enlace al texto completo (gratuito o de pago) 1097/ALN.0b013e318279f925
AUTORES / AUTHORS: - Kraeva N; Zvaritch E; Frodis W; Sizova O; Kraev A; MacLennan DH; Riazi S
INSTITUCIÓN / INSTITUTION: - Malignant Hyperthermia Investigation Unit, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
RESUMEN / SUMMARY: - BACKGROUND: Malignant hyperthermia (MH, MIM# 145600) is a complex pharmacogenetic disorder that is manifested in predisposed individuals as a potentially lethal reaction to volatile anesthetics and depolarizing muscle relaxants. Studies of CASQ1-null mice have shown that CASQ1, encoding calsequestrin 1, the major Ca2+ binding protein in the lumen of the sarcoplasmic reticulum, is a candidate gene for MH in mice. The aim of this study was to establish whether the CASQ1 gene is associated with MH in the North American population. METHODS: The entire coding region of CASQ1 in 75 unrelated patients diagnosed by caffeine-halothane contracture test as MH susceptible (MHS) was analyzed by DNA sequencing. Subsequently, three groups of unrelated individuals (130 MHS, 100 MH negative, and 192 normal controls) were genotyped for a variant that was identified by sequencing. Levels of CASQ1 expression in the muscle from unrelated MHS and MH negative individuals were estimated by Western blotting. RESULTS: Screening of the entire coding sequence of the CASQ1 gene in 75 MHS patients revealed a single variant c.260T > C (p.Met87Thr) in exon 1. This variant is unlikely to be pathogenic, because its allele frequency in the MHS group was not significantly different from that of controls. There was also no difference in calsequestrin 1 protein levels between muscle samples from MHS and controls, including those carrying the p.Met87Thr variant. CONCLUSIONS: This study revealed a low level of protein coding sequence variability within the human CASQ1 gene, indicating that CASQ1 is not a major MHS locus in the North American population.
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[340]
TÍTULO / TITLE: - Novel ternary vanadium-betaine-peroxido species suppresses H-ras and matrix metalloproteinase-2 expression by increasing reactive oxygen species-mediated apoptosis in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Mar 6. pii: S0304-3835(13)00215-2. doi: 10.1016/j.canlet.2013.02.052.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.052
AUTORES / AUTHORS: - Petanidis S; Kioseoglou E; Hadzopoulou-Cladaras M; Salifoglou A
INSTITUCIÓN / INSTITUTION: - Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
RESUMEN / SUMMARY: - Vanadium is known for its antitumorigenicity. Poised to investigate the impact of well-defined forms of vanadium on processes and specific biomolecules (oncogenes-proteins) involved in cancer cell physiology, a novel ternary V(V)-peroxido-betaine compound was employed in experiments targeting cell viability, apoptosis, reactive oxygen species (ROS) production, H-ras signaling, and matrix metalloproteinase-2 (MMP-2) expression in human breast cancer epithelial and lung adenocarcinoma cells. The results reveal that vanadium imparts a significant decrease in cancer cell viability, reducing H-ras and MMP-2 expression by increasing ROS-mediated apoptosis, distinctly emphasizing the nature, structure and properties of ternary ligands on vanadium anti-tumor activity and its future potential as a metallodrug.
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[341]
TÍTULO / TITLE: - Matrix protein of vesicular stomatitis virus: a potent inhibitor of vascular endothelial growth factor and malignant ascites formation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar;20(3):178-85. doi: 10.1038/cgt.2013.7. Epub 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.7
AUTORES / AUTHORS: - Zhou Y; Wen F; Zhang P; Tang R; Li Q
INSTITUCIÓN / INSTITUTION: - The Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China.
RESUMEN / SUMMARY: - Malignant ascites is common in various types of cancers and is difficult to manage. Vascular endothelial growth factor (VEGF) has a pivotal role in malignant ascites. The matrix protein of vesicular stomatitis virus (VSVMP) has been shown to inhibit host gene expression and induce the apoptosis of cancer cells. The present study was designed to determine whether VSVMP suppresses the formation of ascites in ascites-producing peritoneal carcinomatosis. BALB/c female mice, 6-8 weeks old, bearing peritoneal tumors of H22 or MethA cells received an intraperitoneal administration of 50 mug VSVMP/250 mug liposome complexes, 50 mug empty plasmid/250 mug liposome complexes or 0.9% NaCl solution, respectively, every 2 days for 3 weeks. Administration of VSVMP resulted in a significant inhibition in ascites formation, improvement in health condition and prolonged survival of the treated mice. Decreased peritoneum osmolarity and reduced tumor vascularity coincided with dramatic reductions in the VEGF level in ascites fluid and plasma. Examination of floating tumor cells collected from the peritoneal wash revealed an apparently increased number of apoptotic cells and profound downregulation of VEGF mRNA in the VSVMP-treated mice. Our data indicate for the first time that in BALB/c mice bearing H22 or MethA cell peritoneal tumors, VSVMP may inhibit VEGF production and suppress angiogenesis, consequently abolishing ascites formation.
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[342]
TÍTULO / TITLE: - Susceptibility of hepatoma-derived cells to histone deacetylase inhibitors is associated with ID2 expression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1159-66. doi: 10.3892/ijo.2013.1811. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1811
AUTORES / AUTHORS: - Tsunedomi R; Iizuka N; Harada S; Oka M
INSTITUCIÓN / INSTITUTION: - Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
RESUMEN / SUMMARY: - Downregulation of inhibitor of DNA binding 2 (ID2) is associated with poor prognosis in cases of hepatocellular carcinoma (HCC). Therefore, to search for effective antitumor drugs for the treatment of HCC exhibiting poor prognostic indicators, we used two HCC-derived cell lines (HuH-7 and HLE) to alter ID2 levels. Specifically, ID2 expression was knocked down in HuH-7 cells via transfection with ID2-specific small interfering RNAs and separately ID2 was overexpressed in HLE cells via an ID2 expression plasmid vector. To assess the effect of antitumor drugs, MTS assay was performed. Annexin V staining was used to evaluate apoptosis and real-time RT-PCR was used to measure mRNA levels. ID2 knockdown cells were more susceptible to histone deacethylase (HDAC) inhibitors including sodium butyrate (NaB), sodium 4-phenyl-butyrate, tricostatin A, suberoylanilide hydroxamic acid, MS-275, apicidin and HC-toxin. Conversely, cells that overexpressed ID2 were less susceptible than control cells to HDAC inhibitors. NaB-induced apoptosis was inversely correlated with ID2 expression. Expression of the anti-apoptotic mRNA BCL2 was induced by NaB in control cells, but this induction of BCL2 was inhibited by ID2 knockdown and strengthened by ID2 overexpression. Expression of another anti-apoptotic mRNA, BCL2L1, was decreased by NaB administration and then partially recovered. However, in ID2 knockdown cells, BCL2L1 levels did not recover from NaB-induced suppression. ID2 affected the susceptibility of two HCC-derived cell lines to an HDAC inhibitor by regulating the expression of anti-apoptotic genes. Therefore, HDAC inhibitors may be effective for the treatment of HCC for which the prognosis is poor based on ID2 downregulation and ID2 could serve as a marker that is predictive of the clinical response to HDAC inhibitors.
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[343]
TÍTULO / TITLE: - Looking deeper into the tumour cell genome for a better diagnosis, a better understanding of cell biology, a better prognostication and finally a better treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Ophthalmol. 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1136/bjophthalmol-2012-302910
AUTORES / AUTHORS: - Desjardins L
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[344]
TÍTULO / TITLE: - Multifunctional Carboxymethyl Cellulose-Based Magnetic Nanovector as a Theragnostic System for Folate Receptor Targeted Chemotherapy, Imaging, and Hyperthermia against Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Langmuir. 2013 Mar 12;29(10):3453-66. doi: 10.1021/la305048m. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1021/la305048m
AUTORES / AUTHORS: - Sivakumar B; Aswathy RG; Nagaoka Y; Suzuki M; Fukuda T; Yoshida Y; Maekawa T; Sakthikumar DN
INSTITUCIÓN / INSTITUTION: - Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University , Kawagoe, Japan.
RESUMEN / SUMMARY: - A multifunctional biocompatible nanovector based on magnetic nanoparticle and carboxymethyl cellulose (CMC) was developed. The nanoparticles have been characterized using TEM, SEM, DLS, FT-IR spectra, VSM, and TGA studies. We found that the synthesized carboxymethyl cellulose magnetic nanoparticles (CMC MNPs) were spherical in shape with an average size of 150 nm having low aggregation and superparamagnetic properties. We found that the folate-tagged CMC MNPs were delivered to cancer cells by a folate-receptor-mediated endocytosis mechanism. 5-FU was encapsulated as a model drug for delivering cytotoxicity, and we could demonstrate the sustained release of 5-FU. It was also observed that the FITC-labeled CMC MNPs could effectively enter cells, and the fate of nanoparticles was tracked with Lysotracker. The CMC MNPs could induce significant cell death when an alternating magnetic field was applied. These results indicate that the multifunctional CMC MNPs possess a high drug loading efficiency and high biocompatibility and with low cell cytotoxicity and can be considered to be promising candidates for CMC-based targeted drug delivery, cellular imaging, and magnetic hyperthermia (MHT).
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[345]
TÍTULO / TITLE: - The unfolded protein response regulator GRP78 is a novel predictive biomarker in colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Mar 2. doi: 10.1002/ijc.28137.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28137
AUTORES / AUTHORS: - Thornton M; Aslam MA; Tweedle EM; Ang C; Campbell F; Jackson R; Costello E; Rooney PS; Vlatkovic N; Boyd MT
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, L69 3GA, UK; Departments of Surgery, Pathology of the Royal Liverpool University Hospital, Prescott St, Liverpool L7 8XP, UK.
RESUMEN / SUMMARY: - Adjuvant fluoropyrimidine-based (5-FU) chemotherapy is a mainstay of treatment for colorectal cancer (CRC), but only provides benefit for a sub-set of patients. To improve stratification we examined (for the first time in CRC), whether analysis of GRP78 expression provides a predictive biomarker and performed functional studies to examine the role of GRP78 in sensitivity to 5-FU. 396 CRC patient samples were collected in a prospective uniform manner and GRP78 expression was determined by immunohistochemistry on tissue microarrays using a well-validated antibody. Expression was correlated with clinicopathological parameters and survival. The role of GRP78 in 5-FU sensitivity was examined in CRC cells using siRNA, drug inhibition and flow cytometry. GRP78 expression was significantly elevated in cancer tissue (P<.0001), and correlated with depth of invasion (P=.029) and stage (P=.032). Increased overall 5-year survival was associated with high GRP78 expression (P=.036). Patients with stage II cancers treated by surgery alone, with high GRP78 also had improved survival (71% v 50%; P=.032). Stage III patients with high GRP78 showed significant benefit from adjuvant chemotherapy (52% v 28%; P=.026), whereas patients with low GRP78 failed to benefit (28% v 32%; P=.805). Low GRP78 was an independent prognostic indicator of reduced overall 5-year survival (P=.004; HR=1.551; 95%CI 1.155-2.082). In vitro, inhibition of GRP78 reduces apoptosis in response to 5-FU in p53 wild-type cells. GRP78 expression may provide a simple additional risk stratification to inform the adjuvant treatment of CRC and future studies should combine analysis with determination of p53 status. © 2013 Wiley Periodicals, Inc.
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[346]
TÍTULO / TITLE: - GM-CSF-DFF40: a novel humanized immunotoxin induces apoptosis in acute myeloid leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0840-8
AUTORES / AUTHORS: - Mathew M; Zaineb KC; Verma RS
INSTITUCIÓN / INSTITUTION: - Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, Tamil Nadu, India.
RESUMEN / SUMMARY: - DNA fragmentation factor 40 (DFF40) is an endonuclease that acts downstream in the apoptotic cascade. The objective of this study was to generate a novel humanized chimeric protein with human DFF40 fused with GM-CSF for targeting acute myeloid leukemia (AML) cells. cDNA cloning of human DFF40 and GM-CSF was done and the chimeric gene GM-CSF-DFF40 was generated by overlap extension PCR. The fusion protein was expressed in E.coli, purified, refolded and characterized. In vitro cytotoxicity was evaluated on various AML cell lines. Treated cell lines were screened for various morphological and biochemical changes that are characteristic of apoptosis, by different assays like annexin V-FITC staining, TUNEL assay, JC-1 staining and immunocytochemistry of pro-apoptotic proteins and caspases. Cell cycle analysis of treated cells was done to quantify the percentage of apoptotic cells. The chimeric protein was found to be cytotoxic to AML cells in a dose and time dependent manner. Morphological changes such as formation of apoptotic bodies were revealed by microscopic examination of treated cells after staining. Immunocytochemical staining demonstrated biochemical changes such as changes in mitochondrial membrane potential, mitochondrial co-localization of Bax, cytochrome c release, presence of activated caspase-3 and DNA fragmentation. FACS analysis proved the presence of apoptotic cells following treatment. The chimeric protein GM-CSF-DFF40 was found to mediate targeted killing of AML cells by inducing apoptosis. Thus, this chimeric construct can act as a prospective candidate for targeted therapy of AML and other malignancies where GM-CSF receptor expression is upregulated.
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[347]
TÍTULO / TITLE: - Parguerenes: Marine red alga bromoditerpenes as inhibitors of P-glycoprotein (ABCB1) in multidrug resistant human cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Pharmacol. 2013 May 1;85(9):1257-68. doi: 10.1016/j.bcp.2013.02.005. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bcp.2013.02.005
AUTORES / AUTHORS: - Huang XC; Sun YL; Salim AA; Chen ZS; Capon RJ
INSTITUCIÓN / INSTITUTION: - Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.
RESUMEN / SUMMARY: - High intrinsic or acquired expression of membrane spanning, adenosine triphosphate binding cassette (ABC) transporter proteins, such as P-glycoprotein (P-gp), in cancers represents a major impediment to chemotherapy, with accelerated drug efflux leading to multi-drug resistance (MDR). Although ABC transporter inhibitors offer the prospect of reversing the MDR phenotype, no inhibitors have advanced to the clinic. We employed a range of intracellular fluorescence and radio-ligand accumulation and efflux assays, together with cytotoxicity and MDR reversal assays, as well as flow cytometry, fluorescence microscopy and radioimmunoprecipitation, to discover and evaluate new P-gp inhibitors from a unique library of southern Australian and Antarctic marine natural products. This study successfully characterized two rare bromoditerpenes, parguerenes I and II, sourced from a southern Australian collection of the red alga Laurencia filiformis, as P-gp inhibitors. We determined that the parguerenes were non-cytotoxic, dose-dependent inhibitors of P-gp mediated drug efflux, that modify the extracellular antibody binding epitope of P-gp in a manner that differs markedly from that of the known inhibitors verapamil and cyclosporine A. We confirmed that parguerenes were capable of reversing P-gp mediated vinblastine, doxorubicin and paclitaxel MDR, that inhibitory properties span both P-gp and multidrug resistant protein 1 (MRP1), but do not extend to breast cancer resistance protein (BCRP), and that parguerene II is superior (more potent) to verapamil. Our investigations validate the proposition that marine natural products can deliver new ABC transporter inhibitor scaffolds, with structure characteristics fundamentally different from existing inhibitor classes.
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[348]
TÍTULO / TITLE: - COX-2 overexpression Induced by gene transfer reduces sensitivity of TE13 esophageal carcinoma cells to 5-fluorouracil and cisplatin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):537-42.
AUTORES / AUTHORS: - Okamura H; Fujiwara H; Umehara S; Okamura S; Todo M; Furutani A; Yoneda M; Shiozaki A; Komatsu S; Kubota T; Ichikawa D; Okamoto K; Ochiai T; Sakakura C; Takahashi Y; Yoshimoto T; Otsuji E
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine. 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. hfuji@koto.kpu-m.ac.jp
RESUMEN / SUMMARY: - Previous clinicopathological studies demonstrated that overexpression of cyclooxygenase-2 (COX-2) is associated with a poor treatment response of esophageal carcinoma. The aim of this study was to elucidate the role of COX-2 overexpression in the chemosensitivity of esophageal carcinoma cells. TE13 human esophageal squamous cell carcinoma cells were transfected with a COX-2 constitutive expression vector, and stable transfectants overexpressing COX-2 were established. COX-2 overexpression in COX-2 transfectants was confirmed with western blotting and prostaglandin-E(2) (PGE(2)) assay. Chemosensitivity testing revealed that sensitivity of COX-2 transfectants to 5-fluorouracil and cisplatin was significantly lower than in control vector-only transfectants, and that sensitivity of COX-2 transfectants was restored by the transfection of COX-2-specific siRNA. In addition, expression of antiapoptotic B-cell lymphoma-extra large (BCL-xL) and myeloid cell leukaemia-1 (MCL-1) was increased in COX-2 transfectants. These results indicate that COX-2 overexpression may reduce the chemosensitivity of esophageal carcinoma cells through up-regulation of the expression of antiapoptotic BCL-2 family proteins.
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[349]
TÍTULO / TITLE: - Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIP(L) and IAP proteins.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0808-8
AUTORES / AUTHORS: - Yang L; Wang Q; Li D; Zhou Y; Zheng X; Sun H; Yan J; Zhang L; Lin Y; Wang X
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular and Translational Medicine, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
RESUMEN / SUMMARY: - Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with other agents is a promising strategy to overcome TRAIL resistance in malignant cells. Wogonin, a flavonoid originated from Scutellaria baicalensis Georgi, has been shown to enhance TRAIL-induced apoptosis in malignant cells in in vitro studies. However, whether wogonin enhances TRAIL’s antitumor activity in vivo has never been studied. In this study, the effect of combination of TRAIL and wogonin was tested in a non-small-cell lung cancer xenografted tumor model in nude mice. Consistent with the in vitro study showing that wogonin sensitized A549 cells to TRAIL-induced apoptosis, wogonin greatly enhanced TRAIL-induced suppression of tumor growth, accompanied with increased apoptosis in tumor tissues as determined by TUNEL assay. The expression levels of antiapoptotic proteins including long form of cellular FLICE-like inhibitory protein (cFLIP(L)), X-linked inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis protein 1 and 2 (cIAP-1 and cIAP-2) were markedly reduced in both cultured cells and xenografted tumor tissues after co-treatment with wogonin and TRAIL. The down-regulation of these antiapoptotic proteins was likely mediated by proteasomal degradation that involved intracellular reactive oxygen species (ROS), because wogonin robustly induced ROS accumulation and ROS scavengers butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) and the proteasome inhibitor MG132 restored the expression of these antiapoptotic proteins in cells co-treated with wogonin and TRAIL. These results show for the first time that wogonin enhances TRAIL’s antitumor activity in vivo, suggesting this strategy has an application potential for clinical anticancer therapy.
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[350]
TÍTULO / TITLE: - Oleanane-type triterpenoid saponins from the roots of Pulsatilla koreana and their apoptosis-inducing effects on HL-60 human promyelocytic leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Pharm Res. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s12272-013-0042-5
AUTORES / AUTHORS: - Li W; Ding Y; Sun YN; Yan XT; Yang SY; Choi CW; Kim EJ; Kang HK; Kim YH
INSTITUCIÓN / INSTITUTION: - College of Pharmacy, Chungnam National University, Daejeon, 305-764, Korea.
RESUMEN / SUMMARY: - Twenty-four oleanane-type triterpenoid saponins were isolated from a methanol extract of the Pulsatilla koreana roots. Their structures were elucidated by comparing spectroscopic data to published values. Among them, compounds 8-12 and 20-24 significantly diminished the proliferation of HL-60 human promyelocytic leukemia cells with IC50 values from 0.3 to 4.2 muM, whereas compounds 7 and 19 showed moderate cytotoxic activity. Furthermore, apoptotic characteristics such as chromatin condensation and increase in the population of sub-G1 hypodiploid cells were observed after the HL-60 cells were treated with these compounds.
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[351]
TÍTULO / TITLE: - Tocotrienols promote apoptosis in human breast cancer cells by inducing poly(ADP-ribose) polymerase cleavage and inhibiting nuclear factor kappa-B activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Prolif. 2013 Apr;46(2):203-13. doi: 10.1111/cpr.12014.
●● Enlace al texto completo (gratuito o de pago) 1111/cpr.12014
AUTORES / AUTHORS: - Loganathan R; Selvaduray KR; Nesaretnam K; Radhakrishnan AK
INSTITUCIÓN / INSTITUTION: - Malaysian Palm Oil Board, Selangor, 43000, Malaysia; Pathology Division, Faculty of Medicine and Health, International Medical University, Kuala Lumpur, 57000, Malaysia.
RESUMEN / SUMMARY: - OBJECTIVES: Tocotrienols and tocopherols are members of the vitamin E family, with similar structures; however, only tocotrienols have been reported to achieve potent anti-cancer effects. The study described here has evaluated anti-cancer activity of vitamin E to elucidate mechanisms of cell death, using human breast cancer cells. MATERIALS AND METHODS: Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (alpha-tocopherol, alpha-, delta- and gamma-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-kappaB were determined using commercial ELISA kits. RESULTS: Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-kappaB), which in turn can increase sensitivity of cancer cells to apoptosis. CONCLUSION: Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-kappaB inhibition in the two human breast cancer cell lines.
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[352]
TÍTULO / TITLE: - Combination of bendamustine and entinostat synergistically inhibits proliferation of multiple myeloma cells via induction of apoptosis and DNA damage response.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 28. pii: S0304-3835(13)00172-9. doi: 10.1016/j.canlet.2013.02.046.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.046
AUTORES / AUTHORS: - Cai B; Lyu H; Huang J; Wang S; Lee CK; Gao C; Liu B
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Chinese PLA General Hospital, Beijing, China; Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
RESUMEN / SUMMARY: - Bendamustine, a hybrid molecule of purine analog and alkylator, induces cell death by activation of apoptosis, DNA damage response, and mitotic catastrophe. Entinostat, a selective class I inhibitor of histone deacetylase (HDAC), exerts anti-tumor activity in various cancer types, including multiple myeloma (MM). We sought to determine the combinatorial effects of bendamustine and entinostat on MM cells. Cell growth assays showed that bendamustine or entinostat inhibited proliferation in a dose-dependent manner, and their combinations synergistically induced growth inhibition in all MM cells tested. An apoptotic-ELISA and western blot assays on PARP cleavage and caspase-8 and caspase-3 revealed that bendamustine in combination with entinostat exhibited a much more potent activity than either agent alone to promote the MM cells undergoing apoptosis in a dose-dependent manner. Flow cytometric analysis found that entinostat exhibited distinct effects on cell cycle progression in different lines and bendamustine mainly arrested the cells at S phase, whereas their combinations dramatically blocked the S cells entering G2/M phase. Furthermore, studies on DNA damage response indicated that phospho-histone H2A.X (P-H2A.X), a hall marker of DNA double strand break, along with phosphorylated CHK2 (P-CHK2) was significantly enhanced by the combinations of bendamustine and entinostat as compared to either agent alone. These molecular changes were correlated with the increases in mitotic catastrophe. Collectively, our data demonstrate that bendamustine in combination with entinostat exhibit potent anti-proliferative/anti-survival activity in MM cells via induction of apoptosis and DNA damage response. Regimens consisting of bendamustine and/or entinostat may represent novel therapeutic strategies against MM.
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[353]
TÍTULO / TITLE: - The anti-proliferative and pro-apoptotic effects of the trans9,trans11 conjugated linoleic acid isomer on MCF-7 breast cancer cells are associated with LXR activation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prostaglandins Leukot Essent Fatty Acids. 2013 Jan 31. pii: S0952-3278(13)00005-7. doi: 10.1016/j.plefa.2012.12.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.plefa.2012.12.006
AUTORES / AUTHORS: - El Roz A; Bard JM; Huvelin JM; Nazih H
INSTITUCIÓN / INSTITUTION: - EA2160, “Mer, Molecules, Sante”, IUML: Institut Universitaire Mer et Littoral FR3473 CNRS, Faculty of Pharmacy, Nantes, France.
RESUMEN / SUMMARY: - Conjugated linoleic acids (CLA), naturally found in dairy products and ruminant meat, are positional and geometric isomers (trans: t or cis: c) of linoleic acid, and have been widely reported to possess anti-tumoral activity against breast cancer both in vitro and in vivo. CLA isomer t9,t11 was recently proposed as an agonist of the transcriptional factor LXR, which is known for inducing genes implicated in cholesterol efflux. In this study, the growth inhibitory effect of three CLA isomers (c9,t11-CLA, t9,t11-CLA and t10,c12-CLA) was investigated on MCF-7 breast cancer cells, as well as their effect on LXR target genes. Our results revealed that t9,t11-CLA was the most efficient isomer by decreasing MCF-7 proliferation, inhibiting migration, and inducing apoptosis after 24h of treatment. t9,t11-CLA treatment led to an increase in the mRNA levels of LXR target genes involved in cholesterol efflux (ABCG1 and ARL7), as well as an increase of HMG-CoA-reductase which is the rate-limiting step of cholesterol biosynthesis. Interestingly, confocal microscopy analysis showed that t9,t11-CLA treatment remarkably reduced the intracellular and membrane-associated cholesterol levels. LXR activation through t9,t11-CLA isomer could lead to cholesterol cell deprivation by stimulating its efflux, which results in the inhibition of cell proliferation and stimulation of apoptosis.
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[354]
TÍTULO / TITLE: - Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 22. pii: S0006-291X(13)00443-9. doi: 10.1016/j.bbrc.2013.03.028.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.03.028
AUTORES / AUTHORS: - Felipe KB; Benites J; Glorieux C; Sid B; Valenzuela M; Kviecinski MR; Pedrosa RC; Valderrama JA; Leveque P; Gallez B; Verrax J; Buc Calderon P
INSTITUCIÓN / INSTITUTION: - Laboratorio de Bioquimica Experimental, Departamento de Bioquimica, Universidade Federal de Santa Catarina, Florianopolis, Brasil.
RESUMEN / SUMMARY: - Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 and Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.
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[355]
TÍTULO / TITLE: - Houttuynia cordata Thunb extract modulates G0/G1 arrest and Fas/CD95-mediated death receptor apoptotic cell death in human lung cancer A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biomed Sci. 2013 Mar 19;20:18. doi: 10.1186/1423-0127-20-18.
●● Enlace al texto completo (gratuito o de pago) 1186/1423-0127-20-18
AUTORES / AUTHORS: - Chen YF; Yang JS; Chang WS; Tsai SC; Peng SF; Zhou YR
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, College of Medicine, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan. yfchen@mail.cmu.edu.tw.
RESUMEN / SUMMARY: - BACKGROUND: Houttuynia cordata Thunb (HCT) is commonly used in Taiwan and other Asian countries as an anti-inflammatory, antibacterial and antiviral herbal medicine. In this study, we investigated the anti-human lung cancer activity and growth inhibition mechanisms of HCT in human lung cancer A549 cells. RESULTS: In order to investigate effects of HCT on A549 cells, MTT assay was used to evaluate cell viability. Flow cytometry was employed for cell cycle analysis, DAPI staining, and the Comet assay was used for DNA fragmentation and DNA condensation. Western blot analysis was used to analyze cell cycle and apoptotic related protein levels. HCT induced morphological changes including cell shrinkage and rounding. HCT increased the G0/G1 and Sub-G1 cell (apoptosis) populations and HCT increased DNA fragmentation and DNA condensation as revealed by DAPI staining and the Comet assay. HCT induced activation of caspase-8 and caspase-3. Fas/CD95 protein levels were increased in HCT-treated A549 cells. The G0/G1 phase and apoptotic related protein levels of cyclin D1, cyclin A, CDK 4 and CDK 2 were decreased, and p27, caspase-8 and caspase-3 were increased in A549 cells after HCT treatment. CONCLUSIONS: The results demonstrated that HCT-induced G0/G1 phase arrest and Fas/CD95-dependent apoptotic cell death in A549 cells.
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[356]
TÍTULO / TITLE: - Cell-free microRNAs as diagnostic, prognostic, and predictive biomarkers for lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genes Chromosomes Cancer. 2013 Apr;52(4):356-69. doi: 10.1002/gcc.22032. Epub 2012 Dec 10.
●● Enlace al texto completo (gratuito o de pago) 1002/gcc.22032
AUTORES / AUTHORS: - Zandberga E; Kozirovskis V; Abols A; Andrejeva D; Purkalne G; Line A
INSTITUCIÓN / INSTITUTION: - Latvian Biomedical Research and Study Centre, Riga, Latvia.
RESUMEN / SUMMARY: - Lung cancer is the most common cancer worldwide, accounting for over 1.37 million deaths annually. The clinical outcome and management of lung cancer patients could be substantially improved by the implementation of non-invasive biomarker assays for the early detection, prognosis as well as prediction and monitoring of treatment response. MicroRNAs (miRNAs) have been implicated in the regulation of virtually all signaling circuits within a cell and their dysregulation has been shown to play an essential role in the development and progression of cancer. Recently, miRNAs were found to be released into the circulation and to exist there in a remarkably stable form. Furthermore, various cancers were shown to leave specific miRNA fingerprints in the blood of patients suggesting that cell-free miRNAs could serve as non-invasive biomarkers for the detection or monitoring of cancer and putative therapeutic targets. Since that, a considerable effort has been devoted to decode the information carried by circulating miRNAs. In the current review, we give an insight into the mechanisms of miRNA release into the bloodstream, their putative functional significance and systematically review the studies focused on the identification of cell-free miRNAs with the diagnostic, prognostic, and predictive significance in lung cancer and discuss their potential clinical utility.
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[357]
TÍTULO / TITLE: - Clinical and Marketed Proteasome Inhibitors for Cancer Treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Med Chem. 2013 Mar 15.
AUTORES / AUTHORS: - Zhang J; Wu P; Hu Y
INSTITUCIÓN / INSTITUTION: - ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. huyz@zju.edu.cn.
RESUMEN / SUMMARY: - The ubiquitin-proteasome pathway (UPP), which influences essential cellular functions including cell growth, differentiation, apoptosis, signal transduction, antigen processing and inflammatory responses, has been considered as one of the most important cellular protein degradation approaches. Proteasome functions as a gatekeeper, which controls the execution of protein degradation and plays a critical role in the ubiquitin-proteasome pathway. Recent studies have clarified relationships between proteasome and various diseases involving cancer, thus providing a possible strategy for cancer treatment with proteasome inhibitors. Small molecular inhibitors of varied structures and potency have been discovered, among which, some promising candidates are currently under clinical trials with exciting drugs bortezomib and carfilzomib have already been applied for clinical usage. Herein, we review the development histories of drugs and drug candidates targeting the 20S proteasome, key medicinal actions with proteasome catalytic sites, structure-activity relationships (SARs) of various proteasome inhibitors and clinical trials completed or underway.
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[358]
TÍTULO / TITLE: - Pharmacogenomics of breast cancer therapy: An update.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacol Ther. 2013 Mar 13. pii: S0163-7258(13)00057-0. doi: 10.1016/j.pharmthera.2013.03.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pharmthera.2013.03.001
AUTORES / AUTHORS: - Westbrook K; Stearns V
INSTITUCIÓN / INSTITUTION: - Duke University Medical Center, Duke Cancer Institute, Breast Cancer Program, DUMC Box 3893, 10 Searle Dr., Sealy Mudd Bldg. Room 449A, Durham, NC 27710, United States. Electronic address: Kelly.mitchell@duke.edu.
RESUMEN / SUMMARY: - Clinical and histopathologic characteristics of breast cancer have long played an important role in treatment decision-making. Well-recognized prognostic factors include tumor size, node status, presence or absence of metastases, tumor grade, and hormone receptor expression. High tumor grade, presence of hormone receptors, and HER2-positivity are a few predictive markers of response to chemotherapy, endocrine manipulations, and anti-HER2 agents, respectively. However, there is much heterogeneity of outcomes in patients with similar clinical and pathologic features despite equivalent treatment regimens. Some of the differences in response to specific therapies can be attributed to somatic tumor characteristics, such as degree of estrogen receptor expression and HER2 status. In recent years, there has been great interest in evaluating the role that pharmacogenetics/pharmacogenomics, or variations in germline DNA, play in alteration of drug metabolism and activity, thus leading to disparate outcomes among patients with similar tumor characteristics. The utility of these variations in treatment decision-making remains debated. Here we review the data available to date on genomic variants that may influence response to drugs commonly used to treat breast cancer. While none of the variants reported to date have demonstrated clinical utility, ongoing prospective studies and increasing understanding of pharmacogenetics will allow us to better predict risk of toxicity or likelihood of response to specific treatments and to provide a more personalized therapy.
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[359]
TÍTULO / TITLE: - Serum HER-2 predicts response and resistance to trastuzumab treatment in breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Chem. Acceso gratuito al texto completo a partir de 1 año de la fecha de publicación.
●● Enlace a la Editora de la Revista journals.uchicago.edu/
●● Cita: Clinical Infectious Diseases: <> Lab Med. 2013 Feb 18:1-10. doi: 10.1515/cclm-2012-0558.
●● Enlace al texto completo (gratuito o de pago) 1515/cclm-2012-0558
AUTORES / AUTHORS: - Petersen ER; Sorensen PD; Jakobsen EH; Madsen JS; Brandslund I
RESUMEN / SUMMARY: - Abstract Background: Serum HER2 (S-HER2) was approved in 2003 by the US Food and Drug Administration (FDA) for monitoring trastuzumab treatment in tissue HER2 positive breast cancer patients. Information of the value of S-HER2 is scarce. We hypothesised that S-HER2 would reflect the clinical effect of trastuzumab. Methods: We followed 48 patients eligible for trastuzumab treatment for up to 6 years or until death. S-HER2 was measured on an ADVIA Centaur System and S-Trastuzumab was measured by an in-house developed fluorescent enzyme immunoassay system on the ImmunoCap 100. Results: A decrease in S-HER2 of >/=20% was correlated to no progression in the disease in 20 out of 21 clinical courses (p<0.0001). An increase in S-HER2 of >/=20% was correlated to progression in the disease in 40 out of 44 clinical courses (p<0.0001). Patients with no recurrence after trastuzumab treatment (n=18) had a median S-HER2 concentration of 10.5 mug/L, whereas patients alive with recurrence (n=13) had a median S-HER2 of 20.1 mug/L (p=0.002). Patients who died prompted by recurrence (n=17) had a median S-HER2 of 232.4 mug/L at latest measurement before death (p=<0.0001) compared to patients without recurrence. In two patients with S-HER2 values above 1000 mug/L the concentrations of S-trastuzumab were measured below the target trough concentration in serum of 10 mg/L. Conclusions: Decreasing values of S-HER2 predicts response to treatment whereas increasing levels predict resistance. S-HER2 above 1000 mug/L warns that standard doses of trastuzumab may be insufficient as reflected by low concentrations of S-trastuzumab.
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[360]
TÍTULO / TITLE: - Dominant Negative Epidermal Growth Factor Receptor Inhibits Growth of Human Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1399
AUTORES / AUTHORS: - Liao G; Wang Z; Zhang N; Dong P
INSTITUCIÓN / INSTITUTION: - 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China .
RESUMEN / SUMMARY: - Abstract Epidermal growth factor receptor (EGFR) promotes proliferation of cancer cells. Dominant negative EGFR (DNEGFR) can block EGFR signal pathway by competing with endogenous EGFR for ligands. However, whether EGFR is overexpressed in gastric cancer and whether DNEGFR contributes to the inhibition of gastric cancer growth are not known. In this study, with the methods of immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytoflowmetry, Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling assay and western blotting; we demonstrate that EGFR is expressed in 29 of 60 of human gastric cancer. In addition, DNEGFR induces G0/G1 arrest by decreasing expression of phosphorylated retinoblastoma protein, phosphorylated GSK-3beta, cyclin D1, and by increasing expression of p21 and p27 in human gastric cancer cell lines SGC-7901 and NCI-N87. Finally, DNEGFR induces apoptosis in these cells. Our results indicate that DNFGFR may provide promising treatment strategy for a subgroup of human gastric cancers that express EGFR.
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[361]
TÍTULO / TITLE: - Anti-tumor action of trichosanthin, a type 1 ribosome-inactivating protein, employed in traditional Chinese medicine: a mini review.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Feb 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2096-y
AUTORES / AUTHORS: - Sha O; Niu J; Ng TB; Cho EY; Fu X; Jiang W
INSTITUCIÓN / INSTITUTION: - School of Medicine, Shenzhen University, Shenzhen, China, shaou@szu.edu.cn.
RESUMEN / SUMMARY: - Trichosanthin (TCS) as a midterm abortifacient medicine has been used clinically in traditional Chinese medicine for centuries. Additionally, TCS manifests a host of pharmacological properties, for instance, anti-HIV and anti-tumor activities. TCS has been reported to inhibit cell growth of a diversity of cancers, including cervical cancer, choriocarcinoma, and leukemia/lymphoma, etc. This article purported to review the various anti-tumor activities of TCS and the mechanism of apoptosis it induced in these tumor cells. These research progresses provide an insight into cancer research and treatment as well as disclose new pharmacological properties of the ancient but popular Chinese medicine.
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[362]
TÍTULO / TITLE: - Induction of apoptosis and suppression of ERCC1 expression by the potent amonafide analogue 8-c in human colorectal carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Apr;24(4):355-65. doi: 10.1097/CAD.0b013e32835df8b5.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835df8b5
AUTORES / AUTHORS: - Wang Z; Liang X; Cheng Z; Xu Y; Yin P; Zhu H; Li Q; Qian X; Liu J
INSTITUCIÓN / INSTITUTION: - aState Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology bDepartment of Medical Oncology, Putuo Hospital and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
RESUMEN / SUMMARY: - Previous studies have reported that 8-c [6-(2-(2-(dimethylamino)ethylamino)ethylamino)-2-octyl-1H-benzo[de]isoquinoline-1 ,3(2H)-dione], a novel amonafide analogue, was generated as a new anticancer candidate. However, little is known about its activity in chemoresistant cells. In this study, the antitumor effects of 8-c on the multi-drug-resistant human colorectal carcinoma cancer cell lines HCT-116/L-OHP and HCT-8/VCR have been investigated for the first time. 8-c showed similar concentration-dependent inhibitory activities against multi-drug-resistant cells and corresponding parental cell lines by the MTT assay after 48 h of treatment. 8-c treatment resulted in the induction of apoptosis, as evidenced by fluorescent staining analysis, comet assay data, and the increase in the number of apoptotic cells as detected by flow cytometry. Western blot, qPCR, and siRNA techniques were used to elucidate the molecular mechanism. Our study suggested that the apoptotic effect of 8-c can be attributed to the upregulation of p53, caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) and the downregulation of Bcl-2. Furthermore, ERCC1 is essential for nucleotide excision repair. ERCC1 expression was correlated with sensitivity to chemotherapy in various colon cancer cell lines. It is intriguing that decreases in ERCC1 protein and mRNA levels were also observed in the HCT-116/L-OHP and HCT-8/VCR cells after exposure to 8-c. Further transient transfection of multi-drug-resistant cells with ERCC1 siRNA enhanced 8-c-induced cytotoxicity. In contrast, epidermal growth factor-induced increase in ERCC1 protein levels was shown to rescue cell viability upon 8-c treatment. These findings suggest that 8-c has a strong potential to be developed as a new antitumor agent for the treatment of multi-drug-resistant colon cancer cells, and is worthy of further studies.
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[363]
TÍTULO / TITLE: - Colon cancer mutation: prognosis/prediction-letter.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 1;19(5):1300. doi: 10.1158/1078-0432.CCR-12-3765. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-3765
AUTORES / AUTHORS: - Zaanan A; Bonnetain F; Sinicrope FA; Laurent-Puig P; Taieb J
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Department of Gastroenterology and Digestive Oncology, Hopital Europeen Georges Pompidou, AP-HP; Paris Sorbonne Cite, Universite Paris Descartes; UMR-S775, INSERM, Paris; Methodology and Quality of Life in Oncology (EA 3181) and Quality of Life and Cancer Clinical Research Platform, CHU Besancon, France; and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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[364]
TÍTULO / TITLE: - Colon cancer mutation: prognosis/prediction-response.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 1;19(5):1301. doi: 10.1158/1078-0432.CCR-13-0020. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-13-0020
AUTORES / AUTHORS: - Gavin PG; Paik S; Yothers G; Pogue-Geile KL
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Pathology Laboratory, National Surgical Adjuvant Breast and Bowel Project (NSABP); and NSABP Biostatistical Center and University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
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[365]
TÍTULO / TITLE: - A Review of NCI’s Extramural Grant Portfolio: Identifying Opportunities for Future Research in Genes and Environment in Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):501-7. doi: 10.1158/1055-9965.EPI-13-0156. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-13-0156
AUTORES / AUTHORS: - Ghazarian AA; Simonds NI; Bennett K; Pimentel CB; Ellison GL; Gillanders EM; Schully SD; Mechanic LE
INSTITUCIÓN / INSTITUTION: - Corresponding Author: Leah E. Mechanic, Host Susceptibility Factors Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, 6130 Executive Blvd, Room 5126, Bethesda, MD 20892. mechanil@mail.nih.gov.
RESUMEN / SUMMARY: - BACKGROUND: Genetic and environmental factors jointly influence cancer risk. The NIH has made the study of gene-environment (GxE) interactions a research priority since the year 2000. METHODS: To assess the current status of GxE research in cancer, we analyzed the extramural grant portfolio of the National Cancer Institute (NCI) from Fiscal Years 2007 to 2009. Publications attributed to selected grants were also evaluated. RESULTS: From the 1,106 research grants identified in our portfolio analysis, a random sample of 450 grants (40%) was selected for data abstraction; of these, 147 (33%) were considered relevant. The most common cancer type was breast (20%, n = 29), followed by lymphoproliferative (10%, n = 14), colorectal (9%, n = 13), melanoma/other skin (9%, n = 13), and lung/upper aerodigestive tract (8%, n = 12) cancers. The majority of grants were studies of candidate genes (68%, n = 100) compared with genome-wide association studies (GWAS) (8%, n = 12). Approximately one-third studied environmental exposures categorized as energy balance (37%, n = 54) or drugs/treatment (29%, n = 43). From the 147 relevant grants, 108 publications classified as GxE or pharmacogenomic were identified. These publications were linked to 37 of the 147 grant applications (25%). CONCLUSION: The findings from our portfolio analysis suggest that GxE studies are concentrated in specific areas. There is room for investments in other aspects of GxE research, including, but not limited to developing alternative approaches to exposure assessment, broadening the spectrum of cancer types investigated, and conducting GxE within GWAS. Impact: This portfolio analysis provides a cross-sectional review of NCI support for GxE research in cancer. Cancer Epidemiol Biomarkers Prev; 22(4); 501-7. ©2013 AACR.
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[366]
TÍTULO / TITLE: - Role of Dynamic MRI and Clinical Assessment in Predicting Histologic Response to Neoadjuvant Chemotherapy in Bone Sarcomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Clin Oncol. 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827b4f6f
AUTORES / AUTHORS: - Amit P; Patro DK; Basu D; Elangovan S; Parathasarathy V
INSTITUCIÓN / INSTITUTION: - *Department of Orthopaedics, Acharyashree Bhikshu Government Hospital, New Delhi Departments of daggerOrthopaedics double daggerPathology section signRadiodiagnosis parallelRadiotherapy, JIPMER, Pondicherry, India.
RESUMEN / SUMMARY: - BACKGROUND:: Neoadjuvant chemotherapy has become the first-line therapy in management of malignant bone tumors. Response to it is best assessed with evaluation of tumor necrosis postoperatively. This study was carried out to evaluate the role of clinical parameters and dynamic magnetic resonance imaging (MRI) to predict the histologic response before surgery. MATERIALS AND METHODS:: Our study included 14 patients (12 osteosarcoma and 2 malignant fibrous histiocytoma) with mean age of 21.8 years, treated with neoadjuvant chemotherapy followed by surgery, who were evaluated clinically and with dynamic MRI twice, before starting chemotherapy and before surgery. Clinical parameters (pain, tumor girth, maximum tumor diameter, surface temperature, and consistency) and dynamic MRI parameter (slope of signal intensity-time curve) were correlated with histologic response (percentage of necrosis) using Pearson and Spearman correlation test. RESULTS:: Significant correlation with histologic necrosis was seen in change in pain, tumor girth, maximum tumor diameter, surface temperature, and dynamic MRI slope (P<0.01). Change in consistency did not show significant correlation (P>0.05). Complete relieve of pain with reduction of >4 grades, >/=5% reduction in tumor girth, >/=8% reduction in tumor diameter, attainment of normal body temperature or decrease of >/=2 degrees F temperature, and >/=60% reduction in slope proved to be an indicator of good histologic response. CONCLUSIONS:: Both dynamic MRI and clinical evaluation are reliable methods of assessment of response of the bone tumors to neoadjuvant chemotherapy.
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[367]
TÍTULO / TITLE: - Degraded iota-carrageenan can induce apoptosis in human osteosarcoma cells via the Wnt/beta-catenin signaling pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013;65(1):126-31. doi: 10.1080/01635581.2013.741753.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.741753
AUTORES / AUTHORS: - Jin Z; Han YX; Han XR
INSTITUCIÓN / INSTITUTION: - Department of Orthopaedics, First Affiliated Hospital of China Medical University, Shenyang, China. jinzheFH@163.com
RESUMEN / SUMMARY: - Osteosarcoma (OS) is a high-grade malignant bone tumor. Therefore, using both in vitro and in vivo assays, the effects of degraded iota-Carrageenan (iota-CGN) on a human osteosarcoma cell line, HOS, were examined. Degraded iota-CGN was observed to induce apoptosis and G(1) phase arrest in HOS cells. Moreover, degraded iota-CGN suppressed tumor growth in established xenograft tumor models. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors treated with native iota-CGN or PBS. In addition, the formation of intratumoral microvessels was inhibited following treatment with degraded iota-CGN. In Western blot assays, degraded iota-CGN was found to inhibit the Wnt/beta-catenin signaling pathway. Overall, these studies demonstrate the antitumor activity of degraded iota-CGN toward the OS cell line, HOS. Moreover, valuable insight into the mechanisms mediated by degraded iota-CGN was obtained, potentially leading to the identification of novel treatments for OS. However, additional studies are needed to confirm these results in other cell types, particularly in human umbilical vein endothelial cells.
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[368]
TÍTULO / TITLE: - Apigenin induces c-Myc-mediated apoptosis in FRO anaplastic thyroid carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Endocrinol. 2013 Apr 30;369(1-2):130-9. doi: 10.1016/j.mce.2013.01.012. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.mce.2013.01.012
AUTORES / AUTHORS: - Kim SH; Kang JG; Kim CS; Ihm SH; Choi MG; Yoo HJ; Lee SJ
INSTITUCIÓN / INSTITUTION: - Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 200-704, Republic of Korea.
RESUMEN / SUMMARY: - Apigenin promotes apoptosis in cancer cells. We studied the effect of apigenin on cell survival and c-Myc expression in FRO anaplastic thyroid carcinoma (ATC) cells. Apigenin caused apoptosis via the elevation of c-Myc levels in conjunction with the phosphorylation of p38 and p53. In the c-Myc siRNA-transfected and apigenin-treated cells, compared with the apigenin-treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated. In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c-Myc levels. In conclusion, our results indicate that apigenin induces apoptosis mediated via c-Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells. These findings suggest that augmented c-Myc acts as a core regulator and is necessary for apigenin-induced apoptosis in FRO ATC cells.
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[369]
TÍTULO / TITLE: - Thiol Antioxidants in Combination with Vitamin B12Induce Apoptotic Death of Human Lymphocytic Leukemia Cells by Destabilization of Lysosomes with the Involvement of Iron Ions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bull Exp Biol Med. 2013 Jan;154(4):449-52.
AUTORES / AUTHORS: - Solovyeva ME; Faskhutdinova AA; Solovyev VV; Akatov VS
INSTITUCIÓN / INSTITUTION: - Laboratory of Tissue Engineering, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia. groupakatov@rambler.ru.
RESUMEN / SUMMARY: - The extensively used thiol antioxidants (dithiothreitol, glutathione, and N-acetylcysteine) in combination with hydroxycobalamine (vitamin B12) gain toxic activity in relation to human lymphocytic leukemia cell line HL60. Combined treatment with thiol and vitamin B12 was followed by early destabilization of lysosomes and apoptotic death of cells. The cytotoxic effect was abolished by caspase inhibitors. An iron-chelating agent deferoxamine partly prevented cell death, while lysosomal protease inhibitor pepstatin produced no protective effect.
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[370]
TÍTULO / TITLE: - NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Apr;24(4):344-54. doi: 10.1097/CAD.0b013e32835ef440.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835ef440
AUTORES / AUTHORS: - Lewis KM; Harford-Wright E; Vink R; Ghabriel MN
INSTITUCIÓN / INSTITUTION: - Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
RESUMEN / SUMMARY: - Emend, an NK1 antagonist, and dexamethasone are used to treat complications associated with metastatic brain tumours and their treatment. It has been suggested that these agents exert anticancer effects apart from their current use. The effects of the NK1 antagonists, Emend and N-acetyl-L-tryptophan, and dexamethasone on tumour growth were investigated in vitro and in vivo at clinically relevant doses. For animal experiments, a stereotaxic injection model of Walker 256 rat breast carcinoma cells into the striatum of Wistar rats was used. Emend treatment led to a decrease in tumour cell viability in vitro, although this effect was not replicated by N-acetyl-L-tryptophan. Dexamethasone did not decrease tumour cell viability in vitro but decreased tumour volume in vivo, likely to be through a reduction in tumour oedema, as indicated by the increase in tumour cell density. None of the agents investigated altered tumour cell replication or apoptosis in vivo. Inoculated animals showed increased glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 immunoreactivity indicative of astrocytes and microglia in the peritumoral area, whereas treatment with Emend and dexamethasone reduced the labelling for both glial cells. These results do not support the hypothesis that NK1 antagonists or dexamethasone exert a cytotoxic action on tumour cells, although these conclusions may be specific to this model and cell line.
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[371]
TÍTULO / TITLE: - Apoptosis induced by Trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-kappaB and MAPKs signaling pathways.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Toxicol. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s00204-013-1021-9
AUTORES / AUTHORS: - Qing Y; Liang Y; Du Q; Fan P; Xu H; Xu Y; Shi N
INSTITUCIÓN / INSTITUTION: - Department of Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan, 430030, People’s Republic of China.
RESUMEN / SUMMARY: - Trimethyltin chloride (TMT) has been known as a classic neurotoxicant which can cause serious neuronal degeneration diseases. Nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) signaling pathways play pivotal role in the central nerves system. In the present study, the intracellular pathways involved in TMT-induced apoptosis on human neuroblastoma cells SY5Y (SH-SY5Y) were investigated. We observed high level of nuclear NF-kappaB p65 submit, activated JNK, ERK, and p38 by TMT exposure. In contrast, low level of Bcl-2 and XIAP (two known NF-kappaB-regulated endogenous anti-apoptotic molecules) was present. To further investigate the role of these pathways and the relationship between them, specific inhibitors were used and the alteration of each pathway was evaluated. Pretreatment with MG132, an inhibitor of proteasome activity, and BAY11-7082, an inhibitor of IkappaBalpha phosphorylation, both inhibited NF-kappaB p65 translocation and significantly promoted apoptosis. NF-kappaB inhibition also induced down-expression of Bcl-2 and XIAP, exaggerated JNK phosphorylation, and ERK inhibition. SP600125 and U0126, by blocking the phosphorylation of c-Jun and MEK1/2, inhibited JNK and ERK phosphorylation, respectively, and attenuated apoptosis significantly. JNK and ERK inhibition also induced IkappaBalpha degradation and NF-kappaB p65 translocation, leading to expression of Bcl-2 and XIAP. The detrimental role of MG132 and BAY11-7082 appears related to the exaggerated JNK phosphorylation. The SP600125 and U0126 neuroprotection appears related to NF-kappaB-regulated transcriptional control of Bcl-2 and XIAP. These results suggest that the cross-talk and a balance between NF-kappaB and MAPKs may be involved in TMT-induced apoptosis on SH-SY5Y cells.
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[372]
TÍTULO / TITLE: - RAS Mutations in Thyroid FNA Specimens Are Highly Predictive of Predominantly Low-Risk Follicular-Pattern Cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Endocrinol Metab. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1210/jc.2012-3396
AUTORES / AUTHORS: - Gupta N; Dasyam AK; Carty SE; Nikiforova MN; Ohori NP; Armstrong M; Yip L; Lebeau SO; McCoy KL; Coyne C; Stang MT; Johnson J; Ferris RL; Seethala R; Nikiforov YE; Hodak SP
INSTITUCIÓN / INSTITUTION: - Divisions of Endocrinology (N.G., S.O.L., C.C., S.P.H.) and Endocrine Surgery (S.E.C., M.A., L.Y., K.L.M., M.T.S.) and Departments of Radiology (A.K.D.), Otolaryngology (J.J., R.L.F.), and Pathology (M.N.N., N.P.O., R.S., Y.E.N.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213.
RESUMEN / SUMMARY: - Introduction:RAS mutations are common in thyroid tumors and confer a high risk of cancer when detected in fine-needle aspiration (FNA) specimens. Specific characteristics of RAS-positive thyroid cancers are not well described.Methods:From April 2007 to April 2009, 921 consecutive patients undergoing FNA were evaluated prospectively with a panel of molecular markers. Ultrasonographic, cytological, histological, and surgical outcomes were retrospectively assessed.Results:Sixty-eight aspirates from 66 patients were positive for RAS mutations including 63 cytologically indeterminate (93%), 3 malignant (4%), and 2 benign (3%) specimens. Cancer was histologically confirmed in 52 of 63 aspirates (83%) including the following: 46 papillary thyroid cancers, 4 follicular thyroid cancers, 1 medullary cancer, and 1 anaplastic cancer. All 46 RAS-positive papillary thyroid cancers, including 1 metastatic cancer, had follicular variant histology papillary thyroid cancer; only 11 tumors demonstrated vascular/capsular invasion and 4 had infiltrative growth. Of 48 patients with differentiated thyroid cancer, lymph node metastasis was uncommon and bilateral cancer was present in 48%. Only 33% of malignant nodules were suspicious by preoperative ultrasonography. At a mean follow-up of 22 months, 31 of 35 differentiated thyroid cancer patients (89%) have no evidence of recurrence, 4 patients (9%) have detectable thyroglobulin, 1 patient has bone metastases, and both patients with medullary and anaplastic cancer have died.Conclusion:Most RAS-positive thyroid cancers have indeterminate cytology, lack suspicious ultrasound features, and are histologically low-grade follicular variant histology papillary thyroid cancer. Lymph node and distant metastases are uncommon but bilateral disease is frequent. Total thyroidectomy should be considered for initial surgical management of most patients with RAS-positive FNA results. The role of prophylactic lymphadenectomy remains unclear.
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[373]
TÍTULO / TITLE: - Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 15. pii: S0006-291X(13)00406-3. doi: 10.1016/j.bbrc.2013.03.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.03.009
AUTORES / AUTHORS: - Sakamoto T; Ozaki KI; Fujio K; Kajikawa SH; Uesato SI; Watanabe K; Tanimura S; Koji T; Kohno M
INSTITUCIÓN / INSTITUTION: - Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
RESUMEN / SUMMARY: - The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.
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[374]
TÍTULO / TITLE: - Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt074
AUTORES / AUTHORS: - Sandhu SK; Omlin A; Hylands L; Miranda S; Barber LJ; Riisnaes R; Reid AH; Attard G; Chen L; Kozarewa I; Gevensleben H; Campbell J; Fenwick K; Assiotis I; Olmos D; Yap TA; Fong P; Tunariu N; Koh D; Molife LR; Kaye S; Lord CJ; Ashworth A; de Bono J
INSTITUCIÓN / INSTITUTION: - Division of Clinical Studies, Institute of Cancer Research, Sutton.
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[375]
TÍTULO / TITLE: - Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1482-92. doi: 10.3892/ijo.2013.1834. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1834
AUTORES / AUTHORS: - Duan ZL; Wang ZB; Guo JL; Liu WQ; Hu J; Li J; Wang SN; Li Q; Wen JS
INSTITUCIÓN / INSTITUTION: - Department of Microbiology and Immunology, Wenzhou Medical College, Wenzhou 325000, P.R. China.
RESUMEN / SUMMARY: - Squamous cell carcinoma antigen (SCCA) is overexpressed in many squamous cell cancers and SCCAderived peptide-specific CD8+ cytotoxic T lymphocytes can display cytotoxicity against tumor cells. In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8+ Tcell epitopes using two predictive computational algorithms. Seven epitope candidates were selected of which SCCA246-254(llpneidgl), SCCA223-231(sledvqakv), SCCA328336(vlhkafvev) and SCCA324332(vlsgvlhka) significantly stabilized HLA-A*0201 molecules on T2 cells. Both SCCA328336 and SCCA324-332 induced CD8+ IFN-gamma+ Tcell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining. Consistent with this, immunization with either SCCA328-336 or SCCA324332 effectively elicited CD8+ IFN-gamma+ T cells in HLA-A*0201 transgenic mice as visualized by IFN-gamma ELISPOT assay and intracellular cytokine staining. Furthermore, CD8+ T cells induced in vitro or in vivo by SCCA328-336 or SCCA324-332 demonstrated in vitro cytotoxicity against peptide-pulsed T2 cells and splenocytes, respectively. These novel SCCAderived CD8+ Tcell epitopes described, herein, may be potentially important components for diagnostic reagents and immunotherapeutic vaccines for the treatment of squamous cell carcinomas.
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[376]
TÍTULO / TITLE: - Expression of CIDE proteins in clear cell renal cell carcinoma and their prognostic significance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1605-y
AUTORES / AUTHORS: - Yu M; Wang H; Zhao J; Yuan Y; Wang C; Li J; Zhang L; Zhang L; Li Q; Ye J
INSTITUCIÓN / INSTITUTION: - The Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China.
RESUMEN / SUMMARY: - Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of renal cell carcinoma. It is known to derive its histologic appearance from accumulation of abundant lipids and glycogens. The cell death-inducing DFF45-like effector (CIDE) family has been characterized as the lipid droplet proteins involved in the metabolism of lipid storage droplets. The purpose of this study was to evaluate the expression of CIDE proteins in ccRCC cells and to investigate their prognostic significance. We examined consecutive patients with sporadic ccRCC, who underwent nephrectomy, to measure their mRNA and protein expression of CIDE proteins. We found that Cidec and ADRP expression were significantly up-regulated in ccRCC, compared with normal kidney tissues. Cideb was down-regulated. We also found that Cideb was expressed more in low-grade ccRCC than in high-grade tumors. To further clarify the relationship between Cideb expression and patient prognosis, we evaluated 57 ccRCC patients followed up for 120 months. Reduced ccRCC Cideb expression was associated with a higher Fuhrman nuclear grade. Patients with high Cideb expression had better overall survival rate than those with low expression (p < 0.05). Cideb expression was an independent predictor of survival (p = 0.001). Although the biologic function of Cideb in ccRCC remains unknown, the expression level of Cideb might be a novel predictor of prognosis in ccRCC.
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[377]
TÍTULO / TITLE: - Identification of differentially expressed proteins in chemotherapy-sensitive and chemotherapy-resistant diffuse large B cell lymphoma by proteomic methods.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):528. doi: 10.1007/s12032-013-0528-5. Epub 2013 Mar 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0528-5
AUTORES / AUTHORS: - Liu Y; Zeng L; Zhang S; Zeng S; Huang J; Tang Y; Zhong M
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Xiangya Hospital, Central South University, 88 Xiangya Road, Changsha 410008, Hunan, People’s Republic of China.
RESUMEN / SUMMARY: - In the present study, we employed proteomic methods to identify and quantitate differentially expressed proteins between diffuse large B cell lymphoma (DLBCL) tissues with low and high sensitivity to combinatorial cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy and explored protein networks associated with DLBCL chemoresistance to CHOP. For proteomics analysis, DLBCL tissues were collected from 14 untreated patients. Two-dimensional gel electrophoresis combined with mass spectrometry (MS) were employed to identify and quantitate differentially expressed proteins in DLBCL tissues with low or high sensitivity to CHOP chemotherapy in vitro. Nineteen proteins showing an over twofold change in the MS/MS ions score between the low sensitivity and the high sensitivity groups were identified as differentially expressed proteins and confirmed by Western blot analyses. Immunohistochemical analyses were performed in DLBCL tissue samples from 98 patients who had received four cycles of CHOP chemotherapy, which showed that expressions of the identified CHOP sensitivity biomarkers were significantly associated with therapeutic outcomes of DLBCL, suggesting that the biomarkers could be used to predict DLBCL patient outcomes. This study provides important insights into understanding the molecular basis for development of multi-drug chemoresistance in DLBCL, which may serve as a basis for identification of novel therapeutic targets and biomarkers involved in the emergence and maintenance of DLBCL resistance to CHOP.
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[378]
TÍTULO / TITLE: - Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Jun;24(5):519-26. doi: 10.1097/CAD.0b013e32836002ba.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32836002ba
AUTORES / AUTHORS: - Fahey CE; Milner RJ; Kow K; Bacon NJ; Salute ME
INSTITUCIÓN / INSTITUTION: - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, Florida, USA.
RESUMEN / SUMMARY: - Osteosarcoma (OSA) is the most common primary bone tumor in dogs and the guarded prognosis highlights the necessity to find new treatments. Masitinib mesylate is a highly selective tyrosine kinase inhibitor that predominantly targets c-Kit and PDGFR-alpha/beta. This study evaluated the in-vitro activity of masitinib against three canine OSA cell lines after treatment with increasing concentrations of masitinib (0.1-50 micromol/l) at 24, 48, and 72 h. The IC50 values at 72 h for the three OSA cell lines (POS, HMPOS, and COS31) were determined to be 11.04, 7.09, and 9.74 micromol/l, respectively. In addition, increases in caspase-3/7 activity and transferase dUTP nick end labeling-positive cells indicated apoptotic cell death. Because increased levels of vascular endothelial growth factor are found in dogs with OSA, vascular endothelial growth factor in the supernatant was quantified. Overall, the study found that masitinib causes dose-time dependent OSA cell death in vitro through initiation of caspase-mediated apoptosis, which supports future OSA clinical trials.
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[379]
TÍTULO / TITLE: - A case of late onset erythropoietic protoporphyria associated with myelodysplastic syndrome treated by the combination of beta carotene and azacitidine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hematol. 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s00277-013-1720-6
AUTORES / AUTHORS: - Nishikawa Y; Okuda S; Takebayashi C; Tanimoto T; Kami M; Kobayashi K
INSTITUCIÓN / INSTITUTION: - Japan Railway Tokyo General Hospital, Tokyo, Japan, yoshitakanishikawa@gmail.com.
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[380]
TÍTULO / TITLE: - Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 26. doi: 10.3892/or.2013.2306.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2306
AUTORES / AUTHORS: - Spina A; Sorvillo L; Chiosi E; Esposito A; Di Maiolo F; Sapio L; Caraglia M; Naviglio S
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Medical School, I80138 Naples, Italy.
RESUMEN / SUMMARY: - Novel therapeutic approaches are required for the treatment of osteosarcoma. Combination chemotherapy is receiving increased attention in order to identify compounds that may increase the therapeutic index of clinical anticancer drugs. In this regard, naturally occurring molecules with antitumor activity and with limited toxicity to normal tissues have been suggested as possible candidates for investigation of their synergistic efficacy in combination with antineoplastic drugs. Inorganic phosphate (Pi) is an essential nutrient for living organisms. Relevantly, Pi has emerged as an important signaling molecule capable of modulating multiple cellular functions by altering signal transduction pathways, gene expression and protein abundance in many cell types. Previously, we showed that Pi inhibits proliferation and aggressiveness of U2OS human osteosarcoma cells and that Pi is capable of inducing sensitization of osteosarcoma cells to doxorubicin in a p53-dependent manner. In this study, we extended the role of Pi in the chemosensitivity of osteosarcoma cells to other anticancer drugs. Specifically, we report and compare the antiproliferative effects of a combination between Pi and doxorubicin, Taxol® and 5-fluorouracil (5-FU) treatments. We found that Pi increases the antiproliferative response to both Taxol and doxorubicin to a similar extent. On the other hand, Pi did not potentiate the anticancer effects induced by 5-FU. These effects were paralleled by apoptosis induction and were cell cycle-dependent. The clinical significance of our data and their potential therapeutic applications for improving osteosarcoma treatment are discussed.
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[381]
TÍTULO / TITLE: - Practical utility of circulating tumour cells as biomarkers in cancer chemotherapy for advanced colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):625-9.
AUTORES / AUTHORS: - Otsuka K; Imai H; Soeda H; Komine K; Ishioka C; Shibata H
INSTITUCIÓN / INSTITUTION: - Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, Japan. hiroyuki@med.akita-u.ac.jp
RESUMEN / SUMMARY: - Molecular-targeted therapies require the assessment of targets and their related molecules. Circulating tumour cells (CTCs) are considered a very good source of samples for these purposes. In this study, we applied a practical method for examining CTCs to evaluate the effects of chemotherapy on advanced colorectal cancer (CRC). Even in stage IV CRC, CTCs were detected in only 38.5% (n=5/13) of the cases. However, in cases where CTCs were detected, the change in the number of CTCs compared before and after chemotherapy appeared to be associated with the therapeutic outcome. Changes in the number of CTCs may be a good predictive biomarker. Problems with this method are yet to be resolved, including the detection rate and the stability of the sample source for subsequent molecular analysis.
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[382]
TÍTULO / TITLE: - Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt’s lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Mar 1;23(5):1220-4. doi: 10.1016/j.bmcl.2013.01.020. Epub 2013 Jan 12.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.01.020
AUTORES / AUTHORS: - Bright SA; Brinko A; Larsen MT; Sinning S; Williams DC; Jensen HH
INSTITUCIÓN / INSTITUTION: - School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland. brights@tcd.ie
RESUMEN / SUMMARY: - We here report the synthesis of ethylene glycol N-interlinked imipramine dimers of various lengths from the tricyclic antidepressant desipramine via an amide coupling reaction followed by reduction with lithium aluminium hydride. The target molecules were found to be potent inhibitors of cellular viability while inducing cell type specific death mechanisms in three cancer cell lines including a highly chemoresistant Burkitt’s lymphoma cell line. Basic amine analogues were found to be important for increased potency. Imipramine and desipramine were also tested for apoptotic activity and were found to be much less active than the novel dimeric compounds. Imipramine dimers were only found to be moderate inhibitors of the human serotonin transporter (hSERT) having IC(50) values in the micromolar region whilst the induction of cell death occurred independently of hSERT expression. These results demonstrate the potential of newly designed and synthesised imipramines derivatives for use against malignant cells, including those resistant to standard chemotherapy.
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[383]
TÍTULO / TITLE: - Gene expression changes associated with erlotinib response in glioma cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Jan 29. pii: S0959-8049(13)00006-3. doi: 10.1016/j.ejca.2013.01.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.01.002
AUTORES / AUTHORS: - Garcia-Claver A; Lorente M; Mur P; Campos-Martin Y; Mollejo M; Velasco G; Melendez B
INSTITUCIÓN / INSTITUTION: - Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, España.
RESUMEN / SUMMARY: - Erlotinib (ERL), a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor (EGFR), is used as a second line treatment for glioma therapy, with controversial findings regarding its response. Here, we analysed the gene expression profiles of a series of human glioma cell lines with differing sensitivities to ERL to identify the gene expression changes associated with ERL response. The varying responses to ERL were associated with different expression levels of specific genes (HRAS, CTFG, ERCC5 and HDAC3) and genes associated with specific pathways (apoptosis and cell death). PI3K pathway genes were primarily affected by ERL, as we found that PIK3R3 was repressed by ERL treatment in sensitive glioma cell lines. The cell cycle and ubiquitin pathways were also affected by EGFR inhibition, as GAS5, PLK1 and BIRC5 were the most significantly affected genes. In this study we have identified several genes such as PIK3R3 and GAS5, that can be targeted in order to enhance the response to ERL therapy.
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[384]
TÍTULO / TITLE: - Pituitary tumor-transforming gene 1 as a proliferation marker lacking prognostic value in cutaneous squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Dermatol. 2013 Feb 15. doi: 10.1111/exd.12118.
●● Enlace al texto completo (gratuito o de pago) 1111/exd.12118
AUTORES / AUTHORS: - Ishitsuka Y; Kawachi Y; Taguchi S; Maruyama H; Nakamura Y; Fujisawa Y; Furuta JI; Nakamura Y; Ishii Y; Otsuka F
INSTITUCIÓN / INSTITUTION: - Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
RESUMEN / SUMMARY: - Non-melanoma skin cancer is the most frequently occurring type of cancer worldwide and is caused by epidermal carcinogenesis and malignant progression that involve dysregulated expression of proto-oncogenes and tumor suppressor genes. The proto-oncogene pituitary tumor-transforming gene 1 (PTTG1) is a ubiquitously expressed transcription factor that can promote enhanced proliferation of cultured epidermal keratinocytes. To investigate the potential roles of PTTG1 in epidermal carcinogenesis and malignant progression, the expression of PTTG1 was analysed by immunohistochemistry along with Ki67, keratin 10 (K10) and p53 in tissue samples of cutaneous squamous cell carcinomas (SCC), actinic keratoses (AK) and Bowen’s disease (BD). Expression levels of PTTG1 were compared among these disease groups to test for correlations with proliferation, differentiation capacity or the existence of mutated tumor suppressor genes in each disease group. In each disease group, the expression levels of PTTG1 correlated positively with those of Ki67, although the differentiation status, measured by K10 expression, did not show any correlation. In contrast, the existence of mutated p53 proteins showed a positive correlation only in the SCC group. Moreover, the expression levels of PTTG1 in SCC did not correlate with known prognostic factors such as TNM staging or tumor thickness. These results suggest that PTTG1 may represent a proliferation marker associated with mutated p53 proteins but is not an informative predictor of poor clinical outcomes in SCC.
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[385]
TÍTULO / TITLE: - Combination of a novel HDAC inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gynecol Oncol. 2013 Feb 9. pii: S0090-8258(13)00079-6. doi: 10.1016/j.ygyno.2013.02.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ygyno.2013.02.008
AUTORES / AUTHORS: - Yoshioka T; Yogosawa S; Yamada T; Kitawaki J; Sakai T
INSTITUCIÓN / INSTITUTION: - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan; Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
RESUMEN / SUMMARY: - OBJECTIVE: In most endometrial carcinoma, it has been observed that the PI3K/Akt pathway is abnormally accelerated in association with mutations in PIK3CA and PTEN. The present study aimed to examine the combined effect of a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 against human endometrial carcinoma cells. METHODS: The effects of OBP-801/YM753 and LY294002 on the growth of human endometrial carcinoma HEC-1A cells were examined using WST-8 and colony formation assays. The distribution of the cell cycle or apoptosis was analyzed by flow cytometry. The accumulation of intracellular reactive oxygen species (ROS) was measured with a 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) dye. The expression of apoptosis-related proteins was investigated by Western blotting. Mice engrafted with 1x108 HEC-1A cells were treated with OBP-801/YM753, LY294002 or the combination, and tumor volumes were measured. RESULTS: The combination of OBP-801/YM753 and LY294002 significantly inhibited the cell growth on comparison with each agent alone and synergistically increased apoptosis with the induction of Bim, a well-known apoptosis inducer. Additionally, the apoptosis induced by the combination was shown to be dependent on intracellular ROS accumulation and Bim induction. Moreover, the apoptosis-inducing effect of OBP-801/YM753 with LY294002 was more potent than that of SAHA with LY294002. Combined treatment with OBP-801/YM753 and LY294002 significantly suppressed tumor growth compared to the control in vivo. CONCLUSIONS: The combination of OBP-801/YM753 and LY294002 is effective on the inhibition of the growth of HEC-1A cells, and we suggest that this combination is promising a novel therapeutic strategy for endometrial carcinoma.
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[386]
TÍTULO / TITLE: - Histone-lysine methyltransferase EHMT2 is involved in proliferation, apoptosis, cell invasion, and DNA methylation of human neuroblastoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Jun;24(5):484-93. doi: 10.1097/CAD.0b013e32835ffdbb.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835ffdbb
AUTORES / AUTHORS: - Lu Z; Tian Y; Salwen HR; Chlenski A; Godley LA; Raj JU; Yang Q
INSTITUCIÓN / INSTITUTION: - aDepartment of Pediatrics, College of Medicine, University of Illinois at Chicago Departments of bPediatrics cMedicine, University of Chicago, Chicago, Illinois, USA.
RESUMEN / SUMMARY: - Neuroblastoma (NB), a childhood neoplasm arising from neural crest cells, is characterized by a diversity of clinical behaviors ranging from spontaneous remission to rapid tumor progression and death. In addition to genetic abnormalities, recent studies have indicated that epigenetic aberrations also contribute toward NB pathogenesis. However, the epigenetic mechanisms underlying the pathogenesis of NB are largely unknown. Inhibition of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) was evaluated through the measurement of H3K9Me2 levels. Cell proliferation was examined by cell counting in human NB cell lines (LA1-55n, IMR-5, and NMB). The RNA expression of EHMT2, MYCN, and p21 was measured by real-time PCR. The expression of PCNA, MYCN, p53, cyclinD1, H3, H3K27M2, and H3K9Me2 was examined by western blot analysis. In-vitro invasion and the effects of the EHMT2 inhibitor (BIX-01294) were assessed in the Transwell chamber assay. Caspase 3 and 8 activities were measured using a Caspase-Glo assay kit. The level of overall DNA methylation was measured by liquid chromatography-mass spectroscopy. BIX-01294, a specific inhibitor of EHMT2 (a key enzyme for histone H3 dimethylation at lysine-9), specifically decreases the overall H3K9Me2 level but not H3K27Me2. The inhibition of EHMT2 decreased the proliferation of NB cells and induced apoptosis by increasing caspase 8/caspase 3 activity. BIX-01294 inhibited NB cell mobility and invasion. This was accompanied by a decreased expression of the MYCN oncogene. Inhibition of EHMT2 enhanced a doxorubicin-induced inhibitory effect on cell proliferation. Finally, EHMT2 inhibition modulated overall DNA methylation levels in NB cells. Our results show that histone-lysine methylation is involved in cell proliferation, apoptosis, cell invasion, and overall DNA methylation in human NB cells. Further understanding of this mechanism may provide an insight into the pathogenesis of NB progression and lead to novel treatment strategies.
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[387]
TÍTULO / TITLE: - Prognostic Significance of Autophagy-Related Protein Expression in Resected Pancreatic Ductal Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279d0dc
AUTORES / AUTHORS: - Ko YH; Cho YS; Won HS; Jeon EK; An HJ; Hong SU; Park JH; Lee MA
INSTITUCIÓN / INSTITUTION: - From the Divisions of *Oncology and daggerGastroenterology, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, Catholic University, Uijeongbu-si; double daggerDepartment of Maritime Medicine, Maritime Medical Center, Jinhae; section signDepartment of Biomedical Science, College of Medicine, Catholic University; and parallelDivision of Oncology, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University, Seoul, South Korea.
RESUMEN / SUMMARY: - OBJECTIVES: Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. RESULTS: Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270, P = 0.022, respectively). CONCLUSIONS: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.
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[388]
TÍTULO / TITLE: - Altered PTEN function caused by deletion or gene disruption is associated with poor prognosis in rectal but not in colon cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 1. pii: S0046-8177(13)00004-X. doi: 10.1016/j.humpath.2012.12.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.12.006
AUTORES / AUTHORS: - Bohn BA; Mina S; Krohn A; Simon R; Kluth M; Harasimowicz S; Quaas A; Bockhorn M; Izbicki JR; Sauter G; Marx A; Stahl PR
INSTITUCIÓN / INSTITUTION: - General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
RESUMEN / SUMMARY: - Colorectal cancer is the third most common malignancy worldwide. Anti-epidermal growth factor receptor (EGFR)-targeted therapy shows clinical evidence in this malignancy and improves outcome. The tumor suppressor gene phosphatase and tensin homologue (PTEN) is considered a potential predictor of nonresponse to anti-EGFR agents. The purpose of this study was to assess whether associations between PTEN alterations (PTEN gene deletion or PTEN gene disruption) and clinical outcome could be caused by a prognostic (and not predictive) effect of PTEN inactivation. Therefore, we analyzed 404 colorectal cancers not previously treated with anti-EGFR drugs in a tissue microarray format. PTEN deletion and PTEN gene rearrangements were analyzed by fluorescence in situ hybridization. Heterogeneity analysis of all available large tissue sections was performed in 6 cases with genomic PTEN alteration. Twenty-seven (8.8%) of 307 analyzable colorectal cancer spots showed genomic PTEN alterations including 24 hemizygous and 1 homozygous deletion as well as 2 PTEN gene disruptions. Genomic PTEN alterations were associated with reduced patient survival in rectal cancer in univariate and multivariate analyses (P = .012; hazard ratio, 2.675; 95% confidence interval, 1.242-5.759) but not in colon cancer. Large-section evaluation revealed a homogeneous distribution pattern in all 4 analyzed cases with PTEN deletion and in both cases with a PTEN gene disruption. In conclusion, genomic PTEN gene alterations caused by deletion or gene disruption characterize a fraction of rectal cancers with particularly poor outcome.
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[389]
TÍTULO / TITLE: - Knockdown of DEPTOR induces apoptosis, increases chemosensitivity to doxorubicin and suppresses autophagy in RPMI-8226 human multiple myeloma cells in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Med. 2013 Mar 12. doi: 10.3892/ijmm.2013.1299.
●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1299
AUTORES / AUTHORS: - Zhang H; Chen J; Zeng Z; Que W; Zhou L
INSTITUCIÓN / INSTITUTION: - Department of Hematology and Rheumatology, The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, P.R. China.
RESUMEN / SUMMARY: - DEP domain containing mammalian target of rapamycin (mTOR)-interacting protein (DEPTOR) is an mTOR binding protein that is overexpressed in RPMI-8226 human multiple myeloma cells, and plays an important role in maintaining cell survival. However, knowledge on the effects of DEPTOR knockdown on the biological functions of RPMI8226 human multiple myeloma cells, is limited. This study aimed to determine the role of DEPTOR in the proliferation, apoptosis and autophagy in these cells and to elucidate the mechanisms by which DEPTOR contributes to the chemosensitivity of myeloma cells. RNA interference was used to reduce the expression of DEPTOR. Cytotoxicity was evaluated by MTT assay. Apoptosis was examined by flow cytometry. DEPTOR mRNA and protein expression in RPMI8226 cells treated with DEPTOR-specific short hairpin RNA (shRNA) was evaluated by RT-PCR, quantitative PCR and western blot analysis. The expression of apoptosisassociated proteins, autophagyassociated proteins, and the activation of the phosphoinositide 3kinase (PI3K)/Akt signaling pathway were detected by western blot analysis. Autophagy was also measured by transmission electron microscopy and monodansylcadaverine (MDC). In this study, RPMI-8226 cells were transfected with the DEPTOR-specific shRNA, which resulted in the significant inhibition of the transcription and expression of DEPTOR. The downregulation of DEPTOR inhibited proliferation, enhanced the doxorubicininduced growth inhibitory effects on RPMI-8226 cells, and increased the expression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, the downregulation of DEPTOR suppressed autophagy and inhibited the activation of the PI3K/Akt signaling in RPMI8226 cells. In conclusion, our data demonstrated that the downregulation of DEPTOR induces apoptosis, increases chemosensitivity to doxorubicin, and suppresses autophagy and the activation of the PI3K/Akt signaling pathway in RPMI8226 human multiple myeloma cells.
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[390]
TÍTULO / TITLE: - Helicobacter pylori infection and expressions of apoptosis-related proteins p53, ASPP2 and iASPP in gastric cancer and precancerous lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Biol (Paris). 2013 Mar 22. pii: S0369-8114(13)00053-9. doi: 10.1016/j.patbio.2013.02.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.patbio.2013.02.002
AUTORES / AUTHORS: - Meng WD; Chu RX; Wang BZ; Wang LP; Ma LL; Wang LX
INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratory, Liaocheng People’s Hospital of Taishan Medical University, Liaocheng, 252000, Shandong Province, China.
RESUMEN / SUMMARY: - AIMS: There has been limited information about the relations between Helicobacter pylori infection and expressions of apoptosis-related proteins p53, ASPP and iASPP in gastric cancer and precancerous lesions. METHODS: H. pylori in gastric mucosa were identified by W-S staining and rapid urease test. Expression of apoptosis-related proteins P53, ASPP2 and iASPP in the gastric tissues were determined by immunohistochemistry. RESULTS: The concentrations of H. pylori and expressions of p53 and iASPP in gastric carcinoma group and precancerous lesion group were higher than in benign gastric diseases group (P<0.05). The expressions of ASPP2 in gastric carcinoma and precancerous lesion group were lower than in benign gastric diseases group (P<0.05). The expressions of p53 and iASPP in H. pylori positive group were higher than in H. pylori negative group (P<0.05), whereas ASPP2 in H. pylori positive group were lower than in H. pylori negative group (P<0.05). CONCLUSION: There was a higher rate H. pylori infection, an increased expression of apoptosis inhibitor iASPP, and decreased expression of apoptosis stimulator ASPP2 in gastric cancer or precancerous tissues. These results suggest that H. pylori may cause gastric cancer by up-regulating iASPP and down-regulating ASPP2.
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[391]
TÍTULO / TITLE: - VCP gene variation predicts outcome of advanced non-small-cell lung cancer platinum-based chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Apr;34(2):953-61. doi: 10.1007/s13277-012-0631-9. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0631-9
AUTORES / AUTHORS: - Peng J; Yang LX; Zhao XY; Gao ZQ; Yang J; Wu WT; Wang HJ; Wang JC; Qian J; Chen HY; Jin L; Bai CX; Han BH; Wang WM; Lu DR
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, China.
RESUMEN / SUMMARY: - Valosin-containing protein (VCP), or p97, is a member of the ATP-binding protein family, and is involved in numerous cellular events, such as, protein degradation, membrane fusion, and chaperone activity. VCP has been demonstrated playing a critical role in non-small-cell lung cancer (NSCLC) pathogenesis and progression recently. We investigated the association between VCP polymorphisms and clinical outcome in advanced NSCLC patients undergoing platinum-based chemotherapy. We recruited 663 Chinese advanced NSCLC patients who were treated with platinum-based regimens, and using their clinical data, we assessed the efficacy and side effects of their treatment. Three tag-single nucleotide polymorphisms (SNPs) of VCP were genotyped. SNP rs2074549 showed a significant association with severe neutropenia. Its G/G genotype increased the risk of grade 3 or 4 neutropenia compared with wild-type homozygotes A/A (P = .001, odds ratio = 2.975). Haplotype association analysis revealed that CGA was associated with the increased incidence of severe neutropenia (P = .041, odds ratio = 1.439). However, no significant relationship was found between the presence of VCP polymorphisms and treatment efficacy when objective response, progression-free survival, and overall survival (OS) were evaluated. Our study is the first to provide evidence that VCP polymorphisms are associated with a severe chemotherapy-related adverse outcome in platinum-treated advanced NSCLC patients.
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[392]
TÍTULO / TITLE: - Targeted Delivery of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand to Keratinocytes with a Pemphigus mAb.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Invest Dermatol. 2013 Feb 25. doi: 10.1038/jid.2013.85.
●● Enlace al texto completo (gratuito o de pago) 1038/jid.2013.85
AUTORES / AUTHORS: - Kouno M; Lin C; Schechter NM; Siegel D; Yang X; Seykora JT; Stanley JR
INSTITUCIÓN / INSTITUTION: - 1] Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA [2] Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
RESUMEN / SUMMARY: - We determined the feasibility of using an anti-desmoglein (Dsg) mAb, Px44, to deliver a biologically active protein to keratinocytes. Recombinantly produced Px44-green fluorescent protein (GFP) injected into mice and skin organ culture delivered GFP to the cell surface of keratinocytes. We replaced GFP with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to produce Px44-TRAIL. We chose TRAIL as a biological model because it inhibits activated lymphocytes and causes apoptosis of hyperproliferative keratinocytes, features of various skin diseases. Px44-TRAIL formed a trimer, the biologically active form of TRAIL. Standard assays of TRAIL activity showed that Px44-TRAIL caused apoptosis of Jurkat cells and inhibited IFN-gamma production by activated CD4+ T cells. Enzyme-linked immunoassay with Px44-TRAIL showed delivery of TRAIL to Dsg. Immunofluorescence with Px44-TRAIL incubated on skin sections and cultured keratinocytes or injected into mouse skin, human organ culture, or human xenografts detected TRAIL on keratinocytes. Px44-TRAIL caused apoptosis of the hyperproliferative, but not differentiating, cultured keratinocytes through binding to Dsg3. Foldon, a small trimerization domain, cloned into Px44-TRAIL maintained its stability and biological activity at 37 degrees C for at least 48 hours. These data suggest that such targeted therapy is feasible and may be useful for hyperproliferative and inflamed skin diseases.Journal of Investigative Dermatology advance online publication, 4 April 2013; doi:10.1038/jid.2013.85.
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[393]
TÍTULO / TITLE: - Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt011
AUTORES / AUTHORS: - Xu Y; Diao L; Chen Y; Liu Y; Wang C; Ouyang T; Li J; Wang T; Fan Z; Fan T; Lin B; Deng D; Narod SA; Xie Y
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center.
RESUMEN / SUMMARY: - BackgroundBRCA1 function is inactivated through BRCA1 promoter methylation in a substantial number of triple-negative breast cancers. We investigated the impact of BRCA1-methylation status on the efficacy of adjuvant chemotherapy in patients with triple-negative breast cancer or with non-triple-negative breast cancer.MethodsBRCA1 promoter methylation was assessed in 1163 unselected breast cancer patients. Methylation was evaluated using a methylation-specific PCR (MSP) assay.ResultsIn the subgroup of 167 triple-negative breast cancer patients who received adjuvant chemotherapy, patients with BRCA1-methylated tumors had a superior 10-year disease-free survival (DFS)(78% versus 55%, P = 0.009) and 10-year disease-specific survival (DSS) (85% versus 69%, P = 0.024) than those with BRCA1-unmethylated tumors, and BRCA1 methylation was an independent favorable predictor of DFS and DSS in a multivariate analysis in this subgroup [DFS: hazard ratio (HR) = 0.45; 95% confidence interval (CI) 0.24-0.84; P = 0.019; DSS: HR = 0.43; 95% CI = 0.19-0.95; P = 0.044]. In contrast, in 675 non-triple-negative breast cancer patients who received adjuvant chemotherapy, BRCA1 methylation was an unfavorable predictor of DFS and DSS in univariate analysis (DFS: HR = 1.56; 95% CI 1.16-2.12; P = 0.003; DSS: HR = 1.53; 95% CI = 1.05-2.21; P = 0.026).ConclusionsTriple-negative breast cancer patients with BRCA1-methylated tumors are sensitive to adjuvant chemotherapy and have a favorable survival compared with patients with BRCA1-unmethylated triple-negative tumors.
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[394]
TÍTULO / TITLE: - Nobiletin Induces Apoptosis and Potentiates the Effects of the Anticancer Drug 5-Fluorouracil in p53-Mutated SNU-16 Human Gastric Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Feb;65(2):286-95. doi: 10.1080/01635581.2013.756529.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.756529
AUTORES / AUTHORS: - Moon JY; Cho M; Ahn KS; Cho SK
INSTITUCIÓN / INSTITUTION: - a Faculty of Biotechnology, College of Applied Life Sciences , Jeju National University , Jeju , Republic of Korea.
RESUMEN / SUMMARY: - Nobiletin is a typical polymethoxyl flavone from citrus fruits that has anticancer properties, but the molecular mechanism of its inhibitory effects on the growth of p53-mutated SNU-16 human gastric cancer cells has not been explored. In this study, nobiletin was found to be effective at inhibiting the proliferation of SNU-16 cells than other flavonoids. Nobiletin induced the death of SNU-16 cells through apoptosis, as evidenced by the increased cell population in the sub-G1 phase, the appearance of fragmented nuclei, an increase in the Bax/Bcl-2 ratio, the proteolytic activation of caspase-9, an increase in caspase-3 activity, and the degradation of poly(ADP-ribose) polymerase (PARP) protein. We found that the combination of nobiletin plus the anticancer drug 5-fluorouracil (5-FU) reduced the viability of SNU-16 cells in a concentration-dependent manner and exhibited a synergistic anticancer effect (combination index = 0.38) when 5-FU was used at relatively low concentrations. The expression of p53 protein increased after treatment with 5-FU, but not nobiletin, whereas the expression of p21 (WAF1/CIP1) protein increased after treatment with nobiletin, but not 5-FU. The cellular responses to nobiletin and 5-FU occurred through different pathways. The results of this study suggest the potential application of nobiletin to the enhancement of 5-FU efficiency in p53 mutant tumors.
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[395]
TÍTULO / TITLE: - Induction of Cell Cycle Arrest and Apoptosis in Human Osteosarcoma U-2 OS Cells by Solanum lyratum Extracts.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Apr;65(3):469-79. doi: 10.1080/01635581.2013.757627.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.757627
AUTORES / AUTHORS: - Lin YT; Huang AC; Kuo CL; Yang JS; Lan YH; Yu CC; Huang WW; Chung JG
INSTITUCIÓN / INSTITUTION: - a Department of Biological Science and Technology , China Medical University , Taichung , Taiwan.
RESUMEN / SUMMARY: - This research focused on a Chinese herb medicine, Solanum lyratum Thunb (Solanaceae) by ethanol extracts (SLE) for investigating the molecular anticancer mechanism in vitro for exploring the means of cell death through the effects on mitochondrial function. We found that SLE induced cytotoxic effects in human osteosacroma U-2 OS cells, and these effects include cell morphological changes, a decrease of the percentage of viable cells and induction of apoptosis. The results suggest that cell death induced by SLE is closely related to apoptosis based on the observations of DAPI staining and sub-G1 phase in U-2 OS cells. Flow cytometric assays also showed that SLE promoted the production of reactive oxygen species and nitric oxide but decreased the levels of mitochondrial membrane potential and promoted the activations of caspase-8 and -9 in U-2 OS cells. SLE inhibited the level of Bcl-2 but promoted the Bax level, and both proteins led to the release of cytochrome c from mitochondria to cytosol and activation of caspase-9 and -3, resulting in the apoptotic death which is mediated through the mitochondrial pathway. Taken together, SLE was demonstrated to be effective in killing U-2 OS osteosacroma cells via the ROS-promoted and mitochondria- and caspase-dependent apoptotic pathways.
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[396]
TÍTULO / TITLE: - Antioxidant Rich Morus alba leaf Extract Induces Apoptosis in Human Colon and Breast Cancer Cells by the Downregulation of Nitric Oxide Produced by Inducible Nitric Oxide Synthase.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Feb;65(2):305-10. doi: 10.1080/01635581.2013.748924.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.748924
AUTORES / AUTHORS: - Deepa M; Sureshkumar T; Satheeshkumar PK; Priya S
INSTITUCIÓN / INSTITUTION: - a Centre for Bio-Separation Technology , VIT University , Tamil Nadu , India.
RESUMEN / SUMMARY: - Morus species had been used widely in the traditional medicines for various diseases. In this study we report the in vitro antiproliferative activity of the methanol extract of Morus alba. The extract is capable of inducing cytotoxicity in human colon cancer (HCT-15) cells (IC(50) = 13.8 mug/ml) and breast cancer (MCF-7) cells (IC(50) = 9.2 mug/ml), resulted in significant morphological changes of the cells, fragmentation of DNA, and caspase-3 activation- characteristics of apoptosis. It downregulated the amount of nitric oxide (NO) produced as a result of inducible nitric oxide (iNOS) activation. The HPLC analysis of the extract showed epicatechin (20%), myricetin (10%), quercetin hydrate (12%), luteolin (12%), and kaempferol (6%) as the major active components and ascorbic acid, gallic acid, pelargonidine, and p-coumaric acid as the minor components. To the best of our knowledge, this is the first report showing the downregulation of iNOS and induction of apoptosis by M. alba extract.
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[397]
TÍTULO / TITLE: - Tumor STAT3 tyrosine phosphorylation status, as a predictor of benefit from adjuvant chemotherapy for breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Apr;138(2):407-13. doi: 10.1007/s10549-013-2453-x. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2453-x
AUTORES / AUTHORS: - Sonnenblick A; Uziely B; Nechushtan H; Kadouri L; Galun E; Axelrod JH; Katz D; Daum H; Hamburger T; Maly B; Allweis TM; Peretz T
INSTITUCIÓN / INSTITUTION: - Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Ein Kerem, P.O. Box 12000, Jerusalem, 91120, Israel, amirsonn@gmail.com.
RESUMEN / SUMMARY: - Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signaling pathways. In breast cancer cell lines and xenograft models activated STAT3 participates in breast tumorigenesis, while studies in humans have demonstrated that phosphorylated (tyrosine705)-STAT3 is a marker of good prognosis in breast cancer. In order to resolve this paradox we hypothesized that in clinic, phospho-STAT3 has a predictive role of benefit from adjuvant chemotherapy; therefore the goal of this study was to determine the usefulness of phospho-STAT3 status as a predictor of benefit from adjuvant chemotherapy in breast cancer patients. Immunohistochemical analysis of phospho-STAT3 was performed on a tissue microarray of breast cancer specimens. The expression pattern of phospho-STAT3 was retrospectively correlated with pathological parameters and overall survival in patients who were or were not treated with adjuvant chemotherapy. Of 375 tissue specimens interpretable for phospho-STAT3, 134 (36 %) exhibited positive phospho-STAT3 nuclear expression. Among 234 patients who received adjuvant therapy, those with tumors displaying positive phospho-STAT3 nuclear expression had a better ten-year rate of overall survival than patients with tumors displaying negative phospho-STAT3 nuclear expression (P = 0.001). Among patients who did not received adjuvant chemotherapy, positive phospho-STAT3 nuclear status was not correlated with increased overall survival (P = 0.54). Positive phospho-STAT3 was correlated with improved overall survival only among patients who received adjuvant chemotherapy in a multivariate analysis adjusted for stage, grade, hormonal status, Her2 status, and age, irrespective of the chemotherapy regimen received (hazard ratio for death, 0.35 [95 % CI 0.188-0.667]; P = 0.001). These findings support the role of phospho-STAT3 as a marker of favorable outcome in breast cancer patients treated with adjuvant chemotherapy. Whether phospho-STAT3 has a predictive role of benefit from adjuvant chemotherapy has to be validated on prospective, randomized, controlled studies.
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[398]
TÍTULO / TITLE: - Serum Isoform [-2]proPSA Derivatives Significantly Improve Prediction of Prostate Cancer at Initial Biopsy in a Total PSA Range of 2-10 ng/ml: A Multicentric European Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Urol. 2013 Jan 24. pii: S0302-2838(13)00023-7. doi: 10.1016/j.eururo.2013.01.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.eururo.2013.01.011
AUTORES / AUTHORS: - Lazzeri M; Haese A; de la Taille A; Palou Redorta J; McNicholas T; Lughezzani G; Scattoni V; Bini V; Freschi M; Sussman A; Ghaleh B; Le Corvoisier P; Alberola Bou J; Esquena Fernandez S; Graefen M; Guazzoni G
INSTITUCIÓN / INSTITUTION: - Department of Urology, Ospedale San Raffaele Turro, San Raffaele Scientific Institute, Milan, Italy. Electronic address: lazzeri.maximus@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: Strategies to reduce prostate-specific antigen (PSA)-driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary. OBJECTIVE: To test the accuracy of serum isoform [-2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)-called index tests-in discriminating between patients with and without PCa. DESIGN, SETTING, AND PARTICIPANTS: This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2-10 ng/ml who were subjected to initial prostate biopsy for suspected PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS AND LIMITATIONS: Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p=0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p<0.001), %fPSA (0.14 vs 0.17; p<0.001), %p2PSA (2.1 vs 1.6; p<0.001), and PHI (48.2 vs 38; p<0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p<0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values. CONCLUSIONS: In patients with a tPSA range of 2-10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA. TRIAL REGISTRATION: The study is registered at controlled-trials.com, ref. ISRCTN04707454.
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[399]
TÍTULO / TITLE: - Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28078.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28078
AUTORES / AUTHORS: - Avan A; Pacetti P; Reni M; Milella M; Vasile E; Mambrini A; Vaccaro V; Caponi S; Cereda S; Peters GJ; Cantore M; Giovannetti E
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on the outcome and a substantial increase in hematologic and extra-hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The Xeroderma-Pigmentosum group-D polymorphism at codon-751 (XPD-Lys751Gln) emerged as the most significant independent predictor for death- and progression-risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with cisplatin-docetaxel-capecitabine-gemcitabine and cisplatin-epirubicin-capecitabine-gemcitabine (or EC-GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of XPD-Lys751Gln with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy-Weinberg equilibrium, and XPD-Lys751Gln was associated with differential progression-free and overall-survival. Multivariate analysis confirmed its prognostic significance in platinum-based regimens. In particular, XPD-Gln751Gln was significantly associated with risk of death (hazard ratio, HR = 1.7, 95% confidence interval [CI], 1.1-2.6, p = 0.011) and risk of progression (HR = 1.7, 95% CI, 1.1-2.5, p = 0.013). No correlation was observed in gemcitabine monotherapy-treated patients. The analysis of DNA damage using extra-long-PCR in lymphocytes supported the association of XPD-Gln751Gln with greater resistance to cisplatin-induced damage. The increasing evidence of XPD-Lys751Gln impact on the outcome of gemcitabine-cisplatin-based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer.
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[400]
TÍTULO / TITLE: - Combined temozolomide and sunitinib treatment leads to better tumour control but increased vascular resistance in O-methylguanine methyltransferase-methylated gliomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Mar 14. pii: S0959-8049(13)00149-4. doi: 10.1016/j.ejca.2013.02.019.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.02.019
AUTORES / AUTHORS: - Czabanka M; Bruenner J; Parmaksiz G; Broggini T; Topalovic M; Bayerl SH; Auf G; Kremenetskaia I; Nieminen M; Jabouille A; Mueller S; Harms U; Harms C; Koch A; Heppner FL; Vajkoczy P
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Universitatsmedizin Charite, Berlin, Germany.
RESUMEN / SUMMARY: - INTRODUCTION: Combined antiangiogenic and cytotoxic treatment represents an appealing treatment approach for malignant glioma. In this study we characterised the antitumoural and microvascular consequences of sunitinib (Su) and temozolomide (TMZ) therapy and verified the ideal treatment protocol, with special focus on a potential therapeutic window for combined scheduling. MATERIALS AND METHODS: O6-Methylguanine methyltransferase (MGMT) status was analysed by pyrosequencing. Tumour growth of subcutaneous xenografts was assessed under different treatment protocols (TMZ, SU, SU followed by TMZ, TMZ followed by SU, combined TMZ/SU). Intravital microscopy (dorsal skinfold chamber model) assessed microvascular consequences. Immunohistochemistry included tumour and endothelial cell proliferation, apoptosis and vascular pericyte coverage. Real-time polymerase chain reaction (RT-PCR) analysed the expression of angiogenesis-related pathways in response to therapy. RESULTS: Combined TMZ/SU resulted in significantly reduced tumour growth compared to either monotreatment (TMZ: 106+/-13mm3; SU: 114+/-53mm3; TMZ/SU: 34+/-7mm3) by additional antiangiogenic effects and synergistic induction of apoptosis versus TMZ monotreatment. Sequential treatment protocols did not show additive antitumour responses. TMZ/SU aggravated vascular resistance mechanisms characterised by significantly higher blood flow rate (TMZ: 74+/-34mul/s; SU: 164+/-36mul/s; TMZ/SU: 254+/-95mul/s), reduced permeability (TMZ: 1.05+/-0.02; SU: 0.99+/-0.07; TMZ/SU: 0.89+/-0.05) and recovery of pericyte-endothelial interactions (TMZ: 89+/-7%; SU: 67+/-9%, TMZ/SU:80+/-10%) versus either monotreatment. Vascular resistance was paralleled by an increase in Ang-1 and Tie-2 and by the downregulation of Dll4. CONCLUSION: Sequential application of TMZ and SU in the angiogenic window does not add antitumour efficacy to monotherapy. Simultaneous application yields beneficial tumour control due to additive antiangiogenic and proapoptotic effects. Combined treatment may aggravate pericyte-mediated vascular resistance mechanisms by altering Ang-1-Tie-2 and Dll4/Notch pathways.
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[401]
TÍTULO / TITLE: - BAL1/ARTD9 represses the anti-proliferative and pro-apoptotic IFNgamma-STAT1-IRF1-53 axes in diffuse large B-cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Sci. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1242/jcs.118174
AUTORES / AUTHORS: - Camicia R; Bachmann SB; Winkler HC; Beer M; Tinguely M; Haralambieva E; Hassa PO
RESUMEN / SUMMARY: - The B-aggressive lymphoma-1 protein and ADP-ribosyltransferase BAL1/ARTD9 has been recently identified as a novel risk-related gene product in aggressive diffuse large B-cell lymphoma (DLBCL). BAL1 is constitutively expressed in a subset of high-risk DLBCL with an active host inflammatory response and suggested to be associated with interferon related gene expression. Here we identify BAL1 as a novel oncogenic survival factor in DLBCL and show that constitutive overexpression of BAL1 in DLBCL tightly associates with intrinsic interferon-gamma (IFNgamma) signaling and constitutive activity of signal transducer and activator of transcription (STAT)-1. Remarkably, BAL1 stimulates the phosphorylation of both STAT1 isoforms STAT1alpha and STAT1beta, on Y701 and thereby promoting the nuclear accumulation of the antagonistically acting and transcriptionally repressive isoform STAT1beta. Moreover, BAL1 physically interacts with both isoforms of STAT1, STAT1alpha and STAT1beta through its macro domains in an ADP-ribosylation dependent manner. BAL1 directly inhibits together with STAT1beta the expression of tumor suppressor and interferon response factor (IRF)-1. Conversely, BAL1 enhances the expression of the proto-oncogenes IRF2 and B-cell CLL/lymphoma (BCL)-6 in DLBCL. Our results show the first time that BAL1 represses the anti-proliferative and pro-apoptotic IFNgamma-STAT1-IRF1-53 axes and mediates proliferation, survival and chemo-resistance in DLBCL. As a consequence constitutive IFNgamma-STAT1 signaling does not lead to apoptosis but rather to chemo-resistance in DLBCL overexpressing BAL1. Our results suggest that BAL1 may induce an oncogenic switch in STAT1 from a tumor suppressor to an oncogene in high-risk DLBCL.
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[402]
TÍTULO / TITLE: - Antitumor effects of a tetradentate amido-carboxylate ligands and corresponding square-planar palladium(II) complexes toward some cancer cells. Crystal structure, DFT modeling and ligand to DNA probe Docking simulation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Inorg Biochem. 2013 Apr;121:134-44. doi: 10.1016/j.jinorgbio.2013.01.006. Epub 2013 Jan 16.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jinorgbio.2013.01.006
AUTORES / AUTHORS: - Matovic ZD; Mrkalic E; Bogdanovic G; Kojic V; Meetsma A; Jelic R
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, Faculty of Science, University of Kragujevac, SRB-34000 Kragujevac, Serbia. Electronic address: zmatovic@kg.ac.rs.
RESUMEN / SUMMARY: - Novel square-planar palladium(II) complexes with O-N-N-O-type ligands Hmda (Hmda=malamido-N,N’-diacetic acid) and Hobp (Hobp=oxamido-N,N’-di-3-propionic acid) were prepared and characterized. The ligands coordinate to the palladium(II) ion via two pairs of deprotonated ligating atoms with square chelation. A four coordinate, square-planar geometry was verified crystallographicaly for the K[Pd(mda)]HO complex. The binary and ternary systems of Pd(II) ion with Hmda or Hobp (L) as primary ligands and guanosine (A) as secondary ligand were studied in aqueous solutions in 0.1M NaCl ionic medium at 25 degrees C by potentiometric titrations. In addition, calculations based on density functional methods (DFT) were carried out. A natural bonding orbital analysis indicated that the Pd-N bonds are three-centric in nature and mainly governed by charge transfer via a strong delocalization of the oxygen lone pair with “p” character into the bonding Pd-N orbital. Mononuclear palladium(II) complexes together with amido acid N,O-containing ligands were tested against several tumor cells and reveal significant antitumor activity and lower resistance of tumor cells in vitro than cisplatin. In this paper, interactions of palladium complexes with DNA are discussed in order to provide guidance and determine structure and antitumor activity relationships for continuing studies of these systems. Docking simulation on DNA dodecamer or 29-mer (Lippard solved crystal structures), suggests several favorable interactions with the hydrogen pocket/binding site for the incoming ligands. These results support amidoacids/Pd complexes as novel antitumor drugs and suggest that their potent cell life inhibition may contribute to its anti-cancer efficacy.
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[403]
TÍTULO / TITLE: - The prognostic relevance of tumour-infiltrating plasma cells and immunoglobulin kappa C indicates an important role of the humoral immune response in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Jan 28. pii: S0304-3835(13)00080-3. doi: 10.1016/j.canlet.2013.01.036.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.036
AUTORES / AUTHORS: - Lohr M; Edlund K; Botling J; Hammad S; Hellwig B; Othman A; Berglund A; Lambe M; Holmberg L; Ekman S; Bergqvist M; Ponten F; Cadenas C; Marchan R; Hengstler JG; Rahnenfuhrer J; Micke P
INSTITUCIÓN / INSTITUTION: - Dept. of Statistics, TU Dortmund University, Dortmund, Germany.
RESUMEN / SUMMARY: - A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma-infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.
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[404]
TÍTULO / TITLE: - Bcl-2 proapoptotic proteins distribution in U-87 MG glioma cells before and after hypericin photodynamic action.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gen Physiol Biophys. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 4149/gpb_2013021
AUTORES / AUTHORS: - Balogova L; Maslanakova M; Dzurova L; Miskovsky P; Stroffekova K
INSTITUCIÓN / INSTITUTION: - Department of Biophysic, Institute of Physical Sciences, P. J. Safarik University, Kosice, Slovak Republic.
RESUMEN / SUMMARY: - Apoptosis is a key process in the development and maintenance of tissue homeostasis. This process of controlled cell death is tightly regulated by a balance between cell survival and damage signals. We focused our attention towards one apoptotic pathway, the intrinsic mitochondrial one where Bcl-2 family of proteins plays the major role. We are particularly interested in two pro-apoptotic players Bak and Bax from this family. Here we investigated their role in apoptosis triggered by photodynamic action. Targeted photodynamic therapy (PDT) is a promising approach to diagnose and treat different types of cancer. We show the localization of Bax and Bak in U-87 MG human glioma cells incubated with photosensitizer hypericin (Hyp) before and after photodynamic action. Apoptotic stimulus by Hyp photodynamic action causes Bax translocation into mitochondria. However our results suggest that under these conditions there are two populations of mitochondria: one which contains Bax and Bak simultaneously, and is almost exclusively localized near the plasma membrane; the other which contains Bax only and is distributed throughout the cell. The different protein content and spatial distribution of these two populations suggest that they can play different roles in response to apoptotic stimuli.
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[405]
TÍTULO / TITLE: - Crude saponins from Platycodon grandiflorum induce apoptotic cell death in RC-58T/h/SA#4 prostate cancer cells through the activation of caspase cascades and apoptosis-inducing factor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1421-8. doi: 10.3892/or.2013.2256. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2256
AUTORES / AUTHORS: - Lee JH; Oh EK; Cho HD; Kim JY; Lee MK; Seo KI
INSTITUCIÓN / INSTITUTION: - Department of Food and Nutrition, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea.
RESUMEN / SUMMARY: - Saponins are a major active component of Platycodon grandiflorum (P. grandiflorum) and are known to induce apoptosis in metastatic prostate cancer cell lines. However, thus far, no research has been conducted on the anticancer activity of saponins in RC-58T/h/SA#4 primary prostate cancer cells. In this study, we show that the treatment of prostate cancer cells with saponins extracted from P. grandiflorum (SPG) inhibits cell proliferation in a dose-dependent manner. SPG significantly induced apoptotic cell death, resulting in an increase in the sub-G1 apoptotic cell population, apoptotic DNA fragmentation and morphological changes. Pre-treatment with a caspase inhibitor modestly attenuated the SPG-induced increase in the sub-G1 cell population, suggesting that caspases play a role in SPG-induced apoptosis. Moreover, SPG-induced apoptosis was associated with changes in caspase activity, the upregulation of the apoptotic protein, Bax and the downregulation of the anti-apoptotic protein, Bcl-2. Furthermore, the caspase-independent mitochondrial apoptosis factor, apoptosis-inducing factor (AIF) was upregulated following SPG treatment. These findings indicate that SPG exerts its anticancer effects on RC-58T/h/SA#4 primary prostate cancer cells through mitochondrial caspase-dependent and -independent apoptotic pathways.
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[406]
TÍTULO / TITLE: - Intratumor BRAF(V600E) Heterogeneity and Kinase Inhibitors in the Treatment of Thyroid Cancer: A Call for Participation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thyroid. 2013 Apr;23(4):517-9. doi: 10.1089/thy.2012.0614. Epub 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1089/thy.2012.0614
AUTORES / AUTHORS: - Vitale M
INSTITUCIÓN / INSTITUTION: - Departments of Medicine and Surgery, University of Salerno , Salerno, Italy .
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[407]
TÍTULO / TITLE: - Active Surveillance of Very-low-risk Prostate Cancer in the Setting of Active Treatment of Benign Prostatic Hyperplasia With 5alpha-reductase Inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urology. 2013 Mar 20. pii: S0090-4295(13)00171-4. doi: 10.1016/j.urology.2012.10.089.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.10.089
AUTORES / AUTHORS: - Shelton PQ; Ivanowicz AN; Wakeman CM; Rydberg MG; Norton J; Riggs SB; Teigland CM
INSTITUCIÓN / INSTITUTION: - McKay Department of Urology, Carolinas Medical Center, Charlotte, NC.
RESUMEN / SUMMARY: - OBJECTIVE: To review the efficacy of treating benign prostatic hyperplasia and very-low-risk prostate cancer (PCa) in patients receiving active surveillance and 5alpha-reductase inhibitor (5-ARI; finasteride or dutasteride) treatment. MATERIALS AND METHODS: Eighty-two men with very-low-risk PCa (clinical stage T1c, Gleason score </=6, <3 biopsy cores positive with </=50% involvement, and prostate-specific antigen density </=0.15 ng/mL/g) and benign prostatic hyperplasia (>/=30 cm3) received active surveillance and were treated with a 5-ARI. RESULTS: All 82 men completed 1 year of 5-ARI therapy (n = 79) or underwent early biopsy for cause (n = 3). Restaging biopsies were performed for 76 men (22 underwent a second restaging biopsy and 1 a third restaging biopsy), 4 patients were awaiting biopsy, and 2 were lost to follow-up before the first restaging biopsy. At the first restaging biopsy, of the 76 men, 41 (54%) had no PCa, 16 (21%) continued to have very-low-risk PCa, 15 (20%) had progressed to low-risk PCa (>2 cores positive and Gleason score </=6), and 4 (5%) had progressed to intermediate-risk PCa (Gleason score 7). Of the 76 biopsies, 20 were performed early for cause, with 11 (55%) showing PCa progression. Of the 82 patients, 22 (27%) underwent treatment of PCa. CONCLUSION: Active surveillance of very-low-risk PCa in the setting of 5-ARI therapy for benign prostatic hyperplasia appears to be a safe therapeutic option, because most (57 of 82; 70%) patients maintained very-low-risk PCa or had negative follow-up biopsies during a 3-year follow-up period. Complementary to the Prostate Cancer Prevention Trial, our results indicate that 5-ARI therapy increases prostate-specific antigen sensitivity and can aid the clinician in appropriately targeting biopsies.
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[408]
TÍTULO / TITLE: - MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surgery. 2013 Feb 28. pii: S0039-6060(12)00751-9. doi: 10.1016/j.surg.2012.12.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.12.004
AUTORES / AUTHORS: - Luo M; Shen D; Zhou X; Chen X; Wang W
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China. Electronic address: luomin_guangzhou@163.com.
RESUMEN / SUMMARY: - BACKGROUND: Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of microRNA (miR)-497 in human cervical cancer still remain unclear. Our aim was to analyze the clinicopathologic and prognostic significance of miR-497 in human cervical cancer and to investigate the effects of miR-497 on the malignant phenotype of cervical cancer cells. METHODS: First, we detected miR-497 expression in the HPV-16-immortalized cervical epithelial cell lines and 4 other cervical cancer cell lines (HeLa, Caski, SiHa, and HeLa-S3). Then the expression of miR-497 was analyzed in cervical cancer tissues and paired nontumor tissues, and its correlation with clinicopathologic features and survival was analyzed. Finally, the roles of miR-497 in regulation of tumor proliferation, apoptosis, migration, invasion, and target gene expression were further investigated. RESULTS: MiR-497 was downregulated in cervical cancer cells or tissues compared with HPV-16-immortalized cervical epithelial cell lines or the paired nontumor tissues. Also, the decrease in miR-497 correlated closely with the criteria of the International Federation of Gynaecology and Obstetrics stage and lymph node metastases in patients with cervical cancer. Multivariate Cox analysis showed that low miR-497 expression appeared to be an unfavorable prognostic factor. Transient forced expression of miR-497 decreased the growth and colony-formation capacity of HeLa and SiHa cells by inducing Caspase-3-dependent apoptosis. Forced expression of miR-497 suppressed the migration and invasiveness of cervical cancer cells. By computational miRNA target prediction and functional analysis, miR-497 was demonstrated to bind to the 3’ untranslated regions of IGF-1R mRNA, and upregulation of miR-497 downregulated IGF-1R protein expression. Further investigation showed that small interfering RNA-mediated IGF-1R knockdown could mimic the effect of enforced miR-497 expression on the malignant phenotypes of cervical cancer cells. CONCLUSION: MiR-497 may be a potential prognostic marker and functions as a tumor suppressor in human cervical cancer by post-transcriptionally targeting IGF-1R.
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[409]
TÍTULO / TITLE: - beta-1,4-Galactosyltransferase III Enhances Invasive Phenotypes Via beta1-Integrin and Predicts Poor Prognosis in Neuroblastoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 1;19(7):1705-1716. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2367
AUTORES / AUTHORS: - Chang HH; Chen CH; Chou CH; Liao YF; Huang MJ; Chen YH; Wang WJ; Huang J; Hung JS; Ho WL; Jeng YM; Che MI; Lee H; Lu MY; Yang YL; Jou ST; Lin DT; Lin KH; Hsu WM; Huang MC
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Pediatrics, Pathology, Laboratory Medicine, and Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine; Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine; Institute of Cellular and Organismic Biology, Academia Sinica; Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital; Department of Life Science and Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei; and School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
RESUMEN / SUMMARY: - PURPOSE: Neuroblastoma (NB) is a neural crest-derived tumor that commonly occurs in childhood. beta-1,4-Galactosyltransferase III (B4GALT3) is highly expressed in human fetal brain and is responsible for the generation of poly-N-acetyllactosamine, which plays a critical role in tumor progression. We therefore investigated the expression and role of B4GALT3 in NB. EXPERIMENTAL DESIGN: We examined B4GALT3 expression in tumor specimens from 101 NB patients by immunohistochemistry and analyzed the correlation between B4GALT3 expression and clinicopathologic factors or survival. The functional role of B4GALT3 expression was investigated by overexpression or knockdown of B4GALT3 in NB cells for in vitro and in vivo studies. RESULTS: We found that B4GALT3 expression correlated with advanced clinical stages (P = 0.040), unfavorable Shimada histology (P < 0.001), and lower survival rate (P < 0.001). Multivariate analysis showed that B4GALT3 expression is an independent prognostic factor for poor survival of NB patients. B4GALT3 overexpression increased migration, invasion, and tumor growth of NB cells, whereas B4GALT3 knockdown suppressed the malignant phenotypes of NB cells. Mechanistic investigation showed that B4GALT3-enhanced migration and invasion were significantly suppressed by beta1-integrin blocking antibody. Furthermore, B4GALT3 overexpression increased lactosamine glycans on beta1-integrin, increased expression of mature beta1-integrin via delayed degradation, and enhanced phosphorylation of focal adhesion kinase. Conversely, these properties were decreased by knockdown of B4GALT3 in NB cells. CONCLUSIONS: Our findings suggest that B4GALT3 predicts an unfavorable prognosis for NB and may regulate invasive phenotypes through modulating glycosylation, degradation, and signaling of beta1-integrin in NB cells. Clin Cancer Res; 19(7); 1705-16. ©2013 AACR.
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[410]
TÍTULO / TITLE: - Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Haematol. 2013 Feb 21. doi: 10.1111/bjh.12256.
●● Enlace al texto completo (gratuito o de pago) 1111/bjh.12256
AUTORES / AUTHORS: - Lee YG; Kim I; Yoon SS; Park S; Cheong JW; Min YH; Lee JO; Bang SM; Yi HG; Kim CS; Park Y; Kim BS; Mun YC; Seong CM; Park J; Lee JH; Kim SY; Lee HG; Kim YK; Kim HJ
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - The present study aimed to directly compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndromes (MDS). We compared the overall response rate (ORR) (complete responses, partial responses, marrow complete responses, and haematological improvements), overall survival (OS), event-free survival (EFS), time to leukaemic transformation, and adverse outcomes between azacitidine and decitabine. To minimize the effects of treatment selection bias in this observational study, adjustments were made using the propensity-score matching method. Among 300 patients, 203 were treated with azacitidine and 97 with decitabine. Propensity-score matching yielded 97 patient pairs. In the propensity-matched cohort, there were no significant differences between the azacitidine and decitabine groups regarding ORR (44% vs. 52%), OS (26 vs. 22.9 months), EFS (7.7 vs. 7.0 months), and rate of leukaemic transformation (16% vs. 22% at 1 year). In patients >/=65 years of age, survival was significantly better in the azacitidine group (P = 0.017). Patients who received decitabine experienced more frequent episodes of grade 3 or 4 cytopenia and infectious episodes. We found that azacitidine and decitabine showed comparable efficacy. Among patients >/=65 years of age, survival was significantly better in the azacitidine group (ClinicalTrials.gov Identifier: NCT01409070).
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[411]
TÍTULO / TITLE: - Everolimus in Metastatic Renal Cell Carcinoma after Failure of Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor (VEGFr-TKI) Therapy: Results of an Interim Analysis of a Non-Interventional Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onkologie. 2013;36(3):95-100. doi: 10.1159/000348522. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1159/000348522
AUTORES / AUTHORS: - Bergmann L; Goebell PJ; Kube U; Kindler M; Herrmann E; Janssen J; Schmitz J; Weikert S; Steiner G; Jakob A; Staehler MD; Steiner T; Overkamp F; Albrecht M; Guderian G; Doehn C
INSTITUCIÓN / INSTITUTION: - University Hospital Frankfurt, Medical Clinic II, Frankfurt/Main, Germany.
RESUMEN / SUMMARY: - Background: Everolimus is approved for treatment of anti-vascular endothelial growth factor (VEGF)-refractory patients with metastatic renal cell carcinoma (mRCC). Clinical trials rarely mirror treatment reality. Thus, a broader evaluation of everolimus is valuable for routine use. Patients and Methods: A German multicenter non-interventional study documented mRCC patients starting everolimus after failure of initial VEGF-targeted therapy. Primary endpoint was effectiveness, defined as time to progression (TTP) according to investigator assessment (time from first dose to progression). Results: Of 382 documented patients, 196 were included in this interim analysis. In the efficacy population (n = 165), median TTP was 7.0 months (95% confidence interval (CI) 5.1-9.0). Among patients with < or >/= 6 months of previous VEGF-targeted therapy, median TTP was 6.6 months (95% CI 3.8-not estimable) and 7.4 months (95% CI 4.6-9.6), respectively. Most common adverse events were anemia (13%) and dyspnea (14%). Physicians assessed high tolerance and documented high adherence to everolimus therapy (approximately 97%). Conclusion: In routine clinical practice, everolimus is effective, as measured by median TTP (longer than median progression-free survival in RECORD-1 trial), and well tolerated. Our results support everolimus use in anti-VEGF-refractory patients with mRCC.
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[412]
TÍTULO / TITLE: - Cytotoxic effect of gambogic acid on SH-SY5Y neuroblastoma cells is mediated by intrinsic caspase-dependent signaling pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 May;377(1-2):187-96. doi: 10.1007/s11010-013-1584-z. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1584-z
AUTORES / AUTHORS: - Rahman MA; Kim NH; Huh SO
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon, Gangwon-do, 200-702, South Korea.
RESUMEN / SUMMARY: - Gambogic acid (GA) is the dry resin of Garcinia hanburyi (Guttiferae) with potent anti-tumor activity, various bioactivities, including detoxification, homeostasis, anti-inflammatory, and parasiticide, whereas the effect of this natural compound on cancer cells has not been clearly clarified. Here, we examined cellular cytotoxicity by cell viability assay and DNA fragmentation by DNA-ladder assay. Activation of different protein expressions were detected by western blot analyses. We first demonstrated that GA reduces the human SH-SY5Y neuroblastoma cell viability with IC50 of 1.28 muM at 6 h which has less toxicity in fibroblast cells. However, lower concentration GA significantly downregulated the expression of anti-apoptotic protein including Bcl-2, Bcl-xL, and Mcl-1, which also dramatically activated cleaved caspase-9 and -3 in a dose- and time-dependent manner. Consequently, GA-induced cytotoxicity was not mediated by the Fas/FasL and PI3 K/AKT/GSK-3beta signaling pathway. In addition, GA-induced cells showed damage morphology which had become cell rounding, neurite retraction, membrane blebbing and shrunken in a dose- and time-dependent manner that clearly indicates this morphological change might be due to the process of apoptosis which shows fragmented DNA. Therefore, the findings presented in this study demonstrate that apoptotic effects of GA on SH-SY5Y cells are mediated by intrinsic mitochondrion-dependent caspase pathway which suggests this natural compound might be effective as an anti-cancer agent for neuroblastoma malignancies.
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[413]
TÍTULO / TITLE: - CD34 expression on bone marrow blasts is a novel predictor of poor prognosis independent of FlT3-ITD in acute myeloid leukemia with the NPM1-mutation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Mar 5. pii: S0145-2126(13)00045-3. doi: 10.1016/j.leukres.2013.02.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.02.007
AUTORES / AUTHORS: - Zhu HH; Liu YR; Jiang H; Lu J; Qin YZ; Jiang Q; Bao L; Ruan GR; Jiang B; Huang X
INSTITUCIÓN / INSTITUTION: - Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China.
RESUMEN / SUMMARY: - To explore the prognostic value of CD34 expression in NPM1-mutated acute myeloid leukemia (NPM1m+AML), seventy-one NPM1m+AML patients were retrospectively analyzed. The patients with >7% CD34 expression (according to the ROC analysis) had a lower complete remission (CR) rate after 1 course of induction, disease-free survival (DFS), and overall survival (OS) compared to those with </=7% CD34 expression (p=0.0038; p=0.001; p<0.0001). A multivariate analysis revealed that CD34 expression is a prognostic factor that is independent of FlT3-ITD for relapse, DFS and OS. We established a novel prognostic model based on the CD34 and FLT3 status at diagnosis, which could facilitate the segregation of patients into three prognostically different subgroups. We demonstrate that CD34 expression on blasts is a novel, poor predictor independent of FlT3-ITD in NPM1-mutated patients and established a new prognostic model based on the CD34 and FLT3 status at diagnosis, which may facilitate immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.
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[414]
TÍTULO / TITLE: - Pharmacogenomic approaches for tailored anti-leukemic therapy in children.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Med Chem. 2013 Feb 21.
AUTORES / AUTHORS: - Stocco G; Franca R; Verzegnassi F; Londero M; Rabusin M; Decorti G
INSTITUCIÓN / INSTITUTION: - Department of Life Sciences, University of Trieste, Via Fleming 22, Trieste, Italy, 34127. stoccog@units.it.
RESUMEN / SUMMARY: - Several lympholytic and cytotoxic agents are used in acute lymphoblastic leukemia (ALL) polychemotherapy. Genetic variants for any of the cellular components involved in the pharmacokinetics and pharmacodynamics of these drugs can influence the pharmacological response, and molecular characterization of these genetic variants could be helpful for the comprehension of the mechanism of resistance or increased sensitivity. The purpose of this review is to carry out an update of recent publications on genes that might influence ALL treatment in terms of outcome and/or toxicity and to underlie the role of genetic variants, particularly single nucleotide polymorphisms (SNP), in predicting clinical response, with particular reference to the current protocol for ALL therapy used in Italy, AIEOP-BFM ALL 2009.
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[415]
TÍTULO / TITLE: - Ribonuclease binase apoptotic signature in leukemic Kasumi-1 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochimie. 2013 Mar 13. pii: S0300-9084(13)00073-4. doi: 10.1016/j.biochi.2013.02.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biochi.2013.02.016
AUTORES / AUTHORS: - Mitkevich VA; Kretova OV; Petrushanko IY; Burnysheva KM; Sosin DV; Simonenko OV; Ilinskaya ON; Tchurikov NA; Makarov AA
INSTITUCIÓN / INSTITUTION: - Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str 32, 119991 Moscow, Russia; University of Oslo, Centre for Medical Studies in Russia, Moscow, Russia.
RESUMEN / SUMMARY: - Cytotoxic exogenous RNases triggering apoptotic response in malignant cells have potential as anticancer drugs; surprisingly, detailed characterization of the RNase-induced apoptosis has not been conducted so far. Here we show that a cytotoxic RNase from Bacillus intermedius (binase) induces extrinsic and intrinsic apoptotic pathways in leukemic Kasumi-1 cells. The experiments were performed using TaqMan Array Human Apoptosis 96-well Plate for gene expression analysis, and flow cytometry. Cytometric studies demonstrated dissipation of the mitochondrial membrane potential, opening of mitochondrial permeability transition pores, activation of caspases, increase of intracellular Ca2+ and decrease of reactive oxygen species levels. We found that expression of 62 apoptotic genes is up-regulated, including 16 genes that are highly up-regulated, and only one gene was found to be down-regulated. The highest, 16 fold increase of the expression level was observed for TNF gene. Highly up-regulated genes also include the non-canonical NF-kappaB signaling pathway and inflammatory caspases 1,4. The obtained results suggest that binase induces evolutionary acquired cellular response to a microbial agent and triggers unusual apoptosis pathway.
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[416]
TÍTULO / TITLE: - Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Life Sci. 2013 Feb 9. pii: S0024-3205(13)00070-2. doi: 10.1016/j.lfs.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lfs.2013.02.001
AUTORES / AUTHORS: - Singh M; Bhui K; Singh R; Shukla Y
INSTITUCIÓN / INSTITUTION: - Proteomics Laboratory, Council of Scientific & Industrial Research, (Indian Institute of Toxicology Research), P.O. Box 80, M.G. Marg, Lucknow-226001, India.
RESUMEN / SUMMARY: - AIM: Constitutive activation of nuclear factor-kappaB (NF-kappaB) and Akt has been implicated in chemoresistance as well as inhibition of apoptosis to cisplatin (CDDP), therefore, we examined whether (-) epigallocateocatechin-3-gallate (EGCG) or theaflavins (TF) could sensitize human cancer cells to CDDP via induction of apoptosis mediated by the inactivation of NF-kappaB and Akt signaling. MAIN METHODS: Human cervical cancer cells (HeLa and SiHa cells) were treated with EGCG or TF and CDDP alone and with their combinations, further their effects on cell viability were evaluated. Western blotting was used for examining the apoptotic signaling proteins and inhibition of NF-kappaB activation. Levels of reactive oxygen species (ROS) production and mitochondria membrane potential (DeltaPsim) were examined by flow cytometry. KEY FINDINGS: The combined treatment of EGCG or TF with CDDP elicited significant inhibition of cell growth in comparison to either of them in both cell lines (p<0.05). Combinatorial treatment of both compounds potentially induced apoptosis by inhibiting the activation of Akt and NF-kappaB through blocking phosphorylation of inhibitor kappa Balpha. These combinations acted in concert to induce increase in ROS level, release of cytochrome-c and expression of p53 and Bax, with decrease in cellular glutathione contents, DeltaPsim, and Bcl-2 expression, thereby eventually resulting in the activation of caspases, poly(ADP)ribose polymerase cleavage and apoptosis of cancer cells. SIGNIFICANCE: Study suggests that both EGCG and TF chemosensitize the cervical cancer cells to CDDP-induced growth inhibition and apoptosis. By these combinations ~4 folds increase in CDDP induced-apoptosis with dose advantage of ~3 times could be achieved.
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[417]
TÍTULO / TITLE: - Biomarkers as Prognostic Factors for cN2 or 3 Non-small Cell Lung Cancer Treated by Induction Chemoradiotherapy and Surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1107-15.
AUTORES / AUTHORS: - Yokomise H; Liu D; Chang S; Go T; Ishikawa S; Misaki N; Nakashima N
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. yokomise@kms.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: We have reported promising results of surgery after induction chemoradiotherapy (carboplatin-taxane, 50 Gy radiation) for cN2,3 non-small cell lung cancer (NSCLC). In order to understand the underlying mechanism, expression of excision repair cross-complementing 1 (ERCC1), class III beta-tubulin (tubulin), thymidylate synthase (TYMS), and ribonucleotide reductase M1 (RRM1) were investigated. PATIENTS AND METHODS: Immunohistochemistry was performed in 45 patients with cN2,3 NSCLC, but only in twelve pathologically-complete response cases to evaluate intratumoral expression of these biomarkers. RESULTS: High expression of ERCC1, tubulin, TYMS and RRM1 was observed in 25 (55.6%), 19 (42.2%), 20 (44.4%) and 25 (55.6%) patients, respectively. Low expressions of ERCC1, tubulin, TYMS and RRM1 were favorable prognostic factors (p=0.044, p=0.025, p=0.039 and p=0.037, respectively). The simultaneously low expression of ERCC1 and tubulin was observed to be the most significant prognostic factor, by Cox regression analysis (hazard ratio=2.381; p=0.0059). CONCLUSION: Patients with simultaneous low expression of ERCC1 and tubulin are promising candidates for surgery after carboplatin-taxane chemoradiotherapy. For patients with high expression of ERCC1 and tubulin, uracil-tegafur, pemetrexed, and gemcitabine may be the alternative agents for personalized chemotherapy.
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[418]
TÍTULO / TITLE: - Arsenic trioxide induced apoptosis in retinoblastoma cells by abnormal expression of microRNA-376a.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasma. 2013;60(3):247-53. doi: 10.4149/neo_2013_033.
●● Enlace al texto completo (gratuito o de pago) 4149/neo_2013_033
AUTORES / AUTHORS: - Zhang Y; Wu JH; Han F; Huang JM; Shi SY; Gu RD; Chen XL; He B
RESUMEN / SUMMARY: - Arsenic trioxide (ATO) has been demonstrated to induce apoptosis in retinoblastoma cells, however, mechanisms responsible for this phenomenon are not fully understood. In the present study, we determined whether ATO induced apoptosis by abnormal expression of microRNA. In an apoptosis model of retinoblastoma cells subjected to 4 muM ATO for 72 hours, we found 14 miRNAs changed more than 2-fold by using miRNA microarray analysis. Most of these aberrantly expressed miRNAs were confirmed by quantitative RT-PCR. MiR-376a, asignificantly down-regulated miRNA, was selected for further study. The overexpression of miR-376a resulting from miR-376a mimic transfection significantly inhibited ATO-induced apoptosis. By contrast, miR-376a deficiency resulting from miR-376a inhibitor transfection aggravated ATO-induced apoptosis. Using bioinformatic algorithms, caspase-3, akey apoptosis executioner, was predicted as aputative target of miR-376a. The quantitative RT-PCR showed no effects of miR-376a mimic or inhibitor on caspase-3 mRNA level. However, the amount of caspase-3 proteins was reduced by miR-376a mimic, whereas increased by miR-376a inhibitor. Furthermore, the luciferase reporter assay confirmed caspase-3 to be atarget of miR-376a, and the apoptosis caused by miR-376a inhibitor were abolished by acaspase-3 inhibitor. These results suggest that ATO -induced apoptosis in retinoblastoma cells is part mediated by decreasing expression of miR-376a, which subsequently increased caspase-3 expression. Keywords: arsenic trioxide, apoptosis, retinoblastoma, microRNA.
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[419]
TÍTULO / TITLE: - Corosolic acid induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Chem Toxicol. 2013 Feb 20;56C:8-17. doi: 10.1016/j.fct.2013.02.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.fct.2013.02.002
AUTORES / AUTHORS: - Nho KJ; Chun JM; Kim HK
INSTITUCIÓN / INSTITUTION: - Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
RESUMEN / SUMMARY: - Corosolic acid (CRA), a triterpenoid from medicinal herbs, has been shown to induce apoptosis in several cell lines, with the exception of A549 cells. In this report, we investigated the apoptotic effect and mechanism of CRA in A549 cells. The present study shows that CRA significantly inhibits cell viability in a concentration- and time-dependent manner. Exposure to CRA induces sub-G1 cell cycle arrest and causes apoptotic death in A549 cells. CRA also triggers the activation of caspases and poly(ADP-ribose) polymerase, an effect antagonized by z-vad-fmk. In addition, exposure to CRA leads to a significant increase in the levels of reactive oxygen species (ROS) inA549 cells. Furthermore, exposure to the ROS scavenger N acetylcysteine (NAC)prevents CRA-induced apoptosis, suggesting a role for ROS in CRA-induced apoptosis. ROS are critical regulators of caspase-mediated apoptosis in A549 cells. These results indicate that CRA induces mitochondria-mediated and caspase-dependent apoptosis inA549 cells by altering anti-apoptotic proteins in a ROS-dependent manner.
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[420]
TÍTULO / TITLE: - Administration of PLGA nanoparticles carrying shRNA against focal adhesion kinase and CD44 results in enhanced antitumor effects against ovarian cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar 15. doi: 10.1038/cgt.2013.12.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.12
AUTORES / AUTHORS: - Zou L; Song X; Yi T; Li S; Deng H; Chen X; Li Z; Bai Y; Zhong Q; Wei Y; Zhao X
INSTITUCIÓN / INSTITUTION: - Department of Gynecology and Obstetrics, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China.
RESUMEN / SUMMARY: - The two membrane-bound proteins, focal adhesion kinase (FAK) and CD44, are involved in processes critical to cancer progression. FAK has an active role in angiogenesis, cell proliferation and cell apoptosis, whereas the heavily glycosylated CD44 has been implicated in cancer metastasis. Here, using short hairpin RNA (shRNA) against FAK and CD44, we demonstrate that simultaneous knockdown of both these genes inhibits cancer growth more efficiently than knockdown of either gene individually. Plasmids targeting these genes or non-relative control sequences were constructed and delivered to ovarian cancer targets by biodegradable poly D,L-lactide-co-glycolide acid nanoparticles (PLGANPs). Nude mice were utilized in an intraperitoneal model of ovarian carcinomatosis to assess antitumor efficacy in vivo. Single gene knockdown resulted in significantly smaller tumors than those observed in the empty-vector control (P’s<0.001). More importantly, knockdown of both genes resulted in tumors smaller than both the empty-vector group (P<0.0001) and the single gene knockdown groups (P’s<0.001). Knockdown of both FAK and CD44 resulted in tumors with inhibited angiogenesis, reduced proliferation and increased apoptosis as compared with controls (P’s<0.001) and single knockdown groups (P’s<0.05). These results indicate that dual knockdown of FAK and CD44 in the tumors of patients with ovarian cancer may have an enhanced therapeutic effect, and point toward a mechanism involving the inhibition of angiogenesis, cellular proliferation and the induction of apoptosis.Cancer Gene Therapy advance online publication, 15 March 2013; doi:10.1038/cgt.2013.12.
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[421]
TÍTULO / TITLE: - RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 21. doi: 10.3892/or.2013.2295.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2295
AUTORES / AUTHORS: - He M; Sun HG; Hao JY; Li YL; Yu JK; Yan YY; Zhao L; Li N; Wang Y; Bai XF; Yu ZJ; Zheng ZH; Mi XY; Wang EH; Wei MJ
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
RESUMEN / SUMMARY: - In the present study, we downregulated FANCF expression by small interfering RNA (siRNA) in OVCAR ovarian cancer cells to address the effects of decreased FANCF expression on the function of the Fanconi anemia (FA)/breast cancer susceptibility gene (BRCA) pathway. Furthermore, we investigated whether this method increases the sensitivity of OVCAR3 cells to adriamycin (ADM) and the possible mechanism(s). We found that silencing of FANCF inactivated the FA/BRCA pathway by decreasing the monoubiquitination and focus formation of FANCD2 and reduced the function of the FA/BRCA pathway, resulting in the inhibition of cell proliferation, increased cell apoptosis and DNA damage in OVCAR3 cells. Moreover, we observed that silencing of FANCF enhanced the antiproliferative effect of ADM in OVCAR3 cells and increased ADM intracellular accumulation consequently sensitizing OVCAR3 cells to ADM. Furthermore, silencing of FANCF increased cell apoptosis of OVCAR3 cells which was caused by decreased mitochondrial membrane potential (MMP)-induced DNA damage, activated Jun N-terminal kinase (JNK), increased release of cytochrome c, increased expression of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) dependent on JNK activation following treatment of ADM. Collectively, we confirm that silencing of FANCF sensitizes OVCAR3 ovarian cancer cells to ADM, suggesting that FANCF may serve as a potential target for therapeutic strategies in the treatment of ovarian cancer.
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[422]
TÍTULO / TITLE: - DNA ploidy: a prognostic factor of response to chemotherapy and survival in metastatic gastric adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1209-14.
AUTORES / AUTHORS: - Syrios J; Kechagias G; Agrogiannis G; Xynos ID; Kavantzas N; Lazaris AC; Amptoulach S; Mourati A; Sougioultzis S; Patsouris ES; Tsavaris N
INSTITUCIÓN / INSTITUTION: - 6A Samou Street, Gerakas 15344, Attiki, Greece. syriosi@yahoo.gr.
RESUMEN / SUMMARY: - BACKGROUND: Metastatic gastric adenocarcinoma confers a dismal prognosis. Several prognostic factors are needed to distinguish patients that will benefit from chemotherapy. In this setting, the prognostic impact of DNA ploidy is still unclear. MATERIALS AND METHODS: The records of 61 patients with metastatic gastric adenocarcinoma were retrospectively reviewed. Response to chemotherapy and overall survival (OS) were assessed and correlated to tumour DNA ploidy index, which was calculated by cytometric image analysis. RESULTS: The median value of DNA ploidy index was 2.3. Patients with a low index responded better to chemotherapy than those with a higher index (p<0.01). Nevertheless, when the median value was used as a cut-off, no significant correlation of DNA ploidy index with response to chemotherapy (p=0.41) or OS (p=0.09) was observed. CONCLUSION: The prognostic role of DNA ploidy in metastatic gastric adenocarcinoma is still debatable. In this study, a low DNA ploidy index was associated with favorable prognosis; however, a suitable cut-off value is not yet available.
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[423]
TÍTULO / TITLE: - In silico identification of poly(ADP-ribose)polymerase-1 inhibitors and their chemosensitizing effects against cisplatin-resistant human gastric cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Mar 1. pii: S0960-894X(13)00281-3. doi: 10.1016/j.bmcl.2013.02.094.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.02.094
AUTORES / AUTHORS: - Le TV; Suh JH; Kim N; Park HJ
INSTITUCIÓN / INSTITUTION: - School of Pharmacy, Sunkyunkwan University, Suwon 440-746, Republic of Korea.
RESUMEN / SUMMARY: - Poly(ADP-ribose)polymerase-1 (PARP-1) enzyme is involved in the repair of DNA damages made by certain anticancer agents. It is suggested that PARP-1 inhibitors potentiate the cytotoxic effects and circumvent the resistance of DNA-modifying anticancer agents such as cisplatin. In this study, we conducted virtual screening of Korea Chemical Bank database targeting PARP-1 and identified several potent PARP-1 inhibitors with submicromolar IC50 values (77-79nM). We then examined the chemosensitization of cisplatin by pre-treatment of PARP-1 inhibitors in cisplatin-resistant human gastric cancer cells. Our results show that PARP-1 inhibitors suppress the formation of poly(ADP-ribose) and enhance the cytotoxicity of cisplatin.
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[424]
TÍTULO / TITLE: - Cell cycle arrest and apoptosis induced by O-acetyl-GD2-specific monoclonal antibody 8B6 inhibits tumor growth in vitro and in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Jan 28. pii: S0304-3835(13)00075-X. doi: 10.1016/j.canlet.2013.01.032.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.032
AUTORES / AUTHORS: - Cochonneau D; Terme M; Michaud A; Dorvillius M; Gautier N; Frikeche J; Alvarez-Rueda N; Bougras G; Aubry J; Paris F; Birkle S
INSTITUCIÓN / INSTITUTION: - Inserm U. 892, Centre de Recherche en Cancerologie de Nantes-Angers, Institut de Recherche en Sante de l’Universite de Nantes, 8 quai Moncousu, F-44007 Nantes cedex 1, France; CNRS 6299, Centre de Recherche en Cancerologie de Nantes-Angers, Institut de Recherche en Sante de l’Universite de Nantes, 8 quai Moncousu, F-44007 Nantes cedex, France.
RESUMEN / SUMMARY: - O-Acetyl-GD2 ganglioside is suitable antigen for tumor immunotherapy with specific therapeutic antibody. Here, we investigate the anti-tumor activity of O-acetyl-GD2-specific monoclonal antibody 8B6 on O-acetyl-GD2-positive tumor cells. The results indicated that mAb 8B6 induced growth inhibition of O-acetyl-GD2-expressing tumor cell lines in vitro with features of cell cycle arrest and apoptosis. Monoclonal antibody 8B6 treatment was also very effective in suppression of tumor growth in mice by reducing the proliferation index and increasing the apoptotic index. Such a study represents a useful framework to optimize immunotherapy with O-acetyl-GD2-specific antibody in combination with chemotherapeutic agents.
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[425]
TÍTULO / TITLE: - Analysis of Factors that Influence the Accuracy of Magnetic Resonance Imaging for Predicting Response after Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2925-6
AUTORES / AUTHORS: - Ko ES; Han BK; Kim RB; Ko EY; Shin JH; Hahn SY; Nam SJ; Lee JE; Lee SK; Im YH; Park YH
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - PURPOSE: The purpose of this study was to evaluate the accuracy of breast magnetic resonance imaging (MRI) to predict residual lesion size after neoadjuvant chemotherapy (NAC) and to determine the factors that influence the accuracy of response prediction. METHODS: This study comprised 166 patients who underwent MRI before and after NAC, but before surgery. The longest diameter of the residual cancer was measured using MRI and correlated with pathologic findings. Patients were further divided into subgroups according to various radiologic and histopathologic factors. Pathologic complete response (pCR) was defined as the absence of residual invasive cancer cells. The Pearson correlation was used to correlate tumor size as determined by MRI and pathology, and the Mann-Whitney U test and Kruskal-Wallis test were used to compare MRI-pathologic size discrepancies according to various clinical, histopathologic factors, and MRI findings. RESULTS: Of the 166 women, 40 achieved pCR. The overall sensitivity, specificity, and accuracy for diagnosing invasive residual disease by using MRI were 96, 65, and 89 %, respectively. The Pearson’s correlation coefficient between the tumor sizes measured using MRI and pathology was 0.749 (P < 0.001). The size discrepancy was significantly greater in patients with estrogen receptor-positive cancer (P = 0.037), in cancers with low nuclear grade (P = 0.007), and in cancers shown as diffuse non-mass-like enhancement on MRI (P = 0.001). CONCLUSIONS: Size prediction is less accurate in cases with estrogen receptor-positive breast cancer, low nuclear grade, and diffuse non-mass-like enhancement on initial MRI.
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[426]
TÍTULO / TITLE: - Induction of apoptosis in multiple myeloma cells by a statin-thalidomide combination can be enhanced by p38 MAPK inhibition.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 20. pii: S0145-2126(13)00038-6. doi: 10.1016/j.leukres.2013.01.022.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.01.022
AUTORES / AUTHORS: - Slawinska-Brych A; Zdzisinska B; Mizerska-Dudka M; Kandefer-Szerszen M
INSTITUCIÓN / INSTITUTION: - Department of Cell Biology, Maria Curie-Sklodowska University, Lublin, Poland.
RESUMEN / SUMMARY: - The mechanisms involved in anti-myeloma activity of statins combined with thalidomide were studied in multiple myeloma (MM) cells. In addition, the effect of p38 MAPK inhibition on the induction of apoptosis in MM cells by the combination of thalidomide and simvastatin was investigated. Thalidomide was observed to significantly potentiate the antiproliferative activity of statins and enhance the proapoptotic effect of simvastatin and lovastatin. What is more, the combination of thalidomide with statins inhibited cell migration and decreased the production of VEGF and MMP-9 in MM cells more effectively than each of these drugs used separately. The combination of simvastatin and thalidomide augmented caspase 8 and 3 activation, and the additional application of p38 MAPK inhibitor resulted in enhanced apoptosis of MM cells concomitant with increased caspase 9 and 3 activation, as well as JNK phosphorylation. The results suggest that p38 inhibitors together with the combination of simvastatin and thalidomide have the potential to be used in MM treatment.
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[427]
TÍTULO / TITLE: - Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chem Biol Interact. 2013 Mar 22. pii: S0009-2797(13)00072-0. doi: 10.1016/j.cbi.2013.03.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cbi.2013.03.011
AUTORES / AUTHORS: - Yu SY; Liu HF; Wang SP; Chang CC; Tsai CM; Chao JI
INSTITUCIÓN / INSTITUTION: - Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu 300, Taiwan.
RESUMEN / SUMMARY: - Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), has been used to treat numerous cancers; however, evidence has shown that cancer cells can become resistant to gefitinib during therapy. Here, we report a human proto-oncogene, securin, which displays resistance to death in cancer cells. Gefitinib treatment decreases securin levels at the protein level by inducing protein instability but did not affect on the securin gene expression. Treatment with gefitinib induced cytotoxicity in various human cancer cell types, including RKO (colon cancer), A549 (lung cancer), BFTC905 (bladder cancer), MCF7 (breast cancer) and A375 (skin cancer). BFTC905 and A549 cells expressed relatively high levels of the phosphorylated and total EGFR proteins; however, A375, MCF7 and RKO cells did not markedly express these proteins. Moreover, following treatment with gefitinib, the securin-wild type cancer cells were more resistant to apoptotic induction than the securin-null cancer cells. Surprisingly, both the securin-wild type and securin-null cancer cells expressed the EGFR protein at similar levels. Treatment with gefitinib induced mitochondrial dysfunction, cytochrome c release, caspase-3 activation and poly (ADP-ribose) polymerase protein cleavage, indicating that apoptosis occurred in these cancer cells. The transfection of a GPF-securin expression vector increased both the proliferation rates and resistance to gefitinib-induced death in these cancer cells. Taken together, these findings demonstrate that the presence of securin promotes resistance to gefitinib-induced apoptosis via an EGFR-independent pathway in human cancer cells.
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[428]
TÍTULO / TITLE: - Polypeptide cationic micelles mediated co-delivery of docetaxel and siRNA for synergistic tumor therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Apr;34(13):3431-8. doi: 10.1016/j.biomaterials.2013.01.053. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.053
AUTORES / AUTHORS: - Zheng C; Zheng M; Gong P; Deng J; Yi H; Zhang P; Zhang Y; Liu P; Ma Y; Cai L
INSTITUCIÓN / INSTITUTION: - CAS Key Lab of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
RESUMEN / SUMMARY: - Combination of two or more therapeutic strategies with different mechanisms can cooperatively impede tumor growth. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a single nanoparticle (NP) provides a rational strategy for combined cancer therapy. Here, we prepared polypeptide micelle nanoparticles (NPs) of a triblock copolymer poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) to systemically codeliver docetaxel (DTX) and siRNA-Bcl-2 for an effective drug/gene vector. The hydrophobic PLLeu core entrapped with anticancer drugs, while the PLL polypeptide cationic backbone allowed for electrostatic interaction with the negatively charged siRNA. The resulting micelle NP exhibited very stable, good biocompatible and excellent passive targeted properties. The micelle complexes with siRNA-Bcl-2 effectively knocked down the expression of Bcl-2 mRNA and protein. Moreover, the co-delivery system of DTX and siRNA-Bcl-2 (DTX-siRNA-NPs) obviously down-regulation of the anti-apoptotic Bcl-2 gene and enhanced antitumor activity with a smaller dose of DTX, resulting the significantly inhibited tumor growth of MCF-7 xenograft murine model as compared to the individual siRNA and only DTX treatments. Our results demonstrated well-defined PEG-PLL-PLLeu polypeptide cationic micelles with the excellent synergistic effect of DTX and siRNA-Bcl-2 in combined cancer therapy.
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[429]
TÍTULO / TITLE: - Tumor blood flow from arterial spin labeling perfusion MRI: A key parameter in distinguishing high-grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high-grade gliomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Magn Reson Imaging. 2013 Feb 6. doi: 10.1002/jmri.24026.
●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24026
AUTORES / AUTHORS: - Yoo RE; Choi SH; Cho HR; Kim TM; Lee SH; Park CK; Park SH; Kim IH; Yun TJ; Kim JH; Sohn CH; Han MH; Chang KH
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - PURPOSE: To evaluate the usefulness of pseudo-continuous arterial spin labeling (pCASL) imaging in differentiating high-grade gliomas from lymphomas and in noninvasively predicting genetic biomarkers in high-grade gliomas. MATERIALS AND METHODS: Twelve glioblastoma multiforme (GBM), 3 anaplastic astrocytoma (AA), 5 recurred GBM, and 9 lymphoma patients underwent conventional MR and pCASL imaging. On pCASL perfusion map, mean absolute tumor blood flow (mTBF) was calculated from five regions of interest (ROIs) within the enhancing portion of the tumor. Relative TBF (rTBF = mTBF/mBF(gm) x 100) was also calculated. mTBF and rTBF of high-grade gliomas and lymphomas were compared using unpaired Student’s t-test and receiver operating characteristic (ROC) analysis. Additionally, the association of TBF and six immunohistochemically confirmed genetic biomarkers was analyzed by Pearson correlation analysis in the group of high-grade gliomas. RESULTS: Both mTBF and rTBF of the high-grade gliomas were significantly higher than those of the lymphomas: 92.1 +/- 34.7 versus 53.6 +/- 30.5 mL/min/100 mg (P = 0.008) and 182.3 +/- 69.5 versus 92.5 +/- 44.9 (P = 0.002), respectively. Only epidermal growth factor receptor (EGFR) expression status showed a significant positive correlation with mTBF(P = 0.015) and rTBF(P = 0.007). CONCLUSION: pCASL imaging may facilitate differentiation of high-grade gliomas from lymphomas and prediction of EGFR expression status in high-grade gliomas. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 Wiley Periodicals, Inc.
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[430]
TÍTULO / TITLE: - A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2475-4
AUTORES / AUTHORS: - Szekely B; Iwamoto T; Szasz AM; Qi Y; Matsuoka J; Symmans WF; Tokes AM; Kulka J; Swanton C; Pusztai L
INSTITUCIÓN / INSTITUTION: - 2nd Department of Pathology, Semmelweis University, Budapest, Hungary, szekelybora@gmail.com.
RESUMEN / SUMMARY: - The goal of this study was to assess the prognostic value of a 3-gene (TOP2A, FOXM1, and MKI67) proliferation score and use it to risk stratify grade-2, estrogen receptor (ER)-positive breast cancers into low- and high-risk groups. We used 4 different breast cancer gene expression datasets including two cohorts of patients who received no systemic adjuvant therapy (Mainz: n = 206, TRANSBIG: n = 134) and two other cohorts that received adjuvant tamoxifen (JBI: n = 227, MDACC/SET: n = 192). We compared individual and combined expression values of the 3 genes between grade 1, 2, and 3 tumors and plotted distant metastasis-free survival (DMFS) curves by the 3-gene score for grade-2 cancers. We compared the prognostic value of the 3-gene score to the Genomic Grade Index (GGI). The individual and combined expression of TOP2A, FOXM1, and MKI67 were significantly different between the 3 histological grade groups with the highest expression in grade-3 and the lowest in grade-1 cancers. Expression levels were variable in grade-2 cancers. Grade-2 tumors with high expression of the 3 genes (>median) showed significantly worse DMFS in one prognostic and one tamoxifen-treated set and showed a similar but non-significant trend for worse survival in the remaining two datasets. The 3-gene score performed equally well in risk stratification as the GGI. A 3-gene proliferation score shows similar prognostic value as the GGI in ER-positive, grade-2 cancers and may serve as basis for a PCR-based assay that could aid prognostic prediction for clinically intermediate-risk cancers.
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[431]
TÍTULO / TITLE: - Striatal TH-immunopositive fibers recover after an intrastriatal injection of 6-hydroxydopamine in golden hamsters treated with prednisolone: Roles of tumor necrosis factor-alpha and inducible nitric oxide synthase in neurodegeneration.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neurosci Res. 2013 Mar 5. pii: S0168-0102(13)00038-2. doi: 10.1016/j.neures.2013.02.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.neures.2013.02.004
AUTORES / AUTHORS: - Rodriguez S; Uchida K; Nakayama H
INSTITUCIÓN / INSTITUTION: - Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo 113-8657, Japan. Electronic address: sebastian.rodriguez1978@hotmail.com.
RESUMEN / SUMMARY: - Neuroinflammation has been implicated in the pathology of neurodegenerative processes such as Parkinson’s disease (PD). Using the golden hamster (GH) 6-hydroxydopamine (6-OHDA) model, we investigated whether the attenuation of neuroinflammation influences the onset and progression of dopamine cell degeneration. 6-OHDA-injected GH received a treatment of minocycline (MINO), prednisolone (Pred) or a combination of minocycline and prednisolone (MINO+Pred). Immunohistochemistry for tyrosine hydroxylase (TH), Iba-1 and glial fibrillary acidic protein (GFAP) was used to evaluate lesions in the nigrostriatal axis and the amount of activated microglia and astroglia, respectively. RT-PCR was used to measure mRNA levels of cytokines and trophic neuroprotective factors. The three anti-inflammatory treatments dramatically reduced activated microglia in the nigrostriatal axis. In addition, TH-immunostaining showed that the positive areas in the ipsilateral striatum of either MINO or Pred groups were higher than that of control. However, only in Pred group this recovery was significant. mRNA measurements demonstrated lower levels of TNF-alpha, iNOS, BDNF and GDNF in Pred group when compared with controls. The results suggest that TH-immunopositive fibers have the ability to recover after 6-OHDA-induced toxicity of dopaminergic neurons, and this recovery may be due to a decrease in the microglial production of TNF-alpha and iNOS.
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[432]
TÍTULO / TITLE: - Skin rash during erlotinib for advanced non-small cell lung cancer: is age a clinical predictor?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Dermatol Res. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s00403-013-1345-6
AUTORES / AUTHORS: - Giuliani J; Marzola M
INSTITUCIÓN / INSTITUTION: - Palliative Care Unit, Mater Salutis Hospital, ULSS 21, Via Gianella 1, 37045, Legnago (Verona), Italy, giuliani.jacopo@alice.it.
RESUMEN / SUMMARY: - The aim of this study was to evaluate the intensity and the duration of acneiform skin rash in young and elderly patients, to define a possible relationship between age and skin rash. We retrospectively analyzed all consecutive patients with advanced NSCLC who developed acneiform skin rash during erlotinib treatment at our Clinical Oncology Unit from June 2006 to May 2011. We divided the general case study into two subgroups: young and elderly patients (>/=65 years) and we compared clinical, pathological and therapeutical characteristics of both subgroups. Among 25 patients affected by advanced NSCLC treated with erlotinib during the reference period, 19 patients (76.0 %) developed acneiform skin rash. Fourteen (73.7 %) of 19 patients were elderly. The majority of elderly patients has developed acneiform skin rash (82.4 vs 62.5 %). In addition, in elderly patients, acneiform skin rash has a higher intensity (for mild rash 7.1 vs 20.0 %, for moderate rash 57.1 vs 60.0 %, for severe rash 35.7 vs 20.0 %) and longer duration, especially for mild and moderate rash (for mild rash 154 vs 40 days, for moderate rash 120 vs 76 days, for severe rash 31 vs 85 days). The univariate analysis showed no statistical significant difference in OS between young and elderly patients (p = 0.191), such as age, does not seem to influence the appearance (p = 0.386), duration (p = 0.455) and grade of acneiform skin rash (p = 0.765). In conclusion, we can affirm that age is an insufficient predictor of acneiform skin rash during erlotinib treatment in advanced NSCLC and does not seem to statistically influence the appearance, duration and grade of skin rash.
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[433]
TÍTULO / TITLE: - mTOR inhibitor RAD001 (everolimus) induces apoptotic, not autophagic cell death, in human nasopharyngeal carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Med. 2013 Apr;31(4):904-12. doi: 10.3892/ijmm.2013.1282. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1282
AUTORES / AUTHORS: - Cai Y; Xia Q; Su Q; Luo R; Sun Y; Shi Y; Jiang W
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P.R. China.
RESUMEN / SUMMARY: - Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key element in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Moreover, it is a negative regulator of autophagy and acts as a central regulator in cell growth. For the treatment of cancer, mTOR is a novel and validated therapeutic target. Previous studies have shown that Akt is frequently activated in nasopharyngeal carcinoma (NPC) tissues; thus, the inhibition of mTOR may be a treatment strategy for this tumor type. To evaluate the effect of the mTOR inhibitor RAD001 on NPC cell lines, we performed 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assays, lactate dehydrogenase (LDH) assays, western blotting and flow cytometry to evaluate the mechanisms of cell death. The growth of both CNE-1 and HONE-1 cells was inhibited in a time- and dose-dependent manner. CNE-1 was more sensitive, with a 50% growth inhibition (GI50) of 30.0+/-1.0 microM compared to HONE-1, cells which had a GI50 of 56.9+/-13.1 microM. RAD001 induced apoptosis and autophagy in both cell lines. RAD001 induced a significant increase in growth inhibition in the two cell lines when used in combination with the autophagy inhibitor, 3-methyladenine; however, the percentages of apoptotic cells decreased when RAD001 was combined with the caspase inhibitor, z-VAD-fmk. In conclusion, the main mechanism of the mTOR inhibitor RAD001 in these two NPC cells was apoptotic, not autophagic cell death. The combination of RAD001 with autophagy inhibitors may be a useful therapeutic strategy for nasopharyngeal carcinoma.
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[434]
TÍTULO / TITLE: - PEGylation of interferon alpha2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Control Release. 2013 Mar 15. pii: S0168-3659(13)00149-1. doi: 10.1016/j.jconrel.2013.03.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jconrel.2013.03.006
AUTORES / AUTHORS: - Kaminskas LM; Ascher DB; McLeod VM; Herold MJ; Le CP; Sloan EK; Porter CJ
INSTITUCIÓN / INSTITUTION: - Drug Delivery Disposition and Dynamics Group, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia. Electronic address: lisa.kaminskas@monash.edu.
RESUMEN / SUMMARY: - The efficacy of protein-based therapeutics with indications in the treatment of lymphatic diseases is expected to be improved by enhancing lymphatic disposition. This study was therefore aimed at examining whether PEGylation can usefully be applied to improve the lymphatic uptake of interferon alpha2 and whether this ultimately translates into improved therapeutic efficacy against lymph-resident cancer. The lymphatic pharmacokinetics of interferon alpha2b (IFN, 19kDa) and PEGylated interferon alpha2b (IFN-PEG12, 31kDa) or alpha2a (IFN-PEG40, 60kDa) was examined in thoracic lymph duct cannulated rats. IFN was poorly absorbed from the SC injection site (Fabs 36%) and showed little uptake into lymph after SC or IV administration (</=1%). In contrast, IFN-PEG12 was efficiently absorbed from the SC injection site (Fabs 82%) and approximately 20% and 8% of the injected dose were recovered in thoracic lymph over 30h after SC or IV administration respectively. IFN-PEG40, however, was incompletely absorbed from the SC injection site (Fabs 23%) and showed similar lymphatic access after SC administration to IFN-PEG12 (21%). The recovery of IFN-PEG40 in thoracic lymph after IV administration, however, was significantly greater (29%) when compared to IV IFN-PEG12. The anti-tumour efficacy of interferon against axillary metastases of a highly lymph-metastatic variant of human breast MDA-MB-231 carcinoma was significantly increased by SC administration of lymph-targeted IFN-PEG12 when compared to the administration of IFN on the ipsilateral side to the axillary metastasis. Optimal PEGylation may therefore represent a viable approach to improving the lymphatic disposition and efficacy of therapeutic proteins against lymphatic diseases.
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[435]
TÍTULO / TITLE: - Expression and prognostic significance of GATA-binding protein 2 in colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):498. doi: 10.1007/s12032-013-0498-7. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0498-7
AUTORES / AUTHORS: - Chen L; Jiang B; Wang Z; Liu M; Ma Y; Yang H; Xing J; Zhang C; Yao Z; Zhang N; Cui M; Su X
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China.
RESUMEN / SUMMARY: - GATA-binding protein 2 (GATA2) is a nuclear transcription factor that plays a critical role in tumorigenesis. High levels of GATA2 expression are correlated with poor survival outcomes in many types of cancer. However, the expression and prognostic significance of GATA2 in colorectal cancer remain unknown. In this study, GATA2 protein expression was examined using immunohistochemistry in 307 colorectal cancer tissues, and its association with clinicopathological features and prognosis was analyzed. The expression of GATA2 was found to be significantly higher in colorectal cancer tissues than in matched adjacent noncancerous tissues (60.3 vs. 9.0 %, P < 0.0001). The expression of GATA2 was significantly correlated with tumor location (P = 0.005), histological type (P = 0.019), and recurrence (P = 0.009). Kaplan-Meier survival analysis demonstrated that patients with high levels of GATA2 expression had worse disease-free survival outcomes than those with low levels of GATA2 expression (P = 0.016). Univariate analysis showed high levels of GATA2 expression to be significantly associated with shorter periods of disease-free survival (HR 2.196; 95 % CI 1.142-4.226; P = 0.018). Multivariate analysis showed GATA2 expression to be an independent prognostic factor for patients with colorectal cancer (HR 1.952; 95 % CI 1.010-3.775; P = 0.047). These findings suggest that high levels of GATA2 expression may be a useful indicator of disease recurrence after curative colorectal cancer treatment.
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[436]
TÍTULO / TITLE: - miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 7. doi: 10.3892/or.2013.2338.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2338
AUTORES / AUTHORS: - Xu Y; An Y; Wang Y; Zhang C; Zhang H; Huang C; Jiang H; Wang X; Li X
INSTITUCIÓN / INSTITUTION: - Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu 210029, P.R. China.
RESUMEN / SUMMARY: - Hepatocellular carcinoma (HCC) ranks third in cancer-related mortality due to late diagnosis and poor treatment options. Autophagy is a lysosome-mediated protein and organelle degradation process which is characterized by the formation of double-membrane vesicles, known as autophagosomes. Increasing evidence reveals that autophagy functions as a survival mechanism in liver cancer cells against drug-induced apoptosis. In this study, we found that autophagy was suppressed by miR-101 in the HCC cell line HepG2. miR-101 inhibited autophagy via targets including RAB5A, STMN1 and ATG4D. Moreover, miR-101 enhanced apoptosis induced by cisplatin in the HepG2 cell line. The possible mechanism of this effect may be through inhibition of autophagy. Our results indicate a novel and critical role for miR-101 and autophagy in the chemoresistance of cisplatin in HCC. We propose that gene therapy targeting miR-101/autophagy should be investigated further as a potential alternative therapeutic strategy for HCC.
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[437]
TÍTULO / TITLE: - Lithium enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biometals. 2013 Feb 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10534-012-9607-x
AUTORES / AUTHORS: - Lan Y; Liu X; Zhang R; Wang K; Wang Y; Hua ZC
INSTITUCIÓN / INSTITUTION: - The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
RESUMEN / SUMMARY: - Non-small cell lung cancer (NSCLC) A549 cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Therefore, combination therapy using sensitizing agents to overcome TRAIL resistance may provide new strategies for treatment of NSCLC. Here, we investigated whether lithium chloride (LiCl), a drug for mental illness, could sensitize A549 cells to TRAIL-induced apoptosis. We observed that LiCl significantly enhanced A549 cells apoptosis through up-regulation of death receptors DR4 and DR5 and activation of caspase cascades. In addition, G2/M arrest induced by LiCl also contributed to TRAIL-induced apoptosis. Concomitantly, LiCl strongly inhibited the activity of c-Jun N-terminal kinases (JNKs), and the inhibition of JNKs by SP600125 also induced G2/M arrest and augmented cell death caused by TRAIL or TRAIL plus LiCl. However, glycogen synthase kinase-3beta (GSK3beta) inhibition was not involved in TRAIL sensitization induced by LiCl. Collectively, these findings indicated that LiCl sensitized A549 cells to TRAIL-induced apoptosis through caspases-dependent apoptotic pathway via death receptors signaling and G2/M arrest induced by inhibition of JNK activation, but independent of GSK3beta.
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[438]
TÍTULO / TITLE: - Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: Mineralization and its effect on tumor targetability in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Control Release. 2013 Mar 6. pii: S0168-3659(13)00119-3. doi: 10.1016/j.jconrel.2013.02.022.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jconrel.2013.02.022
AUTORES / AUTHORS: - Han HS; Lee J; Kim HR; Chae SY; Kim M; Saravanakumar G; Yoon HY; You DG; Ko H; Kim K; Kwon IC; Park JC; Park JH
INSTITUCIÓN / INSTITUTION: - Department of Polymer Science and Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
RESUMEN / SUMMARY: - The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery. In this study, to develop biostable nanoparticles with high tumor targetability, poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method. The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153.7+/-4.5nm) than bare PEG-HANPs (265.1+/-9.5nm), implying that mineralization allows the formation of compact nanoparticles. Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions (<pH6.5), their sizes increased rapidly due to dissolution of the inorganic minerals. Doxorubicin (DOX), chosen as the model anticancer drug, was effectively encapsulated into the bare and mineralized nanoparticles. For bare PEG-HANPs, DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution. On the other hand, DOX release from M-PEG-HANPs was pH-dependent: i.e. DOX was slowly released from nanoparticles under physiological condition (pH7.4), whereas its release rates were much higher at mildly acidic environments (<pH6.5). From in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs. The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice. Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs. Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.
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[439]
TÍTULO / TITLE: - An analysis of protein-protein interactions in cross-talk pathways reveals CRKL as a novel prognostic marker in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Proteomics. 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1074/mcp.O112.020404
AUTORES / AUTHORS: - Liu CH; Chen TC; Chau GY; Jan YH; Chen CH; Hsu CN; Lin KT; Juang YL; Lu PJ; Cheng HC; Chen MH; Chang CF; Ting YS; Kao CY; Hsiao M; Huang CY
INSTITUCIÓN / INSTITUTION: - National Taiwan University, Taiwan;
RESUMEN / SUMMARY: - Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKL-FLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition (EMT) process. Our immunohistochemical analysis shows high expression levels of CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.
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[440]
TÍTULO / TITLE: - Genistein alleviates the mitochondria-targeted DNA damage induced by beta-amyloid peptides 25-35 in C6 glioma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neurochem Res. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s11064-013-1019-y
AUTORES / AUTHORS: - Ma WW; Hou CC; Zhou X; Yu HL; Xi YD; Ding J; Zhao X; Xiao R
INSTITUCIÓN / INSTITUTION: - School of Public Health and Family Medicine, Capital Medical University, No.10 Xitoutiao, No.10 Xitoutiao, You An Men, Beijing, 100069, People’s Republic of China.
RESUMEN / SUMMARY: - Reactive oxygen species (ROS) are mainly produced by mitochondria which can cause oxidative stress. It has been considered that mitochondrial damage induced by oxidative stress is related to Alzheimer’s disease (AD). Besides, mitochondrial DNA (mtDNA) is more vulnerable to oxidative damage than other biomacromolecules, causing serious dysfunction to mitochondria. beta-amyloid peptides (Abeta) is a main factor responsible for the occurence and development of AD. Astrocytes is an important target cell for Abeta’ toxicity and can be activated to neglect their normal fountain in the central nervous system. Genistein (Gen), a main active ingredient of soybean isoflavone, has been shown to have neuroprotective effects by antagonizing oxidative damage induced by Abeta. Thus, in the present study, we evaluated Abeta25-35 induced mitochondrial DNA (mtDNA) damage and the protective effect of Gen in C6 glioma cells (C6 cells). The study design was consisted of four groups: control group (vehicle), Abeta group treated with Abeta25-35, Gen + Abeta group treated with Gen + Abeta25-35 and Gen group treated with Gen only. C6 cells were pre-incubated with or without Gen (50 muM) for 2 h followed by the incubation with Abeta25-35 (25 muM) for another 24 h. Then the cells were harvested and processed to perform the analysis according to protocols. The mitochondrial ROS in C6 cells were measured by fluorescence spectrometer. Enzyme-linked immunosorbent assay (ELISA) was used to detect the mitochondrial reduced glutathione (GSH) and oxidized glutathione (GSSG) in C6 cells, then the ratio of GSH and GSSG was calculated. The levels of 8-hydroxydeoxyguanosine (8-OHdG) in C6 cells was also detected by ELISA. In addition, mtDNA deletion was detected by polymerase chain reaction (PCR). The mRNA and protein expression of 8-oxoguanine DNA glycosylase (OGG1) in both C6 cells and its mitochondria, and manganese superoxide dismutase (MnSOD) in mitochondria were detected by using reverse transcription-PCR and Western blot. The results showed that the increased mitochondrial ROS accumulation in C6 cells induced by Abeta was profoundly reversed by pre-treaded with Gen (p < 0.05). The ratio of GSH and GSSG in mitochondria was significantly increased in both Gen + Abeta group and Gen group compared with Abeta group (p < 0.05). The levels of 8-OHdG in C6 cells and mtDNA deletion were decreased after pre-treated with Gen (p < 0.05). Gen could also up-regulate the mRNA and protein expression of OGG1 in both C6 cells and its mitochondria and mitochondrial MnSOD compared with the Abeta group (p < 0.05). These results confirmed that Gen could alleviate the mitochondria-targeted oxidative damage induced by beta-amyloid 25-35 in C6 cells which might be useful for the treatment of neurodegenerative diseases.
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[441]
TÍTULO / TITLE: - Cadmium telluride quantum dots cause oxidative stress leading to extrinsic and intrinsic apoptosis in hepatocellular carcinoma HepG2 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Toxicology. 2013 Feb 26;306C:114-123. doi: 10.1016/j.tox.2013.02.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.tox.2013.02.010
AUTORES / AUTHORS: - Nguyen KC; Willmore WG; Tayabali AF
INSTITUCIÓN / INSTITUTION: - Biotechnology Laboratory, Mechanistic Studies Division, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 50 Colombine Driveway, Ottawa, ON, Canada K1A 0K9; Biology Department, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada K1S 5B6.
RESUMEN / SUMMARY: - The mechanisms of toxicity related to human hepatocellular carcinoma HepG2 cell exposures to cadmium telluride quantum dots (CdTe-QDs) were investigated. CdTe-QDs caused cytotoxicity in HepG2 cells in a dose- and time-dependent manner. Treated cells showed an increase in reactive oxygen species (ROS). Altered antioxidant levels were demonstrated by depletion of reduced glutathione (GSH), a decreased ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and an increased NF-E2-related Factor 2 (Nrf2) activation. Enzyme assays showed that superoxide dismutase (SOD) activity was elevated whereas catalase (CAT) and glutathione-S-transferase (GST) activities were depressed. Further analyses revealed that CdTe-QD exposure resulted in apoptosis, indicated by changes in levels of caspase-3 activity, poly ADP-ribose polymerase (PARP) cleavage and phosphatidylserine externalization. Extrinsic apoptotic pathway markers such as Fas levels and caspase-8 activity increased as a result of CdTe-QD exposure. Involvement of the intrinsic/mitochondrial apoptotic pathway was indicated by decreased levels of B-cell lymphoma 2 (Bcl2) protein and mitochondrial cytochrome c, and by increased levels of mitochondrial Bcl-2-associated X protein (Bax) and cytosolic cytochrome c. Further, mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (Erk1/2), and p38 were all activated. Our findings reveal that CdTe-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein kinases, leading to apoptosis via both extrinsic and intrinsic pathways. Since the effects of CdTe-QDs on selected biomarkers were similar or greater compared to those of CdCl2 at equivalent concentrations of cadmium, the study suggests that the toxicity of CdTe-QDs arises from a combination of the effects of cadmium and ROS generated from the NPs.
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[442]
TÍTULO / TITLE: - Induction of endoplasmic reticulum stress-mediated apoptosis and non-canonical autophagy by luteolin in NCI-H460 lung carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Chem Toxicol. 2013 Feb 20;56C:100-109. doi: 10.1016/j.fct.2013.02.022.
●● Enlace al texto completo (gratuito o de pago) 1016/j.fct.2013.02.022
AUTORES / AUTHORS: - Park SH; Park HS; Lee JH; Chi GY; Kim GY; Moon SK; Chang YC; Hyun JW; Kim WJ; Choi YH
INSTITUCIÓN / INSTITUTION: - Department of Pathology, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.
RESUMEN / SUMMARY: - In this study, we investigated the anti-cancer effects of luteolin, a member of the flavonoid family, in NCI-H460 human lung carcinoma cells. It was shown that luteolin induces apoptotic cell death through modulating both the extrinsic pathway and intrinsic pathways, which are suppressed by z-VAD-fmk, indicating that luteolin triggers caspase-dependant apoptosis. Furthermore, we found that the alpha subunit of the eukaryotic initiation factor 2 (eIF2alpha/C/EBP homologous protein pathway, but not the c-Jun N-terminal kinase pathway, played a critical role in induction of apoptosis by luteolin. The data indicated that luteolin also induces autophagy; evidence for this is the accumulation of microtubule-associated protein light chain-3 (LC3) II protein, the increase of LC3 puncta as well as an enhanced autophagy flux. In addition, inhibiting autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that luteolin-induced autophagy functions as a cell death mechanism. Notably, the activated caspases that appeared with luteolin treatment cleaved Beclin-1, and the expression of LC3II remained the same even after cells were challenged with Beclin-1 siRNA, demonstrating that luteolin induces Beclin-1-independent autophagy. Taken together, our findings showed that luteolin triggers both endoplasmic reticulum stress-related apoptosis and non-canonical autophagy, which function as a cell death mechanism in NCI-H460 human lung cancer cells.
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[443]
TÍTULO / TITLE: - Oligosaccharide from apple induces apoptosis and cell cycle arrest in HT29 human colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Biol Macromol. 2013 Mar 16. pii: S0141-8130(13)00120-7. doi: 10.1016/j.ijbiomac.2013.03.034.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijbiomac.2013.03.034
AUTORES / AUTHORS: - Li Q; Zhou S; Jing J; Yang T; Duan S; Wang Z; Mei Q; Liu L
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China. Electronic address: hbnuliqian@yahoo.com.cn.
RESUMEN / SUMMARY: - It is reported that apple polysaccharide can prevent colon cancer growth and impede colon cancer progression. Apple oligosaccharide was prepared by the combination of alkaline hydrolysis and enzymolysis of apple polysaccharides, and purified by anion column chromatography. The aim of this study is to explore the effect of apple oligosaccharide on the cellular viability of human colon carcinoma cells (HT29 cells) and its mechanism. The results showed that apple oligosaccharide decreased the cellular viability of HT29 cells in dose-dependent manner. Meanwhile it enhanced the expression of Bax; and decreased the levels of Bcl-2 and Bcl-xl. Apple oligosaccharide induced cell cycle arrest in S phase, which correlated with the decreased expression of Cdk 2 and cyclin B1. These results indicated that apple oligosaccharide attenuated HT29 cell viability by inducing cell apoptosis and cell cycle arrest. Apple oligosaccharide is a potential chemoprevention agent or anti-tumor agent and is worthy of further study.
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[444]
TÍTULO / TITLE: - TNFalpha and Fas/FasL pathways are involved in 9-Methoxycamptothecin-induced apoptosis in cancer cells with oxidative stress and G2/M cell cycle arrest.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Chem Toxicol. 2013 May;55:396-410. doi: 10.1016/j.fct.2012.12.059. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.fct.2012.12.059
AUTORES / AUTHORS: - Wang H; Ao M; Wu J; Yu L
INSTITUCIÓN / INSTITUTION: - Institute of Resource Biology and Biotechnology, Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Key Laboratory of Molecular Biophysics, Ministry of Education, Wuhan 430074, China; Wuhan Institute of Biotechnology, Wuhan 430075, China; Department of Chemical Engineering and Food Science, Hubei University of Arts and Science, Hubei 441053, China.
RESUMEN / SUMMARY: - 9-Methoxycamptothecin (MCPT) has been recently reported to have a strong anticancer activity. However, its detailed mechanism of action in human cancer cells has not been well clarified. The results showed that MCPT induced cytotoxicity in seven human cancer cell lines in a dose dependent manner after 72h, with A2780 and Hela cell lines more sensitive, so the two cell lines were chosen to do further studies. MCPT induced strong G2/M arrest in both A2780 cells and Hela cells after 24h, following by substantial sub-G1 arrest (indicating apoptosis). The apoptosis was verified by staining with Annexin V-FITC and propidium iodide. ROS generation increased significantly in MCPT-induced apoptosis. Meanwhile, the apoptosis appeared to be dependent on caspase-3, -8 and -9 in A2780 cells, and caspase-3 in Hela cells. In addition, MCPT induced up-regulation expression of most of seventeen genes in both cell lines. Western blot verified that changes of TNFalpha, Fas, P53 and P27 protein level were consistent with their gene expression changes. Taken together, MCPT plays an important role in tumor growth suppression by inducing apoptosis in both cell lines via extrinsic and intrinsic apoptotic pathways, and has the potential to be developed into an antitumor agent.
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[445]
TÍTULO / TITLE: - The Combination of Sorafenib and Everolimus abrogates mTORC-1 and mTORC2 up-regulation in preclinical models of Osteosarcoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2293
AUTORES / AUTHORS: - Pignochino Y; Dell’aglio C; Basirico M; Capozzi F; Soster M; Marchio S; Bruno S; Gammaitoni L; Sangiolo D; Torchiaro E; D’Ambrosio L; Fagioli F; Ferrari S; Alberghini M; Picci P; Aglietta M; Grignani G
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, University of Torino Medical School, Institute for Cancer Research and Treatment.
RESUMEN / SUMMARY: - PURPOSE: The multikinase inhibitor sorafenib displays antitumor activity in preclinical models of osteosarcoma. However, in sorafenib-treated metastatic-relapsed osteosarcoma patients, disease stabilization and tumor shrinkage were short-lived and drug resistance occurred. We explored the sorafenib treatment escape mechanisms to overcome their drawbacks. Experimental design: Immunoprecipitation, Western blotting, and immunohistochemistry were employed to analyze the mammalian target of rapamycin (mTOR) pathway (mTORC1 and mTORC2). Cell viability, colony growth, and cell migration were evaluated in different osteosarcoma cell lines (MNNG-HOS, HOS, KHOS/NP, MG63, U-2OS, SJSA-1, SAOS-2) after scalar dose treatment with sorafenib (10-0.625 muM), rapamycin-analog everolimus (100-6.25 nM), and combinations of the two. Cell cycle, reactive oxygen species (ROS) production, and apoptosis were assessed by flow cytometry. NOD/SCID mice injected with MNNG-HOS cells were utilized to determine anti-tumor and anti-metastatic effects. Angiogenesis and vascularization were evaluated in vitro by exploiting endothelial branching morphogenesis assays and in vivo in xenografted mice and chorioallantoic membranes. RESULTS: After sorafenib treatment, mTORC1 signaling was reduced (downstream target P-S6) while mTORC2 was increased (phospho-mTOR Ser2481) in MNNG-HOS xenografts compared to vehicle-treated mice. Combining sorafenib with everolimus resulted in complete abrogation of both mTORC1 (through ROS-mediated AMPK activation) and mTORC2 (through complex disassembly). The sorafenib/everolimus combination yielded: 1) enhanced anti-proliferative and pro-apoptotic effects, 2) impaired tumor growth, 3) potentiated anti-angiogenesis, and 4) reduced migratory and metastatic potential. CONCLUSION: mTORC2 activation is an escape mechanism from sorafenib treatment. When sorafenib is combined with everolimus, its anti-tumor activity is increased by complete inhibition of the mTOR pathway in the preclinical setting.
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[446]
TÍTULO / TITLE: - The role of p38 in irinotecan-induced DNA damage and apoptosis of colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mutat Res. 2013 Feb 17. pii: S0027-5107(13)00015-8. doi: 10.1016/j.mrfmmm.2013.02.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.mrfmmm.2013.02.002
AUTORES / AUTHORS: - Rudolf E; Kralova V; Rudolf K; John S
INSTITUCIÓN / INSTITUTION: - Department of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Simkova 870, 500 38 Hradec Kralove, Czech Republic. Electronic address: rudolf@lfhk.cuni.cz.
RESUMEN / SUMMARY: - The role of p38 in irinotecan (CPT-11)-induced damage and cell death in colon cancer cell line SW620 was investigated. We demonstrate that CPT-11 treatment activates p38 in exposed cells, however with concentration dependent dynamics and differing consequences. Higher CPT-11 concentrations induce a massive early but relatively short-lasting p38 activity leading to apoptosis mediated by mitochondria and caspases. Pharmacological or siRNA inhibition of p38 then significantly prevents CPT-11-dependent cell death. Conversely, lower CPT-11 concentrations activate p38 in a delayed, however sustained manner, with apoptosis occurring only in a fraction of cells and in the absence of significant autophagy. Blocking p38 in thus treated cells increases their sensitivity toward CPT-11 and increases cell death. In summary, our results confirm the involvement of p38 in colon cancer cells response to CPT-11 while indicating a varying role of p38 in the final biological response.
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[447]
TÍTULO / TITLE: - Methylated Tissue Factor Pathway Inhibitor 2 (TFPI2) DNA in Serum Is a Biomarker of Metastatic Melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Invest Dermatol. 2013 Feb 14. doi: 10.1038/jid.2012.493.
●● Enlace al texto completo (gratuito o de pago) 1038/jid.2012.493
AUTORES / AUTHORS: - Nigro CL; Wang H; McHugh A; Lattanzio L; Matin R; Harwood C; Syed N; Hatzimichael E; Briasoulis E; Merlano M; Evans A; Thompson A; Leigh I; Fleming C; Inman GJ; Proby C; Crook T
INSTITUCIÓN / INSTITUTION: - Laboratory of Cancer Genetics and Translational Oncology, S Croce General Hospital, Cuneo, Italy.
RESUMEN / SUMMARY: - Transcriptional silencing of tissue factor pathway inhibitor 2 (TFPI2) occurs in several human tumors including melanoma. We investigated methylated TFPI2 as a biomarker of metastatic melanoma using qRT-PCR to assess TFPI2 expression and pyrosequencing to analyze CpG island methylation in malignant melanoma cell lines, in benign nevi, in 112 primary and metastatic melanomas, and in serum from 6 healthy individuals and 35 patients: 20 patients with primary and 15 patients with metastatic melanoma. The TFPI2 CpG island is unmethylated in nevi but methylation is associated with metastatic melanoma. Circulating methylated TFPI2 DNA is undetectable in sera from healthy individuals and detectable in sera from patients with primary and metastatic melanomas, but the presence of methylated TFPI2 DNA in serum is strongly associated with metastatic disease (P<0.01). Detection of TFPI2-methylated DNA in the serum of patients with resected melanoma is a sensitive and specific biomarker of metastatic melanoma. Confirmation of our results in independent patient cohorts would encourage prospective evaluation as a biomarker of disease state.Journal of Investigative Dermatology advance online publication, 14 February 2013; doi:10.1038/jid.2012.493.
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[448]
TÍTULO / TITLE: - Sustained tumour eradication after induced caspase-3 activation and synchronous tumour apoptosis requires an intact host immune response.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Differ. 2013 Feb 15. doi: 10.1038/cdd.2013.8.
●● Enlace al texto completo (gratuito o de pago) 1038/cdd.2013.8
AUTORES / AUTHORS: - Melis MH; Simpson KL; Dovedi SJ; Welman A; Macfarlane M; Dive C; Honeychurch J; Illidge TM
INSTITUCIÓN / INSTITUTION: - Targeted Therapy, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
RESUMEN / SUMMARY: - Effective anticancer treatments often result in the induction of large amounts of tumour cell death. In vivo, such dying tumour cells are a potential source of antigens for T-cell stimulation. Although apoptosis is generally considered nonimmunogenic, recent evidence suggests that some anticancer therapies that induce apoptosis can elicit antitumour immune responses. Here, a doxycycline-inducible, constitutively active caspase-3 (‘death switch’) was constructed in a murine tumour model to explore the impact of the host immune response to rapid, synchronous and substantial tumour cell apoptosis. In vitro, up to 80% of tumour cells underwent apoptotic cell death within 24 h and death was accompanied by the release of potential ‘danger signal’ molecules HMGB1 and HSP90. In vivo, death switch induction provoked rapid, pronounced tumour regression in immune-competent and immune-deficient mice, but sustained tumour eradication was observed only in immune-competent mice. Moreover, the majority of mice that were tumour free after death switch induction were protected from further tumour rechallenge. In addition, long-term remission after induction of the death switch was completely abrogated following depletion of CD8 T cells. These data suggest that sustained tumour eradication after substantial tumour apoptosis requires an antitumour host immune response that prevents tumour relapse. In many patients, cancer therapies produce encouraging initial responses that are only short lived. These results provide new insights that may have important implications for further development of strategies that result in long-term tumour clearance after initially effective anticancer treatment.Cell Death and Differentiation advance online publication, 15 February 2013; doi:10.1038/cdd.2013.8.
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[449]
TÍTULO / TITLE: - Stromal protein periostin identified as a progression associated and prognostic biomarker in glioma via inducing an invasive and proliferative phenotype.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Mar 5. doi: 10.3892/ijo.2013.1847.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1847
AUTORES / AUTHORS: - Wang H; Wang Y; Jiang C
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
RESUMEN / SUMMARY: - To explore the expression pattern, prognostic value and functional role of stromal periostin (POSTN) in glioma patients, POSTN expression was measured using the Agilent Whole Human Genome Oligo Microarray in 220 frozen glioma tissues. We analyzed POSTN expression in 71 independent validated glioma samples using immuno-histochemistry. The expression levels of POSTN were relative to glioma grade progression and inversely correlated with overall survival in high-grade glioma patients (anaplastic gliomas and glioblastomas). Gene ontology (GO) analysis performed using DAVID showed that the gene sets related to cell migration and proliferation were significantly enriched in the cases with POSTN overexpression. Functional analyses in LN229 and U87 cells revealed that POSTN was involved in cell invasion and proliferation. MMP-9 was an effector of POSTN signaling in glioma cells. The expression of stromal protein POSTN is relative to glioma grade progression and confers a poor prognosis via promoting cellular invasion and proliferation in high-grade glioma patients.
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[450]
TÍTULO / TITLE: - The detection of ESR1/PGR/ERBB2 mRNA levels by RT-QPCR: a better approach for subtyping breast cancer and predicting prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Feb;138(1):59-67. doi: 10.1007/s10549-013-2432-2. Epub 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2432-2
AUTORES / AUTHORS: - Du X; Li XQ; Li L; Xu YY; Feng YM
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, He-Xi District, Tianjin, 300060, China.
RESUMEN / SUMMARY: - The molecular classification of breast cancer mainly focuses on ER, PR, and HER2 status detected by immunohistochemistry (IHC) analysis. To explore the clinical value of breast cancer classification based on gene-based diagnosis of the triple markers, we measured ESR1, PGR, and ERBB2 mRNA levels in 294 breast cancer patients by reverse transcription quantitative polymerase chain reaction (RT-QPCR), and examined their correlation with ER, PR, and HER2 status detected by IHC. We observed a significant positive correlation between the mRNA levels of the triple markers and their protein status (ESR1 vs. ER, Spearman’s rho = 0.527, P = 2.3 x 10; PGR vs. PR, Spearman’s rho = 0.631, P = 5.1 x 10; ERBB2 vs. HER2, Spearman’s rho = 0.439, P = 3.0 x 10). Furthermore, the subtypes determined by mRNA levels of the triple markers were significantly correlated to the subtypes determined based on their protein status (Spearman’s rho = 0.342, P = 2.0 x 10). Kaplan-Meier analysis showed that the subtypes determined by mRNA levels of the triple-marker could predict the disease-free survival (DFS) in breast cancer patients. Multivariate analysis showed that the predictive value of DFS could be confirmed for the subtypes determined by mRNA levels of the triple markers (HR = 2.285, P = 0.008) but not for those determined by their protein status. Taken together, our results suggest that the detection of ESR1/PGR/ERBB2 mRNA levels by RT-QPCR is a better approach for subtyping breast cancer and predicting the prognosis.
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[451]
TÍTULO / TITLE: - Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem. 2013 Feb 27. pii: S0968-0896(13)00166-1. doi: 10.1016/j.bmc.2013.02.033.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmc.2013.02.033
AUTORES / AUTHORS: - Misra S; Ghatak S; Patil N; Dandawate P; Ambike V; Adsule S; Unni D; Venkateswara Swamy K; Padhye S
INSTITUCIÓN / INSTITUTION: - Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: misra@musc.edu.
RESUMEN / SUMMARY: - Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme have been found to play a role in promoting growth in colon cancer cell lines. The di-tert-butyl phenol class of compounds has been found to inhibit both COX-2 and 5-LOX enzymes with proven effectiveness in arresting tumor growth. In the present study, the structural analogs of 2,6 di-tert-butyl-p-benzoquinone (BQ) appended with hydrazide side chain were found to inhibit COX-2 and 5-LOX enzymes at micromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactions supporting the observed cytototoxicities. The signaling interaction between endogenous hyaluronan and CD44 has been shown to regulate COX-2 activities through ErbB2 receptor tyrosine kinase (RTK) activation. In the present studies it has been observed for the first time, that three of our COX/5-LOX dual inhibitors inhibit proliferation upon hydrazide substitution and prevent the activity of pro-angiogenic factors in HCA-7, HT-29, Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the hyaluronan/CD44v6 cell survival pathway. Since there is a substantial enhancement in the antiproliferative activities of these compounds upon hydrazide substitution, the present work opens up new opportunities for evolving novel active compounds of BQ series for inhibiting colon cancer.
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[452]
TÍTULO / TITLE: - Molecular profiling of aromatase inhibitor-treated post-menopausal breast tumors identifies immune-related correlates of resistance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-1000
AUTORES / AUTHORS: - Dunbier AK; Ghazoui Z; Anderson H; Salter J; Nerurkar A; Osin P; A’hern R; Miller WR; Smith IE; Dowsett M
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, University of Otago.
RESUMEN / SUMMARY: - PURPOSE: Estrogen withdrawal by treatment with aromatase inhibitors is the most effective form of endocrine therapy for postmenopausal estrogen receptor positive (ER+) breast cancer. However, response to therapy varies markedly and understanding of the precise molecular effects of AIs and causes of resistance is limited. We aimed to identify in clinical breast cancer those genes and pathways most associated with resistance to aromatase inhibitors by examining the global transcriptional effects of aromatase inhibitor treatment. EXPERIMENTAL DESIGN: Baseline and 2-week post-treatment biopsies were obtained from 112 postmenopausal women with ER+ breast cancer receiving neoadjuvant anastrozole. Gene expression data was obtained from 81 baseline and 2-week paired samples. Pathway analysis identified (i) the most prevalent changes in expression and (ii) the pretreatment genes/pathways most related to poor antiproliferative response. RESULTS: 1327 genes were differentially expressed after 2 weeks treatment (FDR<0.01). Proliferation-associated genes and classical estrogen-dependent genes were strongly downregulated while collagens and chemokines were upregulated. Pre-treatment expression of an inflammatory signature correlated with antiproliferative response to anastrozole and this observation was validated in an independent study. Higher expression of immune-related genes such as SLAMF8 and TNF as well as lymphocytic infiltration were associated with poorer response (p<0.001) and validated in an independent cohort. CONCLUSIONS: The molecular response to AI treatment varies greatly between patients consistent with the variable clinical benefit from AI treatment. Higher baseline expression of an inflammatory signature is associated with poor antiproliferative response and should be assessed further as a novel biomarker and potential target for AI-treated patients.
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[453]
TÍTULO / TITLE: - Clinicopathological and Prognostic Significance of alpha5beta1-integrin and MMP-14 Expressions in Colorectal Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasma. 2013;60(3):254-61. doi: 10.4149/neo_2013_034.
●● Enlace al texto completo (gratuito o de pago) 4149/neo_2013_034
AUTORES / AUTHORS: - Yang B; Gao J; Rao Z; Shen Q
RESUMEN / SUMMARY: - The purpose of this study was to evaluate the association of expression level of alpha5beta1-integrin and MMP-14 with clinicopathologic features and prognosis in colorectal cancer (CRC). The expressions of alpha5beta1-integrin and MMP-14 in normal colorectal mucosa and CRC tissue were detected with immunohistochemistry. We estimated the five-year survival rate by the Kaplan-Meier method. The positive expressions rates of alpha5beta1-integrin and MMP-14 in CRC tissue were 60.6% and 63.3% respectively, and there were significant differences on their positive expression rates between in CRC tissue and in normal colorectal mucosa(P<0.05). The expression rates of alpha5beta1-integrin and MMP-14 in patients with poor histological differentiation, lymph node metastasis and high clinical staging were heightened. There was asignificant difference (P<0.05) on the five-year survival rate for alpha5beta1-integrin expression, which was 44.6% in positive groups and 75.5% in negative groups. And there was asignificant difference (P<0.05) on the five-year survival rate for MMP-14 expression, which was 48.2% in positive group and 73.1% in negative group. The expression of alpha5beta1-integrin and MMP-14 is correlated with the progression and metastasis of CRC, and alpha5beta1-integrin and MMP-14 may be used as prognostic markers in CRC. Keywords: CRC, immunohistochemistry, alpha5beta1-integrin, MMP-14, prognosis, survival.
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[454]
TÍTULO / TITLE: - Extracellular domain c-kit mutation with duplication of Ser501Ala502 found in gastrointestinal stromal tumors is more imatinib- and nilotinib-sensitive than that with duplication of Ala502Tyr503.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lab Invest. 2013 Mar 4. doi: 10.1038/labinvest.2013.43.
●● Enlace al texto completo (gratuito o de pago) 1038/labinvest.2013.43
AUTORES / AUTHORS: - Liu NN; Ohkouchi M; Hashikura Y; Kajimoto N; Matsuda I; Isozaki K; Toh Y; Takahashi T; Nishida T; Hirota S
INSTITUCIÓN / INSTITUTION: - Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
RESUMEN / SUMMARY: - The great majority of gastrointestinal stromal tumors (GISTs) have gain-of-function mutations of the c-kit gene, which encodes KIT receptor tyrosine kinase. Most of the mutations are located at exon 11, but some are at exon 9 or at other exons. Mutation types at exon 11 vary, while most mutations at exon 9 are a particular duplication of Ala502Tyr503 (KIT-Dup-Ala502Tyr503). Recently a duplication of Ser501Ala502 (KIT-Dup-Ser501Ala502) at exon 9 has been reported in two cases of pediatric mastocytosis and one case of adult mast cell leukemia. Although KIT-Dup-Ser501Ala502 had not been reported in GISTs, we found two GIST cases possessing the mutation in 45 GIST cases with exon 9 c-kit gene mutations, among a total of approximately 500 GIST cases examined. In this report, we briefly summarize clinicopathological findings of the two cases, and characterize the biology of the mutation. When autophosphorylation of KIT-Dup-Ser501Ala502 was examined by transient transfection of c-kit cDNA with Dup-Ser501Ala502 into CHO-K1 cells, KIT-Dup-Ser501Ala502 was ligand-independently activating. The inhibitory effect of selective tyrosine kinase inhibitors, imatinib and nilotinib, on KIT-Dup-Ser501Ala502 was examined and compared with that of KIT-Dup-Ala502Tyr503. Imatinib efficiently inhibited constitutive activation of KIT-Dup-Ser501Ala502 at a concentration of 0.1 muM, whereas it inhibited that of KIT-Dup-Ala502Tyr503 at a concentration of 10 muM. Constitutive activation of KIT-Dup-Ser502Ala503 was not inhibited by nilotinib even at a concentration of 10 muM but that of KIT-Dup-Ala501Tyr502 was almost completely inhibited at a concentration of 1 muM. The results suggest that imatinib and nilotinib could be more effective on GISTs with KIT-Dup-Ser501Ala502 than those with KIT-Dup-Ala502Tyr503. In fact, a patient with KIT-Dup-Ser501Ala502 showed long-term stable disease with administration of the usual dose of 400 mg imatinib. Although mutation sites of KIT-Dup-Ser501Ala502 and KIT-Dup-Ala502Tyr503 are closely located, imatinib- and nilotinib-sensitive KIT-Dup-Ser501Ala502 are distinguishable from KIT-Dup-Ala502Tyr503.Laboratory Investigation advance online publication, 4 March 2013; doi:10.1038/labinvest.2013.43.
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[455]
TÍTULO / TITLE: - The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Amino Acids. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00726-013-1485-1
AUTORES / AUTHORS: - Murray-Stewart T; Woster PM; Casero RA Jr
INSTITUCIÓN / INSTITUTION: - The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Bunting Blaustein Bldg, Room 551, 1650 Orleans Street, Baltimore, MD, 21287, USA.
RESUMEN / SUMMARY: - Aberrant epigenetic silencing of tumor suppressor genes is a common feature observed during the transformation process of many cancers, including those of hematologic origin. Histone modifications, including acetylation, phosphorylation, and methylation, collaborate with DNA CpG island methylation to regulate gene expression. The dynamic process of histone methylation is the latest of these epigenetic modifications to be described, and the identification and characterization of LSD1 as a demethylase of lysine 4 of histone H3 (H3K4) has confirmed that both the enzyme and the modified histone play important roles as regulators of gene expression. LSD1 activity contributes to the suppression of gene expression by demethylating promoter-region mono- and dimethyl-H3K4 histone marks that are associated with active gene expression. As most post-translational modifications are reversible, the enzymes involved in the modification of histones have become targets for chemotherapeutic intervention. In this study, we examined the effects of the polyamine analogue LSD1 inhibitor 2d (1,15-bis{N 5-[3,3-(diphenyl)propyl]-N 1-biguanido}-4,12-diazapentadecane) in human acute myeloid leukemia (AML) cell lines. In each line studied, 2d evoked cytotoxicity and inhibited LSD1 activity, as evidenced by increases in the global levels of mono- and di-methylated H3K4 proteins. Global increases in other chromatin modifications were also observed following exposure to 2d, suggesting a broad response to this compound with respect to chromatin regulation. On a gene-specific level, treatment with 2d resulted in the re-expression of e-cadherin, a tumor suppressor gene frequently silenced by epigenetic modification in AML. Quantitative chromatin immunoprecipitation analysis of the e-cadherin promoter further confirmed that this re-expression was concurrent with changes in both active and repressive histone marks that were consistent with LSD1 inhibition. As hematologic malignancies have demonstrated promising clinical responses to agents targeting epigenetic silencing, this polyamine analogue LSD1 inhibitor presents an exciting new avenue for the development of novel therapeutic agents for the treatment of AML.
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[456]
TÍTULO / TITLE: - Terrein induces apoptosis in HeLa human cervical carcinoma cells through p53 and ERK regulation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1600-8. doi: 10.3892/or.2013.2288. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2288
AUTORES / AUTHORS: - Porameesanaporn Y; Uthaisang-Tanechpongtamb W; Jarintanan F; Jongrungruangchok S; Thanomsub Wongsatayanon B
INSTITUCIÓN / INSTITUTION: - Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
RESUMEN / SUMMARY: - Terrein, a fungal metabolite derived from Aspergillus terreus, has been shown to have a variety of biological activities in human cells including inhibition of melanogenesis, as well as anti-inflammatory, antioxidant and anticancer properties. In the present study, terrein was shown to have marked anticancer activity on HeLa human cervical carcinoma cells. Terrein exhibited inhibition of proliferation within the same ranges for other cancer cell types with an IC50 at 0.29 mM. The growth inhibition that induced cell death was via apoptosis mechanisms. Chromatin condensation was observed using the Hoechst 33342 stain, a DNA-specific dye. The increase of DNA fragmentation or the sub-G0 peak was also detected by flow cytometry. The signaling used by terrein to induce apoptosis was via the death-receptor and mitochondrial pathways; the cleavage of specific fluorogenic substrates by caspase-3, -8 and -9 activities are clearly demonstrated. The mitochondria were damaged as demonstrated by the decrease of the red/green ratio of the JC-1 staining and the increase of the Bax/Bcl-2 expression ratio. Further analysis of the upstream signaling by the quantitative real-time polymerase chain reaction showed that p53, p21 and ERK were upregulated which indicates the importance of their roles on terrein signaling. This study is the first to show that terrein has an effect on the anticancer properties in cervical cancer cells by inducing apoptosis through p53 and ERK regulation. Our data may help expand the function of the terrein compound and may also aid in the discovery of new anticancer agents.
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[457]
TÍTULO / TITLE: - Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 20. doi: 10.3892/or.2013.2353.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2353
AUTORES / AUTHORS: - Chae JI; Jeon YJ; Shim JH
INSTITUCIÓN / INSTITUTION: - Department of Dental Pharmacology, School of Dentistry, Brain Korea 21 Project, Chonbuk National University, Jeonju 561756, Republic of Korea.
RESUMEN / SUMMARY: - Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer and is associated with a poor patient prognosis due to its rapid progression. Novel therapeutic agents such as honokiol (HNK) improve the clinical outcomes of cancer therapy, yet the mechanisms involved have not been fully elucidated. The present study examined the regulatory effects of HNK on the growth and apoptosis of MSTO-211H mesothelioma cells and investigated its anticancer mechanism. The results revealed that HNK significantly reduced the cell viability and increased the sub-G1 population in MSTO-211H cells and suppressed the expression of the specificity protein 1 protein (Sp1). HNK reduced the transcriptional activity of Sp1 regulatory proteins, including cyclin D1, Mcl-1 and survivin, and, thus, induced apoptosis signaling pathways by increasing Bax, reducing Bid and Bcl-xl and activating caspase-3 and PARP in mesothelioma cells. The results suggest that Sp1, a novel molecular target of HNK, may be related to cell cycle arrest and apoptosis induction through the modulation of signal transduction pathways in MPM.
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[458]
TÍTULO / TITLE: - 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol induces apoptosis via induction of endoplasmic reticulum stress in human colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1365-70. doi: 10.3892/or.2013.2270. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2270
AUTORES / AUTHORS: - Zhang R; Chung Y; Kim HS; Kim DH; Kim HS; Chang WY; Hyun JW
INSTITUCIÓN / INSTITUTION: - School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju 690-756, Republic of Korea.
RESUMEN / SUMMARY: - Previously, we reported that 20-O-(beta-D-gluco-pyranosyl)-20(S)-protopanaxadiol (Compound K, a meta-bolite of ginseng saponin) induces mitochondria-dependent and caspase-dependent apoptosis in HT-29 human colon cancer cells via the generation of reactive oxygen species. The aim of the present study was to elucidate the mechanism underlying apoptosis induced by Compound K with respect to endoplasmic reticulum (ER) stress in HT-29 cells. In the present study, Compound K induced apoptotic cell death as confirmed by DNA fragmentation and apoptotic sub-G1 cell population. Compound K also induced ER stress as indicated by staining with ER tracker, cytosolic and mitochondrial Ca2+ overloading, phosphorylation of protein-kinase-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), phosphorylation of IRE-1, splicing of ER stress-specific X-box transcription factor-1 (XBP-1), cleavage of activating transcription factor-6 (ATF-6), upregulation of glucose-regulated protein-78 (GRP-78/BiP) and CCAAT/enhancer-binding protein-homologous protein (CHOP), and cleavage of caspase-12. Furthermore, downregulation of CHOP expression using siCHOP RNA attenuated Compound K-induced apoptosis. Taken together, these results support the important role of ER stress response in mediating Compound K-induced apoptosis in human colon cancer cells.
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[459]
TÍTULO / TITLE: - Suppression of CLIC4/mtCLIC enhances hydrogen peroxide-induced apoptosis in C6 glioma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1483-91. doi: 10.3892/or.2013.2265. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2265
AUTORES / AUTHORS: - Xu Y; Kang J; Yuan Z; Li H; Su J; Li Y; Kong X; Zhang H; Wang W; Sun L
INSTITUCIÓN / INSTITUTION: - Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.
RESUMEN / SUMMARY: - CLIC4/mtCLIC (referred to here as CLIC4) is one of the seven-member family of chloride intracellular channels (CLIC). CLIC4 localizes to the mitochondria, nucleus, cytoplasm and other organellular compartments and participates in the apoptotic response to stress. However, the role of CLIC4 in oxidative stress and apoptosis is not well understood. In this study, we showed the important role of CLIC4 in apoptosis of C6 glioma cells induced by hydrogen peroxide (H2O2). Our results showed that CLIC4 protein expression was upregulated following H2O2-induced C6 cell apoptosis. The upregulation of CLIC4 protein expression was paralleled with an increased Bax/Bcl-2 ratio, cytochrome c and cleaved caspase-3 protein expression upon H2O2-induced C6 cell apoptosis. Suppression of CLIC4 expression by RNA interference enhanced cell apoptosis, but the ratio of Bax/Bcl-2 was not involved in this process. Dissipation of mitochondrial membrane potential and nuclear translocation of CLIC4 were involved in the activation of apoptosis induced by H2O2. Our data indicate that CLIC4 protein may be a key element in the apoptotic response to oxidative stress.
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[460]
TÍTULO / TITLE: - The promise of heat shock protein inhibitors in the treatment of castration resistant prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Opin Urol. 2013 May;23(3):194-200. doi: 10.1097/MOU.0b013e32835e9f1a.
●● Enlace al texto completo (gratuito o de pago) 1097/MOU.0b013e32835e9f1a
AUTORES / AUTHORS: - Ischia J; Saad F; Gleave M
INSTITUCIÓN / INSTITUTION: - aVancouver Prostate Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia bThe Division of Urology, University of Montreal Hospital Center (CHUM), University of Montreal, Montreal, Quebec, Canada.
RESUMEN / SUMMARY: - PURPOSE OF REVIEW: To present the recent advances in novel agents that target heat shock proteins (Hsps) to treat or delay the development of castration resistant prostate cancer (CRPC). RECENT FINDINGS: Multiple preclinical studies have shown that silencing Hsp27, Hsp90, or clusterin sensitizes prostate cancer cells to modern chemotherapy and radiation treatments; and overexpression of these chaperones confers resistance to these therapies. Antisense oligonucleotides targeting Hsp27 and clusterin have shown good biological activity in human phase II trials and phase III studies are ongoing. Despite promising preclinical efficacy, a number of phase I/II human trials with various Hsp90 inhibitors have been disappointing with negligible anticancer activity and dose-limiting toxicity profiles. Newer Hsp90 inhibitors with better toxicity profiles, and inhibitors that target Hsp90 cofactors, such as FKBP52, are currently being investigated in human studies. SUMMARY: Many Hsp chaperone client proteins are key components of alternative growth factor pathways upregulated in CRPC and are involved in key resistance pathways to current chemotherapy and radiotherapy regimes. New treatments that inhibit Hsps are attractive anticancer strategies as they have the ability to simultaneously target multiple pathways involved in CRPC.
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[461]
TÍTULO / TITLE: - Erratum to: Synergistic effect and mechanism of vitamin A and vitamin D on inducing apoptosis of prostate cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biol Rep. 2013 May;40(5):3875. doi: 10.1007/s11033-013-2490-x.
●● Enlace al texto completo (gratuito o de pago) 1007/s11033-013-2490-x
AUTORES / AUTHORS: - Sha J; Pan J; Ping P; Xuan H; Li D; Bo J; Liu D; Huang Y
INSTITUCIÓN / INSTITUTION: - Department of Urology, Renji Hospital, School of Medicine, ShanghaiJiaotong University, Shanghai, 200001, China.
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[462]
TÍTULO / TITLE: - Regulatory effects of resveratrol on antioxidant enzymes: A mechanism of growth inhibition and apoptosis induction in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cells. 2013 Mar;35(3):219-25. doi: 10.1007/s10059-013-2259-z. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s10059-013-2259-z
AUTORES / AUTHORS: - Khan MA; Chen HC; Wan XX; Tania M; Xu AH; Chen FZ; Zhang DZ
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan, 410013, China.
RESUMEN / SUMMARY: - Resveratrol (RSV) is a natural polyphenol that is known as a powerful chemopreventive and chemotherapeutic anticancer molecule. This study focused on the effects of RSV on the activities and expression levels of antioxidant enzymes in the cancer cells. Prostate cancer PC-3 cells, hepatic cancer HepG2 cells, breast cancer MCF-7 cells and the non-cancerous HEK293T kidney epithelial cells were treated with a wide range of RSV concentrations (10-100 muM) for 24-72 h. Cell growth was estimated by trypan blue staining, activities of the antioxidant enzymes were measured spectrophotometrically, expression levels of the antioxidant enzymes were quantified by digitalizing the protein band intensities on Western blots, and the percentage of apoptotic cells was determined by flow cytometry. Treatment with a low concentration of RSV (25 muM) significantly increased superoxide dismutase (SOD) activity in PC-3, HepG2 and MCF-7 cells, but not in HEK293T cells. Catalase (CAT) activity was increased in HepG2 cells, but no effect was found on glutathione peroxidase (GPX) upon RSV treatment. RSV-induced SOD2 expression was observed in cancer cells, although the expression of SOD1, CAT and GPX1 was unaffected. Apoptosis increased upon RSV treatment of cancer cells, especially in PC-3 and HepG2 cells. Together, our data demonstrated that RSV inhibits cancer cell growth with minimal effects on non-cancerous cells. We postulate that the disproportional up-regulation of SOD, CAT and GPX expression and enzymatic activity in cancer cells results in the mitochondrial accumulation of H2O2, which in turn induces cancer cell apoptosis.
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[463]
TÍTULO / TITLE: - Synergistic effect and mechanism of vitamin A and vitamin D on inducing apoptosis of prostate cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biol Rep. 2013 Apr;40(4):2763-8. doi: 10.1007/s11033-012-1925-0. Epub 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s11033-012-1925-0
AUTORES / AUTHORS: - Sha J; Pan J; Ping P; Xuan H; Li D; Bo J; Liu D; Huang Y
INSTITUCIÓN / INSTITUTION: - Department of Urology, Renji Hospital, School of Medicine, ShanghaiJiaotong University, Shanghai, 200001, China.
RESUMEN / SUMMARY: - To explore the mechanism and synergistic effect of vitamin A and vitamin D in inducing apoptosis of prostate cancer cells. The cell proliferation activity was determined by MTT assay. The proportion of apoptotic cells was analyzed by FACS and fluorescence intensity. TUNEL was used to evaluate vitamin A and vitamin D’s induction of apoptosis in prostate cancer cells. The protein and mRNA expression level of Cyclin D1 and Bax were determined by real time-PCR and western blot. The results of MTT showed vitamin A and vitamin D’s inhibition on proliferation ratio in prostate cancer cells is time and concentration dependent. FACS and fluorescence intensity analysis proved that the proportion of apoptotic cells increased after vitamin A and vitamin D treatment. TUNEL showed vitamin A and vitamin D induced prostate cancer cells apoptosis. The combination of vitamin A and vitamin D markedly enhanced the expression of Bax and reduced the expression of Cyclin D1 by real time-PCR and western blot assay. In conclusion, vitamin A and vitamin D could synergistically induce apoptosis in prostate cancer cells.
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[464]
TÍTULO / TITLE: - Corrigendum to “Regulatory effects of resveratrol on antioxidant enzymes: a mechanism of growth inhibition and apoptosis induction in cancer cells”
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cells. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s10059-013-1259-3
AUTORES / AUTHORS: - Khan MA; Chen HC; Wan XX; Tania M; Xu AH; Chen FZ; Zhang DZ
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan, 410013, China.
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[465]
TÍTULO / TITLE: - CT-based response assessment of advanced gastrointestinal stromal tumor: Dual energy CT provides a more predictive imaging biomarker of clinical benefit than RECIST or Choi criteria.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Radiol. 2013 Feb 11. pii: S0720-048X(13)00016-8. doi: 10.1016/j.ejrad.2013.01.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2013.01.006
AUTORES / AUTHORS: - Meyer M; Hohenberger P; Apfaltrer P; Henzler T; Dinter DJ; Schoenberg SO; Fink C
INSTITUCIÓN / INSTITUTION: - Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. Electronic address: mr.meyer.mathias@gmail.com.
RESUMEN / SUMMARY: - OBJECTIVES: Dual-energy CT (DECT) allows quantification of intravenously injected iodinated contrast media in tumors, and therefore may be considered as a surrogate marker for perfusion and tumor vascularity. This study evaluated whether newly developed DECT response criteria allow better correlation with survival than established response criteria. METHODS: Seventeen patients with advanced GIST treated with tyrosine-kinase-inhibitors were assessed by contrast-enhanced DECT 2 and 6 months after beginning of treatment. Response to treatment of 165 tumor lesions was evaluated according to RECIST, Choi criteria and newly developed DECT criteria, defining non-responders as an increase of both tumor size >20% and iodine related attenuation or either a >50% increase of tumor size or iodine related attenuation. All other patients were classified as responders. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier analysis. RESULTS: Choi criteria and DECT showed a significantly longer median PFS of patients rated as responders than patients rated as non-responders (9-29 months vs. 2-6 months; p<0.02) at follow-up. Only DECT analysis at 6 months follow-up allowed a valid prediction of OS. CONCLUSION: This study indicates that DECT allows a better prediction of therapeutic benefit in advanced GIST patients treated with tyrosine-kinase-inhibitors than established response criteria. However, the most important predictive biomarker of therapeutic benefit was absence of progression, no matter which response evaluation criteria were applied.
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[466]
TÍTULO / TITLE: - Prognostic significance of heat shock proteins in urothelial carcinoma of the urinary bladder.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Histopathology. 2013 Apr;62(5):788-98. doi: 10.1111/his.12087. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1111/his.12087
AUTORES / AUTHORS: - Yu HJ; Chang YH; Pan CC
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Cardinal Tien Hospital and School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
RESUMEN / SUMMARY: - AIMS: Heat shock proteins (HSPs) are a group of molecules induced by a variety of environmental and pathophysiological stresses, including cancer. The expression of HSPs has been implicated in the regulation of apoptosis and immunity in neoplasia. The purpose of this study was to evaluate the expression and clinicopathological relevance of several HSPs in urothelial carcinomas of the urinary bladder. METHODS AND RESULTS: Immunohistochemical staining for HSP27, HSP60, HSP70 and HSP90 was performed on samples collected from 744 clinical cases. The results were correlated with clinicopathological characteristics using univariate and multivariate analyses. High expression of HSP70 predicted recurrence of non-muscle-invasive urothelial carcinoma treated by transurethral resection, and low expression of HSP27 correlated with progression and cancer-specific mortality for non-muscle-invasive cancers treated by transurethral resection. Low expression of HSP27 also predicted cancer-specific mortality for patients who underwent cystectomy. CONCLUSIONS: Both HSP27 and HSP70 impact on the biological behaviour of urothelial carcinomas of the urinary bladder. Immunohistochemical assessment of HSPs can provide useful prognostic information that could ultimately help to develop individualized surveillance programmes.
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[467]
TÍTULO / TITLE: - Enzyme-activated nanoconjugates for tunable release of doxorubicin in hepatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Mar 21. pii: S0142-9612(13)00281-0. doi: 10.1016/j.biomaterials.2013.02.070.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.02.070
AUTORES / AUTHORS: - Medina SH; Chevliakov MV; Tiruchinapally G; Durmaz YY; Kuruvilla SP; Elsayed ME
INSTITUCIÓN / INSTITUTION: - University of Michigan, Department of Biomedical Engineering, Cellular Engineering and Nano-Therapeutics Laboratory, 1101 Beal Avenue, Ann Arbor, MI 48109, USA.
RESUMEN / SUMMARY: - We report the synthesis of a series of aromatic azo-linkers (L1-L4), which are selectively recognized and cleaved by azoreductase enzymes present in the cytoplasm of hepatic cancer cells via a NADPH-dependent mechanism. We utilized L1-L4 azo-linkers to conjugate doxorubicin to generation 5 (G5) of poly(amidoamine) dendrimers to prepare G5-L(x)-DOX nanoconjugates. We incorporated electron-donating oxygen (O) or nitrogen (N) groups in the para and ortho positions of L1-L4 azo-linkers to control the electronegativity of G5-L(x)-DOX conjugates and investigated their cleavage by azoreductase enzymes and the associated release of loaded DOX molecules. Hammett sigma values of G5-L(x)-DOX conjugates ranged from -0.44 to -1.27, which is below the reported sigma threshold (-0.37) required for binding to azoreductase enzymes. Results show that incubation of G5-L1-DOX (sigma = -0.44), G5-L2-DOX (sigma = -0.71), G5-L3-DOX (sigma = -1.00), and G5-L4-DOX (sigma = -1.27) conjugates with human liver microsomal (HLM) enzymes and the S9 fraction isolated from HepG2 hepatic cancer cells results in release of 4%-8%, 17%, 60%, and 100% of the conjugated DOX molecules, respectively. These results show that increasing the electronegativity (i.e. lower sigma value) of L1-L4 azo-linkers increases their susceptibility to cleavage by azoreductase enzymes. Intracellular cleavage of G5-L(x)-DOX nanoconjugates, release of conjugated DOX molecules, and cytotoxicity correlated with conjugate’s electronegativity (sigma value) was investigated, with G5-L4-DOX conjugate exhibiting the highest toxicity towards hepatic cancer cells with an IC50 of 13 nm +/- 5 nm in HepG2 cells. Cleavage of G5-L(x)-DOX conjugates was specific to hepatic cancer cells as shown by low non-specific DOX release upon incubation with non-enzymatic insect proteins and the S9 fraction isolated from rat cardiomyocytes. These enzyme-activated G5-L(x)-DOX conjugates represent a drug delivery platform that can achieve tunable and cell-specific release of the loaded cargo in hepatic cancer cells.
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[468]
TÍTULO / TITLE: - RNA Interference with EAG1 Enhances Interferon Gamma Injury to Glioma Cells In Vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):865-70.
AUTORES / AUTHORS: - Cunha LC; Del Bel E; Pardo L; Stuhmer W; Titze-DE-Almeida R
INSTITUCIÓN / INSTITUTION: - Technology for Gene Therapy Laboratory, University of Brasilia - UnB/FAV, Darcy Ribeiro campus, ICC - ASS 128, Brasilia, DF, Brazil. ricardo.titze@hotmail.com.
RESUMEN / SUMMARY: - Aim: The aim of this study was to silence Ether a go-go 1 (EAG1) in glioma cells by RNAi in order to further analyze whether silencing this channel would improve injury caused by interferon gamma (IFN-gamma). MATERIALS AND METHODS: EAG1 silencing by the siRNAs EAG1hum_287 and EAG1hum_1727 (sequence targets 5’-GGCCTATTGTGTACAGCAATT-3’ and 5’-GGGACTTCCTGAAGCTCTATT-3’, respectively) was determined by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability was measured by the 3-(4,5)-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay. U-138MG glioma cells were injured by IFN-gamma (25 ng/ml, 24 h) with or without the RNAi for EAG1 by a non-viral vector (pKV10.1-3, 0.2 mug). RESULTS: EAG1hum_287 and EAG1hum_1727 caused 0.46- and 0.52-fold decrease in EAG1 mRNA content, respectively. RNAi for EAG1 by pKv10.1-3 strengthened the reduction in cell viability caused by IFN-gamma (11.4% versus 40.4%, p<0.05). CONCLUSION: The present study reinforces the notion that EAG1 has a role in glioma biology, suggesting that this channel is a relevant player preserving the cell viability during IFN-gamma injury.
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[469]
TÍTULO / TITLE: - Cyclin-dependent kinase 2-associated protein 1 suppresses growth and tumorigenesis of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1376-82. doi: 10.3892/ijo.2013.1813. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1813
AUTORES / AUTHORS: - Sun M; Jiang R; Wang G; Zhang C; Li J; Jin C; Zhang X
INSTITUCIÓN / INSTITUTION: - Department of Pathology, The Second Hospital of Jilin University, Changchun 130041, P.R. China.
RESUMEN / SUMMARY: - Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), a growth suppressor that negatively regulates CDK2 activity, has been implicated in various types of cancer; yet its role in lung cancer remains unclear. In the present study, a lentivirus-based system was used to specifically downregulate or upregulate CDK2AP1 expression. A549 lung cancer cells were treated with RNAi (RNA interference) or lentiviral vectors for overexpression. Ectopic overexpression of CDK2AP1 in A549 cells in vitro greatly impaired their proliferation and colony-forming ability and enhanced their chemosensitivity to cisplatin and paclitaxel and caused cell cycle arrest at G1/S transition accompanied by the reduction of expression of CDK4 and CDK7. Injection of the ectopically CDK2AP1-overexpressing A549 cells into nude mice resulted in growth arrest of solid lung cancer tumors in vivo. Knockdown of CDK2AP1 in A549 cells, however, gave rise to the opposite effects including promoting cell proliferation/growth, cell cycling in vitro and enhancing tumorigenesis in vivo. These results suggest that CDK2AP1 plays an important role in modulating the growth and tumorigenesis of lung cancer cells and also has significant effects on the chemosensitivity of pulmonary malignancies to chemotherapeutics. Hence, this study extends our knowledge on the relationship between CDK2AP1 and oncogenesis of lung cancer, indicating that CDK2AP1 may serve as a new molecular target for future lung cancer therapy.
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[470]
TÍTULO / TITLE: - Inhibitory effect of oleanolic acid on hepatocellular carcinoma via ERK-p53-mediated cell cycle arrest and mitochondrial-dependent apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt058
AUTORES / AUTHORS: - Wang X; Bai H; Zhang X; Liu J; Cao P; Liao N; Zhang W; Wang Z; Hai C
INSTITUCIÓN / INSTITUTION: - Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, Shaanxi 710032, China.
RESUMEN / SUMMARY: - Incidence of hepatocellular carcinoma (HCC) is dramatically increasing and is the third cause of cancer death worldwide. One key approach to control HCC is chemoprevention by naturally occurring agents. This study aims at investigating the antitumor effect of oleanolic acid (OA) and the molecular mechanisms. BALB/c mice were injected subcutaneously with HepG2 cells to establish transplanted tumors. Apoptosis and cell cycle arrest-related markers and signaling cascades were determined by western blot, immunofluorescence, reverse transcriptase-polymerase chain reaction and flow cytometric analysis. OA exhibited inhibitory effect on HCC through induction of apoptosis and cell cycle arrest both in transplanted tumors and in HepG2 cells. OA induced apoptosis through mitochondrial pathway, evidenced by inhibition of Akt/mammalian target of rapamycin pathway, mitochondrial dysfunction, transient increase of adenosine triphosphate, increase of Bax/Bcl-2 ratio, increased release of cytochrome c and activation of caspase/poly (ADP-ribose) polymerase. Activation of mitochondrial apoptotic pathway may be due to reactive oxygen species generated by mitochondrial fatty acid oxidation, resulted from enhancement of lipolysis regulated by cyclic adenosine 3’,5’-monophosphate response element-binding protein-hormone-sensitive lipase/peroxisome proliferator-activated receptor gamma signaling. OA induced G2/M cell cycle arrest through p21-mediated downregulation of cyclin B1/cdc2. Cyclooxygenase-2 (COX-2) and p53 were involved in OA-exerted effect, and extracellular signal-regulated kinase-p53 signaling played a central role in OA-activated cascades responsible for apoptosis and cell cycle arrest. OA demonstrated significant antitumor activities in HCC in vivo and in vitro models. These data provide new insights into the mechanisms underlying the antitumor effect of OA.
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[471]
TÍTULO / TITLE: - Characterization and prognostic significance of mitochondrial DNA variations in acute myeloid leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Haematol. 2013 Feb 27. doi: 10.1111/ejh.12090.
●● Enlace al texto completo (gratuito o de pago) 1111/ejh.12090
AUTORES / AUTHORS: - Silkjaer T; Norgaard JM; Aggerholm A; Ebbesen LH; Kjeldsen E; Hokland P; Nyvold CG
INSTITUCIÓN / INSTITUTION: - Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
RESUMEN / SUMMARY: - Recent studies have suggested that mutations in the mitochondrial genome (mtDNA) may play a role in the development and response to treatment for human cancer. The aim of this study was to investigate whether mtDNA variations have any prognostic relevance, to clarify the spectra of mtDNA variation and to determine whether there was any correlation to known prognostic factors in acute myeloid leukemia (AML). To elucidate this, we sequenced the entire mtDNA in 56 AML patients and 14 control subjects. When analyzing the biologic impact of the non-synonymous variations in the mtDNA coding genes, we found an inferior disease-free survival for patients exhibiting variations in the two most important catalytic genes of the complex IV of the oxidative phosphorylation complexes (OXPHOS), that is, the cytochrome c oxidase subunit I and the cytochrome c oxidase subunit II (hazard ratio 2.6, P = 0.03; multivariate analysis). In addition, the most frequent variation was the T16311C in the control region, which was found in 11 (20%) of the 56 patients. This observation was confirmed in another cohort of 173 diagnostic AML samples. In this expanded group, the T16311C variation tended to be associated with chromosomal abnormalities.
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[472]
TÍTULO / TITLE: - Aberrant expression of beta-catenin and E-cadherin is correlated with poor prognosis of nasopharyngeal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Jan 31. pii: S0046-8177(12)00431-5. doi: 10.1016/j.humpath.2012.10.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.10.025
AUTORES / AUTHORS: - Xu L; Jiang Y; Zheng J; Xie G; Li J; Shi L; Fan S
INSTITUCIÓN / INSTITUTION: - Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
RESUMEN / SUMMARY: - Nasopharyngeal carcinoma has a high incidence in southern China. The Wnt/beta-catenin signaling pathway plays a major role in cancer development and progression. Our current study aims to determine the clinical significance of the Wnt/beta-catenin pathway components such as beta-catenin, cyclooxygenase 2, cyclin D1, c-Myc, and E-cadherin in 148 nasopharyngeal carcinomas by immunohistochemistry. We found that nasopharyngeal carcinoma stage T(3)+T(4) had significantly higher expression of beta-catenin, cyclooxygenase 2, cyclin D1, and c-Myc and lower expression of E-cadherin than nasopharyngeal carcinoma stage T(1)+T(2) (P < .001, P < .05, respectively).There was significantly higher expression of beta-catenin (P = .001) and cyclooxygenase 2 (P = .003) and lower expression of E-cadherin (P = .001) in nasopharyngeal carcinoma with lymph node metastasis than in nasopharyngeal carcinoma without lymph node metastasis. The expression of beta-catenin in nasopharyngeal carcinoma was positively correlated with cyclooxygenase 2 (r = 0.458, P < .0001), cyclin D1 (r = 0.700, P < .0001), and c-Myc expression (r = 0.144, P = .006) but negatively correlated with E-cadherin expression (r = -0.601, P < .0001), respectively. The univariate analysis confirmed that overexpression of beta-catenin and cyclooxygenase 2 and decreased expression of E-cadherin were significantly correlated with disease-free survival (P < .01, P < .05, respectively). Overexpression of beta-catenin and cyclooxygenase 2 and reduced expression of E-cadherin significantly correlated with a poor prognosis (P = .005, P = .044, P = .019, respectively) by Kaplan-Meier survival curves and the log-rank test. Multivariate analysis indicated that high expression of beta-catenin and decreased expression of E-cadherin were independent prognostic factors (P = .002, P = .011, respectively) regardless of TNM stage and lymph node status. In conclusion, the aberrant high expression of beta-catenin and decreased expression of E-cadherin is associated with poor prognosis in nasopharyngeal carcinoma.
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[473]
TÍTULO / TITLE: - Platelet apoptosis and agonist-mediated activation in myelodysplastic syndromes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thromb Haemost. 2013 Feb 14;109(5).
●● Enlace al texto completo (gratuito o de pago) 1160/TH12-09-0670
AUTORES / AUTHORS: - Martin M; de Paz R; Jimenez-Yuste V; Fernandez Bello I; Garcia Arias Salgado E; Alvarez MT; Butta NV
INSTITUCIÓN / INSTITUTION: - Nora Butta, Haematology Unit, Hospital Universitario La Paz-IDIPaz, Madrid, España, E-mail: nora.butta@salud.madrid.org.
RESUMEN / SUMMARY: - Patients with myelodysplastic syndromes (MDS) have a defect in the differentiation of bone marrow multipotent progenitor cells. Thrombocytopenia in MDS patients may be due to premature megakaryocyte death, but platelet apoptotic mechanisms may also occur. This study aimed to study function and apoptotic state of platelets from MDS patients with different platelet count. Reticulated platelets, platelet activation, activated caspases and annexin-V binding were evaluated by flow cytometry. Pro-apoptotic Bax and Bak proteins were determined by western blots and plasma thrombopoietin by ELISA. Microparticle-associated procoagulant activity and thrombin generation capacity of plasma were determined by an activity kit and calibrated automated thrombography, respectively. High plasma thrombopoietin levels and low immature circulating platelet count showed a pattern of hypoplastic thrombocytopenia in MDS patients. Platelets from MDS patients showed reduced activation capacity and more apoptosis signs than controls. Patients with the lowest platelet count showed less platelet activation and the highest extent of platelet apoptosis. On this basis, patients with thrombocytopenia should suffer more haemorrhagic episodes than is actually observed. Consequently, we tested whether there were some compensatory mechanisms to counteract their expected bleeding tendency. Microparticle-associated procoagulant activity was enhanced in MDS patients with thrombocytopenia, whereas their plasma thrombin generation capacity was similar to control group. This research shows a hypoplastic thrombocytopenia that platelets from MDS patients possess an impaired ability to be stimulated and more apoptosis markers than those from healthy controls, indicating that MDS is a stem cell disorder, and then, both number and function of progeny cells, might be affected.
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[474]
TÍTULO / TITLE: - The predictive and prognostic significance of pre- and post-treatment topoisomerase IIalpha in anthracycline-based neoadjuvant chemotherapy for local advanced breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Surg Oncol. 2013 Mar 6. pii: S0748-7983(13)00264-3. doi: 10.1016/j.ejso.2013.02.019.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejso.2013.02.019
AUTORES / AUTHORS: - Chen S; Huang L; Liu Y; Chen CM; Wu J; Shao ZM
INSTITUCIÓN / INSTITUTION: - Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
RESUMEN / SUMMARY: - OBJECTIVE: To investigate the predictive and prognostic value of topoisomerase IIalpha (Topo IIalpha, Topo II) expression in the primary tumors and residual tumors of local advanced breast cancer (LABC) patients being treated with anthracycline-based neoadjuvant chemotherapy (NCT). METHODS: The data from 283 LABC patients who had been treated with anthracycline-based neoadjuvant chemotherapy were collected. The expression of Topo IIalpha, HER-2 and other biomarkers was determined via immunohistochemical analysis in pre- and post-chemotherapy specimens. The status of pre-treatment biomarkers was correlated with the clinical response determined by the RECIST 1.1 criteria, whereas the post-treatment biomarkers were studied for prognostic value using the Cox model. RESULTS: By analyzing the complete data from 99 patients, the co-expression of HER-2/Topo IIalpha was found to be significantly correlated with the clinical response to chemotherapy (Logistic regression P = 0.042). Notably, a 20% alteration in the Topo IIalpha status during neoadjuvant chemotherapy was found, which could also influence the sensitivity to treatment. With a survival analysis performed in 245 patients with residual tumors after NCT, node metastasis, HER-2 and Ki-67 were independent predictors of patient outcome. However, post-treatment Topo IIalpha expression demonstrated significant prognostic value in HER-2+ patients (P = 0.002). A relatively lower disease-free survival and overall survival was observed in HER-2+/Topo- patients (log rank P = 0.010 for DFS and P < 0.001 for OS). CONCLUSION: Topo IIalpha, together with HER-2, might help to select for patients who could benefit from anthracycline-based neoadjuvant chemotherapy and identify non-complete responders at a higher risk of disease recurrence or death.
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[475]
TÍTULO / TITLE: - Polymorphisms in the base excision repair pathway modulate prognosis of platinum-based chemotherapy in advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2127-8
AUTORES / AUTHORS: - Zhao W; Hu L; Xu J; Shen H; Hu Z; Ma H; Shu Y; Shao Y; Yin Y
INSTITUCIÓN / INSTITUTION: - Department of Oncology, BenQ Medical Center, Nanjing Medical University, Suzhou, 215000, China.
RESUMEN / SUMMARY: - PURPOSE: Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy. METHODS: We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy. RESULTS: Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11-5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02-3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12-0.92). CONCLUSIONS: We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.
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[476]
TÍTULO / TITLE: - Predictive value of hypoxia, proliferation and tyrosine kinase receptors for EGFR-inhibition and radiotherapy sensitivity in head and neck cancer models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiother Oncol. 2013 Feb 27. pii: S0167-8140(13)00047-9. doi: 10.1016/j.radonc.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2013.02.001
AUTORES / AUTHORS: - Stegeman H; Kaanders JH; van der Kogel AJ; Iida M; Wheeler DL; Span PN; Bussink J
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands. Electronic address: h.stegeman@rther.umcn.nl.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: EGFR-inhibitor Cetuximab (C225) improves the efficacy of radiotherapy in only a subgroup of HNSCC patients. Identification of predictive tumor characteristics is essential to improve patient selection. MATERIAL AND METHODS: Response to C225 and/or radiotherapy was assessed with tumor growth delay assays in 4 HNSCC xenograft models with varying EGFR-expression levels. Hypoxia and proliferation were quantified with immunohistochemistry and the expression of proteins involved in C225-resistance with Western blot. RESULTS: EGFR-expression did not predict response to C225 and/or radiotherapy. Reduction of hypoxia by C225 was only observed in SCCNij202, which was highly sensitive to C225. Proliferation changes correlated with response to C225 and C225 combined with radiotherapy, as proliferation decreased after C225 treatment in C225-sensitive SCCNij202 and after combined treatment in SCCNij185, which showed a synergistic effect to combined C225-radiotherapy. Furthermore, C225-resistant SCCNij153 tumors expressed high levels of (activated) HER3 and MET. CONCLUSIONS: EGFR-expression is needed for C225-response, but is not sufficient to predict response to C225 with or without radiotherapy. However, basal expression of additional growth factor receptors and effects on proliferation, but not hypoxia, correlated with response to combined C225-radiotherapy treatment and are potential clinically relevant predictive biomarkers.
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[477]
TÍTULO / TITLE: - NSAIDs may regulate EGR-1-mediated induction of reactive oxygen species and non-steroidal anti-inflammatory drug-induced gene (NAG)-1 to initiate intrinsic pathway of apoptosis for the chemoprevention of colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1593-y
AUTORES / AUTHORS: - Vaish V; Piplani H; Rana C; Vaiphei K; Sanyal SN
INSTITUCIÓN / INSTITUTION: - Department of Biophysics, Panjab University, Chandigarh, 160 014, India.
RESUMEN / SUMMARY: - This study aims to investigate the unclear molecular relationship involved in the activation of intrinsic pathway of apoptosis and NSAID-activated gene-1 (NAG-1) induction as a putative target in NSAIDs-mediated chemoprevention of colorectal cancer. Male Sprague-Dawley rats were administered with a colon-specific pro-carcinogen, 1,2-dimethylhydrazine dihydrochloride to achieve the early stages of colorectal cancer. Histopathological examination was performed for the analysis of neoplastic lesions while flow cytometry was performed for the relative quantification of intracellular reactive oxygen species (ROS), differential mitochondrial membrane potential (MMP or DeltaPsi (M)), and apoptotic events. Various target biomolecules were analyzed either for their mRNA or protein expression profiles via RT-PCR and quantitative Real-Time PCR, or Western blotting and immunofluorescence, respectively. Enhanced gene as well as protein expression of pro-apoptotic agents was observed with the daily oral administration of two NSAIDs viz. Sulindac (cyclooxygenase (COX)-non-specific) and Celecoxib (a selective COX-2 inhibitor). A significant increase in early growth response-1 (EGR-1) protein expression and nuclear localization in NSAIDs co-administered animals may have positively regulated the expression of NAG-1 with a significant enhancement of intracellular ROS in turn decreasing the DeltaPsi (M) to initiate apoptosis. In silico molecular docking analysis also showed that Sulindac and Celecoxib can block the active site pocket of B-cell lymphoma-extra large (Bcl-xL, anti-apoptotic transmembrane mitochondrial protein) which could be a putative mechanism followed by these NSAIDs to overcome anti-apoptotic properties of the molecule. NSAIDs-mediated up-regulation of EGR-1 and thereby NAG-1 along with implication of higher ROS load may positively regulate the intrinsic pathway of apoptosis for the chemoprevention of colorectal cancer.
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[478]
TÍTULO / TITLE: - Efficacy of cetuximab and panitumumab in oral squamous cell carcinoma cell lines: Prognostic value of MAGE-A subgroups for treatment success.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Craniomaxillofac Surg. 2013 Jan 31. pii: S1010-5182(12)00298-3. doi: 10.1016/j.jcms.2012.12.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jcms.2012.12.006
AUTORES / AUTHORS: - Hartmann S; Kriegebaum U; Lessner G; Brands RC; Linz C; Schneider T; Kubler AC; Muller-Richter UD
INSTITUCIÓN / INSTITUTION: - Department of Oral and Maxillofacial Plastic Surgery (Head: Alexander C. Kubler), University Hospital Wurzburg, Pleicherwall 2, 97070 Wurzburg, Germany. Electronic address: hartmann_s2@klinik.uni-wuerzburg.de.
RESUMEN / SUMMARY: - BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) has been observed in a variety of epithelial tumours. The selective inhibition of the associated signalling pathway using monoclonal antibodies appears to be a promising therapeutic target. Individual differences in response rates, particularly against highly selective chemotherapeutic agents, underline the need for further research of the molecular basis of this process. Previously described resistance mechanisms are not able to explain all refractory responses. Several subgroups of the melanoma-associated antigens (MAGE) tumour antigens were described in connection with regulatory functions relating to the cell cycle and chemosensitivity. METHODS: In the present study, five cell lines of human squamous cell carcinomas were treated with cetuximab and panitumumab (0.01-100 mug/ml) over a period of 24 or 48 h. The efficacy of the agents used was measured dynamically using real-time cell analysis (RTCA). Subsequently, the expression levels of MAGE-A1, -A5, -A8, -A9, -A11 and -A12 were determined by RT-qPCR. A correlation between chemosensitivity and MAGE-A expression was investigated. RESULTS: The tumour cell lines exhibited a very low overall response to the chemotherapy drugs. Only one cell line showed a cytostatic effect after treatment with cetuximab and panitumumab. This effect, however, was significant only for panitumumab. The expression of MAGE-A12 was significantly associated with greater efficacy of panitumumab. The expression of MAGE-A5 and -A8 was associated with poorer response rates after panitumumab treatment. Due to an insignificant effect of cetuximab on the number of viable cells, no correlation with the MAGE-A levels was observed. CONCLUSION: For the first time, these results show a correlation between the efficacies of EGFR inhibitors and various MAGE-A subgroups in the treatment of HNSCC. Determining the MAGE-A status could help to improve the success of anti-tumour drug therapy. In addition, evaluating MAGE-A levels might be an important tool in the development of patient-specific treatment protocols.
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[479]
TÍTULO / TITLE: - The translocator protein (TSPO): A novel target for cancer chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Biochem Cell Biol. 2013 Mar 18. pii: S1357-2725(13)00072-1. doi: 10.1016/j.biocel.2013.03.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biocel.2013.03.004
AUTORES / AUTHORS: - Austin CJ; Kahlert J; Kassiou M; Rendina LM
INSTITUCIÓN / INSTITUTION: - School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: christopher.austin@sydney.edu.au.
RESUMEN / SUMMARY: - The translocator protein (TSPO) is an 18kDa transmembrane protein primarily found in the outer mitochondrial membrane where it forms a key part of the mitochondrial permeability transition pore (MPTP). Omnipresent in almost all tissues, TSPO up-regulation has been connected to neuronal damage and inflammation, making the protein an important bio-imaging marker for disease progression. More recently, TSPO has attracted attention as a possible molecular target for tumour imaging and chemotherapy. In this review we summarize TSPO’s molecular characteristics and highlight research progress in recent years in the field of TSPO-targeted cancer diagnostics and treatments.
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[480]
TÍTULO / TITLE: - Poly (ADP-Ribose) Polymerase Inhibitor MK-4827 together with Radiation as a Novel Therapy for Metastatic Neuroblastoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):755-62.
AUTORES / AUTHORS: - Mueller S; Bhargava S; Molinaro AM; Yang X; Kolkowitz I; Olow A; Wehmeijer N; Orbach S; Chen J; Matthay KK; Haas-Kogan DA
INSTITUCIÓN / INSTITUTION: - Department of Neurology, University of California, San Francisco, 675 Nelson Ring, Sandler Neuroscience Center, UCSF, San Francisco, CA 94148, U.S.A. muellers@neuropeds.ucsf.edu.
RESUMEN / SUMMARY: - Background/Aim: To assess poly (ADP-ribose) polymerase (PARP) inhibitor MK-4827 together with radiation for the treatment of neuroblastoma. MATERIALS AND METHODS: Clonogenic survival assays were used to assess MK-4827, radiation and combination thereof in four neuroblastoma cell lines. In vivo efficacy was tested in a murine xenograft model of metastatic neuroblastoma. In vivo targeted inhibition and biological effects included measurement of cleaved caspase-3, gamma-H2AX, and Ki 67 by immunohistochemistry (IHC) and poly-ADP-ribose by Enzyme-Linked Immunosorbent Assay. RESULTS: Treatment of neuroblastoma cell lines reduced clonogenicity and resulted in additive effects with radiation. In vivo treatment with MK-4827 and radiation prolonged survival (p<0.01) compared to single modalities. In vivo superiority of MK-4827 plus radiation was further documented by significant elevations of cleaved caspase-3 and gamma-H2AX in tumors from the combination group compared to single modality cohorts. CONCLUSION: Combination of MK-4827 and radiation might provide effective therapy for children with high-risk neuroblastoma.
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[481]
TÍTULO / TITLE: - Uncommon Epidermal Growth Factor Receptor mutations in non-small cell lung cancer and their mechanisms of EGFR tyrosine kinase inhibitors sensitivity and resistance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 25. pii: S0169-5002(13)00054-8. doi: 10.1016/j.lungcan.2013.01.018.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.018
AUTORES / AUTHORS: - Massarelli E; Johnson FM; Erickson HS; Wistuba II; Papadimitrakopoulou V
INSTITUCIÓN / INSTITUTION: - Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.
RESUMEN / SUMMARY: - Therapy targeted against the epidermal growth factor receptor (EGFR) has demonstrated dramatic tumor responses and favorable clinical outcomes in a select group of non-small cell lung cancer (NSCLC) patients whose tumors harbor EGFR activating mutations. The best characterized of the mutations conferring sensitivity to EGFR tyrosine kinase inhibitors (TKIs) are deletions in exon 19 and a point mutation in exon 21 (L858R). Likewise, the most common mutation that confers resistance is the T790M point mutation. However several other mutations have been reported and several have been characterized as regards their role in sensitivity or resistance to EGFR TKIs. Resistance to the EGFR TKIs erlotinib and gefitinib, and the newer irreversible EGFR TKIs is a problem of fundamental importance. Recognition of the presence and significance of specific EGFR mutations is important for appropriate therapeutic implementation of EGFR TKIs and research and development of mutation-specific inhibitors. We summarize the literature and present an overview of the subject of less common EGFR mutations and their clinical significance, with an emphasis on EGFR TKI sensitivity or resistance.
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[482]
TÍTULO / TITLE: - Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-1966-0
AUTORES / AUTHORS: - Kim JM; Hyuck C; Kwon D; Joh JW; Lee JH; Paik SW; Park CK
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong Gangnam-Gu, Seoul, 135-710, Korea, yjongman21@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to identify the clinicopathologic characteristics and outcomes of patients with small HCC and analyze the predisposing factors for tumor recurrence after surgery. METHODS: We retrospectively reviewed 180 patients with small HCC who underwent hepatectomy between 2006 and 2010. Independent predictors of tumor recurrence were identified with Cox regression analysis. RESULTS: The 1-year, 3-year, and 5-year disease-free survival rates and overall survival rates were 83.7, 68.0, 65.3, and 98.9, 96.5, 92.7 %, respectively. Multivariate analysis reported that protein induced by the vitamin K antagonist-II (PIVKA-II) >/=200 mAU/mL, alkaline phosphatase (ALP) >/=80 IU/mL, and microvascular invasion were important predisposing factors for tumor recurrence. Elevated serum PIVKA-II level was associated with microvascular invasion in small HCC, which was a powerful predisposing factor. CONCLUSIONS: Although small HCC is generally associated with a good prognosis, serum PIVKA-II level >/=200 mAU/mL, ALP >/= 80 IU/L, and microvascular invasion were predisposing factors for tumor recurrence. These factors can be used to stratify patients with respect to recurrence after resection. Elevated PIVKA-II was closely associated with microvascular invasion in small HCC. These data emphasize the importance of PIVKA-II in small HCC.
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[483]
TÍTULO / TITLE: - Induction of apoptosis in osteosarcoma s180 cells by polysaccharide from dictyophora indusiata.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biochem Funct. 2013 Feb 10. doi: 10.1002/cbf.2961.
●● Enlace al texto completo (gratuito o de pago) 1002/cbf.2961
AUTORES / AUTHORS: - Zhong B; Ma Y; Fu D; Zhang C
INSTITUCIÓN / INSTITUTION: - Department of Orthopaedic Surgery, Shanghai 6th People’s Hospital, Shanghai Jiao Tong University, Shanghai, China.
RESUMEN / SUMMARY: - Polysaccharides have shown great importance in cancer therapy. The current study showed that a polysaccharide from Dictyophora indusiata (PDI) also possessed anti-cancer properties. Methyl thiazolyl tetrazolium assay revealed a dose-dependent reduction of osteosarcoma S180 growth in response to PDI treatment. Apoptosis was observed following treatments with PDI, as reflected by the appearance of the subdiploid fraction and DNA fragmentations. We then investigated effects of PDI on expression of apoptosis-associated genes and the results revealed an increase of expression of bcl-2 and decreases of cdk4 and p53 protein levels. Finally, PDI treatment significantly increased the activation of caspase-3, a key executioner of apoptosis. These findings indicate that PDI may act as a chemopreventive and/or chemotherapeutic agent in osteosarcoma cells by reducing cell viability and inducing apoptosis. Copyright © 2013 John Wiley & Sons, Ltd.
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[484]
TÍTULO / TITLE: - A 36-gene Signature Predicts Clinical Progression in a Subgroup of ERG-positive Prostate Cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Urol. 2013 Mar 7. pii: S0302-2838(13)00222-4. doi: 10.1016/j.eururo.2013.02.039.
●● Enlace al texto completo (gratuito o de pago) 1016/j.eururo.2013.02.039
AUTORES / AUTHORS: - Gasi Tandefelt D; Boormans JL; van der Korput HA; Jenster GW; Trapman J
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands.
RESUMEN / SUMMARY: - BACKGROUND: The molecular basis of the clinical heterogeneity of prostate cancer (PCa) is not well understood. OBJECTIVE: The purpose of our study was to identify and characterize genes in a clinically relevant gene expression signature in a subgroup of primary PCa positive for transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG). DESIGN, SETTING, AND PARTICIPANTS: We studied gene expression profiles by unsupervised hierarchical clustering in 48 primary PCas from patients with a long clinical follow-up. Results were correlated with clinical outcome and validated in an independent patient cohort. Selected genes from a defined classifier were tested in vitro for biologic properties. INTERVENTION: Initial treatment of primary tumors was radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between clinical and histopathologic variables were evaluated by the Pearson chi2 test, Mann-Whitney U test, or Kruskal-Wallis test, where appropriate. The log-rank test or Breslow method was used for statistical analysis of Kaplan-Meier survival curves. RESULTS AND LIMITATIONS: Most tumors that overexpressed ERG clustered separately from other primary PCas. No differences in any clinical end points between ERG-positive and ERG-negative cancers were detected. Importantly, within the ERG-positive samples, two subgroups were identified, which differed significantly in prostate-specific antigen recurrence-free survival, and cancer-specific and overall survival. From our findings, we defined a gene expression classifier of 36 genes. In a second, completely independent tumor set, the classifier also distinguished ERG-positive subgroups with different clinical outcome. In both patient cohorts, the classifier was not predictive in ERG-negative tumors. Biologic processes regulated by genes in the classifier included cell adhesion and bone remodeling. Tumor growth factor-beta signaling was indicated as the main differing signaling pathway between the two ERG subgroups. In vitro biologic assays of two selected genes from the classifier (inhibin, beta A [INHBA] and cadherin 11, type 2, OB-cadherin (osteoblast) [CDH11]) supported a functional role in PCa progression. Possible multifocality and limited number of PCa samples can be limitations of the study. CONCLUSIONS: The classifier identified can contribute to prediction of tumor progression in ERG-positive primary prostate tumors and might be instrumental in therapy decisions.
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[485]
TÍTULO / TITLE: - Paclitaxel-loaded hydroxyapatite/collagen hybrid gels as drug delivery systems for metastatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Pharm. 2013 Mar 25;446(1-2):81-6. doi: 10.1016/j.ijpharm.2013.02.002. Epub 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijpharm.2013.02.002
AUTORES / AUTHORS: - Watanabe K; Nishio Y; Makiura R; Nakahira A; Kojima C
INSTITUCIÓN / INSTITUTION: - Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
RESUMEN / SUMMARY: - Hydroxyapatite (HA) is a biocompatible and porous inorganic material that can behave as an effective drug carrier. In this study, HA nanoparticles were prepared according to the hydrothermal method and used as a drug carrier for a water-insoluble anticancer drug, paclitaxel (Tax). The absorption of Tax onto the HA was dependent on the solvent composition. The Tax-loaded HA (Tax/HA) exhibited a lower level of activity than the free Tax because the HA material was not stably dispersed in aqueous media. The Tax/HA was therefore embedded in a collagen gel to give the Tax/HA-embedded collagen gel (Tax/HA/Col), which exhibited a higher level of activity than the Tax-containing collagen gel (Tax/Col). Interestingly, the highly metastatic MDA-MB-231 cells were more sensitive to the Tax/HA/Col than the poorly metastatic MCF-7 cells. Tax/HA/Col is therefore useful for the drug delivery into metastatic cancer cells.
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[486]
TÍTULO / TITLE: - Human gastrin-releasing peptide triggers growth of HepG2 cells through blocking endoplasmic reticulum stress-mediated apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochemistry (Mosc). 2013 Jan;78(1):102-10. doi: 10.1134/S0006297913010136.
●● Enlace al texto completo (gratuito o de pago) 1134/S0006297913010136
AUTORES / AUTHORS: - Li X; Zhang L; Ke X; Wang Y
INSTITUCIÓN / INSTITUTION: - Department of Thyroid, Mammary Gland, and Blood Vessel Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
RESUMEN / SUMMARY: - Gastrin-releasing peptide (GRP) is a kind of neural peptide that plays an important role in the growth of various human cancer cells. However, very little is known about the relationship between GRP and apoptosis in human hepatocellular carcinoma cells. This study investigated the influences of GRP on apoptosis, as well as the mechanism that triggers HepG2 growth. The effects of GRP on cell proliferation were examined by analysis of lactate dehydrogenase. The GRP, caspase 12, and CHOP protein were detected in HepG2 and HL-7702 cells by Western blot, and endoplasmic reticulum (ER) stress-related mRNA transcription was detected by reverse transcription polymerase chain reaction. To explore the specific pathway by which GRP induces the cell growth, we investigated the apoptosis-related pathway. The expression of GRP in HL-7702 cells inhibited tunicamycin triggered ER stress-associated XBP1, ATF4, and TRAF2 mRNA transcription. Three main ER stress-unfolded protein response pathway proteins, including spliced XBP1, cleaved ATF6, IRE1-alpha, PERK, and eIF2-alpha, were increased significantly. Furthermore, the cleaved caspase 12 activation was blocked and CHOP expression was inhibited when GRP was expressed either in HepG2 or HL-7702 cells. In conclusion, GRP triggers the growth of HepG2 cells through blocking the ER stress-mediated pathway.
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[487]
TÍTULO / TITLE: - The plant alkaloid and anti-leukemia drug homoharringtonine sensitizes resistant human colorectal carcinoma cells to TRAIL-induced apoptosis via multiple mechanisms.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0823-9
AUTORES / AUTHORS: - Beranova L; Pombinho AR; Spegarova J; Koc M; Klanova M; Molinsky J; Klener P; Bartunek P; Andera L
INSTITUCIÓN / INSTITUTION: - Department of Cell Signaling & Apoptosis, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 14220, Praha 4, Czech Republic.
RESUMEN / SUMMARY: - TNF-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand from the TNF-alpha family that is under consideration, along with agonistic anti-TRAIL receptor antibodies, as a potential anti-tumor agent. However, most primary human tumors are resistant to monotherapy with TRAIL apoptogens, and thus the potential applicability of TRAIL in anti-tumor therapy ultimately depends on its rational combination with drugs targeting these resistances. In our high-throughput screening for novel agents/drugs that could sensitize TRAIL-resistant colorectal cancer cells to TRAIL-induced apoptosis, we found homoharringtonine (HHT), a cephalotaxus alkaloid and tested anti-leukemia drug, to be a very effective, low nanomolar enhancer of TRAIL-mediated apoptosis/growth suppression of these resistant cells. Co-treatment of TRAIL-resistant RKO or HT-29 cells with HHT and TRAIL led to the effective induction of apoptosis and the complete elimination of the treated cells. HHT suppressed the expression of the anti-apoptotic proteins Mcl-1 and cFLIP and enhanced the TRAIL-triggered activation of JNK and p38 kinases. The shRNA-mediated down-regulation of cFLIP or Mcl-1 in HT-29 or RKO cells variably enhanced their TRAIL-induced apoptosis but it did not markedly sensitize them to TRAIL-mediated growth suppression. However, with the notable exception of RKO/sh cFLIP cells, the downregulation of cFLIP or Mcl-1 significantly lowered the effective concentration of HHT in HHT + TRAIL co-treatment. Combined HHT + TRAIL therapy also led to the strong suppression of HT-29 tumors implanted into immunodeficient mice. Thus, HHT represents a very efficient enhancer of TRAIL-induced apoptosis with potential application in TRAIL-based, anti-cancer combination therapy.
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[488]
TÍTULO / TITLE: - 5-HT serotonin receptor agonist DOI alleviates cytotoxicity in neuroblastoma cells: Role of the ERK pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prog Neuropsychopharmacol Biol Psychiatry. 2013 Feb 1;44C:64-72. doi: 10.1016/j.pnpbp.2013.01.017.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pnpbp.2013.01.017
AUTORES / AUTHORS: - Marinova Z; Walitza S; Grunblatt E
INSTITUCIÓN / INSTITUTION: - Hospital of Child and Adolescent Psychiatry, University of Zurich, Neumuensterallee 9, 8032 Zurich, Switzerland. Electronic address: Zoya.Marinova@kjpdzh.ch.
RESUMEN / SUMMARY: - Disturbances of serotonergic signaling, including the serotonin 2A (5-HT2A) receptor, have been implicated in neuropsychiatric and neurodegenerative disorders. The aim of the present study was to characterize the effect of a 5-HT2A receptor agonist on cytotoxicity in a neuronal cell line and address the involved mechanism. HTR2A mRNA and protein expression in human neuroblastoma SK-N-SH cells was confirmed. Cells were subjected to serum deprivation and cell viability was monitored continuously with xCELLigence. In a dose-response study the 5-HT2A agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (25nM to 5muM) protected against serum deprivation cytotoxicity. The selective 5-HT2A receptor antagonist MDL 11,939, the general protein tyrosine kinase inhibitor genistein, and the extracellular signal-regulated kinase (ERK) pathway MEK inhibitor U0126, all attenuated DOI’s protective effect. An antibody array suggested that 1muM DOI affected phosphorylation of several tyrosine kinases. Western blot further confirmed that DOI transiently increased ERK phosphorylation, indicating its activation. Finally, protective concentrations of DOI increased cellular mitochondrial mass, an effect prevented by pretreatment with U0126. In conclusion, our results suggest that DOI protects SK-N-SH cells against serum deprivation through ERK pathway activation. They imply 5-HT2A receptor modulation as a potential target for neuroprotection.
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[489]
TÍTULO / TITLE: - Postoperative peak serum C-reactive protein predicts outcome of hepatic resection for hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):705-9.
AUTORES / AUTHORS: - Shiba H; Furukawa K; Fujiwara Y; Futagawa Y; Haruki K; Wakiyama S; Ishida Y; Misawa T; Yanaga K
INSTITUCIÓN / INSTITUTION: - Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan. hs0817@jikei.ac.jp
RESUMEN / SUMMARY: - BACKGROUND: In spite of improvements in surgical techniques, instruments, and perioperative management, hepatocellular carcinoma (HCC) recurs after hepatic resection in as many as 60-70% of patients. Therefore, it is important to predict tumor recurrence and prognosis in regard to decision making of additional adjuvant treatment after surgery. We investigated the relation between postoperative serum C-reactive protein (CRP) and tumor recurrence, as well as survival, in patients with HCC after elective hepatic resection. PATIENTS AND METHODS: The subjects of this study were 77 patients who underwent elective hepatic resection for HCC between January 2001 and December 2008. We retrospectively examined the relation between postoperative serum CRP, clinical variables, and recurrence of HCC, as well as overall survival. RESULTS: For disease-free survival, preoperative ICGR15 (retention rate of indocyanine green at 15 min) of more than 15% (p=0.0039, p=0.0026), and advanced tumor stage (p=0.0380, p=0.0203) were significant and independent predictors of worse survival rate in univariate and multivariate analyses, respectively. For overall survival, female gender (p=0.0052, p=0.0021), preoperative ICGR15 of above 15% (p=0.0043, p=0.0153), advanced tumor stage (p=0.0063, p=0.0023), and postoperative peak serum CRP above 10 mg/dl (p=0.0309, p=0.0116) were significant and independent predictors of worse survival rate in univariate and multivariate analyses, respectively. CONCLUSION: Postoperatively elevated serum CRP may be a prognostic indication after elective hepatic resection for patients with HCC.
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[490]
TÍTULO / TITLE: - Aldehyde dehydrogenase 1/epidermal growth factor receptor coexpression is characteristic of a highly aggressive, poor-prognosis subgroup of high-grade serous ovarian carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 1. pii: S0046-8177(13)00017-8. doi: 10.1016/j.humpath.2012.12.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.12.016
AUTORES / AUTHORS: - Liebscher CA; Prinzler J; Sinn BV; Budczies J; Denkert C; Noske A; Sehouli J; Braicu EI; Dietel M; Darb-Esfahani S
INSTITUCIÓN / INSTITUTION: - Institute of Pathology, Charite Universitatsmedizin Berlin, 10117 Berlin, Germany. Electronic address: catarina.liebscher@charite.de.
RESUMEN / SUMMARY: - In models of triple-negative breast cancer (TNBC), it has recently been shown that the epidermal growth factor receptor (EGFR) pathway is up-regulated in the aldehyde dehydrogenase 1 (ALDH1)-positive cancer stem cell fraction. Because high-grade serous ovarian carcinoma (HGSC) reveals strong molecular similarities to TNBC, we aimed to investigate the potential link between ALDH1 and EGFR in this entity. Expression of ALDH1 was investigated in 131 primary HGSCs using immunohistochemistry. Expression data were correlated with EGFR expression as well as with clinicopathologic parameters and survival. Forty-two carcinomas (32.1%) were positive for ALDH1 protein expression. Data on EGFR expression were available for 112 tumors. In these cases ALDH1 was significantly linked to EGFR expression (P < .0001). ALDH1 positivity was a significant negative prognostic factor for overall survival both in univariate (P = .010) and in multivariate survival analyses (P = .041). Tumors that were positive for both ALDH1 and EGFR had an exceptionally bad prognosis as compared with carcinomas with 1 or both markers negative in univariate analysis (P < .0001) and in the multivariate setting (P = .004). Our study suggests that similar to TNBC, there is a link between ALDH1 and EGFR expression in HGSC. Double positivity for both markers identifies a subgroup of highly aggressive, poor-prognosis cancers for which alternative treatment options-potentially EGFR-targeting drugs-should be evaluated.
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[491]
TÍTULO / TITLE: - The expression of estrogen receptors beta2, 5 identifies and is associated with Prognosis in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocrine. 2013 Mar 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9916-z
AUTORES / AUTHORS: - Liu Z; Liao Y; Tang H; Chen G
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Tongji Hospital, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, 430030, China.
RESUMEN / SUMMARY: - Estrogens play a pivotal role in the development and progression of non-small lung cancer (NSCLC). With the discovery of estrogen receptor beta (ERbeta) isoforms, some controversial roles of ERbeta were explained adequately in NSCLC. In this study, our aim is to elucidate expression, distribution, and prognostic significance of ERbeta 1, 2, 5 in NSCLC. Estrogen receptors beta1, 2, 5 protein expression were confirmed by Western-blot analysis in all frozen tissues, and immunohistochemistry (IHC). Nuclear and cytoplasmic staining was evaluated and correlated with histopathologic characteristics, overall survival (OS) and disease-free survival (DFS) via Pearson chi 2 square, Kaplan-Meier plots and Cox proportional hazard models. ERbeta1 was commonly found in the cytoplasm and was the most abundant isofroms followed by ERbeta2 and ERbeta5 which were localized in the cytoplasm and nucleus. In contrast to BPL, both in nucleus and cytoplasm, ERbeta1, ERbeta2, and ERbeta5 were over expressed all in NSCLC (P < 0.05). IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERbeta1, ERbeta2, and ERbeta5 in NSCLC. nERbeta1 “nuclear”, cERbeta2 and cERbeta5 “cytoplasm” were in a negative correlation with the pathological stage and lymph node metastasis. In a Kaplan-Meier analysis, the expression cERbeta2 and cERbeta5 identified a group of patients with the longest DFS and OS. Cox proportional hazard models revealed that cERbeta2 and cERbeta5 predicted long time to DFS and OS. This is the first study to uncover the expression of ERbeta1, ERbeta2, and ERbeta5, and show that they were over expressed in NSCLC. Meantime, we find that positive expression of cERbeta2 and cERbeta5 were in a positive correlation with DFS, and have prognostic values for the progression of NSCLC.
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[492]
TÍTULO / TITLE: - The prognostic and predictive value of KRAS oncogene substitutions in lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Mar 22. doi: 10.1002/cncr.28039.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.28039
AUTORES / AUTHORS: - Villaruz LC; Socinski MA; Cunningham DE; Chiosea SI; Burns TF; Siegfried JM; Dacic S
INSTITUCIÓN / INSTITUTION: - University of Pittsburgh Cancer Institute, School of Medicine/Hematology-Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania. villaruzl@upmc.edu.
RESUMEN / SUMMARY: - BACKGROUND: The prognostic and therapeutic implications of the spectrum of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogene substitutions in lung cancer remain poorly understood. The objective of this study was to determine whether KRAS oncogene substitutions differed with regard to prognosis or predictive value in lung adenocarcinoma. METHODS: KRAS oncogene substitutions and mutant allele-specific imbalance (MASI) were determined in patients with lung adenocarcinoma, and the associations with overall survival (OS), recurrence-free survival (RFS), and chemotherapy interactions were assessed. RESULTS: KRAS mutational analysis was performed on 988 lung adenocarcinomas, and 318 KRAS mutations were identified. In this predominantly early stage cohort (78.6% of patients had stage I-III disease), OS and RFS did not differ according to the type of KRAS substitution (OS, P = .612; RFS, P = .089). There was a trend toward better OS in the subset of patients with KRAS codon 13 mutations (P = .052), but that trend was not significant in multivariate analysis (P = .076). RFS did not differ according to codon type in univariate analysis (P = .322). There was a marked difference in RFS based on the presence of MASI in univariate analysis (P = .004) and multivariate analysis (P = .009). A test for interaction was performed to determine whether the effect of chemotherapy on OS and RFS differed based on KRAS substitution type, codon type, or the presence of MASI. That test indicated that there were no differences in the effects of chemotherapy for any of variables examined. CONCLUSIONS: KRAS codon 13 mutations and MASI were identified as candidate biomarkers for prognosis, and it may be useful to incorporate them into prospective studies evaluating novel therapies in KRAS-mutant lung adenocarcinoma. Cancer 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 American Cancer Society.
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[493]
TÍTULO / TITLE: - Hyaluronic Acid as a Marker of Sinusoidal Obstruction Syndrome after Oxaliplatin-based Chemotherapy for Colorectal Liver Metastases: Don’t Forget the Tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2916-7
AUTORES / AUTHORS: - Rahbari NN; Weitz J
INSTITUCIÓN / INSTITUTION: - Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
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[494]
TÍTULO / TITLE: - S-100B: A Stronger Prognostic Biomarker than LDH in Stage IIIB-C Melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2949-y
AUTORES / AUTHORS: - Wevers KP; Kruijff S; Speijers MJ; Bastiaannet E; Muller Kobold AC; Hoekstra HJ
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, k.p.wevers@umcg.nl.
RESUMEN / SUMMARY: - BACKGROUND: In melanoma patients with nodal macrometastases, the distinction between good and poor prognosis is based on the presence of primary melanoma ulceration or metastatic involvement of 4 or more lymph nodes in the 7th edition of the American Joint Committee on Cancer (AJCC) classification. We hypothesized that biomarkers would increase the accurateness of staging in these patients. The aim was to assess and compare the prognostic impact of biomarkers S-100B and LDH and to determine the best timing of their measurement in stage IIIB-C melanoma. METHODS: A total of 119 patients underwent therapeutic lymph node dissection (TLND) for nodal macrometastases with serum S-100B and LDH level measurements preoperatively. In 75 of them, S-100B and LDH were also measured on postoperative days 1 and 2. S-100B and LDH levels on days 0, 1, and 2 were compared for their association with disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: At a median follow-up of 17 (range 1-89) months, S-100B levels at all time points were associated with DFS. In multivariable analysis, preoperative S-100B and S-100B measured on day 2 showed the strongest association with DFS (hazard ratio [HR] 2.55, P = 0.007 and HR 3.80, P = 0.01). For DSS, the preoperative S-100B level was the strongest independent predictor (HR 2.81, P = 0.01). LDH measurements showed a significant association with DSS in univariate analysis only when measured preoperatively (HR 2.46, P = 0.01). In multivariable analysis, LDH measurement was not associated with melanoma prognosis. CONCLUSIONS: The S-100B level measured preoperatively is, in contrast to LDH, one of the most important independent predictors of melanoma prognosis in patients undergoing TLND for nodal macrometastases.
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[495]
TÍTULO / TITLE: - Sunitinib for the Treatment of Metastatic Paraganglioma and Vasoactive Intestinal Polypeptide-Producing Tumor (VIPoma).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar;42(2):348-52. doi: 10.1097/MPA.0b013e31825c53fa.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825c53fa
AUTORES / AUTHORS: - Bourcier ME; Vinik AI
INSTITUCIÓN / INSTITUTION: - From the Strelitz Diabetes Center and Neuroendocrine Unit, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA.
RESUMEN / SUMMARY: - OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are rare tumors of the endocrine and nervous systems. Whereas early surgical resection can significantly reduce tumor mass, there are few data available concerning the control of hormonal secretion and associated symptoms. Studies have shown that the tyrosine kinase inhibitor sunitinib significantly prolongs progression-free survival in patients with pancreatic NETs. Here, we present 2 case reports of sunitinib in patients with different types of NETs. METHODS: The patients were a 12-year-old boy with metastatic vasoactive intestinal polypeptide-producing tumor (VIPoma) and a 70-year-old woman with metastatic paraganglioma/NET. Both were treated in an outpatient clinical setting. Sunitinib was titrated to 37.5 mg on a continuous daily dosing schedule in the patient with VIPoma, and the dose was 50 mg/d (4 weeks on, 2 weeks off) in the patient with the paraganglioma/NET. RESULTS: The patient with the paraganglioma/NET had a confirmed complete radiographic response and the patient with VIPoma had a confirmed partial response (Response Evaluation Criteria in Solid Tumors). In both patients, improvements were observed in biochemical tumor markers, clinical responses, and quality of life. CONCLUSIONS: In these patients, sunitinib reduced biochemical markers and stabilized or reduced tumor bulk and may therefore be a potential therapeutic option for these tumor types.
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[496]
TÍTULO / TITLE: - Antiproliferative activity of gambogic acid isolated from Garcinia hanburyi in Hep3B and Huh7 cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 19. doi: 10.3892/or.2013.2291.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2291
AUTORES / AUTHORS: - Lee PN; Ho WS
INSTITUCIÓN / INSTITUTION: - School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
RESUMEN / SUMMARY: - The anticancer activities of gambogic acid (GA) on two hepatocellular carcinoma cells with either p53 deletion (Hep3B) or p53 mutation (Huh7) were investigated in the present study. GA inhibited the growth of Hep3B and Huh7 through similar apoptotic pathways. After treatment of Hep3B and Huh7 with GA for 24 h, the IC50 was determined for both cell lines at 1.8 and 2.2 microM, respectively. The results showed that both cancer cells underwent morphological changes and DNA fragmentation. GA induced apoptosis in the two cell lines through caspases-3/7, -8 and -9 in the mitochondrial pathway. The results suggest that both the caspases in the extrinsic death receptor pathway and the mitochondrial-dependent pathway are involved in the GA-induced cell apoptosis. The inhibitory effects of GA on Hep3B and Huh7 are independent of p53-associated pathway.
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[497]
TÍTULO / TITLE: - Plasma HER2 amplification in cell-free DNA during neoadjuvant chemotherapy in breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cancer Res Clin Oncol. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s00432-013-1413-5
AUTORES / AUTHORS: - Bechmann T; Andersen RF; Pallisgaard N; Madsen JS; Maae E; Jakobsen EH; Bak Jylling AM; Steffensen KD; Jakobsen A
INSTITUCIÓN / INSTITUTION: - The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, troels.bechmann@slb.regionsyddanmark.dk.
RESUMEN / SUMMARY: - PURPOSE: Measurement of human epidermal growth factor receptor 2 (HER2) gene amplification in cell-free DNA (cfDNA) is an evolving technique in breast cancer, enabling liquid biopsies and treatment monitoring. The present study investigated the dynamics of plasma HER2 gene copy number and amplification in cfDNA during neoadjuvant chemotherapy. PATIENTS AND METHODS: The study included 50 patients from a prospective cohort analyzed during neoadjuvant chemotherapy. Fifty healthy women with no history of cancer served as control group and 15 patients with metastatic breast cancer were used to validate the assay. Total cfDNA and HER2 gene amplification were measured by quantitative real-time polymerase chain reaction. RESULTS: Plasma HER2 gene copy number (p = 0.794), HER2 gene amplification (p = 0.127) and total cfDNA (p = 0.440) did not differ significantly from the levels in the control group. Eighteen patients (36 %) obtained pathological complete response (pCR). HER2 gene copy number before the operation was significantly higher than the baseline level (p < 0.0001), but there was no difference between patients with and without pCR (p = 0.569). Likewise, there was no difference in plasma HER2 gene amplification between tissue HER2-positive and -negative patients (p = 0.754). CONCLUSIONS: The results indicate that neither total cfDNA nor HER2 gene copy number is elevated in primary breast cancer patients compared to healthy controls. The level of both parameters increased during neoadjuvant chemotherapy, but without any relation to treatment effect. There was no indication of plasma HER2 gene amplification in the HER2-positive patients in the neoadjuvant setting.
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[498]
TÍTULO / TITLE: - PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Apr;138(2):457-66. doi: 10.1007/s10549-013-2416-2. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2416-2
AUTORES / AUTHORS: - Martin M; Prat A; Rodriguez-Lescure A; Caballero R; Ebbert MT; Munarriz B; Ruiz-Borrego M; Bastien RR; Crespo C; Davis C; Rodriguez CA; Lopez-Vega JM; Furio V; Garcia AM; Casas M; Ellis MJ; Berry DA; Pitcher BN; Harris L; Ruiz A; Winer E; Hudis C; Stijleman IJ; Tuck DP; Carrasco E; Perou CM; Bernard PS
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Instituto de Investigacion Sanitaria Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, España, mmartin@geicam.org.
RESUMEN / SUMMARY: - To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical-pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.
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[499]
TÍTULO / TITLE: - 6 Iodo-delta-lactone: A derivative of arachidonic acid with antitumor effects in HT-29 colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prostaglandins Leukot Essent Fatty Acids. 2013 Jan 29. pii: S0952-3278(13)00004-5. doi: 10.1016/j.plefa.2013.01.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.plefa.2013.01.002
AUTORES / AUTHORS: - Thomasz L; Oglio R; Rossich L; Villamar S; Perona M; Salvarredi L; Dagrosa A; Pisarev MA; Juvenal GJ
INSTITUCIÓN / INSTITUTION: - Nuclear Biochemistry Division, Argentine National Atomic Energy Commission Buenos Aires 1429, Argentina.
RESUMEN / SUMMARY: - BACKGROUND: IL-delta (5-hydroxy-6 iodo-8,11,14-eicosatrienoic delta lactone) an iodinated arachidonic acid (AA) derivative, is one of the iodolipids biosynthesized by the thyroid. Although IL-delta regulates several thyroid parameters such as cell proliferation and goiter growth it was found that this iodolipid inhibits the growth of other non thyroid cell lines. OBJECTIVES: To study the effect of IL-delta on cell proliferation and apoptosis in the colon cancer cell line HT-29. RESULTS: Treatment with IL-delta reduced cell viability in a concentration-dependent manner: 1muM 20%, 5muM 25%, 10muM 31%, 50muM 47% and caused a significant decrease of PCNA expression (25%). IL-delta had pro-apoptotic effects, evidenced by morphological features of programmed cell death such as pyknosis, karyorrhexis, cell shrinkage and cell blebbing observed by fluorescence microscopy, and an increase in caspase-3 activity and in Bax/Bcl-2 ratio (2.5 after 3h of treatment). Furthermore, IL-delta increased ROS production (30%) and lipid peroxidation levels (19%), suggesting that apoptosis could be a result of increased oxidative stress. A maximum increase in c-fos and c-jun protein expression in response to IL-delta was observed 1h after initiation of the treatment. IL-delta also induced a tumour growth delay of 70% compared to the control group in NIH nude mice implanted with HT-29 cells. CONCLUSION: Our study shows that IL-delta inhibits cell growth and induces apoptosis in the colon cancer cell line, HT-29 and opens the possibility that IL-delta could be a potential useful chemotherapy agent.
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[500]
TÍTULO / TITLE: - Jacaric acid and its octadecatrienoic acid geoisomers induce apoptosis selectively in cancerous human prostate cells: a mechanistic and 3-D structure-activity study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Phytomedicine. 2013 Feb 27. pii: S0944-7113(13)00043-3. doi: 10.1016/j.phymed.2013.01.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.phymed.2013.01.012
AUTORES / AUTHORS: - Gasmi J; Thomas Sanderson J
INSTITUCIÓN / INSTITUTION: - Institut National de la Recherche Scientifique (INRS), Institut Armand-Frappier, Universite du Quebec, Laval, Quebec, Canada.
RESUMEN / SUMMARY: - Plant-derived non-essential fatty acids are important dietary nutrients, and some are purported to have chemopreventive properties against various cancers, including that of the prostate. In this study, we determined the ability of seven dietary C-18 fatty acids to cause cytotoxicity and induce apoptosis in various types of human prostate cancer cells. These fatty acids included jacaric and punicic acid found in jacaranda and pomegranate seed oil, respectively, three octadecatrienoic geometric isomers (alpha- and beta-calendic and catalpic acid) and two mono-unsaturated C-18 fatty acids (trans- and cis-vaccenic acid). Jacaric acid and four of its octadecatrienoic geoisomers selectively induced apoptosis in hormone-dependent (LNCaP) and -independent (PC-3) human prostate cancer cells, whilst not affecting the viability of normal human prostate epithelial cells (RWPE-1). Jacaric acid induced concentration- and time-depedent LNCaP cell death through activation of intrinsic and extrinsic apoptotic pathways resulting in cleavage of PARP-1, modulation of pro- and antiapoptotic Bcl-2 family of proteins and increased cleavage of caspase-3, -8 and -9. Moreover, activation of a cell death-inducing signalling cascade involving death receptor 5 was observed. Jacaric acid induced apoptosis in PC-3 cells by activation of the intrinsic pathway only. The spatial conformation cis, trans, cis of jacaric and punicic acid was shown to play a key role in the increased potency and efficacy of these two fatty acids in comparison to the five other C-18 fatty acids tested. Three-dimensional conformational analysis using the PubChem Database (pubchem.ncbi.nlm.nih.gov) showed that the cytotoxic potency of the C-18 fatty acids was related to their degree of conformational similarity to our cytotoxic reference compound, punicic acid, based on optimized shape (ST) and feature (CT) similarity scores, with jacaric acid being most ‘biosimilar’ (STST-opt=0.81; CTCT-opt=0.45). This 3-D analysis of structural similarity enabled us to rank geoisomeric fatty acids according to cytotoxic potency, whereas a 2-D positional assessment of cis/trans structure did not. Our findings provide mechanistic evidence that nutrition-derived non-essential fatty acids have chemopreventive biological activities and Exhibit 3-D structure-activity relationships that could be exploited to develop new strategies for the prevention or treatment of prostate cancer regardless of hormone dependency.
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[501]
TÍTULO / TITLE: - Comparing cost-effectiveness analyses of denosumab versus zoledronic acid for the treatment of bone metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Support Care Cancer. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1790-y
AUTORES / AUTHORS: - Koo K; Lam K; Mittmann N; Konski A; Dennis K; Zeng L; Lam H; Chow E
INSTITUCIÓN / INSTITUTION: - Rapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3 M5, Canada.
RESUMEN / SUMMARY: - BACKGROUND: Bone metastases from various cancers have been traditionally treated with bisphosphonates, such as zoledronic acid (ZA), to prevent future skeletal-related events (SREs). Denosumab (Dmab) has been shown to have more advantages in preventing SREs in clinical trials than ZA, but the cost to administer Dmab is significantly higher. METHODS: A literature review was conducted to investigate the methodologies used to compare the cost-effectiveness of Dmab and ZA. MEDLINE® and EMBASE were searched systematically for all cost-effectiveness analyses published between January week 1, 2006 to August week 1, 2012. Search strategies were designed to retrieve articles analyzing the cost-effectiveness and cost utility of Dmab compared to ZA in patients with bone metastases. From 12 references obtained in the initial database search, eight satisfied the predetermined criteria for full article review. Articles were analyzed for incremental costs per skeletal-related event avoided or incremental cost per quality-adjusted life year gained. RESULTS: All the studies identified received funding from Novartis Pharmaceuticals (the manufacturer of ZA) or Amgen Incorporated (the manufacturer of Dmab). The studies looked at the economic analysis using different associated costs and over various time periods, ranging from a 1-year to a lifetime time horizon. CONCLUSION: It is not clear whether the methods used across studies are consistent, which may account for the differences between estimated costs and effects. Future research is suggested to explore the cost-effectiveness between Dmab and ZA using a standardize time frame and endpoint.
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[502]
TÍTULO / TITLE: - Sorafenib Enhances Radiation-Induced Apoptosis in Hepatocellular Carcinoma by Inhibiting STAT3.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Mar 5. pii: S0360-3016(13)00106-5. doi: 10.1016/j.ijrobp.2013.01.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.01.025
AUTORES / AUTHORS: - Huang CY; Lin CS; Tai WT; Hsieh CY; Shiau CW; Cheng AL; Chen KF
INSTITUCIÓN / INSTITUTION: - Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Radiological Technology, Yuanpei University, Hsinchu, Taiwan.
RESUMEN / SUMMARY: - PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common and lethal human malignancies. Lack of efficient therapy for advanced HCC is a pressing problem worldwide. This study aimed to determine the efficacy and mechanism of combined sorafenib and radiation therapy treatment for HCC. METHODS AND MATERIALS: HCC cell lines (PLC5, Huh-7, Sk-Hep1, and Hep3B) were treated with sorafenib, radiation, or both, and apoptosis and signal transduction were analyzed. RESULTS: All 4 HCC cell lines showed resistance to radiation-induced apoptosis; however, this resistance could be reversed in the presence of sorafenib. Inhibition of phospho-STAT3 was found in cells treated with sorafenib or sorafenib plus radiation and subsequently reduced the expression levels of STAT3-related proteins, Mcl-1, cyclin D1, and survivin. Silencing STAT3 by RNA interference overcame apoptotic resistance to radiation in HCC cells, and the ectopic expression of STAT3 in HCC cells abolished the radiosensitizing effect of sorafenib. Moreover, sorafenib plus radiation significantly suppressed PLC5 xenograft tumor growth. CONCLUSIONS: These results indicate that sorafenib sensitizes resistant HCC cells to radiation-induced apoptosis via downregulating phosphorylation of STAT3 in vitro and in vivo.
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[503]
TÍTULO / TITLE: - Genetic blockade of IGF-1R via recombinant adenovirus in lung cancer can be enhanced by histone deacetylase inhibitor, vorinostat.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gene Med. 2013 Feb 14. doi: 10.1002/jgm.2699.
●● Enlace al texto completo (gratuito o de pago) 1002/jgm.2699
AUTORES / AUTHORS: - Park MY; Kim DR; Eo EY; Lim HJ; Park JS; Cho YJ; Yoon HI; Lee JH; Lee CT
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Respiratory Center, Seoul National University Bundang Hospital, Seongnam, Korea.
RESUMEN / SUMMARY: - BACKGROUND: Many approaches have been suggested as anti-tumor therapy targeting IGF-1R, such as monoclonal antibodies and tyrosine kinase inhibitor (TKI). We introduced recombinant adenoviruses expressing antisense, dominant negative, or short hairpin RNA to IGF-1R. Moreover, we demonstrated that HDAC inhibitor (vorinostat) can increase the transduction efficiency of adenoviruses by increasing CAR-induced transduction and by enhancing the transcription of the adenoviral transgene. In this study, we showed that the combination of ad-sh (short hairpin) IGF-1R with vorinostat leads to a synergistic enhancement of IGF-1R blockade. METHOD: We measured the change in IGF-1R upon co-treatment with vorinostat and ad-shIGF-1R. Changes in transduction efficiency of ad-shIGF-1R were measured by fluorescent microscopy. Changes in apoptotic proportion and cell survival after the co-treatment were measured by the sub-G1 assay and cell counts. The effect of NF-B activation was also measured by NF-B p65 activation ELISA assay. Drug interactions were analyzed upon co-treatment with ad-shIGF-1R, vorinostat and cisplatin. RESULTS: Combined treatment of ad-shIGF-1R and vorinostat synergistically suppressed the IGF-1R expression in lung cancer cell lines and also increased the transduction efficiency of ad-shIGF-1R. Ad-shIGF-1R and vorinostat co-treatment increased apoptotic cell death and synergistically suppressed cell growth, compared with ad-shIGF-1R or vorinostat treatment alone. Vorinostat suppressed NF-B activation, which was activated by ad-shIGF-1R. Moreover, triple combination of ad-shIGF-1R, vorinostat, and cisplatin demonstrated synergistic cytotoxicity on lung cancer cells. CONCLUSION: Vorinostat enhanced the blocking capability of ad-shIGF-1R. The combined treatment of vorinostat and ad-sh-IGF-1R appears to be a promising potential as a new therapeutic approach for lung cancer. Copyright © 2013 John Wiley & Sons, Ltd.
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[504]
TÍTULO / TITLE: - EGFR Tyrosine Kinase Inhibitor Pelitinib Regulates Radiation-Induced p65-Dependent Telomerase Activation in Squamous Cell Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Res. 2013 Mar;179(3):304-12. doi: 10.1667/RR3028.1. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1667/RR3028.1
AUTORES / AUTHORS: - Aravindan N; Aravindan S; Herman TS; Natarajan M
INSTITUCIÓN / INSTITUTION: - Departments of a Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and.
RESUMEN / SUMMARY: - Our earlier studies indicated that ionizing radiation (IR) induces NF-kappaB-dependent clonal expansion of therapy resistant tumor cells. Herein, we investigated whether mitigation of NF-kappaB-dependent telomerase activation by EGFR tyrosine kinase inhibitor can enhance IR-induced celling killing. SCC-4 and SCC-9 cells exposed to IR with or without Pelitinib were examined for NF-kappaB and hTERT transcription using luciferase reporter assays. NF-kappaB-dependent hTERT transcription was confirmed by either muting NF-kappaB or by using hTERT constructs lacking NF-kappaB binding sites. hTERT, mRNA, telomerase activity and cell survival of tumor cells were analyzed using QPCR, TRAP and clonogenic assay, respectively. Pelitinib inhibited IR-induced NF-kappaB, telomerase activity and hTERT transactivation. Ionizing radiation-induced telomerase activity is regulated at the transcriptional level by triggering TERT promoter activation. Functional NF-kappaB mediates telomerase activity by binding to the kappaB binding region in the promoter region of TERT. Elimination of the NF-kappaB recognition site on telomerase or muting NF-kappaB compromises IR-induced telomerase promoter activation. We found that Pelitinib inhibited IR-induced TERT transcription, transactivation and telomerase activation in IR-exposed and NF-kappaB-overexpressed cells. Furthermore, Pelitinib potentiates IR-induced cell killing. Our results strongly suggest that IR-induced NF-kappaB-mediated cell survival is supported by telomerase activation. We propose that if this pathway can be inhibited with Pelitinib treatment, one could further enhance therapeutic outcome in squamous cell carcinoma.
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[505]
TÍTULO / TITLE: - External Qi of Yan Xin Qigong Inhibits Activation of Akt, Erk1/2 and NF-kB and Induces Cell Cycle Arrest and Apoptosis in Colorectal Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Physiol Biochem. 2013;31(1):113-22. doi: 10.1159/000343354. Epub 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 1159/000343354
AUTORES / AUTHORS: - Yan X; Shen H; Jiang H; Hu D; Wang J; Wu X
INSTITUCIÓN / INSTITUTION: - Chongqing Institute of Traditional Chinese Medicine, Chongqing, China.
RESUMEN / SUMMARY: - Background/Aims: Colorectal cancer (CRC) is the second leading cause of cancer death in the Western countries. Novel approaches of treatment are needed for CRC. The purpose of the present study was to investigate cytotoxic effect of external Qi of Yan Xin Qigong (YXQ-EQ) on human colorectal cancer cells. Methods: The effect of YXQ-EQ on viability, cell cycle progression and apoptosis in colorectal cancer HT-29 cells was investigated. Phosphorylation of Akt and Erk1/2, activation of NF-kB and the expression of proteins involved in regulation of cell cycle and apoptosis were examined by Western blot analysis. Results: YXQ-EQ markedly decreased viability and blocked colony formation of HT-29 cells. YXQ-EQ downregulated cyclin D1 expression and increased accumulation of cyclin-dependent kinase inhibitors p21 and p27, resulting in G1 cell cycle arrest. YXQ-EQ induced apoptosis in HT-29 cells in association with decreased expression of antiapoptotic proteins Bcl-xL, XIAP, survivin and Mcl-1 and elevated expression of proapoptotic protein Bax. YXQ-EQ significantly repressed phosphorylation of Akt and Erk1/2 and NF-kB activation in HT-29 cells, suggesting that YXQ-EQ may exert cytotoxic effect through regulating signaling pathways critical for cell proliferation and survival. Furthermore, YXQ-EQ treated PBS and an YXQ-EQ treated plant extract induced apoptosis in HT-29 cells. Conclusion: These findings show that YXQ-EQ has potent cytotoxic effect on HT-29 cells and suggest that YXQ-EQ could be potentially used for colorectal cancer treatment either directly or indirectly via carriers.
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[506]
TÍTULO / TITLE: - The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28097.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28097
AUTORES / AUTHORS: - Errico MC; Felicetti F; Bottero L; Mattia G; Boe A; Felli N; Petrini M; Bellenghi M; Pandha HS; Calvaruso M; Tripodo C; Colombo MP; Morgan R; Care A
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanita, Rome, Italy.
RESUMEN / SUMMARY: - Cutaneous melanoma is the fastest increasing cancer worldwide. Although several molecular abnormalities have been associated with melanoma progression, the underlying mechanisms are still largely unknown and few targeted therapies are under evaluation. Here we show that the HOXB7/PBX2 dimer acts as a positive transcriptional regulator of the oncogenic microRNA-221 and -222. In addition, demonstrating c-FOS as a direct target of miR-221&222, we identify a HOXB7/PBX2-->miR-221&222 -->c-FOS regulatory link, whereby the abrogation of functional HOXB7/PBX2 dimers leads to reduced miR-221&222 transcription and elevated c-FOS expression with consequent cell death. Taking advantage of the treatment with the peptide HXR9, an antagonist of HOX/PBX dimerization, we recognize miR-221&222 as effectors of its action, in turn confirming the HXR9 efficacy in the treatment of human melanoma malignancy, whilst sparing normal human melanocytes. Our findings, besides suggesting the potential therapeutic of HXR9 or its derivatives in malignant melanoma, suggest the disruption of the HOXB7/PBX2 complexes, miR-221&222 inhibition or even better their combination, as innovative therapeutic approaches.
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[507]
TÍTULO / TITLE: - EBV counteracts IL-21-induced apoptosis in an EBV-positive diffuse large B-cell lymphoma cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Jan 30. doi: 10.1002/ijc.28067.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28067
AUTORES / AUTHORS: - Wu L; Ehlin-Henriksson B; Zhu H; Ernberg I; Klein G
INSTITUCIÓN / INSTITUTION: - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
RESUMEN / SUMMARY: - Previously, interleukin (IL)-21 has been found to induce apoptosis by activating the signal transducer and activator of transcription 3 (STAT3) and concomitant upregulation of c-Myc in diffuse large B-cell lymphoma (DLBCL) lines with unknown Epstein-Barr virus (EBV) status. Here, as a first approach toward the characterization of the role of EBV in DLCBL, the EBV gene expression and the IL-21 sensitivity of the EBV-positive DLBCL line, Farage, have been examined. It was found that, surprisingly, despite c-Myc upregulation, IL-21 induced cell proliferation rather than apoptosis in Farage. Expression of a dominant-negative EBNA1 mutant and the consecutive downregulation of EBV gene expression antagonized the IL-21-induced proliferation of Farage and increased apoptosis. These findings reveal a previously unknown role of EBV in DLBCL that is of possible relevance for the current attempt to use IL-21 in therapy.
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[508]
TÍTULO / TITLE: - Multivariate Analysis of Prognostic Factors for Survival following Doxorubicin-eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Vasc Interv Radiol. 2013 Feb 2. pii: S1051-0443(12)01231-6. doi: 10.1016/j.jvir.2012.12.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jvir.2012.12.003
AUTORES / AUTHORS: - Sellers MT; Huggins S; Kegley K; Pollinger HS; Shrestha R; Johnson MW; Stein LL; Panjala C; Tan M; Arepally A; Jacobs L; Caldwell C; Bosley M; Citron SJ
INSTITUCIÓN / INSTITUTION: - Hepatobiliary Service, Piedmont Transplant Institute (M.T.S., S.H., K.K., H.S.P., R.S., M.W.J., L.L.S., C.P., M.T.). Electronic address: marty.sellers@piedmont.org.
RESUMEN / SUMMARY: - PURPOSE: To identify prognostic factors for survival in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (DEBs). MATERIALS AND METHODS: In a retrospective, single-center analysis, tumor- and patient-related factors were recorded for univariate and multivariate analyses via Kaplan-Meier and Cox regression. Infiltrative HCC phenotype and portal vein invasion (PVI) were correlated, and patients with either or both were classified as having radiographically advanced (RAdv) HCC. The primary endpoint was overall survival, which was calculated from the time of first DEB chemoembolization procedure. RESULTS: A total of 168 patients underwent 248 procedures, of which 215 (86.7%) were outpatient procedures. Mean length of stay was 0.33 days, and 25 patients (10.1%) were readmitted within 30 days. A total of 33 patients underwent liver transplantation and were excluded from survival analyses. A total of 130 had cirrhosis; 62, 50, and 18 had Child class A, B, and C disease, respectively. Forty-one patients had infiltrative HCC phenotype, 28 of whom also had PVI. Multivariate analysis of survival in all patients showed alpha-fetoprotein (AFP), performance status (PS), RAdv HCC, Child classification, albumin level, and ascites to predict survival. In patients without RAdv HCC, AFP, PS, Child classification, albumin level, and International Normalized Ratio were independent predictors. Increased bilirubin level was not an independent risk factor for death. CONCLUSIONS: Independent prognostic factors in patients with HCC undergoing DEB chemoembolization have been identified. Increased bilirubin level was not an independent risk factor. These data can be used in HCC patient selection and counseling for DEB chemoembolization.
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[509]
TÍTULO / TITLE: - Pre-treatment C-Reactive Protein as a Prognostic Factor for Recurrence after Surgical Resection of Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1181-8.
AUTORES / AUTHORS: - Nishikawa H; Arimoto A; Wakasa T; Kita R; Kimura T; Osaki Y
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027, Japan. h-nishikawa@osaka-med.jrc.or.jp.
RESUMEN / SUMMARY: - Background and Aims: We examined the prognostic value of pre-treatment C-reactive protein (CRP) after surgical resection (SR) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 298 patients with HCC who underwent SR were analyzed. They were categorized into a CRP-positive group (group A: CRP >0.2 mg/dl, n=130) and a CRP-negative group (group B: CRP <0.2 mg/dl, n=168). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: The 1- and 3-year cumulative OS rates were 87.0% and 68.3% in group A and 95.9% and 81.1% in group B (p=0.194). The corresponding RFS rates were 61.6% and 30.3% in group A and 77.2% and 44.9% in group B (p=0.004). In multivariate analysis, the pre-treatment CRP level was a significant prognostic factor linked to RFS (p=0.046). CONCLUSION: Pre-treatment CRP levels may be a useful predictor of recurrence after SR for HCC.
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[510]
TÍTULO / TITLE: - TRIM16 overexpression induces apoptosis through activation of caspase-2 in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0813-y
AUTORES / AUTHORS: - Kim PY; Rahmanto AS; Tan O; Norris MD; Haber M; Marshall GM; Cheung BB
INSTITUCIÓN / INSTITUTION: - Children’s Cancer Institute Australia for Medical Research, Randwick, NSW, 2031, Australia.
RESUMEN / SUMMARY: - TRIM16 exhibits tumour suppressor functions by interacting with cytoplasmic vimentin and nuclear E2F1 proteins in neuroblastoma and squamous cell carcinoma cells, reducing cell migration and replication. Reduced TRIM16 expression in a range of human primary malignant tissues correlates with increased malignant potential. TRIM16 also induces apoptosis in breast and lung cancer cells, by unknown mechanisms. Here we show that overexpression of TRIM16 induces apoptosis in human breast cancer (MCF7) and neuroblastoma (BE(2)-C) cells, but not in non-malignant HEK293 cells. TRIM16 increased procaspase-2 protein levels in MCF7 and induced caspase-2 activity in both MCF7 and BE(2)-C cells. We show that TRIM16 and caspase-2 proteins directly interact in both MCF7 and BE(2)-C cells and co-localise in MCF7 cells. Most importantly, the induction of caspase-2 activity is required for TRIM16 to initiate apoptosis. Our data suggest a novel mechanism by which TRIM16 can promote apoptosis by directly modulating caspase-2 activity.
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[511]
TÍTULO / TITLE: - MAPK p38 and JNK have opposing activities on TRAIL-induced apoptosis activation in NSCLC H460 cells that involves RIP1 and caspase-8 and is mediated by Mcl-1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0829-3
AUTORES / AUTHORS: - Azijli K; Yuvaraj S; van Roosmalen I; Flach K; Giovannetti E; Peters GJ; de Jong S; Kruyt FA
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713 GZ, The Netherlands.
RESUMEN / SUMMARY: - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce both caspase-dependent apoptosis and kinase activation in tumor cells. Here, we examined the consequences and mechanisms of TRAIL-induced MAPKs p38 and JNK in non-small cell lung cancer (NSCLC) cells. In apoptosis sensitive H460 cells, these kinases were phosphorylated, but not in resistant A549 cells. Time course experiments in H460 cells showed that induction of p38 phosphorylation preceded that of JNK. To explore the function of these kinases in apoptosis activation by TRAIL, chemical inhibitors or siRNAs were employed to impair JNK or p38 functioning. JNK activation counteracted TRAIL-induced apoptosis whereas activation of p38 stimulated apoptosis. Notably, the serine/threonine kinase RIP1 was cleaved following TRAIL treatment, concomitant with detectable JNK phosphorylation. Further examination of the role of RIP1 by short hairpin (sh)RNA-dependent knockdown or inhibition by necrostatin-1 showed that p38 can be phosphorylated in both RIP1-dependent and -independent manner, whereas JNK phosphorylation occurred independent of RIP1. On the other hand JNK appeared to suppress RIP1 cleavage via an unknown mechanism. In addition, only the activation of JNK by TRAIL was caspase-8-dependent. Finally, we identified Mcl-1, a known substrate for p38 and JNK, as a downstream modulator of JNK or p38 activity. Collectively, our data suggest in a subset of NSCLC cells a model in which TRAIL-induced activation of p38 and JNK have counteracting effects on Mcl-1 expression leading to pro- or anti-apoptotic effects, respectively. Strategies aiming to stimulate p38 and inhibit JNK may have benefit for TRAIL-based therapies in NSCLC.
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[512]
TÍTULO / TITLE: - In silico prediction of spleen tyrosine kinase inhibitors using machine learning approaches and an optimized molecular descriptor subset generated by recursive feature elimination method.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Comput Biol Med. 2013 May 1;43(4):395-404. doi: 10.1016/j.compbiomed.2013.01.015. Epub 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1016/j.compbiomed.2013.01.015
AUTORES / AUTHORS: - Li BK; Cong Y; Yang XG; Xue Y; Chen YZ
INSTITUCIÓN / INSTITUTION: - College of Chemistry, Key Laboratory of Green Chemistry and Technology in Ministry of Education, Sichuan University, Chengdu 610064, PR China.
RESUMEN / SUMMARY: - We tested four machine learning methods, support vector machine (SVM), k-nearest neighbor, back-propagation neural network and C4.5 decision tree for their capability in predicting spleen tyrosine kinase (Syk) inhibitors by using 2592 compounds which are more diverse than those in other studies. The recursive feature elimination method was used for improving prediction performance and selecting molecular descriptors responsible for distinguishing Syk inhibitors and non-inhibitors. Among four machine learning models, SVM produces the best performance at 99.18% for inhibitors and 98.82% for non-inhibitors, respectively, indicating that the SVM is potentially useful for facilitating the discovery of Syk inhibitors.
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[513]
TÍTULO / TITLE: - Regulation of microtubule-associated protein tau (MAPT) by miR-34c-5p determines the chemosensitivity of gastric cancer to paclitaxel.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2108-y
AUTORES / AUTHORS: - Wu H; Huang M; Lu M; Zhu W; Shu Y; Cao P; Liu P
INSTITUCIÓN / INSTITUTION: - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: Human miR-34c has been reported to be associated with various human malignancies; however, it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer. The aim of this study was to investigate the role of miR-34c in gastric cancer. MATERIALS AND METHODS: The adenosine triphosphate-based tumor chemosensitivity assay was used to measure drug sensitivity in gastric cancer samples. The expression levels of miRNA were determined by reverse transcriptase polymerase chain reaction (PCR) and those of protein were by Western blot analysis. Luciferase activity assay was used to verify the target genes of miRNAs. MTT assay was used to test the drug-resistant phenotype changes in cancer cells via overregulation of miRNAs. The methylation status of neighboring CpG islands of miR-34c-5p was analyzed by Bisulfite Sequencing PCR and methylation-specific PCR. RESULTS: Quantitative real-time polymerase chain reaction demonstrated that expression of miR-34c-5p was downregulated in paclitaxel-resistant gastric cancer samples (p < 0.01). Cells derived from gastric cancer tissues with low miR-34c-5p expression and high microtubule-associated protein tau (MAPT) protein expression tended to have increased chemoresistance to paclitaxel in vitro. Luciferase activity assay confirmed that the 3’-UTR of MAPT mRNA contains a functional miR-34c-5p binding site. Overexpression of miR-34c-5p significantly downregulated MAPT protein expression and increased the chemosensitivity of paclitaxel-resistant gastric cancer cells. Further investigation demonstrated that differential methylation of CpG islands neighboring the miR-34c promoter regulated the expression of miR-34c-5p in gastric cancer cell lines. CONCLUSIONS: DNA methylation, dysregulation of miR-34c-5p, and MAPT expression are critical factors in the chemoresistance of gastric cancer to paclitaxel.
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[514]
TÍTULO / TITLE: - Role of altholactone in inducing type II apoptosis signalling pathway and expression of cancer-related genes in cervical carcinoma HeLa cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biol Int. 2013 Feb 1. doi: 10.1002/cbin.10059.
●● Enlace al texto completo (gratuito o de pago) 1002/cbin.10059
AUTORES / AUTHORS: - Uthaisang-Tanechpongtamb W; Sriyabhaya P; Wilairat P
INSTITUCIÓN / INSTITUTION: - Faculty of Medicine, Department of Biochemistry, Srinakharinwirot University, Bangkok, 10110, Thailand.
RESUMEN / SUMMARY: - Goniothalamus species (Annonaceae) is a shrub that grows in the rainforest of tropical Asia. Several compounds have been isolated and exhibit the potential use for cancer treatment. In this work, altholactone isolated from Goniothalamus macrophyllus was investigated for its cytotoxicity, apoptosis signalling and the expression of cancer-related genes in the cervical carcinoma HeLa cells. Cytotoxicity was evaluated by MTT assay. Apoptotic characteristics were evaluated by morphological studies. Caspase-3 activity was detected using a fluorogenic substrate. Cytochrome c release from mitochondria and protein Bid were determined by Western blotting and cancer-related genes expression by RT-PCR. The results demonstrated that altholactone was cytotoxic to HeLa (IC50 = 9.6 mug/mL), and apoptotic cell death was manifested by appearance of chromatin condensation and caspase-3 activation, which was inhibited by specific inhibitors of both caspase-8 and -9. Release into the cytosol of cytochrome and cleavage of Bid occurred. Altholactone also caused a decrease in bcl-2 and an increase in p53 expression. These unique properties of altholactone suggest a potential for cancer chemotherapy.
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[515]
TÍTULO / TITLE: - Comparison of 7-day azacitidine and 5-day decitabine for treating myelodysplastic syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hematol. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00277-013-1702-8
AUTORES / AUTHORS: - Lee JH; Choi Y; Kim SD; Kim DY; Lee JH; Lee KH; Lee SM; Cho SH; Lee WS; Joo YD
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul, 138-736, South Korea, jhlee3@amc.seoul.kr.
RESUMEN / SUMMARY: - Two DNA methyltransferase inhibitors, azacitidine and decitabine, are currently approved for the treatment of myelodysplastic syndrome (MDS). Choosing between these drugs is an important practical issue. In this retrospective study, patients receiving AZA-7d (azacitidine 75 mg/m(2) subcutaneously x 7 days, n = 75) or DEC-5d (decitabine 20 mg/m(2) intravenously x 5 days, n = 74) were compared. The rates of hematologic response (complete response [CR]/partial response [PR]/marrow CR) were 12.0 % (AZA-7d) vs. 29.7 % (DEC-5d) (P = 0.008), and the overall response rates (CR/PR/marrow CR/hematologic improvement) were 52.0 % (AZA-7d) vs. 63.5 % (DEC-5d) (P = 0.155). Grade 3 or higher neutropenia occurred more frequently with DEC-5d (79.6 %) than with AZA-7d (72.2 %) (P = 0.040). Overall survival probabilities at 2 years were 42.1 % (AZA-7d) vs. 42.2 % (DEC-5d) (P = 0.944). Subgroup analysis revealed that AZA-7d associated with higher survival rates than DEC-5d in patients whose MDS duration exceeded 1 year or who had poor performance status. In conclusion, both AZA-7d and DEC-5d regimens were effective in treating patients with MDS. However, the two regimens differed in terms of clinical responses and toxicities. One hypomethylating regimen may be superior to the other regimen in particular subgroups.
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[516]
TÍTULO / TITLE: - Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Gynecol Cancer. 2013 Mar 23.
●● Enlace al texto completo (gratuito o de pago) 1097/IGC.0b013e31828c9581
AUTORES / AUTHORS: - Li B; Takeda T; Tsuiji K; Wong TF; Tadakawa M; Kondo A; Nagase S; Yaegashi N
INSTITUCIÓN / INSTITUTION: - *Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kinki University School of Medicine, Osaka; and daggerDepartment of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
RESUMEN / SUMMARY: - OBJECTIVE: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells. METHODS: Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP). RESULTS: Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase ½ activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase ½ pathway and curcumin-induced autophagy. CONCLUSIONS: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.
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[517]
TÍTULO / TITLE: - Overcoming Paclitaxel Resistance in Lung Cancer Cells Via Dual Inhibition of Stathmin and Bcl-2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1323
AUTORES / AUTHORS: - Han ZX; Wang HM; Jiang G; Du XP; Gao XY; Pei DS
INSTITUCIÓN / INSTITUTION: - 1 The First Clinical Medical College, Nanjing Medical University , Nanjing, China .
RESUMEN / SUMMARY: - Abstract Lung cancer is the leading cause of death from malignancy in people and over 85% of these patients eventually die from disseminated disease. Paclitaxel (TAX) is widely used as an antimicrotubule agent for the treatment of lung cancer. Unfortunately, the resistance to this antimicrotubule agent occurs frequently. Stathmin (STMN1) is a ubiquitous microtubule destabilizing protein linked to cancer and cell health and its expression level often correlates with cancer stage progression and prognosis for survival. Overexpression of the antiapoptotic protein Bcl-2 has been shown to prolong drug-induced growth arrest, potentially inducing resistance. In this study, we used a short hairpin RNA (shRNA) approach to evaluate the effect of STMN1 and Bcl-2 downregulation in the sensitivity to TAX in lung cancer cells. We achieved significant downregulation of STMN1 and Bcl-2 mRNA and protein expression by a combination of double shRNA treatment strategy. Our experimental data showed that inhibition of STMN1 and Bcl-2 expression with RNA interference can sensitize lung cancer cells to TAX. These findings suggest a novel approach to improve the efficacy of certain antimicrotubule agents against lung cancer by regulating the function of STMN1 and Bcl-2.
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[518]
TÍTULO / TITLE: - The prognostic value of diagnosing concurrent multiple myeloma in immunoglobulin light chain amyloidosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Haematol. 2013 Feb 23. doi: 10.1111/bjh.12269.
●● Enlace al texto completo (gratuito o de pago) 1111/bjh.12269
AUTORES / AUTHORS: - Dinner S; Witteles W; Witteles R; Lam A; Arai S; Lafayette R; George TI; Schrier SL; Liedtke M
INSTITUCIÓN / INSTITUTION: - Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
RESUMEN / SUMMARY: - The prevalence and prognostic value of a concomitant diagnosis of symptomatic or asymptomatic multiple myeloma (MM), as defined by the current International Myeloma Working Group (IMWG) criteria, in patients with immunoglobulin light chain amyloidosis (AL), are unknown. We studied 46 consecutive patients with AL who underwent quantification of serum M-protein and clonal bone marrow plasma cells, as well as a comprehensive evaluation for end organ damage by MM. Using standard morphology and CD138 immunohistochemical staining, 57% and 80% of patients were found to have concomitant MM, respectively. Nine patients exhibited end organ damage consistent with a diagnosis of symptomatic MM. While overall survival was similar between AL patients with or without concurrent myeloma (1-year overall survival 68% vs. 87%; P = 0.27), a diagnosis of symptomatic myeloma was associated with inferior outcome (1-year overall survival 39% vs. 81%; P = 0.005). Quantification of bone marrow plasma cells by both standard morphology and CD138 immunohistochemistry identified a much higher prevalence of concurrent MM in patients with AL than previously reported. Evaluation of bone marrow plasma cell infiltration and presence of myeloma associated end organ damage could be clinically useful for prognostication of patients with AL.
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[519]
TÍTULO / TITLE: - Up-regulation of miR-182 expression in colorectal cancer tissues and its prognostic value.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Colorectal Dis. 2013 Mar 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s00384-013-1674-0
AUTORES / AUTHORS: - Liu H; Du L; Wen Z; Yang Y; Li J; Wang L; Zhang X; Liu Y; Dong Z; Li W; Zheng G; Wang C
INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan, Shandong, 250012, People’s Republic of China.
RESUMEN / SUMMARY: - PURPOSE: Accumulating evidences indicate that dysregulated microRNAs (miRNA) are involved in cancer tumorigenesis and progression. In the present study, we evaluated the expression of miR-182 in colorectal cancer and adjacent noncancerous tissues and explored its associations with clinicopathological characteristics and prognosis. METHODS: Quantitative real-time PCR was used to analyze the expression of miR-182 in 148 pairs of colorectal cancer and adjacent noncancerous tissues. The relationship between miR-182 expression and clinicopathological characteristics in colorectal cancer tissues was estimated using Mann-Whitney U test or Kruskal-Wallis test, as appropriate. We calculated the survival curves and prognostic values of each variable by the Kaplan-Meier method and Cox proportional hazards regression analysis, respectively. RESULTS: The expression of miR-182 was found up-regulated in colorectal cancer tissues compared with adjacent noncancerous tissues (p < 0.001), and its up-regulation was significantly correlated with large tumor size (p = 0.016), positive regional lymph node metastasis (p = 0.008), and advanced tumor-node-metastasis stage (p = 0.020). Furthermore, Kaplan-Meier analysis demonstrated that high miR-182 expression predicted poor survival (p = 0.001), and Cox proportional hazards risk analysis indicated that miR-182 was an independent prognostic factor for colorectal cancer. CONCLUSIONS: MiR-182 was up-regulated in colorectal cancer tissues and correlated with adverse clinical characteristics and poor prognosis, indicating that miR-182 might be involved in colorectal cancer progression and could be used as a potential prognostic biomarker and therapeutic target in the management of colorectal cancer.
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[520]
TÍTULO / TITLE: - Cotransfection of Survivin and CD44v3 Short Hairpin RNAs Affects Proliferation, Apoptosis, and Invasiveness of Colorectal Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Dis Sci. 2013 Feb 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s10620-012-2539-z
AUTORES / AUTHORS: - Liu Z; Guo Y; Li J; Xu J; Liu B
INSTITUCIÓN / INSTITUTION: - The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, 150086, China, zhaoyy@sj-hospital.org.
RESUMEN / SUMMARY: - INTRODUCTION: Colorectal cancer is one of the common malignant tumors in humans, and the incidence rate is gradually increasing year by year. Survivin and CD44v3 are ideal targets for gene therapy due to their overexpression in colorectal cells. Studies show that downregulation of survivin could promote apoptosis and depress proliferation, and reduction of CD44v3 expression could inhibit tumor invasive capacity. It is difficult to achieve satisfactory curative effect. OBJECTIVE: In this study, we use survivin and CD44v3 short hairpin RNAs (shRNA) combined transfection into colorectal cancer cell line SW480 to investigate its effects on the cell apoptosis, proliferation and invasiveness. METHODS: ShRNA plasmids targeting survivin and CD44v3 were singly or co-transfected into SW480 cells. RESULTS: The co-transfection group exhibited the most significant inhibitory effect on cell growth (P < 0.05) and the highest apoptosis rate (P < 0.05). In addition, the invasive capacity in the co-transfected group was the least. The tumor inhibition rate of the cotransfected group in xenograft tumor mice was significantly higher than other groups (P < 0.05). Moreover, the microvessel density of the co-transfected group was significantly decreased compared with other groups (P < 0.05). CONCLUSION: These results suggest combined transfection of survivin shRNA and CD44v3 shRNA may produce a synergistic effect on gene therapy in colorectal cancer.
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[521]
TÍTULO / TITLE: - AMXT-1501, a novel polyamine transport inhibitor, synergizes with DFMO in inhibiting neuroblastoma cell proliferation by targeting both ornithine decarboxylase and polyamine transport.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Mar 2. doi: 10.1002/ijc.28139.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28139
AUTORES / AUTHORS: - Samal K; Zhao P; Kendzicky A; Yco LP; McClung H; Gerner E; Burns M; Bachmann AS; Sholler G
INSTITUCIÓN / INSTITUTION: - Van Andel Research Institute, Grand Rapids, MI.
RESUMEN / SUMMARY: - Neuroblastoma (NB) is associated with MYCN oncogene amplification occurring in approximately 30% of NBs and is associated with poor prognosis. MYCN is linked to a number of genes including ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. ODC expression is elevated in many forms of cancer including NB. Alpha-difluoromethylornithine (DFMO), an ODC inhibitor, is currently being used in a Phase I clinical trial for treatment of NB. However, cancer cells treated with DFMO may overcome their polyamine depletion by the uptake of polyamines from extracellular sources. A novel polyamine transport inhibitor, AMXT-1501, has not yet been tested in NB. We propose that inhibiting ODC with DFMO, coupled with polyamine transport inhibition by AMXT-1501 will result in enhanced NB growth inhibition. Single and combination drug treatments were conducted on three NB cell lines. DFMO IC50 values ranged from 20.76 to 33.3 mM, and AMXT-1501 IC50 values ranged from 14.13 to 17.72 microM in NB. The combination treatment resulted in hypophosphorylation of retinoblastoma protein (Rb), suggesting growth inhibition via G1 cell cycle arrest. Increased expression of cleaved PARP and cleaved caspase 3 in combination-treated cells starting at 48 hours suggested apoptosis. The combination treatment depleted intracellular polyamine pools and decreased intracellular ATP, further verifying growth inhibition. Given the current lack of effective therapies for relapsed/refractory NB patients and the preclinical effectiveness of DFMO with AMXT-1501, this combination treatment provides promising preclinical results. DFMO and AMXT-1501 may be a potential new therapy for children with NB. © 2013 Wiley Periodicals, Inc.
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[522]
TÍTULO / TITLE: - Increased serum insulin-like growth factor-1 levels are associated with prolonged response to dasatinib-based regimens in metastatic prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prostate. 2013 Jan 31. doi: 10.1002/pros.22645.
●● Enlace al texto completo (gratuito o de pago) 1002/pros.22645
AUTORES / AUTHORS: - Dayyani F; Varkaris A; Araujo JC; Song JH; Chatterji T; Trudel GC; Logothetis CJ; Gallick GE
INSTITUCIÓN / INSTITUTION: - UT MD Anderson Cancer Center, Genitourinary Medical Oncology, Houston, Texas.
RESUMEN / SUMMARY: - BACKGROUND: Dasatinib, an inhibitor of Src-family kinases, combined with docetaxel in men with castrate-resistant prostate cancer (CRPC), affects bone turnover markers in a phase I/II clinical trial in metastatic CRPC. Only a subset of men benefit from this therapy, and predictive markers are lacking. We hypothesized a role for insulin-like growth factor-1 (IGF-1) as a predictive marker, since IGF-1 is important in both prostate cancer progression and bone development. Hence, we determined the association of IGF-1 expression to treatment response, and whether this expression resulted from tumor cells, the microenvironment, or their interactions. METHODS: We measured serum IGF-1 levels in men with CRPC treated with dasatinib plus docetaxel. To investigate the source of IGF-1, we utilized two different mouse models harboring human prostate cancer cells, and used species-specific IGF-1 ELISA kits (mouse vs. human). RESULTS: In men with CRPC, an increase in IGF-1 levels after one cycle of treatment with dasatinib and docetaxel is associated with a higher response rate and longer duration of treatment. Xenograft experiments with subcutaneous and intratibial injection of prostate cancer cells suggest that direct interaction of prostate cancer cells with bone microenvironment is necessary for IGF-1 induction, is entirely host-derived, and occurs only in mice that respond to dasatinib-based therapy. CONCLUSION: Our results support a role for serum IGF-1 as a potential biomarker for benefit from dasatinib-based combination treatments in CRPC. Prostate © 2013 Wiley Periodicals, Inc.
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[523]
TÍTULO / TITLE: - Long interspersed nuclear element ORF-1 protein promotes proliferation and resistance to chemotherapy in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Feb 21;19(7):1068-78. doi: 10.3748/wjg.v19.i7.1068.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i7.1068
AUTORES / AUTHORS: - Feng F; Lu YY; Zhang F; Gao XD; Zhang CF; Meredith A; Xu ZX; Yang YT; Chang XJ; Wang H; Qu JH; Zeng Z; Yang JL; Wang CP; Zhu YF; Cui JJ; Yang YP
INSTITUCIÓN / INSTITUTION: - Fan Feng, Yin-Ying Lu, Xu-Dong Gao, Zhong-Xian Xu, Xiu-Juan Chang, Hong Wang, Jian-Hui Qu, Zhen Zeng, Chun-Ping Wang, Yong-Ping Yang, Clinical Research Center of Hepatocarcinoma, 302 Military Hospital, Beijing 100039, China.
RESUMEN / SUMMARY: - AIM: To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1 (LINE-1), ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma (HCC) cells. METHODS: MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells. Cell proliferation inhibition and the IC50 were calculated by the Origin 8.0 software. Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes, including p53, p27, p15, Bcl-2, mdr, and p-gp. To corroborate the proliferation and anchor-independent growth results, the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF-1p on the apoptosis regulation. RESULTS: LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs (cisplatin and epirubicin) in HepG2 cells. The IC50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L. Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin. The IC50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L. Interestingly, down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel. The IC50 decreased from 35.90 nmol/L to 7.36 nmol/L. However, overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells. Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression. As a protein arrested in the nucleus, LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors. Indeed, LINE-1 ORF-1p promoted HepG2 cell proliferation, anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15, p21, p53, and Bcl-2 genes. CONCLUSION: LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs. By establishing novel roles and defining the mechanisms of LINE-1 ORF-1p in HCC chemotherapeutic drug resistance and cell proliferation regulation, this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.
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[524]
TÍTULO / TITLE: - Prognostic significance of BRCA1-associated protein 1 in colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):541. doi: 10.1007/s12032-013-0541-8. Epub 2013 Mar 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0541-8
AUTORES / AUTHORS: - Tang J; Xi S; Wang G; Wang B; Yan S; Wu Y; Sang Y; Wu W; Zhang R; Kang T
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, No 651, Dongfeng Road East, Guangzhou 510060, China.
RESUMEN / SUMMARY: - Mutations of BRCA1-associated protein 1 (BAP1), a nuclear-localized deubiquitinating enzyme, had been documented in multiple human cancers. However, its role and clinical relevance in colorectal cancer is unknown. The purpose of this study was to reveal the prognostic significance of BAP1 in colorectal cancer. We performed quantitative PCR and Western blotting analyses to examine BAP1 expression in 8 cases of CRC tissues and matched adjacent non-cancerous tissues. And immunohistochemistry was used to evaluate BAP1 expression in archived 252 paraffin-embedded CRC specimens. We found that the mRNA and protein levels of BAP1 were down-regulated in 6 out of 8 cases of CRC tissues compared with their adjacent non-cancerous tissues. The BAP1 expression was closely correlated with age (p = 0.037), clinical stage (p = 0.001), T classification (p < 0.001), N classification (p < 0.001), and pathologic differentiation (p = 0.008) and histological type (p = 0.047) in CRC. The CRC patients with lower BAP1 expression survived shorter than those with higher BAP1 expression. Importantly, multivariate analysis demonstrated that BAP1 expression was an independent prognostic factor for CRC (p = 0.037). Collectively, we provide the first evidence that reduced BAP1 expression is associated with poor prognosis of CRC and BAP1 may serve as a novel prognostic biomarker for CRC.
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[525]
TÍTULO / TITLE: - Prognostic Value of p53 Protein Overexpression in Upper Tract Urothelial Carcinomas in Taiwan.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1091-8.
AUTORES / AUTHORS: - Lee YC; Wu WJ; Li WM; Lin HH; Huang CN; Chai CY; Chang LL; Lin HL; Ke HL
INSTITUCIÓN / INSTITUTION: - Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, TzYou 1st Road, Kaohsiung City 807, Taiwan, R.O.C. hunglungke@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: p53 plays an important role in maintaining genomic stability and regulating the cell cycle. However, the accumulation of p53 protein has been reported to be involved in the carcinogenesis, progression, and metastasis of many types of human cancer. This study evaluates the clinical significance of p53 expression in upper tract urothelial carcinoma. PATIENTS AND METHODS: One-hundred and twelve cases of upper tract urothelial carcinoma were included in this study. p53 expression was evaluated by immunohistochemistry and the association of p53 expression with clinicopathological variables was analyzed. RESULTS: p53 expression was significantly correlated with patients who were undergoing hemodialysis (p=0.005) and had increased serum creatinine levels (p=0.001). High p53 expression was associated with poor progression-free (p=0.025) and cancer-specific survival (p=0.021), Cox regression analysis also revealed that p53 was an independent predictor of poor progression-free (hazard ratio=3.74, p=0.025) and cancer-specific (hazard ratio=5.87, p=0.030) survival. CONCLUSION: Our findings indicate that p53 expression is a potential biomarker for predicting patient survival. Further study is necessary to investigate the role of p53 in the carcinogenesis of upper tract urothelial carcinoma.
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[526]
TÍTULO / TITLE: - Cationic lipid:DNA complexes allow bleomycin uptake by melanoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Pharmacother. 2013 Feb 6. pii: S0753-3322(13)00005-X. doi: 10.1016/j.biopha.2013.01.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biopha.2013.01.002
AUTORES / AUTHORS: - Gil-Cardeza ML; Rossi UA; Villaverde MS; Glikin GC; Finocchiaro LM
INSTITUCIÓN / INSTITUTION: - Unidad de Transferencia Genetica, Instituto de Oncologia Angel H. Roffo”, Universidad de Buenos Aires, Avenida San Martin 5481, 1417 Buenos Aires, Argentina.
RESUMEN / SUMMARY: - Bleomycin is a chemotherapeutic agent barely diffusible through the plasmatic membrane. We evaluated DNA/cationic lipids complexes (lipoplexes) as mediators of its uptake in four spontaneous canine melanoma derived cell lines (Ak, Bk, Br and Rkb). Cell survival after lipofection plus or minus bleomycin was determined by the acid phosphatase method and the cellular uptake of lipoplexes, carrying the E. coli beta-galactosidase gene, was evidenced by SYBR Green I staining. The four cell lines resulted sensitive to the bleomycin/lipoplexes system in both spatial configurations. Survival rates values were lower than 20% in monolayers of the four tested lines and lower than 30% in three lines (Ak, Bk and Rkb) when grown as spheroids. The sensitization to bleomycin depended on lipoplexes in Ak and Rkb while Bk (in both spatial configurations) and Br (as monolayers) were sensitive to bleomycin alone. Although some degree of sensitivity to bleomycin was induced by cationic lipids alone in Ak and Rkb monolayers, the maximal bleomycin effects appeared in the presence of lipoplexes. The sensitization was independent of transcriptional activity. The co-administration of lipoplexes diminished bleomycin IC50: 10-fold in Ak and Rkb monolayers; and sensitized the Ak and Rkb resistant spheroids. The bleomycin cytotoxic effects depended on lipoplexes concentration and diminished when cells were incubated at 8 degrees C. Our results suggest that lipoplexes sensitize cells to bleomycin, increasing its uptake by an active transport mechanism, such as endocytosis. The bleomycin/lipoplexes system appears as a promising combination of chemotherapy and non-viral cancer gene therapy.
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[527]
TÍTULO / TITLE: - Histone deacetylase inhibitors in the treatment for multiple myeloma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Hematol. 2013 Mar;97(3):324-32. doi: 10.1007/s12185-013-1290-3. Epub 2013 Mar 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s12185-013-1290-3
AUTORES / AUTHORS: - Hideshima T; Anderson KC
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA, teru_hideshima@dfci.harvard.edu.
RESUMEN / SUMMARY: - Histone lysine acetylation is regulated by both histone deacetylases (HDACs) and histone acetyl transferases. Inhibition of deacetylases induces hyperacetylate of target proteins and has a crucial role in the epigenetic regulation of gene expression mediating cell survival and proliferation. Therefore, HDAC inhibitors have emerged as novel therapeutic agents for cancers, including multiple myeloma (MM). Recent studies revealed that HDAC inhibitors trigger hyperacetylation of not only histones, but also non-histone proteins regulating cell growth and survival, revealing the complexity of mechanism of action of HDAC inhibitors. Many HDAC inhibitors have already shown significant anti-MM activities in preclinical studies and are under evaluation in clinical trials.
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[528]
TÍTULO / TITLE: - Transient over-expression of TGFBR3 induces apoptosis in human nasopharyngeal carcinoma CNE-2Z cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biosci Rep. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1042/BSR20120047
AUTORES / AUTHORS: - Zheng F; He K; Li X; Zhao D; Sun F; Zhang Y; Nie D; Li X; Chu W; Sun Y; Lu Y
RESUMEN / SUMMARY: - Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China without defined etiology. Recent studies have shown that TGFBR3, a transforming growth factor type III receptor, exhibits anti-cancer activities. This study was to investigate the effects of TGFBR3 on NPC growth and the mechanisms for its actions. Effects of TGFBR3 over-expression on cell viability and apoptosis were measured by MTT, AO/EB staining and electron microscopy in human nasopharyngeal carcinoma CNE-2Z cells. The expression of apoptosis-related proteins, p-Bad, Bad, Xiap, AIF, Bax and Bcl-2, was determined by Western blot or immunofluorescence analysis. Caspase-3 activity was measured by caspase-3 activity kit and intracellular Ca2+ concentration ([Ca2+]i) was detected by confocal microscopy. Transfection of TGFBR3 containing plasmid DNA at concentrations of 0.5 and 1 microg/ml reduced viability and induced apoptosis in CNE-2Z in concentration- and time-dependent manners. Forced expression of TGFBR3 upregulated pro-apoptotic Bad and Bax protein, and down-regulated anti-apoptotic p-Bad, Bcl-2 and Xiap protein. Furthermore, transient overexpression of TGFBR3 also enhanced caspase-3 activity, increased [Ca2+]i and facilitated AIF redistribution from the mitochondria to the nucleus in CNE-2Z cells, which is independent of the caspase-3 pathway. These events were associated with TGFBR3-regulated multiple targets involved in CNE-2Z proliferation. Therefore, transient overexpression of TGFBR3 may be a novel strategy for NPC prevention and therapy.
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[529]
TÍTULO / TITLE: - Sorafenib enhances the chemotherapeutic efficacy of S-1 against hepatocellular carcinoma through downregulation of transcription factor E2F-1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2120-2
AUTORES / AUTHORS: - Zhai JM; Yin XY; Lai YR; Hou X; Cai JP; Hao XY; Liang LJ; Zhang LJ
INSTITUCIÓN / INSTITUTION: - Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
RESUMEN / SUMMARY: - PURPOSE: Sorafenib and S-1 (one mixed formulation containing 5-FU prodrug and dihydropyrimidine dehydrogenase inhibitor) were two effective agents against hepatocellular carcinoma (HCC), but whether they had synergistic effects remained unclear. The present study aimed at evaluating their synergistic effects against HCC and its mechanisms. METHODS: Inhibitory effects of sorafenib, 5-FU and their combination on HCC cells PLC/PRF/5 and SK-HEP-1 were evaluated. Expressions of transcription factor E2F-1 and its downstream thymidylate synthetase (TS) in the treated cells were determined using real-time PCR and Western blot. In vivo anti-tumoral efficacy of S-1 plus sorafenib on HCC was evaluated in NOD/SCID mice. E2F-1 and TS expressions in tumors were determined by immunohistochemical staining. RESULTS: Sorafenib inhibited growth of HCC cells in dose-dependent manner, with IC50 of 5.4 +/- 0.3 mumol/L for PLC/PRF/5 and 5.3 +/- 0.5 mumol/L for SK-HEP-1. Sorafenib (1 mumol/L) enhanced inhibitory efficacy of 5-FU on HCC cells in vitro, dropping IC50 of 5-FU from 167.7 +/- 12.1 to 105.4 +/- 8.4 mumol/L for PLC/PRF/5 and 115 +/- 10.2 to 82 +/- 7.4 mumol/L for SK-HEP-1 (both p < 0.01). Sorafenib downregulated E2F-1 and TS expressions on HCC cells, and its combination with 5-FU yielded a synergistic downregulation of TS expression on HCC cells. In NOD/SCID mice with subcutaneously inoculated HCC, sorafenib combined with S-1 yielded greater inhibition on tumor growth and remarkable TS suppression when compared with sorafenib or S-1 alone (all p < 0.05). CONCLUSIONS: Sorafenib enhanced therapeutic efficacy of 5-FU/S-1 against HCC through downregulation of E2F-1 and TS expressions. Sorafenib combined with S-1 might represent as valuable therapeutic regimen against HCC.
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[530]
TÍTULO / TITLE: - Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 19. doi: 10.1002/ijc.28114.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28114
AUTORES / AUTHORS: - Ohashi T; Akazawa T; Aoki M; Kuze B; Mizuta K; Ito Y; Inoue N
INSTITUCIÓN / INSTITUTION: - Department of Molecular Genetics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu, Japan.
RESUMEN / SUMMARY: - The activation of oncogenic signaling pathways induces the reprogramming of glucose metabolism in tumor cells and increases lactic acid secretion into the tumor microenvironment. This is a well-known characteristic of tumor cells, termed the Warburg effect, and is a candidate target for antitumor therapy. Previous reports show that lactic acid secreted by tumor cells is a proinflammatory mediator that activates the IL-23/IL-17 pathway, thereby inducing inflammation, angiogenesis and tissue remodeling. Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. Accordingly, we hypothesized that counteraction of the immune effects by lactic acid might suppress tumor development. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. Furthermore, lactic acid-pretreated macrophages inhibited CD8+ T-cell proliferation, but CD8+ T-cell proliferation was restored when macrophages were pretreated with lactic acid and DCA. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-gamma-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen. Although DCA treatment alone did not suppress tumor growth, it increased antitumor immunotherapeutic activity of Poly(IC) in both CD8+ T cell- and NK cell-sensitive tumor models. Therefore, DCA acts not only on tumor cells to suppress glycolysis but also on immune cells to improve the immune status modulated by lactic acid and to increase the effectiveness of antitumor immunotherapy.
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[531]
TÍTULO / TITLE: - Phase I study of ON 01910.Na (Rigosertib), a multikinase PI3K inhibitor in relapsed/refractory B-cell malignancies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leukemia. 2013 Mar 14. doi: 10.1038/leu.2013.79.
●● Enlace al texto completo (gratuito o de pago) 1038/leu.2013.79
AUTORES / AUTHORS: - Roschewski M; Farooqui M; Aue G; Wilhelm F; Wiestner A
INSTITUCIÓN / INSTITUTION: - Metabolism Branch, National Cancer Institute, NIH, Bethesda, MD.
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[532]
TÍTULO / TITLE: - Long Pentraxin-3 As An Epithelial-Stromal Fibroblast Growth Factor-Targeting Inhibitor In Prostate Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pathol. 2013 Feb 19. doi: 10.1002/path.4181.
●● Enlace al texto completo (gratuito o de pago) 1002/path.4181
AUTORES / AUTHORS: - Ronca R; Alessi P; Coltrini D; Salle ED; Giacomini A; Leali D; Corsini M; Belleri M; Tobia C; Garlanda C; Bonomi E; Tardanico R; Vermi W; Presta M
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, 25123, Brescia, Italy.
RESUMEN / SUMMARY: - Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumor growth. Here dihydrotestosterone (DHT) upregulates FGF2 and FGF8b production in murine TRAMP-C2 prostate cancer cells, activating a FGF-dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin-3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N-terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3-derived pentapeptide Ac-ARPCA-NH(2) abolishes the mitogenic response of murine TRAMP-C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT-activated TRAMP-C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP-C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP-C2 cells show a dramatic decrease of their angiogenic and tumorigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP-C2 cells overexpress only the FGF-binding N-terminal PTX3 domain. In keeping with the anti-tumor activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high-grade prostatic intraepithelial neoplasia and in invasive tumor areas. These results identify PTX3 as a potent FGF antagonist endowed with antiangiogenic and antineoplastic activity in prostate cancer.
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[533]
TÍTULO / TITLE: - Cisplatin in combination with zoledronic acid: A synergistic effect in triple-negative breast cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1263-70. doi: 10.3892/ijo.2013.1809. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1809
AUTORES / AUTHORS: - Ibrahim T; Liverani C; Mercatali L; Sacanna E; Zanoni M; Fabbri F; Zoli W; Amadori D
INSTITUCIÓN / INSTITUTION: - Osteoncology Center, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), I-47014 Meldola (FC), Italy.
RESUMEN / SUMMARY: - Zoledronic acid (ZA) is the most widely used bisphos-phonate to treat cancer-induced bone disease. There is evidence that bisphosphonates have direct antitumor activity and that their combination with anticancer agents can significantly enhance the effect of treatment. We evaluated whether the combination of ZA with different platinum compounds exerts a synergistic effect in breast cancer cell lines and we investigated the mechanisms of action involved. This study was performed on four breast cancer cell lines, MCF-7, SKBR3, MDA-MB-231 and BRC-230, and confirmed on a primary culture obtained from a breast cancer bone metastasis specimen. ZA (50 microM) was administered for 72 h alone or in combination with cisplatin (Cis) or carboplatin. Drug-induced growth inhibition was detected by sulforhodamine B assay, apoptosis and cell cycle regulation were detected by flow cytometry, and protein expression was evaluated by western blot analysis. MCF-7 and SKBR3 showed very low sensitivity to the three drugs tested. The ZA + Cis combination exerted a high antitumor activity in the two triple-negative lines MDA-MB-231 and BRC-230. An important synergistic effect was obtained in MDA-MB-231 and an additive effect was observed in BRC-230. The p21, pMAPK and m-TOR pathways were regulated by this combined treatment, particularly at lower Cis doses. Carboplatin did not show antitumor activity either alone or in combination with ZA. In conclusion, the potential novel treatment schedule identified for triple-negative breast cancer could prove beneficial in view of the limited therapeutic options available for patients and also since the synergism with ZA would enable lower Cis doses to be used, thus reducing toxicity. Although further research in a clinical setting is warranted, our results on cell lines has been confirmed on a human primary bone metastasis culture.
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[534]
TÍTULO / TITLE: - Prognostic significance of combinations of RNA-dependent protein kinase and EphA2 biomarkers for NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):301-8. doi: 10.1097/JTO.0b013e318282def7.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318282def7
AUTORES / AUTHORS: - Guo C; Shao R; Correa AM; Behrens C; Johnson FM; Raso MG; Prudkin L; Solis LM; Nunez MI; Fang B; Roth JA; Wistuba II; Swisher SG; Lin T; Pataer A
INSTITUCIÓN / INSTITUTION: - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
RESUMEN / SUMMARY: - INTRODUCTION: RNA-dependent protein kinase (PKR) is an independent prognostic variable in patients with non-small-cell lung cancer (NSCLC). In the current study, we investigated the correlation between PKR and 25 other biomarkers for NSCLC, identified the markers that could further improve the prognostic significance of PKR and elucidated the mechanisms of interaction between these markers and PKR. METHODS: Tissue microarray samples obtained from 218 patients with lung cancer were stained with an anti-PKR antibody and antibodies against 25 biomarkers. Immunohistochemical expression was scored and used for Kaplan-Meier survival analysis. The interaction between PKR and EphA2 in NSCLC cell lines was examined. RESULTS: We found that PKR was associated with EphA2 and that the prognostic information regarding NSCLC provided by the combination of PKR and EphA2 (P/E) was significantly more accurate than that provided by either marker alone. The 5-year overall survival rate in patients with PKR/EphA2 (20%) was significantly lower than that of patients with PKR/EphA2 (74%), patients with PKR/EphA2 (55%), and patients with PKR/EphA2 (55%) (p < 0.0001). We also found that the PKR:EphA2 (P/E) ratio was significantly associated with prognosis (p < 0.0001). Univariate and multivariate Cox analyses revealed that this P/E combination or ratio was an independent predictor of overall survival. In addition, induction of PKR expression reduced EphA2 protein expression levels in NSCLC cell lines. CONCLUSIONS: PKR/EphA2 is a significant predictor of prognosis for NSCLC. PKR/EphA2 may be a promising approach to improving screening efficiency and predicting prognosis in patients with NSCLC.
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[535]
TÍTULO / TITLE: - miR-21 Down-Regulation Suppresses Cell Growth, Invasion and Induces Cell Apoptosis by Targeting FASL, TIMP3, and RECK Genes in Esophageal Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Dis Sci. 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s10620-013-2612-2
AUTORES / AUTHORS: - Wang N; Zhang CQ; He JH; Duan XF; Wang YY; Ji X; Zang WQ; Li M; Ma YY; Wang T; Zhao GQ
INSTITUCIÓN / INSTITUTION: - College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China, wnsky@zzu.edu.cn.
RESUMEN / SUMMARY: - BACKGROUND: miR-21 is overexpressed in esophageal squamous cell carcinoma (ESCC) and is thought to be correlated with the development of the cancer. The target gene of miR-21 including FASL, TIMP3 and RECK is revealed by researchers. miR-21 may be involved in the tumorgenesis of ESCC by targeting FASL, TIMP3 and RECK. AIMS: The purpose of this study was to explore the mechanism of miR-21 in the development of ESCC. METHODS: miR-21 expression in ESCC and the matched non-malignant adjacent tissues (NMATs) was examined by qRT-PCR. Cell growth, cell apoptosis and cell invasion ability of EC9706 and EC-1 cells was examined after the cells were transfected with miR-21 inhibitor. The potential target genes of miR-21 including FASL, TIMP3 and RECK were examined by western blot and Luciferase reporter assay. RESULTS: miR-21 expression was increased significantly in ESCC tissues compared with NMAT. miR-21 down-regulation inhibits cell growth, cell invasion and induces cells to apoptosis. FASL, TIMP3 and RECK are direct targets of miR-21. CONCLUSIONS: miR-21 down-regulation inhibits cell growth, invasion and induces cells to apoptosis by targeting FASL, TIMP3 and RECK genes.
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[536]
TÍTULO / TITLE: - Fibrotic Focus in Breast Carcinomas: Relationship with Prognostic Parameters and Biomarkers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2955-0
AUTORES / AUTHORS: - Mujtaba SS; Ni YB; Tsang JY; Chan SK; Yamaguchi R; Tanaka M; Tan PH; Tse GM
INSTITUCIÓN / INSTITUTION: - Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
RESUMEN / SUMMARY: - BACKGROUND: Fibrotic focus (FF) has been observed in breast cancers and is suggested to be an important prognostic marker. However, most of these observations were reported by the same group of investigators with similar sample cohort. The relationship of FF and molecular subtypes as well as its associated prognosis has not been elucidated. METHODS: In this study, 450 cases of breast carcinomas were evaluated for the presence of FF and its association with clinicopathologic parameters and biomarkers. RESULTS: FF was found in 18.7 % of all consecutive cases. FF was associated positively with infiltrative margins (p = 0.03) but negatively with extensive in situ component (p < 0.001) and lymphocytic infiltration (p < 0.001). It was positively associated with estrogen receptor (p = 0.007) but negatively with human epidermal growth factor receptor 2 (HER2; p = 0.001), epidermal growth factor receptor (p = 0.021), Ki-67 (p = 0.001), and c-kit (p = 0.009). Concomitantly, FF was seen more commonly in luminal A cancers (p < 0.001) but less so in luminal B (p = 0.045) and HER2-overexpressing cancers (p = 0.011). Analysis on patient outcome (median 41 months, range 1-69 months) indicated that FF was an independent poor prognostic factor for disease-free survival (hazard ratio = 2.57; 95 % confidence interval = 1.267-5.214, p = 0.009), particularly in the luminal B subtype. CONCLUSIONS: The findings suggested that FF is associated with specific tumor morphology of an infiltrative, stellate pattern (typical invasive ductal carcinoma-not otherwise specified) rather than round, cellular mass with intense lymphocytic infiltrate (basal-like breast cancers). The poor prognostic implication of FF is additional and independent of other adverse prognostic indicators.
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[537]
TÍTULO / TITLE: - CHAG priming regimen containing of cytarabine, aclacinomycin homoharringtonine and G-CSF for relapsed refractory acute myelogenous Leukemia: a modified combination chemotherapeutic combination.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.772295
AUTORES / AUTHORS: - Chen L; Yin Q; Mi R; Wei X
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University , Zhengzhou , China.
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[538]
TÍTULO / TITLE: - A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt076
AUTORES / AUTHORS: - Simons CC; Hughes LA; Smits KM; Khalid-de Bakker CA; de Bruine AP; Carvalho B; Meijer GA; Schouten LJ; van den Brandt PA; Weijenberg MP; van Engeland M
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht.
RESUMEN / SUMMARY: - BackgroundWe studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths.Patients and methodsMolecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%.ResultsMSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P </= 0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03).Conclusion(s)This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.
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[539]
TÍTULO / TITLE: - Knockdown of Phospholipase C-Epsilon by Short-Hairpin RNA-Mediated Gene Silencing Induces Apoptosis in Human Bladder Cancer Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1216
AUTORES / AUTHORS: - Zhang Y; Yan L; Zhao Y; Ou L; Wu X; Luo C
INSTITUCIÓN / INSTITUTION: - 1 Department of Laboratory Medical Diagnostics, Chongqing Medical University , Chongqing, China .
RESUMEN / SUMMARY: - Abstract Transitional cell carcinoma of bladder (TCCB) is a common malignancy worldwide, and outcomes for patients with advanced bladder cancer remain poor. To study the pathogenesis of TCCB, we investigated roles of Phospholipase C (PLC)varepsilon, an effector of Ras and Rap small GTPases. RNA interference was used to knockdown PLCvarepsilon expression in human bladder cancer cell lines (BIU-87 and T24). The expression levels of PLCvarepsilon mRNA and protein were detected by reverse transcriptase-polymerase chain reaction and Western blot, respectively. Flow cytometry (FCM) was used to detect distribution of cell cycle. Cellular apoptosis was reflected by transmission electron microscopy and the expression of bcl-2 and bax. We found that PLCvarepsilon could be efficiently knocked down by shRNA. FCM assay showed that the pGenesil-PLCvarepsilon-transfected cells were arrested at the G0/G1 phase. Silence of PLCvarepsilon might induce apoptosis via modulation of bcl-2 and bax. In conclusion, our results suggest that PLCvarepsilon plays an important role in the pathogenesis of human bladder cancer cells. PLCvarepsilon may be used as a potential target of gene therapy for bladder cancer in future.
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[540]
TÍTULO / TITLE: - Tumor necrosis factor-related apoptosis-inducing ligand as an independent predictor of mortality in hemodialysis patents.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cytokine. 2013 Mar;61(3):912-6. doi: 10.1016/j.cyto.2012.12.030. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cyto.2012.12.030
AUTORES / AUTHORS: - Mori K; Okuno S; Shoji T; Emoto M; Kakutani Y; Yamakawa K; Imanishi Y; Ishimura E; Yamakawa T; Shoji S; Inaba M
INSTITUCIÓN / INSTITUTION: - Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. Electronic address: ktmori@med.osaka-cu.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis in transformed cells. In addition to tumor surveillance, recent findings suggest that TRAIL and its receptor system have a protective role against infection and cardiovascular disease (CVD). Patients undergoing hemodialysis have a high mortality rate with a unique risk factor profile. Considering that the leading causes of death in these patients are infection and CVD, TRAIL represents an attractive candidate for predicting mortality in this population. We therefore investigated whether TRAIL predicted mortality in hemodialysis patients. METHODS: The study was a retrospective observational cohort design of 45-month duration in 149 male hemodialysis patients. The subjects were divided into two groups according to their baseline TRAIL level measured by ELISA (low or high TRAIL group). The main outcome was all-cause mortality. RESULTS: During the follow-up period, 33 patients died, mostly because of CVD (n=11) or infection (n=9). Crude survival analyses showed that a low TRAIL level was a powerful predictor of all-cause (p=0.011) and infectious mortality (p=0.048). The predictive power of TRAIL remained after adjustment for various confounding factors. CONCLUSIONS: The serum TRAIL level may be a novel biomarker for predicting prognosis in hemodialysis patients.
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[541]
TÍTULO / TITLE: - Optimal predictive value of preoperative serum carcinoembryonic antigen for surgical outcomes in stage I non-small cell lung cancer: Differences according to histology and smoking status.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Oncol. 2013 Feb 5. doi: 10.1002/jso.23294.
●● Enlace al texto completo (gratuito o de pago) 1002/jso.23294
AUTORES / AUTHORS: - Kato T; Ishikawa K; Aragaki M; Sato M; Okamoto K; Ishibashi T; Oba K; Kaji M
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Sapporo Minami-Sanjo Hospital, Sapporo, Japan; Department of Cardiovascular and Thoracic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. katotatu7@msn.com.
RESUMEN / SUMMARY: - BACKGROUND: The cutoff value of preoperative serum carcinoembryonic antigen (CEA) levels has not been investigated using appropriate subgroup analyses for non-small cell lung carcinoma (NSCLC). This study was undertaken to determine whether the most predictive preoperative CEA level for risk of recurrence differs according to histological type, and how smoking status influences predictive values in stage I NSCLC. METHODS: Subjects comprised stage I NSCLC patients (141 patients with adenocarcinoma (ADC) and 36 with squamous cell carcinoma (SCC)). RESULTS: In patients with stage I ADC, recurrence-free survival (RFS) differed most significantly at a preoperative CEA level of 2.5 ng/ml, regardless of smoking status. Cases with preoperative CEA >2.5 ng/ml correlated with male sex, high maximum standard uptake value on (18) F-fluorodeoxyglucose positron emission tomography, poorer histopathological grade, lymphatic invasion, and smoking status. Importantly, preoperative CEA >2.5 ng/ml was identified as an independent risk factor for recurrence (P = 0.0015). Conversely, in patients with SCC, a preoperative CEA level of 3.0 ng/ml was the most predictive threshold. CONCLUSIONS: Thresholds of preoperative CEA should be considered when predicting risk of relapse, even if these levels are within normal limits, as optimal cutoff levels may vary according to histological type. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.
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[542]
TÍTULO / TITLE: - The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced nonsmall cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Opin Oncol. 2013 Mar;25(2):121-9. doi: 10.1097/CCO.0b013e32835d8175.
●● Enlace al texto completo (gratuito o de pago) 1097/CCO.0b013e32835d8175
AUTORES / AUTHORS: - D’Arcangelo M; Wynes MW; Hirsch FR
INSTITUCIÓN / INSTITUTION: - University of Colorado Cancer Center, Aurora, Colorado 80045, USA.
RESUMEN / SUMMARY: - PURPOSE OF REVIEW: Treatment of advanced nonsmall cell lung cancer (NSCLC) has rapidly changed over the last decade. On the basis of the progress made in cancer biology, the old-fashioned ‘one size fits all’ chemotherapeutic approach is shifting to a novel approach in which treatment choice is mainly based on the tumor’s biological genotype. The aim of the present review is to describe the anaplastic lymphoma kinase (ALK) translocation as a prominent molecular driver aberration in NSCLC, its prognostic and predictive role, and the new available treatment options. RECENT FINDINGS: Crizotinib is a tyrosine kinase inhibitor of MET, ALK and ROS1. Its impressive clinical activity shown in a phase IB trial led to accelerated approval for patients with ALK-positive advanced NSCLC. More recently, a phase III trial confirmed the high activity of crizotinib in this subset of lung tumors. Many new-generation ALK inhibitors are currently also in clinical development. SUMMARY: ALK-positive NSCLC has emerged as a distinct, well defined subset of lung malignancies. The use of ALK inhibitors deeply impacts the therapy of patients harboring such translocation. Nevertheless, to date, several issues remain open, such as the most suitable screening and diagnostic method for the detection of ALK gene rearrangement and expression and particularly the mechanisms of acquired resistance for further clinical development of these agents.
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[543]
TÍTULO / TITLE: - Imaging integrin alpha(v)beta(3) positive glioma with a novel RGD dimer probe and the impact of antiangiogenic agent (Endostar) on its tumor uptake.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 8. pii: S0304-3835(13)00111-0. doi: 10.1016/j.canlet.2013.01.053.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.053
AUTORES / AUTHORS: - Wu H; Chen H; Sun Y; Wan Y; Wang F; Jia B; Su X
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China. Electronic address: wuhua1025@163.com.
RESUMEN / SUMMARY: - Integrin alpha(v)beta(3) has been recognized to play an important role in angiogenesis, tumor growth and metastasis. It will be of interest to apply this promising target for tumor imaging and visualization of tumor angiogenesis in vivo. In this study, a novel integrin alpha(v)beta(3) targetting imaging probe, (99m)Tc-HYNIC-E[c(RGDfK)](2), was used to investigate the glioma uptake in vitro and in vivo before and after treatment with an antiangiogenic agent, endostar. The results indicated that U87MG glioma cells have high expression of integrin alpha(v)beta(3) and special uptake of (99m)Tc-HYNIC-E[c(RGDfK)](2) both in cell line and in tumor xenograft. The endostatin analogue endostar can inhibit the expression of integrin alpha(v)beta(3) receptors in both U87MG cells in vitro and glioma tissues, which suggested that integrin pathway may play a role in antiangiogenic effect of Endostar. (99m)Tc-HYNIC-E[c(RGDfK)](2) may be a promising molecular imaging probe for integrin alpha(v)beta(3) positive tumor imaging and open up the possibility to establish an molecular imaging modality for assessment of tomor antiangiogenic therapy.
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[544]
TÍTULO / TITLE: - The prognostic value of vascular endothelial growth factor in hepatocellular carcinoma for predicting metastasis after curative resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncology. 2013;84 Suppl 1:75-81. doi: 10.1159/000345894. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1159/000345894
AUTORES / AUTHORS: - Minata M; Harada KH; Kudo M; Ikai I; Nishida N
INSTITUCIÓN / INSTITUTION: - Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: Hepatocellular carcinoma (HCC) frequently recurs even after curative resection. The purpose of this study was to identify factors predictive for postoperative recurrence of HCC in patients who underwent curative resection using immunohistochemistry. METHODS: Expression of vascular endothelial growth factor (VEGF), E-cadherin and cyclin D1 in HCC tissue were analyzed for 133 HCC patients who underwent curative resection of tumors using immunohistochemical analysis. Relationships of expressions and disease-free survival of HCC were evaluated using univariate and multivariate analyses. RESULTS: The average period of follow-up of the patients was 6.7 years. Multivariate analyses revealed that only strong expression of VEGF in HCC tissue was significantly associated with metastatic recurrence (p < 0.001, hazard ratio, HR, 3.32). CONCLUSIONS: Evaluating VEGF in HCC tissue after surgical resection has predictive value for metastatic HCC recurrence. The ability to risk stratify should improve the treatment strategies after hepatectomy.
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[545]
TÍTULO / TITLE: - Periarticular Bone Gain at Proximal Interphalangeal Joints and Changes in Bone Turnover Markers in Response to Tumor Necrosis Factor Inhibitors in Rheumatoid and Psoriatic Arthritis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Rheumatol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 3899/jrheum.120397
AUTORES / AUTHORS: - Szentpetery A; McKenna MJ; Murray BF; Ng CT; Brady JJ; Morrin M; Radovits B; Veale DJ; Fitzgerald O
INSTITUCIÓN / INSTITUTION: - From the Department of Rheumatology, the Metabolism Laboratory, and the DXA Unit, St. Vincent’s University Hospital, Dublin, Ireland; and the Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
RESUMEN / SUMMARY: - OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterized by periarticular bone erosion; periarticular bone formation is a feature in PsA. The effect of anti-tumor necrosis factor-alpha (TNF-alpha) on periarticular bone remodeling is unclear in both diseases. Our aim was to assess the response of bone turnover markers (BTM) and hand bone mineral density (BMD) to anti-TNF over 3 years in RA and PsA. METHODS: We measured serum bone-specific alkaline phosphatase (bone ALP), procollagen type-I N-propeptide (PINP), intact osteocalcin, C-terminal cross-linking telopeptides (CTX-I), urinary N-terminal cross-linking telopeptide of type-I collagen (NTX-I), and free deoxypyridinoline crosslinks (fDPD) at baseline, 1, 12, and 36 months. BMD measurements (hands/spine/hip) were obtained at 3 timepoints. RESULTS: We recruited 62 patients (RA 35; PsA 27). BTM correlated significantly with hand BMD but not with central BMD. Low hand BMD was associated with RA and increased BTM. Following anti-TNF therapy, hip BMD declined while spine and hand BMD were unchanged. Periarticular BMD at proximal interphalangeal (PIP) joints increased while it decreased at metacarpophalangeal joints. Bone ALP increased steadily and was always higher in PsA. PINP and intact osteocalcin increased to a lesser extent, but resorption markers did not change. CONCLUSION: At baseline, hand BMD was inversely associated with BTM. Bone formation rather than resorption markers better showed the bone response to anti-TNF. Despite a lack of effect on central BMD, the modest effect of anti-TNF on PIP BMD may provide evidence that BTM reflect specifically bone remodeling activity at periarticular sites of inflammation in RA and PsA.
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[546]
TÍTULO / TITLE: - The identification of predictive factors for perioperative chemotherapy in esophago-gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt111
AUTORES / AUTHORS: - Lordick F; Rocken C
INSTITUCIÓN / INSTITUTION: - University Cancer Center Leipzig, University of Leipzig.
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[547]
TÍTULO / TITLE: - Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochimie. 2013 Feb 27. pii: S0300-9084(13)00070-9. doi: 10.1016/j.biochi.2013.02.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biochi.2013.02.013
AUTORES / AUTHORS: - Gomez LS; Zancan P; Marcondes MC; Ramos-Santos L; Meyer-Fernandes JR; Sola-Penna M; Da Silva D
INSTITUCIÓN / INSTITUTION: - Laboratorio de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Farmacos, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Ilha do Fundao, Rio de Janeiro - RJ 21941-590, Brazil.
RESUMEN / SUMMARY: - Cancer cells are highly dependent on glycolysis to supply the energy and intermediates required for cell growth and proliferation. The enzyme 6-phosphofructo-1-kinase (PFK) is critical for glycolysis, and its activity is directly correlated with cellular glucose consumption. Resveratrol is a potential anti-tumoral drug that decreases glucose metabolism and viability in cancer cells. However, the mechanism involved in resveratrol-mediated anti-tumor activity is not entirely clear. In this work, it is demonstrated that resveratrol decreases viability, glucose consumption and ATP content in the human breast cancer cell line MCF-7. These effects are directly correlated with PFK inhibition by resveratrol in these cells. Moreover, resveratrol directly inhibits purified PFK, promoting the dissociation of the enzyme from fully active tetramers into less active dimers. This effect is exacerbated by known negative regulators of the enzyme, such as ATP and citrate. On the other hand, positive modulators that stabilize the tetrameric form of the enzyme, such as fructose-2,6-bisphosphate and ADP, prevent the inhibition of PFK activity by resveratrol, an effect not observed with increased pH. In summary, our results provide evidence that resveratrol directly inhibits PFK activity, therefore disrupting glucose metabolism and reducing viability in cancer cells.
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[548]
TÍTULO / TITLE: - Predictive and prognostic values of Tau and BubR1 protein in prostate cancer and their relationship to the Gleason score.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):526. doi: 10.1007/s12032-013-0526-7. Epub 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0526-7
AUTORES / AUTHORS: - Cirak Y; Sarsik B; Cakar B; Sen S; Simsir A; Uslu R
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege Universtiy, Bornova, 35100 Izmir, Turkey. yalcincrk@gmail.com
RESUMEN / SUMMARY: - The aim of this study is to detect the expression levels of spindle assembly checkpoint protein-BubR1 and microtubule-associated protein-Tau in human prostate cancer tissues of different Gleason score, and to test whether there is a relationship between their expression levels and clinicopathologic parameters including response to docetaxel treatment, Gleason score, and overall survival (OS). Moreover, to test whether Tau protein expressed in the cancerous prostate tissue is phosphorylated. Thirty patients who received at least three cycles docetaxel for metastatic castrate-resistant prostate cancer were included into the trial. The patients’ formalin-fixed and paraffin-embedded prostate tissue specimens were retrospectively obtained from the pathology department archives of Ege University School of Medicine. The expression status of BubR1 protein was defined by immunohistochemical (IHC) using the anti-BubR1 antibody. The expression status of Tau protein was defined by IHC using the two types of Tau antibodies: anti-Tau-1 antibody (that recognizes Tau only in its dephosphorylated form) and anti-PHF-Tau antibody (that recognizes all isoforms of human Tau proteins independent of its phosphorylation status). The BubR1 and Tau were overexpressed in about 63 and 23 % of the study group, respectively. Tau overexpression was significantly associated with lower Gleason score. There was no significant association between the expression levels of BubR1 and Tau proteins, and docetaxel response. Reduced BubR1 expression was strongly associated with longer survival (P = 0.008), whereas Tau expression status did not effect survival. Moreover, the Tau expression of cancerous prostate tissue was highly dephosphorylated. In this clinicopathological study, our findings did not confirm the preclinical observations that low BubR1 and Tau expression confer selective sensitivity to microtubulisin drugs. Our data imply that reduced BubR1 expression was a predictor for longer OS, and the possibility that high Tau expression may be involved in better prognosis due to its relationship to the Gleason score. Furthermore, our data suggest that both Tau and BubR1 may be a promising prognostic marker rather than predictive marker in patients with prostate cancer.
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[549]
TÍTULO / TITLE: - Anticancer efficacy of cisplatin and trichostatin A or 5-aza-2’-deoxycytidine on ovarian cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Feb 19;108(3):579-86. doi: 10.1038/bjc.2013.10. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.10
AUTORES / AUTHORS: - Meng F; Sun G; Zhong M; Yu Y; Brewer MA
INSTITUCIÓN / INSTITUTION: - Division of Gynecologic Oncology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
RESUMEN / SUMMARY: - BACKGROUND: To evaluate the anticancer efficacy of the combination of epigenetic modifiers and cisplatin in human ovarian cancer. METHODS: The effect of trichostatin A (TSA) and 5-aza-2’-deoxycytidine alone or in combination with low-dose cisplatin was evaluated on human ovarian cancer cell lines in vitro. We measured drug interaction by MTS assay, migration by transwell assay, expression of epithelial to mesenchymal transition (EMT) markers (Twist, Snail, Slug, E-cadherin, and N-cadherin), pluripotency markers (Oct4, Sox2, and Nanog), and epigenetic markers (DNMT3A, LSD1 and H3K4me2, H3K4me3, H3K9me2, and H3K9me3) by western blot, and the impact on and characteristics of spheroid growth when exposed to these drugs. Mouse xenografts were used to evaluate the anticancer effect of sequential drug treatment. RESULTS: Combination treatment had greater efficacy than single drugs and significantly suppressed cell viability, migration, and spheroid formation and growth. Sequential treatment of cisplatin (1 mg kg(-1)) followed by TSA (0.3 mg kg(-1)) significantly suppressed tumorigenicity of HEY xenografts through inhibition of EMT and decreased pluripotency of ovarian cancer cells. CONCLUSION: Epigenetic modifiers potentiate the anticancer efficacy of low-dose cisplatin in ovarian cancer through regulation of EMT and pluripotency, and may provide a promising treatment for ovarian cancer patients.
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[550]
TÍTULO / TITLE: - Arginine modified PAMAM dendrimer for interferon beta gene delivery to malignant glioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Pharm. 2013 Mar 10;445(1-2):79-87. doi: 10.1016/j.ijpharm.2013.01.057. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijpharm.2013.01.057
AUTORES / AUTHORS: - Bai CZ; Choi S; Nam K; An S; Park JS
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - A xenograft brain tumor model was established by the subcutaneous injection of U87MG cells into nude mice to investigate the efficacy of a non-viral vector, arginine-modified polyamidoamine dendrimer (PAMAM-R), in delivering a therapeutic gene, human interferon beta (IFN-beta). We used 4’,6-diamidino-2-phenylindole staining, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and the caspase-3 activity assay to determine the induction of apoptosis upon transfection with the PAMAM-R/IFN-beta gene polyplex in vitro. The polyplex was injected into xenograft brain tumors. Mice treated with PAMAM-R/pORF-IFN-beta exhibited a significantly smaller tumor size than control mice and PAMAM-R/pORF treated mice. Hematoxylin/eosin staining and immunohistochemistry with the endothelial growth factor receptor antibody also revealed inhibition of tumor growth. Furthermore, reverse transcription polymerase chain reaction and the TUNEL assay also verified the expression of IFN-beta and induction of apoptosis in vivo. These results indicate that the PAMAM-R/pORF-IFN-beta polyplex is an effective therapeutic candidate for glioblastoma multiforme due to its selective induction of apoptosis in tumor cells.
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[551]
TÍTULO / TITLE: - Molecular pathology of prostate cancer revealed by next-generation sequencing: opportunities for genome-based personalized therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Opin Urol. 2013 May;23(3):189-93. doi: 10.1097/MOU.0b013e32835e9ef4.
●● Enlace al texto completo (gratuito o de pago) 1097/MOU.0b013e32835e9ef4
AUTORES / AUTHORS: - Huang J; Wang JK; Sun Y
INSTITUCIÓN / INSTITUTION: - Departments of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center for Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
RESUMEN / SUMMARY: - PURPOSE OF REVIEW: This article reviews recently identified genomic mutations in prostate cancer. RECENT FINDINGS: Advanced sequencing technologies have made it possible to obtain large amounts of data on genomes and transcriptomes of cancers. Such technologies have been used to sequence prostate cancer of different stages, from treatment-naive cancers, to advanced, castration-resistant cancers to the aggressive small cell neuroendocrine carcinomas. For each category of prostate cancer, distinct and overlapping DNA sequence alterations were discovered, including point mutations, small insertions or deletions, copy number changes and chromosomal rearrangements. There appears to be a stepwise increase in genomic alterations from low risk to high risk to advanced cancers. SUMMARY: These novel findings have significantly increased our knowledge of the genetic basis of human prostate cancer and the molecular mechanisms responsible for disease progression and treatment resistance. Some of the lesions are potential therapeutic targets. Studies along this direction will eventually make it possible to design personalized management plans for individual patients.
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[552]
TÍTULO / TITLE: - Low Expression of CyclinH and Cyclin-Dependent Kinase 7 Can Decrease the Proliferation of Human Esophageal Squamous Cell Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Dis Sci. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10620-013-2597-x
AUTORES / AUTHORS: - Zhang J; Yang X; Wang Y; Shi H; Guan C; Yao L; Huang X; Ding Z; Huang Y; Wang H; Cheng C
INSTITUCIÓN / INSTITUTION: - Department of Immunology, Medical College, Nantong University, 19 Qi-Xiu Road, Nantong, 226001, Jiangsu, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: Increased expression of cyclinH (CCNH) and cyclin-dependent kinase 7 (CDK7) has a relationship with poor prognosis in most human cancers. AIM: Investigate the expression of CCNH and CDK7 in human esophageal squamous cell carcinoma (ESCC) and the effect of chemotherapy on their expression. METHODS: Western blotting and immunohistochemistry were used to measure the expression of CCNH and CDK7 proteins in ESCC and adjacent normal tissue in 98 patients. We use Cell Counting Kit-8 and cell flow to analyze the effects of cisplatin and interference of CCNH and CDK7 in cell cycle process. RESULTS: Immunohistochemical analysis showed that CCNH and CDK7 expression were significantly associated with unfavorable clinicopathologic variables. CCNH and CDK7 protein levels were elevated in ESCC tissues in comparison with adjacent normal tissues. Survival analysis revealed that CCNH and CDK7 overexpression were significantly associated with overall survival (P < 0.001). Cisplatin or interference of CCNH or CDK7 led cells to grow slowly. Overexpression of CCNH and CDK7 in TE1 cells can lead to resistance to cisplatin. CONCLUSIONS: We can conclude that CCNH and CDK7 may play an important role in the tumorigenesis and development of ESCC. CCNH and CDK7 expression affected the chemotherapy of tumor.
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[553]
TÍTULO / TITLE: - PTK787/ZK222584 Combined with Interferon Alpha and 5-Fluorouracil Synergistically Inhibits VEGF Signaling Pathway in Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2948-z
AUTORES / AUTHORS: - Katsura Y; Wada H; Murakami M; Akita H; Hama N; Kawamoto K; Kobayashi S; Marubashi S; Eguchi H; Tanemura M; Umeshita K; Doki Y; Mori M; Nagano H
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
RESUMEN / SUMMARY: - BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus remains poor. We previously reported the beneficial effects of interferon alpha (IFN) and 5-fluorouracil (5-FU) combination therapy for these patients. We showed that the mechanism of therapy was regulation of vascular endothelial growth factor (VEGF). Here, we combined IFN/5-FU therapy with the VEGF receptor-selective inhibitor PTK787/ZK222584 (PTK/ZK) and examined the antitumor effects and the mechanism of action. METHODS: We studied two HCC cell lines, PLC/PRF/5 and HuH7, and a human umbilical vein endothelial cell line, HUVEC. We studied the effects of IFN/5-FU with or without PTK/ZK in growth inhibition assays, immunohistochemistry, Western blot analysis, and immunocytochemistry. RESULTS: In a HuH7 xenograft model, the combination of PTK/ZK and IFN/5-FU significantly inhibited proliferation, induced apoptosis, decreased microvessel density, reduced the number of tumor cells that expressed VEGF receptor 2 (VEGFR-2), and repressed the phosphorylation of Akt in vivo. In HCC cells and HUVECs in vitro, IFN/5-FU plus PTK/ZK repressed the expression of VEGFR-2 and repressed the phosphorylation of VEGFR, Akt, Erk, and p38MAPK. CONCLUSIONS: VEGF signaling inhibition enhanced the antitumor effects of IFN/5-FU therapy on HCC cells and endothelial cells via Erk, Akt, and p38MAPK pathways.
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[554]
TÍTULO / TITLE: - Functional polymorphism in the MicroRNA-367 binding site as a prognostic factor for colonic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):513-9.
AUTORES / AUTHORS: - Chae YS; Kim JG; Kang BW; Lee SJ; Lee YJ; Park JS; Choi GS; Lee WK; Jeon HS
INSTITUCIÓN / INSTITUTION: - Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-Gu, Daegu, 702-210, Korea. jkk21c@knu.ac.kr
RESUMEN / SUMMARY: - BACKGROUND: As microRNAs play important roles in cancer development and progression by regulating the expressions of oncogenes and tumor suppressor genes though interacting with the 3’ untranslated region (UTR) of target genes, we aimed to evaluate the association between genetic variants of miRNAs and their binding sites and prognosis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Three miRNA variants and four variants in the miRNA binding sites were selected based on allelic frequencies, while their potential impact has been described in previous studies. DNA was extracted from fresh-frozen tissues of 344 patients with CRC who underwent curative surgery and genotyping analyses were performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: Among seven target variants, rs1044129 at the miR-367 binding site of calcium channel ryanodine receptor gene 3 (RYR3) was associated with relapse-free survival (RFS) for colon cancer patients as a recessive model in a univariate analysis. Moreover, a multivariate analysis revealed that patients carrying the GG genotype had poor RFS, compared to those with the AA or AG genotype (hazard ratio, HR=2.864; p=0.005), yet there was only a marginal trend for disease-specific survival (HR=2.226; p=0.087) regardless of patient and tumor characteristics. CONCLUSION: The current study suggests that the functional variant (rs1044129) in the miR-367 binding site of RYR3 may be a potential marker for prognosis in patients following curative surgery for CRC.
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[555]
TÍTULO / TITLE: - Protective Effect of Taurine on Triorthocresyl Phosphate (TOCP)-Induced Cytotoxicity in C6 Glioma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Adv Exp Med Biol. 2013;776:231-40. doi: 10.1007/978-1-4614-6093-0_22.
●● Enlace al texto completo (gratuito o de pago) 1007/978-1-4614-6093-0_22
AUTORES / AUTHORS: - Li Y; Piao F; Liu X
INSTITUCIÓN / INSTITUTION: - Department of Occupational and Environmental Health, Dalian Medical University, Dalian, Liaoning, 116044, China.
RESUMEN / SUMMARY: - Triorthocresyl phosphate (TOCP) an organophosphorus ester can cause neurotoxicity via oxidative stress pathway. Taurine is an antioxidant. The objective of this study was to investigate the protective effect of taurine on TOCP-induced cytotoxicity in C6 glioma cell. The C6 glioma cells were pretreated with 0, 1, 3, and 9 mM of taurine for 30 min prior to 1 mM TOCP treatment. After 48 h, cell survival was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. The content of glutathione (GSH) and the activity of glutathione peroxidase (GPx) were also analyzed by kits. Our results showed that survival of the glioma cells decreased in the group treated with TOCP alone and increased significantly in the groups pretreated with taurine in a concentration-dependent manner. TOCP induced decrease in the activity of GPx and the content of GSH. However, taurine prevented these decreases. Our results suggested that taurine has protective effect on TOCP-induced toxicity to glioma cells via elevating antioxidant capacity.
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[556]
TÍTULO / TITLE: - Down-regulation of DNA methyltransferase 3B in staurosporine-induced apoptosis and its mechanism in human hepatocarcinoma cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 Apr;376(1-2):111-9. doi: 10.1007/s11010-012-1556-8. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-012-1556-8
AUTORES / AUTHORS: - Zhao C; Yin P; Mei C; Li N; Yao W; Li X; Qi J; Fan K; Li Z; Wang L; Shi Y; Qiu S; Fan J; Zha X
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - Abnormal DNA methylation is one of the important characteristics in tumor cells. Apoptosis plays an essential role in cell survival and processing. It is not clear whether DNA methyltransferases (DNMTs) change in apoptosis and how DNMTs are regulated in apoptosis. In this study, we found that SMMC-7721 or BEL-7404 cells were induced to apoptosis by STS, meanwhile the DNMT3B protein and mRNA level were decreased. To explore the mechanism of DNMT3B down-regulation, we found that the mRNA decay was not changed and core promoter activity of DNMT3B gene was decreased in STS-induced apoptosis. In order to figure out the signal molecule involved in transcriptional regulation of DNMT3B gene by STS, p-JNK, p-ERK, and p-p38 were examined. In STS-induced apoptosis p-JNK level was increased, and p-ERK and p-p38 were decreased. Furthermore, the inhibitor of p-JNK significantly alleviated the decline of DNMT3B protein. We also found that the siRNA of DNMT3B strengthened the cleavage of PARP and pro-caspase-3 as well as up-regulated the p16 gene expression in STS-treated cells. We concluded here that STS-regulated DNMT3B gene expression via p-JNK and down-regulation of DNMT3B-mediated STS-induced apoptosis through the up-regulation p16 expression.
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[557]
TÍTULO / TITLE: - Oestrogen receptors are prognostic factors in malignant peritoneal mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cancer Res Clin Oncol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1007/s00432-013-1408-2
AUTORES / AUTHORS: - Pillai K; Pourgholami MH; Chua TC; Morris DL
INSTITUCIÓN / INSTITUTION: - Department of Surgery, St. George Hospital, University of New South Wales, Kogarah, NSW, 2217, Australia.
RESUMEN / SUMMARY: - BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer. Females are found to survive longer than males after treatment, suggesting a possible involvement of hormonal factors. Estradiol is involved in cellular proliferation of a number of cancers and acts mainly through oestrogen receptors (ERs). Hence, we examined the expression of oestrogen receptors with correlation to prognosis. METHODS: Oestrogen receptors expression was examined using immunohistochemistry on 42 paraffin-embedded sections of MPM tumours. Kaplan-Meier survival curves were analysed to determine the significance of ER expression in relation to prognosis. RESULTS: ER-beta (nuclear) was detected in 33 (79 %) patients. ER-beta was also detected in the cellular cytoplasm of 9 (21 %) patients. Presence of ER-beta (nuclear) was associated with favourable survival (univariate analysis, P = 0.001), whereas the presence of ER-beta (cytoplasm) was associated with a poor survival (P = 0.014). Multivariate Cox regression analysis revealed the absence of ER-beta (nuclear) and the presence of ER-beta (cytoplasm) to be independent predictive factors for poor disease outcome (hazard ratio 5.4, 95 % confidence interval 1.86-15.75; P = 0.002 and hazard ratio 8.0, 95 % confidence interval 1.8-34; P = 0.005), respectively. ER-alpha (nuclear) was detected in only 4 (9 %) of patients and not statistically significant (univariate analysis, P = 0.066). CONCLUSION: The presence of ER-beta (cytoplasm) is associated with poor prognosis. The favourable survival association observed in patients with ER-beta (nuclear) raises a question about the molecular mechanisms of the tumorigenic roles of ER-beta in each cellular compartment and requires further studies.
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[558]
TÍTULO / TITLE: - Head-to-Head Comparison of Prostate Health Index and Urinary Prostate Cancer Antigen 3 in Predicting the Presence of Cancer at Initial or Repeat Biopsy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Urol. 2013 Mar 1. pii: S0022-5347(13)03460-5. doi: 10.1016/j.juro.2013.02.3184.
●● Enlace al texto completo (gratuito o de pago) 1016/j.juro.2013.02.3184
AUTORES / AUTHORS: - Scattoni V; Lazzeri M; Lughezzani G; De Luca S; Passera R; Bollito E; Randone D; Abdollah F; Capitanio U; Larcher A; Lista G; Gadda GM; Bini V; Montorsi F; Guazzoni G
INSTITUCIÓN / INSTITUTION: - Department of Urology - University Vita-Salute, Scientific Institute H San Raffaele, Milan, Italy. Electronic address: scattoni.vincenzo@hsr.it.
RESUMEN / SUMMARY: - PURPOSE: We performed a head-to-head comparison of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 (PCA3) METHODS: The performance of PHI and PCA3 were evaluated in 211 patients undergoing first (n=116) or repeat prostate biopsy (PBx) (n=95). Multivariable logistic regression analyses tested the accuracy (AUC) of PHI and PCA3 in predicting PCa in the overall population and in both settings. Decision curve analyses (DCA) were used to compare the clinical benefit of different models. RESULTS: Overall, the AUC value of PHI (0.70) was significantly higher relative to those of PCA3 (0.59) (p=0.043), tPSA (0.56) (p=0.002) and %fPSA (0.60) (p=0.037). PHI was more accurate than PCA3 in predicting PCa in the initial setting (AUC: 0.69 vs. 0.57) and in the repeat setting (AUC: 0.72 vs. 0.63), even if no statistically significant difference was observed. The inclusion of PCA3 to the base multivariable model (BMM: PSA + %fPSA + prostate volume) did not increase the predictive accuracy in both settings (AUC:0.79 vs. 0.80 and 0.75 vs.0.76, respectively). Conversely, the inclusion of PHI to BMM improved the predictive accuracy by a 5% (AUC:0.79 to 0.84) and a 6% extent (AUC:0.75 to 0.81) in the initial and repeat PBx settings, respectively. At DCA, the highest net-benefit was observed when PHI was added to BMM. CONCLUSIONS: Both PHI and PCA3 offer a significant increase in sensitivity and specificity compared to all other examined markers and may help to guide biopsy decisions. PCA3 does not increase the accuracy in predicting the presence of PCa when PHI is assessed.
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[559]
TÍTULO / TITLE: - Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urology. 2013 Feb;81(2):467.e1-7. doi: 10.1016/j.urology.2012.10.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urology.2012.10.011
AUTORES / AUTHORS: - Li Y; Xu S; Wang X; Shi H; Sun Z; Yang Z
INSTITUCIÓN / INSTITUTION: - Department of Urology, Second Affiliated Hospital, Fujian Medical University, Quanzhou Fujian, China.
RESUMEN / SUMMARY: - OBJECTIVE: To explore the exact mechanism of Pokemon in prostate cancer. MATERIALS AND METHODS: Pokemon is a member of the POK family of transcriptional repressors. Its main function is suppression of the p14ARF (alternate reading frame) tumor suppressor gene. Although Pokemon expression has been found to be increased in various types of lymphoma, the exact mechanism of the gene in prostate cancer is not clear. In the present study, prostate cancer cells were transfected with the specific short hairpin ribonucleic acid (RNA) expression vector targeting Pokemon. The expression of Pokemon messenger RNA and its protein was detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The cell growth and cell apoptosis were also examined using the methyl thiazolyl tetrazolium assay and flow cytometry. RESULTS: The results demonstrated that specific RNA interference (RNAi) could decrease the expression levels of Pokemon gene messenger RNA and protein in prostate cancer cells. In addition, that specific RNAi significantly inhibited the cell proliferation and increased the apoptotic rate. In vivo experiments showed that specific RNAi inhibited the tumorigenicity of prostate cancer cells and significantly suppressed tumor growth. CONCLUSION: Therefore, an RNAi-targeted Pokemon gene strategy could be a potential approach to prostate cancer therapy.
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[560]
TÍTULO / TITLE: - Expression of Fibroblast Growth Factor 19 Is Associated with Recurrence and Poor Prognosis of Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Dis Sci. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10620-013-2609-x
AUTORES / AUTHORS: - Hyeon J; Ahn S; Lee JJ; Song DH; Park CK
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea, jy.hyeon@samsung.com.
RESUMEN / SUMMARY: - BACKGROUND: Fibroblast growth factor 19 (FGF19)-mediated activation of mitogen-activated protein kinase and the beta-catenin pathway may be involved in the development and progression of hepatocellular carcinoma. This study aimed to elucidate the prognostic significance of FGF19 protein expression in hepatocellular carcinoma patients. METHODS: By immunohistochemistry, we investigated the expression of FGF19 protein in tumor tissue from 281 hepatocellular carcinoma patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of patients. The median follow-up period was 75.6 months. RESULTS: FGF19 protein expression was observed in 135 (48.0 %) of the 281 hepatocellular carcinomas. FGF19 expression was significantly associated with larger tumor size (P < 0.001), and higher BCLC stage (P = 0.001). FGF19 expression was correlated with the early recurrence (P < 0.001), but not with the late recurrence (P = 0.582). FGF19 expression (P = 0.002), viral etiology (P = 0.028), and intrahepatic metastasis (P < 0.001) were independent predictors of early recurrence. Multivariate analyses of survival revealed that FGF19 expression (P < 0.001), intrahepatic metastasis (P < 0.001), and liver cirrhosis (P = 0.019) were independent predictors of shorter disease-free survival. FGF19 expression (P = 0.005), larger tumor size (P = 0.038), major portal vein invasion (P = 0.048), intrahepatic metastasis (P < 0.001), lower albumin level (P = 0.024), and liver cirrhosis (P = 0.031) were independent predictors of shorter disease-specific survival. CONCLUSIONS: FGF19 protein expression might be an effective predictor of early recurrence and a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy, indicating that FGF19 might be a potential preventive target in hepatocellular carcinoma patients.
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[561]
TÍTULO / TITLE: - High expression of cyclic nucleotide phosphodiesterase 7B mRNA predicts poor prognosis in mantle cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Res. 2013 Feb 27. pii: S0145-2126(13)00044-1. doi: 10.1016/j.leukres.2013.02.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.leukres.2013.02.006
AUTORES / AUTHORS: - Fang C; Dong HJ; Zou ZJ; Fan L; Wang L; Zhang R; Xu J; Xu W; Li JY
INSTITUCIÓN / INSTITUTION: - Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China.
RESUMEN / SUMMARY: - In order to determine the relationship between expression of cyclic nucleotide phosphodiesterase isoform 7B (PDE7B) and mantle cell lymphoma (MCL) progression, PDE7B mRNA expression was measured by qRT-PCR in 21 untreated MCL patients with bone marrow involvement and 20 healthy donors. The expression level of PDE7B was markedly higher in MCL patients compared with normal controls (P=0.001), and the higher level of PDE7B expression was associated with unfavorable cytogenetic characteristics in MCL. It was showed that higher expression of PDE7B might be a novel unfavorable prognostic indicator in MCL, which possess important clinical significance.
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[562]
TÍTULO / TITLE: - N-acetyl-L-cysteine inhibits bleomycin induced apoptosis in malignant testicular germ cell tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Biochem. 2013 Feb 5. doi: 10.1002/jcb.24510.
●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24510
AUTORES / AUTHORS: - Kucuksayan E; Cort A; Timur M; Ozdemir E; Yucel SG; Ozben T
INSTITUCIÓN / INSTITUTION: - Department of Clinical Biochemistry, Faculty of Medicine, Akdeniz University, 07070 Antalya, Turkey.
RESUMEN / SUMMARY: - Antioxidants may prevent apoptosis of cancer cells via inhibiting reactive oxygen species (ROS). However, to date no study has been carried out to elucidate the effects of strong antioxidant N-acetylcysteine (NAC) on Bleomycin induced apoptosis in human testicular cancer (NTERA-2, NT2) cells. For this reason, we studied the effects of Bleomycin and NAC alone and in combination on apoptotic signalling pathways in NT2 cell line. We determined the cytotoxic effect of bleomycin on NT2 cells and measured apoptosis markers such as Caspase-3, -8, -9 activities and Bcl-2, Bax, Cyt-c, Annexin V-FTIC and PI levels in NT2 cells incubated with different agents for 24 h. Early apoptosis was determined using FACS assay. We found half of the lethal dose (LD(50) ) of Bleomycin on NT2 cell viability as 400; 100; and 20 microg/ml after incubations for 24 h; 48 h; and 72 h, respectively. Incubation with bleomycin (LD(50) ) and H(2) O(2) for 24 h increased Caspase-3, -8, -9 activities, Cyt-c and Bax levels and decreased Bcl-2 levels. The concurrent incubation of NT2 cells with bleomycin/H(2) O(2) and NAC (5 mM) for 24 h abolished bleomycin/H(2) O(2) -dependent increases in Caspase-3,-8,-9 activities, Bax and Cyt-c levels and bleomycin/H(2) O(2) -dependent decrease in Bcl-2 level. Our results indicate that bleomycin/H(2) O(2) induce apoptosis in NT2 cells by activating mitochondrial pathway of apoptosis, while NAC diminishes bleomycin/H(2) O(2) induced apoptosis. We conclude that NAC has antagonistic effects on Bleomycin-induced apoptosis in NT2 cells and causes resistance to apoptosis which is not a desired effect in eliminating cancer cells. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
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[563]
TÍTULO / TITLE: - Dichloromethane fraction of Melissa officinalis induces apoptosis by activation of intrinsic and extrinsic pathways in human leukemia cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Immunopharmacol Immunotoxicol. 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 3109/08923973.2013.768268
AUTORES / AUTHORS: - Ebrahimnezhad Darzi S; Amirghofran Z
INSTITUCIÓN / INSTITUTION: - Department of Immunology, Medicinal and Natural Products Chemistry Research Center and Autoimmune Disease Research Center, Shiraz University of Medical Sciences , Shiraz , Iran.
RESUMEN / SUMMARY: - Abstract Various components from medicinal plants are currently used in cancer therapy because of their apoptosis-inducing effects. The present study has aimed to investigate the growth inhibitory and apoptotic effects of Melissa officinalis on tumor cells. We prepared different fractions of this plant to investigate their inhibitory effects on two leukemia cell lines, Jurkat and K562. Fractions with the highest inhibitory effects were examined for induction of apoptosis by the annexin V/propidium iodide assay and cell cycle changes by flow cytometry. Real-time polymerase chain reaction evaluated the changes in expression of apoptosis-related genes. Among different fractions, dichloromethane and n-hexane dose-dependent showed the strongest inhibitory effects on both K562 and Jurkat cells. The dichloromethane fraction significantly induced apoptosis at concentration of 50 microg/ml on Jurkat (85.66 +/- 4.9%) and K562 cells (65.04 +/- 0.93%) at 24 h after treatment (p < 0.002). According to cell cycle analysis, more than 70% of the cells accumulated in the sub-G1 phase when cultured in the presence of the dichloromethane fraction. This fraction up-regulated Fas and Bax mRNA expression as well as the Bax/Bcl-2 ratio according to cell type, showing its effect on the activation of both extrinsic and intrinsic pathways of apoptosis. The expression of apoptosis-related genes did not significantly change following treatment with the n-hexane fraction. These data indicated that the dichloromethane fraction of M. officinalis had the ability to induce apoptosis and change apoptosis-related gene expression in leukemia cells.
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[564]
TÍTULO / TITLE: - Suppression of BCRP expression and restoration of sensitivity to chemotherapy in multidrug-resistant HCC cell line HEPG2/ADM by RNA interference.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatogastroenterology. 2012 Oct;59(119):2238-42. doi: 10.5754/hge11781.
●● Enlace al texto completo (gratuito o de pago) 5754/hge11781
AUTORES / AUTHORS: - Li H; Zhou S; Li T; Liu Z; Wu J; Zeng G; Liu C; Gong J
INSTITUCIÓN / INSTITUTION: - Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, China.
RESUMEN / SUMMARY: - BACKGROUND/AIMS: Breast cancer resistance protein (BCRP) is an ATP-binding cassette multidrug transporter that confers resistance to various anticancer drugs like Adriamycin. Overexpression of BCRP confers multidrug resistance (MDR) in hepatocellular carcinoma cells and is a frequent impediment to successful chemotherapy. METHODOLOGY: We evaluated a new approach using RNA interference for the specific knockdown of BCRP in hepatocellular carcinoma cells. To overcome the BCRP-mediated atypical multidrug drug resistance, one small interfering RNA construct (RNAi) targeting one special region of BCRP gene were designed to inhibit the atypical MDR expression by transfecting them into HepG2/ADM cell lines. RESULTS: We found that the overexpression of BCRP gene was suppressed efficiently by the introduction of small interfering RNA, which caused sequence specific gene silence. The level of BCRP mRNA reduced to 22.55% after transfected by pSUPER-BCRPs compared with those of the controls. Similarly, the level of BCRP decreased too. Furthermore, the sensitivity to Adriamycin of pSUPER-BCRPs-treated HEPG2/ADM cells is increased 3.55-fold compared to their control (p<0.05). The relative reverse rate of HepG2/ADM cell to Adriamycin is 72.2%. CONCLUSIONS: These data indicated that pSUPER-BCRPs could modulate MDR and may present a new approach to overcome BCRP-mediated drug resistance in HEPG2/ADM cells. It may reverse multidrug resistance phenotype and therefore provide promising therapeutic modalities in the treatment of hepatocellular carcinoma.
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[565]
TÍTULO / TITLE: - A phase I/II pharmacokinetic and pharmacogenomic study of calcitriol in combination with cisplatin and docetaxel in advanced non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2109-x
AUTORES / AUTHORS: - Ramnath N; Daignault-Newton S; Dy GK; Muindi JR; Adjei A; Elingrod VL; Kalemkerian GP; Cease KB; Stella PJ; Brenner DE; Troeschel S; Johnson CS; Trump DL
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA, nithyar@umich.edu.
RESUMEN / SUMMARY: - BACKGROUND: Preclinical studies demonstrated antiproliferative synergy of 1,25-D(3) (calcitriol) with cisplatin. The goals of this phase I/II study were to determine the recommended phase II dose (RP2D) of 1,25-D(3) with cisplatin and docetaxel and its efficacy in metastatic non-small-cell lung cancer. METHODS: Patients were >/=18 years, PS 0-1 with normal organ function. In the phase I portion, patients received escalating doses of 1,25-D(3) intravenously every 21 days prior to docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) using standard 3 + 3 design, targeting dose-limiting toxicity (DLT) rate <33 %. Dose levels of 1,25-D(3) were 30, 45, 60, and 80 mcg/m(2). A two-stage design was employed for phase II portion. We correlated CYP24A1 tagSNPs with clinical outcome and 1,25-D(3) pharmacokinetics (PK). RESULTS: 34 patients were enrolled. At 80 mcg/m(2), 2/4 patients had DLTs of grade 4 neutropenia. Hypercalcemia was not observed. The RP2D of 1,25-D(3) was 60 mcg/m(2). Among 20 evaluable phase II patients, there were 2 confirmed, 4 unconfirmed partial responses (PR), and 9 stable disease (SD). Median time to progression was 5.8 months (95 % CI 3.4, 6.5), and median overall survival 8.7 months (95 % CI 7.6, 39.4). CYP24A1 SNP rs3787554 (C > T) correlated with disease progression (P = 0.03) and CYP24A1 SNP rs2762939 (C > G) trended toward PR/SD (P = 0.08). There was no association between 1,25-D(3) PK and CYP24A1 SNPs. CONCLUSIONS: The RP2D of 1,25-D(3) with docetaxel and cisplatin was 60 mcg/m(2) every 21 days. Pre-specified endpoint of 50 % confirmed RR was not met in the phase II study. Functional SNPs in CYP24A1 may inform future studies individualizing 1,25-D(3).
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[566]
TÍTULO / TITLE: - Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Exp Dermatol. 2013 Mar 27. doi: 10.1111/ced.12138.
●● Enlace al texto completo (gratuito o de pago) 1111/ced.12138
AUTORES / AUTHORS: - Wright TJ; McKee C; Birch-Machin MA; Ellis R; Armstrong JL; Lovat PE
INSTITUCIÓN / INSTITUTION: - Dermatological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
RESUMEN / SUMMARY: - Early-stage cutaneous squamous cell carcinoma (cSCC) has a favourable prognosis. Metastatic disease is probably associated with chemoresistance mediated through the activation of pro-survival phosphatidylinositol 3-kinase/AKT signalling. Inhibition of activated AKT partially increases chemosensitivity but induces autophagy, the principal lysosomal mechanism for the bulk degradation and recycling of proteins and damaged organelles. The aim of the current study was to test the hypothesis that combined inhibition of AKT signalling and autophagy by the lysosomal inhibitor chloroquine increases the susceptibility to docetaxel-induced apoptosis of cSCC cells isolated from a lymph-node metastasis. Combined AKT inhibition and chloroquine treatment of MET 4 cSCC cells resulted in significantly enhanced inhibition of cell viability and apoptosis induced by clinically achievable concentrations of docetaxel (P < 0.001). Inhibition of both autophagy and AKT thus represents an effective and viable therapeutic strategy to increase the cytotoxicity of docetaxel for the treatment of advanced cSCC.
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[567]
TÍTULO / TITLE: - Preparation and Biological Evaluation of [Tc/EDDA/Tricine/HYNIC, BzThi]-Octreotide for Somatostatin Receptor-Positive Tumor Imaging.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1270
AUTORES / AUTHORS: - Erfani M; Shafiei M; Mazidi M; Goudarzi M
INSTITUCIÓN / INSTITUTION: - Nuclear Science Research School, Nuclear Science and Technology Research Institute (NSTRI) , Atomic Energy Organization of Iran (AEOI), Tehran, Iran .
RESUMEN / SUMMARY: - Abstract Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with 99mTc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC0), beta-(3-benzothienyl)-Ala (BzThi3)]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N’-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with 99mTc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%+/-0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%+/-0.36% injected dose per gram tissue (%ID/g). These data show that [99mTc/EDDA/Tricine/HYNIC0, BzThi3]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.
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[568]
TÍTULO / TITLE: - ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Mar 8. doi: 10.3892/ijo.2013.1854.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1854
AUTORES / AUTHORS: - Tsunedomi R; Iizuka N; Yoshimura K; Iida M; Tsutsui M; Hashimoto N; Kanekiyo S; Sakamoto K; Tamesa T; Oka M
INSTITUCIÓN / INSTITUTION: - Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
RESUMEN / SUMMARY: - The poor prognosis of hepatocellular carcinoma (HCC) can be explained largely by the high rate of intrahepatic recurrence (IHR). Identification of genes related to IHR is needed to improve the poor prognosis and important for personalized medicine. Eighty-one HCC specimens were used in this study. We screened for IHR-related genes by DNA microarray analysis. The validation of screening was performed by using real-time PCR. The methylation levels in genomic DNAs were measured by quantitative methylation-specific PCR. Six hepatoma cell lines were used for examination of ABCB6 expressional regulation. Time-to-event analyses for recurrence after surgery were analyzed by Kaplan-Meier analysis and Cox regression analysis with cutoff values obtained from receiver operating characteristic (ROC) analysis. We confirmed that ABCB6 mRNA levels were signi-ficantly higher in hepatitis C virus (HCV)-related HCCs with early IHR compared to HCV-related HCCs without early IHR (2.5-fold, P=0.01) and the corresponding non-cancerous livers (3.1-fold, P=0.05). Experiments with cell lines showed correlation between DNA methylation and mRNA levels of ABCB6. ROC analysis revealed that mRNA levels (0.81 area under the curve, 88% sensitivity and 72% specificity) and DNA methylation levels (0.81 area under the curve, 80% sensitivity and 80% specificity) of ABCB6 in HCV-related HCCs allowed for the accurate discrimination of the development of early IHR. Cox regression analysis revealed that ABCB6 mRNA levels was an independent risk factor for IHR of HCV-related HCC. Aberrant mRNA and DNA methylation levels of ABCB6 may serve as useful predictive biomarkers for early IHR of HCV-related HCC.
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[569]
TÍTULO / TITLE: - Prognostic value of microsatellite instability in sporadic locally advanced rectal cancer following neoadjuvant radiotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Histopathology. 2013 Apr;62(5):723-30. doi: 10.1111/his.12069. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1111/his.12069
AUTORES / AUTHORS: - Du C; Zhao J; Xue W; Dou F; Gu J
INSTITUCIÓN / INSTITUTION: - Department of Colorectal Surgery, Peking University Cancer Hospital, Beijing, China.
RESUMEN / SUMMARY: - AIMS: This study was conducted to investigate the clinicopathological significance and prognostic value of microsatellite instability (MSI) in locally advanced rectal cancer (LARC) following neoadjuvant radiotherapy. METHODS AND RESULTS: A total of 316 consecutive patients with LARC who underwent neoadjuvant radiotherapy and curative surgery were included retrospectively. Microsatellite instability in pretreatment biopsy tissue was assessed using the pentaplex panel of mononucleotides. Twenty-five tumours (7.9%) were assessed as high-frequency MSI (MSI-H) and 291 were low-frequency MSI (MSI-L; n = 42) or microsatellite stable (MSS; n = 249). There were no significant differences in terms of gender, age, tumour location or pretreatment serum carcinoembryonic antigen between the MSI-H and MSI-L + MSS groups. Microsatellite instability was not associated statistically with pathological stage, radiation-induced tumour regression or downstaging. No significant difference was found in disease-free survival (DFS) between the two groups but, within the subgroup of ypN0 stage, patients with MSI-H tumours presented a significantly improved DFS compared with those with MSI-L or MSS tumours (100% versus 79.8%, P < 0.05), whereas no DFS improvement was observed for patients with MSI-H tumours in the ypN + subgroup. CONCLUSIONS: Microsatellite instability could not predict a histopathological response to neoadjuvant radiotherapy, but was a good prognostic marker for patients without lymph node metastasis after neoadjuvant radiotherapy.
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[570]
TÍTULO / TITLE: - Dietary supplementation of silymarin is associated with decreased cell proliferation, increased apoptosis, and activation of detoxification system in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 May;377(1-2):163-76. doi: 10.1007/s11010-013-1582-1. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1582-1
AUTORES / AUTHORS: - Gopalakrishnan R; Sundaram J; Sattu K; Pandi A; Thiruvengadam D
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, University of Madras, Guindy campus, Chennai, 600025, Tamil Nadu, India.
RESUMEN / SUMMARY: - Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world. HCC’s limited treatment remedies and the poor prognosis emphasize the importance in developing an effective chemoprevention for this disease. Here, we investigated the molecular mechanisms involved in the chemoprevention of silymarin in N-nitrosodiethylamine (NDEA)-induced rat model of HCC. Liver of the rats treated with NDEA showed higher proliferation index and glycoconjugates. NDEA treatment also increased the level of anti-apoptotic proteins with simultaneous decrease in the level of pro-apoptotic proteins along with increased accumulation of Cytochrome c in mitochondria. The carcinogenic insult also increased microsomal phase I metabolizing enzymes with a simultaneous decrease in the Phase II detoxifying enzyme glutathione-S-transferase (GST). Whereas dietary silymarin administration along with NDEA treatment significantly decreased the proliferation and down regulated the expression of anti-apoptotic proteins with simultaneously increased expression of pro-apoptotic proteins along with the release of Cytochrome c to cytosol there by activating the intrinsic apoptotic pathway. Silymarin administration also decreased the level of glycoproteins and activated the phase II detoxifying enzyme GST. These results demonstrate that suppression of HCC by silymarin in vivo involves inhibition of proliferation, activation of apoptosis, and efficient detoxification.
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[571]
TÍTULO / TITLE: - “Apoptotic induction by anti-CD20 antibodies in Chronic Lymphocytic Leukemia: Comparison of rituximab and obinutuzumab”
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.788175
AUTORES / AUTHORS: - Reslan L; Dalle S; Herveau S; Perrial E; Dumontet C
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[572]
TÍTULO / TITLE: - Microcystin-LR Induces Endoplasmatic Reticulum Stress and Leads to Induction of NFkappaB, Interferon-Alpha, and Tumor Necrosis Factor-Alpha.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Environ Sci Technol. 2013 Apr 2;47(7):3378-85. doi: 10.1021/es304886y. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1021/es304886y
AUTORES / AUTHORS: - Christen V; Meili N; Fent K
INSTITUCIÓN / INSTITUTION: - University of Applied Sciences and Arts Northwestern Switzerland , School of Life Sciences, Grundenstrasse 40, CH-4132 Muttenz, Switzerland.
RESUMEN / SUMMARY: - Microcystins (MCs) are hepatotoxins produced by cyanobacteria responsible for toxicity in humans and animals. Here, we investigate unexplored molecular pathways by which microcystin-LR (MC-LR) acts on hepatocytes to elucidate unknown modes of action. We focus on the endoplasmatic reticulum (ER) stress response or unfolded protein response (UPR), and on mechanisms that may contribute to the tumor-promoting effect of MCs in animals, including the activation of NFkappaB, the expression of interferon alpha (IFN-alpha) and the induction of interferon stimulated genes (ISGs), as well as the expression of tumor necrosis factor alpha (TNF-alpha). To this end, we exposed human hepatoma cells (Huh7) to 0.5 muM (nontoxic concentration), 5 muM (EC50 concentration), 25 muM and 50 muM (cytotoxic concentrations) MC-LR for 6, 24, 48, and 72 h. The expression of phosphatase 2A (PP2A) mRNA and protein was induced at 5 muM MC-LR. Phosphorylated P-CREB, a transcription factor for PP2A, leads to elevated expression of PP2A. Furthermore, all of the three ER stress pathways, the UPR and the endoplasmic reticulum-associated degradation were activated after exposure to 5, 25, and 50 muM MC-LR. Additionally, the expression of NFkappaB, IFN-alpha, and several INF-alpha-stimulated genes was strongly activated. The proinflammatory cytokine TNF-alpha was also induced. Our data demonstrate that MC-LR induces all ER stress response pathways. Consequently NFkappaB is activated, which in turn induces the expression of IFN-alpha and TNF-alpha. All of these activated pathways, which are analyzed here for the first time in detail, may contribute to the hepatotoxic, inflammatory, and tumorigenic action of MC-LR.
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[573]
TÍTULO / TITLE: - Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar;42(2):193-7. doi: 10.1097/MPA.0b013e31825e354d.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825e354d
AUTORES / AUTHORS: - Poruk KE; Firpo MA; Scaife CL; Adler DG; Emerson LL; Boucher KM; Mulvihill SJ
INSTITUCIÓN / INSTITUTION: - From the *Department of Surgery, daggerHuntsman Cancer Institute, double daggerDivision of Gastroenterology and Hepatology, Department of Internal Medicine, section signDepartment of Pathology, and parallelDepartment of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT.
RESUMEN / SUMMARY: - OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of 5%. There is an urgent need for early detection while the tumors are small and surgically resectable. We assessed serum osteopontin (OPN) and tissue inhibitor of metalloproteinase 1 (TIMP-1) as possible diagnostic and prognostic biomarkers in a novel cohort of patients with pancreatic cancer. METHODS: Osteopontin and TIMP-1 levels were determined in sera from 86 patients with PDAC, 86 healthy control subjects, and 48 patients with chronic pancreatitis. Regression models were used to relate OPN and TIMP-1 to sex, age, stage, class, and treatment. Survival analyses were performed using univariate and multivariate Cox models. RESULTS: The serum levels of both OPN and TIMP-1 distinguished PDAC from chronic pancreatitis (P </= 0.0001) and healthy control subjects (P < 0.0001). The serum levels of both OPN and TIMP-1 also distinguished early-stage resectable PDAC cases from chronic pancreatitis (P < 0.04) and healthy control subjects (P < 0.01). High serum levels of OPN were significantly correlated with reduced patient survival. CONCLUSIONS: Serum OPN and TIMP-1 have use as diagnostic biomarkers in PDAC. Our data suggest a potential benefit of using OPN, TIMP-1, and CA 19-9 in a panel to improve diagnostic accuracy in PDAC.
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[574]
TÍTULO / TITLE: - Expression Staus of Fatty Acid Synthase (FAS) but not HER2 is Correlated with the Differentiation Grade and Prognosis of Esophageal Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatogastroenterology. 2013 Jan-Feb;60(121):99-106. doi: 10.5754/hge12415.
●● Enlace al texto completo (gratuito o de pago) 5754/hge12415
AUTORES / AUTHORS: - Wu D; Xu J; Yu G; Zhang B; Wang H; Wang C; Ru G; Sun A; Shen L; Wei Q
RESUMEN / SUMMARY: - KEY WORDS: Esophageal carcinoma; Immunohistochemistry; FAS; HER2; Prognosis.
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[575]
TÍTULO / TITLE: - Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res Treat. 2013 Feb;138(1):69-79. doi: 10.1007/s10549-013-2440-2. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s10549-013-2440-2
AUTORES / AUTHORS: - Chandra-Kuntal K; Lee J; Singh SV
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 2.32A Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
RESUMEN / SUMMARY: - Diallyl trisulfide (DATS) is a structurally simple but biologically active constituent of processed garlic with in vivo activity against chemically induced as well as oncogene-driven cancer in experimental rodents. This study offers novel insights into the mechanisms underlying anticancer effects of DATS using human breast cancer cells as a model. Exposure of human breast cancer cells (MCF-7 and MDA-MB-231) and a cell line derived from spontaneously developing mammary tumor of a transgenic mouse (BRI-JM04) to DATS resulted in a dose-dependent inhibition of cell viability that was accompanied by apoptosis induction. A non-tumorigenic normal human mammary cell line (MCF-10A) was resistant to growth inhibition and apoptosis induction by DATS. The DATS-induced apoptosis in MDA-MB-231, MCF-7, and BRI-JM04 cells was associated with reactive oxygen species (ROS) production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Overexpression of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as well as Mn-SOD conferred significant protection against DATS-induced ROS production and apoptotic cell death in MDA-MB-231 and MCF-7 cells. Activation of Bak, but not Bax, resulting from DATS treatment was markedly suppressed by overexpression of Mn-SOD. The DATS treatment caused ROS generation, but not activation of Bax or Bak, in MCF-10A cells. Furthermore, the DATS-mediated inhibition of cell migration was partially but significantly attenuated by Cu,Zn-SOD and Mn-SOD overexpression in association with changes in levels of proteins involved in epithelial-mesenchymal transition. The DATS-mediated induction of heme oxygenase-1 was partially attenuated by overexpression of Mn-SOD. These results provide novel mechanistic insights indicating a critical role for ROS in anticancer effects of DATS.
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[576]
TÍTULO / TITLE: - Hepatic Arterial Infusion with Oxaliplatin and 5-FU/Folinic Acid for Advanced Biliary Tract Cancer: A Phase II Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Dis Sci. 2013 Mar 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s10620-013-2624-y
AUTORES / AUTHORS: - Sinn M; Nicolaou A; Gebauer B; Podrabsky P; Seehofer D; Ricke J; Dorken B; Riess H; Hildebrandt B
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology and Haematology, Charite-School of Medicine Berlin, Charite-Universitatsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany, marianne.sinn@charite.de.
RESUMEN / SUMMARY: - BACKGROUND: Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer (BTC) has been established recently. However, overall prognosis is still poor, and additional therapeutic approaches are needed for patients with locally advanced, irresectable and/or pretreated tumors. Hepatic arterial infusion (HAI) of chemotherapy represents a safe and well-established treatment modality, but data on its use in patients with BTC are still sparse. METHODS: Patients with irresectable BTC predominant to the liver were included in a prospective, open phase II study investigating HAI provided through interventionally implanted port catheters. Intraarterial chemotherapy consisted of biweekly oxaliplatin (O) 85 mg/m2 and folinic acid (F) 170 mg/m2 with 5-FU (F) 600 mg/m2. RESULTS: Between 2004 and 2010, 37 patients were enrolled. A total of 432 cycles of HAI were applied with a median of 9 (range 1-46) cycles. Objective response rate was 16 %, and tumor control was achieved in 24 of 37 (65 %) patients. Median progression-free survival was 6.5 months (range 0.5-26.0; 95 % CI 4.3-8.7), median overall survival was 13.5 (range 0.9-50.7; 95 % CI 11.1-15.9) months. The most frequent adverse event was sensory neuropathy grade ½ in 10/14 patients. CONCLUSIONS: Using a minimal invasive technique, repetitive HAI with OFF is feasible and results in clinically relevant tumor control with low toxicity in patients with liver predominant advanced BTC.
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[577]
TÍTULO / TITLE: - Homoharringtonine and granulocyte colony-stimulating factor priming for acute myeloid leukemia: is it ready for prime time?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.776169
AUTORES / AUTHORS: - Al Ustwani O; Wetzler M
INSTITUCIÓN / INSTITUTION: - Leukemia Section, Department of Medicine, Roswell Park Cancer Institute , Buffalo, NY , USA.
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[578]
TÍTULO / TITLE: - Arginine homozygosity in codon 72 of p53 correlates with failure to imatinib response in chronic myeloid leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Pharmacother. 2013 Mar;67(2):103-7. doi: 10.1016/j.biopha.2012.11.004. Epub 2012 Nov 23.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biopha.2012.11.004
AUTORES / AUTHORS: - Camelo-Santos J; do Prado Barbosa A; de Paula Silveira-Lacerda E; Guillo LA
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, Biological Sciences Institute, Universidade Federal de Goias, Campus II, Jardim Samambaia, CP 131, 74001-970, Goiania GO, Brazil.
RESUMEN / SUMMARY: - PURPOSE: In this study, the role of the polymorphism at codon 72 of tumor protein p53 gene (TP53) was investigated regarding the response to treatment with imatinib in chronic myeloid leukemia (CML). METHODS: A total of 85 patients with CML were treated according to the Brazilian National Cancer Institute (INCA) guidelines and at the end of the 18th month a blood sample were collected for genotyping. Genomic DNA was extracted and TP53 codon 72 genotyping was performed by allele-specific polymerase chain reaction (AS-PCR), which detects argine or proline alleles. RESULT: Of the 85 CML samples, 27 samples were homozygous for arginine (Arg/Arg), 12 homozygous for proline (Pro/Pro) and 46 samples heterozygous (Arg/Pro). TP53 codon 72 polymorphism was in Hardy-Weinberg equilibrium (chi=1.17, P=0.37). We did not find significant association between codon 72 polymorphism and age at diagnosis and sex (P=0.76 and P=0.33, respectively). High Sokal score are significantly associated with Arg/Arg genotype carriers (Odds ratio, OR=4.09; 95% confidence interval, CI 1.01=15.89; P=0.036). The arginine allele in homozygosis also have an increased risk of failure response to imatinib when compared with both, the heterozygous (Arg/Pro) and proline homozygous patients (P=0.021; OR=2.99, 95% CI=1.16-7.67). Additionally, interaction analysis with age at diagnosis revealed that among patients over 40-yr old, Arg/Arg genotype was significantly associated with non-responder patients (P=0.007; OR=5.13, 95% CI=1.5-17.55). CONCLUSION: The findings suggest that in CML patients, TP53 codon 72 polymorphism may contribute to a high Sokal score and failure to imatinib treatment.
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[579]
TÍTULO / TITLE: - Selective aminopeptidase-N (CD13) inhibitors with relevance to cancer chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem. 2013 Apr 1;21(7):2135-44. doi: 10.1016/j.bmc.2012.12.038. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmc.2012.12.038
AUTORES / AUTHORS: - Schmitt C; Voegelin M; Marin A; Schmitt M; Schegg F; Henon P; Guenot D; Tarnus C
INSTITUCIÓN / INSTITUTION: - Universite de Haute-Alsace, Ecole Nationale Superieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue Alfred Werner, 68093 Mulhouse Cedex, France.
RESUMEN / SUMMARY: - Aminopeptidase-N (APN/CD13) is highly expressed on the surface of numerous types of cancer cells and particularly on the endothelial cells of neoangiogenic vessels during tumourigenesis. This metallo-aminopeptidase has been identified as a potential target for cancer chemotherapy. In this work, we evaluated the efficacy of a novel series of benzosuberone analogues, which were previously reported to be highly potent, selective APN inhibitors with Ki values in the micromolar to sub-nanomolar range. Endothelial cell morphogenesis as well as cell motility were inhibited in vitro in a dose-dependent manner at concentrations that correlated with the potency of the compounds, thus confirming the key role of APN in these established models of angiogenesis. We report toxicity studies in mice showing that these compounds are well tolerated. We report the effects of the compounds, used alone or in combination with rapamycin, on the growth of a select panel of tumours that were subcutaneously xenografted onto Swiss nude mice. Our data indicate that the in vivo efficacy of these new APN inhibitors during the initial phase of tumour growth can be ascribed to their anti-angiogenic activities. However, we also provide evidence that these compounds are effective against established solid tumours. For colonic tumours, the anti-tumour effect depends on the level of APN expression in epithelial cells, and APN expression is associated with down-regulation of the transcription factor HIF-1alpha. These effects seem to be distinct from those of rapamycin. Our finding that the anti-tumour effect of the inhibitors in the colon requires APN expression strongly suggests that APN plays a crucial function in tumour cells that is distinct from its known role in neovascularisation.
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[580]
TÍTULO / TITLE: - Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 5. doi: 10.3892/or.2013.2327.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2327
AUTORES / AUTHORS: - Hoffmann M; Quabius ES; Tribius S; Hebebrand L; Gorogh T; Halec G; Kahn T; Hedderich J; Rocken C; Haag J; Waterboer T; Schmitt M; Giuliano AR; Kast WM
INSTITUCIÓN / INSTITUTION: - Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, D-24105 Kiel, Germany.
RESUMEN / SUMMARY: - We previously showed that secretory leukocyte protease inhibitor (SLPI) gene and protein expression is significantly lower in metastatic versus non-metastatic head and neck squamous cell carcinoma (HNSCC). However, we did not assess the human papillomavirus (HPV) status of these cases. Since SLPI plays a role in HIV and herpes simplex virus (HSV) infections, we hypothesized that SLPI may be involved in HPV-infected HNSCC. In HNSCC tissue (n=54), HPV DNA was determined and correlated with SLPI expression. Additionally, to investigate a possible role of smoking on SLPI expression in clinically normal mucosa, 19 patients treated for nonmalignant diseases (non-HNSCC) were analyzed for SLPI expression and correlated with smoking habits. In HNSCC patients, SLPI expression showed a significant inverse correlation with HPV status. In patients with moderate/strong SLPI expression (n=19), 10.5% were HPV-positive. By contrast, patients with absent/weak SLPI expression (n=35), 45.7% were HPV-positive. Low SLPI expression was correlated with metastasis (P=0.003) independent of HPV status. HPV-positivity was clearly associated with lymph node status (81.3% N1-3 cases). In smoking non-HNSCC patients (n=7), 42.9% showed absent/weak and 57.1% moderate/strong SLPI staining. In non-smoking non-HNSCC patients (n=10) 83.3% showed absent/weak and 16.7% moderate/strong SLPI expression. For the first time, a correlation between SLPI downregulation and HPV infection was demonstrated, suggesting that high levels of SLPI, possibly induced by environmental factors such as tobacco smoking, correlate with protective effects against HPV infection. SLPI may be a potential biomarker identifying head and neck cancer patients not at risk of developing metastases (SLPI-positive), and those at risk to be infected by HPV (SLPI-negative) and likely to develop metastases.
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[581]
TÍTULO / TITLE: - Visfatin, a potential biomarker and prognostic factor for endometrial cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gynecol Oncol. 2013 Feb 22. pii: S0090-8258(13)00093-0. doi: 10.1016/j.ygyno.2013.02.022.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ygyno.2013.02.022
AUTORES / AUTHORS: - Tian W; Zhu Y; Wang Y; Teng F; Zhang H; Liu G; Ma X; Sun D; Rohan T; Xue F
INSTITUCIÓN / INSTITUTION: - Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
RESUMEN / SUMMARY: - OBJECTIVE: Visfatin, a newly discovered adipocytokine, is thought to play a role in the pathogenesis of metabolic-syndrome-related cancers. The aim of this study was to assess the clinical significance of serum levels and tissue expression of visfatin in relation to endometrial cancer (EC). METHODS: A total of 234 EC patients were included in this study. Serum visfatin, metabolic and anthropometric parameters were measured in EC patients and controls. Serum visfatin levels were detected using ELISA. Tissue expression of visfatin was analyzed using immunohistochemistry in tissue microarrays. The correlation between clinicopathological variables and visfatin in EC tissues and the prognostic value of visfatin for overall survival was evaluated. RESULTS: Serum levels of visfatin were significantly higher in EC patients than in controls (P<0.05). In univariate and multivariate logistic regression models, a positive association between EC and serum visfatin, BMI, waist-to-hip ratio, diabetes, and hypertension was evident (P<0.05). Visfatin expression was significantly higher in EC tissue than in normal endometrial tissue (P=0.001). Moreover, serum visfatin levels were significantly positively correlated with tissue expression of visfatin in EC patients (P<0.05). High visfatin expression in EC tissues was significantly associated with advanced FIGO stage (P=0.016) and myometrial invasion >/=1/2 (P=0.023). The overall survival rate of EC patients was significantly higher in the group with negative visfatin expression than with positive visfatin expression (P=0.035). CONCLUSIONS: Visfatin is a potential serum biomarker and prognostic factor for EC that may indicate high risk for EC and EC progression. It may also be a novel potential therapeutic target for EC.
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[582]
TÍTULO / TITLE: - Insulin-like growth factor receptor polymorphism defines clinical outcome in estrogen receptor-positive breast cancer patients treated with tamoxifen.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacogenomics J. 2013 Mar 5. doi: 10.1038/tpj.2013.8.
●● Enlace al texto completo (gratuito o de pago) 1038/tpj.2013.8
AUTORES / AUTHORS: - Winder T; Giamas G; Wilson PM; Zhang W; Yang D; Bohanes P; Ning Y; Gerger A; Stebbing J; Lenz HJ
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.
RESUMEN / SUMMARY: - Compelling evidence points to a key role for insulin-like growth factor 1 (IGF1) signaling in breast cancer development and progression. In addition, IGF1 receptor (IGF1R) expression has been correlated and functionally linked with estrogen receptor (ER) signaling. Recent translational studies support a cross talk between IGF1R and ERalpha at different levels and data suggest enhanced IGF1R signaling as a causative mechanism of tamoxifen (TAM) resistance. We tested whether functional germline variations in the IGF pathway are associated with clinical outcome in ER-positive primary invasive breast cancer patients, who were treated with surgery and adjuvant TAM. Tissue samples of 222 patients with ER+ primary invasive breast cancer, who had undergone surgery at Charing Cross Hospital, London, UK between 1981 and 2003, were analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue samples and six functional IGF1 pathway polymorphisms were analyzed using direct DNA sequencing and PCR-restriction fragment length polymorphism. In multivariable analysis, patients with primary invasive breast cancer carrying IGF1R_rs2016347 G allele had a significantly increased risk of early tumor progression (hazard ratio (HR) 2.01; adjusted P=0.004) and death (HR 1.84; adjusted P=0.023) compared with patients carrying G/T or T/T, independent of established clinicopathological determinants. This association remained significant after adjusting for multiple testing. In addition, we were able to demonstrate that IRS1_rs1801123 and IGFBP3_rs2854744 were significantly associated with lymph node involvement and tumor size, respectively. We provide the first evidence for IGF1R_rs2016347 as an independent prognostic marker for ER+ breast cancer patients treated with TAM and support a rational for combined treatment strategies.The Pharmacogenomics Journal advance online publication, 5 March 2013; doi:10.1038/tpj.2013.8.
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[583]
TÍTULO / TITLE: - The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Immunobiology. 2013 Jan 7. pii: S0171-2985(13)00004-1. doi: 10.1016/j.imbio.2012.12.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.imbio.2012.12.002
AUTORES / AUTHORS: - Bae S; Oh K; Kim H; Kim Y; Kim HR; Hwang YI; Lee DS; Kang JS; Lee WJ
INSTITUCIÓN / INSTITUTION: - Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - Alloferon is a novel immunomodulatory peptide originally isolated from infected insects. It has anti-viral and anti-tumor effects via the activation of NK cells. However, specific mechanisms leading to NK cell activation and anti-tumor responses yet to be clarified. In this study, we demonstrate that alloferon increases killing activity of NK cells to cancer cells via the up-regulation of the expression of NK-activating receptors, 2B4. In addition, the production of IFN-gamma and TNF-alpha and granule exocytosis from NK cells against cancer cell were increased by alloferon. Lastly, the anti-tumor effect of alloferon was confirmed in vivo to demonstrate effective retardation of tumor growth in the human-to-mouse xenograft model. All taken together, these results suggest that alloferon has anti-tumor effects through up-regulation of NK-activating receptor 2B4 and the enhancement of granule exocytosis from NK cells.
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[584]
TÍTULO / TITLE: - Tumor necrosis factor-related apoptosis-inducing ligand promotes microvascular endothelial cell hyperpermeability through phosphatidylinositol 3-kinase pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Surg. 2013 Apr;205(4):419-25. doi: 10.1016/j.amjsurg.2012.10.027. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1016/j.amjsurg.2012.10.027
AUTORES / AUTHORS: - Stagg HW; Bowen KA; Sawant DA; Rodriguez M; Tharakan B; Childs EW
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Texas A&M Health Science Center College of Medicine and Scott & White Memorial Hospital, 702 SW H.K. Dodgen Loop, Temple, TX 76504, USA.
RESUMEN / SUMMARY: - BACKGROUND: Microvascular hyperpermeability that occurs in hemorrhagic shock and burn trauma is regulated by the apoptotic signaling pathway. We hypothesized that tumor necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand (TRAIL) would promote hyperpermeability directly or by interacting with other signaling pathways. METHODS: Rat lung microvascular endothelial cells (RLMECs) grown on Transwell membranes (Corning Life Sciences, Lowell, MA) were treated with recombinant human TRAIL (10, 50, and 100 ng/mL) for 6 hours or TRAIL (100 ng/mL) + LY294002 (a PI3K inhibitor; 20 mumol/L), Z-DEVD-FMK (a caspase-3 inhibitor; 10 mumol/L), or the inhibitors alone. Fluorescein isothiocyanate (FITC)-albumin flux was an indicator of permeability. Caspase-3 activity was measured fluorometrically. Adherens junction integrity was studied using beta-catenin immunofluorescence. RESULTS: TRAIL + LY294002, but not TRAIL alone, induced monolayer hyperpermeability (P < .05), and caspase-3 activity (P < .05), and disrupted the adherens junctions. Z-DEVD-FMK attenuated hyperpermeability and protected the adherens junctions. CONCLUSIONS: TRAIL-induced microvascular hyperpermeability is phosphatidylinositol 3-kinase (PI3K)-dependent and may be mediated by caspase-3 cleavage of the endothelial adherens junctional complex.
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[585]
TÍTULO / TITLE: - Genetic variants in AR and SHBG and resistance to hormonal castration in prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Mar;30(1):490. doi: 10.1007/s12032-013-0490-2. Epub 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0490-2
AUTORES / AUTHORS: - Monteiro C; Sousa MV; Ribeiro R; Mauricio J; Fraga A; Medeiros R
INSTITUCIÓN / INSTITUTION: - Molecular Oncology Group-CI, Portuguese Institute of Oncology, Edificio Laboratorios-Piso 4, Rua Dr Antonio Bernardino Almeida, 4200-072 Porto, Portugal. catiapmonteiro@gmail.com
RESUMEN / SUMMARY: - Castration resistance is a life-threatening event that may develop in prostate cancer patients with advanced disease following hormonal castration therapy (HCT). Current understanding of the molecular mechanisms behind resistance to hormonal castration suggests a role for androgen receptor signaling and bioavailability of androgens. We evaluated whether common functional polymorphisms in AR and SHBG genes associate with response to HCT. The study included 203 prostate cancer patients with advanced disease treated with hormonal castration. Genomic DNA was isolated from whole blood, and the genetic polymorphisms AR +1733 G>A and SHBG +5790 G>A were determined by real-time PCR. Genetic variants were associated with response to treatment and time to resistance to hormonal castration. Multivariate analysis showed increased risk of developing resistance to hormonal castration in homozygous GG carriers of the SHBG +5790 G>A (HR = 1.9, 95 % CI 1.1-3.3, P = 0.019) polymorphism alone and when functionally combined with AR +1733 G>A into a high AR pathway activation genetic profile (HR = 1.9, 95 % CI 1.1-3.1, P = 0.015), after adjustment for age, PSA, Gleason’s score and clinical stage. Our results suggest that the SHBG +5790 G>A polymorphism may be a useful marker to include in the pharmacogenomic profile of prostate cancer resistant to hormonal castration.
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[586]
TÍTULO / TITLE: - The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Dermatol. 2013 Feb;22(2):119-24. doi: 10.1111/exd.12086.
●● Enlace al texto completo (gratuito o de pago) 1111/exd.12086
AUTORES / AUTHORS: - Dobbeling U; Waeckerle-Men Y; Zabel F; Graf N; Kundig TM; Johansen P
INSTITUCIÓN / INSTITUTION: - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
RESUMEN / SUMMARY: - Mycosis fungoides and its leukaemic counterpart Sezary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients with Sezary syndrome were cultured with antihistamines, and the cell were analysed for proliferation, apoptosis and expression of programmed death molecules and transcription factors. The two antihistamines clemastine and desloratadine, currently used for symptom alleviation in allergy, induced potent reduction of the activities of the constitutively active transcription factors c-Myc, STAT3, STAT5a and STAT5b in mycosis fungoides and Sezary syndrome cell lines. This inhibition was followed by apoptosis and cell death, especially in the Sezary syndrome-derived cell line Hut78 that also showed increased expression of the programmed death-1 (PD-1) after clemastine treatment. In lymphocytes isolated from Sezary syndrome patients, the CD4-positive fraction underwent apoptosis after clemastine treatment, while CD4-negative lymphocytes were little affected. Because both c-Myc and STAT transcription factors are highly expressed in proliferating tumours, their inhibition by clemastine, desloratadine and other inhibitors could complement established chemotherapies not only for cutaneous T-cell lymphomas but perhaps also other cancers.
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[587]
TÍTULO / TITLE: - Expression of Hepatocyte growth factor activator inhibitor type-1 (HAI-1) in prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):575-81.
AUTORES / AUTHORS: - Yasuda K; Komiya A; Watanabe A; Morii A; Oya T; Nagakawa O; Fujiuchi Y; Fuse H
INSTITUCIÓN / INSTITUTION: - Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Hepatocyte growth factor activator inhibitor type-1 (HAI-1) inhibits hepatocyte growth factor activator and matriptase. In the present study it was investigated whether the expression of HAI-1 is associated with the progression of prostate cancer. PATIENTS AND METHODS: The expression of HAI-1 was evaluated by immunohistochemistry (IHC) of samples from 51 patients with negative prostate biopsies and 75 patients with untreated prostate cancer. Furthermore, the expression of HAI-1 was evaluated in 24 patients with castration-resistant prostate cancer (CRPC), and the relationship between HAI-1 expression and the prostate-specific antigen (PSA) progression-free rate was investigated. RESULTS: Expression of HAI-1 by IHC in patients with prostate cancer was significantly higher than in those with negative prostate biopsy. CRPC exhibited significantly lower HAI-1 expression than untreated metastatic prostate cancer. The PSA progression-free rate was worse in patients without HAI-1 expression than in those with positive HAI-1 expression. CONCLUSION: It is suggested that HAI-1 may play an important role in the pathogenesis of CRPC.
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[588]
TÍTULO / TITLE: - Induction of pancreatic cancer cell apoptosis, invasion, migration, and enhancement of chemotherapy sensitivity of gemcitabine, 5-FU, and oxaliplatin by hnRNP A2/B1 siRNA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e3283608bc5
AUTORES / AUTHORS: - Gu WJ; Liu HL
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, the Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
RESUMEN / SUMMARY: - We investigated the effects of inhibiting heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) expression on apoptosis, invasion, migration, and the chemotherapy sensitivity of pancreatic cancer cells to gemcitabine, 5-FU, and oxaliplatin chemotherapy using small interfering RNA (siRNA). Chemically synthesized siRNA hnRNP A2/B1 was transfected into the human pancreatic cancer cell lines SW1990 and BxPC-3. The IC50 of gemcitabine, 5-FU, and oxaliplatin was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and cycle were detected using flow cytometry. The expressions of apoptosis-related genes, p53, Bax, Bcl-2, TRAIL, Survivin, multidrug resistance 1 (MDR1), E-cadherin, and matrix metalloproteinases-2 (MMP-2) were detected using real-time PCR and western blot. Plate colony formation assay, wound scratch assay, invasion, and migration were also examined. Gemcitabine, 5-FU, and oxaliplatin inhibit the proliferation of SW1990 and BxPC-3 cells in a concentration-dependent manner. Inhibition of hnRNP A2/B1 expression significantly reduced the IC50 of gemcitabine, 5-FU, and oxaliplatin (P<0.01). hnRNP A2/B1 siRNA combined with gemcitabine, 5-FU and Oxaliplatin significantly increased (P<0.01) apoptosis of pancreatic cancer cell lines SW1990 and BxPC-3, increased the expression level of Bax mRNA, decreased Bcl-2 mRNA and MDR1 mRNA expression (P<0.01), and induced no change in p53, TRAIL, and Survivin mRNA expression in SW1990. In the western blot analysis, the expression level of Bax protein increased (P<0.01); the expression of both P-glycoprotein (Pg-p) protein and Bcl-2 protein decreased (P<0.01). Silencing hnRNP A2/B1 decreased invasion and migration in the cell line SW1990. Silencing hnRNP A2/B1 in SW1990 also correlated with an increase in E-cadherin expression and a decrease in MMP-2 expression at the same time. Inhibition of hnRNP A2/B1 expression can induce apoptosis in pancreatic cancer cells and improve chemosensitivity to gemcitabine, 5-FU, and oxaliplatin. hnRNP A2/B1 may play a role in invasion and migration in the pancreatic cancer cell line SW1990 through the regulation of E-cadherin and expression of MMP-2.
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[589]
TÍTULO / TITLE: - Increased detection rates of EGFR and KRAS mutations in NSCLC specimens with low tumour cell content by 454 deep sequencing.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Virchows Arch. 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1007/s00428-013-1376-6
AUTORES / AUTHORS: - Moskalev EA; Stohr R; Rieker R; Hebele S; Fuchs F; Sirbu H; Mastitsky SE; Boltze C; Konig H; Agaimy A; Hartmann A; Haller F
INSTITUCIÓN / INSTITUTION: - Department of Pathology, University Medical Center, Erlangen, Germany.
RESUMEN / SUMMARY: - Detection of activating EGFR mutations in NSCLC is the prerequisite for individualised therapy with receptor tyrosine kinase inhibitors (TKI). In contrast, mutant downstream effector KRAS is associated with TKI resistance. Accordingly, EGFR mutation status is routinely examined in NSCLC specimens, but the employed methods may have a dramatic impact on the interpretation of results and, consequently, therapeutic decisions. Specimens with low tumour cell content are at particular risk for false-negative EGFR mutation reporting by sequencing with Sanger chemistry. To improve reliability of detecting clinically relevant mutant variants of EGFR and KRAS, we took full advantage of 454 deep sequencing and developed a two-step amplification protocol for the analysis of EGFR exons 18-21 and KRAS exons 2 and 3. We systematically addressed the sensitivity, reproducibility and specificity of the developed assay. Mutations could be reliably identified down to an allele frequency of 0.2-1.5 %, as opposed to 10-20 % detection limit of Sanger sequencing. High reproducibility (0-2.1 % variant frequency) and very low background level (0.4-0.8 % frequency) further complement the reliability of this assay. Notably, re-evaluation of 16 NSCLC samples with low tumour cell content </=40 % and EGFR wild type status according to Sanger sequencing revealed clinically relevant EGFR mutations at allele frequencies of 0.9-10 % in seven cases. In summary, this novel two-step amplification protocol with 454 deep sequencing is superior to Sanger sequencing with significantly increased sensitivity, enabling reliable analysis of EGFR and KRAS in NSCLC samples independent of the tumour cell content.
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[590]
TÍTULO / TITLE: - Prognostic Vascular Imaging Biomarkers in High-Grade Gliomas: Tumor Permeability as an Adjunct to Blood Volume Estimates.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acad Radiol. 2013 Apr;20(4):478-85. doi: 10.1016/j.acra.2012.11.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.acra.2012.11.011
AUTORES / AUTHORS: - Jain R; Narang J; Griffith B; Bagher-Ebadian H; Scarpace L; Mikkelsen T; Littenberg B; Schultz LR
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202; Department of Neurosurgery, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202. Electronic address: rajanj@rad.hfh.edu.
RESUMEN / SUMMARY: - RATIONALE AND OBJECTIVES: Despite recent advances in the treatment of high-grade gliomas, overall survival (OS) remains poor, which underlines the importance of searching for and determining prognostic imaging biomarkers. The purpose of our retrospective study was to correlate patient survival with relative cerebral blood volume (rCBV) and permeability surface area-product (PS) measured using perfusion computed tomography (PCT) in patients with high-grade gliomas. METHODS: This study was composed of 54 patients with high-grade gliomas (World Health Organization [WHO] grade III, n = 14; WHO grade IV, n = 40) who underwent pretreatment PCT. Kaplan-Meier survival estimates were computed to describe OS for patients with high-versus-low PCT parameters, as well as grade III and IV gliomas. RESULTS: Differences in OS between high and low rCBV, PS, and rCBV + PS were significant (P < .001) for all high-grade gliomas. After adjustment for WHO grade, rCBV (P = .041) and rCBV + PS (P = .013) estimates remained significant, whereas PS estimates were not (P = .214). PS estimates showed a statistically significant difference for OS in the grade III glioma group (P = .011), whereas for grade IV gliomas, rCBV estimates were statistically significant (P = .019). rCBV + PS was statistically significant for OS in both grade III (P = .001) and grade IV (P = .004) glioma groups. CONCLUSIONS: Blood volume and permeability estimates measured using PCT can help predict survival in patients with high-grade gliomas. Patients with high PCT parameters showed worse OS compared to the patients with low PCT. Both rCBV and rCBV + PS remained statistically significant even after adjustment for WHO grade, suggesting these may be better predictors of OS than histological grade.
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[591]
TÍTULO / TITLE: - A liquid crystal-related compound induces cell cycle arrest at the G2/M phase and apoptosis in the A549 human non-small cell lung cancer cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1205-11. doi: 10.3892/ijo.2013.1804. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1804
AUTORES / AUTHORS: - Wakasaya T; Yoshino H; Fukushi Y; Yoshizawa A; Kashiwakura I
INSTITUCIÓN / INSTITUTION: - Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
RESUMEN / SUMMARY: - Liquid crystals are the state of matter existing between liquid and crystalline phases, and recently there has been increasing interest in their biological effects. Following our recently reported work, we investigated the cell suppressive effects of liquid crystal-related compounds (LCRCs), which are precursors of liquid crystals, in the human non-small lung cancer cell line A549. We found that 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl)pyrimidine (LCRC-1) dramatically suppressed cell growth. Treatment with 12 microM LCRC-1 for 12 h induced cell cycle arrest at the G2/M phase. Furthermore, LCRC-1 increased the sub-G1 fraction and Annexin V-positive cells and activated caspase-3 in A549 cells, which showed that it can induce apoptosis in these cells. Furthermore, because the induction of apoptosis by LCRC-1 was partly inhibited by treatment with pan-caspase inhibitor, it appeared that LCRC-1 induced apoptosis by a caspase-dependent pathway. The ability of LCRC-1 to cause DNA damage was assessed, but LCRC-1 did not induce expression of gamma-H2AX, which is a marker of DNA damage. Treatment with LCRC-1 did not inhibit the proliferation of WI-38 normal fibroblast cells, which makes the tumor-specific suppressive effect of LCRC-1 attractive for its application as a new antitumor drug.
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[592]
TÍTULO / TITLE: - IDH mutation analysis in gliomas as a diagnostic and prognostic biomarker.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Neurosurg. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 3109/02688697.2013.771139
AUTORES / AUTHORS: - Kurian KM; Haynes HR; Crosby C; Hopkins K; Williams M
INSTITUCIÓN / INSTITUTION: - Neuropathology and Neurosurgery, Frenchay Hospital , Bristol , UK.
RESUMEN / SUMMARY: - Introduction. There is a high rate of IDH1/2 mutations in low grade gliomas and in high grade gliomas deriving from them. IDH analysis of gliomas is a novel method of classification and an independent prognostic marker. We compared antibody and sequencing methods for the detection of IDH mutations. Method. 88 samples from 74 patients were identified. For immunohistochemistry: sections were stained with anti-IDH1R132H antibody. For sequencing: DNA was extracted from fresh, frozen tissue. Results. 28% (20/71) of cases were positive for the R132H IDH1 mutation by antibody. An IDH1 mutation was detected by molecular genetics in 37% (21/57) of cases and no IDH2 mutations were detected. 24% (5/21) had rare IDH1 mutations not detected by immunohistochemistry. Where sufficient tissue was available, immunohistochemistry and DNA analysis were fully concordant for the p.Arg132His mutation. Both Grade II gliomas and anaplastic astrocytomas showed a statistically different distribution of IDH1 mutation load compared to GBMs (p < 0.0001; p = 0.0021 respectively). Conclusion. A rationalised combined approach involving R132H antibody testing and sequencing of negative cases would be ideal for the detection of IDH1 mutations - antibody testing is cheaper than sequencing but sequencing demonstrates rare IDH1 mutations not detected by immunohistochemistry.
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[593]
TÍTULO / TITLE: - Lack of Prognostic Significance of Neuroendocrine Differentiation and Stem Cell Antigen Co-Expression in Resected Early-stage Non-small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):981-90.
AUTORES / AUTHORS: - Gottschling S; Jensen K; Herth FJ; Thomas M; Schnabel PA; Herpel E
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Oncology, Thorax Clinic/University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany. sandra.gottschling@thoraxklinik-heidelberg.de.
RESUMEN / SUMMARY: - BACKGROUND: Neuroendocrine (NE) carcinomas of the lung exhibit expression of various stem cell antigens, and except for carcinoid tumours, carry a poor prognosis. Despite the fact that 10%-30% of all non-small cell lung carcinomas (NSCLC) which are not classified as NE carcinomas also show expression of NE markers, data on their prognostic significance are conflicting and analyses of the expression and relevance of stem cell antigens in this subgroup are lacking. MATERIALS AND METHODS: Tissue specimens of 100 resected early-stage NSCLC were analyzed by immunohistochemistry for the expression and prognostic significance of NE markers. Moreover, the subgroup of NSCLC with NE differentiation (ND) were assessed for the expression and prognostic significance of the stem cell antigens CD117, CD133 and breast cancer resistance protein-1 (ABCG2). RESULTS: ND correlated significantly with adenocarcinoma histology (p=0.035), but not with prognosis. In the subgroup of ND-NSCLC (n=80), the stem cell antigens CD117, CD133 and ABCG2 were expressed in 51%, 14% and 33% of the cases, but likewise, showed no association with prognosis or clinicopathological characteristics. CONCLUSION: This study indicates that neither ND, nor co-expression of the stem cell antigens CD117, CD133 or ABCG2, have a prognostic significance in resected early-stage NSCLC.
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[594]
TÍTULO / TITLE: - Proteasome inhibition as a novel mechanism of the proapoptotic activity of gamma-secretase inhibitor I in cutaneous T-cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Dermatol. 2013 Mar;168(3):504-12. doi: 10.1111/bjd.12071.
●● Enlace al texto completo (gratuito o de pago) 1111/bjd.12071
AUTORES / AUTHORS: - Biskup E; Kamstrup MR; Manfe V; Gniadecki R
INSTITUCIÓN / INSTITUTION: - Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, Copenhagen-2400, Denmark.
RESUMEN / SUMMARY: - Background We have previously discovered that Notch1 is expressed on malignant T cells in cutaneous T-cell lymphoma (CTCL), and is required for survival of CTCL cell lines. Notch can be inhibited by gamma-secretase inhibitors (GSIs), which differ widely in their ability to induce apoptosis in CTCL. Objectives To investigate whether GSI-I, in addition to inhibiting Notch, induces apoptosis in CTCL by proteasome inhibition, as GSI-I is very potent and has structural similarity to the proteasome inhibitor MG-132. Methods Cell lines derived from CTCL (MyLa, SeAx, JK, Mac1 and Mac2a) were treated with GSI-I and two other proteasome inhibitors (MG-132 and bortezomib). The effects on cell viability, apoptosis and proteasome activity were measured, as was the impact on the prosurvival, nuclear factor kappaB (NF-kappaB) pathway. Results In CTCL, GSI-I had proteasome-blocking activity with a potency comparable to the proteasome inhibitors MG-132 and bortezomib. Proteasome inhibition was the main mechanism responsible for GSI-I-induced cell death, as tiron, a compound known to reverse the effect of MG-132, restored proteasome activity and largely abrogated the cytotoxic effect of GSI-I. Although inactivation of NF-kappaB is an important mechanism of action for proteasome inhibitors, we demonstrated an apparent activation of NF-kappaB. Furthermore, we showed that while the tumour suppressor protein p53 was induced during proteasome inhibition, it was dispensable for CTCL apoptosis, as both SeAx cells, which harbour p53 mutations that attenuate the apoptotic capacity, and HuT-78 cells, which have a deleted p53 gene, demonstrated potent apoptotic response. Conclusions GSI-I represents an interesting drug with a dual mechanism of action comprising inhibition of both Notch and the proteasome.
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[595]
TÍTULO / TITLE: - Concomitant overexpression of EGFR and CXCR4 is associated with worse prognosis in a new molecular subtype of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1524-32. doi: 10.3892/or.2013.2254. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2254
AUTORES / AUTHORS: - Al Zobair AA; Al Obeidy BF; Yang L; Yang C; Hui Y; Yu H; Zheng F; Yang G; Xie C; Zhou F; Zhou Y
INSTITUCIÓN / INSTITUTION: - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China.
RESUMEN / SUMMARY: - Although the relationships between CXCR4 and EGFR expression and survival in nonsmall cell lung cancer (NSCLC) have been studied independently, dual CXCR4/EGFR tumor status and its relationship with survival has not been previously investigated. In the present study, we examined the relationship between CXCR4 expression, EGFR expression and dual CXCR4/EGFR expression and survival in patients with NSCLC (n=125) using immunohistochemical techniques. Overall survival was estimated using Kaplan-Meier and Cox proportional hazards models adjusting for patient age, tumor stage and type of treatments. Patients with CXCR4-positive tumors were significantly associated with distant metastasis and tended to have poorer prognosis compared to patients with CXCR4-negative tumors (HR=2.172, 95% CI=1.2293.839). No significant association between EGFR expression and survival was found; however co-expression of CXCR4/EGFR was a significant prognostic factor of worse overall survival (HR=2.741, 95% CI=1.3305.741). Furthermore, we showed that EGF enhanced the expression of CXCR4 in NSCLC cells through the PI-3K pathway, and treatment of NSCLC cells with EGFR phosphorylation inhibitor, AG1478, resulted in downregulation of the expression of CXCR4. These results suggest an important interaction between CXCR4 and EGFR intra-cellular pathways that may activate signals of tumor progression and may provide a valid explanation for the poor overall survival rate of patients whose co-expression of CXCR4 and EGFR is detected in tissue sections. Based on EGFR and CXCR4 expression, new molecular subtypes of NSCLC established in the present study can be used for customization of NSCLC treatment. Our results also showed that EGFR and CXCR4 are potential therapeutic targets for NSCLC and that simultaneous inhibition of EGFR and CXCR4 in NSCLC patients with concomitant expression of both CXCR4 and EGFR may be an effective treatment strategy.
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[596]
TÍTULO / TITLE: - Characteristics of fatty acid distribution is associated with colorectal cancer prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prostaglandins Leukot Essent Fatty Acids. 2013 Mar 2. pii: S0952-3278(13)00046-X. doi: 10.1016/j.plefa.2013.02.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.plefa.2013.02.005
AUTORES / AUTHORS: - Zhang J; Zhang L; Ye X; Chen L; Zhang L; Gao Y; Kang JX; Cai C
INSTITUCIÓN / INSTITUTION: - Lijian Zhang, Guangdong Medical College. No.2, Eastern Wenming Road, Zhanjiang, Guangdong, 524023, P.R. China.
RESUMEN / SUMMARY: - To investigate tissue fatty acid distribution in relation to the incidence of colorectal cancer prognosis, adjacent normal tissue and cancerous tissue from 35 samples of clinically incident colorectal cancer were obtained. Fatty acids were measured in the colorectal mucosa phospholipid fraction by gas chromatography mass spectrometry. Palmitoleic acid and oleic acid were significantly lower in colorectal cancerous tissue, ranging from 20% to 50% less than the adjacent normal tissue. The omega-6 (n-6) fatty acid family members (20:2, 20:3, 20:4 and 22:4) were higher by 1-3 fold in cancerous colorectal tissue. Contrary with the high level of n-6 fatty acids, about a 37% to 87% reduction in EPA and DHA was observed in colorectal cancerous tissue. A higher level of linoleic acid and arachidonic acid was detected in the C cancer stage than in the B cancer stage (p<0.05), but a lower level of oleic acid and docosahexenoic acid was detected in the C cancer stage (p<0.05). The fatty acid distribution of colorectal tissue is strongly linked to the incidence of colorectal cancer. This study also provides scientific basis for identifying novel biomarkers for the diagnosis and treatment of cancer.
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[597]
TÍTULO / TITLE: - Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor-kappa B activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Surg. 2013 Apr;205(4):387-96. doi: 10.1016/j.amjsurg.2013.01.008. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1016/j.amjsurg.2013.01.008
AUTORES / AUTHORS: - Krosch TC; Sangwan V; Banerjee S; Mujumdar N; Dudeja V; Saluja AK; Vickers SM
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 195, Minneapolis, MN 55455, USA. Electronic address: kend0057@umn.edu.
RESUMEN / SUMMARY: - BACKGROUND: Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. We assessed triptolide as a potential therapy. METHODS: SH-SY5Y and IMR-32 neuroblastoma cell lines were treated with triptolide. Viability, intracellular calcium, caspase activation, protein, and mRNA levels were measured. Autophagy was evaluated with confocal microscopy. Nuclear factor-kappa B (NF-kappaB) activation was measured using a dual luciferase assay. RESULTS: Triptolide treatment resulted in death in both cell lines within 72 hours, with sustained increases in intracellular calcium. IMR-32 cells underwent cell death by apoptosis. Conversely, light chain 3II (LC3II) protein levels were elevated in SH-SY5Y cells, which is consistent with autophagy. Confocal microscopy confirmed increased LC3 puncta in SH-SY5Y cells compared with control cells. Heat shock pathway protein and mRNA levels decreased with treatment. NF-kappaB assays demonstrated inhibition of tumor necrosis factor (TNF)-alpha-induced activity with triptolide. CONCLUSIONS: Triptolide treatment induces cell death in neuroblastoma by different mechanisms with multiple pathways targeted. Triptolide may serve a potential chemotherapeutic role in advanced cases of neuroblastoma.
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[598]
TÍTULO / TITLE: - Prognostic value of circulating cytokines in colon cancer recurrence.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Res. 2013 Feb 26. pii: S0022-4804(13)00089-9. doi: 10.1016/j.jss.2013.02.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jss.2013.02.004
AUTORES / AUTHORS: - Kilzi GM; Lavu H
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
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[599]
TÍTULO / TITLE: - Overexpression of keratin 17 is associated with poor prognosis in epithelial ovarian cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0703-5
AUTORES / AUTHORS: - Wang YF; Lang HY; Yuan J; Wang J; Wang R; Zhang XH; Zhang J; Zhao T; Li YR; Liu JY; Zeng LH; Guo GZ
INSTITUCIÓN / INSTITUTION: - Department of Radiological Medicine and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 17, Changle West Road, Xi’an, 710032, China.
RESUMEN / SUMMARY: - The aim of this study was to investigate the association between keratin 17 (K17) expression and the clinicopathological features of patients with epithelial ovarian cancer (EOC). K17 expression was detected by real-time quantitative RT-PCR in EOC and adjacent noncancerous tissues. In addition, K17 expression was analyzed by immunohistochemistry in 104 clinicopathologically characterized EOC cases. The expression levels of K17 mRNA and protein in EOC tissues were both significantly higher than those in noncancerous tissues. In addition, positive expression of K17 correlated with the clinical stage (p = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high expression level of K17 resulted in a significantly poor prognosis of EOC patients. Multivariate analysis revealed that EOC expression level was an independent prognostic parameter for the overall survival rate of EOC patients. Our data are the first to suggest that increased K17 expression in EOC is significantly associated with aggressive progression and poor prognosis. K17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of EOC.
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[600]
TÍTULO / TITLE: - Prognostic significance of USP22 as an oncogene in papillary thyroid carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0696-0
AUTORES / AUTHORS: - Wang H; Li YP; Chen JH; Yuan SF; Wang L; Zhang JL; Yao Q; Li NL; Bian JF; Fan J; Yi J; Ling R
INSTITUCIÓN / INSTITUTION: - Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, No. 127, Changle West Rd., Xi’an, 710032, Shanxi Province, China.
RESUMEN / SUMMARY: - Ubiquitin-specific protease 22 (USP22), a novel deubiquitinating enzyme, has been associated with metastasis, therapy resistance, and cell cycle progression. The purpose of this study was to investigate the expression level of USP22 in papillary thyroid carcinoma (PTC) samples and to evaluate its clinical significance in PTC patients. USP22 expression was examined in 30 fresh PTC tissues and paired adjacent noncancerous tissues by real-time quantitative RT-PCR. Immunohistochemistry for USP22 was performed on additional 156 PTC tissues. The clinical significance of USP22 expression was analyzed. We found that the expression levels of USP22 mRNA and protein in PTC tissues were both significantly higher than those in noncancerous tissues. Clinicopathological analysis showed that USP22 expression was significantly correlated with tumor size (p = 0.036), extracapsular invasion (p = 0.012), multifocality (p = 0.014), lymph node metastasis (p = 0.022), distant metastasis (p = 0.005), and TNM stage (p = 0.002). The Kaplan-Meier survival curves revealed that USP22 expression was associated with poor prognosis in PTC patients. USP22 expression was an independent prognostic marker of overall patient survival in a multivariate analysis. Our findings suggest that USP22 is an independent predictor of poor prognosis of PTC patients.
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[601]
TÍTULO / TITLE: - MiR-30d induces apoptosis and is regulated by the Akt/FOXO pathway in renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Signal. 2013 Feb 15;25(5):1212-1221. doi: 10.1016/j.cellsig.2013.01.028.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cellsig.2013.01.028
AUTORES / AUTHORS: - Wu C; Jin B; Chen L; Zhuo D; Zhang Z; Gong K; Mao Z
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, 100191 Beijing, China.
RESUMEN / SUMMARY: - MicroRNAs (miRNAs) play critical roles in tumorigenesis by modulating the expression of target gene mRNAs. However, their role in cell signaling is not well defined. In this study, we identified miR-30d as a downstream effector of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in renal cell carcinoma (RCC) cells. We show that Akt inhibition transcriptionally up-regulates miR-30d expression through activation of the transcription factor forkhead box O (FOXO) 3A. Functional analysis revealed that miR-30d overexpression suppresses cell proliferation and induces apoptosis in RCC cells, suggesting that miR-30d acts as a tumor suppressor. In searching for downstream targets of miR-30d, we found that miR-30d post-transcriptionally suppresses expression of the oncoprotein metadherin (MTDH) by destabilizing its mRNA. Furthermore, we found that FOXO down-regulates MTDH expression through up-regulating expression of miR-30d. Thus, our findings reveal a new Akt/FOXO/miR-30d/MTDH signaling transduction pathway and identify miR-30d as a tumor suppressor, providing a new potential target for the treatment of RCC.
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[602]
TÍTULO / TITLE: - Proteomic-based analysis for identification of proteins involved in 5-fluorouracil resistance in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Pharm Des. 2013 Mar 19.
AUTORES / AUTHORS: - Tan Y; Qin S; Hou X; Qian X; Xia J; Li Y; Wang R; Chen C; Yang Q; Miele L; Wu Q; Wang Z
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China. qiongwu68@yahoo.com.cn; zwang6@bidmc.harvard.edu.
RESUMEN / SUMMARY: - Background: Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance. Methods: We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resistance in HCC. The differentially expressed proteins were validated by Western blot analysis. Results: We identified 102 unique proteins including p16, maspin, PRDX6, PSMB7, MYL6, PHB, and HSP27 with alteration in SMMC-7721/5-FU. Furthermore, down-regulation of PRDX6 and PSMB7 enhanced SMMC-7721/5-FU cells to 5-FU sensitivity. Conclusions: Our study suggests that targeting drug resistant genes such as PRDX6 and PSMB7 could be a novel approach to overcome 5-FU resistance in HCC cells.
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[603]
TÍTULO / TITLE: - Expression of Rac1, HIF-1alpha, and VEGF in Gastric Carcinoma: Correlation with Angiogenesis and Prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onkologie. 2013;36(3):102-7. doi: 10.1159/000348525. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1159/000348525
AUTORES / AUTHORS: - Zhan H; Liang H; Liu X; Deng J; Wang B; Hao X
INSTITUCIÓN / INSTITUTION: - Department of Gastric Cancer Surgery, Tianjin Medical University Cancer Hospital and City Key Laboratory of Tianjin Cancer Center, Tianjin, China.
RESUMEN / SUMMARY: - Background: The aim of this study was to investigate the relationship between the expression of hypoxia-inducible factor-1alpha (HIF-1alpha), Ras-related C3 botulinum toxin substrate 1 (Rac1), and vascular endothelial growth factor (VEGF), as well as their correlation with angiogenesis and prognosis in gastric carcinoma. Material and Methods: The expression of Rac1, HIF-1alpha, VEGF, and CD34 (described in terms of microvessel density, MVD) was determined by immunohistochemical staining of tissues from 60 radically resected gastric cancer specimens. Results: The proportion of specimens expressing Rac1, HIF-1alpha, and VEGF was 37/60 (61.7%), 35/60 (58.3%), and 40/60 (66.7%), respectively. The levels of Rac1, HIF-1alpha, and VEGF expression were significantly correlated with Lauren’s classification, lymph node metastasis, and pathologic staging (p < 0.05). There were positive correlations between MVD and the expression of Rac1, HIF-1alpha, and VEGF. The mean survival time and 5-year survival rate in cases with positive Rac1, HIF-1alpha, and VEGF expression and MVD >/= 26.3 were significantly shorter than those with negative Rac1, HIF-1alpha, and VEGF expression and MVD < 26.3. Conclusion: Rac1, HIF-1alpha, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis. Thus, testing the expression of Rac1, HIF-1alpha, and VEGF may be a useful index for treatment and prognosis.
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[604]
TÍTULO / TITLE: - Response of mucocutaneous lesions to rituximab in a case of melanoma differentiation antigen 5-related dermatomyositis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dermatology. 2012;225(4):376-80. doi: 10.1159/000346573. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1159/000346573
AUTORES / AUTHORS: - Clottu A; Laffitte E; Prins C; Chizzolini C
INSTITUCIÓN / INSTITUTION: - Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland.
RESUMEN / SUMMARY: - We report the first case in Western Europe of a person presenting with dermatomyositis associated with melanoma differentiation antigen 5 antibodies. She sequentially developed severe mucocutaneous erythematous and itchy lesions of the face, scalp, neck, knees and recurrent aphthae. In addition she presented painful, periungual, edematous digital lesions and small ulcers with digital necrosis. Her rapidly evolving, near-fatal interstitial lung disease responded to high-dose intravenous cyclophosphamide. However, her recurrent mucocutaneous mani-festations improved only after rituximab administration.
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[605]
TÍTULO / TITLE: - Prediction of bioactivity of HIV-1 integrase ST inhibitors by multilinear regression analysis and support vector machine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Mar 15;23(6):1648-55. doi: 10.1016/j.bmcl.2013.01.081. Epub 2013 Jan 27.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.01.081
AUTORES / AUTHORS: - Xuan S; Wu Y; Chen X; Liu J; Yan A
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, PO Box 53, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, Beijing 100029, PR China.
RESUMEN / SUMMARY: - In this study, four computational quantitative structure-activity relationship models were built to predict the biological activity of HIV-1 integrase strand transfer (ST) inhibitors. 551 Inhibitors whose bioactivities were detected by radiolabeling method were collected. The molecules were represented with 20 selected MOE descriptors. All inhibitors were divided into a training set and a test set with two methods: (1) by a Kohonen’s self-organizing map (SOM); (2) by a random selection. For every training set and test set, a multilinear regression (MLR) analysis and a support vector machine (SVM) were used to establish models, respectively. For the test set divided by SOM, the correlation coefficients (rs) were over 0.91, and for the test set split randomly, the rs were over 0.86.
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[606]
TÍTULO / TITLE: - Engineered breast tumor targeting peptide ligand modified liposomal doxorubicin and the effect of peptide density on anticancer activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 May;34(16):4089-97. doi: 10.1016/j.biomaterials.2013.02.019. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.02.019
AUTORES / AUTHORS: - Shahin M; Soudy R; Aliabadi HM; Kneteman N; Kaur K; Lavasanifar A
INSTITUCIÓN / INSTITUTION: - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
RESUMEN / SUMMARY: - This study aimed to develop actively targeted liposomal formulations of doxorubicin (DOX) using an engineered breast tumor targeting peptide ligand, p18-4 (WxEAAYQrFL). Towards this goal, stealth liposomes bearing different molar ratios of p18-4 peptide (1.5 and 0.3 peptide/total lipid mol %), namely HD and LD liposomes, were successfully prepared. The effect of p18-4 peptide modification and density on breast cancer cell uptake, selective cytotoxicity as well as inhibition of tumor growth and the tissue disposition of encapsulated DOX in breast tumor xenograft models in mice were assessed. The results showed a 2.4 and 5 folds decrease in the IC50 of HD liposomes in MDA-MB-435 and MCF-7 breast tumor cells, respectively. Although LD liposomes showed less (1.6 and 2.2 folds) decrease in the IC50 of DOX in the same breast cancer cell lines, they were more selective in their cytotoxic effect and uptake towards breast cancer over normal breast epithelial cells, MCF10A. Evaluation of the anticancer activity in NOD-SCID mice bearing MDA-MB-435 xenografts after receiving six i.v. injections of 2.5mg/kg/week DOX equivalent showed a superior anticancer activity for LD liposomal DOX compared to HD and unmodified liposomal formulations. Mice treated with LD liposomal DOX illustrated 4.8 folds reduction in the mean relative tumor volume compared to non-targeted DOX liposomes. This was despite similar tumor accumulation of DOX as part of LD liposomes compared to that for unmodified liposomes 24h following the last injection. In contrast, HD liposomes showed decreased DOX accumulation in the tumor and preferential uptake by liver and spleen. Treatment with unmodified and LD liposomes did not have any adverse impact on the activity level and mean body weight of live animals during the study period. In conclusion, surface modification of liposomal DOX with engineered p18-4 peptide at an optimum density can improve the antitumor efficacy and selectivity of liposomal DOX.
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[607]
TÍTULO / TITLE: - Overexpression of immunoglobulin G prompts cell proliferation and inhibits cell apoptosis in human urothelial carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0717-z
AUTORES / AUTHORS: - Liang PY; Li HY; Zhou ZY; Jin YX; Wang SX; Peng XH; Ou SJ
INSTITUCIÓN / INSTITUTION: - Department of Urology, The Affiliated Hospital of Medical College of Hainan, NO.31 Longhua Road, Meilan District, Haikou, 570102, Hainan Province, China.
RESUMEN / SUMMARY: - Only B lymphocytes can express immunoglobulins according to the traditional immunological theories, and the expression of immunoglobulin G (IgG) messenger RNA (mRNA) and protein was found in certain human cancer cells recently. However, the expression pattern of IgG and its possible role in human urothelial carcinoma are still elusive. In this study, we investigated the expression of IgG in two human urothelial carcinoma cell lines, T24 and BIU-87, and in 56 cases of clinical urothelial carcinoma tissues. The mRNA of IgG was positively detected by in situ hybridization and reverse transcription PCR; furthermore, IgG protein was also positively detected by immunohistochemistry and Western blot. Moreover, blockade of tumor-derived IgG by either antihuman IgG antibody or antisense oligonucleotides increased cell apoptosis and inhibited cell growth in bladder cancer cell lines in vitro, and antihuman IgG antibody could suppress the growth of xenotransplant tumor in vivo. In addition, either antihuman IgG antibody or antisense oligonucleotides enhanced the sensitivity to mitomycin C in bladder cancer cell line T24. Furthermore, blockade of IgG in bladder cancer cell T24 resulted in upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. Our results indicated that bladder cancer cells were capable of expressing IgG, and blockade of IgG expression induced cell apoptosis through activation of caspase-dependent pathway. A novel potential targeted therapy for bladder cancer will be possibly developed based on these data.
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[608]
TÍTULO / TITLE: - Integrative genomic analyses of recepteur d’origine nantais and its prognostic value in cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Med. 2013 Mar 11. doi: 10.3892/ijmm.2013.1296.
●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1296
AUTORES / AUTHORS: - Yu H; Yuan J; Xiao C; Qin Y
INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratory of the Traditional Chinese Medical Hospital of Nantong City, Nantong, Jiangsu, P.R. China.
RESUMEN / SUMMARY: - Recepteur d’origine nantais (RON) is a receptor tyrosine kinase (RTK) normally expressed at low levels in epithelial cells. RON is a 180-kDa heterodimeric protein composed of a 40-kDa alpha-chain and a 150-kDa transmembrane beta-chain with intrinsic tyrosine kinase activity. The extracellular sequences of RON contain several domains including an N-terminal semaphorin (sema) domain, followed by the plexin, semaphorin, integrin (PSI) domain, and four immunoglobulin, plexin, transcription factor (IPT) domains. Here, we identified RON genes from 14 vertebrate genomes and found that RON exists in all types of vertebrates including fish, amphibians, birds and mammals. We found that the human RON gene showed predominant expression in the liver, lymph node, thymus, intestine, lung, mammary gland, bone marrow, brain, heart, placenta, bladder, cortex, cervix, skin, kidney and prostate. When searched in the PrognoScan database, human RON was also found to be expressed in bladder, blood, breast, glioma, esophageal, colorectal, head and neck, ovarian, lung and skin cancer. The relationship between the expression of RON and prognosis was found to vary in different cancer types, even in the same cancer from different databases. This suggests that the function of RON in these tumors may be multidimensional, not just as a tumor suppressor or oncogene. Six available single-nucleotide polymorphisms (SNPs) disrupting existing exonic splicing enhancers were identified in RON. This may contribute to the generation of active RON variants by alternative splicing, which is frequently observed in primary tumors.
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[609]
TÍTULO / TITLE: - Novel MicroRNAs regulating proliferation and apoptosis in uterine papillary serous carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 26. pii: S0304-3835(13)00169-9. doi: 10.1016/j.canlet.2013.02.043.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.043
AUTORES / AUTHORS: - Mach CM; Kim J; Soibam B; Creighton CJ; Hawkins SM; Zighelboim I; Goodfellow P; Gunaratne PH; Odunsi K; Salem PA; Anderson ML
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA; College of Pharmacy, University of Houston, Houston, TX 77030, USA.
RESUMEN / SUMMARY: - MicroRNAs (miRNAs) are endogenous, non-coding RNA transcripts that regulate gene expression. Here, we report 175 putative novel miRNAs identified in uterine cancers profiled by Next Generation Sequencing. Our data indicate that one of these putative miRNAs (BCM-173) is conserved across multiple species and is expressed at levels similar to known human miRNAs. Functionally, this miRNA promotes the growth and migration of uterine cancer cell lines by targeting vinculin and altering the distribution of focal adhesions. These results expand our insight into the repertoire of human miRNAs and identify novel pathways by which dysregulated miRNA expression promotes uterine cancer growth.
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[610]
TÍTULO / TITLE: - Apoptosis and p53 are not involved in the anti-tumor efficacy of I-labeled monoclonal antibodies targeting the cell membrane.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nucl Med Biol. 2013 Mar 19. pii: S0969-8051(13)00017-6. doi: 10.1016/j.nucmedbio.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.nucmedbio.2013.02.001
AUTORES / AUTHORS: - Paillas S; Boudousq V; Piron B; Kersual N; Bardies M; Chouin N; Bascoul-Mollevi C; Arnaud FX; Pelegrin A; Navarro-Teulon I; Pouget JP
INSTITUCIÓN / INSTITUTION: - IRCM, Institut de Recherche en Cancerologie de Montpellier, Montpellier, F-34298, France; INSERM, U896, Montpellier, F-34298, France; Universite Montpellier1, Montpellier, F-34298, France; CRLC Val d’Aurelle Paul Lamarque, Montpellier, F-34298, France.
RESUMEN / SUMMARY: - INTRODUCTION: 125I-labeled monoclonal antibodies (125I-mAbs) can efficiently treat small solid tumors. Here, we investigated the role of apoptosis, autophagy and mitotic catastrophe in 125I-mAb toxicity in p53-/- and p53+/+ cancer cells. METHODS: We exposed p53-/- and p53+/+ HCT116 cells to increasing activities of internalizing (cytoplasmic location) anti-HER1 125I-mAbs, or non-internalizing (cell surface location) anti-CEA 125I-mAbs. For each targeting model we established the relationship between survival and mean nucleus absorbed dose using the MIRD formalism. RESULTS: In both p53-/- and p53+/+ HCT116 cells, anti-CEA 125I-mAbs were more cytotoxic per Gy than anti-HER1 125I-mAbs. Sensitivity to anti-CEA 125I-mAbs was p53-independent, while sensitivity to anti-HER1 125I-mAbs was higher in p53-/- HCT 116 cells, suggesting that they act through different signaling pathways. Apoptosis was only induced in p53+/+ HCT116 cells and could not explain cell membrane radiation sensitivity. Inhibition of autophagy did not modify the cell response to 125I-mAbs. By contrast, mitotic death was similarly induced in both p53-/- and p53+/+ HCT116 cells by the two types of 125I-mAbs. We also showed using medium transfer experiments that gamma-H2AX foci were produced in bystander cells. CONCLUSION: Cell membrane sensitivity to 125I-mAbs is not mediated by apoptosis and is p53-independent. Bystander effects-mediated mitotic death could be involved in the efficacy of 125I-mAbs binding cell surface receptors.
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[611]
TÍTULO / TITLE: - Arterial thrombotic events and acute coronary syndromes with cancer drugs: Are growth factors the missed link?: What both cardiologist and oncologist should know about novel angiogenesis inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cardiol. 2013 Feb 12. pii: S0167-5273(13)00092-2. doi: 10.1016/j.ijcard.2013.01.052.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijcard.2013.01.052
AUTORES / AUTHORS: - Conti E; Romiti A; Musumeci MB; Passerini J; Zezza L; Mastromarino V; D’Antonio C; Marchetti P; Paneni F; Autore C; Volpe M
INSTITUCIÓN / INSTITUTION: - Cardiology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Ospedale Sant’Andrea, Rome, Italy. Electronic address: elena.conti@uniroma1.it.
RESUMEN / SUMMARY: - We aimed to revise the increasingly accruing data about the association between anti-tyrosinkinase, “targeted” cancer drugs and the development of arterial thrombotic events or acute coronary syndromes. Further insights into the involved pathophysiologic mechanisms, and into the clinical implications are overviewed. Antiangiogenesis has become a mainstream of cancer therapy, leading to development of a specific class of drugs. Besides, a “wider” angiogenesis network made up of several growth factors, can be recognized as target of a higher number of compounds. Their widespread use has been progressively favored over conventional chemotherapy, because of their better safety/efficacy profile, even allowing a prolonged administration. However, there is a growing awareness of an association between these useful drugs and serious cardiovascular side effects including myocardial infarction, stroke, heart failure and cardiovascular death, in addition to the known relation with the most frequent hypertension onset. Observational studies indeed report that combined cardiovascular events may reach figures of 20-40%, and, for their management, several monitoring, diagnostic and therapeutic regimens have been suggested. On the basis of the available data we recommend an active screening program for acute coronary syndromes in the “at risk” period, immediately after the beginning of the “targeted” drug therapy, and during the whole administration time. Likewise, a mandatory cardiological specialistic evaluation is warranted to plan a schedule of follow-up evaluations for diagnostics, including ECG, echocardiogram, and multimarker evaluation. An appropriate treatment with antiplatelet or anticoagulant drugs, endothelial protective agents or cardiovascular interventions is similarly advised.
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[612]
TÍTULO / TITLE: - IbACP, a sixteen-amino-acid peptide isolated from Ipomoea batatas leaves, induces carcinoma cell apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Peptides. 2013 Feb 18. pii: S0196-9781(13)00044-2. doi: 10.1016/j.peptides.2013.02.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.peptides.2013.02.005
AUTORES / AUTHORS: - Chang VH; Yang DH; Lin HH; Pearce G; Ryan CA; Chen YC
INSTITUCIÓN / INSTITUTION: - Program for Translation Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
RESUMEN / SUMMARY: - A 16-amino-acid peptide was isolated from the leaves of sweet potato. The peptide caused a rapid alkalinization response in tomato suspension culture media, a characteristic of defense peptides in plants. No post-translational modification was observed on the peptide according to MALDI-MS analysis. We have named the peptide Ipomoea batatas anti-cancer peptide (IbACP). IbACP also was shown with the ability to dose-dependently inhibit Panc-1, a pancreatic cancer line, cell proliferation. The morphological observations of the Panc-1 cells by phase contrast microscopy showed significant changes after treatment with IbACP. Moreover, caspase-3 and PARP [poly(ADP-ribose) polymerase] were activated by IbACP treatment, followed by cell death. An increase in the levels of cleaved caspase-3 and -9 was also detected by an immunoblot assay after treatment with IbACP. In addition, genomic DNA fragmentation and decreased cellular proliferation were induced when IbACP was supplied to the Panc-1 cells, further demonstrating its biological relevance. The combined data indicates that IbACP peptide may have an important role in the regulation of cellular proliferation by inducing and promoting apoptosis through the mitochondrial apoptotic pathway. This report also showed that IbACP peptide contains potent anti-cancer effects and may play an important role in herbal medicine development.
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[613]
TÍTULO / TITLE: - WWOX induces apoptosis and inhibits proliferation in cervical cancer and cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Med. 2013 Mar 21. doi: 10.3892/ijmm.2013.1314.
●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1314
AUTORES / AUTHORS: - Qu J; Lu W; Li B; Lu C; Wan X
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of China Welfare Institute affiliated with Shanghai Jiao Tong University, Shanghai 200032, P.R. China.
RESUMEN / SUMMARY: - Cervical cancer is the second most common gynecological malignancy, but the molecular events involved in its development remain unclear. The tumorsuppressor gene, WW domain-containing oxidoreductase (WWOX), has been found to be lost in various types of cancers. Few studies have been reported detailing the function of WWOX in human cervical cancer; therefore we aimed to investigate the role played by WWOX in human cervical cancer. Immunohistochemistry was used to study preinvasive and invasive primary cervical cancer. Full length cDNA was transfected into HeLa cells to overexpress WWOX, and short hairpin RNA (shRNA) was transfected into SiHa cells to deplete its expression, respectively. The cellular levels of WWOX RNA and protein were detected by real-time PCR and western immunoblotting. Proliferation rates were assessed by methyl thiazolyl tetrazolium (MTT), plate colony formation and soft agar colony assays. Cellular apoptosis was measured by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The activity of caspase-3 and its protein levels were determined by caspase-3 activity assay and western blot analysis. Xenografts were established by injecting cells into nude mice. The results showed that WWOX expression was decreased in human cervical cancer and cervical cancer cell lines. Reconstitution of WWOX in HeLa cells inhibited their proliferation and induced apoptosis, while knockdown of WWOX in SiHa cells promoted proliferation and inhibited apoptosis. Xenografts in groups of mice verified the effect in vivo. These data suggest that underexpression of WWOX is associated with cervical cancer development. Modulation of WWOX expression may be an effective and novel method for the treatment of cervical cancer.
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[614]
TÍTULO / TITLE: - Forkhead-box A1 transcription factor is a novel adverse prognosis marker in human glioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Neurosci. 2013 Mar 16. pii: S0967-5868(12)00525-5. doi: 10.1016/j.jocn.2012.03.055.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jocn.2012.03.055
AUTORES / AUTHORS: - Wang L; Qin H; Li L; Feng F; Ji P; Zhang J; Li G; Zhao Z; Gao G
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Tangdu Hospital, 569 Xinsi Road, Baqiao District, Xi’an City 710038, China.
RESUMEN / SUMMARY: - Forkhead-box A1 (FOXA1), a member of the FOX family of transcription factors, has been implicated in certain tumor types including breast, prostate, lung, thyroid and esophageal squamous cell carcinomas. The aim of this study was to investigate the clinicopathological significance of FOXA1 expression in human malignant glioma. FOXA1 expression in human glioma and non-neoplastic brain tissue was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry. The association of FOXA1 immunostaining with clinicopathological factors and prognosis in patients with glioma was also investigated. The expression levels of FOXA1 messenger RNA (mRNA) and protein in glioma tissues were significantly higher than those in corresponding non-neoplastic brain tissue (both p<0.001). In addition, the expression of FOXA1 was upregulated in high-grade glioma tissue compared with that in low-grade tissues, and increased with ascending World Health Organization (WHO) tumor grade (p=0.001). The increased expression of FOXA1 protein was also significantly correlated with low Karnofsky performance scale score (p=0.02). Moreover, the overall survival rate for patients with high FOXA1 protein expression was clearly lower than that for patients with low FOXA1 protein expression (p=0.01). Multivariate analysis showed that high FOXA1 protein expression was an independent prognostic factor for overall survival (p=0.02) in patients with glioma. In conclusion, our results suggest, for the first time, that FOXA1 might be a potential regulator of progression of human glioma and its upregulation might be closely associated with a poor clinical outcome for patients with this serious disease.
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[615]
TÍTULO / TITLE: - DNA polymerase zeta as a potential biomarker of chemoradiation resistance and poor prognosis for cervical cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):500. doi: 10.1007/s12032-013-0500-4. Epub 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0500-4
AUTORES / AUTHORS: - Shi TY; Yang L; Yang G; Tu XY; Wu X; Cheng X; Wei Q
INSTITUCIÓN / INSTITUTION: - Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
RESUMEN / SUMMARY: - DNA Polymerase zeta (Polzeta), an error-prone DNA polymerase involved in translesion DNA synthesis, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of several cancers. To evaluate the association of Polzeta with chemoradiation resistance and prognosis in cervical cancer, we enrolled 123 patients with squamous cell carcinoma of cervical cancer, who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Cancer Center between 2008 and 2009, and tested their in vitro tumor inhibition rates using the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide method and Polzeta protein expression in paraffin-embedded tissues using immunohistochemistry. We found that the Polzeta-positive expression was detected in 22 % of the cases. The median in vitro inhibition rate of tumor cell growth by cisplatin, carboplatin, nedaplatin, and oxaliplatin was 80, 37, 78, and 51 %, respectively. Among the tumor-related variables, FIGO stage, tumor grade, and Polzeta protein expression (adjusted HR 6.7, 4.2 and 6.7; 95 % CI 1.7-26.3, 1.0-17.3 and 1.8-25.4; P = 0.007, 0.046 and 0.005, respectively) were found to be significant predictors for recurrence. Kaplan-Meier survival estimates showed that the patients with more advanced stage (IIB) or Polzeta-positive expression had a significantly shorter progression-free survival. Polzeta-positive expression was significantly associated with depth of cervical stromal invasion (P = 0.012). However, the association between Polzeta expression and in vitro tumor inhibition rates was not significant. Taken together, Polzeta expression can be used as the predictor for poor prognosis, which might be caused by the potential chemoradiation resistance of the cervical cancer patients. The mechanism deserves further exploration.
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[616]
TÍTULO / TITLE: - Adalimumab and Infliximab are Equally Effective for Crohn’s disease in Patients not Previously Treated with Anti-Tumor Necrosis Factor-alpha Agents.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Gastroenterol Hepatol. 2013 Jan 29. pii: S1542-3565(13)00120-1. doi: 10.1016/j.cgh.2013.01.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2013.01.012
AUTORES / AUTHORS: - Kestens C; van Oijen MG; Mulder CL; van Bodegraven AA; Dijkstra G; de Jong D; Ponsioen C; van Tuyl SA; Siersema PD; Fidder HH; Oldenburg B
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology and Hepatology, University Medical Center Utrecht.
RESUMEN / SUMMARY: - BACKGROUND & AIMS: Infliximab (IFX) and adalimumab (ADA) are thought to have equal efficacies for treatment of Crohn’s disease (CD), although no direct comparison has been performed. We compared the effectiveness and safety of IFX and ADA in carefully matched cohorts. METHODS: We performed a retrospective cohort study of 200 patients with CD (100 treated with IFX and 100 with ADA, starting in 2006 or later) who had not previously received anti-tumor necrosis factor (TNF)a -agents; the patients were identified from databases of 6 hospitals in the Netherlands. The groups were carefully matched for indication, duration of disease, age, and Montreal classification. The primary endpoint was the steroid-free clinical response, defined by a combination of multiple clinical parameters, after 1 year. RESULTS: Of the total patient population, 63.5% and 45% had a clinical response after 1 and 2 years respectively. There were no significant differences between treatment groups-at 1 and 2 years, 62% and 41% of those receiving ADA vs 65% and 49% of those receiving IFX had responses, respectively. Kaplan-Meier curves showed identical decreases in response rates over time. Combining IFX or ADA with immunomodulator therapy was associated with a higher clinical response than monotherapy, although this was only significant among patients that received IFX ( P =.03). There were no differences in numbers of side effects or opportunistic infections. CONCLUSIONS: The effectiveness of ADA or IFX treatment in anti-TNFa- naive patients with CD is comparable after 1 and 2 years of follow up. The efficacies of IFX and ADA each seem increase when given with immunomodulator therapy, although only significantly for IFX.
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[617]
TÍTULO / TITLE: - Doxorubicin delivery to 3D multicellular spheroids and tumors based on boronic acid-rich chitosan nanoparticles.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Mar 25. pii: S0142-9612(13)00290-1. doi: 10.1016/j.biomaterials.2013.03.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.03.008
AUTORES / AUTHORS: - Wang X; Zhen X; Wang J; Zhang J; Wu W; Jiang X
INSTITUCIÓN / INSTITUTION: - Laboratory of Mesoscopic Chemistry and Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
RESUMEN / SUMMARY: - Boronic acid-rich chitosan-poly(N-3-acrylamidophenylboronic acid) nanoparticles (CS-PAPBA NPs) with the tunable size were successfully prepared by polymerizing N-3-acrylamidophenylboronic acid in the presence of chitosan in an aqueous solution. The CS-PAPBA NPs were then functionalized by a tumor-penetrating peptide iRGD and loading doxorubicin (DOX). The interaction between boronic acid groups of hydrophobic PAPBA and the amino groups of hydrophilic chitosan inside the nanoparticles was examined by solid-state NMR measurement. The size and morphology of nanoparticles were characterized by dynamic light scattering and electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using three-dimensional (3-D) multicellular spheroids (MCs) as the in vitro model and H22 tumor-bearing mice as the in vivo model. It was found that the iRGD-conjugated nanoparticles significantly improved the efficiency of DOX penetration in MCs, compared with free DOX and non-conjugated nanoparticles, resulting in the efficient cell killing in the MCs. In vivo antitumor activity examination indicated that iRGD-conjugated CS-PAPBA nanoparticles promoted the accumulation of nanoparticles in tumor tissue and enhanced their penetration in tumor areas, both of which improved the efficiency of DOX-loaded nanoparticles in restraining tumor growth and prolonging the life time of H22 tumor-bearing mice.
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[618]
TÍTULO / TITLE: - Onconeuronal antigen Cdr2 correlates with HIF prolyl-4-hydroxylase PHD1 and worse prognosis in renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Mol Pathol. 2013 Mar 24. pii: S0014-4800(13)00043-9. doi: 10.1016/j.yexmp.2013.03.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.yexmp.2013.03.005
AUTORES / AUTHORS: - Kaufmann MR; Schraml P; Hermanns T; Wenger RH; Camenisch G
INSTITUCIÓN / INSTITUTION: - Institute of Physiology, University of Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
RESUMEN / SUMMARY: - Neoplastic expression of the onconeuronal cerebellar degeneration-related antigen Cdr2 in ovary and breast tumors is associated with paraneoplastic cerebellar degeneration (PCD). Cdr2 protein expression is normally restricted to neurons, but aberrant Cdr2 expression has mainly been described for breast and ovarian tumors. Previously, we found strong Cdr2 protein expression in the papillary subtype of renal cell carcinoma (pRCC) and showed that Cdr2 interacts with the hypoxia-inducible factor (HIF) prolyl-4-hydroxylase PHD1. High Cdr2 protein levels are associated with decreased HIF-dependent gene expression in cells as well as in clinical pRCC samples, providing a possible explanation why pRCCs are the most hypovascular renal tumors. Here, we demonstrate that strong Cdr2 protein expression in clinical samples from pRCC patients correlates with elevated PHD1 protein levels, suggesting that increased PHD1 activity attenuates HIF-dependent gene expression. Interestingly, survival analysis revealed a significant correlation between high levels of Cdr2 expression and worse patient outcome in clear cell (cc) RCC patients. These findings provide evidence that Cdr2 might represent an important tumor antigen in kidney cancer and possibly in other cancer types as well. In contrast to ovary and breast tumor patients who develop PCD, no Cdr2 auto-antibodies were detected in the serum of pRCC patients, which is in line with the fact that pRCC patients have not been reported to display paraneoplastic neurodegenerative syndromes. This suggests that, despite a shared target antigen, tumor immunity and autoimmunity only partially overlap, and also highlights to which extent immuno-surveillance against cancer can be clinically silent.
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[619]
TÍTULO / TITLE: - Tumor Necrosis Factor-alpha Levels Early in Severe Acute Pancreatitis: Is There Predictive Value Regarding Severity and Outcome?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Gastroenterol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/MCG.0b013e31828a6cfc
AUTORES / AUTHORS: - Surbatovic M; Radakovic S
INSTITUCIÓN / INSTITUTION: - *Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy daggerFaculty of Medicine of the Military Medical Academy, University of Defense double daggerSector of Preventive Medicine, Military Medical Academy, Belgrade, Serbia.
RESUMEN / SUMMARY: - GOAL AND BACKGROUND:: One of the most important cytokines in pathogenesis of acute pancreatitis is tumor necrosis factor (TNF)-alpha. The aim of our study was to determine whether the plasma levels of TNF-alpha in patients with severe acute pancreatitis (SAP) on admission correlate with severity and outcome of SAP. STUDY:: Blood samples were obtained from 100 patients with SAP. Patients were divided into 2 groups according to severity: SAP group (n=69) and SAP-induced multiple organ dysfunction syndrome (MODS) group (n=31). Survivors were patients who were alive 90 days after taking the blood sample for cytokine measurement (53/100). Blood sample for cytokine measurement was drawn immediately after admission. TNF-alpha was measured by commercial ELISA test in plasma. RESULTS:: When comparing SAP group with SAP-induced MODS group, we found that mean values of TNF-alpha on admission were 191.5-fold lower in group with SAP-induced MODS (P<0.01). When comparing nonsurvivors with survivors, we found that mean values of TNF-alpha on admission were 63-fold higher in survivors (P<0.01). At cut-off level of 7.95 pg/mL sensitivity was 83.9% and specificity was 72.5%. Patients with TNF-alpha level lower than 7.95 pg/mL had 3.2-fold higher probability to develop SAP with MODS. At cut-off level of 10.5 pg/mL sensitivity was 83% and specificity was 77.4%. Patients with TNF-alpha level higher than 10.5 pg/mL had 4.8-fold higher probability to survive. CONCLUSIONS:: TNF-alpha is good predictor of severity and outcome. Low TNF-alpha concentration in patients with SAP predicts development of MODS and fatal outcome.
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[620]
TÍTULO / TITLE: - Acid Ceramidase (AC)-A Key Enzyme of Sphingolipid Metabolism-Correlates With Better Prognosis in Epithelial Ovarian Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Gynecol Pathol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1097/PGP.0b013e3182673982
AUTORES / AUTHORS: - Hanker LC; Karn T; Holtrich U; Gatje R; Rody A; Heinrich T; Ruckhaberle E; Engels K
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology (L.C.H, T.K., U.H., R.G., T.H., E.R.) Senckenberg’s Institute of Pathology (K.E.), Goethe-University, Frankfurt Department of Gynecology and Obstetrics (A.R.), University of Homburg, Homburg, Germany.
RESUMEN / SUMMARY: - Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, seems to play an important role in cancer progression. The objective of this study was to explore the expression of AC in ovarian cancer and its impact on prognosis. Expression analysis of AC in n=112 ovarian cancer patients was performed by immunohistochemical analysis of primary paraffin-embedded tumor samples. The results were scored on the basis of the staining intensity and percentage of positive tumor cells, resulting in an immunoreactive score from 0 to 12. These results were correlated to clinical and pathologic characteristics and survival. AC expression correlated significantly only with FIGO stage (0.047). In serous carcinoma, low level of AC was independently associated with reduced progression-free survival and overall survival of 12.0 mo [95% confidence interval (CI), 5.78-18.23] versus 18.1 mo (95% CI, 11.61-24.59; P=0.008) and 35.7 mo (95% CI, 22.24-47.16) versus 58.7 mo (95% CI, 36.48-80.91; P=0.032), respectively. In multivariate analysis, AC presents as an independent prognostic factor for progression-free survival (hazard ratio 1.88; 95% CI, 1.13-3.11; P=0.015). AC is a prognostic factor in epithelial ovarian cancer. Low AC expression can be associated with tumor progression in carcinoma of the ovaries. These results are in contrast to the concept of AC as a promoter for cancer progression. Nevertheless, they are supported by the lately discovered tumor-suppressing function of sphingosine, the enzymatic product of AC.
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[621]
TÍTULO / TITLE: - Does obesity affect the accuracy of prostate-specific antigen (PSA) for predicting prostate cancer among men undergoing prostate biopsy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BJU Int. 2013 Feb 21. doi: 10.1111/j.1464-410X.2012.11766.x.
●● Enlace al texto completo (gratuito o de pago) 1111/j.1464-410X.2012.11766.x
AUTORES / AUTHORS: - Oh JJ; Jeong SJ; Lee BK; Jeong CW; Byun SS; Hong SK; Lee SE
INSTITUCIÓN / INSTITUTION: - Department of Urology, CHA Bundang Medical Center, CHA University; CHA Cancer Research Center, Seoul, Korea.
RESUMEN / SUMMARY: - WHAT’S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: As most urologist known, obesity significantly lowers serum PSA levels. So there is some concern about delayed diagnosis of prostate cancer in obese men. In the present study, we found that the accuracy level of PSA for detecting prostate cancer was not significantly different between different obesity levels. A well-designed study adjusting for several factors, e.g. diet, exercise, medication and comorbidity, which may possibly compensate for the associated effects on PSA levels, is needed for confirmation of the present findings. OBJECTIVE: To investigate prostate-specific antigen (PSA) accuracy in detecting prostate cancer according to body mass index (BMI) in Asian men with a PSA level of <30 ng/mL using contemporary multicore (>/=12) prostate biopsy. PATIENTS AND METHODS: We reviewed the records of 3471 patients, whose initial PSA levels were <30 ng/mL, who underwent multicore (>/=12) transrectal ultrasound-guided prostate biopsy between January 2004 and May 2011. BMI was categorised as performed previously for the Asian population: <23, 23-24.9, 25-29.9, and >/=30 kg/m(2) . PSA accuracy for detecting prostate cancer in each BMI group was assessed based on the receiver operating characteristics-derived area under the curve. RESULTS: The mean age and median PSA level were inversely associated with BMI; the median PSA level in each BMI category was 7.84, 7.75, 7.33 and 5.79 ng/mL, respectively (P < 0.001). In all, prostate cancer was detected from biopsy in 1102 (31.7%) patients. The PSA accuracy for predicting prostate cancer in all patients was estimated to be 0.607, and PSA accuracies in each BMI category were 0.638, 0.572, 0.613 and 0.544, respectively; there was no significant difference among the groups in terms of PSA accuracy. CONCLUSIONS: The accuracy of PSA in predicting prostate cancer did not change regardless of BMI category in Asian men. However, as patients with higher BMIs had lower PSA levels than those with lower BMIs, it can therefore be suggested that the PSA threshold should be lower in obese men to discriminate between prostate cancer and benign conditions in the real clinical situation.
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[622]
TÍTULO / TITLE: - Low Perioperative Prealbumin Level Predicts Early Recurrence After Curative Pulmonary Resection for Non-small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-1985-x
AUTORES / AUTHORS: - Kawai H
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Akita Red Cross Hospital, Akita, Japan, kawai-h@akita-rch.com.
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[623]
TÍTULO / TITLE: - Low Perioperative Serum Prealbumin Predicts Early Recurrence After Curative Pulmonary Resection for Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg. 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-1937-5
AUTORES / AUTHORS: - Cavallin F; Scarpa M; Cagol M; Alfieri R; Castoro C
INSTITUCIÓN / INSTITUTION: - Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy, cescocava@libero.it.
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[624]
TÍTULO / TITLE: - 15-Deoxy-Delta12,14-prostaglandin J2 induces growth inhibition, cell cycle arrest and apoptosis in human endometrial cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Med. 2013 Apr;31(4):778-88. doi: 10.3892/ijmm.2013.1268. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 3892/ijmm.2013.1268
AUTORES / AUTHORS: - Li H; Narahara H
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan.
RESUMEN / SUMMARY: - 15-Deoxy-12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor gamma ligand, has been reported to have antiproliferative activity in certain types of cancer. The purpose of this study was to elucidate the effect of 15d-PGJ2 on endometrial cancer cells, as well as the mechanism of action. Endometrial cancer-derived cells (HHUA, Ishikawa and HEC-59) were treated with various concentrations of 15d-PGJ2, and its effects on cell growth, the cell cycle and apoptosis were investigated in vitro. Using cDNA microarrays, some potential targets of this drug were identified. All endometrial cancer cell lines were sensitive to the growth-inhibitory effect of 15d-PGJ2. Cell cycle arrest at the G2/M phase of the cell cycle and induction of apoptosis were observed. Concerning the gene expression changes induced by 15d-PGJ2 treatment, the upregulation of aldo-keto reductase family 1 member C3 (AKR1C3) and the downregulation of anterior gradient homolog 3 (AGR3) and nitric oxide synthase 2A (NOS2A) were confirmed using western blot analysis in all the cell lines examined. These results suggest that 15d-PGJ2 may be a novel therapeutic option for the treatment of endometrial cancer.
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[625]
TÍTULO / TITLE: - Livistona chinensis seed suppresses hepatocellular carcinoma growth through promotion of mitochondrial-dependent apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 1. doi: 10.3892/or.2013.2319.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2319
AUTORES / AUTHORS: - Lin W; Zhao J; Cao Z; Zhuang Q; Zheng L; Cai Q; Chen D; Wang L; Hong Z; Peng J
INSTITUCIÓN / INSTITUTION: - Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
RESUMEN / SUMMARY: - The Livistona chinensis seed has been used for centuries to clinically treat various types of cancer. However, the precise mechanism of its anticancer activity remains to be elucidated. In the present study, we evaluated the efficacy of the ethanol extract of Livistona chinensis seed (EELC) against tumor growth using a hepatocellular carcinoma (HCC) mouse xenograft model and an HCC cell line, HepG2, and investigated the molecular mechanisms mediating its biological activities. We found that EELC inhibited HCC growth both in vivo and in vitro, without apparent signs of toxicity. In addition, EELC treatment resulted in the induction of HCC cell apoptosis. Moreover, EELC-induced apoptosis was accompanied by the loss of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and increase in the pro-apoptotic Bax/Bcl-2 ratio. Our findings suggest that promotion of mitochondrial-dependent apoptosis in cancer cells may be one of the mechanisms by which the Livistona chinensis seed is effective in cancer treatment.
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[626]
TÍTULO / TITLE: - Camptothecin Resistance in Cancer: Insights into the Molecular Mechanisms of a DNA damaging Drug.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Med Chem. 2013 Jan 31.
AUTORES / AUTHORS: - Beretta GL; Gatti L; Perego P; Zaffaroni N
INSTITUCIÓN / INSTITUTION: - Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133 Milan, Italy. giovanni.beretta@istitutotumori.mi.it.
RESUMEN / SUMMARY: - Poisoning of DNA topoisomerase I is the mechanism by which camptothecins interfere with tumor growth. Although the clinical use of camptothecins has had a significant impact on cancer therapy, de novo or acquired clinical resistance to these drugs is common. Clinical resistance to camptothecins is still a poorly understood phenomenon, likely involving pharmacological and tumor-related factors. Experimental models including yeast and mammalian cell cultures suggest three general mechanisms of camptothecin resistance: i) reduced cellular accumulation of drugs, ii) alteration in the structure/expression of topoisomerase I, and iii) alterations in the cellular response to camptothecin-DNA-ternary complex formation. Some lines of evidence have also suggested links between cellular camptothecin resistance, the existence of a subset of tumorinitiating cells and miRNA deregulation. In this regard, a better definition of the molecular events clarifying the regulation of tumorigenesis and gene expression might contribute to gain insight into the molecular mechanisms on the basis of camptothecin resistance of tumors and to identify new molecular tools for targeting cancer cells. The relevance of these mechanisms to clinical drug resistance has not yet been completely defined, but their evaluation in clinical specimens should help to define personalized treatments including camptothecins as single agents or in combination with other cytotoxic and target-specific anticancer agents. The present review focuses on the cellular/molecular aspects involved in resistance of tumor cells to camptothecins, including the potential role of cancer stem cells and deregulated miRNAs, and on the approaches proposed for overcoming resistance.
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[627]
TÍTULO / TITLE: - Association of post-cardioversion transcardiac concentration gradient of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) and inflammatory biomarkers to atrial fibrillation recurrence.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Biochem. 2013 Feb 24. pii: S0009-9120(13)00062-3. doi: 10.1016/j.clinbiochem.2013.02.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinbiochem.2013.02.003
AUTORES / AUTHORS: - Deftereos S; Giannopoulos G; Kossyvakis C; Raisakis K; Angelidis C; Efremidis M; Panagopoulou V; Kaoukis A; Theodorakis A; Toli K; Zavitsanakis P; Mantas I; Pyrgakis V; Stefanadis C; Cleman MW
INSTITUCIÓN / INSTITUTION: - Department of Cardiology, Athens General Hospital “G. Gennimatas”, Athens, Greece.
RESUMEN / SUMMARY: - OBJECTIVES: Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) has been shown to have both pro- and anti-apoptotic activities and is associated to better prognosis in heart failure. The aim of this study was to determine the transcardiac concentration gradient of sTRAIL and inflammatory biomarkers after AF cardioversion and assess their relation to AF recurrence. DESIGN AND METHODS: We measured transcardiac gradients (coronary sinus concentration minus aortic root concentration) of sTRAIL, C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with non-valvular AF after electrical cardioversion. Six-month AF recurrence was the study endpoint. RESULTS: There were no differences in sTRAIL and hsCRP concentrations in peripheral venous blood between patients with and without AF recurrence (p=0.066 and 0.149, respectively), while IL-6 was higher in patients with recurrence (p=0.032). Only sTRAIL showed a significant transcardiac gradient [3pg/mL (IQR 1-4pg/mL); p=0.01]. sTRAIL gradient was 4pg/mL (IQR 3-5pg/mL) in patients without recurrence versus -1pg/mL (IQR -2-1pg/mL) in those with recurrence (p<0.001). IL-6 (p=0.281) and hsCRP (p=0.979) aortic concentrations were not significantly different from coronary sinus concentrations. In multivariate analysis, sTRAIL transcardiac gradient (beta -0.81, p=0.004) remained a negative predictor of AF recurrence. CONCLUSION: This study demonstrates the existence of a significant transcardiac sTRAIL concentration gradient in patients with non-valvular AF, inversely associated to AF recurrence. These results suggest production of sTRAIL by the heart and a protective role against substrate-altering processes in AF-prone atria. This could have implications for TRAIL-targeting therapies currently under development.
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[628]
TÍTULO / TITLE: - The induction of apoptosis in pre-malignant keratinocytes by omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is inhibited by albumin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Toxicol Lett. 2013 Apr 12;218(2):150-8. doi: 10.1016/j.toxlet.2013.01.021. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.toxlet.2013.01.021
AUTORES / AUTHORS: - Nikolakopoulou Z; Shaikh MH; Dehlawi H; Michael-Titus AT; Parkinson EK
INSTITUCIÓN / INSTITUTION: - Centre for Clinical & Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK. Electronic address: z.nikolakopoulou@qmul.ac.uk.
RESUMEN / SUMMARY: - The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. At the 10% (v/v) foetal bovine serum (FBS) medium, limited growth inhibition (3-20% for 50muM DHA and EPA respectively) and negligible apoptosis were observed with PUFA use. However, at 3% (v/v) FBS medium, 30-50muM of PUFA caused impressive levels of growth inhibition (82-83% for 50muM DHA and EPA respectively) and increase of apoptosis (8-19% increase in 72h). None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-alpha-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1-0.3%, w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses.
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[629]
TÍTULO / TITLE: - Metformin Synergistically Enhances Antitumor Activity of Histone Deacetylase Inhibitor Trichostatin A Against Osteosarcoma Cell Line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - DNA Cell Biol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1089/dna.2012.1926
AUTORES / AUTHORS: - Duo J; Ma Y; Wang G; Han X; Zhang C
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Cancer Prevention and Therapy, Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
RESUMEN / SUMMARY: - Oral hypoglycemic agent metformin is commonly used for treating type II diabetes; however, initial reports demonstrated that it could be used for suppressing tumor growth in vitro and in vivo. Moreover, novel potential anticancer drug histone deacetylase (HDAC) and inhibitor trichostatin A (TSA) have been extensively studied for inducing various malignancies growth inhibition, cell cycle arrest, and apoptosis. The object of the present study was to investigate the anti-proliferation and apoptosis induction effects of metformin and TSA in osteosarcoma cell line, and to explore the mechanism of metformin and TSA in combination to inhibit the proliferation of osteosarcoma cells. After treating with metformin and TSA, the viability of osteosarcoma cell lines (MG-63 and LM8) was analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) at various concentrations, cell cycle analysis of MG-63 and LM8 cell was performed by flow cytometry. Real-time polymerase chain reaction and Western Blotting were performed to determine the expression of apoptosis-related genes and proteins such as Caspase-3, Bcl-2/Bax, Cyclin D1, and p21. Protein expression of the molecules involved in 5’-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway after treatment with combination was determined by Western blotting. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish the murine model; tumor weight and tumor volume were monitored after drug administration separately or combined via the intraperitoneal (i.p.) route. MTT assays showed that the viability of osteosarcoma cell lines in the combination group (10 mM metformin, 0.3 muM TSA) decreased in a concentration- and time-dependent manner; moreover, the cell cycle of MG-63 and LM8 in the combination group could be arrested in G1/G2 phase higher number compared with drug use separately. Furthermore, a combination of these drugs does not act via the AMPK signaling pathway to induce MG-63 osteosarcoma cell line growth inhibition and apoptosis. As data have showed here, metformin cotreatment increased TSA antitumor effects and have a synergistic effect on osteosarcoma cell line proliferation and apoptosis.
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[630]
TÍTULO / TITLE: - Translational predictive biomarker analysis of the phase 1b sorafenib and bevacizumab study expansion cohort.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Proteomics. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1074/mcp.M112.026427
AUTORES / AUTHORS: - Azad N; Yu M; Davidson B; Choyke P; Chen CC; Wood BJ; Venkatesan A; Henning R; Calvo K; Minasian L; Edelman DC; Meltzer P; Steinberg SM; Annunziata CM; Kohn EC
INSTITUCIÓN / INSTITUTION: - Center for Cancer Research, NCI, United States;
RESUMEN / SUMMARY: - Predictive biomarkers are needed to triage patients to best therapy. We prospectively planned examination of sequential blood, biopsy, and functional imaging with which to confirm mechanism and identify potential predictive biomarkers in a phase Ib clinical trial expansion cohort of solid tumor patients receiving sorafenib/bevacizumab. The maximally-tolerated doses of sorafenib 200mg twice daily with bevacizumab 5mg/kg every other week were given to biopsiable patients. Patients were randomized to receive either sorafenib or bevacizumab monotherapy for the first 28 day cycle with the second drug added with cycle 2. Biopsies, dynamic contrast-enhanced MRI, and FDG-PET were done pre-therapy, and at 2, and 6 weeks (2 weeks into combination therapy). Tumor and serum proteomics, Ras/Raf mutational analysis, and functional imaging results were examined individually and across the dataset to identify potential changes predictive of response to therapy and those which confirm biochemical drug mechanism(s). Therapy with sorafenib/bevacizumab resulted in clinical benefit in 45% of this mixed solid tumor group. ERK activation and microvessel density were decreased with monotherapy treatment with sorafenib or bevacizumab, respectively; whereas, decreased signal over the group of total AKT, phospho(p)-VEGF receptor2, p-endothelial nitric oxide synthase, BRAF and cleaved PARP was associated with earlier progression of disease. Tumor metabolic activity decreased in those patients with clinical benefit lasting longer than 4 months, and increased with progressive disease. Cleavage of caspase 3 and PARP were increased, and Ki67 expression decreased in patients with prolonged clinical benefit, consistent with decreased proliferation and increased apoptosis. The conglomerate analysis, incorporating pharmacodynamic and tumor biochemistry, demonstrated sorafenib/bevacizumab targeted vascular activity in the tumor. Results suggest potential biomarkers for which changes, as a group, during early therapeutic exposure may predict clinical benefit.
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[631]
TÍTULO / TITLE: - Functional inhibition of BCL2 is needed to increase the susceptibility to apoptosis to SMO inhibitors in diffuse large B-cell lymphoma of germinal center subtype.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hematol. 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1007/s00277-013-1684-6
AUTORES / AUTHORS: - Kunkalla K; Liu Y; Qu C; Leventaki V; Agarwal NK; Singh RR; Vega F
INSTITUCIÓN / INSTITUTION: - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Unit 72, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
RESUMEN / SUMMARY: - Previously, we have demonstrated that inhibition of Hedgehog pathway induces predominantly apoptosis in diffuse large B-cell lymphoma (DLBCL) cell lines of activated B-cell (ABC) type but predominantly cell cycle arrest in those of germinal center (GC). Here, we explored the possibility of overcoming the resistance to apoptosis to SMO inhibitors in five DLBCL cells of GC type using the combination of the SMO inhibitor HhAntag (Genentech Inc) with the BH3 mimetic ABT-737 (Abbott Laboratories). As controls we have used two DLBCL of ABC type (OCI-LY10 and OCI-LY3). Combinatorial treatments were performed with increasing concentrations of the HhAntag with low doses (equal or less than the IC(20)) of ABT-737. MTS assays were used to detect changes in cell viability and Annexin-V and PARP1 cleavage assays were used to detect apoptosis. Combining low doses of ABT-737 with increasing concentrations of HhAntag in GC DLBCL cell lines resulted in significantly increase of apoptosis in comparison to treatments with the SMO inhibitor alone. We concluded that in GC DLBCL cell lines, in contrast to those of ABC type, functional inhibition of BCL2 family members is usually needed to overcome the resistance to apoptosis to SMO inhibitors. These findings provide a rationale to explore the use of SMO and BCL2 inhibitors as adjuvant therapy for treatment of DLBCL of GC type.
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[632]
TÍTULO / TITLE: - HISTONE DEACETYLASE INHIBITION AFFECTS SODIUM IODIDE SYMPORTER (NIS) EXPRESSION AND INDUCES (1)(3)(1)I CYTOTOXICITY IN ANAPLASTIC THYROID CANCER CELLS.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thyroid. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1089/thy.2012.0359
AUTORES / AUTHORS: - Pugliese M; Fortunati N; Germano A; Asioli S; Marano F; Palestini N; Frairia R; Boccuzzi G; Catalano MG
INSTITUCIÓN / INSTITUTION: - University of Turin, Medical Sciences, Turin, Italy ; mariateresa.pugliese@unito.it.
RESUMEN / SUMMARY: - Background: Anaplastic thyroid cancers (ATC) represent only 1-2% of all thyroid tumors, but they account for up to 50% of the mortality. Treatment of differentiated thyroid carcinomas is well standardized and the use of radioiodine represents an essential step; in contrast, there is no standardized therapeutic approach for anaplastic tumors and their prognosis is poor. The resistance of anaplastic thyroid cancer to radioiodine treatment is principally due to the absence of expression of the sodium iodide symporter (NIS), mainly due to epigenetic silencing. The acetylation status of histones is involved in the epigenetic control of gene expression and is usually disrupted in advanced thyroid cancer. Histone deacetylase inhibitors have been demonstrated as potent anticancer drugs with several different effects on cell viability and differentiation. Methods: Stabilized anaplastic thyroid cancer cell lines (BHT-101 and CAL-62) and primary cultures from patients who underwent thyroidectomy for anaplastic thyroid cancer were treated with the histone deacetylase inhibitor LBH589. After treatment, we evaluated the expression and function of NIS. Gene expression was evaluated by real-time PCR (RT-PCR); NIS promoter activity was determined with a luciferase reporter assay; and protein expression was assessed through immunofluorescence. We tested the protein function by 125I uptake and efflux experiments; finally the cytotoxic effect of 131I was determined with a clonogenic assay. Results: Our results demonstrate that treatment with LBH589 leads to NIS RNA expression as shown by RT-PCR and luciferase assay, and to protein expression as determined by immunofluorescence in vitro and by immunohistochemistry in xenograft tumors. Moreover, 125I uptake and efflux experiments show the correct protein function and iodine retention, that translate into cytotoxicity effects, as demonstrated by a clonogenic assay with 131I . Conclusions: This study supplies a new potential strategy for the treatment of ATC by modifying gene expression with the aim of inducing responsiveness towards radioiodine therapy.
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[633]
TÍTULO / TITLE: - Apparent diffusion coefficient as a prognostic biomarker of upper urinary tract cancer: a preliminary report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Radiol. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s00330-013-2805-2
AUTORES / AUTHORS: - Yoshida S; Kobayashi S; Koga F; Ishioka J; Ishii C; Tanaka H; Nakanishi Y; Matsuoka Y; Numao N; Saito K; Masuda H; Fujii Y; Kihara K
INSTITUCIÓN / INSTITUTION: - Department of Urology, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: To investigate the role of apparent diffusion coefficient (ADC) as a biomarker reflecting the aggressiveness of upper urinary tract urothelial cell carcinoma (UUT-UCC). METHODS: Thirty-four consecutive patients treated with nephroureterectomy for non-metastatic disease were prospectively enrolled in this study. ADC was compared with clinicopathological variables including Ki-67 labelling index (LI) and cancer-specific survival (CSS). RESULTS: The overall 3-year CSS rate was 82 % (median follow-up, 36 months). ADC was significantly lower in grade 3 disease than in grades 1-2 disease (P = 0.011) and significantly and inversely correlated with Ki-67 LI (rho = -0.59, P = 0.0002). Low ADCs (<1.10 x 10-3 mm2/s) were significantly associated with shorter CSS (P = 0.039). Multivariate analysis of preoperative variables identified ADC and MRI-based clinical T stage as independent indicators of shorter CSS; the patients were stratified into high-risk (8 patients with low ADC and at least clinical T3) and low-risk (26 patients with high ADC or not more than clinical T2) groups with 3-year CSS rates of 43 % and 93 % (P = 0.0003). CONCLUSIONS: Our preliminary data suggest the potential role of ADC as a quantitative biomarker reflecting the aggressiveness of UUT-UCC. ADC might be useful for preoperative risk stratification of UUT-UCC patients. KEY POINTS : * Diffusion-weighted MRI offers new information about the aggressiveness of urinary tract cancers. * The apparent diffusion coefficient acts as a quantitative biomarker for upper urinary tract cancers. * ADC inversely correlates with immunohistochemical and histological grading of UUT-UCC. * ADC offers a prognosis for UUT-UCC patients treated with nephroureterectomy.
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[634]
TÍTULO / TITLE: - Antiestrogen fulvestrant enhances the antiproliferative effects of epidermal growth factor receptor inhibitors in human non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):270-8. doi: 10.1097/JTO.0b013e31827d525c.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827d525c
AUTORES / AUTHORS: - Garon EB; Pietras RJ; Finn RS; Kamranpour N; Pitts S; Marquez-Garban DC; Desai AJ; Dering J; Hosmer W; von Euw EM; Dubinett SM; Slamon DJ
INSTITUCIÓN / INSTITUTION: - Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90404, USA. egaron@mednet.ucla.edu
RESUMEN / SUMMARY: - INTRODUCTION: Estrogen receptor (ER) signaling and its interaction with epidermal growth factor receptor (EGFR) is a potential therapeutic target in non-small-cell lung cancer (NSCLC). To explore cross-communication between ER and EGFR, we have correlated ER pathway gene and protein expression profiles and examined effects of antiestrogens with or without EGFR inhibitors in preclinical models of human NSCLC. METHODS: We evaluated 54 NSCLC cell lines for growth inhibition with EGFR inhibitors, antiestrogen treatment, or the combination. Each line was evaluated for baseline ER pathway protein expression. The majority were also evaluated for baseline ER pathway gene expression. Human NSCLC xenografts were evaluated for effects of inhibition of each pathway, either individually, or in combination. RESULTS: The specific antiestrogen fulvestrant has modest single agent activity in vitro, but in many lines, fulvestrant adds to effects of EGFR inhibitors, including synergy in the EGFR-mutant, erlotinib-resistant H1975 line. ERalpha, ERbeta, progesterone receptor-A, progesterone receptor-B, and aromatase proteins are expressed in all lines to varying degrees, with trends toward lower aromatase in more sensitive cell lines. Sensitivity to fulvestrant correlates with greater baseline ERalpha gene expression. Tumor stability is achieved in human tumor xenografts with either fulvestrant or EGFR inhibitors, but tumors regress significantly when both pathways are inhibited. CONCLUSIONS: These data provide a rationale for further investigation of the antitumor activity of combined therapy with antiestrogen and anti-EGFR agents in the clinic. Future work should also evaluate dual ER and EGFR inhibition in the setting of secondary resistance to EGFR inhibition.
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[635]
TÍTULO / TITLE: - Integrin-facilitated transcytosis for enhanced penetration of advanced gliomas by poly(trimethylene carbonate)-based nanoparticles encapsulating paclitaxel.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Apr;34(12):2969-79. doi: 10.1016/j.biomaterials.2012.12.049. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2012.12.049
AUTORES / AUTHORS: - Jiang X; Sha X; Xin H; Xu X; Gu J; Xia W; Chen S; Xie Y; Chen L; Chen Y; Fang X
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.
RESUMEN / SUMMARY: - The treatment of cerebral tumor, especially advanced gliomas, represents one of the most formidable challenges in oncology. In this study, integrin-mediated poly(trimethylene carbonate)-based nanoparticulate system (c(RGDyK)-NP) was proposed as a delivery vehicle for enhancing drug penetration and chemotherapy of malignant gliomas. Following the recognition by integrin proteins on cell surface, c(RGDyK)-NP could be energy-dependently internalized by human U87MG glioma cells through a multiple endocytic pathway. The tumor penetration, homing specificity and anticancer efficacy of PTX-loaded c(RGDyK)-NP (c(RGDyK)-NP/PTX) were performed on the 3D glioma spheroids, the U87MG glioma cells and the intracranial glioma mice model, respectively. Compared with conventional nanoparticles (NP/PTX) and Taxol, c(RGDyK)-NP/PTX showed the strongest penetration and accumulation into 3D glioma spheroids, an obvious microtubule stabilization effect to U87MG glioma cells, a significant homing specificity to malignant glioma in vivo, and an extended median survival time in the intracranial glioma-bearing mice. Furthermore, preliminary in vivo subacute toxicity was also evaluated by measuring the histopathology, blood cell counts and clinical biochemistry parameters, and the results revealed no obvious subacute toxicity to hematological system, major organs or tissues were observed post successive intravenous injection of c(RGDyK)-NP. Therefore, our results suggested that cyclic RGD-conjugated PEG-PTMC nanoparticle could be a promising vehicle for enhancing the penetration and cxhemotherapy of high-grade malignant gliomas.
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[636]
TÍTULO / TITLE: - Naftopidil Induces Apoptosis in Malignant Mesothelioma Cell Lines Independently of alpha1-Adrenoceptor Blocking.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):887-94.
AUTORES / AUTHORS: - Masachika E; Kanno T; Nakano T; Gotoh A; Nishizaki T
INSTITUCIÓN / INSTITUTION: - Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan. tomoyuki@hyo-med.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: Naftopidil, an alpha-adrenoceptor blocker, has been clinically used for the treatment of benign prostate hyperplasia and hypertension. Emerging evidence has shown that naftopidil exhibits an antitumor effect on a variety of cancer types including prostate cancer. The aim of the present study was to investigate naftopidil-induced apoptosis in human malignant mesothelioma cells and to shed light on the underlying mechanism. MATERIALS AND METHODS: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, western blotting, and enzymatic assay of caspase-3, -8, and -9 activities were carried out on human malignant mesothelioma cell lines NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells. To knock-down alpha-adrenoceptor, siRNA to silence human alpha-adrenoceptor-targeted gene was constructed and transfected into cells. RESULTS: Naftopidil induced apoptosis in all the investigated malignant mesothelioma cells, and a similar effect was obtained with prazosin, another alpha-adrenoceptor blocker. alpha-Adrenoceptor is linked to G protein involving activation of protein kinase C (PKC). Naftopidil-induced reduction in cell viability was inhibited by GF109203X, while prazosin-induced in cell viability was less affected. Knocking-down alpha-adrenoceptor promoted malignant mesothelioma cell proliferation. Both naftopidil and prazosin activated caspase-3 and -8 in all the investigated malignant mesothelioma cells. CONCLUSION: Naftopidil, as well as prazosin, has the potential to induce apoptosis in malignant mesothelioma cells by activating caspase-8 and the effector caspase-3, regardless of alpha-adrenoceptor blocking.
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[637]
TÍTULO / TITLE: - Betulinic acid suppresses NGAL-induced epithelial-to-mesenchymal transition in melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biol Chem. 2013 Feb 12. pii: /j/bchm.just-accepted/hsz-2013-0106/hsz-2013-0106.xml. doi: 10.1515/hsz-2013-0106.
●● Enlace al texto completo (gratuito o de pago) 1515/hsz-2013-0106
AUTORES / AUTHORS: - Gheorgheosu D; Jung M; Schmid T; Oren B; Dehelean C; Muntean D; Brune B
RESUMEN / SUMMARY: - Abstract Betulinic acid (BA) exhibits antitumoral activity by blocking proliferation, invasion, and angiogenesis. However, the impact of BA on epithelial-to-mesenchymal transition (EMT), a hallmark of cancer metastasis induced among others by neutrophil gelatinase-associated lipocalin (NGAL), remains unknown. The present study aimed at determining the effect of BA on NGAL-induced EMT. In A375 melanoma cells BA downregulated mesenchymal and increased epithelial markers, and inhibited cytoskeletal reorganization. In addition, BA limited endogenous NGAL production and further suppressed EMT induced by exogenously added NGAL and the corresponding invasive cellular phenotype. In conclusion, BA interferes with EMT-associated changes, a mechanism to antagonize invasive melanoma cells.
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[638]
TÍTULO / TITLE: - The prognostic role of tumor associated macrophages and angiogenesis in classical Hodgkin lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Leuk Lymphoma. 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 3109/10428194.2013.778405
AUTORES / AUTHORS: - Panico L; Ronconi F; Lepore M; Tenneriello V; Cantore N; Dell’angelo AC; Ferbo U; Ferrara F
RESUMEN / SUMMARY: - ABSTRACT We studied by immunohistochemistry CD68+ tumor-associated macrophages (TAM) and angiogenesis in 121 consecutive cases of uniformly treated classical Hodgkin’s lymphoma (cHL). High TAM count showed a significant correlation with age >/= 45, mixed cellularity subtype, high Beta2 microglobulin levels. Vessel density (VD) was unrelated to clinico-pathological features, while a significant correlation was found between TAM count and VD. Patients with high TAM showed a trend toward a reduced progression free survival and a significantly shorter overall survival (OS). No correlation was found between VD and survival. At multivariate analysis bulky disease was an independent predictor of reduced progression free survival, while independent adverse prognostic factors for OS were male sex, age >/= 45, advanced stage and bulky disease. High TAM count results in adverse overall outcome in cHL and is significantly correlated to VD. Since VD has no prognostic relevance, the adverse effect of TAM is presumably unrelated to angiogenesis.
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[639]
TÍTULO / TITLE: - Aurora kinase inhibitor AZD1152 has an additional effect of platinum on a sequential application at the human ovarian cancer cell line SKOV3.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Gynecol Obstet. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1007/s00404-013-2719-x
AUTORES / AUTHORS: - Ma Y; Weimer J; Fredrik R; Adam-Klages S; Sebens S; Caliebe A; Hilpert F; Eckmann-Scholz C; Arnold N; Schem C
INSTITUCIÓN / INSTITUTION: - Department of Gynecology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, People’s Republic of China.
RESUMEN / SUMMARY: - PURPOSE: The treatment of ovarian tumors is carried out with platinum medicine which can lead to incompatibilities or resistances. Thus, it is of great interest to check new medicine suitability for its application. AZD1152 is an Aurora kinase inhibitor predominantly works against Aurora kinase B involved in the chromosome segregation. Cells become polyploidy and reduce the proliferation by this impairment. To investigate whether AZD1152, may play a role in the treatment of ovarian carcinoma we serving it to the cisplatinum-resistant cell line SKOV3 alone and in combination with platinum. METHODS: We look at the proliferation, the ploidy, the phases of cell cycle and the apoptosis activity of the cells. RESULTS AND CONCLUSION: We could show that the combination of both medicines in the preclinical experiment produces a working advantage.
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[640]
TÍTULO / TITLE: - S39, a novel Aurora B kinase inhibitor, shows potent antineoplastic activity in human Hela cervical cancer cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biotechnol Lett. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s10529-013-1164-z
AUTORES / AUTHORS: - Li J; Lang Q; Zhang H; Huang Q; Yu L
INSTITUCIÓN / INSTITUTION: - Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People’s Republic of China, lijiejocelin@gmail.com.
RESUMEN / SUMMARY: - Aurora kinases, frequently detected to be over-expressing in human tumors, regulate many essential events during mitosis progression and have been regarded as potentially important targets for cancer therapy. S39 is a novel potent inhibitor of Aurora B kinase with the IC(50) 90.07 nM in the biochemical assay in an ATP competitive manner. S39 treatment on human tumor cells can inhibit the phosphorylation of Histone H3 (Ser10), a direct downstream substrate of Aurora B kinase, indicating S39 inhibits endogenous Aurora B kinase activity in cell-based level. Furthermore, S39 treatment blocks cell proliferation, inhibits colony formation and induces apoptosis in a wide range of human tumor cell lines. These results indicate that S39 is a potential lead compound to be an Aurora B inhibitor.
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[641]
TÍTULO / TITLE: - Apoptosis and In Situ and Invasive Squamous Cell Carcinoma in Sun-Exposed Sites.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Dermatopathol. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1097/DAD.0b013e318284e61f
AUTORES / AUTHORS: - Aung PP; Batrani M; Yang S; Mahalingam M
INSTITUCIÓN / INSTITUTION: - *Department of Dermatology, Dermatopathology Section, Boston University School of Medicine, Boston, MA; and daggerDepartment of Pathology, Boston University School of Medicine, Boston, MA.
RESUMEN / SUMMARY: - : In vitro evidence indicates that the E6 protein of human papillomavirus (HPV) targets Bak, a proapoptotic protein, expression of which is enhanced in epidermal keratinocytes in response to ultraviolet B radiation. Given this, our aim was to ascertain Bak expression and prevalence of beta-HPV (beta-HPV) in cutaneous squamous cell carcinoma (SCC) from sun-exposed sites to test our hypothesis that the virus plays a role in the neoplastic process by suppressing UV-induced apoptosis. This retrospective study included 30 cases of cutaneous SCC and 30 cases of SCC in situ (SCCIS) from sun-exposed sites. Immunohistochemical staining for Bak protein was performed on all, and beta-HPV subtyping on 10 randomly selected cases from each group, using a broad-spectrum polymerase chain reaction-reverse hybridization assay. A semiquantitative scoring system for immunohistochemical expression of Bak was used based on the percentage positivity of the cells. Of cases studied, 30 of 30 (100%) of SCCIS and SCC (mean score 4.2 and 4.6, respectively, demonstrated immunopositivity, albeit to varying degrees, with Bak. Of the selected cases studied with reverse hybridization assay, 7 of 10 (70%) of SCCIS and 3 of 10 (30%) of SCC had beta-HPV with HPV-5 being the most common subtype detected. Enhanced Bak immunoexpression confirms the presence of UV-induced apoptosis in both in situ as well as invasive epithelial malignancies, although the lack of differences in expression of Bak between both groups studied suggests that its relevance in disease progression is minimal. Expression of Bak in 100% of HPV-containing lesions from sun-exposed sites suggests that the virus does not abrogate UV-induced apoptosis.
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[642]
TÍTULO / TITLE: - Alpha-fetoprotein: a controversial prognostic biomarker for small hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Jan 21;19(3):328-30. doi: 10.3748/wjg.v19.i3.328.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i3.328
AUTORES / AUTHORS: - Asrih M; Lenglet S; Mach F; Montecucco F
INSTITUCIÓN / INSTITUTION: - Cardiology Division, Department of Medicine, Geneva University Hospital, Foundation for Medical Research, 1211 Geneva, Switzerland.
RESUMEN / SUMMARY: - The assessment of the prognosis in patients with early hepatocellular carcinoma represents a hot-topic issue that requires further improvements and clarifications. The life expectancy of the patients has been shown to depend on several clinical and histological parameters (such as patient’s general conditions, macroscopic tumor morphology and histopathology). Recently, the prognostic role of some biomarkers [i.e., alpha-fetoprotein (AFP)] has been also investigated with controversial findings mainly on the assessment of patient survival. The study by Giannini et al failed to show a prognostic value of AFP on survival of patients with well-compensated cirrhosis and small hepatocellular carcinoma. Since the study presents some limitations, a larger clinical trial is needed to clarify the potential prognostic role of serum AFP levels in these patients.
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[643]
TÍTULO / TITLE: - Tetrandrine inhibits hepatocellular carcinoma cell growth through the caspase pathway and G2/M phase.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 20. doi: 10.3892/or.2013.2352.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2352
AUTORES / AUTHORS: - Yu VW; Ho WS
INSTITUCIÓN / INSTITUTION: - School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
RESUMEN / SUMMARY: - Activation of p53-independent pathways plays an important role in phytochemical-induced apoptosis and is considered to be a crucial factor in the invasion and metastasis of cancer. Previous studies have shown that combined effects of Stephania tetrandra with medicinal herbs exhibit beneficial effects in cancer patients. Tetrandrine, an active component of Stephania tetrandra has been reported to have anticancer properties in cancer cells. However, the mechanism(s) of action of tetrandrine in liver cancer have yet to be fully elucidated. In this study, we investigated the effects of tetrandrine in hepatocellular carcinoma (HCC) cells. The results showed that tetrandrine inhibited HCC cell proliferation by suppression of cell cycle progression at the G2/M phase. Changes in the expression levels of Bax, Bcl, p53, survivin, PCNA, PARP and p21 were observed. In addition, tetrandrine increased caspase-3 expression and induced DNA fragmentation in Huh-7 cells. The results suggest that the anti-cancer effect of tetrandrine in Huh-7 cells may be mediated by p53-independent pathways.
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[644]
TÍTULO / TITLE: - Mutant tristetraprolin: a potent inhibitor of malignant glioma cell growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Neurooncol. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1112-8
AUTORES / AUTHORS: - Suswam EA; Shacka JJ; Walker K; Lu L; Li X; Si Y; Zhang X; Zheng L; Nabors LB; Cao H; King PH
INSTITUCIÓN / INSTITUTION: - Department of Neurology, University of Alabama at Birmingham, 1720 2nd Avenue South, WTI410C, Birmingham, AL, 35294-3300, USA, easuswam@uab.edu.
RESUMEN / SUMMARY: - Malignant gliomas rely on the production of certain critical growth factors including VEGF, interleukin (IL)-6 and IL-8, to fuel rapid tumor growth, angiogenesis, and treatment resistance. Post-transcriptional regulation through adenine and uridine-rich elements of the 3’ untranslated region is one mechanism for upregulating these and other growth factors. In glioma cells, we have shown that the post-transcriptional machinery is optimized for growth factor upregulation secondary to overexpression of the mRNA stabilizer, HuR. The negative regulator, tristetraprolin (TTP), on the other hand, may be suppressed because of extensive phosphorylation. Here we test that possibility by analyzing the phenotypic effects of a mutated form of TTP (mt-TTP) in which 8 phosphoserine residues were converted to alanines. We observed a significantly enhanced negative effect on growth factor expression in glioma cells at the post-transcriptional and transcriptional levels. The protein became stabilized and displayed significantly increased antiproliferative effects compared to wild-type TTP. Macroautophagy was induced with both forms of TTP, but inhibition of autophagy did not affect cell viability. We conclude that glioma cells suppress TTP function through phosphorylation of critical serine residues which in turn contributes to growth factor upregulation and tumor progression.
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[645]
TÍTULO / TITLE: - Predicting Early and Sustained Virological Responses in Prior Nonresponders to Pegylated Interferon alpha-2b Plus Ribavirin Retreated With Peginterferon alpha-2a Plus Ribavirin and The Benefit-Risk Ratio of Retreatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Gastroenterol. 2013 Feb 24.
●● Enlace al texto completo (gratuito o de pago) 1097/MCG.0b013e31827b9b45
AUTORES / AUTHORS: - Marcellin P; Craxi A; Brandao-Mello CE; Di Bisceglie AM; Andreone P; Freilich B; Rajender Reddy K; Olveira Martin A; Teuber G; Messinger D; Hooper G; Wat C; Tatsch F; Jensen DM
INSTITUCIÓN / INSTITUTION: - *Hopital Beaujon, Boulevard du General Leclerc, Clichy, France daggerInstituto Di Clinica Medica Policlinico, Palermo parallelDepartment of Clinical Medicine, University of Bologna, Bologna, BO, Italy double daggerInternal Medicine Department, Hepatology Division, Gaffree e Guinle University Hospital, College of Medicine & Surgery, University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil section signDepartment of Internal Medicine, Saint Louis University School of Medicine, St Louis paragraph signKansas City Gastroenterology and Hepatology, LLC, Kansas City, MO #Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA **Hospital La Paz de Madrid, Madrid, España daggerdaggerInterdisziplinares Facharztzentrum Sachsenhausen, MVZ-Sachsenhausen, Frankfurt double daggerdouble daggerIST GmbH, Mannheim, Germany section sign section signRoche Products Ltd, Welwyn, UK parallel parallelF. Hoffmann-La Roche Ltd, Basel, Switzerland paragraph sign paragraph signCenter for Liver Diseases, University of Chicago Hospitals, Chicago, IL.
RESUMEN / SUMMARY: - GOALS:: To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to peginterferon alpha-2b (12 kDa). BACKGROUND:: In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA <50 IU/mL at treatment week 12, was an important predictor of SVR. STUDY:: We conducted an exploratory analysis of the retreatment with Pegasys in patients not responding to PegIntron therapy study data to better define the predictive value of cEVR for SVR in this patient population. RESULTS:: In total, 157 of the 942 patients achieved a cEVR (16.7%). SVR rates were higher with 72 versus 48 weeks of retreatment in patients with a cEVR (57% vs. 35%), whereas SVR rates were <5% in patients without cEVR in both groups. The relative adverse event (AE) burden was lower with 72 weeks of treatment (8.1 vs. 10.1 AEs/y of treatment) as was the estimated number of AEs per SVR achieved (55 vs. 100). Cumulative treatment duration required to achieve 1 SVR was lower with 72 weeks of treatment (6.7 vs. 10.0 y/SVR) and lower still assuming that treatment was stopped at week 12 for non-cEVR patients (3.6 vs. 7.1 y/SVR). CONCLUSIONS:: cEVR is a reliable predictor of SVR in patients retreated with peginterferon alpha-2a (40 kDa) plus ribavirin. Seventy-two-week retreatment has a more favorable benefit-risk ratio than 48 weeks, especially when cEVR is used to identify patients most likely to be cured.
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[646]
TÍTULO / TITLE: - ss-catenin, Cox-2 and p53 immunostaining in colorectal adenomas to predict recurrence after endoscopic polypectomy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Colorectal Dis. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s00384-013-1667-z
AUTORES / AUTHORS: - Brand L; Munding J; Pox CP; Ziebarth W; Reiser M; Huppe D; Schmiegel W; Reinacher-Schick A; Tannapfel A
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
RESUMEN / SUMMARY: - BACKGROUND: Endoscopic polypectomy significantly reduces the incidence of colorectal cancer, but recurrence rates are high, especially for adenomas with advanced histology. The present guidelines recommend re-colonoscopy 3 to 5 years later. Due to limited resources, more precise predictions of adenoma recurrence are required. DESIGN: Lesions from 109 patients with colorectal adenomas recruited into a randomized, placebo-controlled chemoprevention trial with mesalazine were included. Formalin-fixed paraffin-embedded tissue sections were stained for ss-catenin, cyclooxygenase-2 (Cox-2), and p53 and scored. Adenoma recurrence rates were recorded after 3 years and associated with clinical and immunohistochemical parameters by contingency table analysis. RESULTS: After 3 years, adenomas recurred in 51.4 % of patients. Out of 109 adenomas, 95 met at least one criterion of advanced adenoma (size >1 cm, villous histology, high-grade intraepithelial neoplasia). There was no influence of age, sex, size or villous histology on adenoma reappearance, whilst the number of adenomas at baseline was positively associated with recurrence (p = 0.003). In contrast, ss-catenin nuclear localisation, Cox-2 expression and p53 nuclear expression were significantly associated with adenoma recurrence after 3 years (ss-catenin: p = 0.002; Cox-2: p = 0.001; p53: p = 0.001). Combining these three markers led to a negative predictive value of 88.5 % and a sensitivity of 94.6 %. (OR = 13.54) CONCLUSIONS: Scoring each single parameter and, more strongly, the combination of all three parameters of the expression of ss-catenin, Cox-2 and p53 in colorectal adenoma tissue may be a useful negative predictor for adenoma recurrence in patients with advanced colorectal adenomas.
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[647]
TÍTULO / TITLE: - Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Prolif. 2013 Apr;46(2):153-63. doi: 10.1111/cpr.12017.
●● Enlace al texto completo (gratuito o de pago) 1111/cpr.12017
AUTORES / AUTHORS: - Bishayee K; Ghosh S; Mukherjee A; Sadhukhan R; Mondal J; Khuda-Bukhsh AR
INSTITUCIÓN / INSTITUTION: - Department of Zoology, Cytogenetics and Molecular Biology Laboratory, University of Kalyani, Kalyani, 741235, West Bengal, India.
RESUMEN / SUMMARY: - OBJECTIVES: Small aromatic compounds like flavonoids can intercalate with DNA molecules bringing about conformational changes leading to reduced replication and transcription. Here, we have examined one dietary flavonoid, quercetin (found in many fruit and vegetables), for possible anti-cancer effects, on HeLa cells originally derived from a case of human cervical cancer. MATERIAL AND METHODS: By circular dichroism spectroscopy we tested whether quercetin effectively interacted with DNA to bring about conformational changes that would strongly inhibit proliferation and migration of the HeLa cells. Cytotoxic effects of quercetin on cancer/normal cells, if any, were determined by MTT assay and such depolarization of mitochondrial membrane potential, as a consequence of quercetin treatment, and accumulation of reactive oxygen species (ROS) also were studied, by FACS analysis and expression profiles of different anti- and pro-apoptotic genes and their products were determined. RESULTS: Quercetin intercalated with calf thymus cell DNA and HeLa cell DNA and inhibition of anti-apoptotic AKT and Bcl-2 expression were observed. Levels of mitochondrial cytochrome-c were elevated and depolarization of mitochondrial membrane potential occurred with increase of ROS; upregulation of expression of p53 and caspase-3 activity were also noted. These alterations in signalling proteins and externalization of phosphotidyl serine residues were involved with initiation of apoptosis. Reduced AKT expression suggested reduction in cell proliferation and metastasis potential, with arrest of the cell cycle at G2/M. CONCLUSION: Quercetin would have potential for use in cervical cancer chemotherapy.
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[648]
TÍTULO / TITLE: - A Kunitz-type FXa inhibitor affects tumor progression, hypercoagulable state and triggers apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Pharmacother. 2013 Apr;67(3):192-6. doi: 10.1016/j.biopha.2012.11.009. Epub 2012 Dec 28.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biopha.2012.11.009
AUTORES / AUTHORS: - Ventura JS; Faria F; Batista IF; Simons SM; Oliveira DG; Morais KL; Chudzinski-Tavassi AM
INSTITUCIÓN / INSTITUTION: - Laboratory of Biochemistry and Biophysics, Butantan Institute, Sao Paulo, SP, Brazil; Biochemistry Department, Federal University of Sao Paulo, Sao Paulo, SP, Brazil.
RESUMEN / SUMMARY: - Cancer is linked to hypercoagulability, and many studies have shown that anticoagulant drugs affect tumor progression. In this study was demonstrated that the Amblyomin-X (which is a recombinant protein that exerts similarity to the Kunitz-type inhibitors and shows pro-apoptotic effects in different tumor cell lines) and heparin (a classic anticoagulant) have similar effects on cancer progression and on normalization of the hypercoagulable state. However, Amblyomin-X showed a distinct mechanism in triggering its effects in vitro, because it exerted a cytotoxic effect in cancer cells by inducing apoptosis and promoting cell cycle arrest.
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[649]
TÍTULO / TITLE: - Genista sessilifolia DC. extracts induce apoptosis across a range of cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Prolif. 2013 Apr;46(2):183-92. doi: 10.1111/cpr.12022.
●● Enlace al texto completo (gratuito o de pago) 1111/cpr.12022
AUTORES / AUTHORS: - Bontempo P; Rigano D; Doto A; Formisano C; Conte M; Nebbioso A; Carafa V; Caserta G; Sica V; Molinari AM; Altucci L
INSTITUCIÓN / INSTITUTION: - Department of General Pathology, Seconda Universita degli Studi di Napoli, Vico Luigi de Crecchio 7, Naples, 80138, Italy.
RESUMEN / SUMMARY: - OBJECTIVES: Restorative properties of medicinal plants such as Genista sessilifolia DC. have often been suggested to occur, in epidemiological studies. However, full characterization of effective principles responsible for this action has never previously been performed. Here, we have characterized G. sessilifolia’s anti-cancer effects and identified the chemical components involved in this anti-tumour action. MATERIALS AND METHODS: Cell cycle, apoptosis, necrosis, differentiation analyses, high-performance liquid chromatography, western blotting, RNA extraction, real-time PCR and primers have all been observed/used in the study. RESULTS: We report that G. sessilifolia methanol extract has anti-cancer activity on solid and haematological cancer cells. G. sessilifolia extract’s anti-proliferative action is closely bound to induction of apoptosis, whereas differentiation is only weakly modulated. Analysis of G. sessilifolia extract, by high-performance liquid chromatography, identifies fraction 18-22 as the pertinent component for induction of apoptosis, whereas fractions 11-13 and 27-30 both seem to contribute to differentiation. G. sessilifolia extract induces apoptosis mediated by caspase activation and p21, Rb, p53, Bcl2-associated agonist of cell death (BAD), tumour necrosis factor receptor super-family, member 10 (TRAIL) overexpression and death receptor 5 (DR5). Accordingly, fraction 18-22 inducing apoptosis was able to induce TRAIL. CONCLUSIONS: Our results indicate that G. sessilifolia extract and its fraction 18-22 containing genistin and isoprunetin, were able to induce anti-cancer effects supporting the hypothesis of a pro-apoptotic intrinsic content of this natural medicinal plant.
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[650]
TÍTULO / TITLE: - Time series analysis of oxidative stress response patterns in HepG2: A toxicogenomics approach.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Toxicology. 2013 Feb 11;306C:24-34. doi: 10.1016/j.tox.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.tox.2013.02.001
AUTORES / AUTHORS: - Deferme L; Briede JJ; Claessen SM; Jennen DG; Cavill R; Kleinjans JC
INSTITUCIÓN / INSTITUTION: - Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6200 MD Maastricht, The Netherlands. Electronic address: l.deferme@maastrichtuniversity.nl.
RESUMEN / SUMMARY: - Oxidative stress plays an important role in chemically induced liver injury, however, our insight into molecular responses to different oxygen radicals is fragmentary. Since these cellular responses will differ over time, examining time-dependent changes in gene expression, and correlating these with markers for oxidative stress, may provide new insights into responses to oxidants. We used the human hepatoma cell line HepG2 to investigate the effects of oxidative stress on the transcriptome level by micro-arrays at seven time points (0.5, 1, 2, 4, 6, 8 and 24h) following exposure to the oxidants menadione, hydrogen peroxide and tert-butyl hydroperoxide including the effects on cell cycle and apoptosis by flow cytometry, protein carbonyl formation by spectrophotometry and oxidative DNA damage by FPG-comet. In total, 3429 genes were differentially expressed, including 136 genes that were significantly modified by all oxidants. Time-dependent biological pathway analysis showed that these genes were particularly involved in inflammatory responses, cell cycle processes and glutathione signaling. These responses were confirmed and supported by phenotypic anchoring to the different cellular endpoints. In addition, using an innovative temporal analysis we established an oxidative stress-related gene expression time cluster. Altogether, this study provides new insights in temporal oxidative stress mechanisms and demonstrates sequential cellular responses that may contribute to a better hazard identification and the mechanisms of toxicological responses in the liver induced by oxidative stress.
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[651]
TÍTULO / TITLE: - Interferon regulatory factor 3 alters glioma inflammatory and invasive properties.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Neurooncol. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1109-3
AUTORES / AUTHORS: - Tarassishin L; Lee SC
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA, leonid.tarassishin@einstein.yu.edu.
RESUMEN / SUMMARY: - Glioblastoma multiforme (GBM) is the most common, highly malignant primary tumor of the brain with poor prognosis. Even with the improved therapy regimen including temozolomide, the average survival rate is less than 2 years. Additional approaches to therapy targeting multiple aspects of glioma progression are in need. In the present work, we have tested the possibility that upregulation of the transcription factor interferon regulatory factor 3 (IRF3) can inhibit glioma invasiveness, proliferation and production of pro-inflammatory and pro-angiogenic factors in cultures of malignant glioma cell lines (U271, U87 and SNB-19). IRF3 is an essential transcription factor involved in TLR3/4-mediated signaling and generation of type I interferons. Although IRF3 has been suggested as a potential tumor suppressor gene, its role in glioma remains uninvestigated. In this study, we find that human glioma immune activation is potently elicited by a cytokine combination, IL-1/IFNgamma (or poly IC), but not by bacterial lipopolysaccharide (LPS), similar to primary human astrocytes. GBM biopsy specimens show little detectable IRF3 immunoreactivity, and in vitro adenovirus-mediated IRF3 gene transfer in glioma cells modulates IL-1/IFNgamma-induced cytokine and chemokine genes, resulting in upregulation of IFNbeta and IP-10 (IRF3-stimulated genes) and downregulation of proinflammatory and angiogenic genes including IL-8, TNFalpha and VEGF (IRF3-represssed genes). Cytokines (IL-1beta and TNFalpha) also induce the expression of miR-155 and miR-155*, the microRNAs crucial in immunity and inflammation-induced oncogenesis and this is dose-dependently suppressed by IRF3. Importantly, IRF3 also inhibits glioma proliferation, migration and invasion. Together, these data suggest that IRF3 can suppress glioma progression. Agents that promote IRF3 activation and expression (such as IRF3 gene transfer) could be explored as potential future therapy.
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[652]
TÍTULO / TITLE: - Hemidesmus indicus induces apoptosis as well as differentiation in a human promyelocytic leukemic cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Ethnopharmacol. 2013 Mar 14. pii: S0378-8741(13)00103-7. doi: 10.1016/j.jep.2013.02.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jep.2013.02.009
AUTORES / AUTHORS: - Ferruzzi L; Turrini E; Burattini S; Falcieri E; Poli F; Mandrone M; Sacchetti G; Tacchini M; Guerrini A; Gotti R; Hrelia P; Cantelli-Forti G; Fimognari C
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy and BioTechnology, Alma Mater Studiorum-University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
RESUMEN / SUMMARY: - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the roots of Hemidesmus indicus is widely used in the Indian traditional medicine for the treatment of blood diseases, dyspepsia, loss of taste, dyspnea, cough, poison, menorrhagia, fever, and diarrhea. Poly-herbal preparations containing Hemidesmus are often used by traditional medical practitioners for the treatment of cancer. The aim of this study was to investigate the cytodifferentiative, cytostatic and cytotoxic potential of a decoction of Hemidesmus indicus’s roots (0.31-3mg/mL) on a human promyelocytic leukemia cell line (HL-60). MATERIALS AND METHODS: The decoction of Hemidesmus indicus was characterized by HPLC to quantify its main phytomarkers. Induction of apoptosis, cell-cycle analysis, levels of specific membrane differentiation markers were evaluated by flow cytometry. The analysis of cell differentiation by nitroblue tetrazolium (NBT) reducing activity, adherence to the plastic substrate, alpha-napthyl acetate esterase activity and morphological analysis was performed through light microscopy (LM) and transmission electron microscopy (TEM). RESULTS: Starting from the concentration of 0.31mg/ml, Hemidesmus indicus induced cytotoxicity and altered cell-cycle progression, through a block in the G0/G1 phase. The decoction caused differentiation of HL-60 cells as shown by NBT reducing activity, adherence to the plastic substrate, alpha-naphtyl acetate esterase activity, and increasing expression of CD14 and CD15. The morphological analysis by LM and TEM clearly showed the presence of granulocytes and macrophages after Hemidesmus indicus treatment. CONCLUSIONS: The cytodifferentiating, cytotoxic and cytostatic activities of Hemidesmus indicus offers a scientific basis for its use in traditional medicine. Its potent antileukemic activity provides a pre-clinical evidence for its traditional use in anticancer pharmacology. Further experiments are worthwhile to determine the in vivo anticancer potential of this plant decoction and its components.
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[653]
TÍTULO / TITLE: - Synergistic effect of a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, and paclitaxel on human multidrug resistance cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Jun;24(5):455-60. doi: 10.1097/CAD.0b013e32835f060d.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835f060d
AUTORES / AUTHORS: - Lee HS; Phat C; Choi SU; Lee C
INSTITUCIÓN / INSTITUTION: - aDepartment of Food Science and Technology, Chung-Ang University, Anseong bKorea Research Institute of Chemical Technology, Daejeon, Korea.
RESUMEN / SUMMARY: - NeoN-methylsansalvamide is a novel low-molecular-weight cyclic pentadepsipeptide that exerts cytotoxic effects on various human cancer cell lines. Its structural analysis using liquid chromatography mass/mass spectrometry showed the cyclic structure sequence -phenylalanine-leucine-valine-N-methylleucine-leucic acid-. The intrinsic cytotoxic and multidrug resistance reversal effects of neoN-methylsansalvamide were evaluated on the human cancer cell lines MES-SA and HCT15 as well as on their multidrug resistance sublines (MES-SA/DX5 and HCT15/CL05, respectively) using the sulforhodamine B assay. The EC50 values of paclitaxel for MES-SA, HCT15, and for the multidrug resistance sublines MES-SA/DX5 and HCT15/CL05 were 1.00+/-0.20, 0.85+/-0.63, 10.00+/-0.53, and >1000 nmol/l, respectively. However, the EC50 values for paclitaxel including 3 mumol/l neoN-methylsansalvamide for MES-SA/DX5, HCT15, and HCT15/CL02 were 1.58+/-0.12, 0.10+/-0.02, and 288.40+/-21.02 nmol/l, respectively. The in-vitro multidrug resistance reversal activity of neoN-methylsansalvamide was similar to that of the control verapamil. These finding suggests that a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, is effective in reversing multidrug resistance in vitro, and this activity may be a major applicable biological function of this compound.
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[654]
TÍTULO / TITLE: - Prediction of response to interferon alpha-1b in HBeAg-positive chronic hepatitis B: a clue from HBsAg levels.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Gastroenterol Hepatol. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1097/MEG.0b013e32835ee611
AUTORES / AUTHORS: - Ma Q; Qin B; Gong X; Lu X
INSTITUCIÓN / INSTITUTION: - Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
RESUMEN / SUMMARY: - BACKGROUND: Quantification of hepatitis B surface antigen (HBsAg) in serum may be of clinical importance in predicting treatment response towards interferon alpha (IFNalpha). AIMS: To explore the predictive role of serum quantitative HBsAg in predicting treatment response towards IFNalpha-1b in hepatitis B e antigen-positive chronic hepatitis B patients. METHODS: Seventy patients received 5 MU of IFNalpha-1b three times weekly for 48 weeks; the quantification of HBsAg was carried out at baseline, weeks 12, 24, 36, and 48 during treatment. At the end of treatment, the predictive role of quantitative HBsAg in predicting treatment response towards IFNalpha-1b was evaluated. RESULTS: From weeks 12 to 48, the serum hepatitis B virus DNA and HBsAg levels were positively correlated; the HBsAg levels were lower in responders than those in nonresponders and the difference was statistically significant (P<0.05). The HBsAg cutoff of 6109.01 IU/ml in serum at week 24 had a positive predictive value of 37.5% and a negative predictive value of 94.7%, and with an area under the receiver operating characteristic curve of 0.816. CONCLUSION: On-treatment, serum HBsAg had a high predictive value to predict treatment response towards IFNalpha-1b.
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[655]
TÍTULO / TITLE: - Proteasomal regulation of caspase-8 in cancer cell apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0821-y
AUTORES / AUTHORS: - Fiandalo MV; Schwarze SR; Kyprianou N
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Cellular Biochemistry and the Markey Cancer Center, University of Kentucky College of Medicine, Combs Cancer Research Building, 306, 800 Rose Street, Lexington, KY, 40536, USA.
RESUMEN / SUMMARY: - Previous studies demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of caspase-8. The present study investigated the impact of proteasome inhibition on caspase-8 stability, ubiquitination, trafficking, and activation in cancer cells. Using caspase-8 deficient neuroblastoma (NB7) cells for reconstituting non-cleavable mutant forms of caspase-8, we demonstrated that the non-cleavable forms of caspase-8 are capable of inducing apoptosis comparably to wild-type caspase-8, in response to proteasome inhibitor and GST-TRAIL. Moreover in the LNCaP human prostate cancer cells, caspase-8 polyubiquitination occurs after TRAIL stimulation and caspase-8 processing. Subcellular fractionation analysis revealed caspase-8 activity in both cytosol and plasma membrane fractions in both NB7 reconstituted caspase-8 cell lines, as well the LNCaP prostate cancer cells. The present results suggest that caspase-8 stabilization through proteasome inhibition leads to reactivation of the extrinsic pathway of apoptosis and identify E3 ligase mediating caspase-8 polyubiquitination, as a novel molecular target. Inhibition of this E3 ligase in combination with TRAIL towards restoring apoptosis signaling activation may have potential therapeutic significance in resistant tumors.
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[656]
TÍTULO / TITLE: - Targeted inhibition of phosphatidyl inositol-3-kinase p110beta, but not p110alpha, enhances apoptosis and sensitivity to paclitaxel in chemoresistant ovarian cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Apr;18(4):509-20. doi: 10.1007/s10495-013-0807-9.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0807-9
AUTORES / AUTHORS: - Jeong JY; Kim KS; Moon JS; Song JA; Choi SH; Kim KI; Kim TH; An HJ
INSTITUCIÓN / INSTITUTION: - Department of Pathology, College of Medicine, CHA University, 351 Yatap-dong, Gyeonggi-Do, Seongnam Si Bundang-gu, 463-712, Republic of Korea.
RESUMEN / SUMMARY: - The phosphatidylinositol 3-kinase (PI3K) pathway is one of the critical signaling cascades playing important roles in the chemoresistance of human cancer cells, including ovarian cancer. In this study, we investigated the potential of targeting the PI3K p110beta-isoform as a novel approach to overcome the chemoresistance in ovarian cancer. The effects on apoptosis, cell viability, proliferation and migration in chemoresistant ovarian cancer cell were determined following targeted p110beta inhibition by small interfering RNA (siRNA). Seven paclitaxel (PTX)-resistant sublines (SKpacs and A2780pac) were produced from SKOV3 and A2780 ovarian cancer cell lines. We, first, evaluated the expression of PI3K p110 isoforms in chemosensitive and chemoresistant ovarian cancer cell lines and patient specimens, and found that p110beta-isoform was significantly overexpressed both in a panel of ovarian cancer samples, and in PTX-resistant sublines compared with their parent cell lines. RNA interference-mediated p110beta silencing augmented PTX-mediated apoptosis (31.15 +/- 13.88 %) and reduced cell viability (67 %) in PTX-resistant cells, whereas targeting p110alpha did not show a significant change in cell viability and apoptosis. In addition, p110beta silencing impaired cell proliferation (60 %) in PTX-resistant SKpac cells. We also found the combined treatment group with p110beta siRNA and PTX showed a significant inhibition of tumor growth of SKpac cells compared to the PTX-only treated group in a xenograft nude mouse model. Thus, the siRNA-mediated silencing of PI3K p110beta resensitizes PTX-resistant ovarian cancer cells, and may be a useful therapeutic strategy for PTX-resistant ovarian cancers.
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[657]
TÍTULO / TITLE: - Momordin Ic induces HepG2 cell apoptosis through MAPK and PI3K/Akt-mediated mitochondrial pathways.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Feb 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0820-z
AUTORES / AUTHORS: - Wang J; Yuan L; Xiao H; Xiao C; Wang Y; Liu X
INSTITUCIÓN / INSTITUTION: - College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, China.
RESUMEN / SUMMARY: - Momordin Ic is a natural triterpenoid saponin enriched in various Chinese and Japanese natural medicines such as the fruit of Kochia scoparia (L.) Schrad. So far, there is little scientific evidence for momordin Ic with regard to the anti-tumor activities. The aim of this work was to elucidate the anti-tumor effect of momordin Ic and the signal transduction pathways involved. We found that momordin Ic induced apoptosis in human hepatocellular carcinoma HepG2 cells, which were supported by DNA fragmentation, caspase-3 activation and PARP cleavage. Meanwhile, momordin Ic triggered reactive oxygen species (ROS) production together with collapse of mitochondrial membrane potential, cytochrome c release, down-regulation of Bcl-2 and up-regulation of Bax expression. The activation of p38 and JNK, inactivation of Erk1/2 and Akt were also demonstrated. Although ROS production rather than NO was stimulated, the expression of iNOS and HO-1 were altered after momordin Ic treatment for 4 h. Furthermore, the cytochrome c release, caspase-3 activation, Bax/Bcl-2 expression and PARP cleavage were promoted with LY294002 and U0126 intervention but were blocked by SB203580, SP600125, PI3K activator, NAC and 1,400 W pretreatment, demonstrating the mitochondrial disruption. Furthermore, momordin Ic combination with NAC influenced MAPK, PI3K/Akt and HO-1, iNOS pathways, MAPK and PI3K/Akt pathways also regulated the expression of HO-1 and iNOS. These results indicated that momordin Ic induced apoptosis through oxidative stress-regulated mitochondrial dysfunction involving the MAPK and PI3K-mediated iNOS and HO-1 pathways. Thus, momordin Ic might represent a potential source of anticancer candidate.
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[658]
TÍTULO / TITLE: - Prediction of drug-drug Interactions Between Various Antidepressants and Efavirenz or Boosted Protease Inhibitors Using a Physiologically Based Pharmacokinetic Modelling Approach.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Pharmacokinet. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s40262-013-0056-7
AUTORES / AUTHORS: - Siccardi M; Marzolini C; Seden K; Almond L; Kirov A; Khoo S; Owen A; Back D
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK, siccardi@liverpool.ac.uk.
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVE: The rate of depression in patients with HIV is higher than in the general population. The use of antidepressants can have a beneficial effect, improving antiretroviral therapy adherence and consequently their efficacy and safety. Efavirenz and protease inhibitor boosted with ritonavir are major components of the antiretroviral therapy and are inducers and/or inhibitors of several cytochrome P450 (CYP) isoforms. Although antidepressants are prescribed to a significant proportion of patients treated with antiretrovirals, there are limited clinical data on drug-drug interactions. The aim of this study was to predict the magnitude of drug-drug interactions among efavirenz, boosted protease inhibitors and the most commonly prescribed antidepressants using an in vitro-in vivo extrapolation (IVIVE) model simulating virtual clinical trials. METHODS: In vitro data describing the chemical characteristics, and absorption, distribution, metabolism and elimination (ADME) properties of efavirenz, boosted protease inhibitors and the most commonly prescribed antidepressants were obtained from published literature or generated by standard methods. Pharmacokinetics and drug-drug interaction were simulated using the full physiologically based pharmacokinetic model implemented in the Simcyp ADME simulator. The robustness of our modeling approach was assessed by comparing the magnitude of simulated drug-drug interactions using probe drugs to that observed in clinical studies. RESULTS: Simulated pharmacokinetics and drug-drug interactions were in concordance with available clinical data. Although the simulated drug-drug interactions with antidepressants were overall weak to moderate according to the classification of the US FDA, fluoxetine and venlafaxine represent better candidates from a pharmacokinetic standpoint for patients on efavirenz and venlafaxine or citalopram for patients on boosted protease inhibitors. CONCLUSION: The modest magnitude of interaction could be explained by the fact that antidepressants are substrates of multiple isoforms and thus metabolism can still occur through CYPs that are weakly impacted by efavirenz or boosted protease inhibitors. These findings indicate that IVIVE is a useful tool for predicting drug-drug interactions and designing prospective clinical trials, giving insight into the variability of exposure, sample size and time-dependent induction or inhibition.
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[659]
TÍTULO / TITLE: - Liposomal cytarabine in neoplastic meningitis from primary brain tumors: a single institutional experience.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neurol Sci. 2013 Mar 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s10072-013-1358-0
AUTORES / AUTHORS: - Gaviani P; Corsini E; Salmaggi A; Lamperti E; Botturi A; Erbetta A; Milanesi I; Legnani F; Pollo B; Silvani A
INSTITUCIÓN / INSTITUTION: - Neuro-Oncology Department, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, 20133, Milan, Italy, paolagaviani@hotmail.com.
RESUMEN / SUMMARY: - Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte®. In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte® regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte® (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte® cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte®, and the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %).
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[660]
TÍTULO / TITLE: - Ulinastatin Exerts Synergistic Effects with Taxotere and Inhibits Invasion and Metastasis of Breast Cancer by Blocking Angiogenesis and the Epithelial-Mesenchymal Transition.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2011.1122
AUTORES / AUTHORS: - Gao F; Sun Z; Sun X; Zhang Y; Wang H; Zhong B; Luo J; Zhao X
INSTITUCIÓN / INSTITUTION: - Department of Breast and Thyroid, The Second Affiliated Hospital, Chongqing University of Medical Sciences , Chongqing, China .
RESUMEN / SUMMARY: - Abstract Urinary trypsin inhibitor (UTI) ulinastatin as a broad-spectrum protease inhibitor has been widely used to treat acute pancreatitis and shock and to improve the surgical outcome in the clinic. In the present study, we investigated the potential antihuman breast cancer effects of UTI and its combination with taxotere (TXT). Human primary breast cancer cells and breast cancer cell line MDA-MB-231 cells were treated with UTI with or without TXT, and invasion and metastasis ability of these cells were evaluated, respectively, by a transwell assay. Reverse transcription-polymerase chain reaction was used to detect fibroblast growth factor, vascular endothelial growth factor c, epidermal growth factor, epidermal growth factor receptor, transforming growth factor-beta1, and protein kinase B/AKT. We also investigated the in vivo role of UTI by using a xenograft mouse model, and immunohistochemical assay was employed to show the expression of factors involved in either angiogenesis or the epithelial-mesenchymal transition (EMT). Our results showed that UTI inhibited invasion and metastasis in both primary and MDA-MB-231 cells both in vivo and in vitro. Especially, UTI presented the significant combined effects with TXT on these cells in terms of angiogenesis blocking and EMT inhibition. These results suggest that UTI and its combination with TXT present therapeutic potential against breast cancer and deserve further preclinical and clinical studies.
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[661]
TÍTULO / TITLE: - Melatonin inhibits cell growth and migration, but promotes apoptosis in gastric cancer cell line, SGC7901.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biotech Histochem. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 3109/10520295.2013.769633
AUTORES / AUTHORS: - Zhang S; Qi Y; Zhang H; He W; Zhou Q; Gui S; Wang Y
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular Biology and Department of Biochemistry.
RESUMEN / SUMMARY: - The pineal hormone, melatonin (MLT), has been shown to have therapeutic effects in patients with gastric cancer; however, the mechanisms for the anti-cancer effects are unknown. We investigated the effects of melatonin on cell proliferation, apoptosis, colony formation and cell migration in the gastric adenocarcinoma cell line, SGC7901, using MTT assay, Hoechst 33258 staining, flow cytometry, western blot, caspase-3 activity assay, soft agar colony formation assay, and scratch-wound assay. Our results showed that melatonin could inhibit cell proliferation, colony formation and migration efficiency, and it promoted apoptosis of SGC7901 cells. Our findings suggest that the anti-cancer effects of melatonin may be due to both inhibition of tumor cell proliferation and reduction of the metastatic potential of tumor cells.
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[662]
TÍTULO / TITLE: - Zerumbone induces apoptosis in human renal cell carcinoma via Gli-1/Bcl-2 pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmazie. 2013 Feb;68(2):141-5.
AUTORES / AUTHORS: - Sun Y; Sheng Q; Cheng Y; Xu Y; Han Y; Wang J; Shi L; Zhao H; Du C
INSTITUCIÓN / INSTITUTION: - Department of Urology, Shaanxi Provincal People’s Hospital, Xi’an, P. R. China. adoremidfall@yahoo.cn
RESUMEN / SUMMARY: - Renal cell carcinoma (RCC) is a malignant disease insensitive to conventional treatments such as radiochemotherapy and immunotherapy. Search for new approaches to induce cancer cell apoptosis will improve the management of RCC. Here, we reported that zerumbone, a monosesquiterpine, shows anticancer effects on human RCC cells via induction of apoptosis in vitro. Human renal clear cell carcinoma 786-0 and 769-P cell lines were used as the model system. Exposure of RCC cells to zerumbone resulted in cell viability inhibition, accompanied by DNA fragmentation and increased apoptotic index. Mechanically, treatment of RCC cells with zerumbone activated caspase-3 and caspase-9, and finally led to cleavage of PARR In addition, downregulation of Gli-1 and Bcl-2, which were closely related to the chemoresistance of RCC, was observed in zerumbone-treated RCC cells. Taken together, our study provided the first evidence that zerumbone imparted strong inhibitory and apoptotic effects on human RCC cells. The zerumbone-induced apoptosis might be related to the activation of the caspase cascade and deregulation of the Gli-1/Bcl-2 pathway. Our results suggest that zerumbone merit further investigation as an apoptosis inducer as well as a novel RCC chemotherapeutic agent in the clinical setting.
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[663]
TÍTULO / TITLE: - Anticancer effect of ursolic acid stearoyl glucoside in chemically induced hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Physiol Biochem. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s13105-013-0245-8
AUTORES / AUTHORS: - Kazmi I; Narooka AR; Afzal M; Singh R; Al-Abbasi FA; Ahmad A; Anwar F
INSTITUCIÓN / INSTITUTION: - Siddhartha Institute of Pharmacy, Dobachi, Near IT Park, Dehra Dun, 248001, Uttarakhand, India.
RESUMEN / SUMMARY: - Hepatocellular carcinoma is one of the leading causes of death in cancer and yet no drug has proven to be a successful candidate for its treatment in advanced stages. Ursolic acid stearoyl glucoside (UASG) is a newly discovered triterpene in Lantana camara and there lies a possibility that it possess anti-hepatocellular carcinoma property. In the present study, we induced hepatocellular carcinoma in Wistar rats by diethylnitrosamine (DENA) and treated it with ursolic acid stearoyl glucoside. The ability to treat hepatocellular carcinoma was measured by comparing biochemical serum markers such as serum alanine aminotransferase, serum aspartate aminotransferase, serum alkaline phosphatase, and the specific marker for hepatocellular carcinoma, alpha fetoprotein. The histological studies of the livers were also performed. The results have shown significant elevated levels of these parameters as compared to normal control and the drug receiving groups have shown significant reduction in these marker levels. Histopathological studies also indicated the reduced liver damage in drug-treated groups. It was noted that a significant and dose-dependent reversal of DENA-diminished activity of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, and the reduced DENA-elevated level of lipid peroxidation (LPO) with a marked change. UASG significantly suppressed free radical formation by scavenging the hydroxyl radicals. It also modulates the levels of LPO and markedly increases the endogenous antioxidant enzymes level in DENA-induced hepatocellular carcinogenesis.
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[664]
TÍTULO / TITLE: - Biomarkers for predicting future metastasis of human gastrointestinal tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Mol Life Sci. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1007/s00018-013-1266-8
AUTORES / AUTHORS: - Ng L; Poon RT; Pang R
INSTITUCIÓN / INSTITUTION: - Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China, luing@hku.hk.
RESUMEN / SUMMARY: - The recent advances in surgery and radiation therapy have significantly improved the prognosis of patients with primary cancer, and the major challenge of cancer treatment now is metastatic disease development. The 5-year survival rate of cancer patients who have distant metastasis at diagnosis is extremely low, suggesting that prediction and early detection of metastasis would definitely improve their prognosis because suitable patient therapeutic management and treatment strategy can be provided. Cancer cells from a primary site give rise to a metastatic tumor via a number of steps which require the involvement and altered expression of many regulators. These regulators may serve as biomarkers for predicting metastasis. Over the past few years, numerous regulators have been found correlating with metastasis. In this review, we summarize the findings of a number of potential biomarkers that are involved in cadherin-catenin interaction, integrin signaling, PI3K/Akt/mTOR signaling and cancer stem cell identification in gastrointestinal cancers. We will also discuss how certain biomarkers are associated with the tumor microenvironment that favors cancer metastasis.
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[665]
TÍTULO / TITLE: - Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 28;13(1):163.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-163
AUTORES / AUTHORS: - Fountzilas G; Dafni U; Bobos M; Kotoula V; Batistatou A; Xanthakis I; Papadimitriou C; Kostopoulos I; Koletsa T; Tsolaki E; Televantou D; Timotheadou E; Koutras A; Klouvas G; Samantas E; Pisanidis N; Karanikiotis C; Sfakianaki I; Pavlidis N; Gogas H; Linardou H; Kalogeras KT; Pectasides D; Dimopoulos MA
RESUMEN / SUMMARY: - BACKGROUND: The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >=2.2 and >=2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated. RESULTS: HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death. CONCLUSION: HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and ACTRN12609001036202.
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[666]
TÍTULO / TITLE: - The prognostic value of breast cancer resistance protein (BCRB/ABCG2) expression in breast carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Environ Pathol Toxicol Oncol. 2012;31(4):367-76.
AUTORES / AUTHORS: - Omran OM
INSTITUCIÓN / INSTITUTION: - Departments of Pathology, Faculty of Medicine, Assiut and Qassim Universities, Egypt and Kingdom of Saudi Arabia. ola67oh@yahoo.com
RESUMEN / SUMMARY: - In cancer, the level of expression of breast cancer resistance protein (BCRP/ABCG2) can vary depending on cell type. However, its precise role in breast cancer has been controversial. The aim of this study was to investigate the expression of ABCG2 in breast carcinomas and relate the results to the established prognostic factors. An immunohistochemical study was conducted on 200 breast carcinoma specimens using the avidin-biotin peroxidase method. ABCG2 was expressed in 77% of cases of invasive ductal carcinoma. There was a statistically significant correlation between ABCG2 expression and each of the tumor grade, clinical stage, lymph node metastasis, and HER2 immunostaining, but no such association with progesterone receptor (PR) and estrogen receptor (ER) status. Increased expression of ABCG2 in invasive ductal carcinoma cells and its statistically significant correlation with HER2 expression are strongly correlated with tumor progression, invasion, and metastasis in human breast cancer and indicates that ABCG2 can be used as a target for the development of novel therapies.
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[667]
TÍTULO / TITLE: - Elevated cyclin D1 expression is predictive for a benefit from TPF induction chemotherapy in oral squamous cell carcinoma patients with advanced nodal disease.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1013
AUTORES / AUTHORS: - Zhong LP; Zhu DW; William WN Jr; Liu Y; Ma J; Yang CZ; Yang X; Wang LZ; Li J; Myers JN; Lee JJ; Zhang CP; Zhang ZY
INSTITUCIÓN / INSTITUTION: - 1Oral & Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine.
RESUMEN / SUMMARY: - Induction chemotherapy is likely to be effective for biologically distinct subgroups of cancer patients with biomarker detection. In order to investigate the prognostic and predictive values of cyclin D1 expression in patients with oral squamous cell carcinoma(OSCC) who were treated in a prospective, randomized, phase 3 trial evaluating standard treatment with surgery and post-operative radiotherapy preceded or not by induction docetaxel, cisplatin and 5-fluorouracil(TPF). Immunohistochemical staining for cyclin D1 was performed in pretreatment biopsy specimens of 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Cyclin D1 index was estimated as the proportion of tumor cells with cyclin D1 nuclear staining. A low cyclin D1 expression predicted significantly better overall survival(P=0.001), disease-free survival(P=0.005), locoregional recurrence-free survival(P=0.003) and distant metastasis-free survival(P=0.002) compared to high cyclin D1 expression. Cyclin D1 expression levels were not predictive of benefit from induction TPF in the population overall. However, patients with nodal stage cN2 whose tumors had high cyclin D1 expression treated with TPF had significantly greater overall survival(P=0.025) and distant metastasis-free survival(P=0.025) when compared to high cyclin D1 cN2 patients treated with surgery upfront. Patients with low cyclin D1 level or patients with cN0 or cN1 disease did not benefit from induction chemotherapy. This study indicates that cN2 OSCC patients with high cyclin D1 expression can benefit from the addition of TPF induction chemotherapy to standard treatment. Cyclin D1 expression could be used as a biomarker in further validation studies to select cN2 patients that could benefit from induction therapy.
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[668]
TÍTULO / TITLE: - Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocr Relat Cancer. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0223
AUTORES / AUTHORS: - Hilfenhaus G; Gohrig A; Pape UF; Neumann T; Jann H; Zdunek D; Hess G; Stassen JM; Wiedenmann B; Detjen K; Pavel M; Fischer C
INSTITUCIÓN / INSTITUTION: - G Hilfenhaus, ECRC, Experimental and Clinical Research Center, a joint cooperation between the Charite Medical Faculty and the Max-Delbruck Center for Molecular Medicine, Berlin, Germany.
RESUMEN / SUMMARY: - Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in sera of NET patients collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF were elevated in patients with pancreatic NETs (pNETs) as compared to control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as prognostic parameter and therapeutic target.
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[669]
TÍTULO / TITLE: - Should all postmenopausal patients with hormone receptor-positive breast cancer receive initial therapy with aromatase inhibitors?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast. 2013 Feb 27. pii: S0960-9776(13)00009-X. doi: 10.1016/j.breast.2013.01.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.breast.2013.01.007
AUTORES / AUTHORS: - Aapro M; van de Velde CJ; Markopoulos C; Bartlett JM; Putter H; Coleman RE
INSTITUCIÓN / INSTITUTION: - Clinique de Genolier, Switzerland. Electronic address: maapro@genolier.net.
RESUMEN / SUMMARY: - BACKGROUND: In the past few years aromatase inhibitors (AIs) have shown superior efficacy to the previous standard adjuvant endocrine therapy, tamoxifen, and are now recommended as part of current adjuvant endocrine therapy. A range of treatment strategies have been explored. MATERIALS AND METHODS: We assess the role of initial AI therapy for postmenopausal women with hormone receptor-positive breast cancer and consider the relative value of initial therapy with an AI compared with switch or extended (>5-yr) adjuvant therapy. RESULTS: Both initial AI therapy and switching/sequential tamoxifen followed by an AI are associated with longer disease- and relapse-free survival versus 5 years of tamoxifen alone. Trials comparing initial therapy with the sequence of tamoxifen followed by an AI have not demonstrated any major efficacy differences between the treatment strategies. Several analyses have been conducted to identify prognostic or predictive markers of treatment benefit to enable selection of the most appropriate adjuvant therapy. CONCLUSIONS: Initial and switching/sequential regimens are equally appropriate adjuvant treatment options for postmenopausal patients with hormone receptor-positive breast cancer. The exact tumour biology which allows for initial AI therapy has not yet been determined with certainty.
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[670]
TÍTULO / TITLE: - A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacogenomics J. 2013 Mar 12. doi: 10.1038/tpj.2013.7.
●● Enlace al texto completo (gratuito o de pago) 1038/tpj.2013.7
AUTORES / AUTHORS: - Han JY; Lee YS; Shin ES; Hwang JA; Nam S; Hong SH; Ghang HY; Kim JY; Yoon SJ; Lee JS
INSTITUCIÓN / INSTITUTION: - Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
RESUMEN / SUMMARY: - We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) influencing overall survival (OS) of small-cell lung cancer (SCLC) patients. We prospectively collected blood samples from 139 SCLC patients who participated in phase II studies of irinotecan and cisplatin (IP) chemotherapy as first-line therapy. Among 334 127 SNPs, which passed quality control, seven showed significant association with OS. The rs16950650CT, rs7186128AG or GG, rs17574269AG, rs8020368CC, rs4655567CC, rs2166219TT or rs2018683TT showed shorter OS compared with control alleles. Among the seven SNPs, rs4655567, rs8020368 and rs2018683 were significantly associated with a resistant relapse (RR). In the multivariate analysis, rs8020368CC was significantly associated with higher risk of RR (odds ratio=16.7, P=0.007). In vitro and in silico analysis showed that SNPs in C14orf49 might be associated with epithelial-to-mesenchymal transition. This exploratory GWAS identified candidate SNPs that may be predictive of the clinical outcome of SCLC patients receiving IP.The Pharmacogenomics Journal advance online publication, 12 March 2013; doi:10.1038/tpj.2013.7.
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[671]
TÍTULO / TITLE: - Nested Case Control Study of Proteomic Biomarkers for Interstitial Lung Disease in Japanese Patients With Non-Small-Cell Lung Cancer Treated With Erlotinib: A Multicenter Phase IV Study (JO21661).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Mar 12. pii: S1525-7304(13)00024-7. doi: 10.1016/j.cllc.2012.12.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.12.006
AUTORES / AUTHORS: - Atagi S; Katakami N; Yoshioka H; Fukuoka M; Kudoh S; Ogiwara A; Imai M; Ueda M; Matsui S
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Oncology, National Hospital, Organization Kinki-chuo Chest Medical Center, Sakai, Japan. Electronic address: s-atagi@kch.hosp.go.jp.
RESUMEN / SUMMARY: - BACKGROUND: Interstitial lung disease (ILD) is a serious adverse drug reaction associated with epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR TKIs). Its risk factors are yet to be fully elucidated. We sought to identify proteomic biomarkers associated with ILD development in erlotinib-treated Japanese patients with non-small-cell lung cancer (NSCLC) to build predictive models. PATIENTS AND METHODS: We conducted a nested case-control study. The participants were patients with NSCLC enrolled in a phase IV study of erlotinib in whom ILD developed within 120 days after erlotinib administration. The controls were randomly selected patients without ILD from the overall study cohort who were also treated with erlotinib. Serum samples were obtained before the first administration of erlotinib and were assayed by liquid chromatography-mass spectroscopy/mass spectroscopy (LC-MS/MS). Logistic regression analysis was performed to identify the peptide and proteins associated with ILD. RESULTS: A total of 645 patients were enrolled in the cohort; 15 case patients and 64 controls were analyzed. When multiplicity was taken into account, we were unable to statistically verify any genuine association between individual markers and ILD. Investigation of the predictive power based on leave-one-out cross-validation (LOOCV) showed that the area under the receiver operating characteristic curve was 0.73 at a maximum. Additional analysis suggested that 3 proteins (C3, C4A/C4B, and APOA1) have a stronger association with ILD than do the other proteins tested. CONCLUSION: We were unable to demonstrate predictive serum protein markers for ILD development. However, C3, C4A/C4B, and APOA1 are worthy of further investigation.
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[672]
TÍTULO / TITLE: - Ki-67 evaluation at the hottest spot predicts clinical outcome of patients with hormone receptor-positive/HER2-negative breast cancer treated with adjuvant tamoxifen monotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s12282-013-0455-5
AUTORES / AUTHORS: - Honma N; Horii R; Iwase T; Saji S; Younes M; Ito Y; Akiyama F
INSTITUCIÓN / INSTITUTION: - Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan, nhonma@tmig.or.jp.
RESUMEN / SUMMARY: - BACKGROUND: The clinicopathological importance of Ki-67 in breast cancers has been intensely studied; however, there have been few systematic large studies of patients treated with predefined adjuvant therapy. Further, Ki-67 evaluation methodology differed among studies, which prevents Ki-67 from being used for clinical practice. We performed a large systematic study using routinely processed tissues and compared various scoring methods. METHODS: Representative slides of archival tissue blocks of 442 consecutive invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and having a long follow-up period were subjected to immunohistochemistry using anti-Ki-67 monoclonal antibody, Mib-1. Both the average score across the section and the score at the hottest spot were assessed. RESULTS: Ki-67 evaluated at the hottest spot, not the average score across the section, independently predicted poor clinical outcomes of patients with hormone receptor-positive/HER2-negative cancer. Ki-67 was not a predictor of clinical outcome in patients with triple-negative breast cancer. Overall, high Ki-67 level significantly correlated with classic unfavorable clinicopathological factors, correlating negatively with the status of estrogen receptor (ER)-alpha and progesterone receptor (PR), and positively with HER2 status and grade. ER-beta status positively correlated with the Ki-67 level. CONCLUSIONS: Ki-67 evaluation at the hottest spot was superior to that determined by average score across the section as a predictor of outcome in patients with hormone receptor-positive/HER2-negative breast cancers treated with endocrine monotherapy. The different result obtained in patients with triple-negative carcinomas needs to be further investigated.
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[673]
TÍTULO / TITLE: - The effect of imatinib therapy on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hematology. 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1179/1607845412Y.0000000052
AUTORES / AUTHORS: - Zhang FH; Ling YW; Zhai X; Zhang Y; Huang F; Fan ZP; Zhou HS; Jiang QL; Sun J; Liu QF
RESUMEN / SUMMARY: - OBJECTIVE: To evaluate the efficacy of imatinib administration before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). METHOD: Patients with imatinib therapy time exceeding 30 days pre-/post-transplant were screened in our data. Imatinib was used in induced or consolidated chemotherapy pre-transplant, or maintenance therapy after 60 days post-transplant (therapy time was less than 180 days) regardless of the molecular status of the disease. RESULTS: Sixty-nine patients with Ph+ ALL were enrolled in the retrospective analysis. Forty-four patients received imatinib therapy, including 24 pre-transplant, 9 post-transplant, and 11 both pre- and post-transplant. With a median follow-up time of 395 days (range, 55-2762 days) post-transplant, 3-year estimated overall survival was 62.3 +/- 16.6, 40.0 +/- 21.9, 41.7 +/- 22.2, and 25.9 +/- 11.4%, respectively (P = 0.221), and disease-free survival (DFS) was 53.6 +/- 17.9, 20.0 +/- 17.9, 33.3 +/- 25.5% and 23.6 +/- 11.4%, respectively (P = 0.421), in patients with imatinib therapy pre-transplant, post-transplant, both pre- and post-transplant, neither pre- nor post-transplant. The incidence of relapse at 3 year for patients with imatinib therapy post-transplant (n = 20) was 63.6%, comparing with 24.2% (P = 0.018) in patients without imatinib therapy post-transplant (n = 49). The ratio of CD4+CD25+Foxp3+ cells in blood was significantly higher at 30 and 60 days after imatinib therapy than that at the time of pre-imatinib in 20 patients (P = 0.019 and 0.001, respectively). CONCLUSIONS: Application of imatinib pre-transplant might have benefited for patients with Ph+ ALL. Whether administration of imatinib, regardless of the molecular status of the disease post-transplant increases relapse, is a worthy goal for further study.
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[674]
TÍTULO / TITLE: - Interferon-Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) as a Prognostic Marker for Local Control in T1-2 N0 Breast Cancer Treated with Breast-Conserving Surgery and Radiation Therapy (BCS + RT).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast J. 2013 Mar 26. doi: 10.1111/tbj.12097.
●● Enlace al texto completo (gratuito o de pago) 1111/tbj.12097
AUTORES / AUTHORS: - Danish HH; Goyal S; Taunk NK; Wu H; Moran MS; Haffty BG
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, The Cancer Institute of New Jersey & UMDNJ/Robert Wood Johnson Medical School, New Brunswick, New Jersey.
RESUMEN / SUMMARY: - Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) expression, involved in the regulation of translation, has been implicated to mediate resistance to chemotherapy and radiation in cancer cells in vitro. The purpose of this study was to evaluate the prognostic significance of IFIT1 protein expression in patients with breast cancer treated with Breast-Conserving Surgery and Radiation Therapy (BCS + RT). A tissue microarray was constructed with specimens from 282 women with node-negative, early-stage (I/II) breast cancer who were treated with BCS + RT. Immunohistochemistry was used to stain for the IFIT1 protein. Cytoplasmic IFIT1 protein expression levels were correlated with clinicopathologic factors, local relapse-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). IFIT1 positivity was found in 123 (49%) of cases. The median follow-up time was 7.3 years. Eighty percent of the patients had T1 disease, 88% were human epidermal growth factor receptor 2 (HER2) negative, and 20% had triple-negative breast cancer (TNBC). IFIT1 positivity was associated with estrogen receptor negative status (p = 0.002), progesterone receptor negative status (p = 0.02), TNBC (p = 0.01), and HER2-positive status (p = 0.006). In univariate and multivariate analysis, IFIT1 positivity was associated with improved LRFS (p = 0.055 and p = 0.04, respectively). Using a log-rank test, IFIT1 positivity was found to be associated with improved LRFS (94% versus 85%, p = 0.046) but not DFS or OS at 10 years. On subset analysis of the TNBC patients, IFIT1 positivity was found to correlate with improved LRFS (100% versus 53%, p = 0.004) and DFS in (87% versus 49%, p = 0.048) at 10 years. Elevated IFIT1 protein expression is associated with improved LRFS. In addition, our data suggest that IFIT1 expression may help risk stratify patients with TNBC who may benefit from more aggressive therapy. As there is limited data on IFIT1 in breast cancer, additional work is needed to ascertain its significance.
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[675]
TÍTULO / TITLE: - HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res. 2013 Feb 7;15(1):R11.
●● Enlace al texto completo (gratuito o de pago) 1186/bcr3384
AUTORES / AUTHORS: - Denkert C; Huober J; Loibl S; Prinzler J; Kronenwett R; Darb-Esfahani S; Brase JC; Solbach C; Mehta K; Fasching PA; Sinn BV; Engels K; Reinisch M; Hansmann ML; Tesch H; von Minckwitz G; Untch M
RESUMEN / SUMMARY: - ABSTRACT: INTRODUCTION: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. METHODS: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. RESULTS: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. CONCLUSIONS: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group.
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[676]
TÍTULO / TITLE: - FGFR4 genetic polymorphisms determine the chemotherapy response of Chinese patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Pharmacol Sin. 2013 Apr;34(4):549-54. doi: 10.1038/aps.2012.206. Epub 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1038/aps.2012.206
AUTORES / AUTHORS: - Fang HM; Tian G; Zhou LJ; Zhou HY; Fang YZ
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
RESUMEN / SUMMARY: - Aim:To investigate the relationship of fibroblast growth factor receptor 4 (FGFR4) gene polymorphisms with the response of Chinese patients with non-small cell lung cancer (NSCLC) to chemotherapy.Methods:A total of 629 patients with Stage III (A+B) or IV NSCLC, as well as 729 age- and gender-matched healthy controls were recruited. All the patients received platinum-based chemotherapy, and the therapeutic effects were evaluated. Three polymorphisms in the FGFR4 gene (rs351855G/A, rs145302848C/G, and rs147603016G/A) were genotyped, and the association between the 3 polymorphisms and the chemotherapy effect was analyzed using SPSS software, version 16.0.Results:The genotype frequencies of rs145302848C/G and rs147603016G/A were not significantly different between NSCLC patients and healthy controls on one hand, and between the responders and non-responders to the chemotherapy on the other hand. The distribution of AA genotype and A-allele of rs351855G/A was significantly lower in NSCLC patients than in healthy controls. Using patients with the GG genotype as a reference, the AA carrier had a significantly reduced risk for the development of NSCLC after normalizing to age, sex and smoking habits. In NSCLC patients, this genotype occurred more frequently in the responders to the chemotherapy than in non-responders. The chance of being a responder was significantly increased with the AA genotype as compared to G genotype. The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers: the overall survival of patients with the AA genotype of rs351855G/A was significantly longer than those with the GG+GA genotype (21.1 vs 16.5 months).Conclusion:The rs351855G/A polymorphisms of FGFR4 gene can be used to predict the occurrence, chemotherapy response and prognosis of NSCLC.
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[677]
TÍTULO / TITLE: - Erratum to: Recovery of visual function in patient with melanoma-associated retinopathy treated with surgical resection and interferon-beta.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Doc Ophthalmol. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s10633-013-9376-z
AUTORES / AUTHORS: - Yamamoto S; Hanaya J; Mera K; Miyata K
INSTITUCIÓN / INSTITUTION: - Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan, shuyama@faculty.chiba-u.jp.
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[678]
TÍTULO / TITLE: - Prognostic value of geriatric assessment in older patients with advanced breast cancer receiving chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast. 2013 Feb 14. pii: S0960-9776(13)00013-1. doi: 10.1016/j.breast.2013.01.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.breast.2013.01.011
AUTORES / AUTHORS: - Aaldriks AA; Giltay EJ; le Cessie S; van der Geest LG; Portielje JE; Tanis BC; Nortier JW; Maartense E
INSTITUCIÓN / INSTITUTION: - Institute of Mental Health, Bouman GGZ, Rotterdam, The Netherlands. Electronic address: a.aaldriks@telfort.nl.
RESUMEN / SUMMARY: - INTRODUCTION: The prognostic value of geriatric assessment in older patients with breast cancer treated with chemotherapy is largely unknown. METHODS: Fifty-five patients with advanced breast cancer aged 70 years or older were assessed by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Levels of albumin, hemoglobin, creatinine and lactate dehydrogenase were measured. Patients completing at least four cycles of chemotherapy were reassessed by GFI and MMSE and mortality was evaluated using Cox regression analysis. RESULTS: The mean age was 76 year (SD 4.8). Inferior MNA and GFI scores were associated with increased hazard ratios for mortality: 3.05 (95% confidence interval [CI]: 1.44-6.45; p = 0.004) and 3.40 (95% CI: 1.62-7.10; p = 0.001), respectively. Physical aspects of frailty worsened during the course of chemotherapy. Laboratory values were not associated with assessment scores nor were they predictive for mortality. CONCLUSIONS: Malnutrition and frailty, rather than cognitive impairment and laboratory values, were associated with an increased mortality risk in these elderly breast cancer patients with advanced breast cancer.
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[679]
TÍTULO / TITLE: - Malignant hypertension in patients treated with vascular endothelial growth factor inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Hypertens (Greenwich). 2013 Mar;15(3):215-6. doi: 10.1111/jch.12052. Epub 2012 Dec 19.
●● Enlace al texto completo (gratuito o de pago) 1111/jch.12052
AUTORES / AUTHORS: - Caro J; Morales E; Gutierrez E; Ruilope LM; Praga M
INSTITUCIÓN / INSTITUTION: - From the Nephrology Department, Hospital 12 de Octubre, Madrid, España.
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[680]
TÍTULO / TITLE: - Safety and treatment patterns of angiogenesis inhibitors in patients with advanced renal cell carcinoma in España.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Drug Saf. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1517/14740338.2013.781581
AUTORES / AUTHORS: - Castellano D; Duh MS; Korves C; Suthoff ED; Neary M; Hernandez Pastor LJ; Bellmunt J
INSTITUCIÓN / INSTITUTION: - Hospital Universitario 12 de Octubre, Madrid , España.
RESUMEN / SUMMARY: - Objective: To examine real-world safety and treatment patterns of angiogenesis inhibitors for advanced renal cell carcinoma (aRCC) using observational data from two Spanish hospitals. Methods: A retrospective medical record review was performed for 93 patients with a histological diagnosis of aRCC who received sunitinib, sorafenib, bevacizumab or temsirolimus as first-line angiogenesis inhibitor therapy, between January 2005 and September 2010 at two Spanish hospitals. Data were collected on adverse events (AEs), dosing to calculate relative dose intensity (RDI), treatment modifications and reasons for modifications. Results: Sixty patients received sunitinib, 23 received sorafenib, 6 received bevacizumab, 1 received temsirolimus and 3 received a bevacizumab-temsirolimus combination. 91.7 and 100.0% of patients receiving sunitinib and sorafenib, respectively, experienced >/= 1 AE; 40.0% and 43.5% had >/= 1 grade ¾ AE. Mean RDI for sunitinib and sorafenib were 0.866 (standard deviation (std) = 0.903) and 0.798 (std = 2.154), respectively. Among patients receiving sunitinib, 15.0% discontinued treatment, 43.3% had an interruption and 33.3% had a reduction due to AEs. For sorafenib, these rates were 4.3, 56.5 and 34.8%, respectively. Conclusions: High rates of AEs were observed which resulted in high rates of treatment interruptions and dose reductions. These results suggest the need for additional treatment options for aRCC with improved tolerability.
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[681]
TÍTULO / TITLE: - ATM-mediated up-regulation of NKG2D ligands on leukemia cells by resveratrol results in enhanced NK cells susceptibility.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Sci. 2013 Feb 27. doi: 10.1111/cas.12141.
●● Enlace al texto completo (gratuito o de pago) 1111/cas.12141
AUTORES / AUTHORS: - Luis Espinoza J; Takami A; Trung LQ; Nakao S
INSTITUCIÓN / INSTITUTION: - Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa, Japan.
RESUMEN / SUMMARY: - NKG2D is a powerful activating receptor expressed by natural killer (NK) cells that promotes cytotoxic lysis of cancer cells expressing NKG2D ligands (NKG2D-Ls). We herein report the effective induction of NKG2D-L which was achieved with the naturally occurring polyphenol resveratrol in a broad range of leukemia cells. In this study, resveratrol upregulated the NKG2D-Ls MICA/B, ULBP1, ULBP2 and ULBP3 in most of the leukemia cells analyzed. Ligand upregulation induced by resveratrol was impaired by pharmacological and genetic disruption of ATM kinase, the main regulator of the NKG2D-L expression. Leukemia cells treated with resveratrol were more susceptible to killing by NK cells than untreated cells, and the enhanced cytotoxicity of NK cells was blocked by treatment of NK cells with anti-NKG2D monoclonal antibodies. Interestingly, resveratrol consistently upregulated the NKG2D receptor expression and enhanced NKG2D-mediated functions in resting NK cells obtained from healthy individuals. Therefore, resveratrol has an attractive immunotherapeutic potential.
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[682]
TÍTULO / TITLE: - The roles of epigenetic modifications of proapoptotic BID and BIM genes in imatinib-resistant chronic myeloid leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hematology. 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 1179/1607845412Y.0000000056
AUTORES / AUTHORS: - Bozkurt S; Ozkan T; Ozmen F; Baran Y; Sunguroglu A; Kansu E
RESUMEN / SUMMARY: - In chronic myeloid leukemia (CML), epigenetic modifications such as promoter hypermethylation and inactive histone modification are known mechanisms of drug resistance. In our study, we investigated the roles of promoter hypermethylation of BIM and BID genes and H3K27me3 histone modification on imatinib resistance. We detected higher expression levels of BIM and BID genes and lower expression levels of EZH2, EED2, SIRT1, and SUZ12 genes in imatinib-resistant K562/IMA-3 cells compared to imatinib-non-resistant K562 cells. While we determined the EZH2 and DNMT enzymes as bounded to the promoter of the BIM gene, we did not detect hypermethylation of this promoter. We also found the H3K27me3 histone modification promoter of BIM and BID genes in both cell lines. In conclusion, our results support the notion that DNA promoter methylation may be formed independently from EZH2-H3K27me3 and pro-apoptotic BIM and BID genes are not methyllated in the imatinib resistance of CML cells.
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[683]
TÍTULO / TITLE: - Clinicopathological and prognostic implications of arginase expression in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lab. 2013;59(1-2):37-43.
AUTORES / AUTHORS: - Mao H; Gao W; Lu G; Fang F; Teng L
INSTITUCIÓN / INSTITUTION: - First Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310003, China. morwindbeiyong@yahoo.com.cn
RESUMEN / SUMMARY: - BACKGROUND: To investigate the correlation of Arg-1 expression with clinicopathologic factors and prognosis of HCC patients, including recurrence and survival rate. METHODS: We examined the expression of Arg-1 in HCC by immunohistochemistry and studied its correlation with a series of clinicopathologic features and prognositic parameters of patients with HCC. RESULTS: We found patients with higher Arg-1 expression showed less aggressive features based on less portal vein invasion (chi2 = 10.794, df = 1, p = 0.001), less microvessel invasion (chi2 = 4.247, df = 1, p = 0.039), lower TNM stage (chi2 = 4.992, df = 1, p = 0.025), and better differentiated histology (chi2 = 24.155, df= 1, p < 0.001). Among them, portal vein invasion (p = 0.024, 95% CI 1.010 - 2.321), microvessel invasion (p = 0.043, 95% CI 1.014 - 3.225), histology (p = 0.001, 95% CI 2.230 - 5.934), and TNM stage (p = 0.001, 95% CI 1.364 - 3.401) have been suggested as prognostic factors in HCC patients. Furthermore, the enhanced expression of Arg-1 in HCC appears to be associated with a lower recurrence rate and prolonged overall survival. CONCLUSIONS: These results suggest that Arg-1 may play a tumor suppressive role in HCC and could be a new, promising prognostic biomarker for HCC patients.
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[684]
TÍTULO / TITLE: - Oral Disinfectants Inhibit Protein-Protein Interactions Mediated by the Anti-Apoptotic Protein Bcl-x and Induce Apoptosis in Human Oral Tumor Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Angew Chem Int Ed Engl. 2013 Mar 19. doi: 10.1002/anie.201208889.
●● Enlace al texto completo (gratuito o de pago) 1002/anie.201208889
AUTORES / AUTHORS: - Graber M; Hell M; Grost C; Friberg A; Sperl B; Sattler M; Berg T
INSTITUCIÓN / INSTITUTION: - Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) uni-leipzig.de/ approximately tberg; Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany).
RESUMEN / SUMMARY: - Chlorhexidine and alexidine have long been used as oral disinfectants by humans. Both compounds inhibit protein-protein interactions mediated by the anti-apoptotic protein Bcl-xL at physiologically relevant concentrations and induce apoptosis in a series of tumor cell lines derived from the tongue and pharynx. Inhibition of protein-protein interactions is a potential mode of action of drugs in current human use.
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[685]
TÍTULO / TITLE: - Evaluation of naproxen and cromolyn activities against cancer cells viability, proliferation, apoptosis, p53 and gene expression of survivin and caspase-3.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Enzyme Inhib Med Chem. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3109/14756366.2012.762645
AUTORES / AUTHORS: - Motawi TM; Bustanji Y; El-Maraghy S; Taha MO; Al-Ghussein MA
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, Faculty of Pharmacy, Cairo University , Cairo , Egypt .
RESUMEN / SUMMARY: - Abstract We previously reported the inhibitory profiles of naproxen and cromolyn against glycogen synthase kinase-3beta, which partly explain the molecular mechanisms of their anti-cancer properties. In this study, we performed a detailed biochemical evaluation of the two drugs against colorectal adenocarcinoma (Caco2), hepatocellular carcinoma (HepG2), mammary gland carcinoma (MCF7), epitheloid cervix carcinoma (Hela), lung carcinoma (A5W9) and epidermoid larynx carcinoma (Hep2) cell lines. Additionally, we performed cellular viability tests using trypan blue, proliferation MTT assay, apoptosis, p53 and real-time polymerase chain reaction for gene expression of survivin and caspase-3. Not only the two drugs were found to significantly reduce the viability of different cell lines, but they also were shown to have potent dose-dependent reduction of cellular proliferation. They exhibited cytotoxicity IC(50) values of 3.69 and 4.16 muM for naproxen and cromolyn, respectively. Viability and proliferation results clearly correlated with apoptosis and p53 experiments in showing that both drugs significantly raised apoptotic percentages. Furthermore, we observed a significant reduction in survivin and elevation of caspase-3 gene expression upon exposure to the two drugs. It can be concluded that both naproxen and cromolyn have significant anti-cancer properties.
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[686]
TÍTULO / TITLE: - Fertility in women survivors of hematological malignancies: what is the real role of GnRH analogue treatment?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Exp Obstet Gynecol. 2012;39(4):504-8.
AUTORES / AUTHORS: - Driul L; Londero AP; Papadakis C; Candoni A; Bertozzi S; Fanin R; Marchesoni D
INSTITUCIÓN / INSTITUTION: - Clinic of Obstetrics and Gynecology, Teaching Hospital SM della Misericordia, Udine, Italy.
RESUMEN / SUMMARY: - PURPOSE OF INVESTIGATION: The aim of this study was to evaluate the ovarian function in women who received or not gonadotropin-releasing hormone (GnRH) analogue co-treatment compared to the control group that did not receive it. MATERIALS AND METHODS: This study analyzed 124 patients affected by hematological diseases between 1998 and 2007. The data were analyzed using R (v 2.9.1). RESULTS: In the women treated with GnRH analogue, the authors found 33% post-treatment secondary amenorrhea and 6% had a pregnancy post-treatment, while in the other group the prevalence were respectively 49% and 4% (p n.s.). Moreover, in multivariate analysis the authors found bone marrow transplantation to be a risk factor for secondary amenorrhea, while the association of chemotherapy with radiotherapy was a protective factor (p < 0.05). Finally, none of the considered factors were predictive of pregnancy achievement post-treatment. CONCLUSIONS: The authors found no statistical evidence to support that Gn-RH analogue treatment preserves ovarian follicular reserve during hematologic cancer treatment, but more evidence must be obtained.
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[687]
TÍTULO / TITLE: - Prognostic significance of telomerase-associated parameters in glioblastoma: effect of patient age.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Oncol. 2013 Apr;15(4):423-32. doi: 10.1093/neuonc/nos329. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos329
AUTORES / AUTHORS: - Lotsch D; Ghanim B; Laaber M; Wurm G; Weis S; Lenz S; Webersinke G; Pichler J; Berger W; Spiegl-Kreinecker S
INSTITUCIÓN / INSTITUTION: - Corresponding Authors: Sabine Spiegl-Kreinecker, PhD, Department of Neurosurgery, Wagner-Jauregg Hospital; Wagner-Jauregg Weg 15, 4020 Linz, Austria. sabine.spiegl-kreinecker@gespag.at); Walter Berger, Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria (walter.berger@meduniwien.ac.at.
RESUMEN / SUMMARY: - Background Glioblastoma multiforme (GBM) is a heterogeneous, highly aggressive primary brain tumor with strongly variable patient survival. Because reliable prognostic biomarkers are lacking, we investigated the relation between telomerase-associated parameters and the disease course. Methods Telomerase-associated parameters were determined in 100 GBM tissues and associated with clinical characteristics and overall survival. Expressions of telomere length, telomerase activity (TA), and human telomerase reverse transcriptase (hTERT) were analyzed by quantitative PCR, telomeric repeat amplification protocol assay, and reverse transcriptase-PCR, respectively. Mutation status of isocitrate dehydrogenase (IDH)1 was determined by direct sequencing, and O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation by methylation-specific PCR. Results Of 100 GBM tissues, 61 were positive for both hTERT mRNA and TA, with a highly significant correlation between both parameters (linear regression, P < .0001). Telomere length determination revealed a significant difference between the hTERT/TA-positive and -negative subgroups, with markedly longer telomeres in the hTERT/TA-negative cohort (unpaired Student’s t-test, P = .0001). Accordingly, significantly shorter telomeres were detected in GBM tissues derived from older patients (>60 y at diagnosis, P < .0001). While no association of telomere parameters with MGMT promoter status was found, all tumors with IDH1 mutation (6/100) were negative for both hTERT expression and TA and harbored significantly longer telomeres. Patients with tumors lacking hTERT expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < .01), which, however, was based exclusively on the younger patient subgroup (</=60 y, both P < .005; >60 y, both ns). Conclusions Telomerase activation is not an independent prognostic parameter in GBM but predicts aggressive tumor behavior solely in a younger patient cohort.
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[688]
TÍTULO / TITLE: - C-reactive protein predicts pleurodesis success in malignant pleural effusion patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Palliat Med. 2013 Apr;16(4):337. doi: 10.1089/jpm.2012.0521. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1089/jpm.2012.0521
AUTORES / AUTHORS: - Lapidot M; Faber DL; Nir RR; Orlovsky M; Kagan M; Best LA; Kremer R
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Rambam Health Care Campus , Haifa, Israel .
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[689]
TÍTULO / TITLE: - Oral cavity tumors in younger patients show a poor prognosis and do not contain viral RNA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oral Oncol. 2013 Mar 9. pii: S1368-8375(13)00035-3. doi: 10.1016/j.oraloncology.2013.02.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.oraloncology.2013.02.003
AUTORES / AUTHORS: - Bragelmann J; Dagogo-Jack I; El Dinali M; Stricker T; Brown CD; Zuo Z; Khattri A; Keck M; McNerney ME; Longnecker R; Bieging K; Kocherginsky M; Alexander K; Salgia R; Lingen MW; Vokes EE; White KP; Cohen EE; Seiwert TY
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA; Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany.
RESUMEN / SUMMARY: - BACKGROUND: Oral cavity and in particular oral tongue cancers occur with a rising incidence in younger patients often lacking the typical risk factors of tobacco use, alcohol use, and human papilloma virus (HPV) infection. Their prognosis when treated with chemoradiation has not been well studied and responsible risk factors remain elusive. A viral etiology (other than HPV) has been hypothesized. METHODS: First we analyzed outcomes from 748 head and neck cancer patients with locoregionally advanced stage tumors treated with curative-intent chemoradiation by anatomic site. Second, we analyzed seven oral tongue (OT) tumors from young, non-smokers/non-drinkers for the presence of viral mRNA using short-read massively-parallel sequencing (RNA-Seq) in combination with a newly-developed digital subtraction method followed by viral screening and discovery algorithms. For positive controls we used an HPV16-positive HNC cell line, a cervical cancer, and an EBV-LMP2A transgene lymphoma. RESULTS: Younger patients with oral cavity tumors had worse outcomes compared to non-oral cavity patients. Surprisingly none of the seven oral tongue cancers showed significant presence of viral transcripts. In positive controls the expected viral material was identified. CONCLUSION: Oral cavity tumors in younger patients have a poor prognosis and do not appear to be caused by a transcriptionally active oncovirus.
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[690]
TÍTULO / TITLE: - A Phase II Study of Temozolomide in Patients with Advanced Aerodigestive Tract and Colorectal Cancers and Methylation of the O6-Methylguanine-DNA Methyltransferase Promoter.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0710
AUTORES / AUTHORS: - Hochhauser D; Glynne-Jones R; Potter V; Gravalos C; Doyle TJ; Pathiraja K; Zhang Q; Zhang L; Sausville EA
INSTITUCIÓN / INSTITUTION: - 1Oncology, Cancer Institute UCL.
RESUMEN / SUMMARY: - Responses of patients with gliomas to temozolomide are determined by O(6)-methylguanine-DNA methyltransferase (MGMT) and mismatch repair (MMR) pathways. This phase II study (NCT00423150) investigated whether MGMT promoter methylation predicts response in patients with advanced aerodigestive tract and colorectal cancers. Tumor and serum samples were screened for MGMT promoter methylation. In methylation-positive patients, 150 mg/m(2) temozolomide was administered daily on a 7-day-on, 7-day-off schedule for each 28-day cycle. The primary efficacy endpoint was response rate (RR). MMR status was determined by a microsatellite instability assay. Among 740 patients screened, 86 were positive for MGMT promoter methylation and enrolled. Nineteen percent of the screened population (137/740) had confirmed tissue and/or serum MGMT promoter methylation, including 25% (57/229) for colorectal cancer, 36% (55/154) for esophageal cancer, 11% (12/113) for head and neck cancer, and 5% (13/242) for non-small cell lung cancer. Among patients with valid methylation results in both tissue and serum samples, concordance was 81% (339/419). The majority of enrolled patients (69/86; 80%) had microsatellite stable cancer. Overall RR was 6% (5/86 partial responses); all responders had microsatellite stable cancer. Temozolomide resulted in low RRs in patients enriched for MGMT methylation. MGMT methylation status varied considerably in the patient population. Although serum methylation assay is an option for promoter methylation detection, tissue assay remains the standard for methylation detection. The low RR of this cohort of patients indicates that MGMT methylation as a biomarker is not applicable to heterogeneous tumor types, and tumor-specific factors may override validated biomarkers.
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[691]
TÍTULO / TITLE: - Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Oncol. 2013 Feb;20(1):e13-20. doi: 10.3747/co.20.1055.
●● Enlace al texto completo (gratuito o de pago) 3747/co.20.1055
AUTORES / AUTHORS: - Aviles A; Neri N; Huerta-Guzman J; Nambo MJ
INSTITUCIÓN / INSTITUTION: - Oncology Research Unit, Oncology Hospital, National Medical Center, imss , Mexico DF, Mexico.
RESUMEN / SUMMARY: - BACKGROUND: A growing body of evidence is demonstrating that the nitrogen-containing bisphosphonate zoledronic acid (zol) improves clinical outcomes in various cancer settings, including multiple myeloma. Those findings provided the rationale for conducting an open-label randomized controlled phase iii trial to evaluate the effect of zol on overall survival (os) and progression-free survival (pfs) in patients with previously untreated high-risk multiple myeloma. METHODS: The trial randomly assigned 308 adult patients less than 65 years of age with previously untreated symptomatic multiple myeloma (1:1) to receive zol 4 mg intravenously once every 28 days for 24 months (n = 151) or no zol (n = 157). Before autologous stem-cell transplantation (asct), all patients received a high-dose noncytotoxic induction regimen of dexamethasone, all-trans-retinoic acid, and interferon alpha 2b. RESULTS: After a median follow-up of 69.8 months (range: 36.5-96 months), the 10-year pfs (66% vs. 52%, p < 0.001) and os (67% vs. 48%, p < 0.001) rates were significantly higher in treated patients than in control patients. Overall response (77% zol vs. 75% control), complete response (52% vs. 46%), and very good partial response (25% vs. 29%) rates were similar between the groups. Treatment was generally well tolerated, with no reports of renal impairment or osteonecrosis of the jaw. CONCLUSIONS: In symptomatic previously untreated multiple myeloma patients, zol combined with high-dose therapy followed by asct improved os and pfs without appreciable toxicity. These findings provide additional evidence of the meaningful anticancer activity of zol in this patient population.
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[692]
TÍTULO / TITLE: - Glyoxylate reductase/hydroxypyruvate reductase: a novel prognostic marker for hepatocellular carcinoma patients after curative resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathobiology. 2013;80(3):155-62. doi: 10.1159/000346476. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1159/000346476
AUTORES / AUTHORS: - Pan Y; Ni R; Deng Q; Huang X; Zhang Y; Lu C; Li F; Huang D; He S; Chen B
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Affiliated Hospital of Nantong University, Jiangsu, China.
RESUMEN / SUMMARY: - Objective: Glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a key enzyme in the glyoxylate cycle. Its deficiency causes primary hyperoxaluria type 2. We first noticed that GRHPR was also lost in human hepatocellular carcinoma (HCC) and proliferative HCC cells. The aim of the present study was to investigate the potential clinical utility of GRHPR in HCC. Methods: The expression of GRHPR in tissues and cells was detected by Western blotting. Immunohistochemistry was utilized to examine the expression patterns of GRHPR and Ki-67 in a surgical cohort of HCC and adjacent liver tissues. Results: We demonstrated that GRHPR showed a lower expression in tumor tissues than in nontumoral tissues. GRHPR was negatively correlated with Ki-67 (R(2) = 0.771, p < 0.05) and GRHPR was reduced in proliferative Huh7 cells (p < 0.05). Patients with negative GRHPR both in tumor tissues and nontumoral tissues had a significantly shorter survival time than those with positive GRHPR (p < 0.001). Multivariate analysis established that GRHPR was detected in nontumoral tissues as an independent prognostic factor for patients with HCC. Conclusions: Our findings suggest that the GRHPR defect in noncancerous tissues may represent an independent predictor of poor survival for HCC patients after curative resection and that there may be a link between GRHPR and prognosis of HCC patients.
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[693]
TÍTULO / TITLE: - Management of Metastatic Bone Disease in the Elderly with Bisphosphonates and Receptor Activator of NF-kB Ligand Inhibitors: Effectiveness and Safety.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Oncol (R Coll Radiol). 2013 Mar 1. pii: S0936-6555(13)00094-0. doi: 10.1016/j.clon.2013.01.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clon.2013.01.008
AUTORES / AUTHORS: - Vassiliou V
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus. Electronic address: vasilis.vasiliou@bococ.org.cy.
RESUMEN / SUMMARY: - The life expectancy of Western populations has risen in the last few decades, resulting in a steep increase in the number of elderly cancer patients. Metastatic bone disease (MBD) is an important problem in such patients as it is associated with the development of skeletal-related events (SREs), such as fractures and spinal cord compression. These complications do not only deteriorate the quality of life of affected patients, but can also reduce expected survival. Due to the fact that elderly patients have an increased risk of SREs, maintaining bone health and implementing effective treatments for managing MBD is of vital importance. Bisphosphonates have been shown to be effective in reducing the risk of SREs considerably in patients with MBD. Moreover, they have been shown to reduce pain and improve the quality of life of affected patients. Bisphosphonates should be used with caution in elderly patients due to the fact that their use can bring about renal function deterioration. Several preventive measures need to be followed in order to minimise the risk of this complication. Denosumab is a monoclonal antibody inhibiting receptor activator of NF-kB ligand and has shown superiority over zoledronic acid in reducing the risk of SREs. In the three comparative trials between denosumab and zoledronic acid, survival and disease progression were similar between the two groups. Denosumab has been shown not to affect renal function and can therefore be safely used in the elderly. Osteonecrosis of the jaws is a devastating complication that may occur after treatment with either denosumab or zoledronic acid. The incidence rates between the two are comparable and percentage differences not statistically significant. In the three randomised trials, hypocalcaemia occurred more frequently in denosumab-treated patients than in those managed with zoledronic acid, with the corresponding percentages being 5.5-13% versus 3.4-6%. In order to minimise the risk of osteonecrosis of the jaws and hypocalcaemia, all precautionary measures and treatment guidelines should be followed closely. Several studies have investigated the cost-effectiveness of denosumab versus zoledronic acid when used for SRE prevention. These studies reported contradictory results due to the application of different analytical perspectives and model parameters.
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[694]
TÍTULO / TITLE: - Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Mar 20;11:69. doi: 10.1186/1479-5876-11-69.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-69
AUTORES / AUTHORS: - Chu SH; Ma YB; Feng DF; Li ZQ; Jiang PC
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Shanghai 3rd People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 280 Mohe Road, Baoshan District, Shanghai 201900, China. shenghuachu@126.com.
RESUMEN / SUMMARY: - BACKGROUND: Our previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy. PATIENTS AND METHODS: SLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients. RESULTS: SLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy. CONCLUSIONS: These results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.
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[695]
TÍTULO / TITLE: - Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hematology. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1179/1607845412Y.0000000042
AUTORES / AUTHORS: - Gokbulut AA; Apohan E; Baran Y
RESUMEN / SUMMARY: - Chronic lymphocytic leukemia (CLL), defined by accumulation of pathogenic B cells, has a very complex biology due to various factors such as inherited, host, and enviromental factors. Recently, finding new therapeutic agents or development of novel treatment strategies have been paid attention. Resveratrol and quercetin, important phytoalexins found in many plants, have been reported to have cytotoxic effects on various types of cancer. In this study, we examined cytotoxic, cytostatic, and apoptotic effects of these two important phenolic compounds on 232B4 human CLL cells. Cytotoxic effects of resveratrol and quercetin were determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using caspase-3 colorimetric assay. Annexin V-FITC/PI double staining was performed to measure apoptotic cell population. Effects of resveratrol and quercetin on cell cycle profiles of CLL cells were investigated by flow cytometry. Treatment of CLL cells with resveratrol and quercetin caused dose dependent inhibition of cell proliferation and increased apoptotic cell population through induction of caspase-3 activity. Cell cycle analysis displayed cell cycle arrest mainly in G0/G1 for both polyphenols. Our data, in total, showed for the first time that resveratrol and quercetin might block CLL growth through inducing apoptosis and cell cycle arrest.
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[696]
TÍTULO / TITLE: - Predictors of Fatigue in Cancer Patients Before and After Chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Health Psychol. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1177/1359105313477675
AUTORES / AUTHORS: - Pertl M; Hevey D; Collier S; Lambe K; O’Dwyer AM
INSTITUCIÓN / INSTITUTION: - School of Psychology, Trinity College Dublin, Ireland.
RESUMEN / SUMMARY: - Fatigue is a debilitating and common condition in cancer patients. This study examined pretreatment predictors of fatigue before chemotherapy and also assessed whether these could prospectively predict fatigue posttreatment. A total of 100 patients completed questionnaires assessing psychological factors, physical activity and sleep. A subsample of 26 participants wore actigraphs to objectively assess sleep/wake and activity/rest. Fatigue was measured pretreatment and posttreatment and at follow-up several months later. Greater pretreatment pain, depression, stress and sleep disruption significantly predicted greater fatigue before chemotherapy, explaining 55 percent of the variance. Pretreatment fatigue significantly predicted posttreatment fatigue. No other significant prospective predictors of posttreatment fatigue emerged.
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[697]
TÍTULO / TITLE: - AY4, an agonistic anti-death receptor 4 monoclonal antibody, induces apoptotic cell death in anaplastic thyroid cancer cells via down-regulation of Bcl-xL with reactive oxygen species generation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocr Relat Cancer. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0405
AUTORES / AUTHORS: - Lee BS; Cha HY; Shin YS; Kim YS; Kim CH
INSTITUCIÓN / INSTITUTION: - B Lee, department of otolaryngology, Ajou University School of Medicine, Suwon, Korea, Republic of.
RESUMEN / SUMMARY: - Anaplastic thyroid carcinoma (ATC) is an aggressive human tumor with a median survival of 6 months. We previously developed an agonistic anti-death receptor 4 monoclonal antibody, AY4, and demonstrated the anti-tumor effects of AY4 in head and neck cancer cells. Presently, we show that ATC cells are sensitive to AY4 and that the sensitivity correlates with the reduced expression level of Bcl-xL and reactive oxygen species (ROS) generation. AY4 induced death of C-643, U-HTH 7, HTH83, and SW1736 cells. To elucidate the role of ROS generation in AY4-induced apoptosis of ATC cells, U-HTH 7 and SW1736 cells were pretreated with an anti-oxidant (N-acetyl-cysteine, NAC) followed by AY4 treatment. The cell death was blocked by NAC. AY4-induced cell death was accompanied by the down-regulation of the anti-apoptotic protein, Bcl-xL. To examine the link between the apoptotic response and Bcl-xL protein expression, U-HTH 7 cells were transfected with Bcl-xL plasmid. The consequence of the over-expression of Bcl-xL appeared to decrease AY4-mediated cell death by blocking ROS generation in U-HTH 7 cells. In contrast, Bcl-xL knock-down using small interfering RNA of Bcl-xL enhanced AY4 sensitivity in HTH83 and C-643 cells, and rendered the cells sensitive to AY4-induced cell death. The results support the conclusion that the expression level of Bcl-xL is important in the AY4-induced apoptosis of ATC cells through ROS generation. AY4 may be a promising tool for ATC therapy.
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[698]
TÍTULO / TITLE: - Prognostic impact of expression of bcl-2 and bax genes in circulating immune cells derived from patients with head and neck carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasia. 2013 Mar;15(3):305-14.
AUTORES / AUTHORS: - Tano T; Okamoto M; Kan S; Nakashiro K; Shimodaira S; Koido S; Homma S; Sato M; Fujita T; Kawakami Y; Hamakawa H
INSTITUCIÓN / INSTITUTION: - Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
RESUMEN / SUMMARY: - Antitumor functions of the host immune system are frequently compromised in patients with malignancies. In the current study, we evaluated the relationship between expression ratio of mRNAs for the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax (the Bcl-2/Bax ratio) in peripheral blood mononuclear cells and clinical outcomes in patients with head and neck carcinomas. The overall survival (OS) time of patients with Bcl-2/Bax ratios >/= 1.2 tended to be longer than that of patients with Bcl-2/Bax ratios < 1.2 but not significantly so (P = .084, n = 61). Disease-free survival (DFS) of patients with Bcl-2/Bax ratios >/= 1.2 was statistically significantly longer than that of patients with Bcl-2/Bax ratios < 1.2 (P = .001, n = 76). All of the patients whose Bcl-2/Bax ratio is >/= 2.0 were alive after 36 months and survived without any evidence of disease for 24 months (Bcl-2/Bax >/= 2.0 versus Bcl-2/Bax < 2.0; P = .035, n = 61 in OS, P < .001, n = 76 in DFS, respectively). In 56 patients who received immunochemoradiotherapy using UFT and OK-432 in combination with radiotherapy, a statistically significant relationship between the Bcl-2/Bax ratio and the therapeutic effect estimated using Response Evaluation Criteria in Solid Tumors was observed, as well as a relation with interferon-gamma (IFN-gamma) induction in response to the therapy [P = .002 in complete response versus partial response + stable disease; P = .046 in IFN-gamma(+) versus IFN-gamma(-)]. In addition, there were significant correlations of the Bcl-2/Bax ratio with both the absolute number of CD4(+) T cells and the rate of CD4(+) T cell and natural killer cell activity. These findings strongly suggest that the balance of expression of Bcl-2 and Bax genes in circulating immune cells has a high prognostic value in head and neck cancer patients.
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[699]
TÍTULO / TITLE: - Adjuvant trastuzumab for breast cancer. A second look. Longer follow-up confirms improved overall survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prescrire Int. 2012 Dec;21(133):285-7.
RESUMEN / SUMMARY: - Adjuvant cytotoxic chemotherapy following surgical treatment of nonmetastatic breast cancer usually includes an anthracycline. The addition of trastuzumab should be considered for women whose tumours overexpress HER-2 protein. Trastuzumab has been approved in the European Union since 2006 for adjuvant treatment of breast cancer. In 2011, the indications were further specified to allow the use of adjuvant trastuzumab in both anthracycline-based and non-anthracycline protocols. In 2006, the results of the first 3 trials of adjuvant chemotherapy showed an absolute gain in overall survival of about 4% after 4 years with trastuzumab. Updates of these trials, with longer follow-up, along with the results of a fourth trial, confirm the overall survival benefit, whether or not the adjuvant regimen includes an anthracycline (about 91% versus 87%). Trastuzumab carries a risk of NYHA class III or IV congestive heart failure with reduced left ventricular ejection fraction. The risk is higher in patients who receive the doxorubicin + cyclophosphamide combination, one-third of whom have a reduction in left ventricular ejection fraction that persists for several years after the end of treatment. The nature of non-cardiac serious adverse effects depends on whether the protocol includes an anthracycline: anthracycline therapy is associated with more frequent arthralgia, myalgia, hand-foot syndrome, vomiting, leukopenia and neutropenia, while regimens not containing an anthracycline are associated with more anaemia and thrombocytopenia. In practice, in 2012, the addition of trastuzumab to cytotoxic chemotherapy remains a valid option for women who have undergone surgery for nonmetastatic invasive breast tumours that overexpress HER-2 protein. It remains to be shown whether anthracycline-free chemotherapy regimens, which are less cardiotoxic, are equally effective.
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[700]
TÍTULO / TITLE: - Y-box binding protein-1 (YB-1) contributes to both HER2/ErbB2 expression and lapatinib sensitivity in human gastric cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1125
AUTORES / AUTHORS: - Shibata T; Kan H; Murakami Y; Ureshino H; Watari K; Kawahara A; Kage M; Hattori S; Ono M; Kuwano M
INSTITUCIÓN / INSTITUTION: - 1Department of Pharmaceutical Oncology, Kyushu University.
RESUMEN / SUMMARY: - Gene amplification of HER2/ErbB2 occurs in gastric cancer, and the therapeutic efficacy of the HER2-targeted antibody, trastuzumab, has recently been improved against HER2-positive advanced stomach cancer. Here we examined whether Y-box-binding protein-1 (YB-1) could selectively control HER2 gene expression and cellular sensitivity to epidermal growth factor receptor (EGFR) family protein-targeted drugs in human gastric cancer cells. HER2 expression was specifically downregulated by YB-1 silencing using its cognate siRNA, whereas there was less change in the expression of EGFR and HER3. A chromatin immunoprecipitation assay revealed the specific binding of YB-1 to its consensus sequence on the 5-regulatory region of HER2. YB-1 knockdown induced drug resistance to lapatinib, a dual EGFR and HER2 kinase inhibitor, and also to erlotinib, an EGFR kinase inhibitor. Moreover, phosphorylation of protein kinase B (Akt) was not markedly affected by lapatinib or erlotinib when YB-1 was silenced. Nuclear YB-1 expression was significantly (p=0.026) associated with HER2 expression, but not with EGFR or HER3, in patients with gastric cancer (n=111). The YB-1-HER2 axis might therefore be useful for the further development of personalized therapeutics against gastric cancer by HER2-targeted drugs.
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[701]
TÍTULO / TITLE: - Thyroglobulin levels and thyroglobulin doubling time independently predict a positive F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Nucl Med Mol Imaging. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2370-6
AUTORES / AUTHORS: - Giovanella L; Trimboli P; Verburg FA; Treglia G; Piccardo A; Foppiani L; Ceriani L
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Via Ospedale 12, 6500, Bellinzona, Switzerland, luca.giovanella@eoc.ch.
RESUMEN / SUMMARY: - PURPOSE: To assess the relationship between serum thyroglobulin (Tg) levels, Tg doubling time (Tg-DT) and the diagnostic performance of 18F-FDG PET/CT in detecting recurrences of 131I-negative differentiated thyroid carcinoma (DTC). METHODS: Included in the present study were 102 patients with DTC. All patients were treated by thyroid ablation (e.g. thyroidectomy and 131I), and underwent 18F-FDG PET/CT due to detectable Tg levels and negative conventional imaging. Consecutive serum Tg measurements performed before the 18F-FDG PET/CT examination were used for Tg-DT calculation. The 18F-FDG PET/CT results were assessed as true or false after histological and/or clinical follow-up. RESULTS: Serum Tg levels were higher in patients with a positive 18F-FDG PET/CT scan (median 6.7 ng/mL, range 0.7-73.6 ng/mL) than in patients with a negative scan (median 1.8 ng/mL, range 0.5-4.9 ng/mL; P < 0.001). In 43 (88 %) of 49 patients with a true-positive 18F-FDG PET/CT scan, the Tg levels were >5.5 ng/mL, and in 31 (74 %) of 42 patients with a true-negative 18F-FDG PET/CT scan, the Tg levels were </=5.5 ng/mL. A Tg-DT of <1 year was found in 46 of 49 patients (94 %) with a true-positive 18F-FDG PET/CT scan, and 40 of 42 patients (95 %) with a true-negative scan had a stable or increased Tg-DT. Moreover, combining Tg levels and Tg-DT as selection criteria correctly distinguished between patients with a positive and a negative scan (P<0.0001). CONCLUSION: The accuracy of 18F-FDG PET/CT significantly improves when the serum Tg level is above 5.5 ng/mL during levothyroxine treatment or when the Tg-DT is less than 1 year, independent of the absolute value.
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[702]
TÍTULO / TITLE: - Transient Exposure to Quizartinib Mediates Sustained Inhibition of FLT3 Signaling while Specifically Inducing Apoptosis in FLT3-Activated Leukemia Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0305
AUTORES / AUTHORS: - Gunawardane RN; Nepomuceno RR; Rooks AM; Hunt JP; Ricono JM; Belli B; Armstrong RC
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliation: Ambit Biosciences, San Diego, California.
RESUMEN / SUMMARY: - Fms-like tyrosine kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML). FLT3-activating internal tandem duplication (ITD) mutations are found in approximately 30% of patients with AML and are associated with poor outcome in this patient population. Quizartinib (AC220) has previously been shown to be a potent and selective FLT3 inhibitor. In the current study, we expand on previous observations by showing that quizartinib potently inhibits the phosphorylation of FLT3 and downstream signaling molecules independent of FLT3 genotype, yet induces loss of viability only in cells expressing constitutively activated FLT3. We further show that transient exposure to quizartinib, whether in vitro or in vivo, leads to prolonged inhibition of FLT3 signaling, induction of apoptosis, and drastic reductions in tumor volume and pharmacodynamic endpoints. In vitro experiments suggest that these prolonged effects are mediated by slow binding kinetics that provide for durable inhibition of the kinase following drug removal/clearance. Together these data suggest quizartinib, with its unique combination of selectivity and potent/sustained inhibition of FLT3, may provide a safe and effective treatment against FLT3-driven leukemia. Mol Cancer Ther; 12(4); 1-10. ©2013 AACR.
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[703]
TÍTULO / TITLE: - Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Sci. 2013 Feb 26. doi: 10.1111/cas.12139.
●● Enlace al texto completo (gratuito o de pago) 1111/cas.12139
AUTORES / AUTHORS: - Watanabe M; Sowa Y; Yogosawa M; Sakai T
INSTITUCIÓN / INSTITUTION: - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
RESUMEN / SUMMARY: - Chemotherapy for colorectal cancer has become more complicated and diversified with the appearance of molecular-targeting agents. 5-Fluorouracil (5-FU) has been a mainstay of chemotherapy for colorectal cancer, but it is still unknown whether the combining of 5-FU with novel molecular-targeting agents is effective. Thymidylate synthase (TS) is a direct target of 5-FU, and the low TS level has been generally supposed to sensitize 5-FU’s efficacy. We therefore hypothesized that RB-reactivating agents could enhance the efficacy of 5-FU, because the RB-reactivating agents could suppress the function of transcription factor E2F of TS gene promoter. We used three RB-reactivating agents, trametinib/GSK1120212 (MEK inhibitor), fenofibrate (PPARalpha agonist), and LY294002 (PI3K inhibitor), with 5-FU against human colon cancer HT-29 and HCT15 cells. Trametinib induced p15 and p27 expression and reduced cyclin D1 levels in HT-29 cells. Fenofibrate also dephosphorlated ERK1/2 and reduced cyclin D1 levels in HT-29 cells. LY294002 induced p27 expression in HCT15 cells. All three agents caused dephosphorylation of RB protein and G1-phase arrest with a reduction of TS expression. As a consequence, the combination of 5-FU with each of the agents resulted in a significant decrease of colony numbers in HT-29 or HCT15 cells. These results suggest “RB-reactivation therapy” using molecular-targeting agents to be a new strategy for 5-FU-based chemotherapy. In particular, we strongly expect trametinib, which was discovered in Japan and was recently submitted to FDA for approval, to be used together with established regimens for colorectal cancer.
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[704]
TÍTULO / TITLE: - Expression of leukemia associated fusion proteins increases sensitivity to histone deacetylase inhibitor induced DNA damage and apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1039
AUTORES / AUTHORS: - Petruccelli LA; Pettersson F; Del Rincon SV; Guilbert C; Licht JD; Miller WH Jr
INSTITUCIÓN / INSTITUTION: - 1Experimental Medicine, Lady Davis Institute for Medical Research / McGill University.
RESUMEN / SUMMARY: - Histone deacetylase inhibitors (HDI) show activity in a broad range of hematological and solid malignancies, yet the percentage of patients in any given malignancy who experience a meaningful clinical response remains small. In this study, we sought to investigate HDI efficacy in acute myeloid leukemia (AML) cells expressing leukemia associated fusion proteins (LAFPs). HDI have been shown to induce apoptosis in part through accumulation of DNA damage and inhibition of DNA repair. LAFPs have been correlated with a DNA repair deficient phenotype, which may make them more sensitive to HDI-induced DNA damage. We found expression of the LAFPs PLZF-RARalpha, PML-RARalpha and RUNX1-ETO (AML1-ETO) increased sensitivity to DNA damage and apoptosis induced by the HDI vorinostat. The increase in apoptosis correlated with an enhanced down-regulation of the pro-survival protein BCL2. Vorinostat also induced expression of the cell cycle regulators p19INK4D and p21WAF1, and triggered a G2-M cell cycle arrest to a greater extent in LAFP expressing cells. The combination of LAFP and vorinostat further led to a greater down-regulation of several base excision repair (BER) enzymes. These BER genes represent biomarker candidates for response to HDI-induced DNA damage. Notably, repair of vorinostat-induced DNA double strand breaks was found to be impaired in PLZF-RARalpha expressing cells, suggesting a mechanism by which LAFP expression and HDI treatment cooperate to cause an accumulation of damaged DNA. These data support the continued study of HDI based treatment regimens in LAFP-positive AMLs.
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[705]
TÍTULO / TITLE: - Regulated cellular exposure to non-thermal plasma allows preferentially directed apoptosis in acute monocytic leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Stud Health Technol Inform. 2013;184:436-42.
AUTORES / AUTHORS: - Thiyagarajan M; Gonzales XF; Anderson H
INSTITUCIÓN / INSTITUTION: - Plasma Engineering Research Lab (PERL), Texas A&M University-Corpus Christi.
RESUMEN / SUMMARY: - This research investigated the modulation of cell death through exposure of non-thermal resistive barrier based indirect air plasma on monocytic leukemia cancer cells (THP-1). Specifically, we explored cell death through apoptosis and necrosis, since generally apoptotic cell death has a limited inflammatory response as compared to necrosis. We have demonstrated a preference for apoptosis in plasma treated THP-1 cells, under specific plasma characteristics and dosage levels, using fluorescent dyes conjugated with annexin V followed by identification of the cells through fluorescent microscopy and flowcytometry diagnostics. At much higher plasma dosages, the necrotic morphologies in the THP-1 cells were observed. The presented outcomes in the death morphologies of plasma treated THP-1 cells signify the need for further investigation on the cellular mechanisms induced by the indirect plasma exposure. The results obtained from this research indicate the significant potential for the use of our portable non-thermal resistive barrier based indirect plasma treatment method as an inexpensive and less invasive method for treating leukemia and other cancerous lesions.
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[706]
TÍTULO / TITLE: - Activating natural cytotoxicity receptors of natural killer cells in cancer and infection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Trends Immunol. 2013 Feb 12. pii: S1471-4906(13)00012-4. doi: 10.1016/j.it.2013.01.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.it.2013.01.003
AUTORES / AUTHORS: - Koch J; Steinle A; Watzl C; Mandelboim O
INSTITUCIÓN / INSTITUTION: - Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Strasse 42-44, D-60596 Frankfurt am Main, Germany. Electronic address: joachim.koch@em.uni-frankfurt.de.
RESUMEN / SUMMARY: - Natural killer (NK) cells are central players in the vertebrate immune system that rapidly eliminate malignantly transformed or infected cells. The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are important mediators of NK cell cytotoxicity, which trigger an immune response on recognition of cognate cellular and viral ligands. Tumour and viral immune escape strategies targeting these receptor-ligand systems impair NK cell cytotoxicity and promote disease. Therefore, a molecular understanding of the function of the NCRs in immunosurveillance is instrumental to discovering novel access points to combat infections and cancer.
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[707]
TÍTULO / TITLE: - Epigenetic reactivation of estrogen receptor-alpha (ERalpha) by genistein enhances hormonal therapy sensitivity in ERalpha-negative breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer. 2013 Feb 4;12:9. doi: 10.1186/1476-4598-12-9.
●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-12-9
AUTORES / AUTHORS: - Li Y; Meeran SM; Patel SN; Chen H; Hardy TM; Tollefsbol TO
INSTITUCIÓN / INSTITUTION: - Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA. lyy@uab.edu
RESUMEN / SUMMARY: - BACKGROUND: Estrogen receptor-alpha (ERalpha)-negative breast cancer is clinically aggressive and normally does not respond to conventional estrogen target-directed therapies. The soybean isoflavone, genistein (GE), has been shown to prevent and inhibit breast cancer and recent studies have suggested that GE can enhance the anticancer capacity of an estrogen antagonist, tamoxifen (TAM), especially in ERalpha-positive breast cancer cells. However, the role of GE in ERalpha-negative breast cancer remains unknown. METHODS: We have evaluated the in vitro and in vivo epigenetic effects of GE on ERalpha reactivation by using MTT assay, real-time reverse transcription-polymerase chain reaction (RT-PCR) assay, western-blot assay, immunoprecipitation (ChIP) assay, immunohistochemistry and epigenetic enzymatic activity analysis. Preclinical mouse models including xenograft and spontaneous breast cancer mouse models were used to test the efficacy of GE in vivo. RESULTS: We found that GE can reactivate ERalpha expression and this effect was synergistically enhanced when combined with a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), in ERalpha-negative MDA-MB-231 breast cancer cells. GE treatment also re-sensitized ERalpha-dependent cellular responses to activator 17beta-estradiol (E2) and antagonist TAM. Further studies revealed that GE can lead to remodeling of the chromatin structure in the ERalpha promoter thereby contributing to ERalpha reactivation. Consistently, dietary GE significantly prevented cancer development and reduced the growth of ERalpha-negative mouse breast tumors. Dietary GE further enhanced TAM-induced anti-cancer efficacy due at least in part to epigenetic ERalpha reactivation. CONCLUSIONS: Our studies suggest that soybean genistein can epigenetically restore ERalpha expression, which in turn increases TAM-dependent anti-estrogen therapeutic sensitivity in vitro and in vivo. The results from our studies reveal a novel therapeutic combination approach using bioactive soybean product and anti-hormone therapy in refractory ERalpha-negative breast cancer which will provide more effective options in breast cancer therapy.
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[708]
TÍTULO / TITLE: - The novel Chk1 inhibitor MK-8776 sensitizes human leukemia cells to HDAC inhibitors by targeting the intra-S checkpoint and DNA replication and repair.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0902
AUTORES / AUTHORS: - Dai Y; Chen S; Kmieciak M; Zhou L; Lin H; Pei XY; Grant S
INSTITUCIÓN / INSTITUTION: - 1medicine, vcu.
RESUMEN / SUMMARY: - Interactions between the novel Chk1 inhibitor MK-8776 and the HDAC inhibitor (HDACI) vorinostat were examined in human leukemia cells harboring wild-type (wt) or deficient p53. MK-8776 synergistically potentiated vorinostat-mediated apoptosis in various p53-wild type (wt) or -deficient leukemia cell lines, while p53 knock-down by shRNA sensitized p53-wt cells to lethality of this regimen. Leukemia cell lines carrying FLT3-ITD were also sensitive to the MK-8776/vorinostat regimen. Synergistic interactions were associated with inhibition of Chk1 activity, interference with the intra-S phase checkpoint, disruption of DNA replication, and down-regulation of proteins involved in DNA replication (e.g.,CDT1) and repair (e.g., CtIP and BRCA1), resulting in sharp increases in DNA damage, reflected by enhanced gammaH2A.X formation, and apoptosis. Moreover, leukemia cells expressing kinase-dead Chk1 (D130A) or Chk1 shRNA were significantly more sensitive to HDACIs compared to their wild-type counterparts, and displayed down-regulation of CtIP and BRCA1 phosphorylation following HDACI exposure. Finally, the MK-8776/vorinostat regimen was active in primary AML blasts, particularly against the CD34+/CD38-/CD123+ population enriched for leukemia-initiating cells. In contrast, identical regimens were relatively sparing toward normal cord blood CD34+ cells. Together, these findings indicate that the novel Chk1 inhibitor MK-8776 markedly potentiates HDACI lethality in leukemia cells displaying various genetic backgrounds through mechanisms involving disruption of the intra-S checkpoint, DNA replication, and DNA repair. They also argue that leukemic cells, including those bearing oncogenic mutations associated with poor prognosis e.g., p53 deletion/mutation or FLT3-ITD, may also be susceptible to this strategy.
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[709]
TÍTULO / TITLE: - Cucurbitacins: potential candidates targeting mitogen-activated protein kinase pathway for treatment of melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Enzyme Inhib Med Chem. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3109/14756366.2012.762646
AUTORES / AUTHORS: - Ahmed MS; Halaweish FT
INSTITUCIÓN / INSTITUTION: - Department of Chemistry and Biochemistry, South Dakota State University , Brookings, SD , USA.
RESUMEN / SUMMARY: - Abstract Cucurbitacins (Cucs) have been classified as signal transducer and activator of transcription 3 inhibitors. Kinase inhibition has been a validated drug target in multiple types of malignancies. B-RAF mutations are highly expressed in the melanoma. Our hypothesis is the Cucs can be a potential candidate to inhibit the signaling kinase pathway. The research presented is the evaluation of Cucs, as B-RAF and MEK1 kinase inhibitors. Virtual screening methods were employed to identify lead compounds. The hypothesis was tested on mutant B-RAF cell lines, A-375 and Sk-Mel-28 cell lines to determine the activity toward melanoma. A series of natural Cucs show an improved activity toward Sk-Mel-28 and A-375 cell lines. Cucs show potential inhibition for the total and phosphorylated ERK using ELISA kits. Cucs could be potential candidate for inhibiting cell growth.
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[710]
TÍTULO / TITLE: - Feasibility of Reduced-Intensity Allogeneic Stem Cell Transplantation With Imatinib in Children With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pediatr Blood Cancer. 2013 Mar 6. doi: 10.1002/pbc.24507.
●● Enlace al texto completo (gratuito o de pago) 1002/pbc.24507
AUTORES / AUTHORS: - Yamada K; Yasui M; Kondo O; Sato M; Sawada A; Kawa K; Inoue M
INSTITUCIÓN / INSTITUTION: - Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi City, Osaka, Japan.
RESUMEN / SUMMARY: - Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) in children is one of the highest-risk ALL groups. Improved outcome in combination with imatinib has been reported. However, intensive chemotherapy or myeloablative conditioning followed by hematopoietic stem cell transplantation (HSCT) can be associated with significant adverse late effects. We report a case series of five children with Ph + ALL underwent reduced-intensity allogeneic HSCT (RIST) after induction and consolidation in chemotherapy combined with imatinib. Four of the five patients remain first complete remission for a median of 3.1 years after RIST. These results are preliminary, but suggest the feasibility and effectiveness of RIST with imatinib. Pediatr Blood Cancer 2013;9999:1-3. © 2013 Wiley Periodicals, Inc.
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[711]
TÍTULO / TITLE: - Sustained molecular remission with a tyrosine kinase inhibitor alone for seven months in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Rinsho Ketsueki. 2013 Feb;54(2):210-3.
AUTORES / AUTHORS: - Takahashi T; Shigeoka T; Suzukawa M; Ishido A; Tominaga T
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Yamaguchi Grand Medical Center.
RESUMEN / SUMMARY: - Herein, we report the case of a 28-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (PhALL). The patient received induction chemotherapy, including imatinib (IM) therapy, which required early cessation because of a severe infection. After the resolution of the infection, general flaccid paralysis was observed, which was diagnosed as critical illness myopathy (CIM). PhALL showed molecular remission (MR) on day 42. We intended to maintain MR with only IM therapy for several months until the improvement of CIM; however, owing to the patient’s intolerance to IM, therapy was changed to dasatinib. Because the symptoms of myopathy gradually improved and disappeared completely, the patient was able to undergo one course of intensive chemotherapy and allogeneic stem cell transplantation from an HLA-matched sibling donor, 8 months after admission (7 months after the re-administration of IM). Thus, this case report suggests that a tyrosine kinase inhibitor is an alternative therapy for maintaining the response of PhALL patients who refrain from conventional chemotherapy.
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[712]
TÍTULO / TITLE: - Potential Advantages of CUDC-101, a Multi-Targeted HDAC, EGFR, and HER2 Inhibitor, in Treating Drug Resistance and Preventing Cancer Cell Migration and Invasion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1045
AUTORES / AUTHORS: - Wang J; Pursell NW; Samson ME; Atoyan R; Ma AW; Selmi A; Xu W; Cai X; Voi M; Savagner P; Lai CJ
INSTITUCIÓN / INSTITUTION: - 1Biology, Curis, Inc.
RESUMEN / SUMMARY: - CUDC-101 is a novel, small-molecule, anti-cancer agent targeting histone deacetylases (HDACs), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2). It is currently in Phase I clinical development in patients with solid tumors. Previously, we reported that CUDC-101 has potent anti-proliferative and pro-apoptotic activity in cultured tumor cells and in vivo xenograft models. We now show that cancer cells that have acquired resistance to single-target EGFR inhibitors through upregulation of AXL or loss of E-cadherin remain sensitive to CUDC-101, which inhibits MET- and AXL-mediated signaling, restores E-cadherin expression, and reduces cell migration. CUDC-101 also efficiently inhibited the proliferation of MET-overexpressing non-small cell lung cancer and gastric cancer cell lines and inhibited the migration and invasion of invasive tumor cells. Taken together, these results suggest that coupling HDAC and HER2 inhibitory activities to an EGFR inhibitor may potentially be effective in overcoming drug resistance and preventing cancer cell migration.
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[713]
TÍTULO / TITLE: - Low ING4 protein expression detected by paraffin-section immunohistochemistry is associated with poor prognosis in untreated patients with gastrointestinal stromal tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastric Cancer. 2013 Mar 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s10120-013-0248-8
AUTORES / AUTHORS: - Nanding A; Tang L; Cai L; Chen H; Geng J; Liu X; Ning X; Li X; Zhang Q
INSTITUCIÓN / INSTITUTION: - Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, 150 Haping Street, Harbin, 150040, China.
RESUMEN / SUMMARY: - BACKGROUND: Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value. METHOD: The expression of ING4 and Ki67 was investigated in 41 samples of various risk gastrointestinal stromal tumors by immunohistochemical technique. The associations of ING4 expression and clinicopathological parameters, and prognosis of the patients, were analyzed by multivariate Cox regression analysis. RESULTS: ING4 expression showed a decreased trend from lower-risk to high-risk gastrointestinal stromal tumors, and an opposite trend for Ki67 expression. In lower-risk tumors, it was found the expression level of ING4 was 78.95 % +/- 27.90 % and that of Ki67 was 4.42 % +/- 3.75 %. However, in high-risk tumors, the expression level of ING4 was 9.23 % +/- 7.66 % and that of Ki67 was 18.50 % +/- 9.09 %. There was a strongly negative correlation between the expression levels of ING4 and Ki67. A significant difference was observed in the expression of ING4 between invasion and non-invasion (p < 0.001). The expression of ING4 was markedly correlated with tumor size (p < 0.001), mitotic index (p < 0.001), tumor necrosis (p = 0.021), invasion (p < 0.001), recurrence and metastasis (p = 0.021), and mortality (p < 0.001). CONCLUSION: The low expression level of ING4 protein was correlated with high-risk GISTs. ING4 might be involved in the progression of GISTs and inhibit its invasion. ING4 might be one of the prognostic indicators in GISTs.
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[714]
TÍTULO / TITLE: - The expressions of MIF and CXCR4 protein in tumor microenvironment are adverse prognostic factors in patients with esophageal squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Mar 8;11(1):60.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-60
AUTORES / AUTHORS: - Zhang L; Ye SB; Ma G; Tang XF; Chen SP; He J; Liu WL; Xie D; Zeng YX; Li J
RESUMEN / SUMMARY: - BACKGROUND: Tumor-derived cytokines and their receptors usually take important roles in the disease progression and prognosis of cancer patients. In this survey, we aimed to detect the expression levels of MIF and CXCR4 in different cell populations of tumor microenvironments and their association with survivals of patients with esophageal squamous cell carcinoma (ESCC). METHODS: MIF and CXCR4 levels were measured by immunochemistry in tumor specimens from 136 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson’s chi-square test and Cox regression analysis. RESULTS: The expression of CXCR4 in tumor cells was positively associated with tumor status (P = 0.045) and clinical stage (P = 0.044); whereas the expression of CXCR4 in tumor-infiltrating lymphocytes (TILs) and the expression of MIF in tumor cells and in TILs were not associated with clinical parameters of ESCC patients. High MIF expression in tumor cells or in TILs or high CXCR4 expression in tumor cells was significantly related to poor survival of ESCC patients (P < 0.05). Multivariate analysis showed that the expression of MIF or CXCR4 in tumor cells and the expression of MIF in TILs were adverse independent factors for disease-free survival (DFS) and overall survival (OS) in the whole cohort of patients (P < 0.05). Furthermore, the expression of MIF and CXCR4 in tumor cells were independent factors for reduced DFS and OS in metastatic/recurrent ESCC patients (P < 0.05). Interestingly, the expressions of MIF and CXCR4 in tumor cells and in TILs were significantly positively correlated (P < 0.05), and the combined MIF and CXCR4 expression in tumor cells was an independent adverse predictive factor for DFS and OS (P < 0.05). CONCLUSION: The expressions of MIF and CXCR4 proteins in tumor cells and TILs have different clinically predictive values in ESCC.
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[715]
TÍTULO / TITLE: - Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Pharmacother. 2013 Apr;14(6):699-706. doi: 10.1517/14656566.2013.779672. Epub 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1517/14656566.2013.779672
AUTORES / AUTHORS: - Fabi A; Merola R; Ferretti G; Di Benedetto A; Antoniani B; Ercolani C; Nistico C; Papaldo P; Ciccarese M; Sperduti I; Vici P; Marino M; Gori S; Botti C; Malaguti P; Cognetti F; Mottolese M
INSTITUCIÓN / INSTITUTION: - Regina Elena National Cancer Institute, Departments of Oncology A , Via Elio Chianesi, 53, 00144 Rome , Italy +390652665144 ; +390652665637 ; fabi@ifo.it.
RESUMEN / SUMMARY: - Objective: Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients. Methods: Lapatinib was given at 1250 mg/day continuously and capecitabine at 2000 mg/m(2)/day every 3 weeks. EGFR protein expression and gene copy number (GCN) were assessed by immunohistochemistry and FISH, respectively. Receiver operating curve (ROC) analysis identified the value of > 3.36 EGFR copies/nucleus as the cut-off point able to discriminate responders versus non-responders. Results: A statistical significant correlation between EGFR GCN value > 3.36 and response to lapatinib (p = 0.01) was found. Cox regression analysis further supported these findings evidencing that HER2 score 3+ and EGFR GCN increase are positive predictor factors of lapatinib response. Conclusions: Though further investigations are needed to confirm these findings, EGFR GCN could be a suitable screening to identify the subset of BC patients particularly responsive to the dual TKI lapatinib.
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[716]
TÍTULO / TITLE: - Erythropoietin treatment in chemotherapy-induced anemia in previously untreated advanced esophagogastric cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Clin Oncol. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s10147-013-0544-7
AUTORES / AUTHORS: - Thomaidis T; Weinmann A; Sprinzl M; Kanzler S; Raedle J; Ebert M; Schimanski CC; Galle PR; Hoehler T; Moehler M
INSTITUCIÓN / INSTITUTION: - 1st Medical Department, Johannes-Gutenberg University Mainz, Langenbeckstr.1, 55101, Mainz, Germany.
RESUMEN / SUMMARY: - BACKGROUND: The impact of erythropoiesis-stimulating agents in chemotherapy-induced anemia has been a constant topic of debate over recent years. We prospectively assessed the efficacy of epoetin beta (Epo-b) in improving hemoglobin (Hb) levels and outcome in patients within an open label, randomized clinical phase II trial with advanced or metastatic gastric/esophagogastric cancer. METHODS: Previously untreated patients were randomized to receive 3-weekly cycles of capecitabine (1000 mg/m2 bid) for 14 days plus on day 1 either irinotecan 250 mg/m2 or cisplatin 80 mg/m2. Epo-b (30000 IU once weekly) was initiated in patients with Hb <11 g/dl and continued until Hb >/=12 g/dl was reached. If after 4 weeks the Hb increase was <0.5 g/dl, Epo-b was increased to 30000 IU, twice weekly. RESULTS: Of 118 patients enrolled, 32 received Epo-b treatment; of these, 65 % achieved an increase in Hb levels of at least 2 g/dl, with 74 % achieving the target Hb of >/=12 g/dl. Within the study population, patients receiving Epo-b showed better overall survival (median 14.5 vs. 8.0 months, P = 0.056) as well as a significantly improved disease control rate (78 vs. 55 %, P = 0.025). Patients in the irinotecan group profited significantly (P < 0.05) in terms of progression-free survival and overall survival under Epo-b treatment (median 6.5 vs 4.1 months and median 15.4 vs 8.4 months, respectively). CONCLUSIONS: Epo-b was effective in raising Hb levels in patients with advanced esophagogastric cancer. Patients receiving Epo-b had a significantly increased response to chemotherapy and a clear trend to improved survival.
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[717]
TÍTULO / TITLE: - Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Oncol. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not028
AUTORES / AUTHORS: - Kanno H; Nishihara H; Wang L; Yuzawa S; Kobayashi H; Tsuda M; Kimura T; Tanino M; Terasaka S; Tanaka S
INSTITUCIÓN / INSTITUTION: - Laboratory of Cancer Research, Department of Pathology (H.K., S.Y., M.T., T.K., M.T., S.T.), Laboratory of Translational Pathology (H.N., L.W., S.T.), and Department of Neurosurgery (H.K., S.T.), Hokkaido University School of Medicine, Sapporo, Japan.
RESUMEN / SUMMARY: - BackgroundCD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients’ poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression.MethodsFirst, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo.ResultsImmunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay.ConclusionsTo our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma.
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[718]
TÍTULO / TITLE: - Enhanced pharmacokinetics and anti-tumor efficacy of PEGylated liposomal rhaponticin and plasma protein binding ability of rhaponticin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Nanosci Nanotechnol. 2012 Oct;12(10):7677-84.
AUTORES / AUTHORS: - Sun Y; Zhao Y
INSTITUCIÓN / INSTITUTION: - Department of Chemistry and Chemical Engineering, Xi’an University of Arts and Science, Xi’an, Shaanxi 710069, China.
RESUMEN / SUMMARY: - Rhaponticin (RA) extracted from many medicinal plants has been demonstrated to possess a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic, antioxidant and vasorelaxant activities. However, its poor solubility and bioavailability restricted the clinical application greatly. In this work, surface modification of liposome with polyethylene glycol (PEG) was developed with the purpose of improving the pharmacokinetics and anti-tumor efficacy of RA. PEGylated liposomal RA (PEGL-RA) was prepared by dry-film method. Its mean particle size was 89.3 +/- 8.7 nm, mean zeta potential was -4.1 mV and encapsulation efficiency was 67.4 +/- 6.4%. Moreover, the results of pharmacokinetic analysis showed that the time of maximum plasma concentration (Tmax) of PEGL-RA was about 4.5 times higher than that of free RA after oral administration due to the lower distribution into the gastrointestinal tract. The mean T1/2 value of PEGL-RA and free RA were 350.12 +/- 0.87 min and 180.02 +/- 1.96 min, respectively. The AUC0-->infinity ratio of PEGL-RA to free RA was about 2.41-fold (93.23 microg/mLmin/40.81 microg/mLmin). Plasma protein binding ability of RA was also studied. The results showed that RA with 33.6 microg/mL concentrations in human plasma and HSA achieved the percent of bound 39.23 +/- 3.78% and 22.28 +/- 2.34%, respectively. In the in vivo studies utilizing solid tumor-bearing rat, it was confirmed that PEGL-RA delivered remarkably larger amount of RA to tumor tissue and provided more significant anti-tumor activity than free RA. Furthermore, the cytotoxicity and fluorescence microscopic studies showed higher intracellular uptake of PEGL-RA than that of RA. In conclusion, PEGylated liposome was an effective delivery formulation for RA to increase the pharmacokinetics and therapeutic efficacy.
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[719]
TÍTULO / TITLE: - Treatment Response to Preoperative Anthracycline-Based Chemotherapy in Locally Advanced Breast Cancer: The Relevance of Proliferation and Apoptosis Rates.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Oncol Res. 2013 Mar 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s12253-013-9621-5
AUTORES / AUTHORS: - Kanjer K; Tatic S; Neskovic-Konstantinovic Z; Abu Rabi Z; Nikolic-Vukosavljevic D
INSTITUCIÓN / INSTITUTION: - Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia, ksenijakanjer@gmail.com.
RESUMEN / SUMMARY: - Objectives were to evaluate the relevance of proliferating fraction (Ki-67) along with apoptotic index (AI) which denoted growth index (Ki-67/AI ratio, GI) to predict pathological response to preoperative chemotherapy, and the pattern of their modifications following chemotherapy in women with locally advanced breast cancer. Archival material of diagnostic biopsies and surgical specimens from 106 patients were examined. Response rate to chemotherapy in this group was 95 %, eight (8 %) patients achieved a pathological complete remission (pCR) and five (5 %) had a progressive/stable disease (PD/SD). The expression of Ki-67 and AI were assessed using immunohistochemistry and in situ DNA nick labeling assay respectively. Higher baseline level of Ki-67 and GI were associated with an improved pathological response (p = 0.0001 and p = 0.008), but the degree of correlation with GI was no greater than that with Ki-67 alone. Ki-67 below 1 % highly indicated a lack of tumor response. High AI which characterized the opposite chemo-sensitive tumors, pCR vs. PD/SD (p = 0.72) implied that treatment response was not influenced by the “presence” or “absence” of apoptosis. A significant decrease in Ki-67 (p < 0.001), AI (p = 0.035) and GI (p = 0.008) was found following chemotherapy, but percentage change in biomarker values revealed an increase in a number of cases. Higher initial Ki-67 and AI was associated with profound reduction of GI and raising value of GI after treatment, respectively. Such a variance of a given parameter elicited by chemotherapy may have various impact on disease outcome.
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[720]
TÍTULO / TITLE: - Pregnancy after a diagnosis of estrogen receptor-positive breast cancer does not affect prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - CA Cancer J Clin. 2013 Mar 5. doi: 10.3322/caac.21178.
●● Enlace al texto completo (gratuito o de pago) 3322/caac.21178
AUTORES / AUTHORS: - Barton MK
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[721]
TÍTULO / TITLE: - Prediction of minimal residual viremia in HCV type 1 infected patients receiving interferon-based therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hepatol. 2013 Mar;12(2):190-8.
AUTORES / AUTHORS: - Knop V; Teuber G; Klinker H; Moller B; Rasenack J; Hinrichsen H; Gerlach T; Spengler U; Buggisch P; Neumann K; Sarrazin C; Zeuzem S; Berg T
INSTITUCIÓN / INSTITUTION: - Universitatsklinikum Charite, Campus Virchow-Klinikum, Universitatsmedizin Berlin, Germany; Medizinische Klinik 1, Klinikum der Goethe-Universitat.
RESUMEN / SUMMARY: - Introduction. Complete suppression of viral replication is crucial in chronic HCV treatment in order to prevent relapse and resistance development. We wanted to find out which factors influence the period from being already HCV RNA negative by bDNA assay (< 615 IU/mL) to become undetectable by the more sensitive TMA test (< 5.3 IU/mL). Material and methods. Evaluated were 433 HCV type 1-infected patients. All of them received 1.5 ug/kg Peg-IFNalpha-2b plus ribavirin for 18-48 weeks. bDNA was performed weekly during the first 8 weeks and thereafter at weeks 12, 24, and 48. Patients who became bDNA undetectable were additionally analysed by TMA. Results. Of the 309 patients with on-treatment response (< 615 IU/mL), 289 also reached undetectable HCV RNA levels by TMA. Multivariate analysis revealed that viremia </= 400,000 IU/mL (p = 0.001), fast initial virologic decline (p = 0.004) and absence of fibrosis (p = 0.035) were independent predictors of an accelerated on-treatment response by TMA assay in already bDNA negative patients. bDNA negative patients becoming HCV RNA undetectable by TMA within the following 3 weeks had a frequency of relapse of 21%, whereas those showing TMA negativity after 3 weeks relapsed in 38% (p = 0.001). In RVR patients (bDNA < 615 IU/mL at week 4) the corresponding relapse rates were 15.3% vs. 37.5%, respectively (p = 0.003). Conclusion. Early viral kinetics, baseline viremia and fibrosis stage are important tools to predict persistent minimal viremia during interferon-based therapy. The data have implications for designing a more refined treatment strategy in HCV infection, even in the setting of protease inhibitor-based triple treatment.
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[722]
TÍTULO / TITLE: - Activity of the Fibroblast Growth Factor Receptor Inhibitors Dovitinib (TKI258) and NVP-BGJ398 in Human Endometrial Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0999
AUTORES / AUTHORS: - Konecny GE; Kolarova T; O’Brien NA; Winterhoff B; Yang G; Qi J; Qi Z; Venkatesan N; Ayala R; Luo T; Finn RS; Kristof J; Galderisi C; Graus Porta D; Anderson L; Shi MM; Yovine A; Slamon DJ
INSTITUCIÓN / INSTITUTION: - 1Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles.
RESUMEN / SUMMARY: - The recent identification of activating fibroblast growth factor receptor 2 (FGFR2) mutations in endometrial cancer (EC) has generated an opportunity for a novel target-based therapy. Here we explore the therapeutic potential of two FGFR inhibitors, the multi-kinase inhibitor dovitinib (TKI258) and the more selective FGFR inhibitor NVP-BGJ398 for the treatment of EC. We examined the effects of both inhibitors on tumor cell growth, FGFR2 signaling, cell cycle and apoptosis using a panel of 20 molecularly characterized human EC cell lines. Anchorage independent growth was studied using soft agar assays. In vivo studies were conducted using EC xenograft models. Cell lines with activating FGFR2 mutations (S252W, N550K) were more sensitive to dovitinib or NVP-BGJ398 when compared to their FGFR2 wild-type counterparts (p=0.073 and p=0.021, respectively). Both agents inhibited FGFR2 signaling, induced cell cycle arrest and significantly increased apoptosis in FGFR2 mutant lines. In vitro, dovitinib and NVP-BGJ398 were both potent at inhibiting cell growth of FGFR2 mutant EC cells but the activity of dovitinib was less restricted to FGFR2 mutant lines when compared to NVP-BGJ398. In vivo, dovitinib and NVP-BGJ398 significantly inhibited the growth of FGFR2 mutated EC xenograft models. In addition, dovitinib showed significant antitumor activity in FGFR2 wild-type EC xenograft models including complete tumor regressions in a long term in vivo study. Dovitinib and NVP-BGJ398 warrant further clinical evaluation in patients with FGFR2 mutated EC. Dovitinib may have antitumor activity in EC beyond FGFR2 mutated cases and may permit greater flexibility in patient selection.
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[723]
TÍTULO / TITLE: - p70S6 kinase is a target of the novel proteasome inhibitor 3,3’-diamino-4’-methoxyflavone during apoptosis in human myeloid tumor cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 Feb 26;1833(6):1316-1328. doi: 10.1016/j.bbamcr.2013.02.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbamcr.2013.02.016
AUTORES / AUTHORS: - Piedfer M; Bouchet S; Tang R; Billard C; Dauzonne D; Bauvois B
INSTITUCIÓN / INSTITUTION: - INSERM U872, Universite Pierre et Marie Curie, Universite Paris-Descartes, Centre de Recherche des Cordeliers, Paris, France.
RESUMEN / SUMMARY: - Acute myeloid leukemia (AML) is a deadly disease characterized by the clonal expansion and accumulation of hematopoietic stem cells arrested at various stages of development. Clinical research efforts are currently focusing on targeted therapies that induce apoptosis in AML cells. Herein, the effects and mechanisms of the novel flavone 3,3’-diamino-4’-methoxyflavone (DD1) on AML cell dysfunction were investigated in AML cells (monoblast U937, myelomonocyte OCI-AML3, promyelocyte NB4, myeloblast HL-60) and blood samples from patients with AML. The administration of DD1 inhibited proliferation and induced death of AML cell lines and reduced the clonogenic activity of AML, but not normal, blood cells. The flavone’s apoptotic action in U937 cells was associated with recruitment of mitochondria, Bax activation, Bad dephosphorylation (at Ser136), activation of caspases -8, -9, and -3 and cleavage of the caspase substrate PARP-1. DD1 induced a marked decrease in (i) Thr389-phosphorylation and (ii) protein levels of the caspase-3 substrate P70 ribosomal S6 kinase (P70S6K, known for its ability to phosphorylate Bad). Caspase-dependent apoptosis and P70S6K degradation were simultaneously prevented by the caspase inhibitors. Importantly, DD1 was shown to directly inhibit the proteasome’s chymotrypsin-like activity in U937 cells. Apoptotic activity of the proteasome inhibitor bortezomib was also related to Bax activation and P70S6K downregulation. Accordingly, DD1 failed to induce P70S6K cleavage, Bax stimulation and apoptosis in K562 cells resistant to bortezomib. These results indicate that DD1 has the potential to eradicate AML cells and support a critical role for Bax and P70S6K in DD1-mediated proteasome inhibition and apoptosis of leukemia cells.
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[724]
TÍTULO / TITLE: - Inhibition of the Growth of Patient-Derived Pancreatic Cancer Xenografts with the MEK Inhibitor Trametinib Is Augmented by Combined Treatment with the Epidermal Growth Factor Receptor/HER2 Inhibitor Lapatinib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasia. 2013 Feb;15(2):143-55.
AUTORES / AUTHORS: - Walters DM; Lindberg JM; Adair SJ; Newhook TE; Cowan CR; Stokes JB; Borgman CA; Stelow EB; Lowrey BT; Chopivsky ME; Gilmer TM; Parsons JT; Bauer TW
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Virginia Health System, Charlottesville, VA.
RESUMEN / SUMMARY: - Mutations of the oncogene KRAS are important drivers of pancreatic cancer progression. Activation of epidermal growth factor receptor (EGFR) and human EGFR2 (HER2) is observed frequent in pancreatic adenocarcinomas. Because of co-activation of these two signaling pathways, we assessed the efficacy of inhibition of EGFR/HER2 receptors and the downstream KRAS effector, mitogen-activated protein kinase/extracellular-signal regulated kinase (ERK) kinase 1 and 2 (MEK1/2), on pancreatic cancer proliferation in vitro and in a murine orthotopic xenograft model. Treatment of established and patient-derived pancreatic cancer cell lines with the MEK1/2 inhibitor trametinib (GSK1120212) inhibited proliferation, and addition of the EGFR/HER2 inhibitor lapatinib enhanced the inhibition elicited by trametinib in three of eight cell lines. Importantly, in the orthotopic xenograft model, treatment with lapatinib and trametinib resulted in significantly enhanced inhibition of tumor growth relative to trametinib treatment alone in four of five patient-derived tumors tested and was, in all cases, significantly more effective in reducing the size of established tumors than treatment with lapatinib or trametinib alone. Acute treatment of established tumors with trametinib resulted in an increase in AKT2 phosphorylation that was blunted in mice treated with both trametinib and lapatinib. These data indicate that inhibition of the EGFR family receptor signaling may contribute to the effectiveness of MEK1/2 inhibition of tumor growth possibly through the inhibition of feedback activation of receptor tyrosine kinases in response to inhibition of the RAS-RAF-MEK-ERK pathway. These studies provide a rationale for assessing the co-inhibition of these pathways in the treatment of pancreatic cancer patients.
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[725]
TÍTULO / TITLE: - The Patient Journey in Chronic Myeloid Leukemia Patients on Tyrosine Kinase Inhibitor Therapies: Qualitative Insights Using a Global Ethnographic Approach.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Patient. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s40271-013-0006-3
AUTORES / AUTHORS: - Guilhot F; Coombs J; Szczudlo T; Zernovak O; Paolantonio M; Bender C; Macdonald NJ; Shapiro A
INSTITUCIÓN / INSTITUTION: - CIC 802 INSERM, CHU de Poitiers, Poitiers, France.
RESUMEN / SUMMARY: - BACKGROUND: The advent and approval of tyrosine kinase inhibitors (TKIs) have dramatically improved the life expectancy of patients with chronic myeloid leukemia (CML), which has been transformed into a chronically manageable disease. OBJECTIVE: The objective was to qualitatively assess the effects of diagnosis and treatment on patients with CML to offer recommendations for health-care providers (HCPs) for the better support of patients. METHODS: By use of an ethnographic approach based on in-home interviews, photo journals, and an optional telephone debriefing interview, this study included 50 patients with CML from Brazil, France, Germany, Russia, and España, including patients within 18 months of diagnosis and receiving frontline TKI therapy (n = 20), patients between >18 months and 7 years from diagnosis and receiving ongoing frontline therapy (n = 20), and patients who switched to second- or third-line TKI therapy (n = 10). In-home interviews were designed to address patient perceptions and experiences regarding such issues as adherence, disease knowledge, disease management, and relationships with HCPs. Transcripts from these interviews and other data were analyzed to identify similar patterns and themes experienced by patients with CML. RESULTS: The investigation generated a five-stage, patient-centered model of the experience of the patient throughout diagnosis, treatment, and management of CML: crisis, hope, adaptation, new normal, and uncertainty. Patients proceeded through these stages in the course of their disease management. The stages were affected by the patients’ emotional and social experiences, their knowledge about CML, their positive experiences with their HCPs and/or treatment, and their optimism about their long-term prognosis. CONCLUSIONS: We identified five common stages experienced by patients with CML and suggest several recommendations for HCPs on the management of patients through their disease journey. By providing support, education, and reassurance, HCPs can help patients as they move through the early stages of crisis and hope. When patients are in the adaptation and new-normal stages, HCPs can help patients achieve and maintain a new normality by setting expectations for the risks/benefits of long-term chronic drug therapy and disease monitoring and by continuing to support patient adherence.
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[726]
TÍTULO / TITLE: - Sterically stabilized gelatin microassemblies of noscapine enhance cytotoxicity, apoptosis and drug delivery in lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Colloids Surf B Biointerfaces. 2013 Feb 24;107C:235-244. doi: 10.1016/j.colsurfb.2013.02.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.colsurfb.2013.02.010
AUTORES / AUTHORS: - Madan J; Pandey RS; Jain UK; Katare OP; Aneja R; Katyal A
INSTITUCIÓN / INSTITUTION: - Department of Biology, Georgia State University, Atlanta, GA 30303, USA; Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab, India. Electronic address: jitenderpharmacy@gmail.com.
RESUMEN / SUMMARY: - Noscapine, recently identified as anticancer due to its microtubule-modulating properties. It is presently in Phase I/II clinical trials. The therapeutic efficacy of noscapine has been established in several xenograft models. Its pharmacokinetic limitations such as low bioavailability and high ED50 impede development of clinically relevant treatment regimens. Here we present design, synthesis, in vitro and in vivo characterization of sterically stabilized gelatin microassemblies of noscapine (SSGMS) for targeting human non-small cell lung cancer A549 cells. The average size of the sterically stabilized gelatin microassemblies of noscapine, SSGMS was 10.0+/-5.1mum in comparison to noscapine-loaded gelatin microassemblies, GMS that was 8.3+/-5.5mum. The noscapine entrapment efficiency of SSGMS and GMS was 23.99+/-4.5% and 24.23+/-2.6%, respectively. Prepared microassemblies were spherical in shape and did not show any drug and polymer interaction as examined by FTIR, DSC and PXRD. In vitro release data indicated that SSGMS and GMS follow first-order release kinetics and exhibited an initial burst followed by slow release of the drug. In vitro cytotoxicity evaluated using A549 cells showed a low IC50 value of SSGMS (15.5muM) compared to GMS (30.1muM) and free noscapine (47.2muM). The SSGMS can facilitate a sustained therapeutic effect in terms of prolonged release of noscapine as evident by caspase-3 activity in A549 cells. Concomitantly, pharmacokinetic and biodistribution analysis showed that SSGMS increased the plasma half-life of noscapine by approximately 9.57-fold with an accumulation of approximately 48% drug in the lungs. Our data provides evidence for the potential usefulness of SSGMS for noscapine delivery in lung cancer.
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[727]
TÍTULO / TITLE: - Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: Calorie restriction is the force to the cytotoxicity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Exp Toxicol. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1177/0960327113475679
AUTORES / AUTHORS: - Fouad M; Agha A; Merzabani MA; Shouman S
INSTITUCIÓN / INSTITUTION: - 1Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Egypt.
RESUMEN / SUMMARY: - The aim of this study was to examine the antitumour activity of resveratrol in human colorectal cancer cell lines (HCT116 and Caco2) and to explore its mechanism of action assuming that it is by calorie-restriction effect. Resveratrol inhibited the proliferation of colon cancer cells with half maximal inhibitory concentration (IC50) equal to 50 and 130 muM for HCT116 and Caco2, respectively. Caco2 cells appeared with significant time-dependent increase in the glycolytic pathway, a behaviour that was absent in HCT116 cells. Resveratrol (100 muM) significantly decreased the glycolytic enzymes (pyruvate kinase and lactate dehydrogenase) in Caco2 cells, while an increase in citrate synthase activity and a decrease in glucose consumption were observed in both cell lines. Moreover, resveratrol downregulated the expressions of leptin and c-Myc, and decreased the content of vascular endothelial growth factor. The apoptotic markers, caspases 3 and 8, were activated and the Bax/BCl2 ratio was increased. The study suggested a promising anticancer activity of resveratrol, calorie-restriction pathway may be one of the driving forces for this activity.
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[728]
TÍTULO / TITLE: - Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacogenomics. 2013 Feb;14(3):315-24. doi: 10.2217/pgs.12.213.
●● Enlace al texto completo (gratuito o de pago) 2217/pgs.12.213
AUTORES / AUTHORS: - Weng L; Zhang L; Peng Y; Huang RS
INSTITUCIÓN / INSTITUTION: - Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
RESUMEN / SUMMARY: - In the past decade, advances in pharmacogenetics and pharmacogenomics (PGx) have gradually unveiled the genetic basis of interindividual differences in drug responses. A large portion of these advances have been made in the field of anticancer therapy. Currently, the US FDA has updated the package inserts of approximately 30 anticancer agents to include PGx information. Given the complexity of this genetic information (e.g., tumor mutation and gene overexpression, chromosomal translocation and germline variations), as well as the variable level of scientific evidence, the FDA recommendation and potential action needed varies among drugs. In this review, we have highlighted some of these PGx discoveries for their scientific values and utility in improving therapeutic efficacy and reducing side effects. Furthermore, examples are also provided for the role of PGx in new anticancer drug development by revealing novel druggable targets.
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[729]
TÍTULO / TITLE: - Expression of Quiescin Sulfhydryl Oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer Res. 2013 Mar 28;15(2):R28.
●● Enlace al texto completo (gratuito o de pago) 1186/bcr3407
AUTORES / AUTHORS: - Katchman BA; Ocal IT; Cunliffe HE; Chang YH; Hostetter G; Watanabe A; Lobello J; Lake DF
RESUMEN / SUMMARY: - INTRODUCTION: Quiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. Tumor specific expression of QSOX1 has been reported for numerous tumor types. In this study, we investigate QSOX1 as a marker of breast tumor progression and evaluate the role of QSOX1 as it relates to breast tumor growth and metastasis. METHODS: Correlation of QSOX1 expression with breast tumor grade, subtype, and Estrogen Receptor (ER) status was gathered through informatic analysis using the “Gene Expression Based Outcome for Breast Cancer Online” (GOBO) web-based tool. Expression of QSOX1 protein in breast tumors tissue microarray (TMA) and in a panel of breast cancer cell lines was used to confirm our informatics analysis. To investigate malignant cell mechanisms for which QSOX1 might play a key role, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in ER+ Luminal A-like MCF7, ER+ Luminal B-like BT474 and ER- Basal-like BT549 breast cancer cell lines. RESULTS: GOBO analysis revealed high levels of QSOX1 RNA expression in ER+ subtypes of breast cancer. In addition, Kaplan Meyer analyses revealed QSOX1 RNA as a highly significant predictive marker for both relapse and poor overall survival in Luminal B tumors. We confirmed this finding by evaluation of QSOX1 protein expression in breast tumors and in a panel of breast cancer cell lines. Expression of QSOX1 in breast tumors correlates with increasing tumor grade and high Ki-67 expression. Suppression of QSOX1 protein slowed cell proliferation as well as dramatic inhibition of MCF7, BT474 and BT549 breast tumor cells from invading through Matrigel in a modified Boyden chamber assay. Inhibition of invasion could be rescued by the exogenous addition of recombinant QSOX1. Gelatin zymography indicated that QSOX1 plays an important role in function of MMP-9 a key mediator of breast cancer invasive behavior. CONCLUSIONS: Taken together, our results suggest that QSOX1 is a novel biomarker for risk of relapse and poor survival in Luminal B breast cancer, and has a pro-proliferative and pro-invasive role in malignant progression partly mediated through a decrease in MMP-9 functional activity.
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[730]
TÍTULO / TITLE: - Gambogic Acid Sensitizes Ovarian Cancer Cells to Doxorubicin Through ROS-Mediated Apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biochem Biophys. 2013 Feb 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s12013-013-9534-7
AUTORES / AUTHORS: - Wang J; Yuan Z
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Jiangyin Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, No. 130 Renmingzhong Road, Jiangyin, 214400, Jiangsu, China, drwangjianxia@gmail.com.
RESUMEN / SUMMARY: - Ovarian cancer is one human malignancy which has response portly to doxorubicin. The anti-cancer activity of gambogic acid has been tested in in vitro and in vivo studies. In this study, we showed that gambogic acid, a natural compound, could potentiate the anticancer activity of doxorubicin in ovarian cancer through ROS-mediated apoptosis. Platinum-resistant human ovarian cancer cell line (SKOV-3) was treated with gambogic acid, doxorubicin, or the combination of both to investigate cell proliferation and apoptosis. We found that the combination of gambogic acid and doxorubicin causes synergistic loss of cell viability in SKOV-3 cells and this synergistic effect correlated with increased cellular ROS accumulation. Moreover, in vivo results showed that gambogic acid and doxorubicin combination resulted in a synergistic suppressing effect on tumor growth in ovarian cancer mice model. Taken together, the results suggested that doxorubicin in combination with gambogic acid might provide a promising therapeutic strategy to enhance chemosensitivity of ovarian cancer to doxorubicin.
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[731]
TÍTULO / TITLE: - MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer. 2013 Mar 26;12(1):23.
●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-12-23
AUTORES / AUTHORS: - Creevey L; Ryan J; Harvey H; Bray IM; Meehan M; Khan AR; Stallings RL
RESUMEN / SUMMARY: - BACKGROUND: Neuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive of neuroblastoma patient survival and has been reported as a tumor suppressor in a variety of other cancers. WEE1, a tyrosine kinase regulator of the cell cycle and predicted target of miR-497, has emerged as an oncogene in several cancer types and therefore represents an attractive potential target for novel therapy approaches in high-risk neuroblastoma. Our aim was to investigate the potential tumor suppressive role of miR-497 in high-risk neuroblastoma. METHODS: Expression levels of miR-497 and WEE1 in tissues and cells were determined using RT-PCR . The effect of miR-497 and siWEE1 on cell viability was evaluated using MTS assays, apoptosis levels were determined using FACS analysis of Annexin V/PI stained cells, and target protein expression was determined using western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean+/-S.E.M and differences were tested for significance using 2-tailed Students t-test. RESULTS: We determined that miR-497 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and that low miR-497 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-497 reduced cell viability and increased apoptosis in MNA cells. We identified WEE1 as a novel target for miR-497 in neuroblastoma. Furthermore, our analysis showed that high WEE1 levels are significantly associated with poor EFS and OS in neuroblastoma and that siRNA knockdown of WEE1 in MNA cell lines results in significant levels of apoptosis, supporting an oncogenic role of WEE1 in neuroblastoma. Cisplatin (CDDP) treatment of both miR-497 over-expressing cells and WEE1 inhibited cells, resulted in a significant increase in apoptosis in MNA cells, describing a synergistic effect and therefore a potential therapeutic for high-risk neuroblastoma. CONCLUSION: Our study’s results are consistent with miR-497 being a candidate tumor suppressor in neuroblastoma, through the direct targeting of WEE1. These findings re-enforce the proposal of WEE1 as a therapeutic target in neuroblastoma.
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[732]
TÍTULO / TITLE: - Crizotinib induces PUMA-dependent apoptosis in colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1146
AUTORES / AUTHORS: - Zheng X; He K; Zhang L; Yu J
INSTITUCIÓN / INSTITUTION: - 1Department of Pathology, University of Pittsburgh, The Hillman Cancer Center.
RESUMEN / SUMMARY: - Oncogenic alterations in MET or ALK have been identified in a variety of human cancers. Crizotinib (PF02341066) is a dual MET and ALK inhibitor and approved for the treatment of a subset of non-small-cell lung carcinoma; and in clinical development for other malignancies. Crizotinib can induce apoptosis in cancer cells while the underlying mechanisms are not well understood. In this study, we found that crizotinib induces apoptosis in colon cancer cells through the BH3-only protein PUMA. In cells with wild-type p53, crizotinib induces rapid induction of PUMA and Bim accompanied by p53 stabilization and DNA damage response. The induction of PUMA and Bim is mediated largely by p53, and deficiency in PUMA or p53, but not Bim, blocks crizotinib-induced apoptosis. Interestingly, MET knockdown led to selective induction of PUMA, but not Bim or p53. Crizotinib also induced PUMA-dependent apoptosis in p53-deficient colon cancer cells, and synergized with gefitinib or sorafenib to induce marked apoptosis via PUMA in colon cancer cells. Furthermore, PUMA deficiency suppressed apoptosis and therapeutic responses to crizotinib in xenograft models. These results establish a critical role of PUMA in mediating apoptotic responses of colon cancer cells to crizotinib, and suggest that mechanisms of oncogenic addiction to MET/ALK-mediated survival might be cell-type specific. These findings have important implications for future clinical development of crizotinib.
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[733]
TÍTULO / TITLE: - PI3K inhibition potentiates Bcl-2-dependent apoptosis in renal carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Mol Med. 2013 Mar;17(3):377-85. doi: 10.1111/jcmm.12019. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1111/jcmm.12019
AUTORES / AUTHORS: - Zhu S; Cohen MB; Bjorge JD; Mier JW; Cho DC
INSTITUCIÓN / INSTITUTION: - Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; School of Biological Science and Technology, State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
RESUMEN / SUMMARY: - Inhibitors of PI3-K/Akt are currently being assessed clinically in patients with advanced RCC. Identification of therapeutic strategies that might enhance the efficacy of PI3-K/Akt inhibitors is therefore of great interest. As PI3-K inhibition would be expected to have many pro-apoptotic effects, we hypothesized that there may be unique synergy between PI3-K inhibitors and BH3-mimetics. Towards this end, we assessed the combination of the PI3K inhibitor LY 294002 and the Bcl-2 family inhibitor ABT-737 in RCC cell lines. We found that the combinatorial treatment with these agents led to a significant increase in PARP cleavage and cell death in all RCC cell lines. The synergized cell death was correlated with decreased levels of Mcl-1 and XIAP, and increased levels in Bim, and appears critically dependent upon the activation of caspase 3 and 8. The enhanced lethality observed with the combination also appears dependent upon the regulation of XIAP, Mcl-1 and Bim levels. Our results suggest that the combination of PI3-K inhibitors with BH3-mimetics may be a viable therapeutic strategy in RCC.
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[734]
TÍTULO / TITLE: - Growth Inhibition and Apoptosis of Neuroblastoma Cells Through ROS-Independent MEK/ERK Activation by Sulforaphane.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biochem Biophys. 2013 Feb 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s12013-013-9522-y
AUTORES / AUTHORS: - Hsu YC; Chang SJ; Wang MY; Chen YL; Huang TY
INSTITUCIÓN / INSTITUTION: - Graduate Institute of Medical Science, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan, jenway@mail.cjcu.edu.tw.
RESUMEN / SUMMARY: - Deregulation of apoptosis alters the balance of cell proliferation and cell death, resulting in a variety of diseases, including cancer. In recent studies, sulforaphane (SFN) has demonstrated potent anti-tumor and chemopreventive activities. A possible signal transduction pathway has also been elucidated for SFN-induced apoptosis in human neuroblastoma SH-SY5Y cells. The present study further investigates the anti-proliferation activities of SFN through induced apoptosis in SH-SY5Y cells. We found that treating SH-SY5Y cells with SFN resulted in the depletion of mitochondrial membrane potential (Deltapsi), which in turn increased caspase 9, caspase 3, and the up-regulation of phosphorylated MEK/ERK without generating reactive oxygen species. Results were confirmed by MTT assay, which demonstrated the cytotoxic activity of SFN against SH-SY5Y cells (IC(50) values of 20 muM).
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[735]
TÍTULO / TITLE: - A hemagglutinin from northeast red beans with immunomodulatory activity and anti-proliferative and apoptosis-inducing activities toward tumor cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Protein Pept Lett. 2013 Mar 15.
AUTORES / AUTHORS: - Chan YS; Wong JH; Fang EF; Pan W; Ng TB
INSTITUCIÓN / INSTITUTION: - School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong. b021770@mailserv.cuhk.edu.hk.
RESUMEN / SUMMARY: - A 64-kDa hemagglutinin from a Phaseolus vulgaris cultivar, the northeast red bean, was purified by a protocol composed of three chromatographic steps involving affinity chromatography on Affi-gel blue gel, cation exchange chromatography on SP-Sepharose and FPLC-gel filtration on Superdex 75. The purified hemagglutinin appeared as a single 32-kDa band in SDS-PAGE indicating its dimeric nature. The N-terminal amino acid sequence of the hemagglutinin resembled the sequences of lectins and hemagglutinins from a number of Phaseolus species. The hemagglutinin manifested moderate thermostability and pH stability. It retained full activity up to 65 degrees C and in the pH range 2-12. It did not interact with simple sugars such as glucose, mannose and galactose. The hemagglutinin exerted immunostimulatory effects by upregulating the expression of cytokines like interferon-gamma and tumor necrosis factor-alpha. It also exhibited antiproliferative activity on a number of tumor cells including MCF7 (breast cancer), HepG2 (liver cancer), CNE1 and CNE2 (nasopharyngeal cancer) cells, with stronger activity toward MCF7 and CNE1 cells. The hemagglutinin induced phophatidylserine externalization, mitochondrial depolarization and DNA condensation in MCF7 cells, indicating initiation of apoptosis. However, at high hemagglutinin concentrations, severe damage to the MCF7 cells was detected.
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[736]
TÍTULO / TITLE: - GX15-070 (Obatoclax) Induces Apoptosis and Inhibits Cathepsin D- and L-Mediated Autophagosomal Lysis in Antiestrogen-Resistant Breast Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0617
AUTORES / AUTHORS: - Schwartz-Roberts JL; Shajahan AN; Cook KL; Warri A; Abu-Asab M; Clarke R
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: 1Department of Oncology, Lombardi Comprehensive Cancer Center; 2Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, District of Columbia; and 3Section of Immunopathology and Laboratory of Immunology, National Eye Institute, NIH, Bethesda, Maryland.
RESUMEN / SUMMARY: - In estrogen receptor-positive (ER+) breast cancer cells, BCL2 overexpression contributes to antiestrogen resistance. Direct targeting of the antiapoptotic BCL2 members with GX15-070 (obatoclax), a BH3-mimetic currently in clinical development, is an attractive strategy to overcome antiestrogen resistance in some breast cancers. Recently, GX15-070 has been shown to induce both apoptosis and autophagy, yet the underlying cell death mechanisms have yet to be elucidated. Here, we show that GX15-070 is more effective in reducing the cell density of antiestrogen-resistant breast cancer cells versus sensitive cells and that this increased sensitivity of resistant cells to GX15-070 correlates with an accumulation of autophagic vacuoles. Formation of autophagosomes in GX15-070-treated cells was verified by changes in expression of the lipidation of microtubule-associated protein-1 light chain-3 and both confocal and transmission electron microscopy. While GX15-070 treatment promotes autophagic vacuole and autolysosome formation, p62/SQSTM1, a marker for autophagic degradation, levels accumulate. Moreover, GX15-070 exposure leads to a reduction in cathepsin D (CTSD) and L (CTSL1) protein expression that would otherwise digest autolysosome cargo. Thus, GX15-070 has dual roles in promoting cell death: (i) directly inhibiting antiapoptotic BCL2 family members, thereby inducing apoptosis; and (ii) inhibiting downstream CTSD and CTSL1 protein expression to limit the ability of cells to use degraded material to fuel cellular metabolism and restore homeostasis. Our data highlight a new mechanism of GX15-070-induced cell death that could be used to design novel therapeutic interventions for antiestrogen resistant breast cancer. Mol Cancer Ther; 12(4); 1-12. ©2013 AACR.
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[737]
TÍTULO / TITLE: - Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 Feb 26;1833(6):1356-1366. doi: 10.1016/j.bbamcr.2013.02.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbamcr.2013.02.014
AUTORES / AUTHORS: - Gallerne C; Prola A; Lemaire C
INSTITUCIÓN / INSTITUTION: - INSERM UMR S-769, LabEx LERMIT, Universite Paris-Sud 11, Chatenay-Malabry, France; Universite Versailles St-Quentin, Versailles, France.
RESUMEN / SUMMARY: - Heat shock protein 90 (Hsp90) has recently emerged as an attractive therapeutic target in cancer treatment because of its role in stabilizing the active form of a wide range of client oncoproteins. This study investigated the mechanism of apoptosis induced by the purine-scaffold Hsp90 inhibitor PU-H71 in different human cancer cell lines and examined the role of Bcl-2 and Bax in this process. We demonstrated that Hsp90 inhibition by PU-H71 generated endoplasmic reticulum (ER) stress and activated the Unfolded Protein Response (UPR) as evidenced by XBP1 mRNA splicing and up-regulation of Grp94, Grp78, ATF4 and CHOP. In response to PU-H71-induced ER stress, apoptosis was triggered in melanoma, cervix, colon, liver and lung cancer cells, but not in normal human fibroblasts. Apoptosis was executed through the mitochondrial pathway as shown by down-regulation of Bcl-2, up-regulation and activation of Bax, permeabilization of mitochondrial membranes, release of cytochrome c and activation of caspases. We also found that, in contrast to the ER stressor thapsigargin, PU-H71 induced apoptosis in cells overexpressing Bcl-2 and thus overcame the resistance conferred by this anti-apoptotic protein. In addition, although Bax deficiency rendered cells resistant to PU-H71, combined treatment with the anticancer drugs cisplatin or melphalan greatly sensitized these cells to PU-H71. Taken together, these data suggest that inhibition of Hsp90 by PU-H71 is a promising strategy for cancer treatment, particularly in the case of tumors resistant to conventional chemotherapy.
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[738]
TÍTULO / TITLE: - Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imaging and therapy of cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Colloids Surf B Biointerfaces. 2013 Jun 1;106:117-25. doi: 10.1016/j.colsurfb.2013.01.051. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1016/j.colsurfb.2013.01.051
AUTORES / AUTHORS: - Heidari Majd M; Asgari D; Barar J; Valizadeh H; Kafil V; Abadpour A; Moumivand E; Mojarrad JS; Rashidi MR; Coukos G; Omidi Y
INSTITUCIÓN / INSTITUTION: - Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
RESUMEN / SUMMARY: - Magnetic nanoparticles (MNPs) have been widely used as drug delivery nanosystems and contrast agent for imaging and detection. To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, in the current study, we synthesized tamoxifen (TMX) loaded folic acid (FA) armed MNPs to target the folate receptor (FR) positive cancer cells. To this end, Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Polyethylene glycol (PEG) was treated with excess bromoacetyl chloride (BrAc) and then with 3-aminopropyltriethoxysilane (APS) to synthesize bromoacetyl-terminal polyethylene glycol silane (APS-PEG-BrAc). The latter complex was treated with protected ethylene diamine to form a bifunctional PEG compound containing triethoxysilane at one end and amino group at the other end (APS-PEG-NH2). The Fe3O4-APS-PEG-NH2 NPs were prepared through self-assembly of APS-PEG-NH2 on MNPs, while the amino groups at the end of Fe3O4-APS-PEG-NH2 were conjugated with folic acid (FA), then loaded with TMX (Fe3O4-APS-PEG-FA-TMX). The average size of “Fe3O4-APS-PEG-FA-TMX” NPs was approximately 40nm. The engineered MNPs were further characterized and examined in the human breast cancer MCF-7 cells that express FR. The TMX loaded MNPs (with loading efficiency of 49.1%) showed sustained liberation of TMX molecules (with 90% release in 72h). Fluorescence microcopy and flow cytometry analyses revealed substantial interaction of Fe3O4-APS-PEG-FA-TMX NPs with the FR-positive MCF-7 cells. Cytotoxicity analysis resulted in significant growth inhibition in MCF-7 cells treated with Fe3O4-APS-PEG-FA-TMX NPs. Based on these findings, the TMX-loaded FA-armed PEGylated MNPs as a novel multifunctional nanomedicine/theranostic for concurrent targeting, imaging and therapy of the FR-positive cancer cells.
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[739]
TÍTULO / TITLE: - Cost Effectiveness of Pegfilgrastim Versus Filgrastim After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Lymphoma and Myeloma : An Economic Evaluation of the PALM Trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Appl Health Econ Health Policy. 2013 Apr;11(2):129-38. doi: 10.1007/s40258-013-0011-7.
●● Enlace al texto completo (gratuito o de pago) 1007/s40258-013-0011-7
AUTORES / AUTHORS: - Perrier L; Lefranc A; Perol D; Quittet P; Schmidt-Tanguy A; Siani C; de Peretti C; Favier B; Biron P; Moreau P; Bay JO; Lissandre S; Jardin F; Espinouse D; Sebban C
INSTITUCIÓN / INSTITUTION: - Department Cancer and Environment, Cancer Centre Leon Berard, University of Lyon, GATE Lyon-St Etienne, UMR-CNRS 5824, 28 rue Laennec, 69373, Lyon Cedex 08, France, lionel.perrier@lyon.unicancer.fr.
RESUMEN / SUMMARY: - BACKGROUND: Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet. OBJECTIVE: We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100 +/- 10 days from transplant. METHODS: The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital’s point of view and are expressed in 2009 euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann-Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5 x 10(9)/L and temperature >/=38 degrees C), duration of neutropenia (ANC <1.0 x 10(9)/L and ANC <0.5 x 10(9)/L), duration of thrombopenia (platelets <50 x 10(9)/L and <20 x 10(9)/L), and days with a temperature >/=38 degrees C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method. RESULTS : 151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n = 74) was <euro>25,024 (SD 9,945). That in the filgrastim arm (n = 76) was <euro>28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0 x 10(9)/L) avoided, days of thrombopenia (platelets <20 x 10(9)/L) avoided, and days with temperature >/=38 degrees C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5 x 10(9)/L avoided and the number of days with platelets <50.0 x 10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67 % for febrile neutropenia, 86 % for neutropenia (ANC <1.0 x 10(9)/L), 59 % for thrombopenia (platelets <20 x 10(9)/L), 86 % for temperature >/=38 degrees C, 32 % for neutropenia (ANC <0.5 x 10(9)/L), and 43 % for thrombopenia (platelets <50 x 10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5 x 10(9)/L) is 5 %. CONCLUSION: This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.
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[740]
TÍTULO / TITLE: - Afatinib prolongs survival compared to gefitinib in an epidermal growth factor receptor-driven lung cancer model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0885
AUTORES / AUTHORS: - Ninomiya T; Takigawa N; Ichihara E; Ochi N; Murakami T; Honda Y; Kubo T; Minami D; Kudo K; Tanimoto M; Kiura K
INSTITUCIÓN / INSTITUTION: - 1Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
RESUMEN / SUMMARY: - An irreversible ErbB family blocker is expected to inhibit tumors with activating epidermal growth factor receptor (EGFR) mutations more strongly than reversible EGFR tyrosine kinase inhibitors and to overcome acquired resistance to the T790M secondary mutation. Eleven-week-old transgenic mice with Egfr exon 19 deletion mutation were treated with afatinib, gefitinib, or vehicle for 4 weeks. All mice were sacrificed at 15 weeks of age, and the number of superficial left lung tumors with a long axis exceeding 1 mm was counted. The afatinib-treated group had significantly fewer tumors than the vehicle group (P < 0.01) and tended to have fewer tumors than the gefitinib-treated group (P = 0.06). Pathologically, gefitinib-treated mice had clearer, more nodular tumors than afatinib-treated mice. Immunoblotting showed that afatinib suppressed not only pEGFR but also pHER2, and induced apoptosis for longer periods than gefitinib. Subsequently, when each drug was administered 5 days per week until death, afatinib significantly enhanced mouse survival compared with gefitinib (median survival time: 456 days versus 376.5 days; logrank test, P < 0.01). Finally, the combination of afatinib with bevacizumab was found to be superior to either drug alone in exon 19 deletion/T790M and L858R/T790M xenograft tumors. Overall, afatinib was more potent than gefitinib in tumors harboring an exon 19 deletion mutation, and the combination of afatinib with bevacizumab efficiently suppressed tumors harboring the T790M secondary mutation.
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[741]
TÍTULO / TITLE: - DNA methyltransferase inhibitors as epigenetic therapy for cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Cancer Drug Targets. 2013 Mar 18.
AUTORES / AUTHORS: - Singh V; Sharma P; Capalash N
INSTITUCIÓN / INSTITUTION: - Department of Biotechnology, Panjab University, Chandigarh, India. caplash@pu.ac.in.
RESUMEN / SUMMARY: - DNA methylation is an epigenetic modification involved in gene expression regulation. In cancer, the DNA methylation pattern becomes aberrant, causing an array of tumor suppressor genes to undergo promoter hypermethylation and become transcriptionally silent. Reexpression of methylation silenced tumor suppressor genes by inhibiting the DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) has emerged as an effective strategy against cancer. The expression of DNA methyltransferase 1 (DNMT1) being high in S-phase of cell cycle makes it a specific target for methylation inhibition in rapidly dividing cells as in cancer. This review discusses nucleoside analogues (azacytidine, decitabine, zebularine, SGI-110, CP-4200), non-nucleoside ihibitors both synthetic (hydralazine, RG108, procaine, procainamide, IM25, disulfiram) and natural compounds (curcumin, genistein, EGCG, resveratrol, equol, parthenolide) which act through different mechanisms to inhibit DNMTs. The issues of bioavailability, toxicity, side effects, hypomethylation resistance and combinatorial therapies have also been highlighted.
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[742]
TÍTULO / TITLE: - The Histone Deacetylase Inhibitor Sodium Butyrate Promotes Cell Death and Differentiation and Reduces Neurosphere Formation in Human Medulloblastoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Neurobiol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s12035-013-8441-7
AUTORES / AUTHORS: - Nor C; Sassi FA; de Farias CB; Schwartsmann G; Abujamra AL; Lenz G; Brunetto AL; Roesler R
INSTITUCIÓN / INSTITUTION: - Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
RESUMEN / SUMMARY: - Increasing evidence suggests that alterations in epigenetic mechanisms regulating chromatin state play a role in the pathogenesis of medulloblastoma (MB), the most common malignant brain tumor of childhood. Histone deacetylase (HDAC) inhibitors, which increase chromatin relaxation, have been shown to display anticancer activities. Here we show that the HDAC inhibitor sodium butyrate (NaB) markedly increases cell death and reduces colony formation in human MB cell lines. In addition, NaB increased the mRNA expression of Gria2, a neuronal differentiation marker, in D283 and DAOY cells and reduced the number of neurospheres in D283 cell cultures. Finally, NaB reduced the viability of D283 cells when combined with etoposide. These data show that NaB displays pronounced inhibitory effects on the survival of human MB cells and suggest that NaB might potentiate the effects of etoposide. In addition, our study suggests that HDAC inhibition might promote the neuronal differentiation of MB cells and provides the first evidence that an HDAC inhibitor might suppress the expansion or survival of MB cancer stem cells.
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[743]
TÍTULO / TITLE: - Interferon-beta is a potent inhibitor of cell growth and cortisol production in vitro and sensitizes human adrenocortical carcinoma cells to mitotane.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocr Relat Cancer. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0217
AUTORES / AUTHORS: - van Koetsveld PM; Vitale G; Feelders RA; Waaijers MM; Sprij-Mooij D; de Krijger RR; Speel EJ; Hofland J; Lamberts SW; de Herder WW; Hofland L
INSTITUCIÓN / INSTITUTION: - P van Koetsveld, Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GD, Netherlands.
RESUMEN / SUMMARY: - Adrenocortical carcinoma (ACC) is an aggressive tumor with very poor prognosis. Novel medical treatment opportunities are required. We investigated the effects of interferon-beta (IFN-beta), alone or in combination with mitotane, on cell growth and cortisol secretion in primary cultures of 13 human ACC, 3 adrenal hyperplasias, 3 adrenal adenomas and in 2 ACC cell lines. Moreover, the interrelationship between the effects of IGF-II and IFN-beta was evaluated. Mitotane inhibited cell total DNA content/well (representing cell number) in 7/11 (IC50: 38+/-9.2 microM), and cortisol secretion in 5/5 ACC cultures (IC50: 4.5+/-0.1 microM). IFN-beta reduced cell number in 10/11 (IC50: 83+/-18 IU/mL) and cortisol secretion in 5/5 ACC cultures (IC50: 7.3+/-1.5 IU/mL). The effect of IFN-beta on cell number included the induction of apoptosis. IFN-beta strongly inhibited mRNA expression of STAR, CYP11A1, CYP17A1 and CYP11B1. Mitotane and IFN-beta induced an additive inhibitory effect on cell number and cortisol secretion. IGF-II (10nM) inhibited apoptosis and increased cell number and cortisol secretion. These effects were counteracted by IFN-beta treatment. Finally, IFN-beta inhibited IGF-II secretion and mRNA expression. In conclusion, IFN-beta is a potent inhibitor of ACC cell growth in human primary ACC cultures, partially mediated by an inhibition of the effects of IGF-II, as well as its production. The increased sensitivity of ACC cells to mitotane induced by treatment with IFN-beta may open the opportunity for combined treatment regimens with lower mitotane doses. The inhibition of the expression of steroidogenic enzymes by IFN-beta is a novel mechanism that may explain its inhibitory effect on cortisol production.
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[744]
TÍTULO / TITLE: - Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast Cancer. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s12282-013-0444-8
AUTORES / AUTHORS: - Noguchi S; Masuda N; Iwata H; Mukai H; Horiguchi J; Puttawibul P; Srimuninnimit V; Tokuda Y; Kuroi K; Iwase H; Inaji H; Ohsumi S; Noh WC; Nakayama T; Ohno S; Rai Y; Park BW; Panneerselvam A; El-Hashimy M; Taran T; Sahmoud T; Ito Y
INSTITUCIÓN / INSTITUTION: - Department of Breast and Endocrine Surgery, Osaka University, Osaka, Japan, noguchi@onsurg.med.osaka-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported. METHODS: Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety. RESULTS: Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade ¾ adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade ½ interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients. CONCLUSION: Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.
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[745]
TÍTULO / TITLE: - Synthesis of novel heterocyclic oleanolic acid derivatives with improved antiproliferative activity in solid tumor cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Org Biomol Chem. 2013 Feb 13;11(10):1726-38. doi: 10.1039/c3ob00011g.
●● Enlace al texto completo (gratuito o de pago) 1039/c3ob00011g
AUTORES / AUTHORS: - Leal AS; Wang R; Salvador JA; Jing Y
INSTITUCIÓN / INSTITUTION: - Laboratorio de Quimica Farmaceutica, Faculdade de Farmacia da Universidade de Coimbra, Polo das Ciencias da Saude, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
RESUMEN / SUMMARY: - A series of new oleanane imidazole carbamates, N-acylimidazoles or N-alkylimidazoles were synthesized, characterized and evaluated for their antiproliferative activity in AsPC-1 pancreatic cancer cells. Structure-activity relationship analysis revealed that the N-alkylimidazole 27 was the most active compound with apoptosis induction abilities correlated with upregulation of NOXA and downregulation of Bcl-xL. The antiproliferative activity of compound 27 was further tested in more solid tumor cell lines with IC(50) values lower than 1 muM.
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[746]
TÍTULO / TITLE: - Relationship Between Gastric Cancer Tau Protein Expression and Paclitaxel Sensitivity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Oncol Res. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s12253-012-9598-5
AUTORES / AUTHORS: - Wang Q; Wang N; Shao G; Qian J; Shen D; Fei Y; Mao W; Wu D
INSTITUCIÓN / INSTITUTION: - Department of Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Wuxi, 214400, People’s Republic of China, qiongwangcn@163.com.
RESUMEN / SUMMARY: - The abnormal expression of Tau protein in breast cancer tissue affects paclitaxel sensitivity. The abnormal expression also exists in gastric carcinoma. Therefore, we speculate that the expression levels of Tau protein is closely related to paclitaxel sensitivity in gastric cancer, thus affecting the efficacy of paclitaxel. In this study, we used immunohistochemical methods to detect Tau protein expression levels in 47 cases of gastric cancer specimens. We also used Western blot to detect the level of Tau protein expression in gastric cancer cell lines and to check the efficacy of paclitaxel in vitro application. Findings indicate that Tau protein expression rate can reach as high as (+ +-+ + +) 63.83 % in gastric cancer. Paclitaxel induces inhibition and apoptosis with low expression of Tau protein in gastric cancer cell lines (P < 0.05). The level of Tau protein expression is significantly correlated with paclitaxel efficacy. If confirmed by further studies, the Tau protein can be another useful marker of gastric cancer, thereby leading to the application of paclitaxel in cancer treatment.
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[747]
TÍTULO / TITLE: - RAD51C-deficient cancer cells are highly sensitive to the poly (ADP-ribose) polymerase inhibitor, olaparib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0950
AUTORES / AUTHORS: - Min A; Im SA; Yoon YK; Song SH; Nam HJ; Hur HS; Kim HP; Lee KH; Han SW; Oh DY; Kim TY; O Connor MJ; Kim WH; Bang YJ
INSTITUCIÓN / INSTITUTION: - 1Cancer Research Institute, Seoul National University College of Medicine.
RESUMEN / SUMMARY: - A poly (ADP-ribose) polymerase (PARP) inhibitor is a rationally designed targeted therapy for cancers with impaired DNA repair abilities. RAD51C is a paralog of RAD51 that has an important role in the DNA damage response. We found that cell lines sensitive to a novel oral PARP inhibitor, olaparib, had low levels of RAD51C expression using microarray analysis, and we therefore hypothesized that low expression of RAD51C may hamper the DNA repair process, resulting in increased sensitivity to olaparib. Compared to the cells with normal RAD51C expression levels, RAD51C-deficient cancer cells were more sensitive to olaparib, and a higher proportion underwent cell death by inducing G2/M cell cycle arrest and apoptosis. The restoration of RAD51C in a sensitive cell line caused attenuation of olaparib sensitivity. In contrast, silencing of RAD51C in a resistant cell line enhanced the sensitivity to olaparib, and the number of RAD51 foci decreased with ablated RAD51C expression. We also found the expression of RAD51C was down-regulated in cancer cells due to epigenetic changes and the RAD51C expression was low in some gastric cancer tissues. Furthermore, olaparib significantly suppressed RAD51C-deficient tumor growth in a xenograft model. In summary, RAD51C-deficient cancer cells are highly sensitive to olaparib and offer preclinical proof-of-principle that RAD51C deficiency may be considered a biomarker for predicting the antitumor effects of olaparib.
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[748]
TÍTULO / TITLE: - Claudin-7 increases chemosensitivity to cisplatin through the upregulation of caspase pathway in human NCI-H522 lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Sci. 2013 Feb 22. doi: 10.1111/cas.12135.
●● Enlace al texto completo (gratuito o de pago) 1111/cas.12135
AUTORES / AUTHORS: - Hoggard J; Fan J; Lu Z; Lu Q; Sutton L; Chen YH
INSTITUCIÓN / INSTITUTION: - Department of Anatomy and Cell Biology, East Carolina University, Greenville, North Carolina, USA; Department of Biology, East Carolina University, Greenville, North Carolina, USA.
RESUMEN / SUMMARY: - Claudins are a family of tight junction (TJ) integral membrane proteins that play a crucial role in maintaining cell polarity, adhesion, and paracellular permeability. Changes in expression levels of claudin proteins have been associated with human lung cancer. Previously, we have reported that claudin-7 expression is significantly downregulated in human lung carcinomas. To investigate the role of claudin-7 in lung cancer cells after anti-cancer drug treatments, we transfected claudin-7 cDNA into human NCI-H522 lung cancer cells, which have no detectable expression of claudin-7 protein. Flow cytometry analysis demonstrated that cells transfected with claudin-7 had a significantly higher percentage of cell apoptosis when compared to that of vector transfected cell population. The cell viability assayed by MTT and Annexin V was significantly decreased and cell apoptosis was dramatically increased in claudin-7 transfected cells compared to that of vector transfected cells after cisplatin treatment. Cisplatin is an anti-cancer drug clinically used to treat tumors in several tissues including lung tumors. Most importantly, after cisplatin treatment, the expression levels of cleaved caspase-3, -8, and poly adenosine 5’-diphosphate ribose polymerase (PARP) were much higher in claudin-7 transfected cells than in control cells. Furthermore, using the site-directed mutagenesis approach, we identified that claudin-7 was phosphorylated at serine 204 by protein kinase C. Non-phosphorylated claudin-7 mutant showed increased cell viability, suggesting that phosphorylation increases chemosensitivity to cisplatin treatment. We concluded that claudin-7 expression in H522 lung cancer cells increases chemosensitivity to cisplatin through the increased activation of caspase pathway.
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[749]
TÍTULO / TITLE: - The Histone Deacetylase Inhibitor, MS-275 (Entinostat), Downregulates c-FLIP, Sensitizes Osteosarcoma Cells to FasL, and Induces the Regression of Osteosarcoma Lung Metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Cancer Drug Targets. 2013 Jan 21.
AUTORES / AUTHORS: - Rao-Bindal K; Koshkina NV; Stewart J; Kleinerman ES
INSTITUCIÓN / INSTITUTION: - Division of Pediatrics and The Metastasis Research Center, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. ekleiner@mdanderson.org.
RESUMEN / SUMMARY: - The purpose of this study was to determine the effects of the histone deacetylase inhibitor, MS-275, on the Fas signaling pathway and susceptibility of osteosarcoma (OS) to Fas ligand (FasL)-induced cell death. OS metastasizes almost exclusively to the lungs. We have shown that Fas expression in OS cells is inversely correlated with their metastatic potential. Fas+ cells are rapidly eliminated when they enter the lungs via interaction with FasL, which is constitutively expressed in the lungs. Fas- OS cells escape this FasL-induced apoptosis and survive in the lung microenvironment. Moreover, upregulation of Fas in established OS lung metastases results in tumor regression. Therefore, agents that upregulate Fas expression or activate the Fas signaling pathway may have therapeutic potential. Treatment of Fas- metastatic OS cell lines with 2 microM MS-275 sensitized cells to FasL-induced cell death in vitro. We found that MS-275 did not alter the expression of Fas on the cell surface; rather it resulted in the downregulation of the anti-apoptotic protein, c-FLIP (cellular FLICE-inhibitory protein), by inhibiting c-FLIP mRNA. Downregulation of c-FLIP correlated with caspase activation and apoptosis induction. Treatment of nu/nu-mice with established OS lung metastases with oral MS-275 resulted in tumor regression, increased apoptosis and a significant inhibition of c-FLIP expression in tumors. Histopathological examination of mice showed no evidence of significant toxicity. Overall, these results suggest that the mechanism by which MS-275 sensitizes OS cells and lung metastases to FasL-induced cell death may be by a direct reduction in the expression of c-FLIP.
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[750]
TÍTULO / TITLE: - Proteasome inhibitors in the treatment of multiple myeloma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Rev Anticancer Ther. 2013 Mar;13(3):339-58. doi: 10.1586/era.13.9.
●● Enlace al texto completo (gratuito o de pago) 1586/era.13.9
AUTORES / AUTHORS: - McBride A; Ryan PY
INSTITUCIÓN / INSTITUTION: - James Cancer Hospital and Solove Research Institute & The Ohio State University, Columbus, OH 43210, USA. ali.mcbride@gmail.com.
RESUMEN / SUMMARY: - Proteasome inhibition has been shown to be an effective strategy for the treatment of multiple myeloma, as demonstrated by the clinical activity of the first-in-class agent bortezomib. Recently, the second-generation proteasome inhibitor carfilzomib has been approved in the USA in the relapsed and refractory setting, and several other investigational agents are in clinical development, including MLN9708, marizomib, oprozomib and delanzomib. Here, the authors provide a comprehensive review of the key role of proteasome inhibitors in the myeloma treatment pathway, and highlight the similarities and differences in pharmacology, routes of administration, and efficacy and safety profiles between bortezomib, carfilzomib and investigational agents. The authors also evaluate the potential for further improving myeloma treatment through the ongoing development of novel proteasome inhibitors.
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[751]
TÍTULO / TITLE: - Commentary on “Predicting metastasized seminoma using gene expression.” Ruf CG, Linbecker M, Port M, Riecke A, Schmelz HU, Wagner W, Meineke V, Abend M, Department of Urology, Federal Armed Forces Hospital, Hamburg, Germany: BJU Int 2012;110:E14.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urol Oncol. 2013 Feb;31(2):278. doi: 10.1016/j.urolonc.2013.02.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urolonc.2013.02.009
AUTORES / AUTHORS: - Richie J
RESUMEN / SUMMARY: - Treatment options for testis cancer depend on the histological subtype as well as on the clinical stage. An accurate staging is essential for correct treatment. The ‘golden standard’ for staging purposes is CT, but occult metastasis cannot be detected with this method. Currently, parameters such as primary tumour size, vessel invasion or invasion of the rete testis are used for predicting occult metastasis. Last year the association of these parameters with metastasis could not be validated in a new independent cohort. Gene expression analysis in testis cancer allowed discrimination between the different histological subtypes (seminoma and non-seminoma) as well as testis cancer and normal testis tissue. In a two-stage study design we (i) screened the whole genome (using human whole genome microarrays) for candidate genes associated with the metastatic stage in seminoma and (ii) validated and quantified gene expression of our candidate genes (real-time quantitative polymerase chain reaction) on another independent group. Gene expression measurements of two of our candidate genes (dopamine receptor D1 [DRD1] and family with sequence similarity 71, member F2 [FAM71F2]) examined in primary testis cancers made it possible to discriminate the metastasis status in seminoma. The discriminative ability of the genes exceeded the predictive significance of currently used histological/pathological parameters. Based on gene expression analysis the present study provides suggestions for improved individual decision making either in favour of early adjuvant therapy or increased surveillance. OBJECTIVE: To evaluate the usefulness of gene expression profiling for predicting metastatic status in testicular seminoma at the time of first diagnosis compared with established clinical and pathological parameters. PATIENTS AND METHODS: Total RNA was isolated from testicular tumours of metastasized patients (12 patients, clinical stage IIa-III), non-metastasized patients (40, clinical stage I) and adjacent ‘normal’ tissue (n = 36). The RNA was then converted into cDNA and real-time quantitative polymerase chain reaction was run on 94 candidate genes selected from previous work. Normalised gene expression of these genes and histological variables, e.g. tumour size and rete testis infiltration, were analysed using logistic regression analysis. RESULTS: Expression of two genes (dopamine receptor D1 [DRD1] and family with sequence similarity 71, member F2 [FAM71F2], P = 0.005 and 0.024 in separate analysis and P = 0.004 and 0.016 when combining both genes, respectively) made it possible to significantly discriminate the metastasis status. Concordance increased from 77.9% (DRD1) and 72.3% (FAM71F2) in separate analysis and up to 87.7% when combining both genes in one model. Only primary tumour size in separate analysis (continuous or categorical with tumour size>6cm) was significantly associated with metastasis (P = 0.039/P = 0.02), but concordance was lower (61%). When we combined tumour size with our two genes in one model there was no further statistical improvement or increased concordance. CONCLUSION: Based on gene expression analysis our study provides suggestions for improved individual decision making either in favour of early adjuvant therapy or increased surveillance.
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[752]
TÍTULO / TITLE: - Silencing glucose-regulated protein 78 induced renal cell carcinoma cell line G1 cell-cycle arrest and resistance to conventional chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urol Oncol. 2013 Feb 18. pii: S1078-1439(12)00352-3. doi: 10.1016/j.urolonc.2012.10.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urolonc.2012.10.006
AUTORES / AUTHORS: - Lin JA; Fang SU; Su CL; Hsiao CJ; Chang CC; Lin YF; Cheng CW
INSTITUCIÓN / INSTITUTION: - Graduate Institute of Clinical Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan.
RESUMEN / SUMMARY: - OBJECTIVE: Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone; it maintains endoplasmic reticulum homeostasis and modulates unfolded protein response. The protein is overexpressed in various cancer types, including renal cell carcinoma (RCC). Increased Grp78 expression in patients with RCC is correlated with more aggressive tumors and poorer prognoses. This study investigated the role of Grp78 in regulating tumorigenesis and evaluated the potential of Grp78-targeted therapy for RCC. METHODS: The expression level of Grp78 was examined in von Hippel-Lindau (VHL)-intact or VHL-null RCC cell lines by reverse transcription polymerase chain reaction and Western blot. Specific Grp78 ribonucleic acid interference was applied as a molecularly Grp78-targeted therapeutic approach. This method enabled us to assess the effects of manipulating Grp78 expression to regulate RCC cell growth. RESULTS: The Grp78 messenger ribonucleic acid and protein were expressed in both VHL-intact and VHL-null RCC cell lines. The specific inhibition of Grp78 expression suppressed RCC cell growth and colony formation significantly, and induced G1 cell-cycle arrest. We also showed that inhibiting Grp78 expression increased the cells’ resistance to the cytotoxicity of the S-phase-specific anticancer drug 5-fluorouracil. This effect was regulated by the unfolded protein response-induced suppression of G1/S transition-related cyclins (D1, E1, and E2) and cyclin-dependent kinase (CDK4 and CDK6) protein expression. CONCLUSION: Overall, our findings indicate the regulatory function of Grp78 in RCC cell proliferation, and provide a molecular-based mechanism of Grp78 positivity in the progression of RCC.
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[753]
TÍTULO / TITLE: - Molecular Analysis of the KIT Gene in Gastrointestinal Stromal Tumors With Novel Mutations.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Appl Immunohistochem Mol Morphol. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e318284a074
AUTORES / AUTHORS: - Calibasi G; Baskin Y; Alyuruk H; Cavas L; Oztop I; Sagol O; Atila K; Ellidokuz H; Yilmaz U
INSTITUCIÓN / INSTITUTION: - *Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University daggerGraduate School of Natural and Applied Sciences double daggerDepartment of Chemistry, Division of Biochemistry, Faculty of Science, Kaynaklar Campus Departments of section signMedical Oncology parallelPathology paragraph signSurgery, Faculty of Medicine #Department of Preventive Oncology, Institute of Oncology, Inciralti, Izmir-Turkey.
RESUMEN / SUMMARY: - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT gene mutations have great importance for GISTs. This study evaluated the relationship between KIT mutations and GIST clinicopathologic features to define region-specific and population-specific differences. Genomic DNA was extracted from 60 GISTs, and polymerase chain reaction was performed for KIT gene exons 9, 11, 13, and 17. Polymerase chain reaction amplicons were sequenced in both directions. This study represents the first mutation data of the KIT gene in GISTs from a Turkish population and reports novel mutations. The mutation rate in exon 11 (46.7%) was remarkably higher than those of the other exons (8.3% for exon 9; 11.7% for exon 13; 1.7% for exon 17). There was an association between malignancy potential and the presence of KIT mutations (odds ratio=3.18). Cases with mutations in codons W557-K558 in exon 11 had 11-fold greater risk of malignancy when compared with those without a mutation in this exon (odds ratio=11). We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.
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[754]
TÍTULO / TITLE: - Evaluation of MMP2 and Caspase-3 expression in 107 cases of papillary thyroid carcinoma and its association with prognostic factors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Res Pract. 2013 Mar;209(3):195-9. doi: 10.1016/j.prp.2012.06.011. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.prp.2012.06.011
AUTORES / AUTHORS: - Saffar H; Sanii S; Emami B; Heshmat R; Panah VH; Azimi S; Tavangar SM
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Shariati Hospital, Tehran University of Medical Science, Iran.
RESUMEN / SUMMARY: - Papillary thyroid carcinoma (PTC), including its variants and widely varying behavior, constitutes about 80% of all thyroid malignancies. Increased knowledge regarding molecular alterations has led to attempts to identify diagnostic or prognostic factors for a reliable preoperative approach to the classification of patients according to risk of recurrence. In this study, 107 cases of PTC with known histological properties, including vascular or capsular invasion, were assessed for expression of MMP2 and Caspase-3 using immunohistochemistry. Considering 10% as a cutoff to discriminate cases with invasive behavior from the non-invasive group, there was no relationship between expression of MMP2 or Caspase-3 in tumor cells and the presence of capsular invasion (p=0.45 and 0.64, respectively), as well as for the expression of Caspase-3 and vascular invasion (p=0.43). In case of MMP2, a borderline correlation was found between the positive reaction of tumor cells with the presence of vascular invasion (p=0.05). So the evaluation of MMP2 in thyroid PTC appears to be of some benefit to the prediction of tumor behavior while Caspase-3 as a marker of prediction seems to be of no use.
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[755]
TÍTULO / TITLE: - Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - OMICS. 2013 Mar;17(3):136-49. doi: 10.1089/omi.2012.0098. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1089/omi.2012.0098
AUTORES / AUTHORS: - Shao J; Zhang J; Zhang Z; Jiang H; Lou X; Huang B; Foltz G; Lan Q; Huang Q; Lin B
INSTITUCIÓN / INSTITUTION: - 1 Systems Biology Division, Zhejiang-California International NanoSystems Institute, Zhejiang University , Hangzhou, China .
RESUMEN / SUMMARY: - Abstract Alternative polyadenylation (APA) is widely present in the human genome and plays a key role in carcinogenesis. We conducted a comprehensive analysis of the APA products in glioblastoma multiforme (GBM, one of the most lethal brain tumors) and normal brain tissues and further developed a computational pipeline, RNAelements ( sysbio.zju.edu.cn/RNAelements/ ), using covariance model from known RNA binding protein (RBP) targets acquired by RNA Immunoprecipitation (RIP) analysis. We identified 4530 APA isoforms for 2733 genes in GBM, and found that 182 APA isoforms from 148 genes showed significant differential expression between normal and GBM brain tissues. We then focused on three genes with long and short APA isoforms that show inconsistent expression changes between normal and GBM brain tissues. These were myocyte enhancer factor 2D, heat shock factor binding protein 1, and polyhomeotic homolog 1 (Drosophila). Using the RNAelements program, we found that RBP binding sites were enriched in the alternative regions between the first and the last polyadenylation sites, which would result in the short APA forms escaping regulation from those RNA binding proteins. To the best of our knowledge, this report is the first comprehensive APA isoform dataset for GBM and normal brain tissues. Additionally, we demonstrated a putative novel APA-mediated mechanism for controlling RNA stability and translation for APA isoforms. These observations collectively lay a foundation for novel diagnostics and molecular mechanisms that can inform future therapeutic interventions for GBM.
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[756]
TÍTULO / TITLE: - Prognostic value of EGFR expression in de novo and progressed atypical and anaplastic meningiomas: an immunohistochemical and fluorescence in situ hybridization pilot study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Neurosurg Sci. 2013 Mar 13.
AUTORES / AUTHORS: - Caltabiano R; Barbagallo GM; Castaing M; Cassenti A; Senetta R; Cassoni P; Albanese V; Lanzafame S
INSTITUCIÓN / INSTITUTION: - Section of Anatomic Pathology, G.F. Ingrassia Department, University of Catania, Catania, Italy - giuseppebarbagal@hotmail.com.
RESUMEN / SUMMARY: - Aim: The aim of this study was to assess both the epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry and the EGFR gene amplification by fluorescence in situ hybridization in meningiomas of different grade, in order to evaluate their possible role in the development of the disease. EGFR protein belongs to the family of tyrosine kinase growth factor receptors, which also includes HER2, HER3 and HER4. Elevated expression or activity of EGFR has been reported in several cancers, including brain tumours. EGFR activation can enhance the malignant potential of epithelial tissues. Methods: We investigated whether there was a difference in the EGFR protein expression and the EGFR gene amplification between the so called de novo malignant meningiomas and recurrent meningiomas with or without malignant progression from a previously lower grade tumor. Our goal was to evaluate if EGFR expression was a useful marker to select patients affected by meningioma with a major risk of recurrences. We also assessed the prognostic value of the EGFR expression on overall survival. Results: Progression from benign meningiomas to atypical or anaplastic meningiomas correlated with an increase in the expression of EGFR protein. Our study shows that EGFR immunostaining in meningiomas directly correlates to the tumor’s grade. The EGFR expression did not correlate with the overall survival and the recurrence-free survival of the patients affected by meningioma (de novo, recurrent and progressed). Conclusion: We submit that the EGFR expression is not a useful prognostic element to identify patients with a major risk of meningioma recurrence.
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[757]
TÍTULO / TITLE: - Twist1 and Y-box-binding protein-1 are potential prognostic factors in bladder cancer().
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Urol Oncol. 2013 Feb 6. pii: S1078-1439(12)00396-1. doi: 10.1016/j.urolonc.2012.11.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.urolonc.2012.11.003
AUTORES / AUTHORS: - Song YH; Shiota M; Yokomizo A; Uchiumi T; Kiyoshima K; Kuroiwa K; Oda Y; Naito S
INSTITUCIÓN / INSTITUTION: - Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - OBJECTIVE: To investigate the expression and possible roles of Twist1 and Y-box-binding protein-1 (YB-1) in bladder cancer tissue. Twist1 belongs to the family of basic helix-loop-helix transcription factors. A functional link between Twist1 and YB-1 has recently been determined to play an important role in bladder cancer cell lines. MATERIALS AND METHODS: Frozen samples from 75 patients with bladder cancer were analyzed by quantitative real-time polymerase chain reaction (PCR). Formalin-fixed and paraffin-embedded tissues from 53 patients with bladder cancer were examined by immunohistochemistry. RESULTS: Twist1 transcript levels were positively correlated with YB-1 transcript levels (coefficient of correlation = 0.42, P<0.001), tumor grade (low grade vs. high grade; P<0.001), invasiveness (non-muscle-invasive bladder cancer vs. muscle invasive bladder cancer; P = 0.0018), and metastasis (meta- vs. meta+; P<0.001). YB-1 transcript level was also correlated with grade (P = 0.029) and invasiveness (P = 0.006). By immunohistochemistry, Twist1 expression was also correlated with YB-1 expression (P<0.001). Further, both Twist1 and YB-1 expression were positively correlated with invasiveness (P = 0.007 and P = 0.002, respectively). Patients with high Twist1 expression and high YB-1 expression had lower overall survival rates, compared with patients with low expression (log-rank test, P = 0.040 and P<0.001, respectively). CONCLUSIONS: These results suggest a functional link between Twist1 and YB-1, and they indicate that Twist1 and YB-1 promote bladder cancer progression.
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[758]
TÍTULO / TITLE: - A Relationship Between Replication Protein A and Occurrence and Prognosis of Esophageal Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biochem Biophys. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s12013-013-9530-y
AUTORES / AUTHORS: - Dahai Y; Sanyuan S; Hong L; Di Z; Chong Z
INSTITUCIÓN / INSTITUTION: - Department of Radiotherapy, Traditional Chinese Medicine Hospital of Jiangsu Province, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
RESUMEN / SUMMARY: - Esophageal carcinoma (EC) is an aggressive and the third most common cancer of the digestive tract with poor prognosis. Replication protein A (RPA) is critically required for DNA replication and its elevated expression has been observed in many malignant tumors. In this study, we investigated the expression of RPA1 and RPA2, subunits of RPA, and assessed their prognostic value in EC patients. We analyzed immunohistochemically the expression of RPA1 and RPA2 proteins in 48 EC resection specimens in relation with clinicopathological parameters and survival. We observed a significant elevated (P < 0.001) RPA1 and RPA2 expressions (labeling index) in the tumor than adjacent non-tumor tissues. In addition, both RPA1 and RPA2 labeling index in lymph node metastasis patients was significantly higher (both P = 0.000) than patients without lymph node metastasis. However, RPA1 and RPA2 labeling index in early stage was significantly lower (P = 0.000 and P = 0.002, respectively) than that of late stage EC patients. Importantly, patient’s survival at early stage was significantly higher (P = 0.016) than late stage EC and lymph node metastasis and RPA1 expression was associated with adverse patient’s outcome in multivariate analysis (P < 0.05 and P < 0.00, respectively). In conclusion, RPA1 could be a useful prognostic indicator in patients with esophageal carcinoma and might be a future attractive therapeutic target for regulation by tumor suppressors.
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[759]
TÍTULO / TITLE: - Protein kinase inhibitors against malignant lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Pharmacother. 2013 Apr;14(6):707-21. doi: 10.1517/14656566.2013.780031.
●● Enlace al texto completo (gratuito o de pago) 1517/14656566.2013.780031
AUTORES / AUTHORS: - D’Cruz OJ; Uckun FM
INSTITUCIÓN / INSTITUTION: - Children’s Hospital Los Angeles, Children’s Center for Cancer and Blood Diseases , Los Angeles, CA 90027 , USA.
RESUMEN / SUMMARY: - Introduction: Tyrosine kinases (TKs) are intimately involved in multiple signal transduction pathways regulating survival, activation, proliferation and differentiation of lymphoid cells. Deregulation or overexpression of specific oncogenic TKs is implicated in maintaining the malignant phenotype in B-lineage lymphoid malignancies. Several novel targeted TK inhibitors (TKIs) have recently emerged as active in the treatment of relapsed or refractory B-cell lymphomas that inhibit critical signaling pathways, promote apoptotic mechanisms or modulate the tumor microenvironment. Areas covered: In this review, the authors summarize the clinical outcomes of newer TKIs in various B-cell lymphomas from published and ongoing clinical studies and abstracts from major cancer and hematology conferences. Expert opinion: Multiple clinical trials have demonstrated that robust antitumor activity can be obtained with TKIs directed toward specific oncogenic TKs that are genetically deregulated in various subtypes of B-cell lymphomas. Clinical success of targeting TKIs is dependent upon on identifying reliable molecular and clinical markers associated with select cohorts of patients. Further understanding of the signaling pathways should stimulate the identification of novel molecular targets and expand the development of new therapeutic options and individualized therapies.
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[760]
TÍTULO / TITLE: - Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Oncol. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not024
AUTORES / AUTHORS: - Kim YW; Koul D; Kim SH; Lucio-Eterovic AK; Freire PR; Yao J; Wang J; Almeida JS; Aldape K; Yung WK
INSTITUCIÓN / INSTITUTION: - Cancer Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea, (Y.-W.K.), Brain Tumor Center, Department of Neuro-Oncology (D.K., S.H.K., A.K.L.-E., J.Y., K.A., W.K.A.Y.), and Department of Bioinformatics and Computational Biology (P.R.F., J.W., J.S.A.), The University of Texas MD Anderson Cancer Center, Houston, Texas.
RESUMEN / SUMMARY: - BackgroundThe Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM).MethodsHere, we describe an in-depth analysis of gene expression data and copy number aberration (CNA) data to classify GBMs into prognostic groups to determine correlates of subtypes that may be biologically significant.ResultsTo identify predictive survival models, we searched TCGA in 173 patients and identified 42 probe sets (P = .0005) that could be used to divide the tumor samples into 3 groups and showed a significantly (P = .0006) improved overall survival. Kaplan-Meier plots showed that the median survival of group 3 was markedly longer (127 weeks) than that of groups 1 and 2 (47 and 52 weeks, respectively). We then validated the 42 probe sets to stratify the patients according to survival in other public GBM gene expression datasets (eg, GSE4290 dataset). An overall analysis of the gene expression and copy number aberration using a multivariate Cox regression model showed that the 42 probe sets had a significant (P < .018) prognostic value independent of other variables.ConclusionsBy integrating multidimensional genomic data from TCGA, we identified a specific survival model in a new prognostic group of GBM and suggest that molecular stratification of patients with GBM into homogeneous subgroups may provide opportunities for the development of new treatment modalities.
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[761]
TÍTULO / TITLE: - Immediate early response gene X-1, a potential prognostic biomarker in cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Ther Targets. 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1517/14728222.2013.768234
AUTORES / AUTHORS: - Wu MX; Ustyugova IV; Han L; Akilov OE
INSTITUCIÓN / INSTITUTION: - Massachusetts General Hospital and Harvard Medical School, Wellman Center for Photomedicine, Department of Dermatology , Edwards 222, 50 Blossom Street, Boston, MA 02114 , USA +1 617 726 1298 ; +1 617 726 1206 ; mwu2@partners.org.
RESUMEN / SUMMARY: - Introduction: The immediate early response gene X-1 (IEX-1) plays a pivotal role in the regulation of cell apoptosis, proliferation, differentiation and metabolism. Deregulation of IEX-1 expression has been confirmed in multiple cancers in humans, in association with either poor or better prognosis depending on the type and progression stages of the cancer. Areas covered: This review summarizes clinical studies of altered IEX-1 expression in ovarian, pancreatic, blood, breast and colorectal cancers, lymphoma and myeloma. The authors also outline the current understandings of the complex functions of IEX-1 gained from studies with animal models and tumor cell lines so as to help us comprehend the significance of the clinical findings. Expert opinion: IEX-1 holds great promise to be a valuable biomarker, either alone or in combination with other genes, for monitoring progression of some cancers. IEX-1 expression is highly sensitive to environmental cues and distinct between normal and cancer cells. However, use of IEX-1 as a biomarker remains a significant challenge because too little is understood about the mechanism underlying the diverse activities of IEX-1 and a standardized clinical assay for IEX-1 detection and validation of clinical results across different studies are still critically lacking.
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[762]
TÍTULO / TITLE: - FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Breast. 2013 Feb 12. pii: S0960-9776(13)00002-7. doi: 10.1016/j.breast.2012.12.020.
●● Enlace al texto completo (gratuito o de pago) 1016/j.breast.2012.12.020
AUTORES / AUTHORS: - Koolen BB; Pengel KE; Wesseling J; Vogel WV; Vrancken Peeters MJ; Vincent AD; Gilhuijs KG; Rodenhuis S; Rutgers EJ; Valdes Olmos RA
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Department of Surgical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - BACKGROUND: Response monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT. METHODS: Evaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response. RESULTS: A (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12-0.64) for HER2-positive, 0.90 (0.76-1.00) for ER-positive/HER2-negative, and 0.96 (0.86-1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response. CONCLUSION: Response monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors.
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[763]
TÍTULO / TITLE: - Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastric Cancer. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s10120-013-0236-z
AUTORES / AUTHORS: - Jacome AA; Wohnrath DR; Scapulatempo Neto C; Carneseca EC; Serrano SV; Viana LS; Nunes JS; Martinez EZ; Santos JS
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP, 14784-400, Brazil, jacome@usp.br.
RESUMEN / SUMMARY: - BACKGROUND: There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer. METHODS: This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. RESULTS: Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Lauren histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence. CONCLUSIONS: According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors.
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[764]
TÍTULO / TITLE: - The possible diagnostic and prognostic use of systemic chemokine profiles in clinical medicine-the experience in acute myeloid leukemia from disease development and diagnosis via conventional chemotherapy to allogeneic stem cell transplantation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Toxins (Basel). 2013 Feb 18;5(2):336-62. doi: 10.3390/toxins5020336.
●● Enlace al texto completo (gratuito o de pago) 3390/toxins5020336
AUTORES / AUTHORS: - Reikvam H; Fredly H; Kittang AO; Bruserud O
INSTITUCIÓN / INSTITUTION: - Section for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway. hakon.reikvam@med.uib.no
RESUMEN / SUMMARY: - Chemokines are important regulators of many different biological processes, including (i) inflammation with activation and local recruitment of immunocompetent cells; (ii) angiogenesis as a part of inflammation or carcinogenesis; and (iii) as a bridge between the coagulation system and inflammation/immune activation. The systemic levels of various chemokines may therefore reflect local disease processes, and such variations may thereby be used in the routine clinical handling of patients. The experience from patients with myeloproliferative diseases, and especially patients with acute myeloid leukemia (AML), suggests that systemic plasma/serum cytokine profiles can be useful, both as a diagnostic tool and for prognostication of patients. However, cytokines/chemokines are released by a wide range of cells and are involved in a wide range of biological processes; the altered levels may therefore mainly reflect the strength and nature of the biological processes, and the optimal clinical use of chemokine/cytokine analyses may therefore require combination with organ-specific biomarkers. Chemokine levels are also altered by clinical procedures, therapeutic interventions and the general status of the patients. A careful standardization of sample collection is therefore important, and the interpretation of the observations will require that the overall clinical context is considered. Despite these limitations, we conclude that analysis of systemic chemokine/cytokine profiles can reflect important clinical characteristics and, therefore, is an important scientific tool that can be used as a part of future clinical studies to identify clinically relevant biomarkers.
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[765]
TÍTULO / TITLE: - Small-Molecule Inhibitor BMS-777607 Induces Breast Cancer Cell Polyploidy with Increased Resistance to Cytotoxic Chemotherapy Agents.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1079
AUTORES / AUTHORS: - Sharma S; Zeng JY; Zhuang CM; Zhou YQ; Yao HP; Hu X; Zhang R; Wang MH
INSTITUCIÓN / INSTITUTION: - 1Biomedical/Pharmaceutical Sciences, Texas Tech University HSC.
RESUMEN / SUMMARY: - The RON receptor tyrosine kinase is a therapeutic target for cancer treatment. Here we report therapeutic effect and phenotypic change of breast cancer cells in response to BMS-777607, a RON tyrosine kinase inhibitor. Treatment of breast cancer cells with BMS-777607 at therapeutic doses inhibited cancerous clonogenic growth but had only minimal effect on cell apoptosis. Significantly, BMS-777607 induced extensive polyploidy with multiple sets of chromosomes in cancer cells. This effect is independent of RON expression. Knockdown of RON in T-47D and ZR-75-1 cells by specific siRNA did not prevent polyploid formation. Immunofluorescent analysis of alpha-tubulin and gamma-tubulin expression in polyploid cells revealed that BMS-777607 disrupts bi-polar spindle formation and causes multi-polar-like microtubule assembly. Also, both metaphase equatorial alignment and chromosomal segregation were absent in polyploid cells. These results suggest that cellular mitosis arrests at prophase/pro-metaphase and fails to undergo cytokinesis. By analyzing kinase-inhibitory profiles, aurora kinase B was identified as the target molecule inhibited by BMS-777607. In BMS-777607 treated cells, aurora kinase B was inhibited followed by protein degradation. Moreover, BMS-777607 inhibited Ser10 phosphorylation of histone H3, a substrate of aurora kinase B. Chemosensitivity analysis indicated the resistance of polyploid cells towards chemotherapeutics. Treatment with doxorubicin, bleomycin, methotrexate, and paclitaxel significantly increased cellular IC50 values. These findings highlight the theory that BMS-777607 acts as a multi-kinase inhibitor at therapeutic doses and is capable of inducing polyploidy by inhibiting aurora kinase B. Increased resistance of polyploid cells to cytotoxic chemotherapeutics could have a negative impact on targeted cancer therapy using BMS-777607.
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[766]
TÍTULO / TITLE: - Proteasome inhibitors in acute leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Rev Anticancer Ther. 2013 Mar;13(3):327-37. doi: 10.1586/era.13.4.
●● Enlace al texto completo (gratuito o de pago) 1586/era.13.4
AUTORES / AUTHORS: - Niewerth D; Dingjan I; Cloos J; Jansen G; Kaspers G
INSTITUCIÓN / INSTITUTION: - Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - Proteasome inhibition has been recognized as a novel treatment modality in hematologic malignancies. Initially, the reversible proteasome inhibitor bortezomib demonstrated efficacy in multiple myeloma (MM), which supported its approval for relapsed and refractory MM in 2003. Later on, carfilzomib, a next-generation irreversible proteasome inhibitor was approved by the US FDA in July 2012 for relapsed/refractory MM. Currently, several other proteasome inhibitors are undergoing preclinical and clinical evaluation. The successes of proteasome inhibitors in MM are now being translated to other hematologic malignancies, including acute leukemia. The first clinical studies with bortezomib in leukemia revealed promising clinical activity, particularly when combined with conventional chemotherapeutics. In this review the position of proteasome inhibitors in acute leukemia treatment is summarized and discussed. Special focus is also attributed to immunoproteasome inhibitors. As a future perspective, it is anticipated that proteasome inhibitors may prove to be of added value in therapeutic interventions for acute leukemia.
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[767]
TÍTULO / TITLE: - Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Enzyme Inhib Med Chem. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 3109/14756366.2013.765417
AUTORES / AUTHORS: - Sadek MM; Serrya RA; Kafafy AH; Ahmed M; Wang F; Abouzid KA
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, MSA University , 6th October, Cairo , Egypt .
RESUMEN / SUMMARY: - Abstract Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 4’ position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC(50) equal to 2.09 and 1.94 muM, respectively, and with IC(50) equal to 3.98 and 1.04 muM on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC(50) range of 2.4 and 2.5 muM, respectively.
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[768]
TÍTULO / TITLE: - Exploiting Protein Phosphatase Inhibitors Based on Cantharidin Analogues for Cancer Drug Discovery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mini Rev Med Chem. 2013 Jan 31.
AUTORES / AUTHORS: - Deng L; Dong J; Wang W
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, Chemistry and Chemical Engineering Institute, Shaoxing University, Shaoxing, Zhejiang 312000, China. wwdlp@126.com.
RESUMEN / SUMMARY: - Cantharidin (CTD), a natural toxin, can inhibit a variety of tumor cell lines, especially hepatocellular carcinoma cells. It is a strong inhibitor of protein phosphatase type 1 (PP1) and type 2A (PP2A). Because of the cytotoxicity, the clinical application of CDT is limited. Here, we review the structure-activity relationships of CDT analogues, including norcantharidin (NCTD), cantharimides and related derivatives of CTDs, which have more powerful antitumor activity but less cytotoxicity than CDT itself. Important advances in the design of the CTD-based inhibitors achieved recently are outlined here in order to establish principles for synthesis, screening, and the applications of promising anti-cancer drug candidates. In addition, efforts to ameliorate the intrinsic cytotoxicity through the use of drug carriers are also discussed. It is conceivable that rational design of the protein phosphatase inhibitors based on cantharidin analogues can be facilitated by studies of mechanism of the protein-inhibitor interactions and the related structural biology in the future.
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[769]
TÍTULO / TITLE: - Cancer pharmacogenomics in children: research initiatives and progress to date.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Paediatr Drugs. 2013 Apr;15(2):71-81. doi: 10.1007/s40272-013-0021-9.
●● Enlace al texto completo (gratuito o de pago) 1007/s40272-013-0021-9
AUTORES / AUTHORS: - Rassekh SR; Ross CJ; Carleton BC; Hayden MR
INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Division of Pediatric Hematology/Oncology/BMT, University of British Columbia, Vancouver, BC, Canada, rrassekh@cw.bc.ca.
RESUMEN / SUMMARY: - Over the last few decades, cure rates for pediatric cancer have increased dramatically, and now over 80 % of children with cancer are cured of their disease. This improvement in cure has come with a significant cost, with many children suffering irreversible, life-threatening, or long-lasting toxicities due to the medications required during their treatment. In the last 2 decades, major technological advances in genomics and the mapping of the human genome have made it possible to identify genetic differences between children in order to investigate differing responses to cancer therapy and to help explain why children treated with the same medications can have different outcomes. The emerging field of pharmacogenomics has had many important findings in pediatric cancer. The focus of this review is drug toxicity in pediatric cancer and the use of pharmacogenomics to reduce these adverse drug reactions, with a specific focus on thiopurines, methotrexate, cisplatin, vincristine and anthracyclines. Future areas of research and the need for international collaboration are discussed.
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[770]
TÍTULO / TITLE: - Successful EGFR-TKI Rechallenge of Leptomeningeal Carcinomatosis after Gefitinib-induced Interstitial Lung Disease.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Apr;43(4):422-5. doi: 10.1093/jjco/hyt012. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt012
AUTORES / AUTHORS: - Nakamichi S; Kubota K; Horinouchi H; Kanda S; Fujiwara Y; Nokihara H; Yamamoto N; Tamura T
INSTITUCIÓN / INSTITUTION: - *Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. kkubota@nms.ac.jp.
RESUMEN / SUMMARY: - We report the case of a 49-year-old non-smoking Japanese woman with backache and difficulty in walking. She was diagnosed as having advanced lung adenocarcinoma, and an epithelial growth factor receptor mutation (in-frame deletions in exon 19) was found. After radiation therapy of bone metastases with spinal cord compression and brain metastases, gefitinib was administered. On day 2, she developed acute interstitial lung disease. Gefitinib therapy was discontinued and treatment with high-dose steroid therapy improved the interstitial lung disease. Cisplatin plus pemetrexed was initiated as second-line chemotherapy, but she was hospitalized again for leptomeningeal carcinomatosis. Considering the poor prognosis of leptomeningeal carcinomatosis, we decided that erlotinib was our only choice of treatment. As a third-line treatment, erlotinib was administered after informing the patient about the high risk of interstitial lung disease. Neurological symptoms were improved within a week and interstitial lung disease did not recur. The patient has received erlotinib successfully for 18 months without the recurrence of leptomeningeal carcinomatosis. Erlotinib rechallenge after gefitinib-induced interstitial lung disease must be carefully chosen based on the balance of a patient’s risk and benefit.
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[771]
TÍTULO / TITLE: - Expression of angiogenesis-related gene profiles and development of resistance to tyrosine-kinase inhibitor in advanced renal cell carcinoma: Characterization of sorafenib-resistant cells derived from a cutaneous metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Urol. 2013 Feb 4. doi: 10.1111/iju.12084.
●● Enlace al texto completo (gratuito o de pago) 1111/iju.12084
AUTORES / AUTHORS: - Karashima T; Fukuhara H; Tamura K; Ashida S; Kamada M; Inoue K; Taguchi T; Kuroda N; Shuin T
INSTITUCIÓN / INSTITUTION: - Department of Urology, Kochi University, Nankoku City, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: To investigate the potential mechanism of development of resistance to tyrosine kinase inhibitor in renal cell carcinoma. METHODS: A primary culture of renal cell carcinoma cells (KMRM-S2) was established from an advanced renal cell carcinoma patient with cutaneous metastasis, who had not responded to sorafenib. A total of 84 human angiogenesis-related genes were compared between cutaneous metastasis and the primary tumor by real time polymerase chain reaction. Spectral karyotyping and cell proliferation assay were carried out to determine the biological features of the cells. RESULTS: Primary tumor was histopathologically diagnosed as high-grade clear cell carcinoma with sarcomatoid change and rhabdoid features. The cutaneous metastasis also consisted of sarcomatoid components. Expression levels of many angiogenesis-related genes in the cutaneous metastasis were relatively higher than those of primary tumor. Chromosomal analysis of the KMRM-S2 showed cytogenetic abnormalities with hypertriploidy and translocation. In vitro proliferation assay showed the relatively higher resistance of KMRM-S2 against sorafenib. CONCLUSIONS: The sarcomatoid change and rhabdoid features of renal cell carcinoma with cytogenetic hyperploidy might be associated with elevated expression of angiogenesis-related genes, which leads to resistance against tyrosine kinase inhibitor. The present study might contribute to discovering novel therapeutic targets for the treatment of patients with advanced renal cell carcinoma resistant to tyrosine kinase inhibitor.
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[772]
TÍTULO / TITLE: - Phosphorylated EGFR at tyrosine 1173 correlates with poor prognosis in oral squamous cell carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oral Dis. 2013 Feb 16. doi: 10.1111/odi.12087.
●● Enlace al texto completo (gratuito o de pago) 1111/odi.12087
AUTORES / AUTHORS: - Monteiro L; Ricardo S; Delgado M; Garcez F; do Amaral B; Lopes C
INSTITUCIÓN / INSTITUTION: - Medicine and Oral Surgery Department, Dental Sciences Group - Health Sciences Research Centre, Higher Institute of Health Sciences (ISCSN), CESPU, Paredes, Portugal.
RESUMEN / SUMMARY: - OBJECTIVES: To evaluate the expression of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (pEGFR), in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome. MATERIALS AND METHODS: We analysed 74 primary OSCC and examined immunohistochemical expression of EGFR and pEGFR (phosphorylated at tyrosine 1173) using tissue microarray technology. Their role in survival was assessed by Kaplan-Meier method and Cox regression models. RESULTS: Epidermal growth factor receptor expression was observed in all cases, and pEGFR expression was observed in 41.1% of the cases. We found a significant correlation between EGFR and pEGFR expression (P = 0.003). In the multivariable analysis for cause-specific survival, we found an independent prognostic value for pEGFR expression (HR 7.94, 95% CI 2.03-31.06, P = 0.003) and for clinical stage (HR 2.88, 95% CI 1.10-7.53, P = 0.031). For recurrence-free survival, clinical stage (HR 6.59, 95% CI 1.36-31.90, P = 0.019) and tumour grade (HR 3.35, 95% CI 1.07-10.44, P = 0.037) presented independent prognostic value. CONCLUSION: Epidermal growth factor receptor is highly expressed in OSCC and is phosphorylated in more than one-third of the cases. The independent value of pEGFR expression in cause-specific survival of OSCC suggests that this marker may serve as reliable biological marker to identify high-risk subgroups and to guide therapy.
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[773]
TÍTULO / TITLE: - Vascular change measured with independent component analysis of dynamic susceptibility contrast MRI predicts bevacizumab response in high-grade glioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Oncol. 2013 Apr;15(4):442-50. doi: 10.1093/neuonc/nos323. Epub 2013 Feb 3.
●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/nos323
AUTORES / AUTHORS: - Laviolette PS; Cohen AD; Prah MA; Rand SD; Connelly J; Malkin MG; Mueller WM; Schmainda KM
INSTITUCIÓN / INSTITUTION: - Corresponding Author: Peter S. LaViolette, PhD, Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226. plaviole@mcw.edu.
RESUMEN / SUMMARY: - Background Standard pre- and postcontrast (T1 + C) anatomical MR imaging is proving to be insufficient for accurately monitoring bevacizumab treatment response in recurrent glioblastoma (GBM). We present a novel imaging biomarker that detects abnormal tumor vasculature exhibiting both arterial and venous perfusion characteristics. We hypothesized that a decrease in the extent of this abnormal vasculature after bevacizumab treatment would predict treatment efficacy and overall survival. Methods Dynamic susceptibility contrast perfusion MRI was gathered in 43 patients with high-grade glioma. Independent component analysis separated vasculature into arterial and venous components. Voxels with perfusion characteristics of both arteries and veins (ie, arterio-venous overlap [AVOL]) were measured in patients with de novo untreated GBM and patients with recurrent high-grade glioma before and after bevacizumab treatment. Treated patients were separated on the basis of an increase or decrease in AVOL volume (+/-DeltaAVOL), and overall survival following bevacizumab onset was then compared between +/-DeltaAVOL groups. Results AVOL in untreated GBM was significantly higher than in normal vasculature (P < .001). Kaplan-Meier survival curves revealed a greater median survival (348 days) in patients with GBM with a negative DeltaAVOL after bevacizumab treatment than in patients with a positive change (197 days; hazard ratio, 2.51; P < .05). Analysis of patients with combined grade III and IV glioma showed similar results, with median survivals of 399 days and 153 days, respectively (hazard ratio, 2.71; P < .01). Changes in T1+C volume and DeltarCBV after treatment were not significantly different across +/-DeltaAVOL groups, and DeltaAVOL was not significantly correlated with DeltaT1+C or DeltarCBV. Conclusions The independent component analysis dynamic susceptibility contrast-derived biomarker AVOL adds additional information for determining bevacizumab treatment efficacy.
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[774]
TÍTULO / TITLE: - 1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prognosis as favorable as anaplastic oligodendrogliomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Oncol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not027
AUTORES / AUTHORS: - Jiang H; Ren X; Cui X; Wang J; Jia W; Zhou Z; Lin S
INSTITUCIÓN / INSTITUTION: - Departments of Neurosurgery (H.J., X.R., W.J., S.L.) and Pharmacy (X.C.), Beijing Tiantan Hospital, Capital Medical University, and Beijing Neurosurgical Institute (J.W.), Beijing, China; and Blood Center Station of Fuzhou, Fuzhou, China (Z.Z.).
RESUMEN / SUMMARY: - BackgroundAnaplastic astrocytoma (AA), anaplastic oligoastrocytoma (AOA), and anaplastic oligodendroglioma (AO) are the major histological subtypes of World Health Organization grade III gliomas. More evidence suggests that AOA is unlikely to be a distinct entity, and re-evaluation of this issue has been recommended. In this study, we divided AOA into 2 subgroups, according to molecular biomarkers, and compared the survivals between them.MethodsOne hundred nine patients with histological diagnosis of anaplastic gliomas enrolled in the study. Molecular biomarkers evaluated included 1p/19q codeletion and IDH1/2 mutation. Kaplan-Meier plots were compared by log-rank method.ResultsThere was no significant difference between AA and AOA with regard to the frequencies of biomarkers and survival plots. According to the status of biomarkers, AOA was classified into 2 subgroups (AOA1 and AOA2), for which Kaplan-Meier plots were significantly different (P = .001 for both progression-free survival [PFS] and overall survival [OS]). AOA1 with 1p/19q codeletion and/or IDH1/2 mutation showed similar Kaplan-Meier plots with AO (P = .169 for PFS and P = .523 for OS). AOA2 without either biomarker showed similar Kaplan-Meier plots with AA (P = .369 for PFS and P = .271 for OS). In addition, patients with AO and AOA1 had significantly longer PFS and OS than did patients with AA and AOA2 (P < .001 for both PFS and OS).ConclusionsAOA is a heterogeneous group and can be divided into 2 subgroups with significantly different prognoses according to the status of 1p/19q and IDH1/2. This will be helpful in estimating patients’ prognosis and guiding reasonable therapy for patients with anaplastic gliomas.
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[775]
TÍTULO / TITLE: - Transcriptional and post-translational regulation of Bim is essential for TGF-beta and TNF-alpha-induced apoptosis of gastric cancer cell.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 Mar 15. pii: S0304-4165(13)00084-6. doi: 10.1016/j.bbagen.2013.03.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbagen.2013.03.006
AUTORES / AUTHORS: - Thi HT; Lim HS; Kim J; Kim YM; Kim HY; Hong S
INSTITUCIÓN / INSTITUTION: - Laboratory of Cancer Cell Biology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
RESUMEN / SUMMARY: - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) are well known as central signaling molecules in natural antitumor mechanisms. However, some cancer cells are resistant to TNF-alpha or TGF-beta-induced death signaling. Herein, we investigated synergistic activities of TGF-beta and TNF-alpha and molecular mechanisms involved in apoptosis of gastric cancer cells. METHODS: SNU620, a human gastric carcinoma cell line was tested for cell viability by treatment of TGF-beta in combination with TNF-alpha. Cell apoptosis, proliferation, caspase activation and gene expression were tested using flow cytometry, Western blot, MTT assay, luciferase assay and real-time qRT-PCR analysis. Knockdown of target genes were performed using lentiviral shRNA system. RESULTS: TGF-beta sensitizes SNU620 cells undergoing TNF-alpha-induced caspase-dependent apoptosis. TNF-alpha and TGF-beta synergistically induced the degradation of poly(ADP-ribose) polymerase (PARP) and caspase cascade activation. We also confirmed that c-Jun NH2-terminal kinase (JNK) and Smad3 play critical roles in the apoptotic pathway. In addition, a pro-apoptotic protein Bim was critical for apoptosis and was regulated by TGF-beta and TNF-alpha at the transcriptional and post-translational levels. Expression of Bim was induced at the transcriptional level by Smad3 while Bim protein stability was maintained by a JNK-mediated pathway. CONCLUSION: By understanding the synergistic activation of TGF-beta and TNF-alpha in apoptosis, we may have a chance to identify good therapeutic approaches for the treatment of cancers that are resistant to death signals. GENERAL SIGNIFICANCE: Our results indicate that TGF-beta and TNF-alpha act in concert to activate apoptosis in gastric cancer cell through crosstalk between Smad and JNK signaling pathways.
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[776]
TÍTULO / TITLE: - Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Crit Rev Toxicol. 2013 Mar;43(3):244-74. doi: 10.3109/10408444.2013.768596.
●● Enlace al texto completo (gratuito o de pago) 3109/10408444.2013.768596
AUTORES / AUTHORS: - Thompson CM; Proctor DM; Suh M; Haws LC; Kirman CR; Harris MA
INSTITUCIÓN / INSTITUTION: - ToxStrategies, Inc. , Katy, TX , USA .
RESUMEN / SUMMARY: - Abstract Chronic exposure to high concentrations of hexavalent chromium (Cr(VI)) in drinking water causes intestinal adenomas and carcinomas in mice, but not in rats. Cr(VI) causes damage to intestinal villi and crypt hyperplasia in mice after only one week of exposure. After two years of exposure, intestinal damage and crypt hyperplasia are evident in mice (but not rats), as are intestinal tumors. Although Cr(VI) has genotoxic properties, these findings suggest that intestinal tumors in mice arise as a result of chronic mucosal injury. To better understand the mode of action (MOA) of Cr(VI) in the intestine, a 90-day drinking water study was conducted to collect histological, biochemical, toxicogenomic and pharmacokinetic data in intestinal tissues. Using MOA analyses and human relevance frameworks proposed by national and international regulatory agencies, the weight of evidence supports a cytotoxic MOA with the following key events: (a) absorption of Cr(VI) from the intestinal lumen, (b) toxicity to intestinal villi, (c) crypt regenerative hyperplasia and (d) clonal expansion of mutations within the crypt stem cells, resulting in late onset tumorigenesis. This article summarizes the data supporting each key event in the MOA, as well as data that argue against a mutagenic MOA for Cr(VI)-induced intestinal tumors.
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[777]
TÍTULO / TITLE: - Tubulin Beta Chain, Filamin A Alpha Isoform 1, and Cytochrome b-c1 Complex Subunit 1 As Serological Diagnostic Biomarkers of Esophageal Squamous Cell Carcinoma: A Proteomics Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - OMICS. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1089/omi.2012.0133
AUTORES / AUTHORS: - Fan NJ; Gao CF; Wang XL
INSTITUCIÓN / INSTITUTION: - Research Institute of Anal-colorectal Surgery , No. 150 Central Hospital of PLA, Luoyang, RP China .
RESUMEN / SUMMARY: - Abstract Despite the major advances in diagnosis and treatment, esophageal squamous cell carcinoma (ESCC) remains a major life-threatening disease. Early diagnosis is critical for guiding the therapeutic management of ESCC. This case-control study focused on the proteomic analysis of serum of healthy volunteers and ESCC patients using the ClinProt profiling technology based on mass spectrometry. A total of 80 healthy volunteers and 119 ESCC patients were enrolled. We identified a pattern of proteins/peptides (including m/z 1867, 2700, and 2094) and differentiated ESCC patients from healthy volunteers with sensitivity and specificity close to 100%. Using mass spectrometry (LTQ orbitrap XL), tubulin beta chain, filamin A alpha isoform 1, and cytochrome b-c1 complex subunit 1 were identified as the three differentially expressed proteins/peptides in the patient serum. These three dysregulated proteins/peptides could be involved in the pathogenesis of ESCC and may serve as putative serological diagnostic biomarkers of ESCC. We suggest that further proteomics and multi-omics research are warranted to identify novel post-genomics diagnostics that can in the future pave the way for personalized medicine for patients with ESCC, a cancer for which we currently lack an integrated battery of diagnostics in the field of oncology.
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[778]
TÍTULO / TITLE: - Clinical characteristics and treatment responses of patients who developed tuberculosis following use of a tumor necrosis factor-alpha inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Intern Med. 2013 Mar;28(2):174-9. doi: 10.3904/kjim.2013.28.2.174. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 3904/kjim.2013.28.2.174
AUTORES / AUTHORS: - Chung KB; Lee EY; Im JP; Han SK; Yim JJ
INSTITUCIÓN / INSTITUTION: - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUNDAIMS: Individuals being treated with tumor necrosis factor (TNF)-alpha inhibitors are at increased risk of developing tuberculosis (TB). We determined the clinical characteristics and treatment response of patients who developed TB after using TNF-alpha inhibitors. METHODS: Patients with TB detected within 12 months of the initiation of TNF-alpha inhibitor treatment were included, if seen from January 1, 2000 to August 31, 2011. We retrospectively reviewed the clinical records, results of bacteriological examinations, and radiographs of the included patients and the response to anti-TB treatment. RESULTS: We indentified seven cases of TB in 457 patients treated with TNF-alpha inhibitors during the study period. TB developed a median of 123 days (range, 48 to 331) after the first dose of TNF-alpha inhibitor. Pulmonary TB, including TB pleuritis, was diagnosed in three patients and extrapulmonary TB in four. Favorable treatment outcomes were achieved in six of seven patients. CONCLUSIONS: Among the TNF-alpha inhibitor users who contracted TB, extrapulmonary sites were common and the treatment response was satisfactory.
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[779]
TÍTULO / TITLE: - Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biol Ther. 2013 Feb 1;14(5).
AUTORES / AUTHORS: - Chopra AS; Kuratnik A; Scocchera EW; Wright DL; Giardina C
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Cell Biology; University of Connecticut; Storrs, CT USA.
RESUMEN / SUMMARY: - Immune and inflammatory death ligands expressed within neoplastic tissue could potentially target apoptosis to transformed cells. To develop approaches that accentuate the anti-cancer potential of the inflammatory response, the Chembridge DIVERSet ™ library was screened for compounds that accentuated apoptosis in a strictly TNFdependent manner. We identified a number of novel compounds with this activity, the most active of these, AK3 and AK10, sensitized colon cancer cells to TNF at 0.5 muM and 2 muM, respectively, without inducing apoptosis on their own. The activity of these compounds was structure-dependent and general, as they accentuated cell death by TNF or Fas ligation in multiple colon cancer cell lines. Both AK3 and AK10 arrested cells in mitosis with live cell imaging indicating that mitotically arrested cells were the source of apoptotic bodies. AK3 accentuated caspase-8 and caspase-9 activation with little effect on NFkappaB target gene activation. Enhanced caspase activation corresponded to an increased expression of TNFR1 on the cell surface. To determine the general interplay between mitotic arrest and TNF sensitivity, Aurora kinase (MLN8054 and MLN8237) and PLK1 (BI2536) inhibitors were tested for their ability to sensitize cells to TNF. PLK1 inhibition was particularly effective and influenced TNFR1 surface presentation and caspase cleavage like AK3, even though it arrested mitosis at an earlier stage. We propose that AK3 and AK10 represent a new class of mitotic inhibitor and that selected mitotic inhibitors may be useful for treating colon cancers or earlier lesions that have a high level of inflammatory cell infiltrate.
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[780]
TÍTULO / TITLE: - Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-alpha in advanced malignant melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Feb 13;11:38. doi: 10.1186/1479-5876-11-38.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-38
AUTORES / AUTHORS: - Daponte A; Signoriello S; Maiorino L; Massidda B; Simeone E; Grimaldi AM; Caraco C; Palmieri G; Cossu A; Botti G; Petrillo A; Lastoria S; Cavalcanti E; Aprea P; Mozzillo N; Gallo C; Comella G; Ascierto PA
INSTITUCIÓN / INSTITUTION: - Department of Melanoma, Istituto Nazionale Tumori Fondazione Pascale, Via Mariano Semmola, 80131, Naples, Italy. paolo.ascierto@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: The effect of the addition of fotemustine and/or interferon (IFN) to standard therapy with dacarbazine alone in patients with advanced malignant melanoma was investigated in a multicenter, randomized 2x2 factorial design trial. METHODS: A total of 260 patients were randomly assigned to one of four treatment groups: (A) fotemustine and dacarbazine repeated on 3-week cycle; (B) same treatment as (A) plus IFN-alpha2b three times per week; (C) dacarbazine alone repeated on 3-week cycle; (D) same treatment as (C) plus IFN-alpha2b three times per week. Two comparisons were planned to assess the efficacy of fotemustine (groups A+B vs. C+D) and IFN-alpha2b (groups A+C vs. B+D). RESULTS: Addition of fotemustine did not significantly improve overall survival (OS) (p=0.28) or progression-free survival (PFS) (p=0.55); Hazard ratio (HR) for OS was 0.93 (95% CI 0.71-1.21). Similarly, addition of IFN-alpha2b did not improve OS (p=0.68) or PFS (p=0.65); HR for OS was 0.92 (95% CI 0.70-1.20). Overall response rate was not improved by the addition of either fotemustine (p=0.87) or IFN-alpha2b (p=0.57). The combination of all three drugs resulted in the highest occurrence of adverse events. CONCLUSIONS: No significant improvement in outcomes were observed with the addition of either fotemustine or IFN-alpha2b to dacarbazine. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01359956.
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[781]
TÍTULO / TITLE: - Bortezomib and SAHA synergistically induce ROS-driven caspase-dependent apoptosis of nasopharyngeal carcinoma and block replication of Epstein-Barr virus.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0811
AUTORES / AUTHORS: - Hui KF; Lam BH; Ho DN; Tsao SW; Chiang AK
INSTITUCIÓN / INSTITUTION: - 1Paediatrics and Adolescent Medicine, The University of Hong Kong.
RESUMEN / SUMMARY: - A novel drug combination of a proteasome inhibitor, bortezomib and a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA) was tested in nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Dose-response of different concentrations of bortezomib and SAHA on inhibition of cell proliferation of NPC was determined. Mechanisms of apoptosis and effects on lytic cycle activation of Epstein-Barr virus (EBV) were investigated. Combination of bortezomib and SAHA (bortezomib/SAHA) synergistically induced killing of a panel of NPC cell lines. Pronounced increase in sub-G1, annexin V-positive and TUNEL-positive cell populations were detected after treatment with bortezomib/SAHA when compared with either drug alone. Concomitantly, markedly augmented proteolytic cleavage of PARP, caspase-3, -7, -8 and -9, reactive oxygen species (ROS) generation and caspase-8-dependent histone acetylation were observed. ROS scavenger, N-acetyl cysteine, diminished the apoptotic effects of bortezomib/SAHA while caspase inhibitor, Z-VAD-FMK, significantly suppressed the apoptosis without decreasing the generation of ROS. Bortezomib inhibited SAHA’s induction of EBV replication and abrogated production of infectious viral particles in NPC cells. Furthermore, bortezomib/SAHA potently induced apoptosis and suppressed the growth of NPC xenografts in nude mice. In conclusion, the novel drug combination of bortezomib and SAHA is highly synergistic in the killing of NPC cells in vitro and in vivo. The major mechanism of cell death is ROS-driven caspase-dependent apoptosis. Bortezomib antagonizes SAHA’s activation of EBV lytic cycle in NPC cells. This study provides a strong basis for clinical testing of the combination drug regimen in NPC patients.
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[782]
TÍTULO / TITLE: - Intense nanosecond pulsed electric fields promote cancer cell apoptosis through centrosome-dependent pathway involving reduced level of PLK1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Rev Med Pharmacol Sci. 2013 Jan;17(2):152-60.
AUTORES / AUTHORS: - Zou H; Gan XL; Linghu LJ; Chen C; Hu LN; Zhang Y
INSTITUCIÓN / INSTITUTION: - Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, Chengdu, P.R. China.
RESUMEN / SUMMARY: - BACKGROUND: Intense nanosecond pulsed electric fields (nsPEFs) have been known to promote apoptosis without physically changing membrane structure or damaging morphology of tumor cells. To determine the contribution of centrosome to the progression of apoptosis by nsPEFs, HeLa cells were exposed to high intensity (6 kV/cm) nsPEFs (8-32 ns) in normal culture condition and cell biology and molecular parameters of cells were investigated. MATERIALS AND METHODS: Apoptotic cell death was identified by TUNEL assay after being exposed to the nsPEFs with various pulse durations, while immunofluorescent staining was performed to detect the number and distribution of centrosomes. To clarify whether nsPEFs-induced centrosome over-duplication is the consequence of DNA damage, we used comet assay to detect simultaneous DNA damage. And additionally Western Blot was used to detect PLK1 protein level to explore the correlation between apoptotic cell death and nsPEFs-induced centrosome over-duplication. Correlation between nsPEFs and molecular parameters was statistically analyzed. RESULTS: NsPEFs induced a clear apoptosis reaching a maximum at 24ns, 24h after exposure (p < 0.05), where DNA fragmentation and over-duplicated centrosomes were observed. This apoptosis may be promoted in a time- and pulse duration-dependent manner. Polo-like kinase (PLK1) protein levels were significantly decreased by such nsPEFs (p < 0.05). Control treatment without the nsPEFs did not cause any damage to the cultured HeLa cells. CONCLUSIONS: Intense nsPEFs promote cell apoptosis through a centrosome-mediated pathway involving a reduction in the level of PLK1, which may provide new therapeutic targets for human cancer treatment.
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[783]
TÍTULO / TITLE: - Apoptosis: its role in pituitary development and neoplastic pituitary tissue.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pituitary. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s11102-013-0481-5
AUTORES / AUTHORS: - Guzzo MF; Carvalho LR; Bronstein MD
INSTITUCIÓN / INSTITUTION: - Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.
RESUMEN / SUMMARY: - Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke’s pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.
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[784]
TÍTULO / TITLE: - Quantitative Chemical Proteomics Profiling Differentiates Erlotinib from Gefitinib in EGFR Wild-Type Non-Small Cell Lung Carcinoma Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0880
AUTORES / AUTHORS: - Augustin A; Lamerz J; Meistermann H; Golling S; Scheiblich S; Hermann JC; Duchateau-Nguyen G; Tzouros M; Avila DW; Langen H; Essioux L; Klughammer B
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: 1Protein and Metabolite Biomarkers, 2Bioinformatics and Exploratory Data Analysis, Translational Research Sciences, and 3Tarceva Clinical Biomarker Subteam, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland; 4Discovery Research Oncology, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Penzberg, Germany; and 5Discovery Chemistry, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Nutley, New Jersey.
RESUMEN / SUMMARY: - Although both erlotinib and gefitinib target the EGF receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective protein interaction profiles, a label-free, quantitative chemical proteomics study was conducted. Using this method, 24 proteins were highlighted in the binding profiles of erlotinib and gefitinib. Unlike gefinitib, erlotinib displaced the ternary complex formed by integrin-linked kinase (ILK), alpha-parvin, and PINCH (IPP). The docking of erlotinib in the three-dimensional structure of ILK showed that erlotinib has the ability to bind to the ATP-binding site, whereas gefitinib is unlikely to bind with high affinity. As the IPP complex has been shown to be involved in epithelial-to-mesenchymal transition (EMT) and erlotinib sensitivity has been correlated with EMT status, we used a cellular model of inducible transition and observed that erlotinib prevented EMT in a more efficient way than gefitinib by acting on E-cadherin expression as well as on IPP levels. A retrospective analysis of the MERIT trial indicated that, besides a high level of E-cadherin, a low level of ILK could be linked to clinical benefit with erlotinib. In conclusion, we propose that, in an EGFR wild-type context, erlotinib may have a complementary mode of action by inhibiting IPP complex activities, resulting in the slowing down of the metastatic process of epithelial tumors. Mol Cancer Ther; 12(4); 1-10. ©2013 AACR.
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[785]
TÍTULO / TITLE: - Prognostication of prostate cancer based on TOP2A protein and gene assessment: TOP2A in prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Feb 11;11:36. doi: 10.1186/1479-5876-11-36.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-36
AUTORES / AUTHORS: - de Resende MF; Vieira S; Chinen LT; Chiappelli F; da Fonseca FP; Guimaraes GC; Soares FA; Neves I; Pagotty S; Pellionisz PA; Barkhordarian A; Brant X; Rocha RM
INSTITUCIÓN / INSTITUTION: - Department of Pathology, A. C. Camargo Cancer Hospital, Sao Paulo, Brazil.
RESUMEN / SUMMARY: - BACKGROUND: TOP2A encodes for topoisomerase IIalpha, a nuclear enzyme that controls DNA topological structure and cell cycle progression. This enzyme is a marker of cell proliferation in normal and neoplastic tissues; however, little information is available about its expression in prostate cancer (PCa). METHODS: Immunohistochemistry (IHC) was automated using mouse monoclonal antibody against TOP2A (clone SWT3D1; DAKO, Carpenteria, CA, USA) at dilution 1:800 and Flex Plus detection system in autostainer 48Ultra (DAKO). FISH was performed using TOP2A (17q21)/ CEP17 probe kit (Kreateck Biotechnology, San Diego, CA, USA). Biochemical and pathological data from 193 patients with PCa were retrieved for the analysis, whose significance was considered when p < 0.05. Also, fractal analysis was performed in a subset of 20 randomly selected cases. RESULTS: TOP2A protein expression correlated with higher Gleason scores and higher levels of preoperative PSA (p = 0.018 and p = 0.011). Patients with higher levels of TOP2A presented shorter biochemical recurrence-free survival (BRFS) (p = 0.001). In multivariate analysis, we found that TOP2A remained an independent prognostic factor of BRFS, with a relative risk of 1.98 (p = 0.001; 95% CI, 1.338-2.93); thus, cases that expressed high levels of this enzyme had a shorter BRFS compared with TOP2A-negative or TOP2A-low cases. No alterations in TOP2A gene status nor correlation between FISH and IHC results were observed. Concerning fractal analysis, patients who expressed higher levels of TOP2A have angiolymphatic invasion and presented higher Gleason scores (p = 0.033 and p = 0.025, respectively). Also, patients with higher expression of TOP2A presented shorter BRFS (p = 0.001). CONCLUSIONS: This is the first study to perform TOP2A protein and gene digital assessment and fractal analysis in association with BRFS in a large series of PCa. Also, we show that TOP2A gene copy number alterations are not observed in this type of tumor. So, higher protein expression of TOP2A is not related to gene amplification in PCa. Furthermore, TOP2A protein assessment has prognostic importance and, due to its relation with poor outcome, TOP2A IHC evaluation in the biopsy can represent an important tool for selecting the most suitable surgical and clinical approach for patients with PCa.
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[786]
TÍTULO / TITLE: - Novel coumarins and benzocoumarins acting as isoform-selective inhibitors against the tumor-associated carbonic anhydrase IX.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Enzyme Inhib Med Chem. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 3109/14756366.2013.777334
AUTORES / AUTHORS: - Sharma A; Tiwari M; Supuran CT
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy, S.G.S.I.T.S , Indore, Madhya Pradesh , India and.
RESUMEN / SUMMARY: - Abstract A series of coumarins and benzocoumarins incorporating methyl and hydroxyl moieties in the heterocyclic ring were investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the house-keeping, offtarget isoforms CA I and II, but showed effective, submicromolar inhibition of the transmembrane, tumor-associated isoforms CA IX and to a slightly less extent, CA XII. The nature and position of the groups substituting the coumarin ring influenced CA inhibitory properties. 4-Methyl-5,7-dihydroydroxycoumarin showed KIs >200 microM against CA I and II, of 0.19 microM against CA IX and of 6.4 microM against CA XII, being thus a selective, efficient inhibitor for the tumor-associated over cytosolic CA isoforms. These compounds are interesting leads for designing isoform-selective enzyme inhibitors.
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[787]
TÍTULO / TITLE: - DIAGNOSTIC AND PROGNOSTIC VALUE OF IMMUNOCYTOCHEMISTRY AND BRAF MUTATION ANALYSIS ON LIQUID BASED BIOPSIES OF THYROID NEOPLASMS SUSPICIOUS FOR CARCINOMA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Endocrinol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1530/EJE-13-0023
AUTORES / AUTHORS: - Rossi ED; Martini M; Capodimonti S; Straccia P; Cenci T; Lombardi CP; Pontecorvi A; Larocca LM; Fadda G
INSTITUCIÓN / INSTITUTION: - E Rossi, Anatomic Pathology, Catholic University, Rome, 00168, Italy.
RESUMEN / SUMMARY: - OBJECTIVE: In the field of Fine Needle Aspiration Cytology (FNAC), the category of suspicious for malignancy (SM) thyroid lesions which bears 55-85% risk of malignant histology, is a challenging topic in which morphology alone is not always able to make a correct diagnosis. Recently, immunocytochemistry (ICC) has been referred as helpful in differentiating low and high malignant risk lesions and BRAF activating mutations have been identified in a significant amount of papillary thyroid carcinomas (PTC). The introduction of the liquid-based cytology (LBC) may simplify the application of these techniques to thyroid cytology.DESIGN Our aim is to evaluate the diagnostic and prognostic role of both ICC and BRAF mutation for the SM category on LBC.METHODS From October 2010 through June 2011, 113 LBC cytological cases (including 37 SM and 76 PTC) underwent surgery. All cases were studied for BRAF mutation and ICC.RESULTS In detail, ICC resulted positive in 26 (86.6%) histologically malignant SM with 15 of which (40.5%) expressed a BRAF mutation. Overall 63 cases showed a BRAF mutation histological resulting as PTC.Concerning the prognostic role of BRAF mutation for the two categories, we reported a significant correlation with multifocality, nodal involvement and extracapsular invasion (p<0.0001).CONCLUSIONS Special techniques such as ICC and molecular might be successfully carried out on LBC- processed material. For both categories, ICC is more sensitive whereas BRAF analysis is an interesting support due to its high specificity adding a prognostic value in both SM and PTCs.
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[788]
TÍTULO / TITLE: - Inhibition of prolyl 4-hydroxylase, beta polypeptide (P4HB) attenuates temozolomide resistance in malignant glioma via the endoplasmic reticulum stress response (ERSR) pathways.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Oncol. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1093/neuonc/not005
AUTORES / AUTHORS: - Sun S; Lee D; Ho AS; Pu JK; Zhang XQ; Lee NP; Day PJ; Lui WM; Fung CF; Leung GK
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, People’s Republic of China (S.S., D.L., A.S.W.H., J.K.S.P., X.Q.Z., N.P.L., W.M.L., C.F.F., G.K.K.L.); Interdisciplinary Molecular Medicine, The Manchester Institute of Biotechnology, University of Manchester, Manchester, UK (P.J.R.D.).
RESUMEN / SUMMARY: - BackgroundGlioblastoma multiforme (GBM), the most aggressive malignant primary brain tumor of the central nervous system, is characterized by a relentless disease recurrence despite continued advancement in surgery, radiotherapy, and chemotherapy. Resistance to temozolomide (TMZ), a standard chemotherapeutic agent for GBM, remains a major challenge. Understanding the mechanisms behind TMZ resistance can direct the development of novel strategies for the prevention, monitoring, and treatment of tumor relapse.Methods and resultsOur research platform, based on the establishment of 2 pairs of TMZ-sensitive/resistant GBM cells (D54-S and D54-R; U87-S and U87-R), has successfully identified prolyl 4-hydroxylase, beta polypeptide (P4HB) over-expression to be associated with an increased IC(50) of TMZ. Elevated P4HB expression was verified using in vivo xenografts developed from U87-R cells. Clinically, we found that P4HB was relatively up-regulated in the recurrent GBM specimens that were initially responsive to TMZ but later developed acquired resistance, when compared with treatment-naive tumors. Functionally, P4HB inhibition by RNAi knockdown and bacitracin inhibition could sensitize D54-R and U87-R cells to TMZ in vitro and in vivo, whereas over-expression of P4HB in vitro conferred resistance to TMZ in both D54-S and U87-S cells. Moreover, targeting P4HB blocked its protective function and sensitized glioma cells to TMZ through the PERK arm of the endoplasmic reticulum stress response.ConclusionsOur study identified a novel target together with its functional pathway in the development of TMZ resistance. P4HB inhibition may be used alone or in combination with TMZ for the treatment of TMZ-resistant GBM.
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[789]
TÍTULO / TITLE: - Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55717. doi: 10.1371/journal.pone.0055717. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055717
AUTORES / AUTHORS: - Iqbal Z; Aleem A; Iqbal M; Naqvi MI; Gill A; Taj AS; Qayyum A; ur-Rehman N; Khalid AM; Shah IH; Khalid M; Haq R; Khan M; Baig SM; Jamil A; Abbas MN; Absar M; Mahmood A; Rasool M; Akhtar T
INSTITUCIÓN / INSTITUTION: - College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), National Guards Health Affairs, Riyadh, Kingdom of Saudi Arabia. iqbalz@ksau-hs.edu.sa
RESUMEN / SUMMARY: - BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48), all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. Thus, mutation testing using CD34+ cells may facilitate improved, patient-tailored treatment.
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[790]
TÍTULO / TITLE: - Maintenance therapy with tyrosine kinase inhibitors after transplant in patients with chronic myeloid leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Compr Canc Netw. 2013 Mar 1;11(3):308-15.
AUTORES / AUTHORS: - Bar M; Radich J
INSTITUCIÓN / INSTITUTION: - From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
RESUMEN / SUMMARY: - Because of their outstanding efficacy and low toxicity, tyrosine kinase inhibitors (TKIs) have replaced allogeneic hematopoietic cell transplant (HCT) as the standard frontline therapy for patients with newly diagnosed chronic myeloid leukemia (CML). Until a decade ago, HCT was the preferred treatment for CML, with 5-year overall survival rates of approximately 80%, 40%, and 20% for patients in chronic, accelerated, and blast crisis phases, respectively. Relapse after transplant is a problem for patients who undergo transplant in advanced phase disease and those undergoing a T-depleted transplant. Until the introduction of TKIs, therapy for relapsed CML after transplant relied on interferon and/or donor leukocyte infusion (DLI). Although effective in inducing remission, DLI is associated with clinically significant graft-versus-host disease or myelosuppression, with an accompanying treatment-related mortality of 5% to 20%. TKIs have emerged as an attractive alternative therapy for persistent or relapsing CML after HCT. Similar to DLI, the effectiveness of TKI posttransplant is largely determined by the phase of disease at relapse, showing very good response in patients experiencing relapse in the chronic phase, with high rates (>60%) of hematologic and cytogenetic remissions, but less favorable outcomes in patients with advanced disease, with only a minority experiencing durable cytogenetic or molecular remissions. Molecular monitoring of the BCR-ABL chimeric mRNA posttransplant is important for early detection of patients at high risk of relapse.
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[791]
TÍTULO / TITLE: - Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57053. doi: 10.1371/journal.pone.0057053. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057053
AUTORES / AUTHORS: - Chen YC; Hsiao CC; Chen KD; Hung YC; Wu CY; Lie CH; Liu SF; Sung MT; Chen CJ; Wang TY; Chang JC; Tang P; Fang WF; Wang YH; Chung YH; Chao TY; Leung SY; Su MC; Wang CC; Lin MC
INSTITUCIÓN / INSTITUTION: - Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan ; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
RESUMEN / SUMMARY: - INTRODUCTION: Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy. METHODS: To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment. RESULTS: Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality. CONCLUSIONS: Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.
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[792]
TÍTULO / TITLE: - Diagnostic value and prognostic significance of pleural C-reactive protein in lung cancer patients with malignant pleural effusions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Yonsei Med J. 2013 Mar 1;54(2):396-402. doi: 10.3349/ymj.2013.54.2.396.
●● Enlace al texto completo (gratuito o de pago) 3349/ymj.2013.54.2.396
AUTORES / AUTHORS: - Park DS; Kim D; Hwang KE; Hwang YR; Park C; Seol CH; Cho KH; Kim BR; Park SH; Jeong ET; Kim HR
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Medicine, Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 895 Muwang-ro, Iksan 570-749, Korea.
RESUMEN / SUMMARY: - PURPOSE: C-reactive protein (CRP) has been implicated in various inflammatory and advanced malignant states. Increased serum CRP (s-CRP) levels have been shown to be associated with independent prognostic factors for survival in patients with advanced lung cancer. However, only few studies have focused on the role of CRP in pleural effusions. This study aimed to evaluate the diagnostic and prognostic value of pleural CRP (p-CRP) in lung cancer patients with malignant pleural effusion (MPE). MATERIALS AND METHODS: Pleural effusion (PE) samples were collected from patients with MPE (68 lung cancers; 12 extrathoracic tumors), and from 68 patients with various benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of p- and s-CRP were measured by enzyme-linked immunosorbent assay. CRP level in pleural fluid and its association with survival were examined. RESULTS: p-CRP levels correlated with s-CRP levels (r=0.82, p<0.0001). For the differential diagnosis of MPE and benign PE, the area under the receiver operating characteristic curve was greater for p-CRP (0.86) than for s-CRP (0.77). High p-CRP expression significantly correlated with shorter overall survival (p=0.006). P-CRP was independent prognostic factor significantly associated with overall survival on multivariated analysis (p=0.0001). The relative risk of death for lung cancer patients with high p-CRP levels was 3.909 (95% confidence interval, 2.000-7.639). CONCLUSION: P-CRP is superior to s-CRP in determining pleural fluid etiology. Quantitative measurement of p-CRP might be a useful complementary diagnostic and prognostic test for lung cancer patients with MPE.
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[793]
TÍTULO / TITLE: - Cyclin D1, EGFR, and Akt/mTOR pathway. Potential prognostic markers in localized laryngeal squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Strahlenther Onkol. 2013 Mar;189(3):202-14. doi: 10.1007/s00066-012-0275-0. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s00066-012-0275-0
AUTORES / AUTHORS: - Dionysopoulos D; Pavlakis K; Kotoula V; Fountzilas E; Markou K; Karasmanis I; Angouridakis N; Nikolaou A; Kalogeras KT; Fountzilas G
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Peripheriaki odos, Nea Efkarpia, 56403, Thessaloniki, Greece. dimitris.dionysopoulos@gmail.com
RESUMEN / SUMMARY: - INTRODUCTION: EGFR (epidermal growth factor receptor), cyclin D1 and Akt/mTOR pathways are active in head and neck cancer. The aim of this study was to explore biomarker expression, their correlations with clinicopathological parameters and their prognostic utility in a cohort of patients with localized squamous laryngeal carcinoma. PATIENTS AND METHODS: We assessed relative messenger RNA expression of EGFR, Akt1, 2, and 3, mTOR and CCND1, copy number variants of the EGFR and CCND1 genes and immunohistochemical protein expression of EGFR, p-Akt308, p-Akt473, pmTOR, PTEN, p53 and cyclin D1 in paraffin-embedded tissue samples of localized laryngeal carcinomas. RESULTS: In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumors of the larynx, high EGFR and CCND1 mRNA correlated with no or ex-smoking, (p = 0.003 and p = 0.029, respectively), while low Akt3 mRNA correlated with alcohol abuse, N0 stage, total laryngectomy, and absence of neck dissection. At a median follow-up of 74.5 months, high mTOR mRNA expression was marginally associated with shorter disease-free survival (hazard ratio [HR] = 1.54; p = 0.093) and high Akt3 mRNA with shorter overall survival (HR = 1.49; p = 0.0786), in univariate analysis. In multivariate analysis, node-positive status, subglottic-transglottic location, surgery other than total laryngectomy and mTOR/CCND1 mRNA interaction with a hazard ratio of 2.16 (p value for interaction: 0.0010) were independent predictors of relapse, while node-positive status and subglottic-transglottic location were associated with higher risk for death. CONCLUSION: In localized laryngeal cancer, clinicopathological parameters and an interaction of high mTOR and CCND1 mRNA expression were found to be associated with poor patient outcome.
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[794]
TÍTULO / TITLE: - Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Feb;126(3):482-7.
AUTORES / AUTHORS: - Chen BB; Xu XP; Shen L; Han TJ; Lin ZG; Chen Z; Kang H; Huang B; Lin GW
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
RESUMEN / SUMMARY: - BACKGROUND: Clinical outcome in patients with primary central nervous lymphoma (PCNSL) is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL. METHODS: One hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxp1, and LMO2 were performed. All cases were followed-up regularly. RESULTS: The common sites of involvement were frontal lobe (54.8%) and thalamus (16.5%). Diffuse large B-cell lymphoma composed of 96.5% of the cases. The median overall survival was 22 (4 - 41) months, and the 5-year survival rate was 22.8%. Age > 65 years, serum globulin > 40 g/L, large size of tumor, lymphocyte count >/= 1 x 10(9)/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxp1, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size, and high serum globulin were independent prognostic factors for PCNSL. CONCLUSIONS: PCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.
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[795]
TÍTULO / TITLE: - C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Med Insights Oncol. 2013;7:31-9. doi: 10.4137/CMO.S10839. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 4137/CMO.S10839
AUTORES / AUTHORS: - Nagata M; Kimura T; Suzumura T; Kira Y; Nakai T; Umekawa K; Tanaka H; Matsuura K; Mitsuoka S; Yoshimura N; Oka T; Kudoh S; Hirata K
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University.
RESUMEN / SUMMARY: - BACKGROUND: Amrubicin hydrochloride (AMR) is a key agent for lung cancer. NADPH quinone oxidoreductase 1 (NQO1) metabolizes the quinone structures contained in both amrubicin (AMR) and amrubicinol (AMR-OH). We hypothesized that NQO1 C609T polymorphism may affect AMR-related pharmacokinetics and clinical outcomes. METHODS: Patients received AMR doses of 30 or 40 mg/m(2)/day on days 1-3. Plasma sampling was performed 24 hours after the first and third AMR injections. Concentrations of AMR and AMR-OH were determined by HPLC and the NQO1 C609T polymorphism was assayed by RT-PCR. RESULTS: A total of 35 patients were enrolled. At a dose of 40 mg/m(2), the T/T genotype exhibited a tendency toward a relationship with decrease concentrations of AMR-OH on days 2 and 4. The genotype also showed a significant decrease of hematological toxicities (P < 0.05). CONCLUSIONS: NQO1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities.
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[796]
TÍTULO / TITLE: - Dystonia in a patient with melanoma metastatic to the brain treated with high-dose interleukin-2, radiation therapy, and levetiracetam.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Oncol. 2013 Jan;6(1):78-83. doi: 10.1159/000346932. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1159/000346932
AUTORES / AUTHORS: - Sreenivasan V; Dudek AZ
INSTITUCIÓN / INSTITUTION: - Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minn., USA.
RESUMEN / SUMMARY: - Dystonia has been described as a potential toxicity of radiation therapy. Management of this rare movement disorder is targeted in symptom improvement. We report a case of a 46-year-old female patient who developed dystonia during treatment of melanoma metastatic to the brain and discuss potential causes of and therapies for this rare complication.
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[797]
TÍTULO / TITLE: - MAP17 and SGLT1 protein expression levels as prognostic markers for cervical tumor patient survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56169. doi: 10.1371/journal.pone.0056169. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056169
AUTORES / AUTHORS: - Perez M; Praena-Fernandez JM; Felipe-Abrio B; Lopez-Garcia MA; Lucena-Cacace A; Garcia A; Lleonart M; Roncador G; Marin JJ; Carnero A
INSTITUCIÓN / INSTITUTION: - Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio, Consejo Superior de Investigaciones Cientificas, Universidad de Sevilla, Sevilla, España.
RESUMEN / SUMMARY: - MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS) generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types.
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[798]
TÍTULO / TITLE: - Counselling and adverse event management for patients with myelodysplastic syndromes undergoing azacitidine therapy: a practice standard for Canadian nurses.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Can Oncol Nurs J. 2012 Autumn;22(4):222-34.
AUTORES / AUTHORS: - Murray C; Wereley A; Nixon S; Hua-Yung C; von Riedemann S; Kurtin S
INSTITUCIÓN / INSTITUTION: - Princess Margaret Hospital, University Health Network, Toronto, ON. Cindy.Murray@uhn.on.ca
RESUMEN / SUMMARY: - Azacitidine (5-azacytidine, VIDAZA) is a disease-modifying agent that improves survival, reduces transfusion dependence, and reduces progression to acute myeloid leukemia in patients with higher risk myelodysplastic syndromes. Azacitidine injection is associated with characteristic adverse events (AEs) that must be managed in order for patients to stay on therapy and achieve optimal therapeutic outcomes. These AEs include injection-site reactions, cytopenias, and gastrointestinal effects. Oncology nurses are uniquely positioned to provide patient support and counselling, thereby helping patients and their families set clear expectations for azacitidine therapy. This article presents a nursing standard designed to support Canadian oncology nurses in the key areas of counselling for patients initiating and continuing azacitidine, as well as nursing strategies for prevention and management of azacitidine-associated AEs. Many of the general principles discussed in this nursing standard can be applied broadly to many diseases and treatments.
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[799]
TÍTULO / TITLE: - Patients treated with a tumor necrosis factor-alpha inhibitor are more likely to develop extrapulmonary tuberculosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Intern Med. 2013 Mar;28(2):159-61. doi: 10.3904/kjim.2013.28.2.159. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 3904/kjim.2013.28.2.159
AUTORES / AUTHORS: - Lee SO
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.
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[800]
TÍTULO / TITLE: - Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Transl Oncol. 2012 Dec;5(6):469-74. Epub 2012 Dec 1.
AUTORES / AUTHORS: - Samrao D; Wang D; Ough F; Lin YG; Liu S; Menesses T; Yessaian A; Turner N; Pejovic T; Mhawech-Fauceglia P
INSTITUCIÓN / INSTITUTION: - Department of Pathology, University of Southern California, Los Angeles, CA.
RESUMEN / SUMMARY: - The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen’s kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.
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[801]
TÍTULO / TITLE: - Response predictors and clinical benefits of hepatitis C retreatment with pegylated interferon and ribavirin in HIV/HCV coinfection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Hepatol. 2013 Mar;12(2):228-35.
AUTORES / AUTHORS: - Peribanez-Gonzalez M; da Silva MH; Vilar FC; Seixas-Santos Nastri AC; Ferreira PA; Focaccia R; Mendes Correa MC
INSTITUCIÓN / INSTITUTION: - Instituto de Infectologia Emilio Ribas, Sao Paulo, Brasill.
RESUMEN / SUMMARY: - Background. Hepatitis C is a leading cause of mortality among HIV-infected individuals. Therefore, eradication of HCV in this population is a priority. There are scarce data regarding retreatment efficacy of HIV/ HCV coinfected patients. The aim of our study was to evaluate efficacy, predictors of response, and long term clinical benefits of sustained virological response (SVR) after hepatitis C retreatment in a population of HIV/HCV coinfected patients. Material and methods. We evaluated efficacy, safety, and clinical benefits of peginterferon(alfa-2a or alfa-2b) and ribavirin in a restrospective, observational, multicentric study, including 47 HIV/HCV coinfected patients, non-responders to previous treatment with conventional interferon alfa-2a and ribavirin. The primary endpoint of efficacy was SVR, defined as undetectable viral load 24 weeks after end of treatment. Death, liver disease progression, CD4 counts, and AIDS defining illness were the endpoints to access clinical benefits of treatment response. Results. In our analysis, 31.9% patients reached SVR. Genotypes 2/3 had a significant better SVR (66.7%) compared to genotypes ¼ (33.3%) (p = 0.022). During follow-up, deaths (6.89%) and hepatic decompensation (28.6%) occurred only in the nonresponder group, while there were no cases of death or hepatic decompensation among the responder group(p = 0.037). Conclusion. Nearly one third of patients (mainly those with genotypes 2/3) reached SVR after hepatitis C retreatment in this group of HIV/HCV coinfected patients. SVR was protective against hepatic decompensation and death in a two-year follow-up period. Retreatment may be an effective and safe way to eradicate HCV until new anti-HCV drugs become available to this group of patients.
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[802]
TÍTULO / TITLE: - Iodinin (1,6-Dihydroxyphenazine 5,10-Dioxide) from Streptosporangium sp. Induces Apoptosis Selectively in Myeloid Leukemia Cell Lines and Patient Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mar Drugs. 2013 Jan 30;11(2):332-49. doi: 10.3390/md11020332.
●● Enlace al texto completo (gratuito o de pago) 3390/md11020332
AUTORES / AUTHORS: - Myhren LE; Nygaard G; Gausdal G; Sletta H; Teigen K; Degnes KF; Zahlsen K; Brunsvik A; Bruserud O; Doskeland SO; Selheim F; Herfindal L
INSTITUCIÓN / INSTITUTION: - Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. lars.herfindal@biomed.uib.no.
RESUMEN / SUMMARY: - Despite recent improvement in therapy, acute myeloid leukemia (AML) is still associated with high lethality. In the presented study, we analyzed the bioactive compound iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from a marine actinomycetes bacterium for the ability to induce cell death in a range of cell types. Iodinin showed selective toxicity to AML and acute promyelocytic (APL) leukemia cells, with EC50 values for cell death up to 40 times lower for leukemia cells when compared with normal cells. Iodinin also successfully induced cell death in patient-derived leukemia cells or cell lines with features associated with poor prognostic such as FLT3 internal tandem duplications or mutated/deficient p53. The cell death had typical apoptotic morphology, and activation of apoptotic signaling proteins like caspase-3. Molecular modeling suggested that iodinin could intercalate between bases in the DNA in a way similar to the anti-cancer drug daunorubicin (DNR), causing DNA-strand breaks. Iodinin induced apoptosis in several therapy-resistant AML-patient blasts, but to a low degree in peripheral blood leukocytes, and in contrast to DNR, not in rat cardiomyoblasts. The low activity towards normal cell types that are usually affected by anti-leukemia therapy suggests that iodinin and related compounds represent promising structures in the development of anti-cancer therapy.
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[803]
TÍTULO / TITLE: - HMGA2 Inhibits Apoptosis through Interaction with ATR-CHK1 Signaling Complex in Human Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasia. 2013 Mar;15(3):263-80.
AUTORES / AUTHORS: - Natarajan S; Hombach-Klonisch S; Droge P; Klonisch T
INSTITUCIÓN / INSTITUTION: - Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
RESUMEN / SUMMARY: - The non-histone chromatin binding protein high mobility group AT-hook 2 (HMGA2) is expressed in stem cells and many cancer cells, including tumor initiating cells, but not translated in normal human somatic cells. The presence of HMGA2 is correlated with advanced neoplastic disease and poor prognosis for patients. We had previously demonstrated a role of HMGA2 in DNA repair pathways. In the present study, we employed different human tumor cell models with endogenous and exogenous expression of HMGA2 and show that upon DNA damage, the presence of HMGA2 caused an increased and sustained phosphorylation of the ataxia telangiectasia and Rad3-related kinase (ATR) and its downstream target checkpoint kinase 1 (CHK1). The presence of activated pCHK1(Ser296) coincided with prolonged G2/M block and increased tumor cell survival, which was enhanced further in the presence of HMGA2. Our study, thus, identifies a novel relationship between the ATR-CHK1 DNA damage response pathway and HMGA2, which may support the DNA repair function of HMGA2 in cancer cells. Furthermore, our data provide a rationale for the use of inhibitors to ATR or CHK1 and HMGA2 in the treatment of HMGA2-positive human cancer cells.
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[804]
TÍTULO / TITLE: - Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Oncol. 2013 Mar 14. pii: S1574-7891(13)00037-9. doi: 10.1016/j.molonc.2013.02.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2013.02.013
AUTORES / AUTHORS: - Smerage JB; Budd GT; Doyle GV; Brown M; Paoletti C; Muniz M; Miller MC; Repollet MI; Chianese DA; Connelly MC; Terstappen LW; Hayes DF
INSTITUCIÓN / INSTITUTION: - Breast Oncology Program of the Comprehensive Cancer Center, Department of Internal Medicine, 6312 CCGC, University of Michigan Health and Hospital System, Ann Arbor, MI 48109, United States. Electronic address: smerage@med.umich.edu.
RESUMEN / SUMMARY: - BACKGROUND: Enumeration of circulating tumor cells (CTC) from whole blood permits monitoring of patients with breast carcinoma. Analysis of apoptosis & Bcl-2 expression in CTC might add additional prognostic and predictive information. We estimated the degree of these markers in CTC from patients being treated for metastatic breast cancer. METHODS: Eighty-three evaluable patients initiating a new therapy for metastatic breast cancer were enrolled. Whole blood was collected at baseline, at one of three short term time windows (24, 48, or 72 h) after initiating treatment, and at first follow-up (3-5 weeks). CTC were isolated, enumerated, and expression of M30 and Bcl2 was determined using the CellSearch® System. RESULTS: At baseline, window, and 3-5 weeks post-treatment, 41/80 (51%), 40/80 (50%) and 21/75 (28%) patients had >/=5 CTC, respectively. At baseline, the proportion of CTC-apoptosis (M30) was inversely correlated with CTC number, and modestly inversely correlated with CTC-Bcl-2. As expected, higher CTC levels at baseline or first follow-up were associated with worse prognosis. Surprisingly, in patients with elevated CTC, higher levels of CTC-apoptosis were associated with worse prognosis, while higher CTC-Bcl-2 levels correlated with better outcomes. CONCLUSIONS: CTC apoptosis and expression of Bcl-2 can be analytically determined in patients with metastatic breast cancer and may have biological and clinical implications. Characterization of CTC for these and other markers could further increase the utility of CTC monitoring patients in clinical investigations of new anti-neoplastic agents.
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[805]
TÍTULO / TITLE: - Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 21;13(1):136.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-136
AUTORES / AUTHORS: - Guo J; Huang Y; Zhang X; Zhou F; Sun Y; Qin S; Ye Z; Wang H; Jappe A; Straub P; Pirotta N; Gogov S
RESUMEN / SUMMARY: - BACKGROUND: In China, there are currently no approved therapies for the treatment of metastatic renal cell carcinoma (mRCC) following progression with vascular endothelial growth factor (VEGF)-targeted agents. In the phase 3 RECORD-1 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus afforded clinical benefit with good tolerability in Western patients with mRCC whose disease had progressed despite VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. This phase 1b study was designed to further evaluate the safety and efficacy of everolimus in VEGFr-TKI-refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801). METHODS: An open-label, multicenter phase 1b study enrolled Chinese patients with mRCC who were intolerant to, or progressed on, previous VEGFr-TKI therapy (N = 64). Patients received everolimus 10 mg daily until objective tumor progression (according to RECIST, version 1.0), unacceptable toxicity, death, or study discontinuation for any other reason. The final data analysis cut-off date was November 30, 2011. RESULTS: A total of 64 patients were included in the study. Median age was 52 years (range, 19--75 years) and 69% of patients were male. Median duration of everolimus therapy was 4.1 months (range, 0.0-16.1 months). Expected known class-effect toxicities related to mTOR inhibitor therapy were observed, including anemia (64%), hypertriglyceridemia (55%), mouth ulceration (53%), hyperglycemia (52%), hypercholesterolemia (50%), and pulmonary events (31%). Common grade ¾ adverse events were anemia (20%), hyperglycemia (13%), increased gamma-glutamyltransferase (11%), hyponatremia (8%), dyspnea (8%), hypertriglyceridemia (6%), and lymphopenia (6%). Median PFS was 6.9 months (95% CI, 3.7-12.5 months) and the overall tumor response rate was 5% (95% CI, 1-13%). The majority of patients (61%) had stable disease as their best overall tumor response. CONCLUSIONS: Safety and efficacy results were comparable to those of the RECORD-1 trial. Everolimus is generally well tolerated and provides clinical benefit to Chinese patients with anti-VEGF-refractory mRCC.
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[806]
TÍTULO / TITLE: - Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Med. 2013 Mar 4;11(1):59.
●● Enlace al texto completo (gratuito o de pago) 1186/1741-7015-11-59
AUTORES / AUTHORS: - Bruera G; Cannita K; Di Giacomo D; Lamy A; Frebourg T; Sabourin JC; Tosi M; Alesse E; Ficorella C; Ricevuto E
RESUMEN / SUMMARY: - BACKGROUND: Prognosis of KRAS wild-type and mutant metastatic colorectal cancer (MCRC) patients (pts) treated with bevacizumab (BEV)-containing chemotherapy is not significantly different. Since specific KRAS mutations confer different aggressive behaviors, the prognostic role of prevalent KRAS mutations was retrospectively evaluated in MCRC pts treated with first line FIr-B/FOx, associating BEV to triplet chemotherapy. METHODS: Tumor samples were screened for KRAS codon 12, 13 and BRAF V600E mutations by SNaPshot and/or direct sequencing. MCRC pts <75-years-old were consecutively treated with FIr-B/FOx: weekly 12 hour-timed-flat-infusion/5-fluorouracil (900 mg/m2 on days 1,2, 8, 9, 15, 16,22, 23), irinotecan plus BEV (160 mg/m2 and 5 mg/kg, respectively, on days 1,15); and oxaliplatin (80 mg/m2, on days 8,22). Pts were classified as liver-limited (L-L) and other/multiple metastatic (O/MM). Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test. RESULTS: Fifty-nine pts were evaluated at a median follow-up of 21.5 months. KRAS mutant pts: c.35 G > A, 15 (25.4%); c.35 G > T, 7 (11.8%); c.38 G > A, 3 (5%); other, 3 (5%). KRAS wild-type, 31 pts (52.7%). The objective response rate (ORR), PFS and OS were, respectively: c.35 G > A mutant, 71%, 9 months, 14 months; other than c.35 G > A mutants, 61%, 12 months, 39 months. OS was significantly worse in c.35 G > A pts compared to KRAS wild-type (P = 0.002), KRAS/BRAF wild-type (P = 0.03), other MCRC patients (P = 0.002), other than c.35 G > A (P = 0.05), other codon 12 (P = 0.03) mutant pts. OS was not significantly different compared to c.35 G > T KRAS mutant (P = 0.142). CONCLUSIONS: KRAS c.35 G > A mutant status may be significantly associated with a worse prognosis of MCRC pts treated with first line FIr-B/FOx intensive regimen compared to KRAS/BRAF wild type and other than c.35 G > A mutant pts.
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[807]
TÍTULO / TITLE: - Vitamin D Receptor Genetic Variants are Associated With Chemotherapy Response and Prognosis in Patients With Advanced Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Mar 21. pii: S1525-7304(13)00030-2. doi: 10.1016/j.cllc.2013.01.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2013.01.004
AUTORES / AUTHORS: - Xiong L; Cheng J; Gao J; Wang J; Liu X; Wang L
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary Disease, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, P.R. China.
RESUMEN / SUMMARY: - BACKGROUND: The aim of this study was to explore the association between vitamin D receptor (VDR) genetic polymorphisms and platinum-based chemotherapy response as well as the prognosis of non-small-cell lung cancer (NSCLC) in a Chinese cohort. PATIENTS AND METHODS: Seven hundred fifty-five patients with advanced NSCLC (stage III [A + B] or stage IV) were enrolled. Platinum-based chemotherapy was given to each patient with NSCLC, and the therapeutic effect was evaluated. The VDR polymorphisms were genotyped. RESULTS: Three hundred twenty-one (42.5%) patients responded to chemotherapy (complete response [CR] or partial response [PR]) and 434 (57.5%) patients were nonresponders (stable disease [SD] or progressive disease [PD]). The genotypic and allelic frequencies of FokI, BsmI, and TaqI were not significantly different between chemotherapy responders and nonresponders. However, the genotypic and allelic frequencies of ApaI thymine (T) > guanine (G) were significantly different between the responders and nonresponders. Multivariate logistic regression analysis showed that GG genotype carriers of ApaI T > G had a higher chance of being responders. The ApaI T > G polymorphisms affected mean overall survival (OS). The GG genotype carriers of ApaI polymorphisms had a longer mean OS compared with TT carriers. Multivariate Cox regression analyses showed that ApaI T > G was significantly associated with OS. CONCLUSION: We found that there was an effect of ApaI T > G polymorphisms of the VDR gene on the chemotherapy response in patients with NSCLC, as well as a prognostic role of the VDR gene polymorphisms in Chinese patients with advanced NSCLC.
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[808]
TÍTULO / TITLE: - The combination of ANT2 shRNA and hNIS radioiodine gene therapy increases CTL cytotoxic activity through the phenotypic modulation of cancer cells: combination treatment with ANT2 shRNA and I-131.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 22;13(1):143.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-143
AUTORES / AUTHORS: - Choi Y; Lee HW; Lee J; Jeon YH
RESUMEN / SUMMARY: - BACKGROUND: It is important to simultaneously induce strong cell death and antitumor immunity in cancer patients for successful cancer treatment. Here, we investigated the cytotoxic and phenotypic modulation effects of the combination of ANT2 shRNA and human sodium iodide symporter (hNIS) radioiodine gene therapy in vitro and in vivo and visualized the antitumor effects in an immunocompromised mouse colon cancer model. METHODS: A mouse colon cancer cell line co-expressing hNIS and the luciferase gene (CT26/hNIS-Fluc, named CT26/NF) was established. CT26/NF cells and tumor-bearing mice were treated with HBSS, scramble, ANT2 shRNA, I-131, and ANT2 shRNA + I-131. The apoptotic rates (%) and MHC class I and Fas gene expression levels were determined in treated CT26/NF cells using flow cytometry. Concurrently, the level of caspase-3 activation was determined in treated cells in vitro. For in vivo therapy, tumor-bearing mice were treated with scramble, ANT2 shRNA, I-131, and the combination therapy, and the anti-tumor effects were monitored using bioluminescence. The killing activity of cytotoxic T cells (CTLs) was measured with a lactate dehydrogenase (LDH) assay. RESULTS: For the in vitro experiments, the combination of ANT2 shRNA and I-131 resulted in a higher apoptotic cell death rate compared with ANT2 shRNA or I-131 alone, and the levels of MHC class I and Fas-expressing cancer cells were highest in the cells receiving combination treatment, while single treatment modestly increased the level of MHC class I and Fas gene expression. The combination of ANT2 shRNA and I-131 resulted in a higher caspase-3 activation than single treatments. Interestingly, in vivo combination treatment led to increased gene expression of MHC class I and Fas than the respective mono-therapies; furthermore, bioluminescence showed increased antitumor effects after combination treatment than monotherapies. The LDH assay revealed that the CTL killing activity against CT26/NF cells was most effective after combination therapy. CONCLUSIONS: Increased cell death and phenotypic modulation of cancer cells in vitro and in vivo were achieved simultaneously after combination therapy with ANT2 shRNA and I-131, and this combination therapy induced remarkable antitumor outcomes through improvements in CTL immunity against CT26/NF. Our results suggest that combination therapy can be used as a new therapeutic strategy for cancer patients who show resistance to single therapy such as radiation or immunotherapy.
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[809]
TÍTULO / TITLE: - Deficiencies in immunoassay methods used to monitor serum Estradiol levels during aromatase inhibitor treatment in postmenopausal breast cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Springerplus. 2013 Dec;2(1):5. Epub 2013 Jan 11.
●● Enlace al texto completo (gratuito o de pago) 1186/2193-1801-2-5
AUTORES / AUTHORS: - Jaque J; Macdonald H; Brueggmann D; Patel SK; Azen C; Clarke N; Stanczyk FZ
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Keck School of Medicine of the University of Southern California, Los Angeles, CA USA.
RESUMEN / SUMMARY: - Optimal care for breast cancer patients undergoing aromatase inhibitor (AI) treatment is ensured when estradiol (E2) levels are adequately suppressed. To assess treatment efficacy accurately, it is important to measure the serum E2 levels using a well validated assay method with high sensitivity and specificity. This translates into the urgent need to evaluate various E2 immunoassay kits, which are frequently used in hospital settings to measure E2 serum levels in patients undergoing AI treatment, so clinicians obtain accurate and reliable measurements allowing appropriate clinical decision making. Our objective was to evaluate the performance of different commercially available and commonly used E2 immunoassay kits regarding measurement of E2 levels in the serum of postmenopausal breast cancer patients treated with AIs, in comparison to a highly accurate and reliable mass spectrometry assay. Clinical and demographic data were obtained from 77 postmenopausal breast cancer patients who were treated with an AI. Serum E2 levels were measured by 6 immunoassay methods and by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which served as the standard for comparison. Analysis of E2 by LC-MS/MS showed that 70% of the samples had levels that were <5 pg/ml. Three of the assays carried out with commercial E2 immunoassay kits had poor sensitivities and were not able to detect E2 levels <10 or <20 pg/ml. Although two of the E2 assays using commercial kits demonstrated a better sensitivity (5 pg/ml), the measured E2 values were substantially higher than those obtained by LC-MS/MS. The assay with the sixth commercial E2 kit grossly underestimated the true E2 values. E2 assays carried out with commercial E2 immunoassay kits lack the accuracy to measure the very low serum E2 levels found in patients being treated with AIs. Serum samples from such patients should be sent to laboratories that use a mass spectrometry assay.
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[810]
TÍTULO / TITLE: - Predictive Value of Baseline Plasma D-dimers for Chemotherapy- induced Thrombocytopenia in Patients with Stage III Colon Cancer: A Pilot Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):293-7.
AUTORES / AUTHORS: - Tanriverdi O
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Mugla Sitki Kocman University Education and Research Hospital, Mugla, Turkey E-mail : ozgurtanriverdi@hotmail.com.
RESUMEN / SUMMARY: - Background: Chemotherapy-induced thrombocytopenia (CIT) is an important cause of morbitity in patients with cancer. Aim: To investigate the effect of the baseline plasma D-dimer level, an important marker for thrombotic activity, on chemotherapy-induced thrombocytopenia in patients with stage III colon cancer. Materials and Methods: A total of 43 (28 men) eligible patients were divided into two groups according to whether they exhibited chemotherapy-induced thrombocytopenia: Group 1 (n=21) and Group 2 (n=22). Comparison was made using demographic, histopathologic, and laboratory variables. Additionally, baseline plasma D-dimer levels underwent receiver operation characteristics curve analysis, and areas under the curve were calculated. Sensitivity, specificity, and positive and negative likelihood rates were then determined. Results: The incidence of chemotherapy-induced thrombocytopenia had a significant correlation with baseline platelet count (r=0.568, P=0.031) and baseline plasma D-dimer levels (r=0.617, P=0.036). When the cut-off point for the latter was set as 498 ng/mL, the area under the curve was 0.89 (95%CI: 0.74-0.93), the sensitivity was 91.4%, the specificity was 89.7%, the positive likelihood rate was 3.64 and the negative likelihood rate was 0.24 for chemotherapy-induced thrombocytopenia diagnosis. Conclusions: The baseline level of plasma D-dimer could help to differentiate high- risk patients for chemotherapy-induced thrombocytopenia.
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[811]
TÍTULO / TITLE: - Gene expression profiles can predict panitumumab monotherapy responsiveness in human tumor xenograft models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasia. 2013 Feb;15(2):125-32.
AUTORES / AUTHORS: - Boedigheimer MJ; Freeman DJ; Kiaei P; Damore MA; Radinsky R
INSTITUCIÓN / INSTITUTION: - Amgen Inc, Thousand Oaks, CA.
RESUMEN / SUMMARY: - BACKGROUND: Epidermal growth factor receptor (EGFR)-targeted agents have demonstrated clinical benefit in patients with cancer. Identifying tissue-of-origin-independent predictive biomarkers is important to optimally treat patients. We sought to identify a gene array profile that could predict responsiveness to panitumumab, a fully human EGFR-binding antibody, using preclinical models of human cancer. METHODS: Mice bearing 25 different xenograft models were treated twice weekly with panitumumab or immunoglobulin G2 control to determine their responsiveness to panitumumab. Samples from these xenografts and untreated xenografts were arrayed on the Affymetrix human U133A gene chip to identify gene sets predicting responsiveness to panitumumab using univariate and multivariate analyses. The predictive models were validated using the leave-one-group-out (LOO) method. RESULTS: Of the 25 xenograft models tested, 12 were responsive and 13 were resistant to panitumumab. Unsupervised analysis demonstrated that the xenograft models clustered by tissue type rather than responsiveness to panitumumab. After normalizing for tissue effects, samples clustered by responsiveness using an unsupervised multidimensional scaling. A multivariate selection algorithm was used to select 13 genes that could stratify xenograft models based on responsiveness after adjustment for tissue effects. The method was validated using the LOO method on a training set of 22 models and confirmed independently on three new models. In contrast, a univariate gene selection method resulted in higher misclassification rates. CONCLUSION: A model was constructed from microarray data that prospectively predict responsiveness to panitumumab in xenograft models. This approach may help identify patients, independent of disease origin, likely to benefit from panitumumab.
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[812]
TÍTULO / TITLE: - The MAD1 1673 G-->A polymorphism alters the function of the mitotic spindle assembly checkpoint and is associated with a worse response to induction chemotherapy and sensitivity to treatment in patients with advanced epithelial ovarian cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacogenet Genomics. 2013 Apr;23(4):190-9. doi: 10.1097/FPC.0b013e32835ea08a.
●● Enlace al texto completo (gratuito o de pago) 1097/FPC.0b013e32835ea08a
AUTORES / AUTHORS: - Santibanez M; Gallardo D; Morales F; Lopez A; Prada D; Mendoza J; Castro C; de Leon DC; Onate LF; Perez D; Mohar A; Herrera LA
INSTITUCIÓN / INSTITUTION: - aUnidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerologia (INCan); Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM) bDepartamento de Oncologia Medica, INCan cSubdireccion de Investigacion Clinica, INCan dSubdireccion de Patologia, INCan, Mexico, D.F., Mexico.
RESUMEN / SUMMARY: - BACKGROUND: Mitotic arrest deficient 1 (MAD1), a protein of the mitotic spindle assembly checkpoint (SAC), recognizes MAD2 through two leucine zippers, transporting and activating MAD2, which promotes a metaphase arrest signal. A single nucleotide polymorphism of MAD1 was found to affect the SAC function that could be involved in a poor response to therapeutic agents that alter the dynamics of microtubules. OBJECTIVE: The aim of this study was to examine the relationship of the polymorphism MAD1 1673 G-->A (rs1801368) with the efficiency of the SAC and the generation of aneuploidies and with the therapeutic response of patients with ovarian cancer. METHODS: The polymorphism was evaluated in 144 healthy individuals and 91 patients. Mitotic arrest and the presence of errors in segregation were analyzed in cultured human lymphocytes treated with nocodazole and paclitaxel. Errors in segregation were also evaluated in 27 biopsies of patients. RESULTS: Allele frequencies in healthy individuals were G: 50%, A: 50%, whereas in the patients they were G: 38%, A: 62% (P<0.05). The percentage of cells with mitotic arrest was higher among GG cells (P<0.05). The frequency of micronuclei and nondisjunction events increased in AA cells (P<0.05). Tumors from polymorphic patients had a higher percentage of aneuploid cells (P<0.05). The GG patients showed a higher biochemical response, optimal cytoreduction, and sensitivity to the treatment. There were no differences in progression-free or overall survival between both groups. CONCLUSION: The polymorphism MAD1 1673 G-->A affects SAC functionality, increasing the frequency of aneuploid cells. This polymorphism modifies the response to agents that alter the dynamics of microtubules in patients with ovarian cancer.
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[813]
TÍTULO / TITLE: - Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Huazhong Univ Sci Technolog Med Sci. 2013 Feb;33(1):43-50. doi: 10.1007/s11596-013-1069-z. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s11596-013-1069-z
AUTORES / AUTHORS: - You H; Kong MM; Wang LP; Xiao X; Liao HL; Bi ZY; Yan H; Wang H; Wang CH; Ma Q; Liu YQ; Bi YY
INSTITUCIÓN / INSTITUTION: - School of Public Health, Wuhan University, Wuhan, 430071, China, yh568739@yahoo.com.cn.
RESUMEN / SUMMARY: - Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.
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[814]
TÍTULO / TITLE: - HOXA4 Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:129715. doi: 10.1155/2013/129715. Epub 2012 Dec 26.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/129715
AUTORES / AUTHORS: - Elias MH; Baba AA; Husin A; Sulong S; Hassan R; Sim GA; Abdul Wahid SF; Ankathil R
INSTITUCIÓN / INSTITUTION: - Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia.
RESUMEN / SUMMARY: - Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673-12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients.
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[815]
TÍTULO / TITLE: - Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 8;13:71. doi: 10.1186/1471-2407-13-71.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-71
AUTORES / AUTHORS: - Keck B; Wach S; Stoehr R; Kunath F; Bertz S; Lehmann J; Stockle M; Taubert H; Wullich B; Hartmann A
INSTITUCIÓN / INSTITUTION: - Department of Urology, University Erlangen, Krankenhausstrasse 12, Erlangen, 91054, Germany. bastian.keck@uk-erlangen.de
RESUMEN / SUMMARY: - BACKGROUND: Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. METHODS: We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC) and 9 micropapillary (MPC) carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. RESULTS: Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis). Backward multivariate Cox s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters) showed a hazard ratio of 3.2 (p=0.045) for PUC in contrast to patients suffering from MPC. CONCLUSIONS: Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.
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[816]
TÍTULO / TITLE: - The prognostic value of the serum level of C-reactive protein for the survival of patients with a primary sarcoma of bone.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bone Joint J. 2013 Mar;95-B(3):411-8. doi: 10.1302/0301-620X.95B3.30344.
●● Enlace al texto completo (gratuito o de pago) 1302/0301-620X.95B3.30344
AUTORES / AUTHORS: - Nakamura T; Grimer RJ; Gaston CL; Watanuki M; Sudo A; Jeys L
INSTITUCIÓN / INSTITUTION: - The Royal Orthopaedic Hospital, Oncology Service, Bristol Road South, Northfield, Birmingham B31 2AP, UK.
RESUMEN / SUMMARY: - The aim of this study was to determine whether the level of circulating C-reactive protein (CRP) before treatment predicted overall disease-specific survival and local tumour control in patients with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a primary sarcoma of bone between 2003 and 2010. Those who presented with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment; these patients had a poorer disease-specific survival (57% at five years) than patients with a normal CRP (79% at five years) (p < 0.0001). They were also less likely to be free of recurrence (71% at five years) than patients with a normal CRP (79% at five years) (p = 0.04). Multivariate analysis showed the pre-operative CRP level to be an independent predictor of survival and local control. Patients with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP before their treatment started had a significantly poorer disease-specific survival than patients with a normal CRP (p = 0.02 and p < 0.0001, respectively). Patients with a conventional osteosarcoma and a raised CRP were at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients with a suspected sarcoma of bone as a further prognostic indicator of survival. Cite this article: Bone Joint J 2013;95-B:411-18.
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[817]
TÍTULO / TITLE: - Application of a stochastic modeling to assess the evolution of tuberculous and non-tuberculous mycobacterial infection in patients treated with tumor necrosis factor inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55017. doi: 10.1371/journal.pone.0055017. Epub 2013 Jan 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055017
AUTORES / AUTHORS: - Agliari E; Asti L; Barra A; Scrivo R; Valesini G; Wallis RS
INSTITUCIÓN / INSTITUTION: - Dipartimento di Fisica, Universita di Parma, Parma, Italy. elena.agliari@fis.unipr.it
RESUMEN / SUMMARY: - In this manuscript we apply stochastic modeling to investigate the risk of reactivation of latent mycobacterial infections in patients undergoing treatment with tumor necrosis factor inhibitors. First, we review the perspective proposed by one of the authors in a previous work and which consists in predicting the occurrence of reactivation of latent tuberculosis infection or newly acquired tuberculosis during treatment; this is based on variational procedures on a simple set of parameters (e.g. rate of reactivation of a latent infection). Then, we develop a full analytical study of this approach through a Markov chain analysis and we find an exact solution for the temporal evolution of the number of cases of tuberculosis infection (re)activation. The analytical solution is compared with Monte Carlo simulations and with experimental data, showing overall excellent agreement. The generality of this theoretical framework allows to investigate also the case of non-tuberculous mycobacteria infections; in particular, we show that reactivation in that context plays a minor role. This may suggest that, while the screening for tuberculous is necessary prior to initiating biologics, when considering non-tuberculous mycobacteria only a watchful monitoring during the treatment is recommended. The framework outlined in this paper is quite general and could be extremely promising in further researches on drug-related adverse events.
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[818]
TÍTULO / TITLE: - Bone Scan Index: a prognostic imaging biomarker for high-risk prostate cancer patients receiving primary hormonal therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - EJNMMI Res. 2013 Feb 6;3(1):9. doi: 10.1186/2191-219X-3-9.
●● Enlace al texto completo (gratuito o de pago) 1186/2191-219X-3-9
AUTORES / AUTHORS: - Kaboteh R; Damber JE; Gjertsson P; Hoglund P; Lomsky M; Ohlsson M; Edenbrandt L
INSTITUCIÓN / INSTITUTION: - Department of Molecular and Clinical Medicine, Clinical Physiology, Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, 413 45, Sweden. kaboteh@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: The objective of this study was to explore the prognostic value of the Bone Scan Index (BSI) obtained at the time of diagnosis in a group of high-risk prostate cancer patients receiving primary hormonal therapy. METHODS: This was a retrospective study based on 130 consecutive prostate cancer patients at high risk, based on clinical stage (T2c/T3/T4), Gleason score (8 to 10) and prostate-specific antigen (PSA) (> 20 ng/mL), who had undergone whole-body bone scans < 3 months after diagnosis and who received primary hormonal therapy. BSI was calculated using an automated method. Cox proportional-hazards regression models were used to investigate the association between clinical stage, Gleason score, PSA, BSI and survival. Discrimination between prognostic models was assessed using the concordance index (C-index). RESULTS: In a multivariate analysis, Gleason score (p = 0.01) and BSI (p < 0.001) were associated with survival, but clinical stage (p = 0.29) and PSA (p = 0.57) were not prognostic. The C-index increased from 0.66 to 0.71 when adding BSI to a model including clinical stage, Gleason score and PSA. The 5-year probability of survival was 55% for patients without metastases, 42% for patients with BSI < 1, 31% for patients with BSI = 1 to 5, and 0% for patients with BSI > 5. CONCLUSIONS: BSI can be used as a complement to PSA to risk-stratify high-risk prostate cancer patients at the time of diagnosis. This imaging biomarker, reflecting the extent of metastatic disease, can be of value both in clinical trials and in patient management when deciding on treatment.
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[819]
TÍTULO / TITLE: - An Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin) [ASCENT].
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 15;13:120. doi: 10.1186/1471-2407-13-120.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-120
AUTORES / AUTHORS: - Clarke S; Burge M; Cordwell C; Gibbs P; Reece W; Tebbutt N
INSTITUCIÓN / INSTITUTION: - Royal North Shore Hospital, St Leonards, NSW 2065, Australia. stephen.clarke@sydney.edu.au.
RESUMEN / SUMMARY: - BACKGROUND: The use of bevacizumab in combination with fluoropyrimidine-containing chemotherapy is a well-established first-line and second-line treatment for patients with metastatic colorectal cancer (mCRC). However, there remains a need for reproducible, validated, inexpensive and accessible prognostic markers to aid treatment selection. The optimal treatment duration and the role of bevacizumab in certain patient subgroups, considered at particular risk of bevacizumab-mediated toxicity, also require further investigation. The aim of the ASCENT study [an Australian translational Study to evaluate the prognostic role of inflammatory markers in patients with metastatic ColorEctal caNcer Treated with bevacizumab (Avastin)] is to evaluate the relationship between the host inflammatory response as measured by neutrophil/lymphocyte ratio (NLR) and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. METHODS/DESIGN: This open-label, prospective, single arm, phase IV, Australian multi-centre study evaluates the relationship between the host inflammatory response as measured by NLR and treatment outcomes in patients with previously untreated mCRC receiving bevacizumab-based first- and second-line treatment. 150 patients will be recruited from 16 centres around Australia. Patients will receive trial treatments in two phases: Phase A: XELOX or mFOLFOX6 plus bevacizumab administered from study start until first disease progression; and Phase B: FOLFIRI plus bevacizumab administered from first disease progression until second disease progression. The primary analysis will test the association between NLR and progression free survival using a proportional Hazards Model. Secondary analyses will investigate whether the relationship can be improved upon with other prognostic biomarkers, and further characterise the safety of bevacizumab following treatment initiation, and when continued after progression in combination with standard chemotherapy regimens (presented through summary statistics and Kaplan Meier curves). DISCUSSION: Quantifying the relationship between NLR and PFS will inform decision making on the extent to which this simple metric may be applied clinically. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01588990.
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[820]
TÍTULO / TITLE: - Allogeneic hematopoietic stem cell transplantation for the treatment of chronic myeloid leukemia in the era of tyrosine kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Feb;126(4):768-74.
AUTORES / AUTHORS: - Xu LP; Huang XJ
INSTITUCIÓN / INSTITUTION: - People’s Hospital and Institute of Hematology, Peking University, Beijing Key laboratory of Hematopoitic Stem Cell Transplantation, Beijing 100044, China.
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[821]
TÍTULO / TITLE: - Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Feb;126(4):688-91.
AUTORES / AUTHORS: - Zhu HL; Wang Y; Li XP; Wang CH; Wang Y; Cui H; Wang JL; Wei LH
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing 100044, China.
RESUMEN / SUMMARY: - BACKGROUND: Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients’ future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists (GnRHa) cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients. METHODS: Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People’s Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy (n = 5) without GnRHa or were historical controls (n = 11). The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups. RESULTS: There were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One (1/16) patient in the study group while 2 (2/16) patients in the control group relapsed 2 years after conclusion of the primary treatment (P > 0.05). All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment (P < 0.05). There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy. CONCLUSIONS: GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.
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[822]
TÍTULO / TITLE: - Gene diagnosis of micrometastases in regional lymph nodes of patients with stage I non-small cell lung cancer: impact on staging and prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1017-1
AUTORES / AUTHORS: - Li J; Li ZN; Yu LC; Shi SB; Ge LP; Wu JR; Hu YM
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, 438 North Jiefang Rood, Zhenjiang, 212001, China, lijian541226@163.com.
RESUMEN / SUMMARY: - PURPOSE: The long-term survival of patients with completely resected stage I non-small cell lung cancer (NSCLC) is not optimal because of undetected lymph node micrometastasis at the time of surgery. The aim of this study is to evaluate the role of survivin and livin mRNA expression in histopathologically negative lymph nodes of stage I NSCLC patients as markers of micrometastasis. METHODS: Clinical data and tissue samples of primary tumor and lymph nodes were collected from 44 patients with stage I NSCLC. Reverse-transcriptase-PCR (RT-PCR) was used to detect survivin and livin mRNA expression in these tumor and lymph node samples. RESULTS: Survivin mRNA was detected in all tumors, and livin mRNA was detectable in 39 of the 44 primary tumors. The cut-off values of survivin and livin mRNA levels for diagnosing micrometastasis in lymph nodes were set up according to the expression of survivin and livin mRNA in control lymph nodes. Fifteen (34.1 %) of 44 stage I NSCCL patients had micrometastasis in lymph nodes by survivin and/or livin mRNA positive expression. Survival analysis showed higher rate of cancer recurrences and tumor-related death in patients with lymph node micrometastasis (P < 0.001 and P = 0.001, respectively). Tumor-free survival and overall survival were significantly worse in patients with lymph node micrometastasis compared with those without such micrometastasis (P = 0.007 and P = 0.01, respectively). CONCLUSION: RT-RCR assay for survivin and livin mRNA can be considered as useful diagnostic tool for the detection of lymph node micrometastasis for stage I NSCLC patients.
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[823]
TÍTULO / TITLE: - A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 18;13(1):126.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-126
AUTORES / AUTHORS: - Pan X; Li Y; Feng J; Wang X; Hao B; Shi R; Zhang G
RESUMEN / SUMMARY: - BACKGROUND: Studies on the association between MDM2 SNP309 (T > G) and gastric cancer have reported conflicting results. Thus, the aim of this study was to investigate whether MDM2 SNP309 is associated with susceptibility and prognosis of gastric carcinoma in Chinese patients. METHODS: Total of 574 gastric carcinoma cases and 574 age- and sex-matched healthy controls were included. MDM2 polymorphism was detected by PCR- RFLP and infection of Helicobacter pylori (H. pylori) by a validated serology test. The functionality of MDM2 SNP309, with or without H. pylori lipopolysaccharide (LPS), was examined by dual-luciferase assay. Kaplan-Meier survival curves were used to evaluate survival. Additional, a meta-analysis was conducted to verity the findings. RESULTS: MDM2 SNP309G/G genotype was associated with an increased risk of gastric carcinoma when compared with T/T genotype or T carriers (both P < 0.01), and a joint effect between MDM2 SNP309G/G and H. pylori infection was observed to intensify gastric carcinoma risk. SNP309G/G was identified as an independent marker of poor overall survival of carcinoma. In vitro, the luciferase assay further showed an increased transcriptional activity of SNP309G allele compared with SNP309T allele, and the function of polymorphism T309G in MDM2 gene promoter was intensified by H. pylori LPS. Pooled results from the meta-analysis confirmed that SNP309G/G genotype had a significantly increased risk of gastric carcinoma compared with T/T genotype or T carriers, consistent with the case—control findings. CONCLUSIONS: MDM2 SNP309G allele is associated with an increased risk and poor prognosis of gastric carcinoma in Chinese patients. Additional, there is a joint effect of MDM2 SNP309G/G allele and H. pylori infection on gastric carcinoma development, which may attribute to H. pylori LPS.
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[824]
TÍTULO / TITLE: - Which imaging modality is superior for prediction of response to neoadjuvant chemotherapy in patients with triple negative breast cancer?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Oncol. 2013;2013:964863. doi: 10.1155/2013/964863. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/964863
AUTORES / AUTHORS: - Atkins JJ; Appleton CM; Fisher CS; Gao F; Margenthaler JA
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8109, St. Louis, MO 63110, USA.
RESUMEN / SUMMARY: - Background and Objectives. Triple negative breast cancer (TNBC) has been shown to be generally chemosensitive. We sought to investigate the utility of mammography (MMG), ultrasonography (US), and breast magnetic resonance imaging (MRI) in predicting residual disease following neoadjuvant chemotherapy for TNBC. Methods. We identified 148 patients with 151 Stage I-III TNBC treated with neoadjuvant chemotherapy. Residual tumor size was estimated by MMG, US, and/or MRI prior to surgical intervention and compared to the subsequent pathologic residual tumor size. Data were compared using chi-squared test. Results. Of 151 tumors, 44 (29%) did not have imaging performed prior to surgical treatment. Thirty-eight (25%) tumors underwent a pathologic complete response (pCR), while 113 (75%) had residual invasive disease. The imaging modality was accurate to within 1 cm of the final pathologic residual disease in 74 (69%) cases and within 2 cm in 94 (88%) cases. Groups were similar with regards to patient age, race, tumor size and grade, and clinical stage (P > 0.05). Accuracy to within 1 cm was the highest for US (83%) and the lowest for MMG (56%) (P < 0.05). Conclusions. Breast US and MRI were more accurate than MMG in predicting residual tumor size following neoadjuvant chemotherapy in patients with TNBC. None of the imaging modalities were predictive of a pCR.
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[825]
TÍTULO / TITLE: - Development of a robust flow cytometry-based pharmacodynamic assay to detect phospho-protein signals for phosphatidylinositol 3-kinase inhibitors in multiple myeloma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Mar 23;11(1):76.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-76
AUTORES / AUTHORS: - Li C; Takahashi C; Zhang L; Huseni M; Stankovich B; Mashhedi H; Lee J; French D; Anderson JE; Kim D; Howell K; Brauer M; Kowanetz M; Yan Y; Humke E; Ebens A; Hampton G; Lackner M; Hegde P; Jia S
RESUMEN / SUMMARY: - BACKGROUND: The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in multiple myeloma (MM), a blood cancer associated with uncontrolled proliferation of bone marrow plasma cells. This study aimed to develop a robust clinical pharmacodynamic (PD) assay to measure the on-target PD effects of the selective PI3K inhibitor GDC-0941 in MM patients. METHODS: We conducted an in vitro drug wash-out study to evaluate the feasibility of biochemical approaches in measuring the phosphorylation of S6 ribosomal protein (S6), one of the commonly used PD markers for PI3K pathway inhibition. We then developed a 7-color phospho-specific flow cytometry assay, or phospho flow, to measure the phosphorylation state of intracellular S6 in bone marrow aspirate (BMA) and peripheral blood (PB). Integrated mean fluorescence intensity (iMFI) was used to calculate fold changes of phosphorylation. Assay sensitivity was evaluated by comparing phospho flow with Meso Scale Discovery (MSD) and immunohistochemistry (IHC) assays. Finally, a sample handling method was developed to maintain the integrity of phospho signal during sample shipping and storage to ensure clinical application. RESULTS: The phospho flow assay provides single-cell PD monitoring of S6 phosphorylation in tumor and surrogate cells using fixed BMA and PB, assessing pathway modulation in response to GDC-0941 with sensitivity similar to that of MSD assay. The one-shot sample fixation and handling protocol herein demonstrated exceptional preservation of protein phosphorylation. In contrast, IHC assay was less sensitive in terms of signal quantification while biochemical approach (MSD) were less suitable to assess PD activities due to the undesirable impact associated with cell isolation on the protein phosphorylation in tumor cells. CONCLUSIONS: We developed a robust PD biomarker assay for the clinical evaluation of PI3K inhibitors in MM, allowing one to decipher the PD response in a relevant cell population. To our knowledge, this is the first report of an easily implemented clinical PD assay that incorporates an unbiased one-shot sample handling protocol, all (staining)-in-one (tube) phospho flow staining protocol, and an integrated modified data analysis for PD monitoring of kinase inhibitors in relevant cell populations in BMA and PB. The methods described here ensure a real-time, reliable and reproducible PD readout, which can provide information for dose selection as well as help to identify optimal combinations of targeted agents in early clinical trials.
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[826]
TÍTULO / TITLE: - Hirsutanol A, a novel sesquiterpene compound from fungus Chondrostereum sp., induces apoptosis and inhibits tumor growth through mitochondrial-independent ROS production: Hirsutanol A inhibits tumor growth through ROS production.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Feb 8;11(1):32.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-32
AUTORES / AUTHORS: - Yang F; Chen WD; Deng R; Zhang H; Tang J; Wu KW; Li DD; Feng GK; Lan WJ; Li HJ; Zhu XF
RESUMEN / SUMMARY: - ABSTRACT: BACKGROUND: Hirsutanol A is a novel sesquiterpene compound purified from fungus Chondrostereum sp. in Sarcophyton tortuosum. Our previous studies had demonstrated that hirsutanol A exhibited potent cytotoxic effect on many kinds of cancer cell lines. In the current study, the antitumor activity of hirsutanol A and its molecular mechanisms were investigated. METHODS: Hirsutanol A induced growth inhibition and apoptotic cell death of human colon cancer SW620 cells and human breast cancer MDA-MB-231cells were determined using MTT assay and flow cytometry assay, respectively. The effect of hirsutanol A on intrinsic ROS level and change in mitochondrial membrane potential ([white up-pointing triangle]psim) of different cell lines were also measured by flow cytometry assay. The function of JNK was compromised by JNK siRNA or JNK inhibitor SP600125. The expression of cytochrome c, p-JNK, p-c-Jun after treatment with hirsutanol A were detected by Western blot analysis. Finally, the in vivo anti-tumor effect of hirsutanol A was examined in human cancer cell SW620 xenograft model. RESULTS: The results showed that hirsutanol A significantly induced apoptosis, mitochondrial-independent increase of Reactive Oxygen Species (ROS) level, change of mitochondrial membrane potential, release of cytochrome c in human cancer cells. Preventing increase of ROS level using the potent antioxidant N-acetyl-L-cysteine (NAC) markedly decreased hirsutanol A-induced apoptosis. In addition, JNK signaling pathway was activated by hirsutanol A through elevating ROS level. Blockade of JNK signaling pathway by JNK specific inhibitor SP600125 enhanced apoptosis and hirsutanol A-induced ROS accumulation. Also, hirsutanol A exhibited antitumor activity in human cancer cell SW620 xenograft model. CONCLUSION: These data suggested that hirsutanol A inhibited tumor growth through triggering ROS production and apoptosis.
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[827]
TÍTULO / TITLE: - Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 15;13:78. doi: 10.1186/1471-2407-13-78.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-78
AUTORES / AUTHORS: - Oh BS; Jang JW; Kwon JH; You CR; Chung KW; Kay CS; Jung HS; Lee S
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, The Catholic University of Korea, Incheon St, Mary’s Hospital, Incheon, Korea. garden@catholic.ac.kr.
RESUMEN / SUMMARY: - BACKGROUND: Accumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC). METHODS: The study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements. RESULTS: With the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, alpha-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001). CONCLUSIONS: CRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.
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[828]
TÍTULO / TITLE: - Detection of EGFR T790M Mutation in Pericardial Effusion from a Non-Small Cell Lung Cancer Patient with Erlotinib Therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Oncol. 2013 Jan;6(1):15-20. doi: 10.1159/000345947. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 1159/000345947
AUTORES / AUTHORS: - Sakai A; Kasahara K; Sone T
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.
RESUMEN / SUMMARY: - We report the case of a Japanese male with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitive lung adenocarcinoma, who had an EGFR mutation and presented in the emergency department with acute cardiac tamponade as the recurrence during EGFR-TKI therapy. We could detect a second mutation, T790M in exon 20 in the pericardial effusion. This is the first report to detect the resistant mutation T790M in pericardial effusion. We suggest that the pericardial effusion may therefore be useful as surrogate tissue for detecting EGFR mutation.
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[829]
TÍTULO / TITLE: - Preoperative serum C- reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 6;13:101. doi: 10.1186/1471-2407-13-101.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-101
AUTORES / AUTHORS: - Stein B; Schrader AJ; Wegener G; Seidel C; Kuczyk MA; Steffens S
INSTITUCIÓN / INSTITUTION: - Department of Urology, Hannover Medical School, Carl-Neuberg-Str, 1, Hannover, D-30625, Germany. steffens.sandra@mh-hannover.de.
RESUMEN / SUMMARY: - BACKGROUND: To analyse the prognostic significance of preoperative C-reactive protein (CRP) serum level in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We evaluated 158 UUT-UC patients who had undergone surgery in the University Hospital of Hannover (MHH). 143 (89.4%) suffered from cancer in the renal pelvis, 13 (8.1%) patients presented with tumour located in the ureter. A preoperative CRP value was available for 115 patients. The mean (median) follow-up for these patients was 28.3 (15.1) months. RESULTS: The median (mean) CRP value of all evaluable patients was 10.0 (40.7) mg/l. The CRP-level, stratified into two subgroups (CRP </=5 vs. >5 mg/l), correlated significantly with muscle invasive tumour stage (36.4 vs. 78.9%; p<0.001), the risk of presenting nodal disease (4.5 vs. 26.8%; p=0.002) and distant metastasis (2.3 vs. 16.9%; p<0.016). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 54.2 and 26.4% for patients with preoperative CRP levels </= and >5 mg/l, respectively (p<0.006). Next to age and the presence of metastasis, multivariate analysis also identified CRP as a continuous variable as an independent prognosticator for CSS. CONCLUSIONS: A high preoperative serum CRP level is associated with locally advanced and metastatic disease in patients with UUT-UC. Its routine use could allow better risk stratification and risk-adjusted follow-up of UUT-UC patients.
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[830]
TÍTULO / TITLE: - Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56208. doi: 10.1371/journal.pone.0056208. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056208
AUTORES / AUTHORS: - Ji X; Xie C; Hu D; Fan X; Zhou Y; Zheng Y
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. xuemei.ji@yahoo.com
RESUMEN / SUMMARY: - BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS), metastasis-free survival (MFS), relapse-free survival (RFS), and disease-free survival (DFS) were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03), patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03), neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.
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[831]
TÍTULO / TITLE: - Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-kappaB/IKK pathway-induced apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e50175. doi: 10.1371/journal.pone.0050175. Epub 2013 Jan 24.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0050175
AUTORES / AUTHORS: - Wang Y; Wang H; Zhang W; Shao C; Xu P; Shi CH; Shi JG; Li YM; Fu Q; Xue W; Lei YH; Gao JY; Wang JY; Gao XP; Li JQ; Yuan JL; Zhang YT
INSTITUCIÓN / INSTITUTION: - Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China.
RESUMEN / SUMMARY: - Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-kappaB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-kappaB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.
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[832]
TÍTULO / TITLE: - Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Mar;126(5):937-41.
AUTORES / AUTHORS: - Chen ZF; Li YB; Han JY; Yin JJ; Wang Y; Zhu LB; Xie GY
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
RESUMEN / SUMMARY: - BACKGROUND: The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells). METHODS: INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation. RESULTS: The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone. CONCLUSIONS: Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.
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[833]
TÍTULO / TITLE: - A three-gene signature as potential predictive biomarker for irinotecan sensitivity in gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Mar 22;11(1):73.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-73
AUTORES / AUTHORS: - Shen J; Wei J; Wang H; Yue G; Yu L; Yang Y; Xie L; Zou Z; Qian X; Ding Y; Guan W; Liu B
RESUMEN / SUMMARY: - OBJECTIVE: Personalized chemotherapy based on molecular biomarkers can maximize anticancer efficiency. We aim to investigate predictive biomarkers capable of predicting response to irinotecan-based treatment in gastric cancer. METHODS: We examined gene expression of APTX, BRCA1, ERCC1, ISG15, Topo1 and methylation of SULF2 in formalin-fixed paraffin-embedded gastric cancer tissues from 175 patients and evaluated the association between gene expression levels or methylation status and in vitro sensitivity to irinotecan. We used multiple linear regression analysis to develop a gene-expression model to predict irinotecan sensitivity in gastric cancer and validated this model in vitro and vivo. RESULTS: Gene expression levels of APTX, BRCA1 and ERCC1 were significantly lower in irinotecan-sensitive gastric cancer samples than those irinotecan-resistant samples (P < 0.001 for all genes), while ISG15 (P = 0.047) and Topo1 (P = 0.002) were significantly higher. Based on those genes, a three-gene signature were established, which was calculated as follows: Index =0.488 - 0.020x expression level of APTX + 0.015x expression level of Topo1 - 0.011 x expression level of BRCA1. The three-gene signature was significantly associated with irinotecan sensitivity (rho = 0.71, P < 0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity based on the three-gene signature reached 73% and 86%, respectively. In another independent testing set, the irinotecan inhibition rates in gastric samples with sensitive-signature were much higher than those with resistant-signature (65% vs. 22%, P < 0.001). Irinotecan therapy with 20 mg/kg per week to immunodeficient mice carrying xenografts with sensitive-signature dramatically arrested the growth of tumors (P < 0.001), but had no effect on mice carrying xenografts with resistant-signature. CONCLUSIONS: The three-gene signature established herein is a potential predictive biomarker for irinotecan sensitivity in gastric cancer.
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[834]
TÍTULO / TITLE: - Comparison of lymphocyte apoptotic index and qualitative DNA damage in yoga practitioners and breast cancer patients: A pilot study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Yoga. 2013 Jan;6(1):20-5. doi: 10.4103/0973-6131.105938.
●● Enlace al texto completo (gratuito o de pago) 4103/0973-6131.105938
AUTORES / AUTHORS: - Ram A; Banerjee B; Hosakote VS; Rao RM; Nagarathna R
INSTITUCIÓN / INSTITUTION: - Division of Yoga Life Sciences, SVYASA, Bangalore, India.
RESUMEN / SUMMARY: - BACKGROUND: Yoga is found to be effective in reducing stress levels and radiation-induced DNA damage, and improving the quality of life, in breast cancer patients. The present study was aimed at comparing the apoptotic index (AI) and DNA damage of advanced yoga practitioners with those of breast cancer patients. MATERIALS AND METHODS: This cross-sectional pilot study compared three groups (n = 9 each) of age-matched subjects viz. (1) Carcinoma breast patients in stage II or III undergoing radiation therapy after completing three cycles of chemotherapy; (2) Senior yoga practitioners who were practicing asanas, pranayama and meditation daily for more than 10 years; and (3) Normal healthy volunteers. Peripheral blood lymphocytes were isolated, and qualitative DNA damage (QDD) and AI were evaluated by single-cell gel electrophoresis assay. Approximately 500 cells were counted in each case. Number of cells that were normal, undergoing apoptosis, and with DNA damage were categorized and percentages were calculated. RESULTS: Data being normally distributed, one-way analysis of variance (ANOVA) showed significant interaction between groups in AI (P = 0.016) and QDD (P = 0.045). On post-hoc analysis using Scheffe test, AI was significantly lower in non-yoga volunteers as compared with the breast cancer group (P = 0.019) and QDD was significantly lower in yoga practitioners when compared with non-yoga volunteers (P = 0.047). CONCLUSION: Cellular dysfunction (QDD) requires restorative mechanisms (AI) to restore the system to a balance. The results of this pilot study show trends, which indicate that in ill-health, there is inadequate restorative mechanisms (AI) although dysfunction (QDD) is high. Through regular practice of yoga, cellular dysfunction can be lowered, thus necessitating reduced restorative mechanisms. AI and QDD could also be useful indicators for predicting the three zones of health viz. disease, health, and positive health.
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[835]
TÍTULO / TITLE: - Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e51021. doi: 10.1371/journal.pone.0051021. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0051021
AUTORES / AUTHORS: - Wang S; An T; Duan J; Zhang L; Wu M; Zhou Q; Chen J; Zhuo M; Yang L; Wang Y; Bai H; Wang J
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.
RESUMEN / SUMMARY: - INTRODUCTION: Genetic aberrancies within epidermal growth factor receptor (EGFR) pathway are associated with therapeutic outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on EGFR-related genes alterations has not been defined in NSCLC. Our study aims to investigate the impact of neoadjuvant chemotherapy (Neoadj-Chemo) on EGFR activating mutations and associated EGFR-TKIs resistance-related genes. PATIENTS AND METHODS: Matched tumor samples were obtained retrospectively from 66 NSCLC patients (stages IIb-IIIb) corresponding to pre- and post- Neoadj-Chemo. EGFR mutations were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by Amplification Refractory Mutation System technology (ARMS), KRAS mutations, T790M mutation and c-MET amplification were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), ARMS, and real-time PCR, respectively. RESULTS: Before Neoadj-Chemo, EGFR mutations were identified in 33.3% (22/66) of NSCLC patients. Only 18.2% (12/66) of patients carried EGFR mutations after Neoadj-Chemo (p = 0.013). The median peak value of EGFR 19 exon mutations decreased non-significantly after Neoadj-Chemo. KRAS mutation rate decreased from 4.6% (3/66) to 3.0% (2/66) with Neoadj-Chemo. Although the overall percentage of patients exhibiting c-MET amplifications (6.1% [4/66]) did not change with Neoadj-Chemo, two patients transitioned from negative to positive c-MET amplification, and two patients reversed these changes post-Neoadj-Chemo. T790M mutations were absent from all samples. CONCLUSION: Neoadjuvant chemotherapy tends to decrease the mutation frequency of EGFR mutation and downstream genes, which suggests that real-time samples analysis for genetic aberrancies within EGFR pathways have important value to delineate specific patient populations and facilitate individualized treatment.
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[836]
TÍTULO / TITLE: - Promoter methylation of Wnt antagonist DKK1 gene and prognostic value in Korean patients with non-small cell lung cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biomark. 2012 Jan 1;12(2):73-9. doi: 10.3233/CBM-2012-00295.
●● Enlace al texto completo (gratuito o de pago) 3233/CBM-2012-00295
AUTORES / AUTHORS: - Na Y; Lee SM; Kim DS; Park JY
INSTITUCIÓN / INSTITUTION: - College of Nursing, Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea.
RESUMEN / SUMMARY: - Dickkopf-1 (DKK1) is known as a negative regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, aberrant expression and the role of DKK1 in human cancers remain controversial. To estimate the role of DKK1 and its prognostic potential in lung cancer, promoter methylation of DKK1 was evaluated in 139 primary non-small cell lung cancers (NSCLCs) by methylation-specific PCR and its association with clinical and prognostic parameters. DKK1 hypermethylation was detected in 48.9% of neoplastic lung tissues and was significantly more frequent in stage I than the more advanced stages II-IIIA (P=0.04). Additionally, patients with DKK1 methylation had a better overall survival than those with no methylation under univariate analysis. When stratified by clinicopathologic features, DKK1 methylation was significantly associated with a favorable survival in a subset of patients. The current findings suggested that DKK1 promoter methylation may be a tumor-associated event in the early stage of NSCLC and could also be useful prognostic indicator for NSCLC. Further work may clarify the molecular basis of DKK1 action in progression of NSCLC.
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[837]
TÍTULO / TITLE: - Imatinib failure and response to dasatinib in a patient with chronic myeloid leukemia in blast crisis and a novel, nine-nucleotide BCR-ABL insertion mutation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Blood Cancer J. 2013 Mar 8;3:e104. doi: 10.1038/bcj.2013.3.
●● Enlace al texto completo (gratuito o de pago) 1038/bcj.2013.3
AUTORES / AUTHORS: - Sigl M; Spoerl S; Schnittger S; Meissner J; Rummelt C; Peschel C; Duyster J; Ho AD; von Bubnoff N
INSTITUCIÓN / INSTITUTION: - III Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universitat Munchen, Munchen, Germany.
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[838]
TÍTULO / TITLE: - 5-HTTLPR polymorphism and anxious preoccupation in early breast cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiol Oncol. 2012 Dec;46(4):321-7. doi: 10.2478/v10019-012-0024-0. Epub 2012 Nov 9.
●● Enlace al texto completo (gratuito o de pago) 2478/v10019-012-0024-0
AUTORES / AUTHORS: - Schillani G; Era D; Cristante T; Mustacchi G; Richiardi M; Grassi L; Giraldi T
INSTITUCIÓN / INSTITUTION: - Department of Life Sciences, University of Trieste, Trieste, Italy.
RESUMEN / SUMMARY: - BACKGROUND: Difficulties in coping with cancer, and the accompanying anxious and depressive symptoms, have been shown to affect the mood and the quality of life in breast cancer patients. 5-Hydroxytryptamine Transporter Gene-linked Polymorphic Region (5-HTTLPR) functional polymorphism of serotonin transporter has been shown to influence the adaptation to stressful life events. The aim of this prospective study was therefore to examine the association of 5-HTTLPR with the mental adaptation to cancer diagnosis and treatment. PATIENTS AND METHODS: Forty eight consecutive patients with early mammary carcinoma were evaluated at enrolment and at follow up after one and three months. The patients were characterized psychometrically using the Hospital Anxiety and Depression Scale (HADS) and the Mini-Mental Adjustment to Cancer Scale (Mini-MAC); 5-HTTLPR allelic variants were determined using PCR-based techniques. RESULTS: In women with early breast cancer, the mental adaptation to the disease was associated with high scores of avoidance and anxious preoccupation of Mini-MAC, which decreased with time at follow up. Anxious preoccupation decreased with time less in patients with the S/S and S/L genetic variant of 5-HTTLPR as compared with the L/L carriers (p=0.023), indicating gene - environment interactions. CONCLUSIONS: These results indicate that the characterization of 5-HTTLPR allows the identification of breast cancer patients in greater risk of mental suffering, for which specific intervention may be focused; in case of drug therapy, they provide indications for the choice of most appropriate agent in a pharmacogenetic perspective.
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[839]
TÍTULO / TITLE: - Inhibition of Androgen Receptor Expression with Small Interfering RNA Enhances Cancer Cell Apoptosis by Suppressing Survival Factors in Androgen Insensitive, Late Stage LNCaP Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ScientificWorldJournal. 2013;2013:519397. doi: 10.1155/2013/519397. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/519397
AUTORES / AUTHORS: - Kim SS; Cho HJ; Kang JY; Kang HK; Yoo TK
INSTITUCIÓN / INSTITUTION: - Eulji Medi-Bio Research Institute, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - Introduction.The aim was to evaluate the changes of androgen receptor (AR) expression quantitatively and to identify influence of AR on cancer related survival markers in LNCap cell line. Materials and Methods. We compared expressions of AR, heat shock protein 27 (HSP27), clusterin (CLU), glucose-related protein 78 (GRP78), and cellular FLICE-like inhibitory protein (c-FLIP) and their genes between es-LNCaP (less than 33 times subcultured, L-33), ls-LNCaP (over 81 times subcultured, H-81), and si-LNCaP (AR siRNA transfected ls-LNCaP) by Western blotting and RT-PCR. Results. The expressions of AR, HSP27, CLU, GRP78, and c-FLIP were increased in ls-LNCaP compared with es-LNCaP (AR, 157%; HSP27, 132%; CLU, 146%; GRP78, 138%; c-FLIP, 152%). However, in si-LNCaP cell line, protein expressions were reversed to the level of es-LNCaP cell lines (25, 102, 109, 98, and 101%), and gene expressions on real-time PCR were also reversed to the expression level of es-LNCaP (ls-LNCaP: 179, 156, 133, 123, and 167%; si-LNCaP: 22, 93, 103, 112, and 107%). Conclusions. This finding suggests that androgen receptor can be related to the increased expression of cancer related survival markers such as HSP27, GRP78, CLU, and c-FLIP in late stage prostate cancer, and also inhibition of AR gene can be a therapeutic target in this stage of cancer.
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[840]
TÍTULO / TITLE: - Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastroenterol Res Pract. 2013;2013:107534. doi: 10.1155/2013/107534. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/107534
AUTORES / AUTHORS: - Wang J; El-Masry N; Talbot I; Tomlinson I; Alison MR; El-Bahrawy M
INSTITUCIÓN / INSTITUTION: - Department of Histopathology, Imperial College London, Hammersmith Hospital, DuCane Road, London W12 0HS, UK.
RESUMEN / SUMMARY: - Introduction. Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway. This results in alterations in cell proliferation and apoptosis. We investigated the expression of beta-catenin and related proliferation and apoptotic factors in FAP patients, exploring the expression along the adenoma-carcinoma sequence. Methods. The expression of beta-catenin, p53, bcl-2, cyclin-D1, caspase-3, CD10, and Ki-67 proteins was studied by immunohistochemistry in samples of colonic nonneoplastic mucosa (n = 71), adenomas (n = 152), and adenocarcinomas (n = 19) from each of the16 FAP patients. Results. The expression of beta-catenin, caspase-3, cyclin-D1, and Ki-67 was increased in both adenomas and carcinomas in FAP patients, compared with normal mucosa. p53 and CD10 expression was only slightly increased in adenomas, but more frequently expressed in carcinomas. Bcl-2 expression was increased in adenomas, but decreased in carcinomas. Conclusion. This is the first study investigating collectively the expression of these molecules together in nonneoplastic mucosa, adenomas, and carcinomas from FAP patients. We find that beta-catenin and related proliferative and apoptotic factors (cyclin-D1, bcl-2, caspase-3, and Ki-67) are expressed early in the sequence, in adenomas. However, p53 and CD10 are often expressed later in the sequence, in carcinomas.
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[841]
TÍTULO / TITLE: - Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Mar;5(3):902-906. Epub 2012 Dec 24.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.878
AUTORES / AUTHORS: - Ghimenti C; Mello-Grand M; Grosso E; Scatolini M; Regolo L; Zambelli A; Chiorino G
INSTITUCIÓN / INSTITUTION: - Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia Valenta, Biella;
RESUMEN / SUMMARY: - Aromatase inhibitors (AIs), such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, approximately 20% of patients with hormone receptor-positive breast tumors treated with anastrozole do not respond and it remains impossible to accurately predict sensitivity. Since polymorphisms in the aromatase gene may influence the response to inhibitory drugs, we evaluated the presence of rs6493497 and rs7176005 polymorphisms (mapping in the 5’-flanking region of the CYP19A1 gene coding for the aromatase protein) in a cohort of 37 patients with postmenopausal breast cancer who received three-month neoadjuvant treatment with anastrozole. We then investigated any association of the polymorphisms with changes in aromatase mRNA expression change and/or response to treatment. We also analyzed five miRNAs computationally predicted to target aromatase, to observe any association between their expression and sensitivity to anastrozole. Three samples carried the two polymorphisms and the remaining samples were wild-type for both, however, no association with response or with aromatase mRNA basal expression level or expression difference after therapy was observed. Polymorphic samples that were resistant to anastrozole showed no change or decrease in aromatase expression following AI treatment, whereas an increase in expression was observed for the polymorphic responsive samples. No statistically significant correlation was observed between miRNA and aromatase mRNA expression, or with response to anastrozole neoadjuvant treatment. These data indicate that the polymorphisms analyzed are not involved in aromatase activity and that other epigenetic mechanisms may regulate aromatase protein expression.
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[842]
TÍTULO / TITLE: - Serum vascular endothelial growth factor (VEGF-C) as a diagnostic and prognostic marker in patients with ovarian cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55309. doi: 10.1371/journal.pone.0055309. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055309
AUTORES / AUTHORS: - Cheng D; Liang B; Li Y
INSTITUCIÓN / INSTITUTION: - Department of Transfusion, The First Hospital of China Medical University, Shenyang, China. dayecheng_cmu@yahoo.cn
RESUMEN / SUMMARY: - VEGF-C is regarded as one of the most efficient factors in regulating lymphangiogenesis. The aim of this study was to better understand the role of VEGF-C in the progression of ovarian cancer and to assess its diagnostic and prognostic significance. A total of 109 patients with ovarian cancer, 76 patients with benign ovarian diseases, and 50 healthy controls were recruited in this study. Serum levels of VEGF-C were determined by ELISA method. The results showed that serum levels of VEGF-C were significantly higher in the patients with ovarian cancer than those with benign ovarian diseases and healthy controls (P<0.01). Serum level of VEGF-C was correlated with FIGO stage, lymph node metastasis, tumor resectability, and survival of the patients (P<0.05). The areas of receiver operating curves of VEGF-C were higher than those of CA125 in different screening groups. Analysis using the Kaplan-meier method indicated that patients with high VEGF-C had significantly shorter overall survival time than those with low VEGF-C (P<0.0001). In a multivariate analysis along with clinical prognostic parameters, serum VEGF-C was identified as an independent adverse prognostic variable for overall survival. These results indicated that serum VEGF-C may be a clinically useful indicator for diagnostic and prognostic evaluation in ovarian cancer patients.
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[843]
TÍTULO / TITLE: - Can cyclo-oxygenase-2 be a useful prognostic and risk stratification marker in breast cancer?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Indian Med Assoc. 2012 Jul;110(7):429-33.
AUTORES / AUTHORS: - Jana D; Sarkar DK; Maji A; Chikkala BR; Hassanujjaman S; Mukhopadhyay M; Ganguly S
INSTITUCIÓN / INSTITUTION: - Breast Cancer Research Unit, Breast Service, Department of Surgery, IPGME&R, Kolkata 700020.
RESUMEN / SUMMARY: - Cyclo-oxygenase-2 (COX-2) is a prostaglandin synthease that catalyses the synthesis of prostaglandin G2 (PGG2) and PGH2 from arachidonic acid. COX-2 plays an important role in tumourigenesis of different carcinoma types and it is thought to take part in breast carcinoma. In this study, the aim was to investigate the relationship of COX-2 with clinical parameters such as menopausal status, tumour size, grade, nodal status, Nottingham prognostic index (NPI), oestrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER-2/ neu). The patients were divided into two groups, first group (group A) comprised 57 primary breast cancer patients and the second group (group B) comprised control group 27 patients consisting of fibro-adenoma and benign breast disease. In control groups COX-2 (0%) is not over expressed and we observed that high frequency of COX-2 (73.68%) over expressed in breast carcinoma. In high grade, large tumour size and positive lymph node metastasis, COX-2 expression rate was 78.6%, 59.5% and 90.5% respectively. COX-2 expression is directly correlated with ER negative (88.1%, p = 0.001) and also associated with higher NPI value (78.6%, p = 0.006). In invasive ductal carcinoma (IDC) COX-2 over expression had a significant relationship with HER-2/neu over expression (p < 0.001). The results indicated that COX-2 over expression correlates with aggressive phenotypic features, such as high histological grade, large tumour size, higher NPI value, ER negativity and HER-2/neu positivity.
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[844]
TÍTULO / TITLE: - The incidence and prognostic value of HER2 overexpression and cyclin D1 expression in patients with gastric or gastroesophageal junction adenocarcinoma in Israel.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):559-563. Epub 2012 Nov 16.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1031
AUTORES / AUTHORS: - Bar-Sela G; Hershkovitz D; Haim N; Kaidar-Person O; Shulman K; Ben-Izhak O
INSTITUCIÓN / INSTITUTION: - Division of Oncology, Rambam Healthcare Campus, Bat-Galim, Haifa 31096;
RESUMEN / SUMMARY: - Human epidermal growth factor 2 (HER2) positivity rates for gastric or gastroesophageal junction (GEJ) adenocarcinoma have been reported at 15-25%. Cyclin D1 (BCL1) is a non-specific proliferative marker. The prognostic significance of HER2 and cyclin D1 is inconclusive, with contradictory data. The aim of this study was to evaluate the incidence of HER2 overexpression in gastric or GEJ patients. The presence of a possible correlation between HER2 status and cyclin D1 staining was assessed; both were evaluated as prognostic markers for survival. The clinical data and histological specimens of 150 consecutive patients diagnosed with gastric or GEJ adenocarcinoma, and treated at our hospital from June 2005 to March 2009, were analyzed. Pathological specimens were immunohistochemically stained for HER2. Immunoreactivity was determined according to the scoring system for gastric carcinoma. Cyclin D1 immunoreactivity was also tested. The results demonstrated that HER2 was positive in 14/150 (9.3%) patients. HER2-positive (HER2(+)) and HER2-negative (HER2(-)) patients did not differ significantly with regard to other clinicopathological parameters. In a multivariate analysis, HER2 positivity was revealed to be a poor prognosis variable (P=0.046; 95% CI, 1.03-3.58). In patients with non-metastatic disease, median survival was 59 months for HER2(-) and 42 months for HER2+ patients, but this difference was not significant. In patients with metastatic disease, median survival was 9.5 months and 2.5 months for HER2(-) and HER2+ patients, respectively (P=0.041). Cyclin D1 was not idemonstrated to be a prognostic factor and was not associated with HER2 overexpression. The rate of positive HER2 status in the current group of unselected patients with gastric and GEJ adenocarcinoma was relatively low compared with that observed in the literature. Nevertheless, HER2 positivity was associated with a poor prognosis.
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[845]
TÍTULO / TITLE: - Adenovirus-mediated Interferon-gamma Gene Therapy Induced Human Pancreatic Carcinoma Capan-2 Cell Apoptosis In Vitro and In Vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anat Rec (Hoboken). 2013 Apr;296(4):604-10. doi: 10.1002/ar.22661. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1002/ar.22661
AUTORES / AUTHORS: - Xie FJ; Zhao P; Zhang YP; Liu FY; Nie XL; Zhu YH; Yu XM; Zheng QQ; Mao WM; Lu HY; Wei H; Huang W
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Zhejiang Cancer Hospital, HangZhou, 310022, China; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, HangZhou, 310022, China.
RESUMEN / SUMMARY: - Pancreatic cancer is one of the most lethal human malignancies with a very low 5-year survival rate, which highlights urgent needs for more effective therapeutic strategies. In this study, we examined the potential therapeutic effects of an adenovirus encoding human interferon gamma (Ad-IFNgamma) on pancreatic carcinoma cells Capan-2 in vitro and in vivo. The results indicated that Ad-IFNgamma could significantly inhibit tumor cell growth via inducing cell apoptosis. After infection, IFNgamma expressed durably and stably in xenografts, predominantly in tumor tissue, while much less in blood and liver. Thus, adenovirus-mediated intratumoral injection of human IFNgamma gene could be an effective gene therapeutic system for the treatment of pancreatic carcinoma. Anat Rec, 296:604-610, 2013. © 2013 Wiley Periodicals, Inc.
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[846]
TÍTULO / TITLE: - The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 4;13:56. doi: 10.1186/1471-2407-13-56.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-56
AUTORES / AUTHORS: - Russo F; Linsalata M; Clemente C; D’Attoma B; Orlando A; Campanella G; Giotta F; Riezzo G
INSTITUCIÓN / INSTITUTION: - Laboratory of Experimental Biochemistry, National Institute for Digestive Diseases I.R.C.C.S. Saverio de Bellis, Castellana Grotte, Bari, Italy.
RESUMEN / SUMMARY: - BACKGROUND: Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD). METHODS: Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21). RESULTS: During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(-) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(-) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14. CONCLUSIONS: Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(-) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions. TRIAL REGISTRATION: Clinical trial NCT01382667.
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[847]
TÍTULO / TITLE: - Modulation of MDR1 and MRP3 Gene Expression in Lung Cancer Cells after Paclitaxel and Carboplatin Exposure.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2012 Dec 5;13(12):16624-35. doi: 10.3390/ijms131216624.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms131216624
AUTORES / AUTHORS: - Melguizo C; Prados J; Luque R; Ortiz R; Caba O; Alvarez PJ; Gonzalez B; Aranega A
INSTITUCIÓN / INSTITUTION: - Institute of Biopathology and Regenerative Medicine (IBIMER), Department of Anatomy and Human Embryology, School of Medicine, University of Granada, Granada E-18071, España. jcprados@ugr.es.
RESUMEN / SUMMARY: - Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 muM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 muM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.
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[848]
TÍTULO / TITLE: - Improved therapeutic effect against leukemia by a combination of the histone methyltransferase inhibitor chaetocin and the histone deacetylase inhibitor trichostatin A.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Korean Med Sci. 2013 Feb;28(2):237-46. doi: 10.3346/jkms.2013.28.2.237. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 3346/jkms.2013.28.2.237
AUTORES / AUTHORS: - Tran HT; Kim HN; Lee IK; Nguyen-Pham TN; Ahn JS; Kim YK; Lee JJ; Park KS; Kook H; Kim HJ
INSTITUCIÓN / INSTITUTION: - Chonnam National University Hwasun Hospital, Hwasun, Korea.
RESUMEN / SUMMARY: - SUV39H1 is a histone 3 lysine 9 (H3K9)-specific methyltransferase that is important for heterochromatin formation and the regulation of gene expression. Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells. Histone deacetylase (HDAC) inhibitors inhibit deacetylases and accumulate high levels of acetylation lead to cell cycle arrest and apoptosis. In this study, we demonstrated that treatment with chaetocin enhanced apoptosis in human leukemia HL60, KG1, Kasumi, K562, and THP1 cells. In addition, chaetocin induced the expression of cyclin-dependent kinase inhibitor 2B (p15), E-cadherin (CDH1) and frizzled family receptor 9 (FZD9) through depletion of SUV39H1 and reduced H3K9 methylation in their promoters. Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes. Furthermore, this combined treatment significantly increased loss of SUV39H1 and reduced histone H3K9 trimethylation responses accompanied by increased acetylation. Importantly, co-treatment with chaetocin and TSA produced potent antileukemic effects in leukemia cells derived from patients. These in vitro findings suggest that combination therapy with SUV39H1 and HDAC inhibitors may be of potential value in the treatment of leukemia.
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[849]
TÍTULO / TITLE: - MTHFR polymorphisms and capecitabine-induced toxicity in patients with metastatic colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmacogenet Genomics. 2013 Apr;23(4):208-18. doi: 10.1097/FPC.0b013e32835ee8e1.
●● Enlace al texto completo (gratuito o de pago) 1097/FPC.0b013e32835ee8e1
AUTORES / AUTHORS: - van Huis-Tanja LH; Gelderblom H; Punt CJ; Guchelaar HJ
INSTITUCIÓN / INSTITUTION: - Departments of aClinical Oncology bClinical Pharmacy and Toxicology, Leiden University Medical Center cDepartment of Medical Oncology, Academic Medical Center, University of Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - OBJECTIVE: The availability of current chemotherapeutic options for metastatic colorectal cancer (mCRC) has increased survival, but it is also accompanied by considerable morbidity. Fluoropyrimidines are the mainstay of systemic therapy. Germline pharmacogenetic markers involved in 5-fluorouracil pharmacodynamics could provide individualized pretreatment tools for predicting toxicity. Research on methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and fluoropyrimidine treatment outcome has focused on intravenous 5-fluorouracil and has yielded inconclusive results. The literature on pharmacogenetics in capecitabine-based chemotherapy is scarce. Therefore, we analysed the association of MTHFR gene polymorphisms and the occurrence of serious toxicity of first-line capecitabine monotherapy and combination therapy. METHODS: One hundred and twenty-seven patients treated with first-line monotherapy capecitabine and 141 patients on capecitabine-irinotecan combination therapy were recruited from the CAIRO trial, an open-label phase III randomized trial, comparing sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in mCRC. All patients were genotyped for MTHFR 1298A>C and 677C>T polymorphisms and analysed in both cohorts separately for the association between the MTHFR genotype and incidence of grade 3-4 overall toxicity and specific adverse events, as well as efficacy parameters. RESULTS: MTHFR 1298A>C and 677C>T genotypes were not associated with grade 3-4 overall toxicity, febrile neutropenia or hand-foot syndrome. MTHFR 1298CC homozygotes showed a borderline significantly higher incidence of grade 3-4 diarrhoea compared with MTHFR 1298AC or AA individuals (25 vs. 5%, P=0.041) in the monotherapy cohort. No significant association was found between the MTHFR genotypes and efficacy parameters in either treatment cohort. CONCLUSION: MTHFR polymorphisms are not associated with toxicity or efficacy in mCRC patients treated with capecitabine-based chemotherapy.
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[850]
TÍTULO / TITLE: - Imatinib as a key inhibitor of the platelet-derived growth factor receptor mediated expression of cell surface heparan sulfate proteoglycans and functional properties of breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS J. 2013 Feb 1. doi: 10.1111/febs.12163.
●● Enlace al texto completo (gratuito o de pago) 1111/febs.12163
AUTORES / AUTHORS: - Malavaki CJ; Roussidis AE; Gialeli C; Kletsas D; Tsegenidis T; Theocharis AD; Tzanakakis GN; Karamanos NK
INSTITUCIÓN / INSTITUTION: - Laboratory of Biochemistry, Department of Chemistry, University of Patras, Greece.
RESUMEN / SUMMARY: - Cell surface heparan sulfate proteoglycans (HSPGs), syndecans and glypicans, play crucial roles in the functional properties of cancer cells, such as proliferation, adhesion, migration and invasion. Platelet-derived growth factor (PDGF)/PDGF receptor (PDGF-R) mediated signaling, on the other hand, is highly associated with cancer progression. Specifically, PDGF-Ralpha and PDGF-Rbeta expressions documented in breast cancer tissue specimens as well as breast cancer cell lines are correlated with tumor aggressiveness and metastasis. Imatinib (Glivec® ) is a tyrosine kinase inhibitor specific for PDGF-Rs, c-KappaIotaTau and BCR-ABL. In this study we evaluated the effects of imatinib on the properties of breast cancer cells as well as on the expression of HSPGs in the presence and absence of PDGF-BB. These studies have been conducted in a panel of three breast cancer cell lines of low and high metastatic potential. Our results indicate that imatinib exerts a significant inhibitory effect on breast cancer cell proliferation, invasion and migration as well as on the cell surface expression of HSPGs even after exposure of PDGF. These effects depend on the aggressiveness of breast cancer cells and the type of HSPG. It is suggested that imatinib may be of potential therapeutic usefulness in breast cancer regimes.
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[851]
TÍTULO / TITLE: - Hsp90 Inhibitor SNX-7081 Dysregulates Proteins Involved with DNA Repair and Replication and the Cell Cycle in Human Chronic Lymphocytic Leukemia (CLL) Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Proteome Res. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1021/pr301055y
AUTORES / AUTHORS: - Che Y; Best OG; Zhong L; Kaufman KL; Mactier S; Raftery M; Graves LM; Mulligan SP; Christopherson RI
INSTITUCIÓN / INSTITUTION: - Cancer Proteomics Laboratory, School of Molecular Bioscience, University of Sydney , Sydney, NSW 2006, Australia.
RESUMEN / SUMMARY: - The proteomic effects of the Hsp90 inhibitor, SNX-7081, have been determined on the p53-mutated B-cell chronic lymphocytic leukemia (CLL) cell line, MEC1. Following SNX-7081 treatment (500 nM, 24 h), 51 proteins changed abundance by more than 2-fold (p < 0.05); 7 proteins increased while 44 proteins decreased. Proteins identified as differentially abundant by LC-MS/MS were validated by Western blotting (DDB1, PCNA, MCM2, Hsp90, Hsp70, GRP78, PDIA6, HLA-DR). RT-PCR showed that SNX-7081 unexpectedly modulates a number of these proteins in MEC1 cells at the mRNA level (PCNA, MCM2, Nup155, Hsp70, GRP78, PDIA6, and HLA-DR). Pathway analysis determined that 3 of the differentially abundant proteins (cyclin D1, c-Myc and pRb) were functionally related. p53 levels did not change upon SNX-7081 treatment of p53 wild-type Raji cells or p53-mutated MEC1 and U266 cells, indicating that SNX-7081 has a p53-independent mechanism. The decreases in DDB1, MCM2, c-Myc, and PCNA and increases of pRb and cyclin D1 were confirmed in MEC1, U266, Raji, and p53 null HL60 cells by Western blotting. These data suggest that SNX-7081 arrests the cell cycle and inhibits DNA replication and r epair and provides evidence for the mechanism of the observed synergy between Hsp90 inhibitors and drugs that induce DNA strand breaks.
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[852]
TÍTULO / TITLE: - Serum Antibodies against CD28- A New Potential Marker of Dismal Prognosis in Melanoma Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58087. doi: 10.1371/journal.pone.0058087. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058087
AUTORES / AUTHORS: - Korner R; Preuss KD; Fadle N; Madjidi D; Neumann F; Bergeler L; Graber S; Muller CS; Grunhage F; Pfreundschuh M; Lammert F; Vogt T; Pfohler C
INSTITUCIÓN / INSTITUTION: - Department of Dermatology, Saarland University Hospital, Homburg/Saar, Germany.
RESUMEN / SUMMARY: - BACKGROUND: Autoantibodies against CD28 have been found in patients with autoimmune and atopic diseases. These antibodies may act as superagonists and activate T cells but may also be antagonistic or induce immunosuppressive effects by activating regulatory T cells. Autoimmunity in melanoma patients has been discussed controversially. OBJECTIVE: We investigated 230 melanoma patients for the occurrence of CD28 antibodies and the effect of the latter on overall and progress-free survival. METHODS: We constructed an ELISA assay to measure CD28 serum antibodies. 230 patients with melanoma and a control-group of 625 patients consistent of 212 patients with virus hepatitis b or c, 149 patients with allergies, 78 patients with psoriasis, 46 patients with plasmocytoma and 140 healthy blood donors were investigated for the occurrence of CD28 antibodies. RESULTS: CD28 abs occur at a higher percentage in patients with melanoma and in patients with viral hepatitis than in other groups investigated (p<0.001). Occurrence of CD28 abs is significantly higher in patients receiving interferons independent from the underlying disease (p<0.001). In vitro CD28 serum antibodies have an inhibitory effect on the CD28 receptor as they lead to reduced stimulation of Jurkat cells. Presence of CD28 was correlated with a higher risk of dying from melanoma (p = 0.043), but not with a significantly shortened overall survival or progression-free survival. CONCLUSION: Interferon therapy appears to induce the production of CD28 abs. In light of reports that these CD28 abs induce immunosuppressive Tregs and - as our data show - that they are inhibitors of CD28 receptor mediated stimulation, the continuation of therapies with interferons in melanoma patients developing CD28 antibodies should be critically reconsidered, since our data indicate a worse outcome of patients with CD28 abs.
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[853]
TÍTULO / TITLE: - De-repression of PDGFRbeta transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0502
AUTORES / AUTHORS: - Akhavan D; Pourzia AL; Nourian AA; Williams KJ; Nathanson D; Babic I; Villa GR; Tanaka K; Nael A; Yang H; Dang J; Vinters HV; Yong WH; Flagg M; Tamanoi F; Sasayama T; James CD; Kornblum HI; Cloughesy TF; Cavenee WK; Bensinger SJ; Mischel PS
INSTITUCIÓN / INSTITUTION: - 1Molecular and Medical Pharmacology, UCLA.
RESUMEN / SUMMARY: - Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI resistance have been identified in several types of human cancer. However, the possibility that cancer cells may also evade treatment by co-opting physiologically regulated receptors has not been addressed. Here we demonstrate the first example of this alternate mechanism in brain tumors by showing that EGFR-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing PDGFRbeta. Mechanistic studies demonstrate that EGFRvIII signaling actively suppresses PDGFRbeta transcription in an mTORC1 and ERK-dependent manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs dependent on the consequently de-repressed PDGFRbeta signaling for growth and survival. Importantly, combined inhibition of EGFR and PDGFRbeta signaling potently suppresses tumor growth in vivo. These data identify a novel, non-genetic TKI resistance mechanism in brain tumors and provide compelling rationale for combination therapy.
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[854]
TÍTULO / TITLE: - Prognostic value of TNF-related apoptosis inducing ligand (TRAIL) in acute coronary syndrome patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e53860. doi: 10.1371/journal.pone.0053860. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053860
AUTORES / AUTHORS: - Osmancik P; Teringova E; Tousek P; Paulu P; Widimsky P
INSTITUCIÓN / INSTITUTION: - Cardiocenter, Department of Cardiology, 3 Medical School, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic. pavel.osmancik@gmail.com
RESUMEN / SUMMARY: - BACKGROUND: Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes. METHODS: The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone. RESULTS: During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03-0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1-54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05-0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004-0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02-1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56-145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters. CONCLUSIONS: Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.
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[855]
TÍTULO / TITLE: - Identification of the Genes Chemosensitizing Hepatocellular Carcinoma Cells to Interferon-alpha/5-Fluorouracil and Their Clinical Significance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56197. doi: 10.1371/journal.pone.0056197. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056197
AUTORES / AUTHORS: - Sakabe T; Tsuchiya H; Kanki K; Azumi J; Gonda K; Mizuta Y; Yamada D; Wada H; Shomori K; Nagano H; Shiota G
INSTITUCIÓN / INSTITUTION: - Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
RESUMEN / SUMMARY: - The incidence of advanced hepatocellular carcinoma (HCC) is increasing worldwide, and its prognosis is extremely poor. Interferon-alpha (IFN-alpha)/5-fluorouracil (5-FU) therapy is reportedly effective in some HCC patients. In the present study, to improve HCC prognosis, we identified the genes that are sensitizing to these agents. The screening strategy was dependent on the concentration of ribozymes that rendered HepG2 cells resistant to 5-FU by the repeated transfection of ribozymes into the cells. After 10 cycles of transfection, which was initiated by 5,902,875 sequences of a ribozyme library, three genes including protein kinase, adenosine monophosphate (AMP)-activated, gamma 2 non-catalytic subunit (PRKAG2); transforming growth factor-beta receptor II (TGFBR2); and exostosin 1 (EXT1) were identified as 5-FU-sensitizing genes. Adenovirus-mediated transfer of TGFBR2 and EXT1 enhanced IFN-alpha/5-FU-induced cytotoxicity as well as 5-FU, although the overexpression of these genes in the absence of IFN-alpha/5-FU did not induce cell death. This effect was also observed in a tumor xenograft model. The mechanisms of TGFBR2 and EXT1 include activation of the TGF-beta signal and induction of endoplasmic reticulum stress, resulting in apoptosis. In HCC patients treated with IFN-alpha/5-FU therapy, the PRKAG2 mRNA level in HCC tissues was positively correlated with survival period, suggesting that PRKAG2 enhances the effect of IFN-alpha/5-FU and serves as a prognostic marker for IFN-alpha/5-FU therapy. In conclusion, we identified three genes that chemosensitize the effects of 5-FU and IFN-alpha/5-FU on HCC cells and demonstrated that PRKAG2 mRNA can serve as a prognostic marker for IFN-alpha/5-FU therapy.
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[856]
TÍTULO / TITLE: - Epirubicin and docetaxel as neoadjuvant treatment of hormone receptor positive, HER-2 negative breast cancer: findings from two successive phase II studies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiol Oncol. 2013 Mar;47(1):57-62. doi: 10.2478/raon-2013-0012. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 2478/raon-2013-0012
AUTORES / AUTHORS: - Tuzi A; Lombardi D; Crivellari D; Militello L; Perin T; La Grassa M; Massarut S; Veronesi A
INSTITUCIÓN / INSTITUTION: - Divisions of Medical Oncology C, Centro di Riferimento Oncologico, Via Franco Gallini 2, 33081 Aviano, Italy.
RESUMEN / SUMMARY: - BACKGROUND: We report on the activity of the combination of epirubicin and docetaxel given in neoadjuvant setting for 4 and 8 cycles respectively in 2 successive series of patients with large operable or locally advanced, hormone receptor positive, HER-2 negative breast cancer. PATIENTS AND METHODS: Patients were treated from 2002 to 2006 with epirubicin 90 mg/m(2) and docetaxel 75 mg/m(2) intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery (Series I - 13 patients), and from 2006 to 2010 with the same regimen administered for 8 cycles preoperatively (Series II - 37 patients), plus hormonal therapy for 5 years and radiation therapy if indicated. All Series I and 32 Series II patients were able to complete the preoperative chemotherapy. RESULTS: A complete response was found in 1 patient from Series I and 13 patients from Series II and the partial remission in 10 patients from Series I and 21 patients from Series II. Two Series I and 3 Series II patients did not respond clinically. Response rate (Series I/Series II) was 84/92%. All 50 patients underwent surgery. In Series I patients, 3 pCR occurred in the breast and the axilla was histologically negative in 2 cases. No evidence of disease both in the breast and in the axilla was achieved in 7.6% (1/13) of patients. In Series II patients, 8 pCR occurred in the breast and axilla was histologically negative in 15 patients. No evidence of disease both in the breast and in the axilla occurred in 10.8% (4/37) of patients. G3-G4 toxicity included myelosuppression in 3 patients from Series I and all patients from Series II, and mucositis in 1 patient from Series I and 4 patients from series II. No other G3-4 toxicities or toxic deaths occurred. Five-year progression free survival was 38% and 90% in Series I and Series II patients respectively. CONCLUSIONS: The incidence of pathologic complete remissions was lower in our patient population, compared to reported data. A longer duration of the preoperative treatment might be associated with a longer progression-free survival.
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[857]
TÍTULO / TITLE: - Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:124747. doi: 10.1155/2013/124747. Epub 2013 Jan 28.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/124747
AUTORES / AUTHORS: - Chen YJ; Wu CS; Shieh JJ; Wu JH; Chen HY; Chung TW; Chen YK; Lin CC
INSTITUCIÓN / INSTITUTION: - Department of Child Care, College of Humanities and Social Sciences, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan.
RESUMEN / SUMMARY: - Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein’s beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy.
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[858]
TÍTULO / TITLE: - Implication of polymorphisms in DNA repair genes in prognosis of hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):355-8.
AUTORES / AUTHORS: - Yue AM; Xie ZB; Guo SP; Wei QD; Yang XW
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Xinxiang Central Hospital, Xinxiang, China E-mail : hezhonglin_9h@163.com.
RESUMEN / SUMMARY: - XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox’s regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.
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[859]
TÍTULO / TITLE: - Loss of TRAIL-Receptors Is a Recurrent Feature in Pancreatic Cancer and Determines the Prognosis of Patients with No Nodal Metastasis after Surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56760. doi: 10.1371/journal.pone.0056760. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056760
AUTORES / AUTHORS: - Gallmeier E; Bader DC; Kriegl L; Berezowska S; Seeliger H; Goke B; Kirchner T; Bruns C; De Toni EN
INSTITUCIÓN / INSTITUTION: - Department of Medicine 2, University Hospital Grosshadern, University of Munich, Munich, Germany.
RESUMEN / SUMMARY: - INTRODUCTION: Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. AIMS AND METHODS: Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated. RESULTS: The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22-0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance. CONCLUSION: This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.
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[860]
TÍTULO / TITLE: - Bridging cancer biology with the clinic: relative expression of a GRHL2-mediated gene-set pair predicts breast cancer metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56195. doi: 10.1371/journal.pone.0056195. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056195
AUTORES / AUTHORS: - Yang X; Vasudevan P; Parekh V; Penev A; Cunningham JM
INSTITUCIÓN / INSTITUTION: - Section of Hematology/Oncology, Department of Pediatrics, Comer Children’s Hospital, The University of Chicago, Chicago, Illinois, United States of America. xyang2@uchicago.edu
RESUMEN / SUMMARY: - Identification and characterization of crucial gene target(s) that will allow focused therapeutics development remains a challenge. We have interrogated the putative therapeutic targets associated with the transcription factor Grainy head-like 2 (GRHL2), a critical epithelial regulatory factor. We demonstrate the possibility to define the molecular functions of critical genes in terms of their personalized expression profiles, allowing appropriate functional conclusions to be derived. A novel methodology, relative expression analysis with gene-set pairs (RXA-GSP), is designed to explore the potential clinical utility of cancer-biology discovery. Observing that Grhl2-overexpression leads to increased metastatic potential in vitro, we established a model assuming Grhl2-induced or -inhibited genes confer poor or favorable prognosis respectively for cancer metastasis. Training on public gene expression profiles of 995 breast cancer patients, this method prioritized one gene-set pair (GRHL2, CDH2, FN1, CITED2, MKI67 versus CTNNB1 and CTNNA3) from all 2717 possible gene-set pairs (GSPs). The identified GSP significantly dichotomized 295 independent patients for metastasis-free survival (log-rank tested p = 0.002; severe empirical p = 0.035). It also showed evidence of clinical prognostication in another independent 388 patients collected from three studies (log-rank tested p = 3.3e-6). This GSP is independent of most traditional prognostic indicators, and is only significantly associated with the histological grade of breast cancer (p = 0.0017), a GRHL2-associated clinical character (p = 6.8e-6, Spearman correlation), suggesting that this GSP is reflective of GRHL2-mediated events. Furthermore, a literature review indicates the therapeutic potential of the identified genes. This research demonstrates a novel strategy to integrate both biological experiments and clinical gene expression profiles for extracting and elucidating the genomic impact of a novel factor, GRHL2, and its associated gene-sets on the breast cancer prognosis. Importantly, the RXA-GSP method helps to individualize breast cancer treatment. It also has the potential to contribute considerably to basic biological investigation, clinical tools, and potential therapeutic targets.
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[861]
TÍTULO / TITLE: - Expression of Plasminogen Activator Inhibitor-2 is Negatively Associated with Invasive Potential in Hepatocellular Carcinoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med Sci J. 2013 Mar;28(1):16-9.
AUTORES / AUTHORS: - Jin Y; Zhou L; Jin KM; Xing BC
INSTITUCIÓN / INSTITUTION: - Clinical Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
RESUMEN / SUMMARY: - To investigate the association between plasminogen activator inhibitor (PAI)-2 expression and invasive potential in hepatocellular carcinoma (HCC) cells. Methods The HCC cell lines with high, low, and non-metastatic potentials, namely MHCC97-H, MHCC97-L, and SMMC-7721 respectively, were cultured in vitro. Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted. Results The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721 (P=0.005), whereas that in MHCC97-H was higher than in MHCC97-L (P=0.017) and SMMC-7721 (P=0.001). Contrarily, PAI-2 protein expression was gradually reducing from SMMC-7721, MHCC97-L, to MHCC97-H (MHCC97-H vs. MHCC97-L, P<0.001; MHCC97-H vs. SMMC-7721, P=0.001; MHCC97-L vs. SMMC-7721, P=0.001). The Pearson’s correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression (r=-0.892, P=0.001). Conclusion PAI-2 expression may be negatively associated with the invasive potential of HCC.
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[862]
TÍTULO / TITLE: - Expression of protein tyrosine kinase 6 (PTK6) in nonsmall cell lung cancer and their clinical and prognostic significance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onco Targets Ther. 2013;6:183-8. doi: 10.2147/OTT.S41283. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S41283
AUTORES / AUTHORS: - Zhao C; Chen Y; Zhang W; Zhang J; Xu Y; Li W; Chen S; Deng A
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Diagnostic, the 89th Hospital, Weifang, Shandong, People’s Republic of China;
RESUMEN / SUMMARY: - AIM: The aim of the study was to validate the expression of protein tyrosine kinase 6 (PTK6) in nonsmall cell lung cancer (NSCLC), and to evaluate its clinicopathological and prognostic significance. METHODS: We first conducted a meta-analysis on the mRNA profiling data sets of NSCLC in the Oncomine database. Then, one of the most significantly upregulated tyrosine kinase targets, PTK6, was further validated by immunohistochemistry in 104 primary NSCLC tumors. Furthermore the association between PTK6 expression, the clinical parameters, and overall survival was further analyzed. RESULTS: Using the Oncomine database, we identified a list of tyrosine kinase genes related to NSCLC, among which PTK6 was the second most overexpressed gene (median rank = 915, P = 2.9 x 10(-5)). We further confirmed that NSCLC tumors had a higher expression level of PTK6 than normal pulmonary tissues. Moreover, high PTK6 expression correlated positively with shorter overall survival time, but not with other clinicopathological characteristics. In the multivariate Cox regression model, high PTK6 expression was demonstrated to be an independent prognostic factor for NSCLC patients. CONCLUSION: Our results validated that PTK6 was found to be overexpressed in a proportion of NSCLC samples, and was associated with a poor prognosis, suggesting that this subgroup of NSCLC patients might benefit from PTK6 inhibitors in the future.
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[863]
TÍTULO / TITLE: - BIRC6 protein, an inhibitor of apoptosis: role in survival of human prostate cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55837. doi: 10.1371/journal.pone.0055837. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055837
AUTORES / AUTHORS: - Low CG; Luk IS; Lin D; Fazli L; Yang K; Xu Y; Gleave M; Gout PW; Wang Y
INSTITUCIÓN / INSTITUTION: - The Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, the University of British Columbia, Vancouver, British Columbia, Canada.
RESUMEN / SUMMARY: - BACKGROUND: BIRC6 is a member of the Inhibitors of Apoptosis Protein (IAP) family which is thought to protect a variety of cancer cells from apoptosis. The main objective of the present study was to investigate whether BIRC6 plays a role in prostate cancer and could be useful as a novel therapeutic target. METHODS: BIRC6 expression in cell lines was assessed using Western blot analysis and in clinical samples using immunohistochemistry of tissue microarrays. The biological significance of BIRC6 was determined by siRNA-induced reduction of BIRC6 expression in LNCaP cells followed by functional assays. RESULTS: Elevated BIRC6 protein expression was found in prostate cancer cell lines and clinical specimens as distinct from their benign counterparts. Increased BIRC6 expression was associated with Gleason 6-8 cancers and castration resistance. Reduction of BIRC6 expression in LNCaP cells led to a marked reduction in cell proliferation which was associated with an increase in apoptosis and a decrease in autophagosome formation. Doxorubicin-induced apoptosis was found to be coupled to a reduction in BIRC6 protein expression. CONCLUSION: The data suggest a role for BIRC6 in prostate cancer progression and treatment resistance, and indicate for the first time that the BIRC6 gene and its product are potentially valuable targets for treatment of prostate cancers.
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[864]
TÍTULO / TITLE: - BRG1 promotes survival of UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pigment Cell Melanoma Res. 2013 Mar 8. doi: 10.1111/pcmr.12088.
●● Enlace al texto completo (gratuito o de pago) 1111/pcmr.12088
AUTORES / AUTHORS: - Saladi SV; Wong PG; Trivedi AR; Marathe HG; Keenen B; Aras S; Liew ZQ; Setaluri V; de la Serna IL
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, OH, USA.
RESUMEN / SUMMARY: - Microphthalmia-associated transcription factor (MITF) is a survival factor in melanocytes and melanoma cells. MITF regulates expression of antiapoptotic genes and promotes lineage-specific survival in response to ultraviolet (UV) radiation and to chemotherapeutics. SWI/SNF chromatin-remodeling enzymes interact with MITF to regulate MITF target gene expression. We determined that the catalytic subunit, BRG1, of the SWI/SNF complex protects melanoma cells against UV-induced death. BRG1 prevents apoptosis in UV-irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis (ML-IAP). Down-regulation of ML-IAP compromises BRG1-mediated survival of melanoma cells in response to UV radiation. BRG1 regulates ML-IAP expression by cooperating with MITF to promote transcriptionally permissive chromatin structure on the ML-IAP promoter. The alternative catalytic subunit, BRM, and the BRG1-associated factor, BAF180, were found to be dispensable for elevated expression of ML-IAP in melanoma cells. Thus, we illuminate a lineage-specific mechanism by which a specific SWI/SNF subunit, BRG1, modulates the cellular response to DNA damage by regulating an antiapoptotic gene and implicate this subunit of the SWI/SNF complex in mediating the prosurvival function of MITF.
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[865]
TÍTULO / TITLE: - An anti-tumor protein produced by Trichinella spiralis induces apoptosis in human hepatoma H7402 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet Parasitol. 2013 Feb 5. pii: S0304-4017(13)00077-0. doi: 10.1016/j.vetpar.2013.01.052.
●● Enlace al texto completo (gratuito o de pago) 1016/j.vetpar.2013.01.052
AUTORES / AUTHORS: - Wang XL; Liu MY; Sun SM; Liu XL; Yu L; Wang XR; Chu LX; Rosenthal B; Shi HN; Boireau P; Wang F; Zhao Y; Wu XP
INSTITUCIÓN / INSTITUTION: - Key Lab for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
RESUMEN / SUMMARY: - Trichinella spiralis infection confers effective resistance to tumor cell expansion. In this study, a T7 phage cDNA display library was constructed to express genes encoded by T. spiralis. Organic phase multi-cell screening was used to sort through candidate proteins in a transfected human chronic myeloid leukemia cell line (K562) and a human hepatoma cell line (H7402) using the display library. The protein encoded by the A200711 gene was identified and analyzed using protein analysis software. To test the antitumor effects of A200711, variations in cell proliferation and apoptosis were monitored after recombinant pEGFP-N1-A200711 was transfected into H7402 cells. The results show that the expressed target gene successfully induced apoptosis in H7402 cells as measured by Hoechst-PI staining, MTT assay (p<0.05). This study warrants further investigation into the therapeutic use of A200711 for anti-hepatocellular carcinomas.
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[866]
TÍTULO / TITLE: - Lentivirus-mediated Silencing of Rhomboid Domain Containing 1 Suppresses Tumor Growth and Induces Apoptosis in Hepatoma HepG2 Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):5-9.
AUTORES / AUTHORS: - Liu XN; Tang ZH; Zhang Y; Pan QC; Chen XH; Yu YS; Zang GQ
INSTITUCIÓN / INSTITUTION: - Department of Infectious Diseases, Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China E-mail : yuyongsheng@medmail.com.cn, guoqingzang@126.com.
RESUMEN / SUMMARY: - Rhomboids were identified as the first intramembrane serine proteases about 10 years ago. Since then, the study of the rhomboid protease family has blossomed. Rhomboid domain containing 1 (RHBDD1), highly- expressed in human testis, contains a rhomboid domain with unknown function. In the present study, we tested the hypothesis that RHBDD1 was associated with proliferation and apoptosis in hepatocellular carcinoma using recombinant lentivirus-mediated silencing of RHBDD1 in HepG2 cells. Our results showed that down-regulation of RHBDD1 mRNA levels markedly suppressed proliferation and colony formation capacity of HepG2 human hepatoma cancer cells in vitro, and induced cell cycle arrest. We also found that RHBDD1 silencing could obviously trigger HepG2 cell apoptosis. In summary, it was demonstrated that RHBDD1 might be a positive regulator for proliferative and apoptotic characteristics of hepatocellular carcinoma.
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[867]
TÍTULO / TITLE: - Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56069. doi: 10.1371/journal.pone.0056069. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056069
AUTORES / AUTHORS: - Yu J; Ren X; Chen Y; Liu P; Wei X; Li H; Ying G; Chen K; Winkler H; Hao X
INSTITUCIÓN / INSTITUTION: - Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
RESUMEN / SUMMARY: - AIM: To investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. METHODS: The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT) related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, beta-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC) staining method. The clinical outcome and overall survival (OS) were compared. RESULTS: A subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS(+) HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036), which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68(+) macrophages and more cancer cells displaying EMT features were found in NTS(+)IL-8(+) samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS(+)IL-8(+) HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022). Accordingly, the OS of NTS(+)IL-8(+) HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR) of 3.457. CONCLUSION: Dysfunctional activation of the NTS/IL-8 pathway was detected in HCC which is associated with increased inflammatory response in microenvironment, enhanced EMT in cancer, and worse prognosis in HCC patients.
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[868]
TÍTULO / TITLE: - E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 25;13:88. doi: 10.1186/1471-2407-13-88.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-88
AUTORES / AUTHORS: - Jordaan G; Liao W; Sharma S
INSTITUCIÓN / INSTITUTION: - Division of Hematology-Oncology, Greater Los Angeles VA Healthcare Center, UCLA School of Medicine, 11301 Wilshire Blvd, 90073, Los Angeles, CA, USA. sasharma@mednet.ucla.edu.
RESUMEN / SUMMARY: - BACKGROUND: The tumor suppressor gene E-cadherin gene is frequently silenced in chronic lymphocytic leukemia (CLL) cells and results in wnt-pathway activation. We analyzed the role of histone epigenetic modifications in E-cadherin gene silencing. METHODS: CLL specimens were treated with histone deacetylase inhibitor (HDACi) MS-275 and analyzed for E-cadherin expression with western blot and RT-PCR analysis. The downstream effects of HDACi treated leukemic cells were studied by analyzing the effect on wnt-pathway signaling. HDACi induced alterations in E-cadherin splicing were investigated by transcript specific real time PCR analysis. RESULTS: Treatment of CLL specimens with histone deacetylase inhibitors (HDACi) treatment resulted in an increase of the E-cadherin RNA transcript (5 to 119 fold increase, n=10) in eight out of ten CLL specimens indicating that this gene is down regulated by histone hypoacetylation in a majority of CLL specimens. The E-cadherin re-expression in CLL specimens was noted by western blot analysis as well. Besides epigenetic silencing another mechanism of E-cadherin inactivation is aberrant exon 11 splicing resulting in an alternatively spliced transcript that lacks exon 11 and is degraded by the non-sense mediated decay (NMD) pathway. Our chromatin immunoprecipitation experiments show that HDACi increased the acetylation of histones H3 and H4 in the E-cadherin promoter region. This also affected the E-cadherin exon 11 splicing pattern as HDACi treated CLL specimens preferentially expressed the correctly spliced transcript and not the exon 11 skipped aberrant transcript. The re-expressed E- cadherin binds to beta-catenin with inhibition of the active wnt-beta-catenin pathway in these cells. This resulted in a down regulation of two wnt target genes, LEF and cyclinD1 and the wnt pathway reporter. CONCLUSION: The E-cadherin gene is epigenetically modified and hypoacetylated in CLL leukemic cells. Treatment of CLL specimens with HDACi MS-275 activates transcription from this silent gene with expression of more correctly spliced E-cadherin transcripts as compared to the aberrant exon11 skipped transcripts that in turn inhibits the wnt signaling pathway. The data highlights the role of epigenetic modifications in altering gene splicing patterns.
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[869]
TÍTULO / TITLE: - Curcumin Enhances the Effect of Chemotherapy against Colorectal Cancer Cells by Inhibition of NF-kappaB and Src Protein Kinase Signaling Pathways.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57218. doi: 10.1371/journal.pone.0057218. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057218
AUTORES / AUTHORS: - Shakibaei M; Mobasheri A; Lueders C; Busch F; Shayan P; Goel A
INSTITUCIÓN / INSTITUTION: - Institute of Anatomy, Ludwig-Maximilian-University Munich, Munich, Germany.
RESUMEN / SUMMARY: - OBJECTIVE: Development of treatment resistance and adverse toxicity associated with classical chemotherapeutic agents highlights the need for safer and effective therapeutic approaches. Herein, we examined the effectiveness of a combination treatment regimen of 5-fluorouracil (5-FU) and curcumin in colorectal cancer (CRC) cells. METHODS: Wild type HCT116 cells and HCT116+ch3 cells (complemented with chromosome 3) were treated with curcumin and 5-FU in a time- and dose-dependent manner and evaluated by cell proliferation assays, DAPI staining, transmission electron microscopy, cell cycle analysis and immunoblotting for key signaling proteins. RESULTS: The individual IC50 of curcumin and 5-FU were approximately 20 microM and 5 microM in HCT116 cells and 5 microM and 1 microM in HCT116+ch3 cells, respectively (p<0.05). Pretreatment with curcumin significantly reduced survival in both cells; HCT116+ch3 cells were considerably more sensitive to treatment with curcumin and/or 5-FU than wild-type HCT116 cells. The IC50 values for combination treatment were approximately 5 microM and 1 microM in HCT116 and 5 microM and 0.1 microM in HCT116+ch3, respectively (p<0.05). Curcumin induced apoptosis in both cells by inducing mitochondrial degeneration and cytochrome c release. Cell cycle analysis revealed that the anti-proliferative effect of curcumin and/or 5-FU was preceded by accumulation of CRC cells in the S cell cycle phase and induction of apoptosis. Curcumin potentiated 5-FU-induced expression or cleavage of pro-apoptotic proteins (caspase-8, -9, -3, PARP and Bax), and down-regulated anti-apoptotic (Bcl-xL) and proliferative (cyclin D1) proteins. Although 5-FU activated NF-kappaB/PI-3K/Src pathway in CRC cells, this was down-regulated by curcumin treatment through inhibition of IkappaBalpha kinase activation and IkappaBalpha phosphorylation. CONCLUSIONS: Combining curcumin with conventional chemotherapeutic agents such as 5-FU could provide more effective treatment strategies against chemoresistant colon cancer cells. The mechanisms involved may be mediated via NF-kappaB/PI-3K/Src pathways and NF-kappaB regulated gene products.
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[870]
TÍTULO / TITLE: - The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by Fak Inhibitor Y15 and Combination of Y15 and Temozolomide.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Agents Med Chem. 2013 Jan 24.
AUTORES / AUTHORS: - Huang G; Ho B; Conroy J; Liu S; Qiang H; Golubovskaya V
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY,USA 14263. Vita.Golubovskaya@roswellpark.org.
RESUMEN / SUMMARY: - Focal adhesion is known to be highly expressed and activated in glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased tumor growth of DBTRG and U87 cells, especially in combination with temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15, temozolomide and combination of Y15 and temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and detected 8087 and 6555 genes, which were significantly either up- or down-regulated by Y15-treatment in DBTRG and U87 cells, respectively (p<0.05). Moreover, DBTRG and U87 cells treated with Y15 changed gene expression of 1332 and 462 genes more than 1.5 fold, p<0.05, respectively and had 237 common genes affected by Y15. The common genes up-regulated by Y15 included GADD45A, HSPA6 (heat-shock 70); DUSP1, DUSP 5 (dual-phosphatase 5); CDKN1A (p21) and common down-regulated genes included kinesins, such as KIF11, 14, 20A, 20B; topoisomerase II, TOP2A; cyclin F; cell cycle protein: BUB1; PARP1, POLA1. In addition, we detected genes affected by temozolomide and by combination of Y15 and temozolomide treatment in U87 cells. Among genes up-regulated by Y15 and temozolomide more significantly than by each agent alone were: COX7B; interferon, gamma-inducible transcript: IFI16; DDIT4; GADD45G and down-regulated: KIF3A, AKT1; ABL; JAK1, GLI3 and ALDH1A3. Thus, microarray gene expression analysis can be effective in establishing genes affected in response to FAK inhibitor alone and to combination of Y15 with temozolomide that is important for glioblastoma therapy.
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[871]
TÍTULO / TITLE: - Inhibition of proliferation of estrogen receptorpositive MCF7 human breast cancer cells by tamoxifen through cJun transcription factors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Apr;7(4):1283-7. doi: 10.3892/mmr.2013.1306. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1306
AUTORES / AUTHORS: - Xu Y; Zou ST; Zhu R; Li W; Gu CW; Wei SH; Xie JM; Wu HR
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R China.
RESUMEN / SUMMARY: - Activator of protein 1 (AP1) is a heterodimeric transcription factor composed of various members of the Jun and Fos families and binds to DNA at specific AP1 binding sites. AP1 transcriptional activity is increased by phosphorylation at serine residues in the cJun component of AP1. In the present study, the proliferation of MCF7 breast cancer cells was found to be suppressed by tamoxifen (TAM)activated cJun through the protein kinase C (PKC) pathway. The molecular mechanism by which cJun activation induces antiproliferative signals in estrogen receptor (ER)positive MCF7 human breast cancer cells remains unknown. TAM inhibited the proliferation of ERpositive MCF7 human breast cancer cells and ERnegative MDAMB435 human breast cancer cells and 48 h incubation with 10 microM TAM led to inhibition of 80% of proliferation. In addition, no significant difference in cJun mRNA and protein levels was detected in MCF7 and MDAMB435 cells stimulated by TAM for 48 h. TAM treatment of MCF7 cells activated the transcriptional activity of AP1, which responds specifically to phorbol ester. To determine the role of cJun in the antiproliferation of MCF7 cells stimulated by TAM, the inhibition rates of MCF7 cells were correlated with cJun expression and stimulation of TAM. Results showed that the inhibition rate of TAMstimulated MCF7 cells was positively regulated by overexpression of cJun and negatively regulated by underexpression of cJun. Overall, these results indicate that the TAMstimulated antiproliferation of MCF7 cells is positively regulated by cJun through activation of the PKC pathway.
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[872]
TÍTULO / TITLE: - Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosine Kinase Inhibitor Treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Pathol. 2013 Feb;47(1):52-60. doi: 10.4132/KoreanJPathol.2013.47.1.52. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 4132/KoreanJPathol.2013.47.1.52
AUTORES / AUTHORS: - Lee HJ; Xu X; Kim H; Jin Y; Sun P; Kim JE; Chung JH
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. ; Department of Pathology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
RESUMEN / SUMMARY: - BACKGROUND: The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs). METHODS: Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21). RESULTS: Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods. CONCLUSIONS: All three EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of EGFR mutations.
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[873]
TÍTULO / TITLE: - Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar;3(3):264-79. doi: 10.1158/2159-8290.CD-12-0362. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0362
AUTORES / AUTHORS: - Dieci MV; Arnedos M; Andre F; Soria JC
INSTITUCIÓN / INSTITUTION: - 1Breast Cancer Unit and 2Early Drug Development Unit (SITEP), Department of Medical Oncology; 3INSERM Unit U981, Gustave Roussy Institute, Villejuif; 4Paris Sud University, Orsay, France; and 5Department of Oncology, Hematology, and Respiratory Diseases, University Hospital, Modena, Italy.
RESUMEN / SUMMARY: - The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifications, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, class-specific toxicity profiles and correctly designing clinical trials to address these different issues.
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[874]
TÍTULO / TITLE: - Skin Rash During Cetuximab Treatment in Advanced Colorectal Cancer: is Age a Clinical Predictor?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointest Cancer. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s12029-013-9485-7
AUTORES / AUTHORS: - Giuliani J; Marzola M
INSTITUCIÓN / INSTITUTION: - Palliative Care Unit, Mater Salutis Hospital, ULSS 21, Via Gianella 1, 37045, Legnago, Verona, Italy, giuliani.jacopo@alice.it.
RESUMEN / SUMMARY: - PURPOSE: The aim of this study is to evaluate the intensity and the duration of skin rash in young and elderly patients treated with cetuximab for advanced colorectal cancer, in order to define a possible relationship between age and skin toxicity. METHODS: We retrospectively analyzed all consecutive patients with advanced colorectal cancer who developed skin rash during cetuximab treatment at the Clinical Oncology Unit from June 2006 to May 2011. We divided the general case study into two subgroups: young and elderly patients (>/=65 years old), and we compared clinical, pathological, and therapeutical characteristics of both subgroups. RESULTS: Among the 31 patients affected by advanced colorectal cancer (64.5 % with colon cancer and 35.5 % with rectal cancer) treated with cetuximab, 19 patients (61.3 %) developed skin toxicities: seven patients (36.8 %) had grade 1 skin rash, nine patients (47.4 %) had grade 2, three patients (15.8 %) had grade 3, and no grade 4 was found. Ten (52.6 %) out of 19 patients were elderly (>65 years). Concerning skin rash, grading was substantially comparable between the two subgroups, but median duration of skin rash was higher in the first subgroup for all grades. The univariate analysis showed no statistical significant difference in overall survival between young and elderly patients (p = 0.171), such as age that does not seem to statistically influence the appearance (p = 0.386), duration (p = 0.455), and grade of skin rash (p = 0.765). CONCLUSIONS: Age is an insufficient predictor of skin toxicity during cetuximab treatment in advanced colorectal cancer and does not seem to statistically influence the appearance, duration, and grade of skin rash.
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[875]
TÍTULO / TITLE: - Induction of mitochondrial-mediated apoptosis by morinda citrifolia (noni) in human cervical cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):237-42.
AUTORES / AUTHORS: - Gupta RK; Banerjee A; Pathak S; Sharma C; Singh N
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, All India Institute of Medical Science, Ansari Nagar, New Delhi, India E-mail : singh_neeta26@rediffmail.com.
RESUMEN / SUMMARY: - Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down- regulation of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.
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[876]
TÍTULO / TITLE: - Lenalidomide induces apoptosis and alters gene expression in non-small cell lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):588-592. Epub 2012 Nov 30.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1054
AUTORES / AUTHORS: - Kim K; An S; Cha HJ; Choi YM; Choi SJ; An IS; Lee HG; Min YH; Lee SJ; Bae S
INSTITUCIÓN / INSTITUTION: - Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu, Seoul 143-701;
RESUMEN / SUMMARY: - Non-small cell lung cancer (NSCLC) is the most deadly type of cancer worldwide. Although a number of therapies are used in NSCLC treatment, their therapeutic efficacy remains low. Lenalidomide was originally approved for use in patients with myelodysplastic syndromes, which are associated with 5q deletions, and multiple myeloma. Recently, lenalidomide was investigated as a new NSCLC treatment, and it exerted anticancer effects. However, the primary cellular mechanism of its effects in NSCLC is largely unknown. Therefore, we attempted to elucidate a molecular portrait of lenalidomide-mediated cellular events in NSCLC. Lenalidomide reduced the viability of several NSCLC cell lines in a concentration-dependent manner. In addition, array-based gene expression analysis revealed that lenalidomide regulated the expression of several genes associated with cell survival, apoptosis and development, including BH3-interacting domain death agonist (BID), v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) and NK2 homeobox1 (NKX2-1). BID and FOS, which are known apoptosis activators, were upregulated by lenalidomide treatment, whereas NKX2-1, which is used as an immunohistochemistry marker for NSCLC, was downregulated. These results provide evidence that lenalidomide directly induces antiproliferative effects by altering the expression of genes associated with cell proliferation and apoptosis.
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[877]
TÍTULO / TITLE: - Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells: tumor suppressive role of klotho in gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 21;13(1):18. doi: 10.1186/1475-2867-13-18.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-18
AUTORES / AUTHORS: - Xie B; Zhou J; Shu G; Liu DC; Zhou J; Chen J; Yuan L
INSTITUCIÓN / INSTITUTION: - Departemt of Geriatric Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. shuguoshun@yahoo.com.
RESUMEN / SUMMARY: - BACKGROUND: The loss of tumor suppressor gene expression is involved in the carcinogenesis of gastric cancer (GC). Klotho is a recently identified tumor suppressor gene that epigenetically inactivated in gastric cancer. However, the signaling pathways involved in the suppressive role of klotho have rarely been reported in gastric cancer. In this study, we investigated the involvement of klotho in gastric cancer cell proliferation, apoptosis, and autophagy as well as the associated signaling. METHODS: Methylation of klotho gene promoter in GC-7901, MNK-45 and AGS gastric cancer cells as well as GES-1 normal gastric epithelial cells was detected by bisulfate-based PCR. Restoration of klotho gene expression was established by applying a demethylating agent and delivering aklotho gene expression vector into GC-7901 cells. Cell viability was measured by CCK-8 assay. Cell apoptosis and cycling were analyzed by flow cytometry. Autophagy was measured by detecting LC3-I and LC3-II expression. Protein levels and phosphorylation were measured by Western blot assay. RESULTS: Methylation of klotho gene promoter and expression of the klotho gene were detected in GC cells. Restoration of klotho gene expression significantly inhibited cell proliferation, induced cell apoptosis, and increased LC3-I/LC3-II expression in GC cells. Restoration of klotho gene expression downregulated the phosphorylation levels of IGF-1 receptor, IRS-1, PI3K, Akt, and mTOR proteins. Both apoptosis and autophagy inhibitors blocked klotho-induced apoptosis and autophagy. CONCLUSION: Klotho is a tumor suppressor in gastric cancer, which regulates IGF-1R phosphorylation and the subsequent activation of IRS-1/PI3K/Akt/mTOR signaling, tumor cell proliferation, apoptosis, and autophagy.
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[878]
TÍTULO / TITLE: - Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 7;13(1):10.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-10
AUTORES / AUTHORS: - Liu K; Cang S; Ma Y; Chiao JW
RESUMEN / SUMMARY: - ABSTRACT: : This study examined whether combining paclitaxel (taxol) with a novel epigenetic agent phenethyl isothiocyanate (PEITC) will yield a synergistic effect on inhibiting breast cancer cells. Two drug-resistant breast cancer cell lines, MCF7 and MDA-MB-231, were treated with PEITC and taxol. Cell growth, cell cycle, and apoptosis were examined. The combination of PEITC and taxol significantly decreased the IC50 of PEITC and taxol over each agent alone. The combination also increased apoptosis by more than two fold over each single agent in both cell lines. A significant increase of cells in the G2/M phases was detected. In conclusion, the combination of PEITC and taxol exhibits a synergistic effect on growth inhibition in breast cancer cells. This combination deserves further study in vivo.
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[879]
TÍTULO / TITLE: - The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Nanomedicine. 2013;8:351-63. doi: 10.2147/IJN.S37465. Epub 2013 Jan 20.
●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S37465
AUTORES / AUTHORS: - Franke K; Kettering M; Lange K; Kaiser WA; Hilger I
INSTITUCIÓN / INSTITUTION: - Institute of Diagnostic and Interventional Radiology, Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology I, University Hospital Jena, Friedrich-Schiller Universitat Jena, Jena, Germany.
RESUMEN / SUMMARY: - PURPOSE: The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. METHODS: BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 mug Fe/cm(2)) or mitomycin C (up to 1.5 mug/cm(2), 24 hours) in the presence or absence of hyperthermia (43 degrees C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. DISCUSSION: The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology.
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[880]
TÍTULO / TITLE: - TRAIL induces apoptosis in oral squamous carcinoma cells - a crosstalk with oncogenic Ras regulated cell surface expression of death receptor 5.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncotarget. 2013 Feb;4(2):206-17.
AUTORES / AUTHORS: - Chen JJ; Mikelis CM; Zhang Y; Gutkind JS; Zhang B
INSTITUCIÓN / INSTITUTION: - Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD.
RESUMEN / SUMMARY: - TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis through its death receptors (DRs) 4 and/or 5 expressed on the surface of target cells. The selectivity of TRAIL towards cancer cells has promoted clinical evaluation of recombinant human TRAIL (rhTRAIL) and its agonistic antibodies in treating several major human cancers including colon and non-Hodgkin’s lymphoma. However, little is known about their ability in killing oral squamous cell carcinoma (OSCC) cells. In this study, we tested the apoptotic responses of a panel of seven human OSCC cell lines (HN31, HN30, HN12, HN6, HN4, Cal27, and OSCC3) to rhTRAIL and monoclonal antibodies against DR4 or DR5. We found that rhTRAIL is a potent inducer of apoptosis in most of the oral cancer cell lines tested both in vitro and in vivo. We also showed that DR5 was expressed on the surface of the tested cell lines which correlated with the cellular susceptibility to apoptosis induced by rhTRAIL and anti-DR5 antibody. By contrast, little or no DR4 was detected on the surface of OSCC3 and HN6 cells rendering cellular resistance to DR4 antibody and a reduced sensitivity to rhTRAIL. Notably, the overall TRAIL sensitivity correlated well with the levels of endogenous active Ras in the cell lines tested. Expression of a constitutively active Ras mutant (RasV12) in OSCC3 cells selectively upregulated surface expression of DR5, but not DR4, and restored TRAIL sensitivity. Our findings could have implications for the use of TRAIL receptor targeted therapies in the treatment of human OSCC tumors particularly the ones harboring constitutively active Ras mutant.
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[881]
TÍTULO / TITLE: - Common Variations of DNA Repair Genes are Associated with Response to Platinum-based Chemotherapy in NSCLCs.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):145-8.
AUTORES / AUTHORS: - Li XD; Han JC; Zhang YJ; Li HB; Wu XY
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Huaihe Hospital, Henan University, Kaifeng, Henan, China E-mail : xiandongli67@126.com.
RESUMEN / SUMMARY: - Aim: Individual differences in chemosensitivity and clinical outcome of non-small-cell lung cancer (NSCLC) patients may be induced by host inherited factors. We investigated the impact of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln gene polymorphisms on the efficacy of platinum-based chemotherapy in NSCLC patients. Methods: A total of 496 were consecutively selected from the Affiliated Hospital of Nantong University between Jan. 2003 and Nov. 2006, and all patients were followed-up until Nov. 2011. The genotyping of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln was conducted by duplex polymerase-chain-reaction with the confronting-two-pair primer methods. Results: Individuals with XPD 312 C/T+T/T and XPD 711 C/T+T/T exhibited poor responses to chemotherapy when compared with the wild- type genotype, with adjusted ORs(95% CI) of 0.67(0.38-0.97) and 0.54(0.35-0.96), respectively. Cox regression showed the median PFS and OS of patients of XPD 312 C/T+T/T genotype and XPD 711 C/T+T/T genotype to be significantly lower than those with wild-type homozygous genotype. Conclusion: We found polymorphisms in XPD to be associated with response to platinum-based chemotherapy in NSCLC, and our findings provide information for therapeutic decisions for individualized therapy.
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[882]
TÍTULO / TITLE: - Can pharmacological receptor tyrosine kinase inhibitors sensitize poor outcome breast tumors to immune-based therapies?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Oncol. 2013;3:23. doi: 10.3389/fonc.2013.00023. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00023
AUTORES / AUTHORS: - Ursini-Siegel J
INSTITUCIÓN / INSTITUTION: - Lady Davis Institute for Medical Research Montreal, QC, Canada.
RESUMEN / SUMMARY: - Receptor tyrosine kinases (RTKs) drive breast cancer progression, particularly in human epidermal growth factor receptor 2 and basal tumors, the two worst prognosis subtypes. Tumor cells recruit host stromal components, including immune cells, which strongly influence disease progression. This has been studied in human breast cancer and translated to murine models of breast cancer. Stromal immune components including cytotoxic T lymphocytes (CTLs) and natural killer cells, destroy cancer cells through a process termed immune surveillance. Unfortunately, clinically detectable tumors escape these immune protective effects through their ability to limit the infiltration, activation, and/or survival of CTLs in breast tumors. The immunosuppressed state of established tumors limits the success rate of immune-based therapies, and possibly other therapeutic modalities that depend on host immunity. Published studies demonstrate that RTKs facilitate breast cancer progression, in part, by establishing immune suppression. This raises the intriguing possibility that pharmacological RTK inhibitors may be exploited to sensitize breast cancer patients to immune-based therapies.
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[883]
TÍTULO / TITLE: - Peripheral helper lymphocytes produce interleukin 12 in cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Med Insights Oncol. 2013;7:75-81. doi: 10.4137/CMO.S11292. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 4137/CMO.S11292
AUTORES / AUTHORS: - Michelin MA; Abdalla DR; Aleixo AA; Murta EF
INSTITUCIÓN / INSTITUTION: - Oncology Research Institute (IPON), Federal University of the Triangulo Mineiro (UFTM). ; Discipline of Immunology, UFTM.
RESUMEN / SUMMARY: - The aim of the study was to seek evidence for the production of IL-12 by CD4(+) T lymphocytes in in vitro and ex vivo trials. We performed in vitro trials with spleen cells from mice subjected to carcinogenesis, as well as ex vivo trials with cells obtained from the peripheral blood of healthy individuals and cancer patients. We were able to verify a significantly increased expression of IL-12 in CD4(+) T lymphocytes from mice and patients with tumors, compared to controls. Follow-up studies are needed to clarify whether this difference is related to being in a chronic disease state or whether it is an attempt by the immune system to produce an anti-tumor response, since T lymphocytes from healthy donors were not able to produce IL-12 when in contact with polyclonal stimuli. We concluded that, in cancer, T helper cells are capable of synthesizing IL-12, raising the question of whether we are faced with another profile, Th12.
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[884]
TÍTULO / TITLE: - Antineoplastic Effects of alpha-Santalol on Estrogen Receptor-Positive and Estrogen Receptor-Negative Breast Cancer Cells through Cell Cycle Arrest at G2/M Phase and Induction of Apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56982. doi: 10.1371/journal.pone.0056982. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056982
AUTORES / AUTHORS: - Santha S; Bommareddy A; Rule B; Guillermo R; Kaushik RS; Young A; Dwivedi C
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, United States of America.
RESUMEN / SUMMARY: - Anticancer efficacy and the mechanism of action of alpha-santalol, a terpenoid isolated from sandalwood oil, were investigated in human breast cancer cells by using p53 wild-type MCF-7 cells as a model for estrogen receptor(ER)-positive and p53 mutated MDA-MB-231 cells as a model for ER-negative breast cancer. alpha-Santalol inhibited cell viability and proliferation in a concentration and time-dependent manner in both cells regardless of their ER and/or p53 status. However, alpha-santalol produced relatively less toxic effect on normal breast epithelial cell line, MCF-10A. It induced G2/M cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cells. Cell cycle arrest induced by alpha-santalol was associated with changes in the protein levels of BRCA1, Chk1, G2/M regulatory cyclins, Cyclin dependent kinases (CDKs), Cell division cycle 25B (Cdc25B), Cdc25C and Ser-216 phosphorylation of Cdc25C. An up-regulated expression of CDK inhibitor p21 along with suppressed expression of mutated p53 was observed in MDA-MB-231 cells treated with alpha-santalol. On the contrary, alpha-santalol did not increase the expression of wild-type p53 and p21 in MCF-7 cells. In addition, alpha-santalol induced extrinsic and intrinsic pathways of apoptosis in both cells with activation of caspase-8 and caspase-9. It led to the activation of the executioner caspase-6 and caspase-7 in alpha-santalol-treated MCF-7 cells and caspase-3 and caspase-6 in MDA-MB-231 cells along with strong cleavage of poly(ADP-ribose) polymerase (PARP) in both cells. Taken together, this study for the first time identified strong anti-neoplastic effects of alpha-santalol against both ER-positive and ER-negative breast cancer cells.
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[885]
TÍTULO / TITLE: - The effect of tissue factor pathway inhibitor on the expression of monocyte chemotactic protein-3 and IkappaB-alpha stimulated by tumour necrosis factor-alpha in cultured vascular smooth muscle cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Cardiovasc Dis. 2013 Jan;106(1):4-11. doi: 10.1016/j.acvd.2012.09.003. Epub 2012 Dec 21.
●● Enlace al texto completo (gratuito o de pago) 1016/j.acvd.2012.09.003
AUTORES / AUTHORS: - Zhao Y; Fu Y; Hu J; Liu Y; Yin X
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, China.
RESUMEN / SUMMARY: - BACKGROUND: In recent years, the importance of inflammation in restenosis has been recognized gradually. When vascular injury occurs, NF-kappaB, which controls transcription of many inflammatory genes in restenosis (such as monocyte chemotactic protein-3 [MCP-3]), is activated by IkappaB degradation, leaving the NF-kappaB dimer-free to translocate to the nucleus to activate specific target genes. AIMS: To investigate the effect of tissue factor pathway inhibitor (TFPI) on MCP-3 expression and IkappaB-alpha degradation stimulated by tumour necrosis factor (TNF)-alpha in vascular smooth muscle cells (VSMCs), thus further elucidating the mechanism of the inhibitory effect of TFPI on restenosis. METHODS: Dulbecco’s modified Eagle’s medium or human recombinant adenoviruses expressing TFPI or bacterial beta-galactosidase (LacZ) were used to infect rat aortic VSMCs in vitro. Enzyme-linked immunosorbent assays were used to detect exogenous TFPI expression and reverse transcription-polymerase chain reactions were used to detect MCP-3 expression after TNF-alpha stimulation in transfected cells. Western blotting and immunofluorescence microscopy were used to examine IkappaB-alpha expression. RESULTS: TFPI protein was detected in the TFPI group after gene transfer. The cells were stimulated with TNF-alpha for 6 hours on the third day after gene transfer. MCP-3 messenger ribonucleic acid expression was lower in the TFPI group than in the LacZ group (P<0.05) and IkappaB-alpha degradation was lower in the TFPI group than in the LacZ group in the cytoplasm (P<0.05). CONCLUSION: TFPI inhibited MCP-3 expression induced by TNF-alpha; this effect may be propagated through the NF-kappaB pathway. TFPI gene transfer may be a new therapeutic strategy for inhibiting restenosis in clinical situations.
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[886]
TÍTULO / TITLE: - Tanshinone IIA Reverses the Malignant Phenotype of SGC7901 Gastric Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):173-7.
AUTORES / AUTHORS: - Xu M; Cao FL; Li NY; Liu YQ; Li YP; Lv CL
INSTITUCIÓN / INSTITUTION: - The 88th Hospital of PLA, Taian, China E-mail : xumin022@163.com.
RESUMEN / SUMMARY: - Backgrounds: Tanshinone IIA (TIIA), a phenanthrenequinone derivative extracted from Salvia miltiorrhiza BUNGE, has been reported to be a natural anti-cancer agent in a variety of tumor cells. However, the effect of TIIA on gastric cancer cells remains unknown. In the present study, we investigated the influence of TIIA on the malignant phenotype of SGC7901 gastric cancer cells. Methods: Cells cultured in vitro were treated with TIIA (0, 1, 5, 10 mug/ml) and after incubation for different periods, cell proliferation was measured by MTT method and cell apoptosis and cell cycling were assessed by flow cytometry (FCM). The sensitivity of SGC7901 gastric cancer cells to anticancer chemotherapy was investigated with the MTT method, while cell migration and invasion were examined by wound-healing and transwell assays, respectively. Results: TIIA (1, 5, 10 mug/ml) exerted powerful inhibitory effects on cell proliferation (P < 0.05, and P < 0.01), and this effect was time- and dose-dependent. FCM results showed that TIIA induced apoptosis of SGC7901 cells, reduced the number of cells in S phase and increased those in G0/G1 phase. TIIA also significantly increased the sensitivity of SGC7901 gastric cancer cells to ADR and Fu. Moreover, wound-healing and transwell assays showed that TIIA markedly decreased migratory and invasive abilities of SGC7901 cells. Conclusions: TIIA can reverse the malignant phenotype of SGC7901 gastric cancer cells, indicating that it may be a promising therapeutic agent.
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[887]
TÍTULO / TITLE: - Estrogen receptor-alpha36 is involved in development of acquired tamoxifen resistance via regulating the growth status switch in breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Oncol. 2013 Feb 26. pii: S1574-7891(13)00025-2. doi: 10.1016/j.molonc.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2013.02.001
AUTORES / AUTHORS: - Li G; Zhang J; Jin K; He K; Zheng Y; Xu X; Wang H; Wang H; Li Z; Yu X; Teng X; Cao J; Teng L
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, 79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China.
RESUMEN / SUMMARY: - Acquired tamoxifen (TAM) resistance limits the therapeutic benefit of TAM in patients with hormone-dependent breast cancer. The switch from estrogen-dependent to growth factor-dependent growth is a critical step in this process. However, the molecular mechanisms underlying this switch remain poorly understood. In this study, we established a TAM resistant cell sub line (MCF-7/TAM) from estrogen receptor-alpha (ER-alpha66) positive breast cancer MCF-7 cells by culturing ER-alpha66-positive MCF-7 cells in medium plus 1 muM TAM over 6 months. MCF-7/TAM cells were then found to exhibit accelerated proliferation rate together with enhanced in vitro migratory and invasive ability. And the estrogen receptor-alpha36 (ER-alpha36), a novel 36-kDa variant of ER-alpha66, was dramatically overexpressed in this in vitro model, compared to the parental MCF-7 cells. Meanwhile, the expression of epidermal growth factor receptor (EGFR) in MCF-7/TAM cells was significantly up-regulated both in mRNA level and protein level, and the expression of ER-alpha66 was greatly down-regulated oppositely. In the subsequent studies, we overexpressed ER-alpha36 in MCF-7 cells by stable transfection and found that ER-alpha36 transfected MCF-7 cells (MCF-7/ER-alpha36) similarly exhibited decreased sensitivity to TAM, accelerated proliferative rate and enhanced in vitro migratory and invasive ability, compared to empty vector transfected MCF-7 cells (MCF-7/V). Real-time qPCR and Western blotting analysis revealed that MCF-7/ER-alpha36 cells possessed increased EGFR expression but decreased ER-alpha66 expression both in mRNA level and protein level, compared to MCF-7/V cells. This change in MCF-7/ER-alpha36 cells could be reversed by neutralizing anti-ER-alpha36 antibody treatment. Furthermore, knock-down of ER-alpha36 expression in MCF-7/TAM cells resulted in reduced proliferation rate together with decreased in vitro migratory and invasive ability. Decreased EGFR mRNA and protein expression as well as increased ER-alpha66 mRNA expression were also observed in MCF-7/TAM cells with down-regulated ER-alpha36 expression. In addition, blocking EGFR/ERK signaling in MCF-7/ER-alpha36 cells could restore the expression of ER-alpha66 partly, suggesting a regulatory function of EGFR/ERK signaling in down-regulation of ER-alpha66 expression. In conclusion, our results indicated for the first time a regulatory role of ER-alpha36 in up-regulation of EGFR expression and down-regulation of ER-alpha66 expression, which could be an underlying mechanism for the growth status switch in breast tumors that contribute to the generation of acquired TAM resistance. And ER-alpha36 could be considered a potential new therapeutic target in breast tumors which have acquired resistance to TAM.
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[888]
TÍTULO / TITLE: - Sustained Low-Dose Treatment with the Histone Deacetylase Inhibitor LBH589 Induces Terminal Differentiation of Osteosarcoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Sarcoma. 2013;2013:608964. doi: 10.1155/2013/608964. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/608964
AUTORES / AUTHORS: - Cain JE; McCaw A; Jayasekara WS; Rossello FJ; Marini KD; Irving AT; Kansara M; Thomas DM; Ashley DM; Watkins DN
INSTITUCIÓN / INSTITUTION: - Centre for Cancer Research, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, VIC 3168, Australia.
RESUMEN / SUMMARY: - Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity.
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[889]
TÍTULO / TITLE: - Neuroglobin upregulation induced by 17beta-estradiol sequesters cytocrome c in the mitochondria preventing H2O2-induced apoptosis of neuroblastoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 21;4:e508. doi: 10.1038/cddis.2013.30.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.30
AUTORES / AUTHORS: - De Marinis E; Fiocchetti M; Acconcia F; Ascenzi P; Marino M
INSTITUCIÓN / INSTITUTION: - Department of Science, University Roma Tre, Roma, Italy.
RESUMEN / SUMMARY: - The sex steroid hormone 17beta-estradiol (E2) upregulates the levels of neuroglobin (NGB), a new neuroprotectant globin, to elicit its neuroprotective effect against H(2)O(2)-induced apoptosis. Several mechanisms could be proposed to justify the NGB involvement in E2 prevention of stress-induced apoptotic cell death. Here, we evaluate the ability of E2 to modulate the intracellular NGB localization and the NGB interaction with mitochondrial cytochrome c following the H(2)O(2)-induced toxicity. Present results demonstrate that NGB is expressed in the nuclei, mitochondria, and cytosol of human neuroblastoma SK-N-BE cells. E2, but not H(2)O(2) treatment of SK-N-BE cells, reallocates NGB mainly at the mitochondria and contemporarily reduces the number of apoptotic nuclei and the levels of cleaved caspase-3. Remarkably, the E2 treatment strongly increases NGB-cytochrome c association into mitochondria and reduces the levels of cytochrome c into the cytosol of SK-N-BE cells. Although both estrogen receptors (ERalpha and ERbeta) are expressed in the nucleus, mitochondria, and cytosol of SK-N-BE cells, this E2 effect specifically requires the mitochondrial ERbeta activity. As a whole, these data demonstrate that the interception of the intrinsic apoptotic pathway into mitochondria (i.e., the prevention of cytochrome c release) is one of the pivotal mechanisms underlying E2-dependent NGB neuroprotection against H(2)O(2) toxicity.
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[890]
TÍTULO / TITLE: - Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59639. doi: 10.1371/journal.pone.0059639. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059639
AUTORES / AUTHORS: - Faiao-Flores F; Coelho PR; Toledo Arruda-Neto JD; Maria-Engler SS; Tiago M; Capelozzi VL; Giorgi RR; Maria DA
INSTITUCIÓN / INSTITUTION: - Laboratory of Biochemistry and Biophysics, Butantan Institute, Sao Paulo, Brazil ; Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
RESUMEN / SUMMARY: - Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and (7)Li, with a range of 5 to 9 microm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT.
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[891]
TÍTULO / TITLE: - Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocrinol Nutr. 2013 Feb 14. pii: S1575-0922(12)00291-4. doi: 10.1016/j.endonu.2012.09.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.endonu.2012.09.005
AUTORES / AUTHORS: - Sanchez-Tejada L; Sanchez-Ortiga R; Moreno-Perez O; Montanana CF; Niveiro M; Tritos NA; Alfonso AM
INSTITUCIÓN / INSTITUTION: - Endocrinology Department, Research Unit, Hospital General Universitario Alicante, Alicante, España.
RESUMEN / SUMMARY: - INTRODUCTION AND OBJECTIVE: The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGFIR), and Ki-67. MATERIALS AND METHODS: In this retrospective study, the normalized copy number (NCN) of PTIG and IGFIR mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46+/-36 months. RESULTS: Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGFIR expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69+/-3.84 NCN vs. 5.44+/-3.55 NCN, p=0.014). CONCLUSIONS: Our results suggest that the IGFIR is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.
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[892]
TÍTULO / TITLE: - High levels of gamma-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 1;13:47. doi: 10.1186/1471-2407-13-47.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-47
AUTORES / AUTHORS: - Shubbar E; Helou K; Kovacs A; Nemes S; Hajizadeh S; Enerback C; Einbeigi Z
INSTITUCIÓN / INSTITUTION: - Sahlgrenska Cancer Center, Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SE-41345, Sweden. emman.shubbar@gu.se
RESUMEN / SUMMARY: - BACKGROUND: Previously, we performed analysis of gene expression in 46 axillary lymph node negative tumors and identified molecular gene signatures that resulted in different clinical outcomes. The aim of this study was to determine the correlation of gamma-glutamyl hydrolase (GGH), fatty acid amide hydrolase (FAAH), Pirin (PIR) and TAF5-like RNA polymerase II, p300/CBP-associated factor (PCAF)-associated factor, 65 kDa (TAF5L), selected from identified gene signatures, with clinical outcomes as well as classical clinicopathological characteristics in primary invasive breast cancer patients. METHODS: The protein levels of GGH, FAAH, PIR and TAF5L were assessed by immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Quantitative real-time PCR (qRT-PCR) and western blot analysis were performed to verify the expression levels of the candidate biomarkers. Patient disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. The prognostic biomarkers were identified by univariate analysis with a log-rank test and by multivariate analysis with Cox proportional hazards regression models. RESULTS: The GGH and FAAH protein levels were significantly up-regulated in invasive breast cancer tumors compared with adjacent non-cancerous tissues. Furthermore, the protein levels of GGH and FAAH were significantly correlated in tumor tissues. Tumoral GGH protein expression was significantly correlated with shorter DSS and RFS. Furthermore, the protein expression of GGH was positively correlated with undifferentiated tumors (BRE grade III) and ER/PR expressing tumors. Multivariate regression analysis showed that only GGH protein expression independently predicts DSS. No such correlations were found for FAAH, PIR and TAF5L protein expression. However, elevated protein levels of FAAH were positively associated with high number of lymph node involvement and upregulated levels of PIR were positively related with lymph node metastasis. The TAF5L was pronouncedly down-regulated in primary invasive breast cancer tissues compared to matched adjacent non-cancerous tissues. CONCLUSION: These data show for the first time that cytoplasmic GGH might play a relevant role in the development and progression of invasive breast cancer, warranting further investigations. Our findings suggest that GGH serve as a potential biomarker of unfavorable clinical outcomes over short-term follow-up in breast cancer. The GGH may be a very attractive targeted therapy for selected patients.
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[893]
TÍTULO / TITLE: - 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:434709. doi: 10.1155/2013/434709. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/434709
AUTORES / AUTHORS: - Zhang Z; Ye T; Cai X; Yang J; Lu W; Hu C; Wang Z; Wang X; Cao P
INSTITUCIÓN / INSTITUTION: - Laboratory of Cellular and Molecular Biology, Jiangsu Province Institute of Traditional Chinese Medicine, 100 Shizi Street, Hongshang Road, Nanjing, Jiangsu 210028, China.
RESUMEN / SUMMARY: - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for the treatment of cancer, because it preferentially induces apoptosis in numerous cancer cells with little or no effect on normal cells. 5,7-Dihydroxyflavone is a dietary flavonoid commonly found in many plants. Here we show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic concentrations induced strong apoptotic response in human hepatocarcinoma HepG2 cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells. We further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL-induced apoptosis in HepG2 cells. 5,7-Dihydroxyflavone up-regulated the expression of pro-apoptotic protein Bax, attenuated the expression of anti-apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the process of apoptosis. Moreover, 5,7-dihydroxyflavone and TRAIL were well tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced tumor burden in vivo in a HepG2 tumor xenograft model. Interestingly, 5,7-dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not observed in normal human hepatocytes L-O2. These results suggest that the 5,7-dihydroxyflavone in combination with TRAIL might be used for cancer prevention and/or therapy.
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[894]
TÍTULO / TITLE: - Clinicopathological correlation and prognostic significance of protein kinase calpha overexpression in human gastric carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56675. doi: 10.1371/journal.pone.0056675. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056675
AUTORES / AUTHORS: - Lin SC; Chen WY; Lin KY; Chen SH; Chang CC; Lin SE; Fang CL
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
RESUMEN / SUMMARY: - OBJECTIVES: This study investigated the PKCalpha protein expression in gastric carcinoma, and correlated it with clinicopathological parameters. The prognostic significance of PKCalpha protein expression in gastric carcinoma was analyzed. METHODS: Quantitative real-time PCR test was applied to compare the PKCalpha mRNA expression in tumorous and nontumorous tissues of gastric carcinoma in ten randomly selected cases. Then PKCalpha protein expression was evaluated in 215 cases of gastric carcinoma using immunohistochemical method. The immunoreactivity was scored semiquantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely PKCalpha overexpression group with score 2 or 3, and non-overexpression group with score 0 or 1. The PKCalpha protein expression was correlated with clinicopathological parameters. Survival analysis was performed to determine the prognostic significance of PKCalpha protein expression in patients with gastric carcinoma. RESULTS: PKCalpha mRNA expression was upregulated in all ten cases of gastric carcinoma via quantitative real-time PCR test. In immunohistochemical study, eighty-eight out of 215 cases (41%) of gastric carcinoma revealed PKCalpha protein overexpression, which was statistically correlated with age (P = 0.0073), histologic type (P<0.0001), tumor differentiation (P = 0.0110), depth of invasion (P = 0.0003), angiolymphatic invasion (P = 0.0373), pathologic stage (P = 0.0047), and distant metastasis (P = 0.0048). We found no significant difference in overall and disease free survival rates between PKCalpha overexpression and non-overexpression groups (P = 0.0680 and 0.0587). However, PKCalpha protein overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 0.632, P = 0.0415). CONCLUSIONS: PKCalpha protein is upregulated in gastric carcinoma. PKCalpha protein expression is statistically correlated with age, histologic type, tumor differentiation, depth of invasion, angiolymphatic invasion, pathologic stage, and distant metastasis. The PKCalpha protein overexpression in patients with gastric carcinoma is a significant independent prognostic factor in multivariate Cox regression analysis.
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[895]
TÍTULO / TITLE: - Knockdown of AXL receptor tyrosine kinase in osteosarcoma cells leads to decreased proliferation and increased apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Immunopathol Pharmacol. 2013 Jan-Mar;26(1):179-88.
AUTORES / AUTHORS: - Zhang Y; Tang YJ; Man Y; Pan F; Li ZH; Jia LS
INSTITUCIÓN / INSTITUTION: - Department of Orthopedics, Zhabei District Central Hospital, Shanghai, China.
RESUMEN / SUMMARY: - Dysregulation of the Axl receptor tyrosine kinase (RTK) has been implicated in the development and progression of a variety of malignancies. Axl is known to activate strong anti-apoptotic signaling pathways that promote oncogenesis. However, the role of Axl plays in osteosarcoma (OS) remains elusive. The present study aimed to investigate the clinical significance and function of Axl in human OS. Forty cases of OS and corresponding adjacent non-cancerous tissues (ANCT) were collected. The expression of Axl was assessed using immunohistochemical assay through tissue microarray procedure. A loss-of-function experiment was performed to investigate the effects of small hairpin RNA (shRNA)-mediated knockdown of Axl on the expression of p-AKT, poly ADP-ribose polymerase (PARP) and Ki-67, the proliferative activities, indicated by MTT assay, and the apoptotic index in OS MG-63 cells. As a result, the expression of Axl was found in OS tissues with higher strong reactivity rate, compared with the ANCT (75.0 percent vs 20.0 percent, P=0.000), but it did not associate with the age, gender, tumor size, TNM staging and distant metastases (each Pgreater than0.05). Furthermore, knockdown of Axl inhibited the proliferative activities and induced apoptosis in MG-63 cells with decreased expression of p-AKT, and Ki-67 and increased expression of PARP. In conclusion, our findings suggest that Axl is highly expressed in most of the OS tissues compared with the ANCT, and knockdown of Axl inhibits proliferation and induces apoptosis of OS cells possibly through downregulation of the AKT pathway, suggesting that our findings may provide new insights into the potential therapeutic target for cancer.
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[896]
TÍTULO / TITLE: - Cytotoxicity of anthrax lethal toxin to human acute myeloid leukemia cells is nonapoptotic and dependent on extracellular signal-regulated kinase ½ activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Transl Oncol. 2013 Feb;6(1):25-32. Epub 2013 Feb 1.
AUTORES / AUTHORS: - Kassab E; Darwish M; Timsah Z; Liu S; Leppla SH; Frankel AE; Abi-Habib RJ
INSTITUCIÓN / INSTITUTION: - Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon.
RESUMEN / SUMMARY: - In this study, we attempt to target the mitogen-activated protein kinase (MAPK) pathway in acute myeloid leukemia (AML) cells using a recombinant anthrax lethal toxin (LeTx). LeTx consists of protective antigen (PrAg) and lethal factor (LF). PrAg binds cells, is cleaved by furin, oligomerizes, binds three to four molecules of LF, and undergoes endocytosis, releasing LF into the cytosol. LF cleaves MAPK kinases, inhibiting the MAPK pathway. We tested potency of LeTx on a panel of 11 human AML cell lines. Seven cell lines showed cytotoxic responses to LeTx. Cytotoxicity of LeTx was mimicked by the specific mitogen-activated protein/extracellular signal-regulated kinase kinase ½ (MEK1/2) inhibitor U0126, indicating that LeTx-induced cell death is mediated through the MEK1/2-extracellular signal-regulated kinase (ERK1/2) branch of the MAPK pathway. The four LeTx-resistant cell lines were sensitive to the phosphatidylinositol 3-kinase inhibitor LY294002. Co-treatment of AML cells with both LeTx and LY294002 did not lead to increased sensitivity, showing a lack of additive/synergistic effects when both pathways are inhibited. Flow cytometry analysis of MAPK pathway activation revealed the presence of phospho-ERK1/2 only in LeTx-sensitive cells. Staining for Annexin V/propidium iodide and active caspases showed an increase in double-positive cells and the absence of caspase activation following treatment, indicating that LeTx-induced cell death is caspase-independent and nonapoptotic. We have shown that a majority of AML cell lines are sensitive to the LF-mediated inhibition of the MAPK pathway. Furthermore, we have demonstrated that LeTx-induced cytotoxicity in AML cells is nonapoptotic and dependent on phospho-ERK1/2 levels.
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[897]
TÍTULO / TITLE: - Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55665. doi: 10.1371/journal.pone.0055665. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055665
AUTORES / AUTHORS: - Knizhnik AV; Roos WP; Nikolova T; Quiros S; Tomaszowski KH; Christmann M; Kaina B
INSTITUCIÓN / INSTITUTION: - Department of Toxicology, Medical University Center, Mainz, Germany.
RESUMEN / SUMMARY: - Apoptosis, autophagy, necrosis and cellular senescence are key responses of cells that were exposed to genotoxicants. The types of DNA damage triggering these responses and their interrelationship are largely unknown. Here we studied these responses in glioma cells treated with the methylating agent temozolomide (TMZ), which is a first-line chemotherapeutic for this malignancy. We show that upon TMZ treatment cells undergo autophagy, senescence and apoptosis in a specific time-dependent manner. Necrosis was only marginally induced. All these effects were completely abrogated in isogenic glioma cells expressing O(6)-methylguanine-DNA methyltransferase (MGMT), indicating that a single type of DNA lesion, O(6)-methylguanine (O(6)MeG), is able to trigger all these responses. Studies with mismatch repair mutants and MSH6, Rad51 and ATM knockdowns revealed that autophagy induced by O(6)MeG requires mismatch repair and ATM, and is counteracted by homologous recombination. We further show that autophagy, which precedes apoptosis, is a survival mechanism as its inhibition greatly ameliorated the level of apoptosis following TMZ at therapeutically relevant doses (<100 microM). Cellular senescence increases with post-exposure time and, similar to autophagy, precedes apoptosis. If autophagy was abrogated, TMZ-induced senescence was reduced. Therefore, we propose that autophagy triggered by O(6)MeG adducts is a survival mechanism that stimulates cells to undergo senescence rather than apoptosis. Overall, the data revealed that a specific DNA adduct, O(6)MeG, has the capability of triggering autophagy, senescence and apoptosis and that the decision between survival and death is determined by the balance of players involved. The data also suggests that inhibition of autophagy may ameliorate the therapeutic outcome of TMZ-based cancer therapy.
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[898]
TÍTULO / TITLE: - Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Photodiagnosis Photodyn Ther. 2013 Feb;10(1):42-50. doi: 10.1016/j.pdpdt.2012.06.003. Epub 2012 Jul 20.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pdpdt.2012.06.003
AUTORES / AUTHORS: - Sun W; Kajimoto Y; Inoue H; Miyatake S; Ishikawa T; Kuroiwa T
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Osaka Medical College, Takatsuki, Osaka, Japan; Department of Neurosurgery, Pu Nan Hospital, Shanghai, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: Since the ATP-binding cassette transporter ABCG2 plays a physiologically significant role of porphyrin efflux from living cells, the expression of ABCG2 may influences the efficacy of photodynamic therapy (PDT). In this study, we evaluated the effect of gefitinib, a potent ABCG2 inhibitor, on 5-aminolevulinic acid (5-ALA)-PDT in brain tumor cell lines in vitro. MATERIALS AND METHODS: Four human glioma cell lines (U87MG, U118MG, A172, and T98G) and a malignant meningioma cell line (IOMM-Lee) were incubated with gefitinib (0.01-1.0muM) before incubation with 5-ALA (1mM). The effects gefitinib on intracellular protoporphyrin IX (PpIX), mRNA and protein expression of ABCG2, and PDT were evaluated, in vitro. RESULTS: At concentrations of 0.1muM or higher, gefitinib enhanced intracellular levels of PpIX in a dose-dependent manner in all those cell lines. Gefitinib decreased mRNA and plasma membrane protein expression of ABCG2, and efficiently enhanced the effect of 5-ALA-PDT in malignant brain tumor cells. CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.
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[899]
TÍTULO / TITLE: - Synthesis of radiolabeled protein disulfide isomerase (PDI) inhibitors as new potential PET agents for imaging of the enzyme PDI in neurological disorders and cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Appl Radiat Isot. 2013 Apr;74:61-9. doi: 10.1016/j.apradiso.2013.01.003. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.apradiso.2013.01.003
AUTORES / AUTHORS: - Gao M; Yang Q; Wang M; Miller KD; Sledge GW; Zheng QH
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16(th) Street, L3-202, Indianapolis, IN 46202, USA.
RESUMEN / SUMMARY: - Carbon-11-labeled substituted beta-tetrahydrocarbolines were prepared from their corresponding phenolic hydroxyl precursors with [C]CHOTf through O-[C]methylation and isolated by simplified SPE in 50-60% decay corrected radiochemical yields at EOB with 185-370GBq/mumol specific activity at EOS. A fluorine-18-labeled substituted beta-tetrahydrocarboline was prepared from its corresponding halo-precursors (X=Cl, Br, I) with K[F]F/Kryptofix 2.2.2 via the nucleophilic substitution and isolated by HPLC combined with SPE in 25-40% decay corrected radiochemical yield with 37-222GBq/mumol specific activity at EOB.
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[900]
TÍTULO / TITLE: - Inactivation of DNA-Dependent Protein Kinase Promotes Heat-Induced Apoptosis Independently of Heat-Shock Protein Induction in Human Cancer Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58325. doi: 10.1371/journal.pone.0058325. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058325
AUTORES / AUTHORS: - Okazawa S; Furusawa Y; Kariya A; Hassan MA; Arai M; Hayashi R; Tabuchi Y; Kondo T; Tobe K
INSTITUCIÓN / INSTITUTION: - First Department of Internal Medicine, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, Toyama, Japan ; Department of Radiological Sciences, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
RESUMEN / SUMMARY: - The inhibition of DNA damage response pathway seems to be an attractive strategy for cancer therapy. It was previously reported that in rodent cells exposed to heat stress, cell growth was promoted by the activity of DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair. The absence of a functioning DNA-PK was associated with down regulation of heat shock protein 70 (HSP70). The objective of this study is thus to investigate the role of DNA-PK inhibition in heat-induced apoptosis in human cell lines. The inhibitors of phosphorylation of the DNA-PK catalytic subunit (DNA-PKcs) at Ser2056, such as NU7026 and NU7441, were utilized. Furthermore, knock down of DNA-PKcs was carried out using small interfering RNA (siDNA-PKcs). For heat exposure, cells were placed in water bath at 44 degrees C for 60 min. Apoptosis was evaluated after 24 h incubation flow cytometrically. Proteins were extracted after 24 h and analyzed for HSP70 and HSP40 expression by Western blotting. Total RNA was extracted 6 h after treatment and analyzed using a GeneChip® microarray system to identify and select the up-regulated genes (>/=1.5 fold). The results showed an enhancement in heat-induced apoptosis in absence of functioning DNA-PKcs. Interestingly, the expression levels of HSP70 and HSP40 were elevated in the absence of DNA-PKcs under heat stress. The results of genetic network analysis showed that HSPs and JUN genes were up-regulated independently of DNA-PKcs in exposed parent and knock out cells. In the presence of functioning DNA-PKcs, there was an observed up-regulation of anti-apoptotic genes, such as NR1D1, whereas in the absence of DNA-PKcs the pro-apoptotic genes, such as EGR2, were preferentially up-regulated. From these findings, we concluded that in human cells, the inactivation of DNA-PKcs can promote heat-induced apoptosis independently of heat-shock proteins.
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[901]
TÍTULO / TITLE: - Caffeic acid phenylethyl ester and MG132, two novel nonconventional chemotherapeutic agents, induce apoptosis of human leukemic cells by disrupting mitochondrial function.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0256-y
AUTORES / AUTHORS: - Cavaliere V; Papademetrio DL; Lombardo T; Costantino SN; Blanco GA; Alvarez EM
INSTITUCIÓN / INSTITUTION: - Laboratorio de Inmunologia Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina, vcavaliere@ffyb.uba.ar.
RESUMEN / SUMMARY: - The ability to modulate balance between cell survival and death is recognized for its great therapeutic potential. Therefore, research continues to focus on elucidation of cell machinery and signaling pathways that control cell proliferation and apoptosis. Conventional chemotherapeutic agents often have a cytostatic effect over tumor cells. New natural or synthetic chemotherapeutic agents have a wider spectrum of interesting antitumor activities that merit in-depth studies. In the present work, we aimed at characterizing the molecular mechanism leading to induction of cell death upon treatment of the lymphoblastoid cell line PL104 with caffeic acid phenylethyl ester (CAPE), MG132 and two conventional chemotherapeutic agents, doxorubicine (DOX) and vincristine (VCR). Our results showed several apoptotic hallmarks such as phosphatidylserine (PS) exposure on the outer leaflet of the cell membrane, nuclear fragmentation, and increase sub-G1 DNA content after all treatments. In addition, all four drugs downregulated survivin expression. CAPE and both chemotherapeutic agents reduced Bcl-2, while only CAPE and MG132 significantly increased Bax level. CAPE and VCR treatment induced the collapse of mitochondrial membrane potential (psim). All compounds induced cytochrome c release from mitochondrial compartment to cytosol. However, only MG132 caused the translocation of Smac/DIABLO. Except for VCR treatment, all other drugs increased reactive oxygen species (ROS) production level. All treatments induced activation of caspases 3/7, but only CAPE and MG132 led to the activation of caspase 9. In conclusion, our results indicate that CAPE and MG132 treatment of PL104 cells induced apoptosis through the mitochondrial intrinsic pathway, whereas the apoptotic mechanism induced by DOX and VCR may proceed through the extrinsic pathway.
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[902]
TÍTULO / TITLE: - EGFR intron-1 CA repeat polymorphism is a predictor of relapse and survival in complete resected only surgically treated esophageal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Feb 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0260-2
AUTORES / AUTHORS: - Vashist YK; Trump F; Gebauer F; Kutup A; Gungor C; Kalinin V; Muddasar R; Vettorazzi E; Yekebas EF; Brandt B; Pantel K; Izbicki JR
INSTITUCIÓN / INSTITUTION: - Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martini Strasse 52, 20246, Hamburg, Germany, vashist@uke.de.
RESUMEN / SUMMARY: - Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted from peripheral blood leukocytes of 241 patients. To determine the number of the CA repeats in the CA-SSR-1, DNA was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters and clinical outcome. Three genotypes were defined based on cut-off points for short allele (S) with </=18 and long allele (L) >18 CA repeats. A steadily increasing risk was evident between LL, SL, and SS genotype for larger tumor size, presence of lymph node metastases, and disseminated tumor cells in bone marrow as well as tumor recurrence (P < 0.001, chi-square test). A gradual decrease in disease-free and overall survival (OS) was present among LL, SL, and SS patients (P < 0.001, log-rank test). The different outcomes were also evident in nodal status and histological type adjusted subgroup analyses. CA-SSR-1 was identified as the strongest independent prognosticator of tumor recurrence and OS (P < 0.001, Cox regression analysis). CA-SSR-1 is a strong predictive factor for tumor recurrence and overall survival in patients with complete resected esophageal cancer without neoadjuvant or adjuvant therapy.
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[903]
TÍTULO / TITLE: - Epidermal growth factor receptor mutation status and rad51 determine the response of glioblastoma to multimodality therapy with cetuximab, temozolomide, and radiation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Oncol. 2013;3:13. doi: 10.3389/fonc.2013.00013. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00013
AUTORES / AUTHORS: - Wachsberger PR; Lawrence RY; Liu Y; Rice B; Daskalakis C; Dicker AP
INSTITUCIÓN / INSTITUTION: - Molecular Radiation Biology, Department of Radiation Oncology, Thomas Jefferson University Philadelphia, PA, USA.
RESUMEN / SUMMARY: - Purpose: EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolomide (TMZ), and radiation therapy (RT).Methods and Materials:In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR) and the other overexpressing EGFRvIII (U87EGFRvIII).Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing.Conclusion: The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant.
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[904]
TÍTULO / TITLE: - Histone deacetylase inhibitors: novel agents in cancer treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin J Oncol Nurs. 2013 Feb;17(1):34-40. doi: 10.1188/13.CJON.34-40.
●● Enlace al texto completo (gratuito o de pago) 1188/13.CJON.34-40
AUTORES / AUTHORS: - Glass E; Viale PH
INSTITUCIÓN / INSTITUTION: - St. Agnes Cancer Institute, Baltimore, MD, USA. ericaglass@hotmail.com
RESUMEN / SUMMARY: - Histone deacetylase inhibitors (HDAC-Is) are agents that have demonstrated anticancer activity in vivo and in vitro, leading to clinical trials evaluating their efficacy in multiple cancer types. Only two HDAC-Is are currently approved by the U.S. Food and Drug Administration, vorinostat and romidepsin, both with indications for cutaneous T-cell lymphoma. Romidepsin has an additional approval in peripheral T-cell lymphoma. Promising clinical trial results in other cancer types will likely lead to expanded use of these and other HDAC-Is. To provide care for patients receiving these agents, oncology nurses should be knowledgeable about the emerging role of HDAC-Is. This article reviews the mechanism of action of HDAC-Is, currently approved therapies, and nursing management of cutaneous T-cell lymphoma.
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[905]
TÍTULO / TITLE: - Reactivation of the homeotic tumor suppressor gene CDX2 by 5-aza-2’-deoxycytidine-induced demethylation inhibits cell proliferation and induces caspase-independent apoptosis in gastric cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Mar;5(3):735-741. Epub 2013 Jan 17.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2013.901
AUTORES / AUTHORS: - Zhang JF; Zhang JG; Kuai XL; Zhang H; Jiang W; Ding WF; Li ZL; Zhu HJ; Mao ZB
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
RESUMEN / SUMMARY: - The DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-aza-CdR) is widely used as an anticancer drug for the treatment of leukemia and solid tumors. Gastric cancer (GC) patients who were positive for caudal type homeobox transcription factor 2 (CDX2) expression showed a higher survival rate compared with those who were CDX2 negative, which suggests that CDX2 performs a tumor suppressor role. However, the molecular mechanisms leading to the inactivation of CDX2 remain unclear. In the present study we demonstrated that the expression levels of CDX2 and DNA methyltransferase enzyme 1 (DNMT1) mRNA were significantly higher in GC compared with distal non-cancerous tissue. The expression of CDX2 mRNA was significantly correlated with Lauren classification, TNM stage and lymph node metastasis. DNMT1 mRNA expression was significantly correlated with TNM stage, pathological differentiation and lymph node metastasis. The expression of CDX2 mRNA was inversely correlated with that of DNMT1 mRNA in GC. Hypermethylation of the CDX2 gene promoter region, extremely low expression levels of CDX2 mRNA and no expression of CDX2 protein were the characteristics observed in MKN-45 and SGC-7901 GC cell lines. Following the treatment of MKN-45 cells with 5-aza-CdR, the hypermethylated CDX2 gene promoter region was demethylated and expression of CDX2 was upregulated, while DNMT1 expression was downregulated. Furthermore, a concentration- and time-dependent growth inhibition as well as increased apoptosis were observed. Caspase-3, -8 and -9 activities increased in a concentration-dependent manner following exposure to different concentrations of 5-aza-CdR. Therefore, our data show that the overexpression of DNMT1 and methylation of the CDX2 gene promoter region is likely to be responsible for CDX2 silencing in GC. 5-Aza-CdR may effectively induce re-expression of the CDX2 gene, inhibit cell proliferation and enhance the caspase-independent apoptosis of MKN-45 cells in vitro.
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[906]
TÍTULO / TITLE: - Downregulation of Mcl-1 through inhibition of translation contributes to benzyl isothiocyanate-induced cell cycle arrest and apoptosis in human leukemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 28;4:e515. doi: 10.1038/cddis.2013.41.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.41
AUTORES / AUTHORS: - Zhou T; Li G; Cao B; Liu L; Cheng Q; Kong H; Shan C; Huang X; Chen J; Gao N
INSTITUCIÓN / INSTITUTION: - Department of Pharmacognosy, School of Pharmacy, 3rd Military Medical University, Chongqing, China.
RESUMEN / SUMMARY: - Benzyl isothiocyanate (BITC) is one of the compounds of ITCs’ family that has attracted a great deal of interest because of its ability to exhibit anticancer activity. In this study, we investigated the effects of BITC on cell cycle arrest and apoptosis in human leukemia cell lines, primary leukemia cells, and nude mice Jurkat xenograft. Exposure of Jurkat cells to BITC resulted in dose- and time-dependent increase in apoptosis, caspase activation, cytochrome c release, nuclear apoptosis-inducing factor (AIF) accumulation, Bcl2-associated X protein (Bax) translocation, and myeloid cell leukemia-1 (Mcl-1) downregulation. Treatment with these cells also resulted in cell cycle arrest at the G2/M phase. The G2/M-arrested cells are more sensitive to undergoing Mcl-1 downregulation and apoptosis mediated by BITC. BITC downregulates Mcl-1 expression through inhibition of translation, rather than through a transcriptional, post-translational, or caspase-dependent mechanism. Dephosphorylation of eukaryotic initiation factor 4G could contribute to the inhibition of Mcl-1 translation mediated by BITC. Furthermore, ectopic expression of Mcl-1 substantially attenuates BITC-mediated lethality in these cells, whereas knockdown of Mcl-1 through small interfering RNA significantly enhances BITC-mediated lethality. Finally, administration of BITC markedly inhibited tumor growth and induced apoptosis in Jurkat xenograft model in association with the downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Mcl-1 potentiate BITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of Jurkat xenograft model.
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[907]
TÍTULO / TITLE: - Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 28;4:e516. doi: 10.1038/cddis.2013.39.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.39
AUTORES / AUTHORS: - Gausdal G; Wergeland A; Skavland J; Nguyen E; Pendino F; Rouhee N; McCormack E; Herfindal L; Kleppe R; Havemann U; Schwede F; Bruserud O; Gjertsen BT; Lanotte M; Segal-Bendirdjian E; Doskeland SO
INSTITUCIÓN / INSTITUTION: - Department of Biomedicine, University of Bergen, Bergen, Norway.
RESUMEN / SUMMARY: - We show that cyclic AMP (cAMP) elevating agents protect blasts from patients with acute promyelocytic leukemia (APL) against death induced by first-line anti-leukemic anthracyclines like daunorubicin (DNR). The cAMP effect was reproduced in NB4 APL cells, and shown to depend on activation of the generally cytoplasmic cAMP-kinase type I (PKA-I) rather than the perinuclear PKA-II. The protection of both NB4 cells and APL blasts was associated with (inactivating) phosphorylation of PKA site Ser118 of pro-apoptotic Bad and (activating) phosphorylation of PKA site Ser133 of the AML oncogene CREB. Either event would be expected to protect broadly against cell death, and we found cAMP elevation to protect also against 2-deoxyglucose, rotenone, proteasome inhibitor and a BH3-only mimetic. The in vitro findings were mirrored by the findings in NSG mice with orthotopic NB4 cell leukemia. The mice showed more rapid disease progression when given cAMP-increasing agents (prostaglandin E analog and theophylline), both with and without DNR chemotherapy. The all-trans retinoic acid (ATRA)-induced terminal APL cell differentiation is a cornerstone in current APL treatment and is enhanced by cAMP. We show also that ATRA-resistant APL cells, believed to be responsible for treatment failure with current ATRA-based treatment protocols, were protected by cAMP against death. This suggests that the beneficial pro-differentiating and non-beneficial pro-survival APL cell effects of cAMP should be weighed against each other. The results suggest also general awareness toward drugs that can affect bone marrow cAMP levels in leukemia patients.
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[908]
TÍTULO / TITLE: - TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 22;13(1):140.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-140
AUTORES / AUTHORS: - Yuan BZ; Chapman J; Ding M; Wang J; Jiang B; Rojanasakul Y; Reynolds SH
RESUMEN / SUMMARY: - BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy closely associated with asbestos exposure and extremely resistant to current treatments. It exhibits a steady increase in incidence, thus necessitating an urgent development of effective new treatments. METHODS: Proteasome inhibitors (PIs) and TNFalpha-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents. To develop effective new treatments, the proapoptotic effects of PIs, MG132 or Bortezomib, and TRAIL were investigated in MPM cell lines NCI-H2052, NCI-H2452 and NCI-H28, which represent three major histological types of human MPM. RESULTS: Treatment with 0.5-1 muM MG132 alone or 30 ng/mL Bortezomib alone induced a limited apoptosis in MPM cells associated with the elevated Mcl-1 protein level and hyperactive PI3K/Akt signaling. However, whereas 10--20 ng/ml TRAIL alone induced a limited apoptosis as well, TRAIL and PI combination triggered a robust apoptosis in all three MPM cell lines. The robust proapoptotic activity was found to be the consequence of a positive feedback mechanism-governed amplification of caspase activation and cleavage of both Mcl-1 and Akt proteins, and exhibited a relative selectivity in MPM cells than in non-tumorigenic Met-5A mesothelial cells. CONCLUSION: The combinatorial treatment using TRAIL and PI may represent an effective new treatment for MPMs.
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[909]
TÍTULO / TITLE: - Combined Treatment of Androgen-Independent Prostate Cancer Cell Line DU145 with Chemotherapeutic Agents and Lithium Chloride: Effect on Growth Arrest and/or Apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Avicenna J Med Biotechnol. 2012 Apr;4(2):75-87.
AUTORES / AUTHORS: - Hossein G; Zavareh VA; Fard PS
INSTITUCIÓN / INSTITUTION: - School of Biology, University College of Science, University of Tehran, Tehran, Iran.
RESUMEN / SUMMARY: - Hormone-independent prostate cancer cell lines are resistant to antineoplastic drugs, this study sought to determine the usefulness of lithium chloride as an inhibitor of glycogen synthase kinase-3beta to increase the cytotoxic effect of doxorubicin, etoposide or vinblastine antineoplastic drugs on DU145 cells. Combination effect was assessed by using low and IC(50) doses of drugs + lithium chloride. Subsequently, cell cycle analysis and p53 levels and its subcellular localization as a key regulator of cell cycle were assessed. Lithium chloride showed cytotoxic effect in a dose and time dependent manner (p<0.001). Both drugs doxorubicin and etoposide in combination with lithium chloride (LiCl) showed higher percent of cells in SubG1 compared to control (p<0.001). Combination of IC(50) dose of doxorubicin and lithium chloride led to S phase arrest (p<0.001, compared to control, lithium chloride or doxorubicin alone). Moreover, G2/M arrest was significantly increased when low dose of doxorubicin and vinblastine were combined with lithium chloride (p<0.001, compared to control and lithium chloride alone). DU145 cells were highly sensitive to vinblastine and no significant changes were observed when combined with lithium chloride. The IC(50) doses of all three drugs combined with lithium chloride demonstrated decreased cell percent in G1 phase compared to control or lithium chloride alone (p<0.001). Moreover, in the presence of lithium chloride there were increased levels of p53 in cytoplasm and nucleus (p<0.05). Our results suggest that combination of lithium chloride with chemotherapeutic agents may increases their cytotoxic effect on hormone non-responsive human prostate cancer cells.
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[910]
TÍTULO / TITLE: - HMG-CoA reductase inhibitors induce apoptosis of lymphoma cells by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 28;4:e518. doi: 10.1038/cddis.2013.44.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.44
AUTORES / AUTHORS: - Qi XF; Zheng L; Lee KJ; Kim DH; Kim CS; Cai DQ; Wu Z; Qin JW; Yu YH; Kim SK
INSTITUCIÓN / INSTITUTION: - Key Laboratory for Regenerative Medicine of Ministry of Education, and Department of Developmental and Regenerative Biology, Ji Nan University School of Life Science and Technology, Guangzhou, People’s Republic of China.
RESUMEN / SUMMARY: - Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used cholesterol-lowering drugs. Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. The objective here was to elucidate the molecular mechanism by which statins induce lymphoma cells death. Statins (atorvastatin, fluvastatin and simvastatin) treatment enhanced the DNA fragmentation and the activation of proapoptotic members such as caspase-3, PARP and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells, which was accompanied by inhibition of cell survival. Both increase in levels of reactive oxygen species (ROS) and activation of p38 MAPK and decrease in mitochondrial membrane potential and activation of Akt and Erk pathways were observed in statin-treated lymphoma cells. Statin-induced cytotoxic effects, DNA fragmentation and changes of activation of caspase-3, Akt, Erk and p38 were blocked by antioxidant (N-acetylcysteine) and metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggests that HMG-CoA reductase inhibitors induce lymphoma cells apoptosis by increasing intracellular ROS generation and p38 activation and suppressing activation of Akt and Erk pathways, through inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.
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[911]
TÍTULO / TITLE: - Low probability activation of Bax/Bak can induce selective killing of cancer cells by generating heterogeneity in apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Healthc Eng. 2013;4(1):47-66. doi: 10.1260/2040-2295.4.1.47.
●● Enlace al texto completo (gratuito o de pago) 1260/2040-2295.4.1.47
AUTORES / AUTHORS: - Raychaudhuri S; Das SC
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, University of California, Davis, CA, USA. scdas@ucdavis.edu
RESUMEN / SUMMARY: - Biomimetic pro-apoptotic agents (e.g., BH3 mimetics) have been shown to activate the intrinsic death pathway (Type 2 apoptosis) selectively in cancer cells, a mechanism that can be key to developing successful anti-cancer therapy. This work reports mathematical modeling and computer simulations to explore the mechanisms for cancer cell apoptosis. The results indicate that a combination of low probability Bid-Bax type reaction along with overexpressed reactant molecules allows specific killing of cancer cells. Low-probability activation of Bax also emerges as a basis for inherent cell-to-cell variability in apoptotic activation. Variations in Bcl-2 to Bax ratio within a cancer cell population can further affect intrinsic fluctuations generated due to the stochastic Bid-Bax reaction. Such heterogeneity in apoptosis resistance can also provide a mechanism for the origin of cells with higher tumorigenic potential (cancer stem-like cells). The implications of our results for cancer therapy, such as in minimizing stochastic fluctuations in cancer cell death, are discussed.
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[912]
TÍTULO / TITLE: - Imaging of Firefly Luciferase Activity under Antiangiogenic Therapy in a Heat Shock Protein 70-Transfected Melanoma Tumor Model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Imaging. 2013 Feb 1;12(2):129-36.
AUTORES / AUTHORS: - Hundt W; Schink C; Steinbach S; O’Connell-Rodwell CE; Burbelko M; Kiessling A; Librizzi D; Pfestroff A; Guccione S
RESUMEN / SUMMARY: - AbstractWe investigated the effect of targeted gene therapy on heat shock protein 70 (Hsp70) expression in a melanoma tumor model (M21). M21 cells transfected with a plasmid containing the firefly luciferase reporter gene (ffluc), whose expression is driven by the hsp70 (hspa1b) or the cytomegalovirus (CMV) promoter, were grown to a size of 600 mm3. Five animals in each group were intravenously treated with an Arg-Gly-Asp peptide-nanoparticle/Raf-1 kinase inhibitor protein [RGD-NP/RAF(-)] complex. Bioluminescence imaging (BLI) (IVIS, Xenogen, Alameda, CA) was performed at set time intervals. Western blot analysis of the HSP70 protein was simultaneously performed. The size of the treated M21 tumors was nearly constant (637.8 +/- 33.4 mm3 vs 674.8 +/- 34.4 mm3). BLI showed that if transcription was controlled by the CMV promoter, firefly luciferase activity decreased to 51.1% +/- 8.3%. When transcription was controlled by the hsp70 promoter, the highest firefly luciferase activity (4.4 +/- 0.3-fold) was observed after 24 hours. In accordance with BLI, Western blot analysis showed an increase in the level of HSP70, with the maximum detection 24 hours after the injection of the RGD-NP/RAF(-) complex. Targeted antiangiogenic therapy can induce luciferase activity where transcription is controlled by an hsp70 promoter and HSP70 protein in melanoma tumors.
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[913]
TÍTULO / TITLE: - Mitotic Arrest and Apoptosis in Breast Cancer Cells Induced by Origanum majorana Extract: Upregulation of TNF-alpha and Downregulation of Survivin and Mutant p53.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56649. doi: 10.1371/journal.pone.0056649. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056649
AUTORES / AUTHORS: - Al Dhaheri Y; Eid A; Abuqamar S; Attoub S; Khasawneh M; Aiche G; Hisaindee S; Iratni R
INSTITUCIÓN / INSTITUTION: - Department of Biology, College of Science, United Arab Emirates University, Al-Ain, United Arab Emirates.
RESUMEN / SUMMARY: - BACKGROUND: In the present study, we investigated the effect of Origanum majorana ethanolic extract on the survival of the highly proliferative and invasive triple-negative p53 mutant breast cancer cell line MDA-MB-231. RESULTS: We found that O. majorana extract (OME) was able to inhibit the viability of the MDA-MB-231 cells in a time- and concentration-dependent manner. The effect of OME on cellular viability was further confirmed by the inhibition of colony growth. We showed, depending on the concentration used, that OME elicited different effects on the MDA-MB 231 cells. Concentrations of 150 and 300 microg/mL induced an accumulation of apoptotic-resistant population of cells arrested in mitotis and overexpressing the cyclin-dependent kinase inhibitor, p21 and the inhibitor of apoptosis, survivin. On the other hand, higher concentrations of OME (450 and 600 microg/mL) triggered a massive apoptosis through the extrinsic pathway, including the activation of tumor necrosis factor-alpha (TNF-alpha), caspase 8, caspase 3, and cleavage of PARP, downregulation of survivin as well as depletion of the mutant p53 in MDA-MB-231 cells. Furthermore, OME induced an upregulation of gamma-H2AX, a marker of double strand DNA breaks and an overall histone H3 and H4 hyperacetylation. CONCLUSION: Our findings provide strong evidence that O. majorana may be a promising chemopreventive and therapeutic candidate against cancer especially for highly invasive triple negative p53 mutant breast cancer; thus validating its complementary and alternative medicinal use.
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[914]
TÍTULO / TITLE: - Common genetic variants in Wnt signaling pathway genes as potential prognostic biomarkers for colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56196. doi: 10.1371/journal.pone.0056196. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056196
AUTORES / AUTHORS: - Ting WC; Chen LM; Pao JB; Yang YP; You BJ; Chang TY; Lan YH; Lee HZ; Bao BY
INSTITUCIÓN / INSTITUTION: - Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.
RESUMEN / SUMMARY: - Compelling evidence has implicated the Wnt signaling pathway in the pathogenesis of colorectal cancer. We assessed the use of tag single nucleotide polymorphisms (tSNPs) in adenomatous polyposis coli (APC)/beta-catenin (CTNNB1) genes to predict outcomes in patients with colorectal cancer. We selected and genotyped 10 tSNP to predict common variants across entire APC and CTNNB1 genes in 282 colorectal cancer patients. The associations of these tSNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis. The 5-year overall survival rate was 68.3%. Survival tree analysis identified a higher-order genetic interaction profile consisting of the APC rs565453, CTNNB1 2293303, and APC rs1816769 that was significantly associated with overall survival. The 5-year survival overall rates were 89.2%, 66.1%, and 58.8% for the low-, medium-, and high-risk genetic profiles, respectively (log-rank P = 0.001). After adjusting for possible confounders, including age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, perineural invasion, and lymph node involvement, the genetic interaction profile remained significant. None of the studied SNPs were individually associated with distant metastasis-free survival and overall survival. Our results suggest that the genetic interaction profile among Wnt pathway SNPs might potentially increase the prognostic value in outcome prediction for colorectal cancer.
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[915]
TÍTULO / TITLE: - Bone mineral density screening among women with a history of breast cancer treated with aromatase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Womens Health (Larchmt). 2013 Feb;22(2):132-40. doi: 10.1089/jwh.2012.3687. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1089/jwh.2012.3687
AUTORES / AUTHORS: - Spangler L; Yu O; Loggers E; Boudreau DM
INSTITUCIÓN / INSTITUTION: - Group Health Research Institute, Seattle, WA 98101, USA. spangler.l@aghe.org
RESUMEN / SUMMARY: - BACKGROUND: Understanding adherence to bone mineral density (BMD) screening after breast cancer (BC) treatment with aromatase inhibitors (AI) is an important first step in preventing or treating BC-related osteoporosis. METHODS: This retrospective cohort study assessed receipt and adherence to BMD screening among 342 women diagnosed with BC who were at high risk for osteoporosis after BC treatment with AI between 2004 and 2007. Nonadherence to baseline and annual BMD screening (recommended by 2003 American Society of Clinical Oncology Guidelines) was assessed using descriptive statistics and Poisson regression models accounting for length of AI use and follow-up. RESULTS: In the year before AI initiation, 16% of women received BMD screening. Fifty-six percent had no BMD screening in the 14 months after a minimum of 9 months of continuous AI use, and 75% and 66% failed to have BMD screens during the second (14.1-26 month) and third (26.1-38 month) annual time periods after continuous AI use for at least 23 and 35 months, respectively. Overall, 24% had no BMD screening after 35 months of continuous AI use. Statistically significant predictors of nonadherence included predominant exemestane use, BMD screening before AI initiation, and diabetes mellitus history. Postcollege education, geographic region of primary care clinic, and never smoking were associated with a reduced risk of nonadherence. CONCLUSIONS: A significant proportion of breast cancer patients treated with AI did not receive guideline-recommended BMD screening. Findings should raise awareness of the importance of BMD screening and targeting women at increased risk of screening nonadherence.
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[916]
TÍTULO / TITLE: - Aromatase inhibitor adjuvant chemotherapy of breast cancer results in cancer therapy induced bone loss.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Osteoporos Rep. 2013 Mar;11(1):61-4. doi: 10.1007/s11914-013-0134-7.
●● Enlace al texto completo (gratuito o de pago) 1007/s11914-013-0134-7
AUTORES / AUTHORS: - Rinaldi RZ
INSTITUCIÓN / INSTITUTION: - Cedars Sinai Medical Center, The David Geffen School of Medicine, UCLA, 150 North Robertson Blvd, Beverly Hills, CA, 90211, USA, rzrinaldi@gmail.com.
RESUMEN / SUMMARY: - Aromatase Inhibitors are anti-estrogen agents that have proven efficacy for adjuvant therapy of estrogen receptor positive breast cancer primarily in post menopausal women with estrogen receptor positive breast cancer but increase the risk of cancer therapy induced bone loss (CTIBL). Recent studies have shown the potential benefit of bisphosphonate therapy to play a dual role in the management of breast cancer. These studies provide evidence that bisphosphonate therapy in conjunction with aromatase inhibitors (AI), not only decreases the risk of osteoporosis but, in addition, may improve survival from breast cancer.
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[917]
TÍTULO / TITLE: - Apoptosis of human breast cancer cells induced by microencapsulated betulinic acid from sour jujube fruits through the mitochondria transduction pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Chem. 2013 Jun 1;138(2-3):1998-2007. doi: 10.1016/j.foodchem.2012.10.079. Epub 2012 Nov 15.
●● Enlace al texto completo (gratuito o de pago) 1016/j.foodchem.2012.10.079
AUTORES / AUTHORS: - Sun YF; Song CK; Viernstein H; Unger F; Liang ZS
INSTITUCIÓN / INSTITUTION: - College of Science, Liaoning Technical University, Fuxin, Liaoning 123000, China. katherineyfs@gmail.com
RESUMEN / SUMMARY: - Betulinic acid (BA), a natural pentacyclic triterpenoid, was isolated from sour jujube fruits for the first time. An inclusion complex comprising BA and beta-cyclodextrin (beta-CD) was formed to improve the dissolution of BA, but little is known about its anticancer effect. In this study, the anti-proliferative and apoptosis mechanisms of BA-beta-CD on human breast cancer MCF-7 cells were further investigated. Experimental results confirmed that the complexation model inhibited the growth of MCF-7 cells in a dose-dependent manner, arrested cell cycle in the G2/M phase and induced apoptosis via the mitochondria transduction pathway. Gene and protein analyses showed that the complexation model significantly inhibited Bcl-2 expression and promoted Bax expression, causing caspase-3 and caspase-9 cascade activation. These findings corroborated evidence on microencapsulated BA as an apoptosis inducer in MCF-7 cells. Thus, sour jujube fruits may have potential use as a breast cancer chemotherapeutic agent.
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[918]
TÍTULO / TITLE: - Embelin-induced MCF-7 breast cancer cell apoptosis and blockade of MCF-7 cells in the G2/M phase via the mitochondrial pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):1005-1009. Epub 2012 Dec 19.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1084
AUTORES / AUTHORS: - Li Y; Li D; Yuan S; Wang Z; Tang F; Nie R; Weng J; Ma L; Tang B
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Affiliated Hospital of Guilin Medical University, Guilin 541001;
RESUMEN / SUMMARY: - Embelin is a small molecular inhibitor extracted from Myrsinaceae plants that specifically inhibits XIAP, affecting the proliferation and apoptosis of various types of tumor cells. In our previous studies, we have demonstrated that embelin is able to induce the apoptosis of MCF-7 breast cancer cells in a dose-dependent manner. However, its mechanism of action is not yet clear. The purpose of this study was to investigate the involvement of the mitochondrial pathway in embelin-induced apoptosis and the effect of embelin on the cell cycle. Different doses of embelin were added to MCF-7 breast cancer cells and it was found that embelin was able to induce apoptosis of MCF-7 breast cancer cells in a dose- and time-dependent manner. Flow cytometry analysis revealed that embelin caused changes in the MCF-7 cell mitochondrial membrane potential and blocked the cell cycle of MCF-7 cells in the G2/M phase. Moreover, embelin was demonstrated to promote mitochondrial release of cytochrome C via regulation of Bax and Bcl-2, resulting in the activation of caspase-3 and -9, while no significant changes in the level of caspase-8 were observed. The results have demonstrated that embelin-induced apoptosis of MCF-7 breast cancer cells involves the mitochondrial pathway.
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[919]
TÍTULO / TITLE: - Functional cooperation of miR-125a, miR-125b, and miR-205 in entinostat-induced downregulation of erbB2/erbB3 and apoptosis in breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 21;4:e556. doi: 10.1038/cddis.2013.79.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.79
AUTORES / AUTHORS: - Wang S; Huang J; Lyu H; Lee CK; Tan J; Wang J; Liu B
INSTITUCIÓN / INSTITUTION: - 1] Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA [2] Fujian Key Laboratory of Transplant Biology, Fuzhou General Hospital, Fuzhou, Fujian, China.
RESUMEN / SUMMARY: - We reported that the class I HDAC inhibitor entinostat induced apoptosis in erbB2-overexpressing breast cancer cells via downregulation of erbB2 and erbB3. Here, we study the molecular mechanism by which entinostat dual-targets erbB2/erbB3. Treatment with entinostat had no effect on erbB2/erbB3 mRNA, suggesting a transcription-independent mechanism. Entinostat decreased endogenous but not exogenous erbB2/erbB3, indicating it did not alter their protein stability. We hypothesized that entinostat might inhibit erbB2/erbB3 protein translation via specific miRNAs. Indeed, entinostat significantly upregulated miR-125a, miR-125b, and miR-205, that have been reported to target erbB2 and/or erbB3. Specific inhibitors were then used to determine whether these miRNAs had a causal role in entinostat-induced downregulation of erbB2/erbB3 and apoptosis. Transfection with a single inhibitor dramatically abrogated entinostat induction of miR-125a, miR-125b, or miR-205; however, none of the inhibitors blocked entinostat action on erbB2/erbB3. In contrast, co-transfection with two inhibitors not only reduced their corresponding miRNAs, but also significantly abrogated entinostat-mediated reduction of erbB2/erbB3. Moreover, simultaneous inhibition of two, but not one miRNA significantly attenuated entinostat-induced apoptosis. Interestingly, although the other HDAC inhibitors, such as SAHA and panobinostat, exhibited activity as potent as entinostat to induce growth inhibition and apoptosis in erbB2-overexpressing breast cancer cells, they had no significant effects on the three miRNAs. Instead, both SAHA- and panobinostat-decreased erbB2/erbB3 expression correlated with the reduction of their mRNA levels. Collectively, we demonstrate that entinostat specifically induces expression of miR-125a, miR-125b, and miR-205, which act in concert to downregulate erbB2/erbB3 in breast cancer cells. Our data suggest that epigenetic regulation via miRNA-dependent or -independent mechanisms may represent a novel approach to treat breast cancer patients with erbB2-overexpressing tumors.
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[920]
TÍTULO / TITLE: - Cytotoxicity and induction of apoptosis of human breast cancer cells by novel platinum(II) complexes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Environ Toxicol Pharmacol. 2013 Mar;35(2):254-64. doi: 10.1016/j.etap.2012.12.010. Epub 2012 Dec 30.
●● Enlace al texto completo (gratuito o de pago) 1016/j.etap.2012.12.010
AUTORES / AUTHORS: - Bielawski K; Czarnomysy R; Muszynska A; Bielawska A; Poplawska B
INSTITUCIÓN / INSTITUTION: - Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland. Electronic address: kbiel@umwb.edu.pl.
RESUMEN / SUMMARY: - The current work investigates the influence of novel dinuclear platinum(II) compounds of structure: Pt(3-ethylpyridine)(berenil) (Pt10) and Pt(3-butylpyridine)(berenil) (Pt11) on growth and viability of MDA-MB-231 and MCF-7 breast cancer cells as well as their putative mechanism of cytotoxicity. Evaluation of the cytotoxicity of Pt10 and Pt11 employing a MTT assay and inhibition of [H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more potent antiproliferative agents than cisplatin. In our study the induction of apoptosis by Pt10 and Pt11 in human breast cancer cells was confirmed by several biochemical markers, such as: phosphatidylserine externalization, loss of mitochondrial membrane potential DeltaPsi, caspase-3, -8, -9 activity, and DNA degradation. Pt10 and Pt11 induce apoptosis of breast cancer cells via mechanisms dependent on caspases activation and associated with mitochondrial membrane potential disruption.
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[921]
TÍTULO / TITLE: - Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Jan 31;4:e479. doi: 10.1038/cddis.2013.5.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.5
AUTORES / AUTHORS: - Bernardo AR; Cosgaya JM; Aranda A; Jimenez-Lara AM
INSTITUCIÓN / INSTITUTION: - Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, Madrid, España.
RESUMEN / SUMMARY: - Due to its ability to regulate the growth, differentiation and apoptosis of cancer cells, retinoic acid (RA) is considered a signaling molecule with promising therapeutic potential in oncology. In this study, we show that RA is able to induce the intrinsic ability of breast cancer cells to recognize double-stranded RNA (dsRNA) through the upregulation of Toll-like receptor 3 (TLR3) expression. RA, co-administered with the dsRNA mimicker polyinosinic-polycytidylic acid (poly(I:C)), synergizes to mount a specific response program able to sense dsRNA through the concurrent upregulation of TLR3, the dsRNA helicases melanoma differentiation-associated antigen-5 (MDA-5) and RA-inducible gene-1 (RIG-1), and the dsRNA-activated protein kinase (PKR) expression, leading breast cancer cells to specifically express downstream transcriptional targets of dsRNA sensors, such as interferon-beta (IFNbeta), interleukin-8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5), and C-X-C motif Chemokine 10 (CXCL10). A TLR3-dependent apoptotic program is also induced by RA and poly(I:C) co-treatment that correlates with the induction of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and contributes to block breast cancer cell proliferation. The mechanisms of apoptosis induced by RA/poly(I:C) in breast cancer cells involve type I IFN autocrine signaling, caspase-8 and caspase-3 activation, as well as TRAIL signaling. Our results reveal important links among RA, TLR3 and TRAIL and highlight the combined use of RA and poly(I:C) as a potential effective tumor therapy by improving the apoptotic response of cancer cells with low sensitivity to the action of synthetic dsRNA.
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[922]
TÍTULO / TITLE: - The prognostic value of estrogen receptor beta and proline-, glutamic acid- and leucine-rich protein 1 (PELP1) expression in ovarian cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 14;13:115. doi: 10.1186/1471-2407-13-115.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-115
AUTORES / AUTHORS: - Aust S; Horak P; Pils D; Pils S; Grimm C; Horvat R; Tong D; Schmid B; Speiser P; Reinthaller A; Polterauer S
INSTITUCIÓN / INSTITUTION: - Department of Gynaecology and Gynaecological Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, 1090, Austria. stephan.polterauer@meduniwien.ac.at.
RESUMEN / SUMMARY: - BACKGROUND: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of the estrogen receptors (ERs) alpha and beta, is a potential proto-oncogene in hormone dependent gynecological malignancies. To better understand the role of PELP1 in epithelial ovarian cancer (EOC), the protein expression and prognostic significance of PELP1 was evaluated together with ERalpha and ERbeta in EOC tissues. METHODS: The expression of PELP1, ERalpha, and ERbeta was characterized in tumor tissues of 63 EOC patients. The prognostic value was calculated performing log-rank tests and multivariate Cox-Regression analysis. In a second step, validation analysis in an independent set of 86 serous EOC patients was performed. RESULTS: Nuclear PELP1 expression was present in 76.2% of the samples. Prevalence of PELP1 expression in mucinous tumors was significantly lower (37.5%) compared to serous (85.7%) and endometrioid tumors (86.7%). A significant association between PELP1 expression and nuclear ERbeta staining was found (p=0.01). Positive PELP1 expression was associated with better disease-free survival (DFS) (p=0.004) and overall survival (OS) (p=0.04). The combined expression of ERbeta+/PELP1+ revealed an independent association with better DFS (HR 0.3 [0.1-0.7], p=0.004) and OS (HR 0.3 [0.1-0.7], p=0.005). In the validation set, the combined expression of ERbeta+/PELP1+ was not associated with DFS (HR 0.7 [0.4-1.3], p=0.3) and OS (HR 0.7 [0.3-1.4], p=0.3). CONCLUSION: Positive immunohistochemical staining for the ER coregulator PELP1, alone and in combination with ERbeta, might be of prognostic relevance in EOC.
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[923]
TÍTULO / TITLE: - AML1/ETO sensitizes via TRAIL acute myeloid leukemia cells to the pro-apoptotic effects of hypoxia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 14;4:e536. doi: 10.1038/cddis.2013.49.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.49
AUTORES / AUTHORS: - Barbetti V; Tusa I; Cipolleschi MG; Rovida E; Dello Sbarba P
INSTITUCIÓN / INSTITUTION: - Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Sezione di Patologia e Oncologia Sperimentali, Universita degli Studi di Firenze and Istituto Toscano Tumori, Firenze, Italy.
RESUMEN / SUMMARY: - We determined the effects of severe hypoxia ( approximately 0.1% O2) on acute myeloid leukemia cells expressing the AML1/ETO oncogene. Incubation of Kasumi-1 cells in hypoxia induced growth arrest, apoptosis and reduction of AML1/ETO protein expression. The conditional expression of AML1/ETO in U937-A/E cells showed that hypoxia induces marked apoptosis in AML1/ETO-expressing cells only, pointing to AML1/ETO as a factor predisposing cells to hypoxia-induced apoptosis. In AML1/ETO-expressing cells, hypoxia enhanced TRAIL expression and its proapoptotic effects. AML1/ETO was found to bind TRAIL promoter and induce TRAIL transcription, although TRAIL expression was restrained by a concomitant relative transcription block. In hypoxia, such a TRAIL repression was removed and an increase of TRAIL expression was induced. Finally, blocking anti-TRAIL antibodies markedly reduced (Kasumi-1 cells) or completely inhibited (U937-A/E cells) hypoxia-induced apoptosis. Taken together, these results indicated that hypoxia induces apoptosis in AML1/ETO-expressing cells via a TRAIL/caspase 8-dependent autocrine loop and that TRAIL is a key regulator of hypoxia-induced apoptosis in these cells.
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[924]
TÍTULO / TITLE: - TGF-beta-activated Kinase-1: A Potential Prognostic Marker for Clear Cell Renal Cell Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):315-20.
AUTORES / AUTHORS: - Wei C; Lai YQ; Li XX; Ye JX
INSTITUCIÓN / INSTITUTION: - Department of Urology, The Peking University Shenzhen Hospital, Shenzhen, China E-mail : yjx66i@126.com, xianxinli@163.com.
RESUMEN / SUMMARY: - Background: TGF-beta-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. Methods: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. Results: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. Conclusions: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.
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[925]
TÍTULO / TITLE: - socs7, a target gene of microRNA-145, regulates interferon-beta induction through STAT3 nuclear translocation in bladder cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 7;4:e482. doi: 10.1038/cddis.2013.11.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.11
AUTORES / AUTHORS: - Noguchi S; Yamada N; Kumazaki M; Yasui Y; Iwasaki J; Naito S; Akao Y
INSTITUCIÓN / INSTITUTION: - United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, Japan. snoguchi@gifu-u.ac.jp
RESUMEN / SUMMARY: - We recently reported that microRNA (miR)-145 is downregulated and induces apoptosis in human bladder cancer cells. Also, it is suggested that the ectopic expression of miR-145 induces apoptosis with the induction of TRAIL expression in several cancer cells. Here, we demonstrated a novel mechanism of apoptosis induction by miR-145 in bladder cancer cells. Exogenous miR-145 in T24 and NKB1 cells markedly increased the expression levels of interferon (IFN)-beta, 2’-5’-oligoadenylate synthetase 1, which lies upstream of 2’-5’ oligoadenylates/RNase L system, and TRAIL, and induced apparent caspase-dependent apoptosis that was suppressed by cotreatment with a pan-caspase inhibitor; moreover, these expression levels were reduced by cotreatment with an miR-145 inhibitor. The apoptosis did not depend on Toll-like receptor 3 (TLR3) expression, because TLR3-silencing failed to inhibit IFN-beta induction by miR-145. Then, we focused on the suppressor of cytokine signaling 7 (socs7), whose expression level was upregulated in bladder cancer cells compared with its level in normal human urothelial cells, as a putative target gene involved in IFN-beta induction by miR-145. Expectedly, exogenous miR-145 decreased the expression level of SOCS7, and socs7-silencing enhanced IFN-beta induction by transfection with a TLR3 ligand, polyinosinic acid-polycytidylic acid (PIC). The results of a luciferase reporter assay revealed that miR-145 targeted socs7. In addition, socs7-silencing significantly decreased the level of p-Akt and suppressed the growth of T24 cells. Furthermore, exogenous miR-145 or socs7-silencing promoted nuclear translocation of STAT3. In conclusion, the machinery of IFN-beta induction through the regulation of SOCS7 by miR-145 was closely associated with the induction of apoptosis. Moreover, exogenous miR-145 promoted IFN-beta induction by targeting socs7, which resulted in the nuclear translocation of STAT3. Additionally, our data indicate that SOCS7 functioned as an oncogene, the finding that revealed a novel mechanism of carcinogenesis in bladder cancer cells.
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[926]
TÍTULO / TITLE: - Low Expression of Tyrosine-protein Phosphatase Nonreceptor Type 12 is Associated with Lymph Node Metastasis and Poor Prognosis in Operable Triple-negative Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):287-92.
AUTORES / AUTHORS: - Wu MQ; Hu P; Gao J; Wei WD; Xiao XS; Tang HL; Li X; Ge QD; Jia WH; Liu RB; Xie XM
INSTITUCIÓN / INSTITUTION: - Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China E-mail : xiexm@sysucc.org.cn, liur@vip.163.com.
RESUMEN / SUMMARY: - Background: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) expression may be associated with breast cancer growth, proliferation, and metastasis. However, the prognostic value of PTPN12 in breast cancer has not been clearly identified. Patients and Methods: 51 triple-negative breast cancer (TNBC) patients and 83 non-TNBC patients with a histopathology diagnosis from October 2001 to September 2006 were included in this study. Immunohistochemical staining for PTPN12 on tissue microarrays was conducted. Results: High PTPN12 expression was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expression was associated with lymph node status (p = 0.002) and distant metastatic relapse (p = 0.002) in TNBC patients. Similarly, low PTPN12 expression in non-TNBC patients was significantly correlated with lymph node status (p = 0.002), stage (p = 0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression group was associated with longer DFS and OS compared with low PTPN12 expression group only in TNBC cases (p = 0.005, p = 0.015), according to univariate Cox regression analysis. Conclusion: These findings provide evidence that low expression of PTPN12 is associated with worse prognosis and may be used as a potential prognostic biomarker in TNBC patients.
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[927]
TÍTULO / TITLE: - Cardiac hormones are potent inhibitors of secreted frizzled-related protein-3 in human cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Feb;5(2):475-478. Epub 2012 Nov 12.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.806
AUTORES / AUTHORS: - Skelton WP 4th; Skelton M; Vesely DL
INSTITUCIÓN / INSTITUTION: - Departments of Medicine, Molecular Pharmacology and Physiology, James A. Haley Veterans Administration Medical Center and University of South Florida Morsani Health Sciences Center, Tampa, FL 33612, USA.
RESUMEN / SUMMARY: - Secreted frizzled-related proteins (sFRPs) are secreted glycoproteins involved in neoplastic growth. Four hormones synthesized in the heart, namely vessel dilator, atrial natriuretic peptide (ANP), kaliuretic peptide (KP) and long-acting natriuretic peptide (LANP), have anticancer effects both in vitro and in vivo. These heart hormones were evaluated for their ability to inhibit sFRP-3, which is associated with tumor invasiveness, in human pancreatic cancer, colorectal cancer and renal adenocarcinoma cell lines. Vessel dilator, KP, ANP and LANP maximally reduced the concentration of sFRP-3 by 83%, 83%, 84% and 83%, respectively (each at P<0.0001), in the human colorectal adenocarcinoma cells. In the human pancreatic carcinoma cells, the concentration of sFRP-3 was maximally reduced by 77%, 77%, 77% and 78% (each at P<0.0001) secondary to treatment with vessel dilator, KP, ANP and LANP, respectively. In the human renal adenocarcinoma cells, the sFRP-3 was maximally reduced by vessel dilator, KP, ANP and LANP by 68%, 66%, 68% and 66% (each at P<0.0001), respectively. The results indicate that these four cardiac hormones are significant inhibitors (up to 84%) of sFRP-3 in a variety of human cancer cells. Furthermore, these data suggest that the metabolic targeting of sFRP-3 by the cardiac hormones contributes to their anti-cancer mechanism(s) of action.
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[928]
TÍTULO / TITLE: - Protein-Carbohydrate Complex Reveals Circulating Metastatic Cells in a Microfluidic Assay.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Small. 2013 Feb 11. doi: 10.1002/smll.201202867.
●● Enlace al texto completo (gratuito o de pago) 1002/smll.201202867
AUTORES / AUTHORS: - Simone G; Malara N; Trunzo V; Perozziello G; Neuzil P; Francardi M; Roveda L; Renne M; Prati U; Mollace V; Manz A; Di Fabrizio E
INSTITUCIÓN / INSTITUTION: - KIST Europe, Campus E71, 66123 Saarbrucken, Germany. giuseppina.simone@unina.it.
RESUMEN / SUMMARY: - Advances in carbohydrate sequencing technologies reveal the tremendous complexity of the glycome and the role that glycomics might have to bring insight into the biological functions. Carbohydrate-protein interactions, in particular, are known to be crucial to most mammalian physiological processes as mediators of cell adhesion and metastasis, signal transducers, and organizers of protein interactions. An assay is developed here to mimic the multivalency of biological complexes that selectively and sensitively detect carbohydrate-protein interactions. The binding of beta-galactosides and galectin-3-a protein that is correlated to the progress of tumor and metastasis-is examined. The efficiency of the assay is related to the expression of the receptor while anchoring to the interaction’s strength. Comparative binding experiments reveal molecular binding preferences. This study establishes that the assay is robust to isolate metastatic cells from colon affected patients and paves the way to personalized medicine.
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[929]
TÍTULO / TITLE: - Downregulation of the non-integrin laminin receptor reduces cellular viability by inducing apoptosis in lung and cervical cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57409. doi: 10.1371/journal.pone.0057409. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057409
AUTORES / AUTHORS: - Moodley K; Weiss SF
INSTITUCIÓN / INSTITUTION: - School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Gauteng, The Republic of South Africa.
RESUMEN / SUMMARY: - The non-integrin laminin receptor, here designated the 37-kDa/67-kDa laminin receptor (LRP/LR), is involved in many physiologically relevant processes, as well as numerous pathological conditions. The overexpression of LRP/LR on various cancerous cell lines plays critical roles in tumour metastasis and angiogenesis. This study investigated whether LRP/LR is implicated in the maintenance of cellular viability in lung and cervical cancer cell lines. Here we show a significant reduction in cellular viability in the aforementioned cell lines as a result of the siRNA-mediated downregulation of LRP. This reduction in cellular viability is due to increased apoptotic processes, reflected by the loss of nuclear integrity and the significant increase in the activity of caspase-3. These results indicate that LRP/LR is involved in the maintenance of cellular viability in tumorigenic lung and cervix uteri cells through the blockage of apoptosis. Knockdown of LRP/LR by siRNA might represent an alternative therapeutic strategy for the treatment of lung and cervical cancer.
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[930]
TÍTULO / TITLE: - Expression of AFP and STAT3 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in AFP-producing gastric cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54774. doi: 10.1371/journal.pone.0054774. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054774
AUTORES / AUTHORS: - Jia Y; Liu D; Xiao D; Ma X; Han S; Zheng Y; Sun S; Zhang M; Gao H; Cui X; Wang Y
INSTITUCIÓN / INSTITUTION: - Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
RESUMEN / SUMMARY: - Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC), represented by the production of AFP, has a more aggressive behavior than common gastric cancer. The underlying mechanisms are not well understood. Arsenic trioxide (As(2)O(3)) is used clinically to treat acute promyelocytic leukemia(APL) and has activity in vitro against several solid tumor cell lines, with induction of apoptosis and inhibition of proliferation the prime effects. Signal transducer and activator of transcription 3 (STAT3) has an important role in tumorigenesis of various primary cancers and cancer cell by upregulating cell-survival and downregulating tumor suppressor proteins. Here, we found decreased expression of AFP and STAT3 after induction of apoptosis by As(2)O(3) in the AFPGC FU97 cells. Also, the level of the STAT3 target oncogene Bcl-2 was decreased with As(2)O(3), and that of the tumor suppressor Bax was increased. Furthermore, STAT3 expression and depth of invasion and lymph node metastasis were associated. Survival of patients with gastric cancer was lower with AFP and STAT3 double overexpression than with overexpression of either alone. Downregulation of AFP and STAT3 expression plays an important role in As(2)O(3)-induced apoptosis of AFPGC cells, which suggests a new mechanism of As(2)O(3)-induced cell apoptosis. As(2)O(3) may be a possible agent for AFPGC treatment.
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[931]
TÍTULO / TITLE: - Impact of adjuvant chemotherapy cycles on prognosis of resectable stomach cancer: a retrospective analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):381-6.
AUTORES / AUTHORS: - Zhang WY; Zhang WJ; Bai Y; Yuan HH; Liu F; Gao J; Gong YF; Jiang B
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China E-mail : bin_jiang@yeah.net.
RESUMEN / SUMMARY: - Aims: The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis. Methods: A total of 128 patients with gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5-fluorouracil, according to a defined schedule, were divided into three groups according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6 cycles); and Group III (>6 cycles). Results: The 5-year overall survival (OS) was 20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow-up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40% in Group II, and 40% in Group III. The OS and RFS in Groups II and III were significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between Groups II and III. Multivariate Cox hazard analysis determined that the number of adjuvant chemotherapy cycles was an independent factor that influenced OS and RFS. Conclusion: Six cycles of adjuvant chemotherapy gave encouraging outcomes in patients with resectable gastric cancer. Further prospective randomized controlled investigations are warranted in a multi-center setting.
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[932]
TÍTULO / TITLE: - A calcium ion-dependent dimeric bean lectin with antiproliferative activity toward human breast cancer mcf-7 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Protein J. 2013 Mar;32(3):208-15. doi: 10.1007/s10930-013-9477-2.
●● Enlace al texto completo (gratuito o de pago) 1007/s10930-013-9477-2
AUTORES / AUTHORS: - Cheung RC; Leung HH; Pan WL; Ng TB
INSTITUCIÓN / INSTITUTION: - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
RESUMEN / SUMMARY: - In this study, a 60.8-kDa dimeric lectin was isolated from the Phaseolus vulgaris cv. jade bean and characterized. The lectin was bound on Blue Sepharose 6 and Q Sepharose and was finally purified by size exclusion chromatography on Superdex 200. Its hemagglutinating activity toward rabbit erythrocytes was dependent on divalent cations, especially calcium ions. Various carbohydrates tested were devoid of any effect on the hemagglutinating activity. The lectin was stable at pH between 4.5 and 9.4 and temperatures between 30 and 70 degrees C. It did not exert antifungal activity toward Valsa mali, Setosphaeria turcica, Mycosphaerella arachidicola, Fusarium oxysporum and Bipolaris maydis. The IC50 of the antiproliferative activity of the lectin toward MCF-7 human breast cancer cells was 174 muM. It did not inhibit proliferation of WRL-68 human normal embryonic hepatocytes. The lectin was dependent on calcium ions for hemagglutinating activity and possessed a blocked N-terminus. These two characteristics make the lectin unique among Phaseolus lectins.
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[933]
TÍTULO / TITLE: - Chemopreventive effect of cactus (Opuntia humifusa) extracts: radical scavenging activity, pro-apoptosis, and anti-inflammatory effect in human colon (SW480) and breast cancer (MCF7) cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Funct. 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1039/c3fo30287c
AUTORES / AUTHORS: - Kim J; Jho KH; Choi YH; Nam SY
INSTITUCIÓN / INSTITUTION: - Natural Science Research Institute, Department of Horticulture, Sahmyook University, Seoul 139-742, Republic of Korea. namsy@syu.ac.kr.
RESUMEN / SUMMARY: - Cactus (Opuntia spp) is widely cultivated as a vegetable, fruit, and forage crop and has been used in traditional medicine in American Indian, Mexican, and Korean cultures. Accumulative evidence from both in vitro and in vivo studies using cacti suggests their biological and pharmacological activities, such as their anti-cancer and anti-inflammatory roles in different cancer cells. In this study, the Opuntia humifusa stem (OHS) was extracted with different solvents and screened for radical scavenging activity using 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS (+)) and 1,1-diphenyl-2-picryl hydrazyl (DPPH). In addition, the total phenolic and flavonoid contents of each extract were analyzed using the Folin-Ciocalteu method and high performance liquid chromatography, respectively. Further, the cacti’s bioactive fractions were evaluated for cell cytotoxicity and to understand their mechanism of action on human colon cancer (SW480) and breast cancer (MCF7) cells. An ethyl acetate (EtOAc) extract exhibited the highest cytotoxicity and resulted in an up-regulated expression of the pro-apoptotic protein Bax (bcl-2 associated X protein) and a down-regulated expression of the anti-apoptotic protein Bcl2 in both SW480 and MCF7 cells. The apoptosis was mediated through activation of caspase 8, 9, and 3/7 activities as well as PARP cleavage in SW480 cells, while the same extract activated only a caspase 9 activity in MCF7 cells. Furthermore, incubation of cells with the EtOAc extract down-regulated the expression of inflammatory molecules such as cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) in SW480 cells but not in MCF7 cells. Taken together, these results suggest that SW480 colon cancer cells are more susceptible to bioactive compounds present in OHS and may have potential in the prevention of cancer through modulation of apoptosis markers and inhibition of inflammatory pathways.
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[934]
TÍTULO / TITLE: - Adjuvant Chemotherapy Decisions in Clinical Practice for Early-Stage Node-Negative, Estrogen Receptor-Positive, HER2-Negative Breast Cancer: Challenges and Considerations.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Compr Canc Netw. 2013 Mar 1;11(3):246-51.
AUTORES / AUTHORS: - Nagaraj G; Ma CX
INSTITUCIÓN / INSTITUTION: - From the aDivision of Medical Oncology and Hematology, Loma Linda University, Loma Linda, California, and bSection of Breast Oncology, Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
RESUMEN / SUMMARY: - Decisions regarding adjuvant chemotherapy for patients with estrogen receptor (ER)-positive, HER2-negative, lymph node-negative breast cancer have traditionally relied on clinical and pathologic parameters. However, the molecular heterogeneity and the complex tumor genome demand more sophisticated approaches to the problem. Several multigene-based assays have been developed to better prognosticate the risk of recurrence and death and predict benefit of therapy in this patient population. Oncologists are often faced with the challenge of incorporating these various complex genome-based biomarkers along with the traditional biomarkers in clinical decision-making. The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer are helpful in providing a general recommendation. However, uncertainty remains in the absence of definitive data for various clinical scenarios. This case report describes a postmenopausal woman with stage I breast cancer that is low-grade and ER-rich, and has an intermediate Oncotype DX recurrence score of 28.
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[935]
TÍTULO / TITLE: - A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 21;13(1):138.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-138
AUTORES / AUTHORS: - Guinan EM; Hussey J; McGarrigle SA; Healy LA; O Sullivan JN; Bennett K; Connolly EM
RESUMEN / SUMMARY: - BACKGROUND: Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers.Methods/design: Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. DISCUSSION: The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence.
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[936]
TÍTULO / TITLE: - Bladder cancer: Bovine milk protein complex has antitumour effect in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Urol. 2013 Feb 12;10(3):126. doi: 10.1038/nrurol.2013.19. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1038/nrurol.2013.19
AUTORES / AUTHORS: - Payton S
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[937]
TÍTULO / TITLE: - MiR-138 and MiR-135 Directly Target Focal Adhesion Kinase, Inhibit Cell Invasion, and Increase Sensitivity to Chemotherapy in Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Agents Med Chem. 2013 Feb 15.
AUTORES / AUTHORS: - Golubovskaya VM; Sumbler B; Ho B; Yemma M; Cance WG
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Vita.Golubovskaya@Roswellpark.org; William.Cance@Roswellpark.org.
RESUMEN / SUMMARY: - Focal Adhesion Kinase is a 125 kDa non-receptor kinase and overexpressed in many types of tumors. Recently, short noncoding RNAs, called microRNAs have been discovered as regulators of gene expression mainly through binding to the untranslated region (UTR) of mRNA. In this report we show that MiR-138 and MiR-135 down-regulated FAK expression in cancer cells. MiR-138 and MiR-135 inhibited FAK protein expression in different cancer cell lines. The computer analysis of 3’FAK-untranslated region (FAK-UTR) identified one conserved MiR-138 binding site (CACCAGCA) at positions 3514-3521 and one conserved MiR-135 (AAGCCAU) binding site at positions 4278-4284 in the FAK-UTR. By a dual-luciferase assay we demonstrate that MiR-138 and MiR-135 directly bound the FAK untranslated region using FAK-UTR-Target (FAK-UTR) luciferase plasmid and inhibited its luciferase activity. The site-directed mutagenesis of the MiR-13 and MiR-135 binding sites in the FAK-UTR abrogated MiR-138 and MiR-135-directed inhibition of FAK-UTR. Real-time PCR demonstrated that cells transfected with MiR-138 and MiR-135 expressed decreased FAK mRNA levels. Moreover, stable expression of MiR-138 and MiR-135 in 293 and HeLa cells decreased cell invasion and increased sensitivity to 5-fluorouracil (5-FU), FAK inhibitor, Y15, and doxorubicin. In addition, MiR-138 significantly decreased 293 xenograft tumor growth in vivo. This is the first report on regulation of FAK expression by MiR-135 and MiR138 that affected invasion, drug sensitivity, and tumor growth in cancer cells, which is important to the development of FAK-targeted therapeutics and understanding their novel regulations and functions.
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[938]
TÍTULO / TITLE: - Antisense oligonucleotide mediated knockdown of HOXC13 affects cell growth and induces apoptosis in tumor cells and over expression of HOXC13 induces 3D-colony formation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - RSC Adv. 2013 Jan 1;3(10):3260-3269. Epub 2012 Dec 18.
●● Enlace al texto completo (gratuito o de pago) 1039/C2RA22006G
AUTORES / AUTHORS: - Kasiri S; Ansari KI; Hussain I; Bhan A; Mandal SS
INSTITUCIÓN / INSTITUTION: - Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019.
RESUMEN / SUMMARY: - HOXC13 is a homeobox containing gene that plays crucial roles in hair development and origin of replication. Herein, we investigated the biochemical functions of HOXC13 and explored its potential roles in tumor cell viability. We have designed a phosphorothioate based antisense-oligonucleotide that specifically knockdown HOXC13 in cultured cells. Cell viability and cytotoxicity assays demonstrated that HOXC13 is essential for cell growth and viability. Antisense-mediated knockdown of HOXC13 affected the cell viability and induced apoptosis in cultured tumor cells. HOXC13 regulates the expression of cyclins and antisense-mediated knockdown of HOXC13 resulted in cell cycle arrest and apoptosis in colon cancer cells. Finally over expression of HOXC13 resulted in 3D-colony formation in soft-agar assay indicating its potential roles in cell proliferation and tumorigenesis.
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[939]
TÍTULO / TITLE: - Carfilzomib: a next-generation proteasome inhibitor for multiple myeloma treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin J Oncol Nurs. 2013 Apr 1;17(2):E35-44. doi: 10.1188/13.CJON.E35-E44.
●● Enlace al texto completo (gratuito o de pago) 1188/13.CJON.E35-E44
AUTORES / AUTHORS: - Bilotti E
INSTITUCIÓN / INSTITUTION: - John Theurer Cancer Center, Hackensack University Medical Center in New Jersey.
RESUMEN / SUMMARY: - Although the incidence of multiple myeloma (MM) is increasing, the median overall survival and the number of agents in the pipeline for treating MM also are increasing. Response rates higher than 80% are not uncommon in the frontline setting when the novel agents thalidomide, lenalidomide, and bortezomib are used in combination. Response rates and survival also have improved in disease that has relapsed after treatment with conventional therapies. The focus of research has now shifted to improving survival and disease response in patients refractory to current treatment paradigms. New agents are targeting new pathways, as well as existing mechanisms known to be effective, but with different safety profiles. Carfilzomib is a potent, selective, irreversible inhibitor of the ubiquitin-proteasome pathway. The drug is a next-generation proteasome inhibitor found to be safe and effective for patients with relapsed and refractory MM, where treatment options are limited. As with any newly approved agent, one should recognize that drugs within the same class will be administered differently and often cause dissimilar treatment-related toxicities. Oncology nurses are crucial to the successful administration of chemotherapeutic agents such as carfilzomib, and an understanding of management techniques is paramount to quality patient care.
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[940]
TÍTULO / TITLE: - 5-Aza-2’-deoxycytidine may influence the proliferation and apoptosis of cervical cancer cells via demethylation in a dose- and time-dependent manner.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genet Mol Res. 2013 Feb 4;12(1):312-8. doi: 10.4238/2013.February.4.5.
●● Enlace al texto completo (gratuito o de pago) 4238/2013.February.4.5
AUTORES / AUTHORS: - Yao TT; Mo SM; Liu LY; Lu HW; Huang ML; Lin ZQ
INSTITUCIÓN / INSTITUTION: - Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, PR China.
RESUMEN / SUMMARY: - The methylation of tumor suppressor genes has been shown to be involved in many human cancers. 5-Aza-2’-deoxycytidine (5-Aza-CdR) can reactivate the expression of methylated tumor suppressor genes. In our study, 2 human cervical cancer cell lines, HeLa and SiHa, were treated with different concentrations (20, 10, 5, and 2.5 muM) of 5-Aza-CdR for 24, 48, and 72 h. After incubation, cells were analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. The expression of RASSF1A and APAF-1 was detected by RT-PCR. 5-Aza-CdR inhibited the growth of HeLa and SiHa cells at different concentrations. The strongest inhibition and apoptosis rates were obtained after incubation for 72 h (5.63 +/- 1.38 and 8.24 +/- 2.40%, respectively). No significant difference in the expression of RASSF1A was found upon drug treatment, while APAF-1 expression increased in HeLa cells after treatment (0.790 +/- 0.056%). Our results suggest that the tumor-suppressive effect of 5-Aza-CdR may result from the reactivation of silenced APAF-1 through demethylation.
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[941]
TÍTULO / TITLE: - Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Epigenetics. 2013 Feb 1;5(1):3. doi: 10.1186/1868-7083-5-3.
●● Enlace al texto completo (gratuito o de pago) 1186/1868-7083-5-3
AUTORES / AUTHORS: - Karahoca M; Momparler RL
INSTITUCIÓN / INSTITUTION: - Departement de Pharmacologie, Universite de Montreal, Montreal, Quebec, Canada. richard.l.momparler@umontreal.ca.
RESUMEN / SUMMARY: - 5-Aza-2’-deoxycytidine (5-AZA-CdR, decitabine), an epigenetic drug that inhibits DNA methylation, is currently used to treat myelodysplastic syndrome (MDS), and is under investigation for treating acute myeloid leukemia (AML) and other malignancies. 5-AZA-CdR can reactivate tumor suppressor genes silenced by aberrant DNA methylation, a frequent event in all types of cancer. Because this epigenetic change is reversible, it is a good target for 5-AZA-CdR therapy. We have reviewed the preclinical data of 5-AZA-CdR to analyze the concentrations and exposure times required to eradicate cancer stem cells. We analyzed the dose-schedules used in animal models that show potent antineoplastic activity of 5-AZA-CdR. We attempted to correlate the preclinical data with the responses obtained in clinical trials of 5-AZA-CdR in patients with cancer. The pharmacokinetics and drug distribution of 5-AZA-CdR are key parameters because adequate therapeutic drug levels are required to eliminate cancer stem cells in all anatomic compartments. The plasma half-life of 5-AZA-CdR in humans is approximately 20 minutes due to the high levels in the liver of cytidine deaminase, the enzyme that inactivates this analogue. This provides a rationale to use an inhibitor of cytidine deaminase in combination with 5-AZA-CdR. Low-dose 5-AZA-CdR is effective for MDS and AML and can induce complete remissions (CR). However, maintenance of CR with low-dose 5-AZA-CdR is difficult. Based on analyses of preclinical and clinical data, low dose 5-AZA-CdR has the potential to be an effective form of therapy in some patients with cancer. For patients who do not respond to low dose therapy we recommend dose-intensive treatment with 5-AZA-CdR. Patients who are candidates for intensive dose 5-AZA-CdR should have a good bone marrow status so as to permit adequate recovery from myelosuppression, the major toxicity of 5-AZA-CdR. Solid tumors are also interesting targets for therapy with 5-AZA-CdR. Both low dose and intensive therapy with 5-AZA-CdR can reduce the proliferative potential of tumor stem cells in animal models. We propose novel dose schedules of 5-AZA-CdR for investigation in patients with cancer. The full chemotherapeutic potential of 5-AZA-CdR to treat cancer merits further clinical investigation and can only be realized when its optimal dose-schedule is determined.
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[942]
TÍTULO / TITLE: - Partial response of a rare malignant metastatic diffuse tenosynovial giant cell tumor with benign histologic features, treated with SCH 717-454, an insulin growth factor receptor inhibitor, in combination with everolimus, an MTOR inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0267-8
AUTORES / AUTHORS: - Sikaria S; Heim-Hall J; Diaz EH; Williams R; Sankhala K; Laabs B; Mita M
INSTITUCIÓN / INSTITUTION: - Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, SCCT Mezzanine MS 35, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
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[943]
TÍTULO / TITLE: - Relevance of the type I interferon signature in multiple sclerosis towards a personalized medicine approach for interferon-beta therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Discov Med. 2013 Jan;15(80):51-60.
AUTORES / AUTHORS: - Verweij CL; Vosslamber S
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Section of Inflammatory Disease Profiling, VU University Medical Center, Amsterdam, Netherlands. c.verweij@vumc.nl
RESUMEN / SUMMARY: - Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system. The disease is characterized by progressive neurological dysfunction due to demyelination of the nerves, which leads to disability. Currently, no curative therapy is available and patients are subjected to a prolonged course of treatment. Interferon-beta (IFNbeta) was the first agent to show clinical efficacy in the treatment of MS, and is still the best available therapy. Unfortunately, clinical experience indicates that approximately 40% of the patients do not or only poorly respond to IFNbeta treatment. Recent advances revealed the presence of an activated type I IFN pathway in a subset of treatment naive patients with relapsing remitting MS (RRMS), as shown by the presence of an “IFN signature” and type I IFN bioactivity in the blood of these patients. Evidence exists that quantification of the IFN signature in RRMS is informative as a biomarker to predict the clinical response to IFNbeta. In this review we summarize the current evidence of type I IFN activation in RRMS and its clinical relevance.
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[944]
TÍTULO / TITLE: - Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 2;13:49. doi: 10.1186/1471-2407-13-49.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-49
AUTORES / AUTHORS: - Pentheroudakis G; Kotoula V; De Roock W; Kouvatseas G; Papakostas P; Makatsoris T; Papamichael D; Xanthakis I; Sgouros J; Televantou D; Kafiri G; Tsamandas AC; Razis E; Galani E; Bafaloukos D; Efstratiou I; Bompolaki I; Pectasides D; Pavlidis N; Tejpar S; Fountzilas G
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. gpenther@otenet.gr.
RESUMEN / SUMMARY: - BACKGROUND: More than half of patients with KRAS-wild type advanced colorectal cancer (CRC) fail anti-EGFR monoclonal antibodies. We studied EGFR-axis messenger RNA (mRNA) expression and RAS, RAF, PIK3CA mutations in order to identify additional biomarkers of cetuximab efficacy. METHODS: Previously genotyped (KRAS, NRAS, BRAF, PIK3CA mutations) formalin-fixed paraffin-embedded tumour biopsies of 226 cetuximab-treated CRC patients (1st to 3rd line therapy) were assessed for mRNA expression of epidermal growth factor receptor (EGFR) and its ligands EGF, Transofrming Growth Factor-a (TGFA), Amphiregulin (AREG) and Epiregulin (EREG) with real time quantitative PCR. Mutations were detected in 72 (31.9%) tumours for KRAS, in 6 (2.65%) for BRAF, in 7 (3.1%) for NRAS and in 37 (16.4%) for PIK3CA. RESULTS: Only PIK3CA mutations occasionally coexisted with other gene mutations. In univariate analysis, prognostic significance for survival ( from metastases until death) was seen for BRAF mutations (Hazard Ratio HR 8.1, 95% CI 3.4-19), codon 12-only KRAS mutations (HR 1.62, 95% CI 1.1-2.4), high AREG mRNA expression only in KRAS wild type CRC (HR 0.47, 95% CI 0.3-0.7) and high EREG mRNA expression irrespective of KRAS mutation status (HR 0.45, 95% CI 0.28-0.7). EREG tumoural mRNA expression was significantly associated with a 2.26-fold increased likelihood of objective response to cetuximab therapy (RECIST 1.1). In multivariate analysis, favourable predictive factors were high AREG mRNA in KRAS wild type tumours, high EREG mRNA, low Ephrin A2 receptor mRNA. Cetuximab-treated patients with AREG-low KRAS wild type CRC fared very poorly, their survival being similar to KRAS mutant CRC. Patients with KRAS codon 13 or other non-codon 12 mutations had a median survival (30 months, 95% CI 20-35) similar to that of patients with KRAS wild-type (median survival 29 months, 95% CI 25-35), in contrast to patients with KRAS codon 12 mutations who fared worse (median survival 19 months, 95% CI 15-26). CONCLUSIONS: BRAF and codon 12 KRAS mutations predict for adverse outcome of CRC patients receiving cetuximab. AREG mRNA reflects EGFR signalling in KRAS wild type tumours, predicting for cetuximab efficacy when high and failure when low. EREG may have a prognostic role independent of KRAS mutation.
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[945]
TÍTULO / TITLE: - Prognostic and Diagnostic Significance of Annexin A2 in Colorectal Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Colorectal Dis. 2013 Mar 12. doi: 10.1111/codi.12207.
●● Enlace al texto completo (gratuito o de pago) 1111/codi.12207
AUTORES / AUTHORS: - Yang T; Peng H; Wang J; Yang J; Nice EC; Xie K; Huang C
INSTITUCIÓN / INSTITUTION: - The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.
RESUMEN / SUMMARY: - AIM: Annexin A2 (ANXA2) is known to be a tumorigenic molecule and is highly expressed in colorectal cancer (CRC). Its diagnostic and prognostic value is not fully understood. This study was designed to investigate the relationship between ANXA2 expression, clinicopathological characteristics, tumour recurrence, and survival. METHOD: Immunohistochemical staining was used to evaluate ANXA2 expression in 150 matched samples from patients with colorectal cancer (CRC). Overall survival and recurrence were determined by Kaplan-Meier analysis. The Cox proportional hazards model was used to determine independent factors contributing to survival and recurrence. Receiver operating characteristic (ROC) curve and liner correlation analysis was used to estimate the sensitivity and specificity of ANXA2 expression for clinical diagnosis. RESULTS: ANXA2 was found to be strongly expressed in poorly differentiated tumours (p < 0.001), late stage (p = 0.020) and lymph node positivity (p = 0.002). ANXA2 expression was significantly related to recurrence (p < 0.001) and survival (p = 0.002). Cox proportional hazards model indicated that ANXA2 expression (p < 0.001, HR=1.366, 95%CI 1.232-1.515) and tumour location (p = 0.039, HR=1.891, 95%CI 1.034-3.456) were independent factors in predicting overall survival while ANXA2 expression (p < 0.001, HR=1.445, 95%CI 1.222-1.709) were independent factors predicting recurrence. Receiver operating characteristic (ROC) (AUC=0.768, 95%CI=0.642-0.894) and liner correlation analysis suggested ANXA2 was suitable for the clinical diagnosis of CRC. CONCLUSION: These results indicate that ANXA2 is a biomarker with diagnostic and prognostic potential for patients with CRC. © 2013 The Authors. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
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[946]
TÍTULO / TITLE: - During twenty years of Cisplatin-based therapy the face of nonseminomatous testicular germ cell tumors is still changing: an evaluation of presentation, management, predictive factors and survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int Braz J Urol. 2013 Jan;39(1):10-21. doi: 10.1590/S1677-5538.IBJU.2013.01.03.
AUTORES / AUTHORS: - Heinzelbecker J; Katzmarzik M; Weiss C; Trojan L; Haecker A
INSTITUCIÓN / INSTITUTION: - Department of Urology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
RESUMEN / SUMMARY: - Purpose: To assess the changing presentation and treatment of nonseminomatous testicular germ cell tumors (NSGCT) and to investigate predictive factors for the status of metastasis at diagnosis and on relapse and death. Materials and Methods: Retrospective record review of 147 patients that underwent inguinal orchiectomy from 1987-2007. Follow-up data was available for 102 patients (median follow-up: 80 months (0-243); 96 patients alive). Results: Mean patients age increased (p = 0.015) and more patients were diagnosed in clinical stage I (CSI) (p = 0.040). The fraction of yolk sac (YS) elements inclined (p = 0.030) and pT2 tumors increased (p < 0.001). Retroperitoneal lymph node dissection (RPLND) declined whereas more patients were treated with chemotherapy (p < 0.001; p = 0.004). There was an increase in relapse free (RFS) and cancer specific survival (CSS) due to an improvement in patients with disseminated disease (p = 0.014; p < 0.001). The presence of YS and teratoma elements showed a reduction in the odds ratio (OR) for metastasis at diagnosis (p = 0.002, OR: 0.262; p = 0.009, OR: 0.428) whereas higher pT-stage was associated to their presence (p = 0.039). Patients with disseminated disease (CS > I) showed a declined CSS compared to CSI patients (p = 0.055). The presence of YS elements was associated to an improved RFS (p = 0.038). Conclusions: In our single institution study the face of NSGCT markedly changed over 20 years even after the introduction of Cisplatin-based chemotherapy. These changes were accompanied by an improvement in RFS and CSS. When dealing with NSGCT patients such observations now and in the future should be taken into account.
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[947]
TÍTULO / TITLE: - Somatic Mutations of K-Ras and BRAF in Thai Colorectal Cancer and their Prognostic Value.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):329-32.
AUTORES / AUTHORS: - Chaiyapan W; Duangpakdee P; Boonpipattanapong T; Kanngern S; Sangkhathat S
INSTITUCIÓN / INSTITUTION: - Tumor Biology Research Unit, Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand E-mail : surasak.sa@psu.ac.th.
RESUMEN / SUMMARY: - Background: The study aimed to determine the incidence of K-ras and BRAF mutations in colorectal cancers (CRCs) in Thai patients and evaluate association with clinicopathological parameters including treatment outcomes in terms of event free survival (EFS). Materials and Methods: Two-hundred colorectal cancer specimens were collected for studies of K-Ras codon 12, 13 and 61, and BRAF codon 600 by polymerase chain reaction and direct nucleotide sequencing. Results: The overall incidence of K-Ras mutations in our patients was 23%. K-ras mutation frequencies in CRC stages (AJCC) I, II, III and IV were 6.7%, 16.1%, 23.3% and 26.6%, respectively (p-value>0.05). The three most common mutation forms were G12D, G12V and G13D. K-Ras mutation status was associated with poorer EFS in stage I-III CRCs (p-value 0.03). Conclusions: The study found a lower mutation frequency of K-Ras and BRAF compared to reports involving other ethnic groups. However, K-Ras mutations did have a negative prognostic value in early-stage CRCs.
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[948]
TÍTULO / TITLE: - A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Mar 15;14(3):6067-73. doi: 10.3390/ijms14036067.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14036067
AUTORES / AUTHORS: - Rahman M; Nakayama K; Ishibashi T; Ishikawa M; Rahman MT; Katagiri H; Katagiri A; Iida K; Kikuchi Y; Miyazaki K
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Shimane 6938501, Japan. kn88@med.shimane-u.ac.jp.
RESUMEN / SUMMARY: - Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. A 53-year-old Japanese woman was diagnosed with stage IIIc ovarian clear cell adenocarcinoma with marked chemoresistance to conventional regimens. She demonstrated a partial response to a multikinase inhibitor. The tumor was resistant to PI3K/mTOR pathway inhibitors despite harboring a PIK3CA mutation. The present case suggests a role for targeted therapies in the treatment of OCCC and a need for the identification of biomarkers that will predict response to targeted therapies.
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[949]
TÍTULO / TITLE: - Cytotoxic T-Lymphocyte Antigen-4 Genetic Variants and Risk of Ewing’s Sarcoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genet Test Mol Biomarkers. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1089/gtmb.2012.0488
AUTORES / AUTHORS: - Feng D; Yang X; Li S; Liu T; Wu Z; Song Y; Wang J; Gao W; Huang Q; Huang W; Zheng W; Xiao J
INSTITUCIÓN / INSTITUTION: - 1 Spine Center, Changzheng Hospital, Second Military Medical University , Shanghai, China .
RESUMEN / SUMMARY: - Despite the knowledge of many genetic alterations present in Ewing’s sarcoma (ES), the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) can decrease T-cell activation and attenuate antitumor responses. Polymorphisms in the CTLA-4 gene have been shown to be associated with different diseases. Here, we investigated the association of four CTLA-4 gene polymorphisms, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with ES in the Chinese population. A total of 308 ES cases and 362 healthy controls were recruited and CTLA-4 polymorphisms were tested by polymerase chain reaction-restriction fragment length polymorphism. Results showed that frequencies of the CTLA-4 gene +49AA genotype, +49A allele, and GTAG haplotype were significantly increased in ES patients compared to healthy controls (odds ratio [OR]=2.42, 95% confidence interval [CI] 1.43-4.09, p<0.001; OR 1.38, 95% CI 1.11-1.73, p=0.005, and OR=1.46, 95% CI 1.06-2.02, p=0.020, respectively). We further compared CTLA-4 polymorphisms in ES patients based on different clinical parameters and data revealed that ES patients with metastasis had higher numbers of the +49AA genotype than those without metastasis (p=0.004). These results indicated that the CTLA-4 polymorphism could be a risk factor for ES and suggested a potential role of CTLA-4 in the metastasis of this malignancy.
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[950]
TÍTULO / TITLE: - Myricetin Induces Apoptosis in Hepg2 Cells through Akt/P70s6k/Bad Signaling and Mitochondrial Apoptotic Pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Agents Med Chem. 2013 Feb 7.
AUTORES / AUTHORS: - Zhang XH; Chen SY; Tang L; Shen YZ; Luo L; Xu CW; Liu Q; Li D
INSTITUCIÓN / INSTITUTION: - Department of Food Science and Nutrition, School of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310029, P.R. China. duoli@zju.edu.cn.
RESUMEN / SUMMARY: - The present investigation was undertaken to gain insight into the molecular mechanism by which myricetin induces apoptosis in human hepatocarcinoma HepG2 cells. Myricetin caused the disruption of mitochondrial membrane potential in a dose-dependent manner. Moreover, myricetin triggered translocation of the pro-apoptotic protein Bax to the mitochondria, downregulation of anti-apoptotic Bcl-2 expression and upregulated the expression of pro-apoptotic protein Bad in the mitochondria. The present study also showed that myricetin promoted the release of cytochrome C from mitochondria into the cytosol followed by an increase in the proteolytic activation of caspase-3 and the concomitant degradation of PARP protein. Additionally, western blot analysis showed that the Akt/p70s6k1 pathway was inhibited in myricetin-treated HepG2 cells, accordingly the phosphorylation of Bad at Ser136 was downregulated. Collectively, these findings indicate that myricetin induced apoptosis in HepG2 cell through mitochondria apoptotic pathway and Akt/p70s6k1/Bad signaling. Present results provide new information on the possible mechanisms for the anti-cancer activity of myricetin.
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[951]
TÍTULO / TITLE: - Immunohistochemical Expression Study of Proapoptotic BH3-Only Protein Bad in Canine Nonneoplastic Tissues and Canine Lymphomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet Pathol. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1177/0300985813478212
AUTORES / AUTHORS: - Dettwiler M; Croci M; Vaughan L; Guscetti F
INSTITUCIÓN / INSTITUTION: - Zurich, Switzerland.
RESUMEN / SUMMARY: - The BH3-only protein Bad is a proapoptotic Bcl-2 family member that acts as a sensitizer in intrinsic apoptosis by inactivating antiapoptotic members through heterodimer formation. Bad has been shown to contribute to tumorigenesis, including lymphoma formation in humans and mice, through alteration in expression or functional status. Here, its immunohistochemical expression was analyzed in canine nonneoplastic and lymphoma tissues using tissue microarrays. Bad was expressed in the cytoplasm of a wide range of nonneoplastic tissues, especially epithelial cells. Nonneoplastic lymph nodes displayed weak immunostaining in the follicular germinal centers only. Immunoblotting supported these observations but also revealed presence of nonspecific labeling in some organs. Of 81 lymphomas, 29 (35.8%) displayed moderate to strong immunohistochemical Bad labeling, and a significant expression increase was found in lymphomas (especially B cell and double negative) compared to nonneoplastic lymph nodes. These findings warrant further investigations of the functional status, the involvement of partner proteins, and a possible impact of Bad on prognosis in canine lymphoma.
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[952]
TÍTULO / TITLE: - Mammalian target of rapamycin inhibitors induce tumor cell apoptosis in vivo primarily by inhibiting VEGF expression and angiogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Oncol. 2013;2013:897025. doi: 10.1155/2013/897025. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/897025
AUTORES / AUTHORS: - Frost P; Berlanger E; Mysore V; Hoang B; Shi Y; Gera J; Lichtenstein A
INSTITUCIÓN / INSTITUTION: - Department of Hematology-Oncology, West Los Angeles VA Medical Center, Los Angeles, CA 90073, USA ; Department of Medicine, The Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
RESUMEN / SUMMARY: - We found that rapalog mTOR inhibitors induce G1 arrest in the PTEN-null HS Sultan B-cell lymphoma line in vitro, but that administration of rapalogs in a HS Sultan xenograft model resulted in significant apoptosis, and that this correlated with induction of hypoxia and inhibition of neoangiogenesis and VEGF expression. Mechanistically, rapalogs prevent cap-dependent translation, but studies have shown that cap-independent, internal ribosome entry site (IRES)-mediated translation of genes, such as c-myc and cyclin D, can provide a fail-safe mechanism that regulates tumor survival. Therefore, we tested if IRES-dependent expression of VEGF could likewise regulate sensitivity of tumor cells in vivo. To achieve this, we developed isogenic HS Sultan cell lines that ectopically express the VEGF ORF fused to the p27 IRES, an IRES sequence that is insensitive to AKT-mediated inhibition of IRES activity and effective in PTEN-null tumors. Mice challenged with p27-VEGF transfected tumor cells were more resistant to the antiangiogenic and apoptotic effects of the rapalog, temsirolimus, and active site mTOR inhibitor, pp242. Our results confirm the critical role of VEGF expression in tumors during treatment with mTOR inhibitors and underscore the importance of IRES activity as a resistance mechanism to such targeted therapy.
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[953]
TÍTULO / TITLE: - PTEN-regulated AKT/FoxO3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 7;4:e481. doi: 10.1038/cddis.2013.3.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.3
AUTORES / AUTHORS: - Luo H; Yang Y; Duan J; Wu P; Jiang Q; Xu C
INSTITUCIÓN / INSTITUTION: - National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China.
RESUMEN / SUMMARY: - Mounting evidence shows that selenium possesses chemotherapeutic potential against tumor cells, including leukemia, prostate cancer and colorectal cancer (CRC) cells. However, the detailed mechanism by which sodium selenite specifically kills tumor cells remains unclear. Herein, we demonstrated that supranutritional doses of selenite-induced apoptosis in CRC cells through reactive oxygen species (ROS)-dependent modulation of the PI3K/AKT/FoxO3a signaling pathway. First, we found that selenite treatment in HCT116 and SW480 CRC cells caused inhibition of AKT and the nuclear accumulation of FoxO3a by western blot and immunofluorescence analyses, respectively, thereby facilitating transcription of the target genes bim and PTEN. Modulation of the AKT/FoxO3a/Bim signaling pathway by chemical inhibitors or RNA interference revealed that these events were critical for selenite-induced apoptosis in CRC cells. Additionally, we discovered that FoxO3a-mediated upregulation of PTEN exerted a further inhibitory effect on the AKT survival pathway. We also corroborated our findings in vivo by performing immunohistochemistry experiments. In summary, our results show that selenite could induce ROS-dependent FoxO3a-mediated apoptosis in CRC cells and xenograft tumors through PTEN-mediated inhibition of the PI3K/AKT survival axis. These results help to elucidate the molecular mechanisms underlying selenite-induced cell death in tumor cells and provide a theoretical basis for translational applications of selenium.
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[954]
TÍTULO / TITLE: - Zinc(ii) complexes containing bis-benzimidazole derivatives as a new class of apoptosis inducers that trigger DNA damage-mediated p53 phosphorylation in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dalton Trans. 2013 Mar 27;42(16):5932-40. doi: 10.1039/c3dt33077j.
●● Enlace al texto completo (gratuito o de pago) 1039/c3dt33077j
AUTORES / AUTHORS: - Liu S; Cao W; Yu L; Zheng W; Li L; Fan C; Chen T
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, Jinan University, Guangzhou, 510632, P. R. China. tchentf@jnu.edu.cn tzhwj@jnu.edu.cn.
RESUMEN / SUMMARY: - In the present study, two zinc(ii) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 () and [Zn(bpbp)2](ClO4)2.CH3CH2OH.H2O () (bpbp = 2,6-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)pyridine), have been designed, synthesized and evaluated for their in vitro anticancer activities. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. The complexes were identified as potent antiproliferative agents against a panel of five human cancer cell lines by comparing with cisplatin. Complex demonstrated dose-dependent growth inhibition on MCF-7 human breast carcinoma cells with IC50 at 2.9 muM. Despite this potency, the complexes possessed great selectivity between human cancer cells and normal cells. Induction of apoptosis in MCF-7 cells by complex was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms revealed that complex was able to induce p53-dependent apoptosis in cancer cells by triggering DNA damage. On the basis of this evidence, we suggest that Zn(ii) complexes containing bis-benzimidazole derivatives may be candidates for further evaluation as chemotherapeutic agents for human cancers.
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[955]
TÍTULO / TITLE: - Phosphorylation of signal transducer and activator of transcription 1 reduces bortezomib-mediated apoptosis in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 28;4:e512. doi: 10.1038/cddis.2013.38.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.38
AUTORES / AUTHORS: - Kao C; Chao A; Tsai CL; Lin CY; Chuang WC; Chen HW; Yen TC; Wang TH; Lai CH; Wang HS
INSTITUCIÓN / INSTITUTION: - 1] Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan 333, Republic of China [2] Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 333, Republic of China.
RESUMEN / SUMMARY: - The potent and selective proteasome inhibitor bortezomib has shown remarkable antitumor activity and is now entering clinical trials for several cancers. However, the molecular mechanisms by which bortezomib induces cytotoxicity in ovarian cancer cells still remain unclear. In this study, we show that bortezomib induced apoptosis, which was demonstrated by the downregulation of antiapoptotic molecules (Bcl-2, Bcl-XL, p-Bad, and p-AKT) and the upregulation of proapoptotic proteins (p21, p27, and cleaved-Bid) in ovarian cancer cell lines. Moreover, bortezomib stimulates Janus kinase (JAK) phosphorylation and activates heat-shock transcription factor-1 (HSF-1) and heat-shock protein 70 (HSP70), ultimately leading to signal transducer and activator of transcription 1 (STAT1) phosphorylation. Phosphorylated STAT1 partially counteracted apoptosis induced by bortezomib in cancer cells. These findings suggest that the antitumor activity of bortezomib in ovarian cancer can be improved by inhibiting bortezomib-induced STAT1 phosphorylation. This effect can be achieved by STAT1 knockdown, HSP70 knockdown, JAK inhibition, or the addition of cisplatin, one of the most commonly used anticancer drugs. These results provide the first evidence that STAT1 phosphorylation can play a role in bortezomib resistance by exerting antiapoptotic effects. They also suggest the possibility to abolish or reduce bortezomib chemoresistance in ovarian cancer by the addition of cisplatin or JAK inhibitors.
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[956]
TÍTULO / TITLE: - Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55457. doi: 10.1371/journal.pone.0055457. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055457
AUTORES / AUTHORS: - Shionome Y; Yan L; Liu S; Saeki T; Ouchi T
INSTITUCIÓN / INSTITUTION: - Department of Medicine, National University of Health Sciences, Pritzker School of Medicine, The University of Chicago, Evanston, Illinois, United States of America.
RESUMEN / SUMMARY: - We have previously shown that mammary tumorigenesis in MMTV-Aurora-A mice is further enhanced when p53 is inactivated, demonstrating that integrity of p53 pathway determines phenotypes induced by this oncogenic kinase. In this study, we investigated the roles of genes involved in p53 pathway (p53, Puma, p21, Bax, and Chk2) in response to Aurora-A inhibitors, VX680 and MK-8745, and explored whether chemoresistant tumor cells would further undergo apoptosis with other therapeutic agents. Isogenic HCT116 cell lines were treated with VX680 or MK-8745. Cell cycle analysis, apoptosis, and tumorigenesity were studied. Chemoresistant cells were recovered from xenograft, and further induction of apoptosis was studied. Induction of apoptosis and aneuploidy with VX680 is much stronger than MK-8745. Xenograft assay indicates that tumor growth of HCT116 and HCT116 p53(-) cells are strongly inhibited by VX680, while that of other cell types are similarly inhibited by two compounds. Among the established cell lines recovered from xenografts, MK-8745-resistant clones contain elevated phosphorylation of mTOR and Akt. When further treated with inhibitors of both mTOR and Akt, those cells undergo apoptosis. These results indicate that p53-associated pathway plays a crucial role in regulating growth inhibition of tumor cells when treated with Aurora-A inhibitors. Combined treatment with Akt/mTOR inhibitors can further induce apoptosis of Aurora-A tumors.
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[957]
TÍTULO / TITLE: - Prognostic Significance of Kit Receptor Tyrosine Kinase Dysregulations in Feline Cutaneous Mast Cell Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet Pathol. 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1177/0300985813476064
AUTORES / AUTHORS: - Sabattini S; Frizzon MG; Gentilini F; Turba ME; Capitani O; Bettini G
INSTITUCIÓN / INSTITUTION: - University of Bologna, Italy.
RESUMEN / SUMMARY: - Feline cutaneous mast cell tumors (FeCMCTs) are characterized by variable biological behavior. Development of multiple nodules and potential visceral involvement, along with inconsistency of conventional prognostic aids, justify uncertainty in differentiating benign from malignant forms. c-Kit proto-oncogene activating mutations have been reported in feline mast cell tumors (MCTs), but their prognostic relevance was not investigated. This study was performed on FeCMCTs with variable clinical outcome to assess whether Kit cytoplasmic immunohistochemical labeling can be regarded as indicative of c-Kit mutations and to evaluate the relationship between Kit dysregulation and survival. Twenty-four cats diagnosed with a primary cutaneous MCT were enrolled. Kit immunohistochemical pattern and c-Kit (exons 8, 9, 11) mutational status were assessed in 34 tumor samples. Risk factors affecting survival were a number of mitoses greater than 5 per 10 HPFs (P = .017) and cytoplasmic Kit labeling (P = .045). Increased mitotic activity was associated with Kit cytoplasmic expression (P = .01). c-Kit encoding mutations were present in 19 (56%) tumors (exon 8, 19%; exon 9, 71%; exon 11, 10%), however, they were not significantly related to protein expression and they had no influence on prognosis. Additionally, in 6 of 9 (67%) cats, multiple nodules from the same cat had different mutational statuses. Mutations in the fifth immunoglobulin-like domain of Kit occur frequently in FeCMCT, but they are variably associated with aberrant protein expression and do not appear to be strictly correlated with biological behavior. These findings need to be confirmed in larger series, and exploration of further genomic regions of c-Kit is warranted.
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[958]
TÍTULO / TITLE: - Metformin Induces Cytotoxicity by Down-Regulating Thymidine Phosphorylase and Excision Repair Cross-Complementation 1 Expression in Non-Small Cell Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Basic Clin Pharmacol Toxicol. 2013 Jan 31. doi: 10.1111/bcpt.12052.
●● Enlace al texto completo (gratuito o de pago) 1111/bcpt.12052
AUTORES / AUTHORS: - Ko JC; Huang YC; Chen HJ; Tseng SC; Chiu HC; Wo TY; Huang YJ; Weng SH; Chiou RY; Lin YW
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan.
RESUMEN / SUMMARY: - Metformin is an antidiabetic drug recently shown to inhibit cancer cell proliferation and growth, although the involved molecular mechanisms have not been elucidated. In many cancer cells, high expression of thymidine phosphorylase (TP) and Excision repair cross-complementation 1 (ERCC1) is associated with poor prognosis. We used A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines to investigate the role of TP and ERCC1 expression in metformin-induced cytotoxicity. Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner. The enforced expression of the constitutively active MEK1 (MEK1-CA) vectors significantly restored cellular TP and ERCC1 protein levels and cell viability. Specific inhibition of TP and ERCC1 expression by siRNA enhanced the metformin-induced cytotoxicity and growth inhibition. Arachidin-1, an antioxidant stilbenoid, further decreased TP and ERCC1 expression and augmented metformin’s cytotoxic effect, which was abrogated in lung cancer cells transfected with MEK1/2-CA expression vector. In conclusion, metformin induces cytotoxicity by down-regulating TP and ERCC1 expression in NSCLC cells.
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[959]
TÍTULO / TITLE: - MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-alpha.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55733. doi: 10.1371/journal.pone.0055733. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055733
AUTORES / AUTHORS: - Zhang X; Daucher M; Armistead D; Russell R; Kottilil S
INSTITUCIÓN / INSTITUTION: - Immunopathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
RESUMEN / SUMMARY: - OBJECTIVE: Increasing evidence suggests that miRNAs have a profound impact on host defense to Hepatitis C virus (HCV) infection and clinical outcome of standard HCV therapy. In this study, we investigated modulation of miRNA expression in Huh7.5 hepatoma cells by HCV infection and in vitro interferon-alphatreatment. METHODS: MiRNA expression profiling was determined using Human miRNA TaqMan® Arrays followed by rigorous pairwise statistical analysis. MiRNA inhibitors assessed the functional effects of miRNAs on HCV replication. Computational analysis predicted anti-correlated mRNA targets and their involvement in host cellular pathways. Quantitative RTPCR confirmed the expression of predicted miRNA-mRNA correlated pairs in HCV-infected Huh7.5 cells with and without interferon-alpha. RESULTS: Seven miRNAs (miR-30b, miR-30c, miR-130a, miR-192, miR-301, miR-324-5p, and miR-565) were down-regulated in HCV-infected Huh7.5 cells (p<0.05) and subsequently up-regulated following interferon-alpha treatment (p<0.01). The miR-30(a-d) cluster and miR-130a/301 and their putative mRNA targets were predicted to be associated with cellular pathways that involve Hepatitis C virus entry, propagation and host response to viral infection. CONCLUSIONS: HCV differentially modulates miRNAs to facilitate entry and early establishment of infection in vitro. Interferon-alpha appears to neutralize the effect of HCV replication on miRNA regulation thus providing a potential mechanism of action in eradicating HCV from hepatocytes.
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[960]
TÍTULO / TITLE: - miR-342 is associated with estrogen receptor-alpha expression and response to tamoxifen in breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Mar;5(3):813-818. Epub 2013 Jan 22.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2013.915
AUTORES / AUTHORS: - He YJ; Wu JZ; Ji MH; Ma T; Qiao EQ; Ma R; Tang JH
INSTITUCIÓN / INSTITUTION: - Surgery Department, The Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221000; ; Breast Surgery, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210000, P.R. China.
RESUMEN / SUMMARY: - Estrogen receptor-alpha (ERalpha) is essential for estrogen-dependent growth and its level of expression is a crucial determinant of response to endocrine therapy and prognosis in ERalpha-positive breast cancer. Breast cancer patients show a wide range of ERalpha expression levels which change in individual patients during disease progression and in response to systemic therapies. However, little is known concerning how the expression of ERalpha is regulated in human breast cancer. Recently, several microRNAs (miRNAs) have been identified to regulate ERalpha expression and to predict ER, progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status. The expression levels of miR-342 and ERalpha mRNA were analyzed in human breast cancer samples and cell lines by quantitative reverse transcription (RT)-PCR analysis. The correlations between the expression levels of miR-342 and clinicopathological factors were analyzed. Statistically significant associations were observed between miR-342 and ER, HER2 and vascular endothelial growth factor (VEGF) status in the human breast cancer samples and the levels of miR-342 gradually increased as ERalpha mRNA expression increased. Moreover, ectopic overexpression of miR-342 upregulated the expression levels of the ERalpha mRNA and significantly sensitized the MCF-7 cells to tamoxifen-induced apoptosis and inhibition of cellular proliferation. These results suggested that miR-342 expression is positively correlated with ERalpha mRNA expression in human breast cancer and that it may be a significant marker for predicting tamoxifen sensitivity in ERalpha-positive breast cancer and a potential target for restoring ERalpha expression and responding to antiestrogen therapy.
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[961]
TÍTULO / TITLE: - Curcumin modulates DNA methylation in colorectal cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57709. doi: 10.1371/journal.pone.0057709. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057709
AUTORES / AUTHORS: - Link A; Balaguer F; Shen Y; Lozano JJ; Leung HC; Boland CR; Goel A
INSTITUCIÓN / INSTITUTION: - Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, United States of America ; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
RESUMEN / SUMMARY: - AIM: Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. MATERIALS AND METHODS: To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2’-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. RESULTS: As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean beta-values of 0.12), however, non-significant changes in mean beta-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. CONCLUSIONS: Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza-CdR, curcumin-induced methylation changes occurred only in a subset of partially-methylated genes, which provides additional mechanistic insights into the potent chemopreventive effect of this dietary nutraceutical.
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[962]
TÍTULO / TITLE: - Expression of the cannabinoid type I receptor and prognosis following surgery in colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):870-876. Epub 2012 Dec 18.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1081
AUTORES / AUTHORS: - Jung CK; Kang WK; Park JM; Ahn HJ; Kim SW; Taek Oh S; Choi KY
INSTITUCIÓN / INSTITUTION: - Departments of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-070, Republic of Korea.
RESUMEN / SUMMARY: - The cannabinoid system has been considered to be a potential target of colorectal carcinoma therapy. The aim of this study was to address the correlation between cannabinoid type 1 (CB1) receptor expression and disease severity/outcomes in patients with colorectal cancer (CRC). CB1 receptor expression was analyzed by immunohistochemistry using tissue microarrays in consecutive patients who underwent surgical resection (n=534). CB1 receptor expression was categorized as a high (>/=66%) vs. low (<66%) immunopercentage as a median split, and was analyzed in relation to disease severity and overall survival. CB1 receptor expression was observed in 409 patients (76.6%). Low CB1 receptor expression was more frequently identified in stage IV than in stage I/II or III cancer (P<0.01 for both). In stage IV CRC, high vs. low CB1 expression was correlated with a statistically significant poorer overall survival (P=0.033) that was independent of age, R0 resection, tumor differentiation and chemotherapy [hazard ratio (HR), 1.805; 95% confidence interval (CI), 1.042-3.094; P=0.035]. However, CB1 expression was not observed to be correlated with patient survival following surgery in stage I/II or III cancer. The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC.
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[963]
TÍTULO / TITLE: - Effect of methanol extracts of Cnidium officinale Makino and Capsella bursa-pastoris on the apoptosis of HSC-2 human oral cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Mar;5(3):789-792. Epub 2012 Dec 21.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.871
AUTORES / AUTHORS: - Lee KE; Shin JA; Hong IS; Cho NP; Cho SD
INSTITUCIÓN / INSTITUTION: - Department of Oral Medicine, Chonbuk National University; Jeonju 561-756;
RESUMEN / SUMMARY: - Cnidium officinale Makino and Capsella bursa-pastoris are used as traditional herbs with diverse medicinal effects, including the inhibition of inflammation, reduction of blood pressure and as diuretics, however, the anti-cancer effects of C. officinale Makino and C. bursa-pastoris are poorly defined. The aims of this study were to evaluate the effects of methanol extracts of C. officinale Makino (MECO) and methanol extracts of C. bursa-pastoris (MECB) on the cell growth and apoptosis of HSC-2 human oral cancer cells. MECO and MECB caused growth inhibition and the induction of apoptosis in a concentration-dependent manner in HSC-2 cells. A marked reduction in specificity protein 1 (Sp1) expression following treatment with MECO or MECB was also observed. The downregulation of Sp1 by siRNA resulted in growth inhibition and a reduction of total poly (ADP-ribose) polymerase (PARP) expression. In addition, MECO significantly increased Bax expression levels and MECB increased Bak expression levels and decreased Mcl-1 expression levels. These results suggest that MECO and MECB inhibit cell growth and induce apoptosis via the Sp1 protein, indicating that MECO and MECB are useful bioactive materials and attractive drug candidates for oral cancer.
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[964]
TÍTULO / TITLE: - Oxidative Stress Induces Mitochondrial DNA Damage and Cytotoxicity through Independent Mechanisms in Human Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:825065. doi: 10.1155/2013/825065. Epub 2012 Dec 26.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/825065
AUTORES / AUTHORS: - Han Y; Chen JZ
INSTITUCIÓN / INSTITUTION: - Division of Urology, Department of Surgery, Research Institute of McGill University Health Center, Room R1-107, 1650 Cedar Avenue, Montreal, QC, Canada H3G 1A4.
RESUMEN / SUMMARY: - Intrinsic oxidative stress through increased production of reactive oxygen species (ROS) is associated with carcinogenic transformation, cell toxicity, and DNA damage. Mitochondrial DNA (mtDNA) is a natural surrogate to oxidative DNA damage. MtDNA damage results in the loss of its supercoiled structure and is readily detectable using a novel, supercoiling-sensitive real-time PCR method. Our studies have demonstrated that mtDNA damage, as measured by DNA strand breaks and copy number depletion, is very sensitive to exogenous H2O2 but independent of endogenous ROS production in both prostate cancer and normal cells. In contrast, aggressive prostate cancer cells exhibit a more than 10-fold sensitivity to H2O2-induced cell toxicity than normal cells, and a cascade of secondary ROS production is a critical determinant to the differential response. We propose a new paradigm to account for different mechanisms governing cellular oxidative stress, cell toxicity, and DNA damage with important ramifications in devising new techniques and strategies in prostate cancer prevention and treatment.
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[965]
TÍTULO / TITLE: - The Pharmacological NF-kappaB Inhibitor BAY11-7082 Induces Cell Apoptosis and Inhibits the Migration of Human Uveal Melanoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2012 Nov 23;13(12):15653-67. doi: 10.3390/ijms131215653.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms131215653
AUTORES / AUTHORS: - Hu S; Luo Q; Cun B; Hu D; Ge S; Fan X; Chen F
INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratories, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. fanxq@sh163.net.
RESUMEN / SUMMARY: - Uveal melanomas are highly metastatic and have high rate of recurrence due to the lack of effective systemic therapy. The identification of important survival pathways in uveal melanomas provides novel therapeutic targets for effective treatment. In the present study, we found that the NF-kappaB signaling pathway was constitutively and highly activated in uveal melanoma cells. Treatment with the pharmacological NF-kappaB specific inhibitor BAY11-7082 markedly decreased the nuclear translocation of NF-kappaB. In a dose-dependent setting, BAY11-7082 inhibited the proliferation and growth of uveal melanoma cells by inducing apoptosis without effect on cell cycle. The migration capacity of uveal melanoma cells was also significantly suppressed by BAY11-7082 treatment. Mechanistically, BAY11-7082 increased the activity of caspase 3 and reduced the expression of anti-apoptotic protein Bcl-2, but did not influence the expression of pro-apoptotic protein Bax. Furthermore, BAY11-7082 induced uveal melanoma cell apoptosis and inhibited xenograft tumor growth in vivo. Collectively, the present study identified NF-kappaB as an important survival signal for uveal melanoma cells and suggested that administration of specific NF-kappaB inhibitor BAY11-7082 could serve as an effective treatment for patients with uveal melanoma.
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[966]
TÍTULO / TITLE: - Computational purification of individual tumor gene expression profiles leads to significant improvements in prognostic prediction.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genome Med. 2013 Mar 28;5(3):29.
●● Enlace al texto completo (gratuito o de pago) 1186/gm433
AUTORES / AUTHORS: - Quon G; Haider S; Deshwar AG; Cui A; Boutros PC; Morris Q
RESUMEN / SUMMARY: - Tumor heterogeneity is a limiting factor in cancer treatment and in the discovery of biomarkers to personalize it. We describe a computational purification tool, ISOpure, to directly address the effects of variable normal tissue contamination in clinical tumor specimens. ISOpure uses a set of tumor expression profiles and a panel of healthy tissue expression profiles to generate a purified cancer profile for each tumor sample and an estimate of the proportion of RNA originating from cancerous cells. Applying ISOpure before identifying gene signatures leads to significant improvements in the prediction of prognosis and other clinical variables in lung and prostate cancer.
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[967]
TÍTULO / TITLE: - Cyclin-Dependent Kinase 4 Phosphorylates and Positively Regulates PAX3-FOXO1 in Human Alveolar Rhabdomyosarcoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e58193. doi: 10.1371/journal.pone.0058193. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058193
AUTORES / AUTHORS: - Liu L; Wu J; Ong SS; Chen T
INSTITUCIÓN / INSTITUTION: - Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America.
RESUMEN / SUMMARY: - Alveolar rhabdomyosarcoma (ARMS) is an aggressive childhood muscle sarcoma with a 5-year survival rate of less than 30%. More than 80% of ARMSs harbor a PAX3-FOXO1 fusion transcription factor. However, expression of PAX3-FOXO1 in muscle cells alone is not sufficient and requires the loss of function of Ink4a/ARF to promote malignant proliferation of muscle cells in vitro or initiate ARMS tumor formation in vivo. This prompted us to examine the signaling pathways required to activate the function of PAX3-FOXO1 and to explore the functional interaction between the Ink4a/ARF and PAX3-FOXO1 signaling pathways. Here we report that inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin (a small molecule selective inhibitor of Cdk4/cyclin D1 that we identified in a screen for compounds that inhibit PAX3-FOXO1) led to inhibition of the transcriptional activity of PAX3-FOXO1 in ARMS cell line Rh30. Consistent with this finding, activation of Cdk4 enhanced the activity of PAX3-FOXO1. In vitro kinase assays revealed that Cdk4 directly phosphorylated PAX3-FOXO1 at Ser(430). Whereas fascaplysin did not affect the protein level of PAX3-FOXO1, it did increase the cytoplasmic level of PAX3-FOXO1 in a portion of cells. Our findings indicate that Cdk4 phosphorylates and positively regulates PAX3-FOXO1 and suggest that inhibition of Cdk4 activity should be explored as a promising avenue for developing therapy for ARMS.
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[968]
TÍTULO / TITLE: - Tamoxifen Benefits and CYP2D6 Testing in Women With Hormone Receptor-Positive Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin J Oncol Nurs. 2013 Apr 1;17(2):174-9. doi: 10.1188/13.CJON.174-179.
●● Enlace al texto completo (gratuito o de pago) 1188/13.CJON.174-179
AUTORES / AUTHORS: - Kaplan M; Mahon SM
INSTITUCIÓN / INSTITUTION: - School of Nursing, Adelphi University, Long Island, NY.
RESUMEN / SUMMARY: - Cancer intervention strategies have been increasingly focused on developing therapies that are personalized and tailored to each individual’s unique genetic profile. Evolving understanding of the metabolism and pharmacogenomics of tamoxifen, an early example of targeted therapy for women with hormone receptor-positive breast cancer, has created decision-making challenges for healthcare providers and their patients. This article reviews the pharmacology of tamoxifen, the genetics and physiology of the CYP2D6 enzyme system that has important effects on tamoxifen metabolism, and subset data analyses from large controlled, clinical trials that cast new light on previously held beliefs about the utility of CYP2D6 genotyping for predicting tamoxifen effectiveness and improved breast cancer outcomes in women with early-stage, hormone receptor-positive breast cancer.
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[969]
TÍTULO / TITLE: - The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 5. doi: 10.3892/mmr.2013.1359.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1359
AUTORES / AUTHORS: - Liao YR; Lu CC; Lai KC; Yang JS; Kuo SC; Wen YF; Fushiya S; Wu TS
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, R.O.C.
RESUMEN / SUMMARY: - We have previously reported that ITR-284, a potent carboxamide-derived anticancer agent, induced apoptosis in leukemia cells. However, there are no reports showing that ITR-284 inhibits human hepatocellular and colorectal cancer cells. In this study, we investigated the antiproliferative effects and apoptotic induction of ITR-284 on various types of human hepatocellular and colorectal cancer cells in vitro. The growth inhibition effect of ITR-284 on cancer cells was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Cell morphology was examined under a phase-contrast microscope. The activities of caspase-3, -8 and -9 were determined by caspase colorimetric assay. ITR-284 reduced the cell viability in human hepatocellular cancer cells (Hep G2, Hep 3B, SK-HEP-1 and J5) and colorectal cancer cells (HT 29, COLO 205, HCT 116 and SW 620). ITR-284 had highly selective effects on Hep 3B and COLO 205 cells. ITR-284 stimulated morphological changes of Hep 3B and COLO 205 cells. The activation of caspase-3, -8 and -9 contributed to ITR-284-induced apoptosis. ITR-284-triggered growth inhibition was significantly attenuated by the inhibitors of caspase-3, -8 and -9 in Hep 3B and COLO 205 cells. ITR-284 induced apoptosis in Hep 3B and COLO 205 cells through the caspase cascade-dependent signaling pathway.
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[970]
TÍTULO / TITLE: - Energy deprivation by silibinin in colorectal cancer cells: A double-edged sword targeting both apoptotic and autophagic machineries.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Autophagy. 2013 Feb 27;9(5).
AUTORES / AUTHORS: - Raina K; Agarwal C; Wadhwa R; Serkova NJ; Agarwal R
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences; Skaggs School of Pharmacy; University of Colorado Anschutz Medical Campus; Aurora, CO USA.
RESUMEN / SUMMARY: - Small molecules with the potential to initiate different types of programmed cell death could be useful ‘adjunct therapy’ where current anticancer modalities fail to generate significant activity due to a defective apoptotic machinery or resistance of cancer cells to the specific death mechanism induced by that treatment. The current study identified silibinin, for the first time, as one such natural agent, having dual efficacy against colorectal cancer (CRC) cells. First, silibinin rapidly induced oxidative stress in CRC SW480 cells due to reactive oxygen species (ROS) generation with a concomitant dissipation of mitchondrial potential (DeltaPsim) and cytochrome c release leading to mild apoptosis as a biological effect. However, with increased exposure to silibinin, cytoplasmic vacuolization intensified within the cells followed by sequestration of the organelles, which inhibits the further release of cytochrome c. Interestingly, this decrease in apoptotic response correlated with increased autophagic events as evidenced by tracking the dynamics of LC3-II within the cells. Mechanistic studies revealed that silibinin strongly inhibited PIK3CA-AKT-MTOR but activated MAP2K1/2-MAPK1/3 pathways for its biological effects. Corroborating these effects, endoplasmic reticulum stress was generated and glucose uptake inhibition as well as energy restriction were induced by silibinin, thus, mimicking starvation-like conditions. Further, the cellular damage to tumor cells by silibinin was severe and irreparable due to sustained interference in essential cellular processes such as mitochondrial metabolism, phospholipid and protein synthesis, suggesting that silibinin harbors a deadly ‘double-edged sword’ against CRC cells thereby further advocating its clinical effectiveness against this malignancy.
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[971]
TÍTULO / TITLE: - Effects of Dual Targeting of Tumor Cells and Stroma in Human Glioblastoma Xenografts with a Tyrosine Kinase Inhibitor against c-MET and VEGFR2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58262. doi: 10.1371/journal.pone.0058262. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058262
AUTORES / AUTHORS: - Navis AC; Bourgonje A; Wesseling P; Wright A; Hendriks W; Verrijp K; van der Laak JA; Heerschap A; Leenders WP
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
RESUMEN / SUMMARY: - Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF Receptor 2 (VEGFR2) inhibitors normalizes tumor vessels, resulting in a profound radiologic response and improved quality of life. This approach however does not halt tumor progression by diffuse infiltration, as this phenotype is less angiogenesis dependent. Combined inhibition of angiogenesis and diffuse infiltrative growth would therefore be a more effective treatment approach in these tumors. The HGF/c-MET axis is important in both angiogenesis and cell migration in several tumor types including glioma. We therefore analyzed the effects of the c-MET- and VEGFR2 tyrosine kinase inhibitor cabozantinib (XL184, Exelixis) on c-MET positive orthotopic E98 glioblastoma xenografts, which routinely present with angiogenesis-dependent areas of tumor growth, as well as diffuse infiltrative growth. In in vitro cultures of E98 cells, cabozantinib effectively inhibited c-MET phosphorylation, concomitant with inhibitory effects on AKT and ERK1/2 phosphorylation, and cell proliferation and migration. VEGFR2 activation in endothelial cells was also effectively inhibited in vitro. Treatment of BALB/c nu/nu mice carrying orthotopic E98 xenografts resulted in a significant increase in overall survival. Cabozantinib effectively inhibited angiogenesis, resulting in increased hypoxia in angiogenesis-dependent tumor areas, and induced vessel normalization. Yet, tumors ultimately escaped cabozantinib therapy by diffuse infiltrative outgrowth via vessel co-option. Of importance, in contrast to the results from in vitro experiments, in vivo blockade of c-MET activation was incomplete, possibly due to multiple factors including restoration of the blood-brain barrier resulting from cabozantinib-induced VEGFR2 inhibition. In conclusion, cabozantinib is a promising therapy for c-MET positive glioma, but improving delivery of the drug to the tumor and/or the surrounding tissue may be needed for full activity.
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[972]
TÍTULO / TITLE: - Analgesic-antitumor peptide induces apoptosis and inhibits the proliferation of SW480 human colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):483-488. Epub 2012 Nov 27.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1049
AUTORES / AUTHORS: - Gu Y; Liu SL; Ju WZ; Li CY; Cao P
INSTITUCIÓN / INSTITUTION: - The First Clinical Medical College, Nanjing University of Traditional Medicine; Nanjing, Jiangsu, P.R. China.
RESUMEN / SUMMARY: - Colorectal cancer is one of the most common malignant tumors, and is associated with significant morbidity and mortality. In this study, recombinant analgesic-antitumor peptide (rAGAP), a protein consisting of small ubiquitin-related modifier (SUMO) linked with a hexa-histidine tag, was used as an antitumor analgesic peptide. The purpose of the present study was to investigate the antitumor activity of rAGAP in human colon adenocarcinoma SW480 cells and its potential molecular mechanisms of action. In this study, cell viability and apoptosis of rAGAP-treated SW480 cells was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and 4’,6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to investigate the effects of rAGAP on p27, Bcl-2/Bax and PTEN/PI3K/Akt cellular signal transduction. Our results showed that rAGAP not only enhanced apoptosis, but also inhibited the proliferation of SW480 cells. rAGAP upregulates the expression of p27 in SW480 cells and leads to cell cycle arrest in the G1 phase. Furthermore, rAGAP significantly increases the production of Bax and PTEN and suppresses the activation of Bcl-2, phosphatidylinositol 3-kinase (PI3K) and phospho-Akt (p-Akt) in SW480 cells. These results suggest that rAGAP may be a potential new anti-colorectal cancer drug.
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[973]
TÍTULO / TITLE: - How to target apoptosis signaling pathways for the treatment of pediatric cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Oncol. 2013;3:22. doi: 10.3389/fonc.2013.00022. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00022
AUTORES / AUTHORS: - Fulda S
INSTITUCIÓN / INSTITUTION: - Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Germany.
RESUMEN / SUMMARY: - Apoptosis represents one of the most important forms of cell death in higher organisms and is typically dysregulated in human cancers, including pediatric tumors. This implies that ineffective engagement of cell death programs can contribute to tumor formation as well as tumor progression. In addition, the majority of cytotoxic therapeutic principles rely on the activation of cell death signaling pathways in cancer cells. Blockade of signaling networks that lead to cell death can therefore confer treatment resistance. A variety of genetic and epigenetic events as well as dysfunctional regulation of signaling networks have been identified as underlying causes of cell death resistance in childhood malignancies. Apoptosis pathways can be therapeutically exploited by enhancing proapoptotic signals or by neutralizing antiapoptotic programs. The challenge in the coming years will be to successfully transfer this knowledge into the development of innovative treatment approaches for children with cancer.
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[974]
TÍTULO / TITLE: - The Role of Estrogen Receptor beta in Transplacental Cancer Prevention by Indole-3-Carbinol.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Prev Res (Phila). 2013 Apr;6(4):339-48. doi: 10.1158/1940-6207.CAPR-12-0311. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0311
AUTORES / AUTHORS: - Benninghoff AD; Williams DE
INSTITUCIÓN / INSTITUTION: - Department of Animal, Dairy and Veterinary Sciences, Utah State University, 4815 Old Main Hill, Logan, UT 84322. abby.benninghoff@usu.edu.
RESUMEN / SUMMARY: - In the present study, the efficacy of indole-3-carbinol (I3C), a key bioactive component of cruciferous vegetables, for prevention of cancer in offspring exposed in utero to the environmental carcinogen dibenzo[def,p]chrysene (DBC) was evaluated using an estrogen receptor beta (ERbeta) knockout mouse model. I3C was provided either through the maternal diet coincident with carcinogen exposure during pregnancy or directly to offspring postinitiation with DBC. I3C was effective at reducing T-cell acute lymphoblastic lymphoma/leukemia (T-ALL)-related mortality in offspring only if provided via the maternal diet, although a gender difference in the role of ERbeta in mediating this response was evident. In female offspring, chemoprevention of T-ALL by maternal dietary I3C required expression of ERbeta; survival in Esr2 wild-type and heterozygous female offspring was more than 90% compared with 66% in Esr2 null females. Alternatively, ERbeta status did not significantly impact the transplacental chemoprevention by I3C in males. The possible role of ERbeta in mediating lung carcinogenesis or chemoprevention by I3C was similarly complicated. Lung tumor incidence was unaltered by either dietary intervention, whereas lung tumor multiplicity was substantially reduced in Esr2 null females on the control diet and marginally lower in Esr2 null males exposed to I3C via the maternal diet compared with their wild-type and heterozygous counterparts. These findings suggest that I3C may act via ERbeta to prevent or suppress DBC-initiated transplacental carcinogenesis but that the involvement of this receptor seems to differ depending on the cancer type and gender of the offspring. Cancer Prev Res; 6(4); 339-48. ©2013 AACR.
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[975]
TÍTULO / TITLE: - Ursolic acid induces apoptosis via Akt/NF-kappaB signaling suppression in T24 human bladder cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 11. doi: 10.3892/mmr.2013.1364.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1364
AUTORES / AUTHORS: - Gai L; Cai N; Wang L; Xu X; Kong X
INSTITUCIÓN / INSTITUTION: - Department of Urologic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 13003, P.R. China.
RESUMEN / SUMMARY: - The Akt/NF-kappaB pathway is involved in numerous antiapoptotic and drug resistance events which occur in various types of bladder cancer. The present study investigated the role of ursolic acid in the regulation of anti-apoptotic Akt and NF-kappaBp65 signaling. T24 human bladder cancer cells were treated with ursolic acid at final concentrations of 12.5, 25 or 50 micromol/l for 48 h. Quantitative PCR (qPCR) and western blotting were performed to detect mRNA and protein expression, respectively. The results showed that anti-apoptotic phospho-Akt1 (pAkt1), phospho-IkappaBalpha (pIkappaBalpha), NF-kappaBp65 and Bcl-2 were inhibited and pro-apoptotic caspase-3 was upregulated in a dosedependent manner. A 50 micromol/l dose of ursonic acid decreased the mRNA expression levels of anti-apoptotic NF-kappaBp65 and Bcl-2 0.17 (8.9/52.6)-fold and 0.22 (9.5/42.3)fold, respectively. The pro-apoptotic caspase-3 mRNA expression levels were upregulated 4.78 (38.7/8.1)-fold. The anti-apoptotic pAkt1, pIkappaBalpha, NF-kappaBp65 and Bcl-2 protein levels were downregulated to 5.1 (blot grayscales vs. control at 32.3), 3.2 (vs. 24.2), 8.5 (vs. 45.1) and 9.2 (vs. 40.3). The protein levels of pro-apoptotic caspase-3 were upregulated to 20.7 (vs. 4.7). The proliferative activity of T24 cells treated with 12.5, 25.0 and 50.0 micromol/l ursolic acid was significantly reduced compared with that of control cells (83.8, 56.2 and 31.5 vs. 97.6%, respectively, P<0.05 for each). In conclusion, ursolic acid is important in inducing apoptosis via the suppression of Akt/NF-kappaB signaling in T24 human bladder cancer cells and this occurs in a dose-dependent manner. Ursolic acid may therefore serve as a naturally occurring candidate drug for the prevention and treatment of bladder cancer.
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[976]
TÍTULO / TITLE: - Homeopathic mother tincture of Phytolacca decandra induces apoptosis in skin melanoma cells by activating caspase-mediated signaling via reactive oxygen species elevation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Integr Med. 2013 Mar;11(2):116-24. doi: 10.3736/jintegrmed2013014.
●● Enlace al texto completo (gratuito o de pago) 3736/jintegrmed2013014
AUTORES / AUTHORS: - Ghosh S; Bishayee K; Paul A; Mukherjee A; Sikdar S; Chakraborty D; Boujedaini N; Khuda-Bukhsh AR
INSTITUCIÓN / INSTITUTION: - Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, West Bengal, India; E-mail: prof_arkb@yahoo.co.in, khudabukhsh_48@rediffmail.com.
RESUMEN / SUMMARY: - OBJECTIVE: Preventive measures against skin melanoma like chemotherapy are useful but suffer from chronic side effects and drug resistance. Ethanolic extract of Phytolacca decandra (PD), used in homeopathy for the treatment of various ailments like chronic rheumatism, regular conjunctivitis, psoriasis, and in some skin diseases was tested for its possible anticancer potential. METHODS: Cytotoxicity of the drug was tested by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on both normal (peripheral blood mononuclear cells) and A375 cells. Fluorescence microscopic study of 4’,6-diamidino-2-phenylindole dihydrochloride-stained cells was conducted for DNA fragmentation assay, and changes in cellular morphology, if any, were also recorded. Lactate dehydrogenase activity assay was done to evaluate the percentages of apoptosis and necrosis. Reactive oxygen species (ROS) accumulation, if any, and expression study of apoptotic genes also were evaluated to pin-point the actual events of apoptosis. RESULTS: Results showed that PD administration caused a remarkable reduction in proliferation of A375 cells, without showing much cytotoxicity on peripheral blood mononuclear cells. Generation of ROS and DNA damage, which made the cancer cells prone to apoptosis, were found to be enhanced in PD-treated cells. These results were duly supported by the analytical data on expression of different cellular and nuclear proteins, as for example, by down-regulation of Akt and Bcl-2, up-regulation of p53, Bax and caspase 3, and an increase in number of cell deaths by apoptosis in A375 cells. CONCLUSION: Overall results demonstrate anticancer potentials of PD on A375 cells through activation of caspase-mediated signaling and ROS generation.
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[977]
TÍTULO / TITLE: - Pramanicin analog induces apoptosis in human colon cancer cells: critical roles for Bcl-2, Bim, and p38 MAPK signaling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56369. doi: 10.1371/journal.pone.0056369. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056369
AUTORES / AUTHORS: - Bodur C; Kutuk O; Karsli-Uzunbas G; Isimjan TT; Harrison P; Basaga H
INSTITUCIÓN / INSTITUTION: - Biological Sciences and Bioengineering Program, Sabanci University, Istanbul, Turkey.
RESUMEN / SUMMARY: - Pramanicin (PMC) is an antifungal agent that was previously demonstrated to exhibit antiangiogenic and anticancer properties in a few in vitro studies. We initially screened a number of PMC analogs for their cytotoxic effects on HCT116 human colon cancer cells. PMC-A, the analog with the most potent antiproliferative effect was chosen to further interrogate the underlying mechanism of action. PMC-A led to apoptosis through activation of caspase-9 and -3. The apoptotic nature of cell death was confirmed by abrogation of cell death with pretreatment with specific caspase inhibitors. Stress-related MAPKs JNK and p38 were both activated concomittantly with the intrinsic apoptotic pathway. Moreover, pharmacological inhibition of p38 proved to attenuate the cell death induction while pretreatment with JNK inhibitor did not exhibit a protective effect. Resistance of Bax -/- cells and the protective nature of caspase-9 inhibition indicate that mitochondria play a central role in PMC-A induced apoptosis. Early post-exposure elevation of cellular Bim and Bax was followed by a marginal Bcl-2 depletion and Bid cleavage. Further analysis revealed that Bcl-2 downregulation occurs at the mRNA level and is critical to mediate PMC-A induced apoptosis, as ectopic Bcl-2 expression substantially spared the cells from death. Conversely, forced expression of Bim proved to significantly increase cell death. In addition, analyses of p53-/- cells demonstrated that Bcl-2/Bim/Bax modulation and MAPK activations take place independently of p53 expression. Taken together, p53-independent transcriptional Bcl-2 downregulation and p38 signaling appear to be the key modulatory events in PMC-A induced apoptosis.
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[978]
TÍTULO / TITLE: - siRNA targeting of PRDX3 enhances cisplatininduced apoptosis in ovarian cancer cells through the suppression of the NFkappaB signaling pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 14. doi: 10.3892/mmr.2013.1370.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1370
AUTORES / AUTHORS: - Duan J; Lang Y; Song C; Xiong J; Wang Y; Yan Y
INSTITUCIÓN / INSTITUTION: - Gynecology, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430070, P.R. China.
RESUMEN / SUMMARY: - The overexpression of peroxiredoxins (prxs) has been shown to be associated with the development, progression and drug resistance of cancer. However, the role of the prxs in the drug resistance of ovarian cancer is unknown. The present study aimed to investigate the effect and mechanism of the downregulation of PRDX3 on cisplatininduced ovarian cancer cell apoptosis. The expression of PRDX3 in ovarian cancer was examined by immunohistochemistry. The effect on cisplatininduced ovarian cancer apoptosis by the silencing of PRDX3 was determined by cell proliferation and colony formation assays and the examination of tumor growth in the nude mice. To further investigate the mechanism behind the downregulation of PRDX3, the expression of the antiapoptotic proteins Bcl2 and BclXL and the proapoptotic proteins Bax, Caspase3 and Caspase9 was examined in various ovarian cancer cells. The results showed that the aberrant expression of PRDX3 in ovarian cancer may be a factor responsible for its progression. SKOV3 ovarian cancer cells transfected with PRDX3/small interfering (Si)1 efficiently downregulated the expression of PRDX3 and thus decreased the growth of the SKOV3 cells in vitro and in vivo. Furthermore, the silencing of PRDX3 triggered cisplatinmediated apoptosis in the ovarian cancer cells, which may act through suppression of the NFkappaB signaling pathway. These data suggest a new mechanism by which the downregulation of PRDX3 enhances cisplatininduced ovarian cancer cell apoptosis. This mechanism may provide new evidence for the potential application of PRDX3siRNA in ovarian cancer therapy.
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[979]
TÍTULO / TITLE: - p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 25;13(1):151.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-151
AUTORES / AUTHORS: - Gersende A; Mira M; Priscillia BM; Dominique A; Michael B; Robert R; Gisela TS; Claudia F; Claire RL
RESUMEN / SUMMARY: - BACKGROUND: To determine whether ceramide is responsible for the induction of p53-independent early or late apoptosis in response to high- and low-Linear-Energy-Transfer (LET) irradiation. METHODS: Four cell lines displaying different radiosensitivities and p53-protein status were irradiated with photons or 33.4 or 184 keV/mum carbon ions. The kinetics of ceramide production was quantified by fluorescent microscopy or High-Performance-Liquid-Chromatogaphy and the sequence of events leading to apoptosis by flow cytometry. RESULTS: Regardless of the p53-status, both low and high-LET irradiation induced an early ceramide production in radiosensitive cells and late in the radioresistant. This production strongly correlated with the level of early apoptosis in radiosensitive cells and delayed apoptosis in the radioresistant ones, regardless of radiation quality, tumor type, radiosensitivity, or p53-status. Inhibition of caspase activity or ceramide production showed that, for both types of radiation, ceramide is essential for the initiation of early apoptosis in radiosensitive cells and late apoptosis following mitotic catastrophe in radioresistant cells. CONCLUSIONS: Ceramide is a determining factor in the onset of early and late apoptosis after low and high-LET irradiation and is the mediator of the p53-independent-apoptotic pathway. We propose that ceramide is the molecular bridge between mitotic catastrophe and the commitment phase of delayed apoptosis in response to irradiation.
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[980]
TÍTULO / TITLE: - An inverse switch in DNA base excision and strand break repair contributes to melphalan resistance in multiple myeloma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55493. doi: 10.1371/journal.pone.0055493. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055493
AUTORES / AUTHORS: - Sousa MM; Zub KA; Aas PA; Hanssen-Bauer A; Demirovic A; Sarno A; Tian E; Liabakk NB; Slupphaug G
INSTITUCIÓN / INSTITUTION: - Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
RESUMEN / SUMMARY: - Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating DNA damage signaling and -repair in RPMI8226 multiple myeloma cells and its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state levels of DNA glycosylases UNG2, NEIL1 and MPG in the resistant cells and cross-resistance to agents inducing their respective DNA base lesions. Conversely, repair of alkali-labile sites was apparently enhanced in the resistant cells, as substantiated by alkaline comet assay, autoribosylation of PARP-1, and increased sensitivity to PARP-1 inhibition by 4-AN or KU58684. Reduced base-excision and enhanced single-strand break repair would both contribute to the observed reduction in genomic alkali-labile sites, which could jeopardize productive processing of the more cytotoxic Melphalan-induced interstrand DNA crosslinks (ICLs). Furthermore, we found a marked upregulation of proteins in the non-homologous end-joining (NHEJ) pathway of double-strand break (DSB) repair, likely contributing to the observed increase in DSB repair kinetics in the resistant cells. Finally, we observed apparent upregulation of ATR-signaling and downregulation of ATM-signaling in the resistant cells. This was accompanied by markedly increased sensitivity towards Melphalan in the presence of ATR-, DNA-PK, or CHK1/2 inhibitors whereas no sensitizing effect was observed subsequent to ATM inhibition, suggesting that replication blocking lesions are primary triggers of the DNA damage response in the Melphalan resistant cells. In conclusion, Melphalan resistance is apparently contributed by modulation of the DNA damage response at multiple levels, including downregulation of specific repair pathways to avoid repair intermediates that could impair efficient processing of cytotoxic ICLs and ICL-induced DSBs. This study has revealed several novel candidate biomarkers for Melphalan sensitivity that will be included in targeted quantitation studies in larger patient cohorts to validate their value in prognosis as well as targets for replacement- or adjuvant therapies.
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[981]
TÍTULO / TITLE: - Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 9;13(1):12.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-12
AUTORES / AUTHORS: - Yang S; Zhao Q; Xiang H; Liu M; Zhang Q; Xue W; Song B; Yang S
RESUMEN / SUMMARY: - ABSTRACT: BACKGROUND: Natural products, including plants, microorganisms and marines, have been considered as valuable sources for anticancer drug discovery. Many Chinese herbs have been discovered to be potential sources of antitumor drugs. METHODS: In the present study, we investigated the antitumor efficacy of the compounds isolated from Toona sinensis, an important herbal medicine. The inhibitory activities of these compounds were investigated on MGC-803, PC3, A549, MCF-7, and NIH3T3 cells in vitro by MTT assay. The mechanism of the antitumor action of active compounds was investigated through AO/EB staining, Hoechst 33258 staining, TUNEL assay, flow cytometry analysis, and western blotting analysis. RESULTS: Fifteen compounds were isolated from the roots of Toona sinensis. Betulonic acid (BTA) and 3-oxours-12-en-28-oic acid (OEA) isolated from the plant inhibited the proliferation of MGC-803 and PC3 cells, with IC50 values of 17.7 muM and 13.6 muM, 26.5 muM and 21.9 muM, respectively. Both could lead to cell apoptosis, and apoptosis ratios reached 27.3% and 24.5% in MGC-803 cells at 72 h after treatment at 20 muM, respectively. Moreover, the study of cancer cell apoptotic signaling pathway indicated that both of them could induce cancer cell apoptosis through the mitochondrial pathway, involving the expressions of p53, Bax, caspase 9 and caspase 3. CONCLUSIONS: The study shows that most of the compounds obtained from Toona sinensis could inhibit the growth of human cancer cells. Furthermore, BTA and OEA exhibited potent antitumor activities via induction of cancer cell apoptosis.
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[982]
TÍTULO / TITLE: - Cisplatin-induced apoptosis inhibits autophagy, which acts as a pro-survival mechanism in human melanoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57236. doi: 10.1371/journal.pone.0057236. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057236
AUTORES / AUTHORS: - Del Bello B; Toscano M; Moretti D; Maellaro E
INSTITUCIÓN / INSTITUTION: - Department of Pathophysiology, Experimental Medicine and Public Health, Istituto Toscano Tumori, University of Siena, Siena, Italy.
RESUMEN / SUMMARY: - The interplay between a non-lethal autophagic response and apoptotic cell death is still a matter of debate in cancer cell biology. In the present study performed on human melanoma cells, we investigate the role of basal or stimulated autophagy in cisplatin-induced cytotoxicity, as well as the contribution of cisplatin-induced activation of caspases 3/7 and conventional calpains. The results show that, while down-regulating Beclin-1, Atg14 and LC3-II, cisplatin treatment inhibits the basal autophagic response, impairing a physiological pro-survival response. Consistently, exogenously stimulated autophagy, obtained with trehalose or calpains inhibitors (MDL-28170 and calpeptin), protects from cisplatin-induced apoptosis, and such a protection is reverted by inhibiting autophagy with 3-methyladenine or ATG5 silencing. In addition, during trehalose-stimulated autophagy, the cisplatin-induced activation of calpains is abrogated, suggesting the existence of a feedback loop between the autophagic process and calpains. On the whole, our results demonstrate that in human melanoma cells autophagy may function as a beneficial stress response, hindered by cisplatin-induced death mechanisms. In a therapeutic perspective, these findings suggest that the efficacy of cisplatin-based polychemotherapies for melanoma could be potentiated by inhibitors of autophagy.
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[983]
TÍTULO / TITLE: - Effects of tubeimoside-1 on the proliferation and apoptosis of BGC823 gastric cancer cells in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):801-804. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1117
AUTORES / AUTHORS: - Zhang Y; Xu XM; Zhang M; Qu D; Niu HY; Bai X; Kan L; He P
INSTITUCIÓN / INSTITUTION: - Departments of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
RESUMEN / SUMMARY: - Natural products isolated from Chinese medicinal herbs are useful sources of new drugs for cancer therapy. Tubeimoside-1 (TBMS1) is a natural compound isolated from the Chinese medicinal herb Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae). Studies have shown that TBMS1 has anticancer effects in various human cancer cell lines. However, the effect of TBMS1 on human gastric cancer cells is unknown. In the present study, it was observed that TBMS1 inhibited BGC823 gastric cancer cell proliferation in a concentration- and time-dependent manner. Fluorescent microscopy and flow cytometric analysis showed that TBMS1 induced BGC823 cell apoptosis in a concentration-dependent manner. Western blot analysis also showed that TBMS1 induced apoptosis by regulation of the Bcl-2 gene family in BGC823 cells. These findings indicate that TBMS1 may be developed as a possible therapeutic agent for the management of gastric cancer.
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[984]
TÍTULO / TITLE: - Bevacizumab-based treatment in colorectal cancer with a NRAS Q61K mutation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0266-9
AUTORES / AUTHORS: - Janku F; Wheler JJ; Hong DS; Kurzrock R
INSTITUCIÓN / INSTITUTION: - Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Box 0455, Houston, TX, 77030, USA, fjanku@mdanderson.org.
RESUMEN / SUMMARY: - Despite development of new therapies, metastatic colorectal cancer (mCRC) largely remains an incurable disease. Approximately 2-6 % of colorectal cancers harbor NRAS mutations. The anti-VEGF antibody bevacizumab is a backbone of most therapeutic regimens; however, biomarkers predicting its activity are not known. We report two cases of mCRC with a Q61K NRAS mutation that had a favorable response to bevacizumab and the histone deacetylase inhibitor valproic acid. In contrast, none of ten patients with wild-type NRAS or unknown NRAS status and mutated KRAS (NRAS and KRAS mutations are mutually exclusive) responded to the same regimen. These results suggest that NRAS mutation merits further investigation as a potential biomarker predicting the efficacy of bevacizumab-based treatment.
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[985]
TÍTULO / TITLE: - Gene co-expression analysis predicts genetic aberration loci associated with colon cancer metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Comput Biol Drug Des. 2013;6(1-2):60-71. doi: 10.1504/IJCBDD.2013.052202. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1504/IJCBDD.2013.052202
AUTORES / AUTHORS: - Zhang J; Ni S; Xiang Y; Parvin JD; Yang Y; Zhou Y; Huang K
INSTITUCIÓN / INSTITUTION: - Comprehensive Cancer Center, Biomedical Informatics Shared Resource, The Ohio State University, Columbus, OH 43201, USA.
RESUMEN / SUMMARY: - Gene Co-expression Network (GCN) analysis has been widely used for gene function and disease biomarker discovery. In this study, we present a workflow for identifying GCN associated with colon cancer metastasis. The workflow includes dense network discovery from weighted GCN followed by network activity analysis using a mutual information-based approach to identify gene networks related to metastasis. Our findings suggest several genomic regions as genetic aberrations related to colon cancer malignancy including chr11q13, 20q13, 8q24 and 14q22-23. Our work also demonstrates a novel way of interpreting gene co-expression analysis results besides functional relationships and the effectiveness of the mutual information based network analysis in detecting subtle changes between different disease states.
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[986]
TÍTULO / TITLE: - Inorganic Phosphate as a Novel Signaling Molecule with Antiproliferative Action in MDA-MB-231 Breast Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biores Open Access. 2013 Feb;2(1):47-54. doi: 10.1089/biores.2012.0266.
●● Enlace al texto completo (gratuito o de pago) 1089/biores.2012.0266 [pii
●● Enlace al texto completo (gratuito o de pago) 1089/biores.2012.0266
AUTORES / AUTHORS: - Spina A; Sapio L; Esposito A; Di Maiolo F; Sorvillo L; Naviglio S
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Biophysics, Medical School, Second University of Naples , Naples, Italy .
RESUMEN / SUMMARY: - Inorganic phosphate (Pi) is an essential nutrient for living organisms. It plays a key role in diverse physiological functions, including osteoblast differentiation and skeletal mineralization. Relevantly, Pi is emerging as an important signaling molecule capable of modulating multiple cellular functions by altering signal transduction pathways, gene expression, and protein abundance in many cell types. To our knowledge, the consequences of elevated Pi on behavior of breast cancer cells have been poorly addressed. In this study we investigate the effects of Pi on proliferation of MDA-MB-231 breast cancer cells. We report that Pi inhibits proliferation of MDA-MB-231 cells by slowing cell cycle progression, without apoptosis occurrence. We found that Pi causes cells to accumulate in G1 phase in a time-dependent manner. Accordingly, G1 accumulation was associated with a decrease of cyclin A and cyclin E and an increase of cell cycle inhibitors p21 and p27 protein levels, respectively. Moreover, the Pi-induced antiproliferative effect was dynamically accompanied by profound changes in ERK1/2 and STAT3 protein and phosphorylation levels in response to Pi. Altogether, our data represent the first evidence of Pi acting as a novel signaling molecule in MDA-MB-231 breast cancer cells, capable of eliciting a strong antiproliferative action and suggest that targeting Pi levels at local sites might represent the rationale for developing novel strategies for therapeutic intervention in triple-negative breast cancer.
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[987]
TÍTULO / TITLE: - Expression of carboxyl terminus of Hsp70-interacting protein (CHIP) indicates poor prognosis in human gallbladder carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):813-818. Epub 2013 Jan 15.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1138
AUTORES / AUTHORS: - Liang ZL; Kim M; Huang SM; Lee HJ; Kim JM
INSTITUCIÓN / INSTITUTION: - Departments of Pathology and Chungnam National University School of Medicine, Jung-Gu, Daejeon 301-131, Republic of Korea.
RESUMEN / SUMMARY: - Gallbladder carcinoma (GBC) is a lethal neoplasm, and new prognostic markers are required. Deregulation of E3 ligases contributes to cancer development and is associated with poor prognosis. Carboxyl terminus of heat shock protein 70-interacting protein (CHIP) is a U-box-type E3 ubiquitin ligase, the role of which has not been evaluated in GBC. Therefore, the present study investigated CHIP expression in GBC and its prognostic significance. In the present study, CHIP expression was measured in 78 tumor specimens of GBC by immunohistochemistry and the correlation between CHIP expression and clinicopathological factors was analyzed. Of the tumor specimens, 26.9% showed high staining intensity [the CHIP high expression group (HEG)]. The CHIP-HEG was not associated with other common clinicopathological parameters, including T stage, and lymph node and distant metastases. CHIP-HEG patients had a significantly worse prognosis than patients with low CHIP expression with median cancer-specific survival times of 8.0 months (range, 1-34 months) and 13.0 months (range, 1-110 months), respectively (P=0.023). Multivariate analyses showed that CHIP expression was close to being an independent risk factor for predicting patient survival. CHIP expression may be associated with a poor prognosis in GBC. Since CHIP is not associated with other clinicopathological prognostic factors, it may serve as an ideal molecular marker for predicting patient outcomes.
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[988]
TÍTULO / TITLE: - Functional disruption of macrophage migration inhibitory factor (MIF) suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Mar 24;13(1):28.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-28
AUTORES / AUTHORS: - Guo Y; Hou J; Luo Y; Wang D
RESUMEN / SUMMARY: - BACKGROUND: Macrophage migration inhibitory factor (MIF) is important in regulating cell proliferation and apoptosis in both normal and cancerous cells, and may be important in cancer progression and metastasis. In human non-small cell lung cancer (NSCLC), the underlying mechanisms responsible for MIF-dependent regulation of cellular proliferation, and cell death remain poorly appreciated. METHODS: The human H460 lung cancer cell-line was treated with an optimally determined dose of 50 pmol/ml MIF siRNA, following which cell proliferation, cell cycle and apoptosis were analyzed. Additionally, known pathways of apoptosis including expression of Annexin-V, enhanced production of caspases-3 and -4 and expression of the Akt signaling protein were assessed in an attempt to provide insights into the signaling pathways involved in apoptosis following disruption of MIF expression. RESULTS: Specific siRNA sequences markedly decreased MIF expression in H460 cells by 2 to 5-fold as compared with the negative control. Moreover, MIF miRNA dampened not only cellular proliferation, but increased the frequency of apoptotic cells as assessed by cell-surface Annexin-V expression. Entry of cells into apoptosis was partly dependent on enhanced production of caspases -3 and -4 while not affecting the expression of either caspase-8 or the Akt signaling pathway. CONCLUSIONS: In a model of NSCLC, knockdown of MIF mRNA expression dampened H460 proliferation by mechanisms partly dependent on entry of cells into apoptosis and enhanced production of caspase-3 and -4. MIF expression may thus be important in NSCLC progression. Targeting MIF may have clinical utility in the management of human lung cancer.
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[989]
TÍTULO / TITLE: - Prognostic impact of cyclin d1, cyclin e and p53 on gastroenteropancreatic neuroendocrine tumours.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):419-22.
AUTORES / AUTHORS: - Liu SZ; Zhang F; Chang YX; Ma J; Li X; Li XH; Fan JH; Duan GC; Sun XB
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology, College of Public Health of Zhengzhou University, Zhengzhou, China E-mail : gcduan@zzu.edu.cn, xbsun21@sina.com.
RESUMEN / SUMMARY: - Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP- NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP- NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (>/= 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (>/= 10% positive nuclei) in 33 (49%) . High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.
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[990]
TÍTULO / TITLE: - Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet Comp Oncol. 2013 Feb 15. doi: 10.1111/vco.12018.
●● Enlace al texto completo (gratuito o de pago) 1111/vco.12018
AUTORES / AUTHORS: - Cannon CM; Pozniak J; Scott MC; Ito D; Gorden BH; Graef AJ; Modiano JF
INSTITUCIÓN / INSTITUTION: - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
RESUMEN / SUMMARY: - We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted.
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[991]
TÍTULO / TITLE: - Pan-BCL-2 Inhibition Sensitizes Leukemic Stem Cells to Kinase Inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar;3(3):249. doi: 10.1158/2159-8290.CD-RW2013-020. Epub 2013 Jan 24.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2013-020
RESUMEN / SUMMARY: - The pan BCL-2 inhibitor sabutoclax sensitizes dormant CML stem cells to dasatinib treatment.
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[992]
TÍTULO / TITLE: - Enhanced Cytotoxic Effects of Combined Valproic Acid and the Aurora Kinase Inhibitor VE465 on Gynecologic Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Oncol. 2013;3:58. doi: 10.3389/fonc.2013.00058. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 3389/fonc.2013.00058
AUTORES / AUTHORS: - Li Y; Liu T; Ivan C; Huang J; Shen DY; Kavanagh JJ; Bast RC Jr; Fu S; Hu W; Sood AK
INSTITUCIÓN / INSTITUTION: - Departments of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center Houston, TX, USA.
RESUMEN / SUMMARY: - Increasing evidence shows that targeting epigenetic changes including acetylation and deacetylation of core nucleosomal histones as well as Aurora kinases hold promise for improving the treatment of human cancers including ovarian cancer. We investigated whether the histone deacetylase (HDAC) inhibitor, valproic acid (VPA), and the Aurora kinase inhibitor VE465 can have additive or synergistic effects on gynecologic cancer cells. We tested the in vitro antitumor activity of VPA and VE465, alone and in combination, in gynecologic cancer cells and assessed potential mechanisms of action. 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) analysis revealed that 72 h of treatment with VPA or VE465 alone induced dose-dependent cytotoxic effects in nine gynecologic cancer cell lines (ovarian: 2008/C13, OVCAR3, SKOV3, and A2780; cervical: ME180 and CaSki; endometrial: HEC-1B; and uterine sarcoma: MES-SA and MES-SA/Dx5). Co-treatment with VPA and VE465 enhanced cytotoxic effects on five of these cell lines: ovarian: 2008/C13, A2780, and OVCAR3; endometrial: HEC-1B; and cervical: ME180. In ovarian 2008/C13 cells, co-treatment with VPA (2 mM) and VE465 (1 muM) induced more apoptosis than either VPA or VE465 alone. Western blot analysis showed that VPA alone increased the expression of cleaved PARP and p21 in a dose-dependent manner in 2008/C13 cells, while co-treatment with VPA and VE465 induced more cleaved PARP than treatment with VPA or VE465 alone did. The combined use of VPA and VE465 enhanced cytotoxic effects in some ovarian cancer cells, via enhanced induction of apoptosis. Targeting epigenetics with the HDAC inhibitor, in combination with Aurora kinase inhibitors, holds promise for more effective therapy of ovarian cancer.
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[993]
TÍTULO / TITLE: - Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57799. doi: 10.1371/journal.pone.0057799. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057799
AUTORES / AUTHORS: - Schwede M; Spentzos D; Bentink S; Hofmann O; Haibe-Kains B; Harrington D; Quackenbush J; Culhane AC
INSTITUCIÓN / INSTITUTION: - Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
RESUMEN / SUMMARY: - Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ovarian cancer.
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[994]
TÍTULO / TITLE: - Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:243859. doi: 10.1155/2013/243859. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/243859
AUTORES / AUTHORS: - Kang XH; Xu ZY; Gong YB; Wang LF; Wang ZQ; Xu L; Cao F; Liao MJ
INSTITUCIÓN / INSTITUTION: - Department of Clinical Oncology, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Department of Clinical Oncology, Ping Ding Shan First People’s Hospital, Henan 467000, China.
RESUMEN / SUMMARY: - The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, have shown promising therapeutic efficacy in nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor- (EGFR-) activating mutation. However, the inevitable recurrence resulting from acquired resistance has limited the clinical improvement in therapy outcomes. Many studies demonstrate that hepatocyte growth factor- (HGF-) Met axis plays an important role in tumor progression and drug sensitivity. HGF may induce resistance to EGFR-TKIs in EGFR mutant lung cancer cells by Met/PI3K/Akt signaling. The purpose of this study was to determine whether bufalin, a major bioactive component of Venenum Bufonis, could reverse HGF-induced resistance to reversible and irreversible EGFR-TKIs in mutant lung cancer cells PC-9, HCC827, and H1975. Our studies showed that bufalin could reverse resistance to reversible and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. These results suggested that bufalin might have a potential to overcome HGF-induced resistance to molecular-targeted drugs for lung cancer.
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[995]
TÍTULO / TITLE: - SMC1A knockdown induces growth suppression of human lung adenocarcinoma cells through G1/S cell cycle phase arrest and apoptosis pathways in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):749-755. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1116
AUTORES / AUTHORS: - Zhang YF; Jiang R; Li JD; Zhang XY; Zhao P; He M; Zhang HZ; Sun LP; Shi DL; Zhang GX; Sun M
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun 130041;
RESUMEN / SUMMARY: - SMC1A (structural maintenance of chromosomes 1A), which encodes a structural subunit of the cohesin protein complex, is necessary for the process of sister chromatid cohesion during the cell cycle. Mutation and deregulation of SMC1A are highly relevant to diverse human diseases, including Cornelia de Lange syndrome and malignant carcinomas. In order to further investigate the role of SMC1A in the oncogenesis of lung cancer, SMC1A-specific short hairpin RNA (shRNA)-expressing lentivirus (Lv-shSMC1A) was constructed and used to infect A549 and H1299 cells. SMC1A mRNA and protein expression levels were downregulated in A549 and H1299 cells as demonstrated by real-time PCR and western blot assays. We found that SMC1A inhibition resulted in significantly impaired proliferation and colony formation as well as reduced invasiveness of tumor cells. Notably, Lv-shSMC1A-infected cancer cells exhibited a greater proportion of cells in the G0/G1 phase, but a lower proportion of S phase cells, compared to the parent or Lv-shCon infected cancer cells. Moreover, a greater proportion of sub-G1 apoptotic cells was observed in Lv-shSMC1A-infected cells. These results suggest that SMC1A is a novel proliferation regulator that promotes the growth of lung cancer cells, and that down-regulation of SMC1A expression induces growth suppression of A549 and H1299 cells via G1/S cell cycle phase arrest and apoptosis pathways. Therefore, SMC1A may serve as a new molecular target for lung cancer therapy.
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[996]
TÍTULO / TITLE: - Bombesin analogue-mediated delivery preferentially enhances the cytotoxicity of a mitochondria-disrupting Peptide in tumor cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57358. doi: 10.1371/journal.pone.0057358. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057358
AUTORES / AUTHORS: - Yang H; Cai H; Wan L; Liu S; Li S; Cheng J; Lu X
INSTITUCIÓN / INSTITUTION: - Key Lab of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China.
RESUMEN / SUMMARY: - Tumor-homing peptides that recognize specific markers on tumor cells have shown potential as drug carriers for targeted cancer therapy. Bombesin receptors are frequently overexpressed or ectopically expressed in a wide range of human tumors. Bombesin and its analogues have been widely used as drug carriers for tumor imaging and tumor therapy. However, the cargos used in previous studies, including radioactive and chemotherapeutic agents, are usually small molecules. Mitochondrial-disrupting peptides depolarize the mitochondria and trigger apoptosis after entering tumor cells. We are interested in whether the bombesin analogue, Bn(6-14), which contains a bombesin receptor-binding motif, can specifically deliver the mitochondria-disrupting peptide, B28, to tumor cells. To this end, we created a chimeric peptide, B28Bn(6-14), by conjugating B28 to Bn(6-14) at its N-terminus. The cytotoxicity of B28Bn(6-14) in tumor cells was much stronger than unconjugated B28. The IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 microM) were approximately 10 times lower than B28. However, conjugation of B28 to Bn(2-7), which lacks the bombesin receptor-binding motif, did not increase its cytotoxicity. In addition, the IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 microM) was 3-10 times lower than in normal cells (10.8-16.8 microM). We found that selective binding of B28Bn(6-14) to tumor cells is Bn(6-14)-dependent. Upon entering the tumor cell, B28Bn(6-14) accumulated in the mitochondria and triggered caspase-dependent apoptosis. Intratumoral and intraperitoneal administration of B28Bn(6-14) substantially suppressed the growth of DU145 tumor xenografts in mice. These results demonstrate that Bn(6-14) is able to deliver the mitochondria-disrupting peptide to tumor cells, and B28Bn(6-14) should be further developed as novel anti-cancer agent.
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[997]
TÍTULO / TITLE: - Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 14;4:e494. doi: 10.1038/cddis.2013.31.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.31
AUTORES / AUTHORS: - Liu Y; Cheng H; Zhou Y; Zhu Y; Bian R; Chen Y; Li C; Ma Q; Zheng Q; Zhang Y; Jin H; Wang X; Chen Q; Zhu D
INSTITUCIÓN / INSTITUTION: - The State Key Laboratory of Biomembrane and Membrane Biotechnology, Chinese Academy of Sciences, Beijing, China.
RESUMEN / SUMMARY: - Myostatin, a member of the transforming growth factor-beta superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells.
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[998]
TÍTULO / TITLE: - CDK4 inhibition restores G(1)-S arrest in MYCN-amplified neuroblastoma cells in the context of doxorubicin-induced DNA damage.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Mar 5;12(7).
AUTORES / AUTHORS: - Gogolin S; Ehemann V; Becker G; Brueckner LM; Dreidax D; Bannert S; Nolte I; Savelyeva L; Bell E; Westermann F
INSTITUCIÓN / INSTITUTION: - Division of Tumor Genetics; German Cancer Research Center (DKFZ); Heidelberg, Germany.
RESUMEN / SUMMARY: - Relapse with drug-resistant disease is the main cause of death in MYCN-amplified neuroblastoma patients. MYCN-amplified neuroblastoma cells in vitro are characterized by a failure to arrest at the G(1)-S checkpoint after irradiation- or drug-induced DNA damage. We show that several MYCN-amplified cell lines harbor additional chromosomal aberrations targeting p53 and/or pRB pathway components, including CDK4/CCND1/MDM2 amplifications, p16INK4A/p14ARF deletions or TP53 mutations. Cells with these additional aberrations undergo significantly lower levels of cell death after doxorubicin treatment compared with MYCN-amplified cells, with no additional mutations in these pathways. In MYCN-amplified cells CDK4 expression is elevated, increasing the competition between CDK4 and CDK2 for binding p21. This results in insufficient p21 to inhibit CDK2, leading to high CDK4 and CDK2 kinase activity upon doxorubicin treatment. CDK4 inhibition by siRNAs, selective small compounds or p19 (INK4D) overexpression partly restored G(1)-S arrest, delayed S-phase progression and reduced cell viability upon doxorubicin treatment. Our results suggest a specific function of p19 (INK4D) , but not p16 (INK4A) , in sensitizing MYCN-amplified cells with a functional p53 pathway to doxorubicin-induced cell death. In summary, the CDK4/cyclin D-pRB axis is altered in MYCN-amplified cells to evade a G(1)-S arrest after doxorubicin-induced DNA damage. Additional chromosomal aberrations affecting the p53-p21 and CDK4-pRB axes compound the effects of MYCN on the G(1) checkpoint and reduce sensitivity to cell death after doxorubicin treatment. CDK4 inhibition partly restores G(1)-S arrest and sensitizes cells to doxorubicin-mediated cell death in MYCN-amplified cells with an intact p53 pathway.
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[999]
TÍTULO / TITLE: - Resveratrol Induces Premature Senescence in Lung Cancer Cells via ROS-Mediated DNA Damage.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e60065. doi: 10.1371/journal.pone.0060065. Epub 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0060065
AUTORES / AUTHORS: - Luo H; Yang A; Schulte BA; Wargovich MJ; Wang GY
INSTITUCIÓN / INSTITUTION: - Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
RESUMEN / SUMMARY: - Resveratrol (RV) is a natural component of red wine and grapes that has been shown to be a potential chemopreventive and anticancer agent. However, the molecular mechanisms underlying RV’s anticancer and chemopreventive effects are incompletely understood. Here we show that RV treatment inhibits the clonogenic growth of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Interestingly, the tumor-suppressive effect of low dose RV was not associated with any significant changes in the expression of cleaved PARP and activated caspase-3, suggesting that low dose RV treatment may suppress tumor cell growth via an apoptosis-independent mechanism. Subsequent studies reveal that low dose RV treatment induces a significant increase in senescence-associated beta-galactosidase (SA-beta-gal) staining and elevated expression of p53 and p21 in NSCLC cells. Furthermore, we show that RV-induced suppression of lung cancer cell growth is associated with a decrease in the expression of EF1A. These results suggest that RV may exert its anticancer and chemopreventive effects through the induction of premature senescence. Mechanistically, RV-induced premature senescence correlates with increased DNA double strand breaks (DSBs) and reactive oxygen species (ROS) production in lung cancer cells. Inhibition of ROS production by N-acetylcysteine (NAC) attenuates RV-induced DNA DSBs and premature senescence. Furthermore, we show that RV treatment markedly induces NAPDH oxidase-5 (Nox5) expression in both A549 and H460 cells, suggesting that RV may increase ROS generation in lung cancer cells through upregulating Nox5 expression. Together, these findings demonstrate that low dose RV treatment inhibits lung cancer cell growth via a previously unappreciated mechanism, namely the induction of premature senescence through ROS-mediated DNA damage.
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[1000]
TÍTULO / TITLE: - The C-Terminal Region Mesd Peptide Mimics Full-Length Mesd and Acts as an Inhibitor of Wnt/beta-Catenin Signaling in Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e58102. doi: 10.1371/journal.pone.0058102. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058102
AUTORES / AUTHORS: - Lin C; Lu W; Zhang W; Londono-Joshi AI; Buchsbaum DJ; Bu G; Li Y
INSTITUCIÓN / INSTITUTION: - Drug Discovery Division, Southern Research Institute, Birmingham, Alabama, United States of America ; Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China.
RESUMEN / SUMMARY: - While Mesd was discovered as a specialized molecular endoplasmic reticulum chaperone for the Wnt co-receptors LRP5 and LRP6, recombinant Mesd protein is able to bind to mature LRP5 and LRP6 on the cell surface and acts as a universal antagonist of LRP5/6 modulators. In our previous study, we found that the C-terminal region of Mesd, which is absent in sequences from invertebrates, is necessary and sufficient for binding to mature LRP6 on the cell surface. In the present studies, we further characterized the interaction between the C-terminal region Mesd peptide and LRP5/6. We found that Mesd C-terminal region-derived peptides block Mesd binding to LRP5 at the cell surface too. We also showed that there are two LRP5/6 binding sites within Mesd C-terminal region which contain several positively charged residues. Moreover, we demonstrated that the Mesd C-terminal region peptide, like the full-length Mesd protein, blocked Wnt 3A- and Rspodin1-induced Wnt/beta-catenin signaling in LRP5- and LRP6- expressing cells, suppressed Wnt/beta-catenin signaling in human breast HS578T cells and prostate cancer PC-3 cells, and inhibited cancer cell proliferation, although the full-length Mesd protein is more potent than its peptide. Finally, we found that treatment of the full-length Mesd protein and its C-terminal region peptide significantly increased chemotherapy agent Adriamycin-induced cytotoxicity in HS578T and PC-3 cells. Together, our results suggest that Mesd C-terminal region constitutes the major LRP5/6-binding domain, and that Mesd protein and its C-terminal region peptide have a potential therapeutic value in cancer.
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[1001]
TÍTULO / TITLE: - Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 21;4:e552. doi: 10.1038/cddis.2013.68.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.68
AUTORES / AUTHORS: - Zhu P; Tong BM; Wang R; Chen JP; Foo S; Chong HC; Wang XL; Ang GY; Chiba S; Tan NS
INSTITUCIÓN / INSTITUTION: - School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
RESUMEN / SUMMARY: - Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2(-):H2O2 ratio and increased .OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable.
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[1002]
TÍTULO / TITLE: - Aiming for the Outliers: Cancer Precision Medicine through Targeting Kinases with Extreme Expression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar;3(3):252-4. doi: 10.1158/2159-8290.CD-13-0016.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-13-0016
AUTORES / AUTHORS: - Yegnasubramanian S; Maitra A
INSTITUCIÓN / INSTITUTION: - 1Sidney Kimmel Comprehensive Cancer Center and 2Department of Pathology, The Sol Golman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, Maryland.
RESUMEN / SUMMARY: - With the increasing availability of highly potent, pharmacologically active, and selective protein kinase inhibitors, identification of individuals who would benefit from targeted kinase inhibitors could facilitate application of precision medicine strategies for cancer therapy. A recent study by Kothari and colleagues reports preclinical studies that highlight the potential of targeting kinases with extreme expression for cancer precision medicine, warranting further clinical investigation of an individual-specific outlier kinase targeting approach. Cancer Discov; 3(3); 252-4. ©2013 AACR.
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[1003]
TÍTULO / TITLE: - Clusterin Protects Hepatocellular Carcinoma Cells from Endoplasmic Reticulum Stress Induced Apoptosis through GRP78.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55981. doi: 10.1371/journal.pone.0055981. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055981
AUTORES / AUTHORS: - Wang C; Jiang K; Gao D; Kang X; Sun C; Zhang Q; Li Y; Sun L; Zhang S; Guo K; Liu Y
INSTITUCIÓN / INSTITUTION: - Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China ; Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - Clusterin (CLU) is a stress-activated chaperone, which plays an important role in cancer development and progression through promoting cell survival. However, the exact mechanism of how CLU exerts its cell protective role under ER stress condition is still unclear. Therefore, in order to explore the molecular mechanisms by which CLU inhibited ER stress-induced apoptosis, HCC cell lines were treated with tunicamycin (TN), an ER stress inducer. We found that the expressions of both CLU and GRP78 were increased after TN treatment. Knockdown of CLU expression in SMMC7721 and HCCLM3 cells inhibited GRP78 expression after TN treatment and enhanced ER stress-induced apoptosis, whereas over-expression of CLU in HepG2 cells increased GRP78 expression after TN induction and abolished the effect of TN on cell apoptosis. Furthermore, knockdown of GRP78 expression in CLU-HepG2 cells abrogated the protective role of CLU under ER stress condition. Co-immunoprecipitation (co-IP) and confocal microscopy experiments confirmed the direct interaction between CLU and GRP78 under ER stress condition. The effect of CLU knockdown on GRP78 expression and cell apoptosis in HCC tumors were further determined in orthotopic xenograft tumor model. Knockdown of CLU expression in HCCLM3 cells inhibited GRP78 expression in tumor tissues, accompanied with increased number of apoptotic cancer cells. Moreover, the correlation between CLU and GRP78 expression was further determined in clinical HCC specimens. Taken together, these findings reveal that CLU protects HCC cells from ER stress induced apoptosis at least partially through interacting with GRP78.
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[1004]
TÍTULO / TITLE: - Liberation of functional p53 by proteasome inhibition in human papilloma virus-positive head and neck squamous cell carcinoma cells promotes apoptosis and cell cycle arrest.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Mar 15;12(6):923-34. doi: 10.4161/cc.23882. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 4161/cc.23882
AUTORES / AUTHORS: - Li C; Johnson DE
INSTITUCIÓN / INSTITUTION: - Department of Medicine; University of Pittsburgh and the University of Pittsburgh Cancer Institute; Pittsburgh, PA USA.
RESUMEN / SUMMARY: - Human papilloma virus (HPV) infection represents an emerging risk factor in head and neck squamous cell carcinoma (HNSCC). In contrast to HPV-negative HNSCC, most cases of HPV-positive HNSCC encode wild-type p53, although the p53 protein in these cells is rapidly degraded via HPV E6-mediated ubiquitination and subsequent proteasomal degradation. This unique feature of HPV-positive HNSCC has raised hope that liberation of wild-type p53 from the E6 protein may have therapeutic benefit in this disease. Indeed, suppression of E6 expression promotes apoptosis in HPV-positive HNSCC cell lines. However, the role of p53 in mediating this cell death has not been determined. Here, we demonstrate that siRNAs targeting the E6/E7 RNA, or treatment with the proteasome inhibitor bortezomib, resulted in upregulation of functional p53 and p53 gene targets in three HPV-positive HNSCC cell lines, but not in HPV-negative HNSCC cells. Apoptosis induced by E6/E7 siRNA in HPV-positive cells was found to be dependent on p53, while bortezomib-induced cell death was modestly p53-dependent. Treatment with subtoxic doses of bortezomib led to cell cycle arrest in HPV-positive, but not HPV-negative HNSCC cells. Moreover, this cell cycle arrest was mediated by p53 and the cell cycle inhibitor p21, the product of a p53 target gene. Collectively, these findings establish that wild-type p53 encoded by HPV-positive HNSCC cells, once liberated from HPV E6, can play important roles in promoting apoptosis and cell cycle arrest.
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[1005]
TÍTULO / TITLE: - The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - DNA Repair (Amst). 2013 Apr 1;12(4):293-9. doi: 10.1016/j.dnarep.2013.01.008. Epub 2013 Feb 16.
●● Enlace al texto completo (gratuito o de pago) 1016/j.dnarep.2013.01.008
AUTORES / AUTHORS: - Caputo M; Frontini M; Velez-Cruz R; Nicolai S; Prantera G; Proietti-De-Santis L
INSTITUCIÓN / INSTITUTION: - Unit of Molecular Genetics of Aging, Department of Ecology and Biology, University of Tuscia, 01100 Viterbo, Italy.
RESUMEN / SUMMARY: - In the present study we show that a number of cancer cell lines from different tissues display dramatically increased expression of the Cockayne Syndrome group B (CSB) protein, a DNA repair factor, that has recently been shown to be involved in cell robustness. Furthermore, we demonstrated that ablation of this protein by antisense technology causes devastating effects on tumor cells through a drastic reduction of cell proliferation and massive induction of apoptosis, while non-transformed cells remain unaffected. Finally, suppression of CSB in cancer cells makes these cells hypersensitive to a variety of commonly used cancer chemotherapeutic agents. Based on these results, we conclude that cancer cells overexpress CSB protein in order to enhance their anti-apoptotic capacity. The fact that CSB suppression specifically affects only cancerous cells, without harming healthy cells, suggests that CSB may be a very attractive target for the development of new anticancer therapies.
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[1006]
TÍTULO / TITLE: - Baicalein induces apoptosis in esophageal squamous cell carcinoma cells through modulation of the PI3K/Akt pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):722-728. Epub 2012 Dec 10.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1069
AUTORES / AUTHORS: - Zhang HB; Lu P; Guo QY; Zhang ZH; Meng XY
INSTITUCIÓN / INSTITUTION: - Department of Anatomy and Cell Biology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001;
RESUMEN / SUMMARY: - Baicalein, a flavone present in Scutellaria baicalensis Georgi, has been demonstrated to possess antitumor activity in a variety of cancer cells in vitro. However, its effects on the growth inhibition and induction of apoptosis in human esophageal carcinoma cells remain unclear. The aims of this study were to determine whether cultured EC-109 esophageal squamous cell carcinoma (ESCC) cells undergo apoptosis when treated with baicalein and to investigate the underlying mechanisms in vitro. Cell growth was measured using MTT and plate colony formation assays. Induction of apoptosis was examined using Hoechst 33258 staining, flow cytometry analysis and a DNA fragmentation assay. The mechanisms underlying the observed growth suppression were examined using western blot analysis. The results demonstrated that treatment of EC-109 cells with baicalein for 48 h markedly decreased the rate of cell viability. Colony formation was almost fully suppressed at 40 muM baicalein. EC-109 cells underwent apoptosis in response to baicalein treatment, demonstrated by an increase in the percentage of cells stainable with Hoechst 33258 and Annexin V-FITC/PI, increased DNA fragmentation and activation of the intrinsic (mitochondrial) pathway for cell death. The latter was characterized by increased expression of the cleaved forms of caspase-9 and -3, and poly (ADP-ribose) polymerase (PARP). Additionally, baicalein was found to downregulate anti-apoptotic components and upregulate apoptotic components of the PI3K/Akt pathway. In conclusion, baicalein induces apoptosis in EC-109 cells through modulation of the PI3K/Akt pathway, thus providing further understanding of the molecular mechanisms of baicalein action in esophageal carcinoma. Therefore, the present study revealed that baicalein significantly inhibits growth and induces apoptosis in EC-109 human ESCC cells in vitro.
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[1007]
TÍTULO / TITLE: - Brazilin inhibits growth and induces apoptosis in human glioblastoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Molecules. 2013 Feb 21;18(2):2449-57. doi: 10.3390/molecules18022449.
●● Enlace al texto completo (gratuito o de pago) 3390/molecules18022449
AUTORES / AUTHORS: - Lee DY; Lee MK; Kim GS; Noh HJ; Lee MH
INSTITUCIÓN / INSTITUTION: - Herbal Crop Utilization Research Team, National Institute of Horticultural and Herbal Science, RDA, Eumseong 369-873, Korea.
RESUMEN / SUMMARY: - Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7.
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[1008]
TÍTULO / TITLE: - Antiproliferative and apoptotic effects of beta-elemene on human hepatoma HepG2 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Mar 14;13(1):27. doi: 10.1186/1475-2867-13-27.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-27
AUTORES / AUTHORS: - Dai ZJ; Tang W; Lu WF; Gao J; Kang HF; Ma XB; Min WL; Wang XJ; Wu WY
INSTITUCIÓN / INSTITUTION: - Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China. dzj0911@126.com.
RESUMEN / SUMMARY: - BACKGROUND: beta-elemene, a natural sesquiterpene extracted from the essential oils of Curcuma aromatica Salisb, has been shown to be effective against a wide range of tumors. In this study, the antitumor effect of beta-elemene on a human hepatoma cell line, HepG2, and the mechanism involved have been investigated. METHODS: MTT assay was used to determine the growth inhibition of hepatoma HepG2 cells in vitro. Apoptosis of HepG2 cells were demonstrated by fluorescence microscope with Hoechst 33258 staining and flow cytometry with Annexin V-FITC/PI double staining. Flow cytometry was performed to analyze the cell cycle distribution of HepG2 cells. The mRNA and protein expression of Fas and FasL were measured by RT-PCR and Western blot analysis. RESULTS: MTT results showed that beta-elemene could inhibit the proliferation of HepG2 cells in a time- and dose- dependent manner. Our results showed beta-elemene had positive effect on apoptosis through fluorescence microscope and flow cytometry assay. Furthermore, beta-elemene could induce the cell cycle arrest of the HepG2 cells in the G2/M phase. Fas and FasL expression were obviously increased after beta-elemene treatment in both mRNA and protein level. CONCLUSION: The present study indicates that beta-elemene can effectively inhibit proliferation and induce apoptosis in hepatoma HepG2 cells, and the apoptosis induction is related with up-regulating of Fas/FasL expression.
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[1009]
TÍTULO / TITLE: - Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 21;4:e507. doi: 10.1038/cddis.2013.29.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.29
AUTORES / AUTHORS: - Marques C; Oliveira CS; Alves S; Chaves SR; Coutinho OP; Corte-Real M; Preto A
INSTITUCIÓN / INSTITUTION: - CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus de Gualtar, Braga, Portugal.
RESUMEN / SUMMARY: - Colorectal carcinoma (CRC) is one of the most common causes of cancer-related mortality. Short-chain fatty acids secreted by dietary propionibacteria from the intestine, such as acetate, induce apoptosis in CRC cells and may therefore be relevant in CRC prevention and therapy. We previously reported that acetic acid-induced apoptosis in Saccharomyces cerevisiae cells involves partial vacuole permeabilization and release of Pep4p, the yeast cathepsin D (CatD), which has a protective role in this process. In cancer cells, lysosomes have emerged as key players in apoptosis through selective lysosomal membrane permeabilization (LMP) and release of cathepsins. However, the role of CatD in CRC survival is controversial and has not been assessed in response to acetate. We aimed to ascertain whether LMP and CatD are involved in acetate-induced apoptosis in CRC cells. We showed that acetate per se inhibits proliferation and induces apoptosis. More importantly, we uncovered that acetate triggers LMP and CatD release to the cytosol. Pepstatin A (a CatD inhibitor) but not E64d (a cathepsin B and L inhibitor) increased acetate-induced apoptosis of CRC cells, suggesting that CatD has a protective role in this process. Our data indicate that acetate induces LMP and subsequent release of CatD in CRC cells undergoing apoptosis, and suggest exploiting novel strategies using acetate as a prevention/therapeutic agent in CRC, through simultaneous treatment with CatD inhibitors.
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[1010]
TÍTULO / TITLE: - Subamolide a induces mitotic catastrophe accompanied by apoptosis in human lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:828143. doi: 10.1155/2013/828143. Epub 2013 Feb 24.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/828143
AUTORES / AUTHORS: - Hung JY; Wen CW; Hsu YL; Lin ES; Huang MS; Chen CY; Kuo PL
INSTITUCIÓN / INSTITUTION: - Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan ; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan.
RESUMEN / SUMMARY: - This study investigated the anticancer effects of subamolide A (Sub-A), isolated from Cinnamomum subavenium, on human nonsmall cell lung cancer cell lines A549 and NCI-H460. Treatment of cancer cells with Sub-A resulted in decreased cell viability of both lung cancer cell lines. Sub-A induced lung cancer cell death by triggering mitotic catastrophe with apoptosis. It triggered oxidant stress, indicated by increased cellular reactive oxygen species (ROS) production and decreased glutathione level. The elevated ROS triggered the activation of ataxia-telangiectasia mutation (ATM), which further enhanced the ATF3 upregulation and subsequently enhanced p53 function by phosphorylation at Serine 15 and Serine 392. The antioxidant, EUK8, significantly decreased mitotic catastrophe by inhibiting ATM activation, ATF3 expression, and p53 phosphorylation. The reduction of ATM and ATF3 expression by shRNA decreased Sub-A-mediated p53 phosphorylation and mitotic catastrophe. Sub-A also caused a dramatic 70% reduction in tumor size in an animal model. Taken together, cell death of lung cancer cells in response to Sub-A is dependent on ROS generation, which triggers mitotic catastrophe followed by apoptosis. Therefore, Sub-A may be a novel anticancer agent for the treatment of nonsmall cell lung cancer.
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[1011]
TÍTULO / TITLE: - Embelin Induces Apoptosis in Human Glioma Cells Through Inactivating NF-kappaB.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pharmacol Sci. 2013;121(3):192-9.
AUTORES / AUTHORS: - Park SY; Lim SL; Jang HJ; Lee JH; Um JY; Kim SH; Ahn KS; Lee SG
INSTITUCIÓN / INSTITUTION: - Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Korea.
RESUMEN / SUMMARY: - Aggressive tumor growth and diffuse tissue invasion are hallmarks of malignant glioma. Embelin is an active compound identified as a novel XIAP inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anti-cancer activities. In the present study, we investigated whether embelin could have a therapeutic effect in glioma. We found that embelin suppressed proliferation of human glioma cells, but not in normal immortalized human astrocytes. In addition, embelin induced apoptosis in human glioma cells by inhibiting NF-kappaB, which is a crucial transcription factor associated with several human diseases including cancer and controls multiple genes involved in tumor progression such as cell proliferation and survival. Intriguingly, embelin had no inhibitory effect on XIAP in glioma cells even though discovered as an XIAP inhibitor, but instead inhibited NF-kappaB activity by reducing nuclear translocation of p65 through decreasing phosphorylation and proteasomal degradation of IkappaBalpha in glioma cells. Furthermore, p65 overexpression decreased embelin-induced apoptosis in glioma cells. Taken together these results indicate that embelin could be a potent novel therapeutic modality for glioma via blocking cancer cell proliferation and inducing apoptosis by inhibiting NF-kappaB activity.
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[1012]
TÍTULO / TITLE: - Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54577. doi: 10.1371/journal.pone.0054577. Epub 2013 Jan 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054577
AUTORES / AUTHORS: - Zhang ZR; Al Zaharna M; Wong MM; Chiu SK; Cheung HY
INSTITUCIÓN / INSTITUTION: - Research Group for Bioactive Products, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China.
RESUMEN / SUMMARY: - Andrographolide (Andro) suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi) has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose) polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC), alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.
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[1013]
TÍTULO / TITLE: - Induction of apoptosis by luteolin involving akt inactivation in human 786-o renal cell carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:109105. doi: 10.1155/2013/109105. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/109105
AUTORES / AUTHORS: - Ou YC; Kuan YH; Li JR; Raung SL; Wang CC; Hung YY; Chen CJ
INSTITUCIÓN / INSTITUTION: - Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan.
RESUMEN / SUMMARY: - There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elucidated. This study provides evidence of an alternative target for luteolin and sheds light on the mechanism of its physiological benefits. Treatment of 786-O renal cell carcinoma (RCC) cells (as well as A498 and ACHN) with luteolin caused cell apoptosis and death. This cytotoxicity was caused by the downregulation of Akt and resultant upregulation of apoptosis signal-regulating kinase-1 (Ask1), p38, and c-Jun N-terminal kinase (JNK) activities, probably via protein phosphatase 2A (PP2A) activation. In addition to being a concurrent substrate of caspases and event of cell death, heat shock protein-90 (HSP90) cleavage might also play a role in driving further cellular alterations and cell death, at least in part, involving an Akt-related mechanism. Due to the high expression of HSP90 and Akt-related molecules in RCC and other cancer cells, our findings suggest that PP2A activation might work in concert with HSP90 cleavage to inactivate Akt and lead to a vicious caspase-dependent apoptotic cycle in luteolin-treated 786-O cells.
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[1014]
TÍTULO / TITLE: - Cinnamaldehyde-induced Apoptosis in Human Hepatoma PLC/PRF/5 Cells Involves the Mitochondrial Death Pathway and is Sensitive to Inhibition by Cyclosporin A and z-VAD-fmk.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Agents Med Chem. 2013 Feb 7.
AUTORES / AUTHORS: - Lin LT; Tai CJ; Chang SP; Chen JL; Wu SJ; Lin CC
INSTITUCIÓN / INSTITUTION: - Department of Nutritional Health, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan, China. aalin@kmu.edu.tw; wsj268@mail.chna.edu.tw.
RESUMEN / SUMMARY: - Cinnamaldehyde (CIN) has been shown to exert chemopreventive activity against several types of human cancer cells. We previously reported that CIN induced apoptosis of human hepatoma PLC/PRF/5 cells and this effect was associated with activation of the pro-apoptotic Bcl-2 family of proteins and the MAPK cascade. To further clarify the underlying mechanism of CIN-induced apoptosis, we examined in this study its relationship with the mitochondrial death pathway using the mitochondrial permeability transition (MPT) inhibitor, cyclosporin A (CsA), and the general caspase inhibitor, z-VAD-fmk. Results indicated that CIN-induced apoptosis involved enhanced ROS generation, disruption of mitochondrial potential, and the mitochondrial release of cytochrome c and Smac/DIABLO into the cytosol, which in turn promoted caspase-3 to its active form and the subsequent cleavage of PARP. Treatment with CIN also down-regulated protein levels of the anti-apoptotic factors XIAP and Bcl-2 with concomitant accumulation of the pro-apoptotic Bax in a time-dependent manner. These mitochondria-related apoptotic effects induced by CIN were however blocked by CsA and z-VAD-fmk pretreatments, which prevented cells from undergoing programmed cell death triggered by CIN. Furthermore, the increase of Bax and decrease of Bcl-2 and XIAP protein expression due to CIN treatment were also reversely modulated by the two inhibitors. Taken together, these results suggested that CIN is an apoptotic inducer that acts on the mitochondrial death pathway in PLC/PRF/5 cells and its effect could be blocked by CsA and z-VAD-fmk.
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[1015]
TÍTULO / TITLE: - MADD Knock-Down Enhances Doxorubicin and TRAIL Induced Apoptosis in Breast Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56817. doi: 10.1371/journal.pone.0056817. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056817
AUTORES / AUTHORS: - Turner A; Li LC; Pilli T; Qian L; Wiley EL; Setty S; Christov K; Ganesh L; Maker AV; Li P; Kanteti P; Das Gupta TK; Prabhakar BS
INSTITUCIÓN / INSTITUTION: - Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
RESUMEN / SUMMARY: - The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.
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[1016]
TÍTULO / TITLE: - Euphorbia formosana root extract induces apoptosis by caspase-dependent cell death via Fas and mitochondrial pathway in THP-1 human leukemic cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Molecules. 2013 Feb 1;18(2):1949-62. doi: 10.3390/molecules18021949.
●● Enlace al texto completo (gratuito o de pago) 3390/molecules18021949
AUTORES / AUTHORS: - Hsieh YJ; Chang CJ; Wan CF; Chen CP; Chiu YH; Leu YL; Peng KC
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Medicine and Biotechnology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
RESUMEN / SUMMARY: - Acute myeloid leukemia (AML), a very rare type of cancer, generally affects patients over 50 years old. While clinical drugs to treat advanced stages of AML exist, the disease becomes increasingly resistant to therapies. Euphorbia formosana Hayata (EF) is a native Taiwanese medicinal plant used to treat rheumatism, liver cirrhosis, herpes zoster, scabies, and photoaging, along with tumor suppression. However, the mechanisms by which it suppresses tumors have not been explored. Here, we provide molecular evidence that a hot-water extract of Euphorbia formosana (EFW) selectively inhibited the growth of human leukemic cancer cells more than other solid human cancer cell lines. Most importantly, the plant extract had limited toxicity toward healthy peripheral blood mononuclear cells (PBMCs). After THP-1 leukemic cells were treated with 50-100 microg/mL EFW for one day, the S phase DNA content of the cells increased, while treatment with 200-400 microg/mL caused the cells to accumulate in the G0/G1 phase. Notably, EFW did not affect A-549 lung cancer cells. The effectiveness of EFW against THP-1 cells may be through caspase-dependent apoptosis in leukemic cells, which is mediated through the Fas and mitochondrial pathways. The potent antileukemic activity of EFW in vitro warrants further investigation of this plant to treat leukemias and other malignancies.
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[1017]
TÍTULO / TITLE: - Silver-based nanoparticles induce apoptosis in human colon cancer cells mediated through p53.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nanomedicine (Lond). 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 2217/nnm.12.176
AUTORES / AUTHORS: - Satapathy SR; Mohapatra P; Preet R; Das D; Sarkar B; Choudhuri T; Wyatt MD; Kundu CN
INSTITUCIÓN / INSTITUTION: - Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa, 751024, India.
RESUMEN / SUMMARY: - Aim: The authors have systematically investigated the anticancer potentiality of silver-based nanoparticles (AgNPs) and the mechanism underlying their biological activity in human colon cancer cells. Materials & methods: Starch-capped AgNPs were synthesized, characterized and their biological activity evaluated through multiple biochemical assays. Results: AgNPs decreased the growth and viability of HCT116 colon cancer cells. AgNP exposure increased apoptosis, as demonstrated by an increase in 4 ,6-diamidino-2-phenylindole-stained apoptotic nuclei, BAX/BCL-XL ratio, cleaved poly(ADP-ribose) polymerase, p53, p21 and caspases 3, 8 and 9, and by a decrease in the levels of AKT and NF-kappaB. The cell population in the G1 phase decreased, and the S-phase population increased after AgNP treatment. AgNPs caused DNA damage and reduced the interaction between p53 and NF-kappaB. Interestingly, no significant alteration was noted in the levels of p21, BAX/ BCL-XL and NF-kappaB after AgNP treatment in a p53-knockout HCT116 cell line. Conclusion: AgNPs are bona fide anticancer agents that act in a p53-dependent manner. Original submitted 16 March 2012; Revised submitted 25 August 2012.
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[1018]
TÍTULO / TITLE: - Bigelovii A induces apoptosis of HL60 human acute promyelocytic leukaemia cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 1. doi: 10.3892/mmr.2013.1353.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1353
AUTORES / AUTHORS: - Guan F; Wang H; Shan Y; Zhang D; Zhao Y; Chen Y; Wang Q; Wang M; Feng X
INSTITUCIÓN / INSTITUTION: - Jiangsu Center for Research and Development of Medicinal Plants, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, Jiangsu, P.R. China.
RESUMEN / SUMMARY: - In the present study, the antitumor effects of the norOleanane type triterpene saponin, Bigelovii A, isolated from Salicornia bigelovii Torr, were examined. Bigelovii A was demonstrated to inhibit HL60 human acute promyelocytic leukaemia cell growth with an IC50 value of 2.15 microg/ml. In addition, Bigelovii A promoted apoptosis in HL60 cells, as shown by apoptotic morphological changes and the hypodiploid cell assay. Apoptotic induction by Bigelovii A was associated with the downregulation of Bcl2, the upregulation of Bax and the activation of caspase3, as demonstrated by RTPCR and western blot analysis. In addition, a lactate dehydrogenase release test indicated that Bigelovii A may exhibit cytotoxic activity by the induction of cell membrane impairment. This study is the first to identify that Bigelovii A exhibits potential antitumor activity and induces marked apoptosis and membrane permeabilisation in HL60 cells. Bigelovii A may be a novel candidate for future cancer therapy.
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[1019]
TÍTULO / TITLE: - Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Oncol. 2013;2013:872957. doi: 10.1155/2013/872957. Epub 2013 Feb 17.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/872957
AUTORES / AUTHORS: - Chen H; Landen CN; Li Y; Alvarez RD; Tollefsbol TO
INSTITUCIÓN / INSTITUTION: - Department of Biology, University of Alabama at Birmingham, CH175, 1300 University Boulevard, Birmingham, AL 35294-1170, USA.
RESUMEN / SUMMARY: - Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG) and cruciferous vegetables (sulforaphane, SFN) is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780/CP20) ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer.
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[1020]
TÍTULO / TITLE: - Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55183. doi: 10.1371/journal.pone.0055183. Epub 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055183
AUTORES / AUTHORS: - Quoc Trung L; Espinoza JL; Takami A; Nakao S
INSTITUCIÓN / INSTITUTION: - Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
RESUMEN / SUMMARY: - Natural killer (NK) cell malignancies, particularly aggressive NK cell leukaemias and lymphomas, have poor prognoses. Although recent regimens with L-asparaginase substantially improved outcomes, novel therapeutic approaches are still needed to enhance clinical response. Resveratrol, a naturally occurring polyphenol, has been extensively studied for its anti-inflammatory, cardioprotective and anti-cancer activities. In this study, we investigated the potential anti-tumour activities of resveratrol against the NK cell lines KHYG-1, NKL, NK-92 and NK-YS. Resveratrol induced robust G0/G1 cell cycle arrest, significantly suppressed cell proliferation and induced apoptosis in a dose- and time-dependent manner for all four cell lines. In addition, resveratrol suppressed constitutively active STAT3 in all the cell lines and inhibited JAK2 phosphorylation but had no effect on other upstream mediators of STAT3 activation, such as PTEN, TYK2, and JAK1. Resveratrol also induced downregulation of the anti-apoptotic proteins MCL1 and survivin, two downstream effectors of the STAT3 pathway. Finally, resveratrol induced synergistic effect on the apoptotic and antiproliferative activities of L-asparaginase against KHYG-1, NKL and NK-92 cells. These results suggest that resveratrol may have therapeutic potential against NK cell malignancies. Furthermore, our finding that resveratrol is a bonafide JAK2 inhibitor extends its potential benefits to other diseases with dysregulated JAK2 signaling.
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[1021]
TÍTULO / TITLE: - Autophagy inhibition promotes 5-fluorouraci-induced apoptosis by stimulating ROS formation in human non-small cell lung cancer A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56679. doi: 10.1371/journal.pone.0056679. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056679
AUTORES / AUTHORS: - Pan X; Zhang X; Sun H; Zhang J; Yan M; Zhang H
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, Binzhou Medical University, Shandong Yantai, China. panxh_2008@126.com
RESUMEN / SUMMARY: - Chemotherapy is an important option for the treatment of various cancers including lung cancer. However, tumor resistance towards cytotoxic chemotherapy has become more common. It has been reported that autophagy is one of the processes contributing to this resistance. In the present study, we found that the anti-cancer drug 5-fluorouraci(5-FU) could induce autophagy in A549 cells. 5-FU treatment could lead to the conversion of LC3 I/II, the up-regulation of Beclin-1, the down-regulation of p62 and the formation of acidic vesicular organelles (AVOs) in A549 cells. Pre-treatment of cancer cells with 3-MA or siAtg7 could enhance 5-FU-induced apoptosis through the activation of caspases, and the caspase inhibitor z-VAD-fmk rescued the cell viability reduction. Furthermore, the inhibition of autophagy also stimulated ROS formation and scavenging of ROS by antioxidant NAC inhibited caspase-3 activity, prevented the release of cyt-c from mitochondria and eventually rescued cancer cells from 5-FU-mediated apoptosis. These results suggest that 5-FU-elicited autophagic response plays a protective role against cell apoptosis and the inhibition of autophagy could sensitize them to 5-FU-induced caspase-dependent apoptosis through the stimulation of ROS formation.
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[1022]
TÍTULO / TITLE: - Deguelin induces both apoptosis and autophagy in cultured head and neck squamous cell carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54736. doi: 10.1371/journal.pone.0054736. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054736
AUTORES / AUTHORS: - Yang YL; Ji C; Bi ZG; Lu CC; Wang R; Gu B; Cheng L
INSTITUCIÓN / INSTITUTION: - Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
RESUMEN / SUMMARY: - Head and neck squamous cell carcinoma (HNSCC) represents more than 5% of all cancers diagnosed annually in United States and around the world. Despite advances in the management of patients with this disease, the survival has not been significantly improved, and the search for potential alternative therapies is encouraging. Here we demonstrate that deguelin administration causes a significant HNSCC cell death. Deguelin induces both cell apoptosis and autophagy by modulating multiple signaling pathways in cultured HNSCC cells. Deguelin inhibits Akt signaling, and down-regulates survivin and cyclin-dependent kinase 4 (Cdk4) expressions, by disrupting their association with heat shock protein-90 (Hsp-90). Deguelin induces ceramide production through de novo synthase pathway to promote HNSCC cell death. Importantly, increased ceramide level activates AMP-activated protein kinase (AMPK), which then directly phosphorylates Ulk1 and eventually leads to cell autophagy. We found that a low dose of deguelin sensitized HNSCC cells to 5-FU. Finally, using a nude mice Hep-2 xenograft model, we also showed a significant anti-tumor ability of deguelin in vivo. Together, we suggest that deguelin may represent a novel and effective chemo-agent against HNSCC.
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[1023]
TÍTULO / TITLE: - AKT signalling and mitochondrial pathways are involved in mushroom polysaccharide-induced apoptosis and G1 or S phase arrest in human hepatoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Chem. 2013 Jun 15;138(4):2130-9. doi: 10.1016/j.foodchem.2012.10.047. Epub 2012 Nov 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.foodchem.2012.10.047
AUTORES / AUTHORS: - Ouyang F; Wang G; Guo W; Zhang Y; Xiang W; Zhao M
INSTITUCIÓN / INSTITUTION: - College of Life Sciences, Northeast Forestry University, Harbin 150040, PR China.
RESUMEN / SUMMARY: - This study describes molecular mechanisms for inhibiting tumour cell proliferation using polysaccharides from medicinal mushrooms in human hepatoma cells. The results show that regarding cell cycle-related proteins, three types of polysaccharides significantly enhance the expression of p27(Kip) in HepG2 and Bel-7404 cells, while suppressing the activity of cyclin D1/CDK4 and/or cyclin E/CDK2. Considering apoptosis-related factors, the polysaccharides suppressed AKT activity through the inhibition of AKT phosphorylation at Thr(308) and/or Ser(473). The growth of HepG2 and Bel-7404 cells was suppressed by the up-regulation of a subunit of PI3K and phospho-PTEN, which are modulators of AKT activity. The polysaccharides also activated the mitochondria-mediated apoptosis pathway by stimulating the activation of Bcl-2 family proteins to release cytochrome c and Smac and cleave caspase-9 and caspase-3 in HepG2 and Bel-7404 cells. These factors have a potent effect on cell cycle arrest in G1 and/or S phase and induce apoptosis in HepG2 and Bel-7404 cells.
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[1024]
TÍTULO / TITLE: - Induction of Apoptosis in Human Breast Cancer Cells via Caspase Pathway by Vernodalin Isolated from Centratherum anthelminticum (L.) Seeds.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56643. doi: 10.1371/journal.pone.0056643. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056643
AUTORES / AUTHORS: - Looi CY; Arya A; Cheah FK; Muharram B; Leong KH; Mohamad K; Wong WF; Rai N; Mustafa MR
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
RESUMEN / SUMMARY: - BACKGROUND: Centratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-alpha (TNF-alpha)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we showed that CACF inhibited growth of MCF-7 human breast cancer cells. CACF induced apoptosis in MCF-7 cells as marked by cell size shrinkage, deformed cytoskeletal structure and DNA fragmentation. To identify the cytotoxic compound, CACF was subjected to bioassay-guided fractionation which yielded 6 fractions. CACF fraction A and B (CACF-A, -B) demonstrated highest activity among all the fractions. Further HPLC isolation, NMR and LC-MS analysis of CACF-A led to identification of vernodalin as the cytotoxic agent in CACF-A, and -B. 12,13-dihydroxyoleic acid, another major compound in CACF-C fraction was isolated for the first time from Centratherum anthelminticum (L.) seeds but showed no cytotoxic effect against MCF-7 cells. Vernodalin inhibited cell growth of human breast cancer cells MCF-7 and MDA-MB-231 by induction of cell cycle arrest and apoptosis. Increased of reactive oxygen species (ROS) production, coupled with downregulation of anti-apoptotic molecules (Bcl-2, Bcl-xL) led to reduction of mitochondrial membrane potential (MMP) and release of cytochrome c in both human breast cancer cells treated with vernodalin. Release of cytochrome c from mitochondria to cytosol triggered activation of caspase cascade, PARP cleavage, DNA damage and eventually cell death. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this is the first comprehensive study on cytotoxic and apoptotic mechanism of vernodalin isolated from the Centratherum anthelminticum (L.) seeds in human breast cancer cells. Overall, our data suggest a potential therapeutic value of vernodalin to be further developed as new anti-cancer drug.
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[1025]
TÍTULO / TITLE: - Alantolactone Induces Apoptosis in HepG2 Cells through GSH Depletion, Inhibition of STAT3 Activation, and Mitochondrial Dysfunction.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:719858. doi: 10.1155/2013/719858. Epub 2012 Dec 27.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/719858
AUTORES / AUTHORS: - Khan M; Li T; Ahmad Khan MK; Rasul A; Nawaz F; Sun M; Zheng Y; Ma T
INSTITUCIÓN / INSTITUTION: - Central Research Laboratory, Jilin University Bethune Second Hospital, Changchun 130041, China ; Department of Zoology, University of the Punjab, Quaid-e-Azam Campus, Lahore 54590, Pakistan.
RESUMEN / SUMMARY: - Signal transducer and activator of transcription 3 (STAT3) constitutively expresses in human liver cancer cells and has been implicated in apoptosis resistance and tumorigenesis. Alantolactone, a sesquiterpene lactone, has been shown to possess anticancer activities in various cancer cell lines. In our previous report, we showed that alantolactone induced apoptosis in U87 glioblastoma cells via GSH depletion and ROS generation. However, the molecular mechanism of GSH depletion remained unexplored. The present study was conducted to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2 cells by focusing on the molecular mechanism of GSH depletion and its effect on STAT3 activation. We found that alantolactone induced apoptosis in HepG2 cells in a dose-dependent manner. This alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation. This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine (NAC). The data demonstrate clearly that intracellular GSH plays a central role in alantolactone-induced apoptosis in HepG2 cells. Thus, alantolactone may become a lead chemotherapeutic candidate for the treatment of liver cancer.
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[1026]
TÍTULO / TITLE: - The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium(ii) asymmetric complexes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Metallomics. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1039/c3mt20270d
AUTORES / AUTHORS: - Qian C; Wang JQ; Song CL; Wang LL; Ji LN; Chao H
INSTITUCIÓN / INSTITUTION: - MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China. cesjln@mail.sysu.edu.cn ceschh@mail.sysu.edu.cn.
RESUMEN / SUMMARY: - Four ruthenium(ii) asymmetric complexes, [Ru(bpy)2(PAIDH)]2+ (bpy = 2,2’-bipyridine, PAIDH = 2-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione, ), [Ru(phen)2(PAIDH)]2+ (phen = 1,10-phenanthroline, ), [Ru(dmp)2(PAIDH)]2+ (dmp = 4,7-dimethyl-1,10-phenanthroline, ) and [Ru(dip)2(PAIDH)]2+ (dip = 4,7-diphenyl-1,10-phenanthroline, ), have been synthesized and characterized. These complexes displayed potent anti-proliferation activity against various cancer cell lines and had high selectivity between tumor cells and normal cells. HeLa cells exhibited the highest sensitivity to complex , accounting for the greatest cellular uptake. Complex was shown to accumulate preferentially in the mitochondria of HeLa cells and induced apoptosis via the mitochondrial pathway, which involved ROS generation, mitochondrial membrane potential depolarisation, and Bcl-2 and caspase family members activation. These results demonstrated that complex induced cancer cell apoptosis by acting on mitochondrial pathways.
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[1027]
TÍTULO / TITLE: - Chemical Perturbation of Mcl-1 Pre-mRNA Splicing to Induce Apoptosis in Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ACS Chem Biol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1021/cb300602j
AUTORES / AUTHORS: - Gao Y; Koide K
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, University of Pittsburgh , 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
RESUMEN / SUMMARY: - The myeloid cell leukemia-1 (MCL1) gene encodes antiapoptotic Mcl-1L and proapoptotic Mcl-1S proteins. In cancer, the Mcl-1L/Mcl-1S ratio is very high, accounting for the antiapoptotic nature of cancer cells. As such, reducing this ratio can render the cancer cells prone to apoptosis. The Mcl-1L/Mcl-1S ratio is determined in the alternative pre-mRNA splicing step that is regulated by splicing factor 3B1 (SF3B1). Here, we report that meayamycin B, a potent inhibitor of SF3B1, reversed the dominant isoform from Mcl-1L to Mcl-1S at the mRNA and protein levels. The resulting proapoptotic cellular environment was further exploited; when meayamycin B was combined with Bcl-xL inhibitor ABT-737, the combination treatment triggered apoptosis in nonsmall cell lung cancer A549 and H1299 cells that were otherwise resistant to ABT-737. These results demonstrate that perturbation of the MCL1 splicing with small molecule inhibitors of SF3B1 provides a means to sensitize cancer cells toward Bcl-xL inhibitors.
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[1028]
TÍTULO / TITLE: - Beclin1 inhibition promotes autophagy and decreases gemcitabine-induced apoptosis in Miapaca2 pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Mar 13;13(1):26. doi: 10.1186/1475-2867-13-26.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-26
AUTORES / AUTHORS: - Li X; Yan J; Wang L; Xiao F; Yang Y; Guo X; Wang H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Shenyang General Hospital of PLA, 83 Wenhua Road, Shenyang, 110016, P,R, China. guoxiaozhong1962@163.com.
RESUMEN / SUMMARY: - BACKGROUND: Beclin1 is a well-known key regulator of autophagy, which is also a haploinsufficient tumor suppressor. Current studies revealed that down-regulation or monoallelic deletions of Beclin1 were frequently found in various cancers. The purpose of this study was to investigate the effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of pancreatic cancer cells. METHODS: Beclin1 expression was inhibited by siRNA transduction and gene expression was determined by Real-time PCR and Western blot. The effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of Miapaca2 cells were analyed through LC3 expression, cell viability, cell cycle and apoptosis by using Western blot. RESULTS: We observed that Beclin1 silence promoted microtubule-associated protein 1 light chain 3-II (LC3-II) protein formation and increased punctate fluorescent signals in Miapaca2 cells transfected with green fluorescent protein (GFP)-tagged LC3. Beclin1 inhibition showed a greater suppressive effect on Gemcitabine-induced apoptosis of Miapaca2 cells. CONCLUSION: Our data suggested that Beclin1 silence not only up-adjusted autophagy process, but also played an important role in the regulation of apoptosis. Beclin1 inhibition could inhibit apoptosis signaling induced by Gemcitabine in Miapaca2 cells.
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[1029]
TÍTULO / TITLE: - Gossypol induces apoptosis in ovarian cancer cells through oxidative stress.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biosyst. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1039/c3mb25461e
AUTORES / AUTHORS: - Wang J; Jin L; Li X; Deng H; Chen Y; Lian Q; Ge R; Deng H
INSTITUCIÓN / INSTITUTION: - The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
RESUMEN / SUMMARY: - In the present work, metabolomic and redox proteomic analyses were carried out on an untreated- and gossypol-treated ovarian cancer cell line, SKOV3. Gossypol treatment resulted in cell death through oxidative stress. Metabolite analysis showed that gossypol induces a decrease of the cellular levels of GSH, aspartic acid, and FAD. Using a combination of double labeling and LC-MS-MS, we identified changes in thiol-redox states of 545 cysteine-containing peptides from 356 proteins. The frequently occurring amino acid residue immediately before or after the cysteine in these peptides is the non-polar and neutral leucine, valine, or alanine. These redox sensitive proteins participate in a variety of cellular processes. We have characterized the redox-sensitive cysteine residues in PKM2, HSP60, malate dehydrogenase and other proteins that play important roles in metabolism homeostasis and stress responses. The three cysteine residues of HSP60 exhibit different responses to gossypol treatment: an increase of thiol/disulfide ratio for the Cys447 residue due to a decrease of the cellular GSH level, and a decrease of thiol/disulfide ratios for Cys442 and Cys237 residues due to oxidation and sulfation. This study suggests that thiol/disulfide ratios are dependent on the level of cellular GSH. Our data provide a valuable resource for deciphering the redox regulation of proteins and for understanding gossypol-induced apoptosis in ovarian cancer cells.
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[1030]
TÍTULO / TITLE: - Casticin Potentiates TRAIL-Induced Apoptosis of Gastric Cancer Cells through Endoplasmic Reticulum Stress.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58855. doi: 10.1371/journal.pone.0058855. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058855
AUTORES / AUTHORS: - Zhou Y; Tian L; Long L; Quan M; Liu F; Cao J
INSTITUCIÓN / INSTITUTION: - Medical College, Hunan Normal University, Changsha, China.
RESUMEN / SUMMARY: - BACKGROUND: Casticin is one of the main active components obtained from Fructus Viticis and has been reported to exert anti-carcinogenic activity on a variety of cancer cells but the precise mechanism underlying this activity remains unclear. MATERIALS AND METHODS: Apoptotic activities of casticin (1.0 micromol/l) and TRAIL (25, 50 ng/ml) alone or in combination in the gastric cancer cell lines BGC-823, SGC-7901 and MGC-803 were detected by the use of a cell apoptosis ELISA detection kit, flow cytometry (FCM) with propidium iodide (PI) staining and activities of caspase-3, -8 and -9 by ELISA and cleavage of polyADP-ribose polymerase (PARP) protein using western blot analysis. Death receptors (DR) expression levels were evaluated using FCM analysis and western blotting. 2’, 7’-dichlorofluorescein diacetate (DCFH-DA) was used as a probe to measure the increase in reactive oxygen species (ROS) levels in cells. Multiple interventions, such as siRNA transfection and pharmacological inhibitors were used to explore the mechanisms of these actions. RESULTS: Subtoxic concentrations of casticin significantly potentiated TRAIL-induced cytotoxicity and apoptosis in BGC-823, SGC-7901 and MGC-803 cells. Casticin dramatically upregulated DR5 receptor expression but had no effects on DR4 or decoy receptors. Deletion of DR5 by siRNA significantly reduced the apoptosis induced by the co-application of TRAIL and casticin. Gene silencing of the CCAAT/enhancer binding protein homologous protein (CHOP) and pretreatment with salubrinal, an endoplasmic reticulum (ER) stress inhibitor, attenuated casticin-induced DR5 receptor expression, and apoptosis and ROS production. Casticin downregulated the expression levels of the cell survival proteins cFLIP, Bcl-2, XIAP, and survivin. In addition, casticin also induced the expressions of DR5 protein in other gastric cancer cells (SGC-7901 and MGC-803). CONCLUSIONSIGNIFICANCE: Casticin enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-ER stress-CHOP pathway.
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[1031]
TÍTULO / TITLE: - tert-Butylcarbamate-Containing Histone Deacetylase Inhibitors: Apoptosis Induction, Cytodifferentiation, and Antiproliferative Activities in Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ChemMedChem. 2013 Mar 25. doi: 10.1002/cmdc.201300005.
●● Enlace al texto completo (gratuito o de pago) 1002/cmdc.201300005
AUTORES / AUTHORS: - Valente S; Trisciuoglio D; Tardugno M; Benedetti R; Labella D; Secci D; Mercurio C; Boggio R; Tomassi S; Di Maro S; Novellino E; Altucci L; Del Bufalo D; Mai A; Cosconati S
INSTITUCIÓN / INSTITUTION: - Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Universita di Roma, P.le A. Moro 5, 00185 Roma (Italy).
RESUMEN / SUMMARY: - Herein we report novel pyrrole- and benzene-based hydroxamates (8, 10) and 2’-aminoanilides (9, 11) bearing the tert-butylcarbamate group at the CAP moiety as histone deacetylase (HDAC) inhibitors. Compounds 8 b and 10 c selectively inhibited HDAC6 at the nanomolar level, whereas the other hydroxamates effected an increase in acetyl-alpha-tubulin levels in human acute myeloid leukemia U937 cells. In the same cell line, compounds 8 b and 10 c elicited 18.4 and 21.4 % apoptosis, respectively (SAHA: 16.9 %), and the pyrrole anilide 9 c displayed the highest cytodifferentiating effect (90.9 %). In tests against a wide range of various cancer cell lines to determine its antiproliferative effects, compound 10 c exhibited growth inhibition from sub-micromolar (neuroblastoma LAN-5 and SH-SY5Y cells, chronic myeloid leukemia K562 cells) to low-micromolar (lung H1299 and A549, colon HCT116 and HT29 cancer cells) concentrations. In HT29 cells, 10 c increased histone H3 acetylation, and decreased the colony-forming potential of the cancer cells by up to 60 %.
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[1032]
TÍTULO / TITLE: - Vitexin-2-O-xyloside, raphasatin and (-)-epigallocatechin-3-gallate synergistically affect cell growth and apoptosis of colon cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Food Chem. 2013 Jun 1;138(2-3):1521-30. doi: 10.1016/j.foodchem.2012.11.112. Epub 2012 Dec 5.
●● Enlace al texto completo (gratuito o de pago) 1016/j.foodchem.2012.11.112
AUTORES / AUTHORS: - Papi A; Farabegoli F; Iori R; Orlandi M; De Nicola GR; Bagatta M; Angelino D; Gennari L; Ninfali P
INSTITUCIÓN / INSTITUTION: - Department of Experimental Evolutive Biology, University of Bologna, Bologna, Italy.
RESUMEN / SUMMARY: - Cytotoxic effects of the combination of the food components vitexin-2-O-xyloside (X), raphasatin (4-methylsulphanyl-3-butenyl isothiocyanates; G) and (-)-epigallocatechin-3-gallate (E) were investigated in colon (LoVo and CaCo-2) and breast (MDA-MB-231 and MCF-7) cancer cells. Breast cancer cells were more resistant than colon cells to X, G and E inhibition. On the contrary, marked synergistic effects among X, G and E on cell growth were found in both colon cancer cells. Further analysis revealed a G0/G1 arrest of the phase cell progression and apoptosis, linked to modulation of Bax, Bcl2, caspase-9 and poly(ADP-ribose) polymerase as well as Reactive Oxygen Species (ROS) generation in both colon cancer cells, whereas apoptosis and ROS were not significantly detected in normal human lymphocytes. We conclude that the X, G and E mixture might act by mitochondrial pathway activation of apoptosis, possibly elicited by ROS and the mixture may be effective in the chemoprevention of colon cancer.
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[1033]
TÍTULO / TITLE: - Lipopeptide Biosurfactant Pseudofactin II Induced Apoptosis of Melanoma A 375 Cells by Specific Interaction with the Plasma Membrane.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57991. doi: 10.1371/journal.pone.0057991. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057991
AUTORES / AUTHORS: - Janek T; Krasowska A; Radwanska A; Lukaszewicz M
INSTITUCIÓN / INSTITUTION: - Department of Biotransformation, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
RESUMEN / SUMMARY: - In the case of melanoma, advances in therapies are slow, which raises the need to evaluate new therapeutic strategies and natural products with potential cancer cell inhibiting effect. Pseudofactin II (PFII), a novel cyclic lipopeptide biosurfactant has been isolated from the Arctic strain of Pseudomonas fluorescens BD5. The aim of this study was to investigate the effect of PFII on A375 melanoma cells compared with the effect of PFII on Normal Human Dermis Fibroblast (NHDF) cells and elucidate the underlying mechanism of PFII cytotoxic activity. Melanoma A375 cells and NHDF cells were exposed to PFII or staurosporine and apoptotic death was assessed by monitoring caspase 3-like activity and DNA fragmentation. From time-dependent monitoring of lactate dehydrogenase (LDH) release, Ca(2+) influx, and a correlation between Critical Micelle Concentration (CMC) we concluded that cell death is the consequence of plasma membrane permeabilisation by micelles. This finding suggests that pro-apoptotic mechanism of PFII is different from previously described cyclic lipopeptides. The mechanism of PFII specificity towards malignant cells remains to be discovered. The results of this study show that PFII could be a new promising anti-melanoma agent.
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[1034]
TÍTULO / TITLE: - Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMB Rep. 2013 Feb;46(2):113-8.
AUTORES / AUTHORS: - Zhou C; Shen Q; Xue J; Ji C; Chen J
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
RESUMEN / SUMMARY: - TTRAP is a multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage. Here, we demonstrated that the lentivirus-mediated overexpression of TTRAP significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. The ectopic TTRAP suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Cell apoptosis was induced in U2OS cells and the cell cycle was arrested at G2/M phase in Saos-2 cells. Exogenous expression of TTRAP in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. In comparison with wild-type TTRAP, mutations in the 5’-tyrosyl-DNA phosphodiesterase activity of TTRAP, in particular TTRAP(E152A), showed decreased inhibitory activity on cell growth. These results may aid in clarifying the physiological functions of TTRAP, especially its roles in the regulation of cell growth and tumorigenesis.
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[1035]
TÍTULO / TITLE: - Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Complement Altern Med. 2013 Feb 25;13:46. doi: 10.1186/1472-6882-13-46.
●● Enlace al texto completo (gratuito o de pago) 1186/1472-6882-13-46
AUTORES / AUTHORS: - Lin CH; Lu WC; Wang CW; Chan YC; Chen MK
INSTITUCIÓN / INSTITUTION: - Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, 135 Nanhsiao St, Changhua, Taiwan. 53780@cch.org.tw.
RESUMEN / SUMMARY: - BACKGROUND: Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. METHODS: The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. RESULTS: We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. CONCLUSIONS: Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.
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[1036]
TÍTULO / TITLE: - A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 21;4:e547. doi: 10.1038/cddis.2013.45.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.45
AUTORES / AUTHORS: - Izidoro-Toledo TC; Borges AC; Araujo DD; Leitao Mazzi DP; Nascimento FO Junior; Sousa JF; Alves CP; Paiva AP; Trindade DM; Patussi EV; Peixoto PM; Kinnally KW; Espreafico EM
INSTITUCIÓN / INSTITUTION: - Department of Cellular and Molecular Biology and Pathogenic Bioagents, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
RESUMEN / SUMMARY: - Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that overexpression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed MVaf/DLCs did not interact with Bmf. Overexpression of DLC2 attenuated MVaf-induced apoptosis. Thus, we suggest that, MVaf induces apoptosis by sequestering DLC2 and DLC1, thereby unleashing the pair of sensitizer and activator BH3-only proteins Bmf and Bim. Murine embryonic fibroblasts (MEFs) lacking Bim and Bmf or Bax and Bak were less sensitive to apoptosis caused by MVaf expression than wild-type MEFs, strengthening the putative role of the intrinsic apoptotic pathway in this response. Finally, MVaf expression attenuated B16-F10 solid tumor growth in mice, suggesting that this peptide may be useful as an apoptosis-inducing tool for basic and translational studies.
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[1037]
TÍTULO / TITLE: - Anticancer effects of 3,3’-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):655-662. Epub 2012 Dec 5.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1063
AUTORES / AUTHORS: - Xu Y; Zhang J; Shi W; Liu Y
INSTITUCIÓN / INSTITUTION: - Departments of Otolaryngology, Wuhan University, Wuhan 430060, Hubei, P.R. China.
RESUMEN / SUMMARY: - The antitumor effects of 3,3’-diindolylmethane (DIM) are exhibited in a number of human cancer cells. However, there have been few studies performed concerning the effect of DIM on nasopharyngeal cancer (NPC) cells. In the present study, we examined the in vitro antitumor activity of DIM on the poorly differentiated NPC cell line CNE-2. The potential molecular mechanisms of the activity were also explored. CNE-2 cells were treated with varying concentrations of DIM for different times. Cell proliferation and apoptosis were detected and the molecular mechanisms involved in these effects were characterized. The results demonstrated that DIM at concentrations of 15-100 muM caused dose- and time-dependent inhibition of CNE-2 cell proliferation. Flow cytometry analysis revealed a high sub-G1 cell peak following treatment with DIM, and the rate of apoptosis increased. DIM may elevate the levels of cleaved Bid and Bax and enhance mitochondrial membrane depolarization, allowing the efflux of cytochrome c, Smac and Omi into the cytosol. The levels of caspases-3, -8 and -9 and cleaved poly (ADP-ribose) polymerase (PARP) were upregulated following DIM treatment in a dose-dependent manner. DIM also inhibits the phosphorylation of IkappaB-alpha, and showed dose-dependent inhibition of Bcl-2, XIAP and NF-kappaB in CNE-2 cells in vitro. These results indicate that DIM inhibits cell proliferation by inducing cell cycle arrest at G0/G1 phase and induces the apoptosis of CNE-2 cells by regulating multiple molecules in a mitochondria-dependent pathway. DIM may be a preventive and therapeutic agent against NPC.
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[1038]
TÍTULO / TITLE: - Induction of apoptosis and cell cycle blockade by helichrysetin in a549 human lung adenocarcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:857257. doi: 10.1155/2013/857257. Epub 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/857257
AUTORES / AUTHORS: - Ho YF; Karsani SA; Yong WK; Abd Malek SN
INSTITUCIÓN / INSTITUTION: - Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
RESUMEN / SUMMARY: - Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent.
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[1039]
TÍTULO / TITLE: - Interleukin-2 Gene Polymorphisms and Prognosis of Breast Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genet Test Mol Biomarkers. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1089/gtmb.2012.0494
AUTORES / AUTHORS: - Hu XB; Ouyang LZ; Tang LL
INSTITUCIÓN / INSTITUTION: - 1 Department of Breast Surgery, Xiangya Hospital, Central South University , Changsha, China .
RESUMEN / SUMMARY: - Breast cancer is the most common malignancy in women. Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural killer cells. It has been reported that polymorphisms in the IL-2 gene are associated with various cancers. The aim of this study was to examine the effect of polymorphisms in the IL-2 gene on the development of breast cancer in Chinese population. IL-2-330T/G and +114T/G polymorphisms were assessed in 638 breast cancer cases and 682 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that individuals with -330TG genotype and -330GG genotype had significantly increased susceptibility to breast cancer (Odds ratio [OR]=1.42, 95% confidence interval [CI]: 1.10-1.79, p=0.0021 and OR=2.26, 95%CI: 1.53-3.30, p<0.0001). The +114T/G polymorphism did not show any correlation with breast cancer. In addition, when analyzing the survival time of breast cancer patients with IL-2-330T/G polymorphism, cases with -330G allele had significantly shorter survival time compared with wild-type patients (p=0.002). These results suggested that polymorphism in the IL-2 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.
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[1040]
TÍTULO / TITLE: - Effect of histone deacetylase inhibitors on cell apoptosis and expression of the tumor suppressor genes RUNX3 and ARHI in ovarian tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 14. doi: 10.3892/mmr.2013.1371.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1371
AUTORES / AUTHORS: - Zhang L; Liu P; Li H; Xue F
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji’nan, Shandong 250000, P.R. China.
RESUMEN / SUMMARY: - The aim of this study was to investigate the expression of Runt box 3 (RUNX3) and aplasia Ras homolog member I (ARHI) in ovarian tumors, and the effects of histone deacetylase inhibitors (HDACIs) on the expression of these genes and the growth of ovarian cancer cells. The mRNA expression of the RUNX3 and ARHI genes in normal ovaries and ovarian tumors was determined using reverse transcription polymerase chain reaction (RT-PCR). The effects of HDACIs on RUNX3 and ARHI expression in four ovarian cancer cell lines (SKOV3, A2780, COC1 and OC3) were determined using RT-PCR and the MTT assay. The expression of RUNX3 and ARHI in normal ovarian cells was 86 and 100%, respectively. Although the two genes were downregulated in ovarian tumors, the extent of downregulation differed. The expression of RUNX3 and ARHI was correlated with the degree of tumor malignancy (P<0.05). ARHI was expressed in all four ovarian cancer cell lines, whereas RUNX3 was expressed only in the OC3 cell line. Treatment with HDACIs upregulated the expression of ARHI and RUNX3 in the SKOV3 cell line only. In A2780 cells, HDACIs upregulated ARHI expression only in the presence of trichostatin A (TSA) plus cisplatin. HDACIs induced significant apoptosis in ovarian cancer cells, which was inversely correlated with the concentration and duration of treatment (P<0.05). In conclusion, RUNX3 and ARHI were shown to be expressed in normal ovarian cells; however, their expression was downregulated or lost in ovarian tumor cells. The combined detection of ARHI and RUNX3 expression may offer improved prediction and monitoring of ovarian malignancies. HDACIs were revealed to inhibit the growth of ovarian tumor cells and may constitute a novel therapeutic option for ovarian tumors.
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[1041]
TÍTULO / TITLE: - Bladder cancer: Aurora kinase inhibitors light up the therapeutic horizon in bladder cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Urol. 2013 Mar 5. doi: 10.1038/nrurol.2013.35.
●● Enlace al texto completo (gratuito o de pago) 1038/nrurol.2013.35
AUTORES / AUTHORS: - Fenner A
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[1042]
TÍTULO / TITLE: - Knock-down of PRAME increases retinoic acid signaling and cytotoxic drug sensitivity of Hodgkin lymphoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55897. doi: 10.1371/journal.pone.0055897. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055897
AUTORES / AUTHORS: - Kewitz S; Staege MS
INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
RESUMEN / SUMMARY: - The prognosis for patients with Hodgkin lymphoma (HL) has improved in recent decades. On the other hand, not all patients can be cured with the currently established therapy regimes and this therapy is associated with several adverse late effects. Therefore it is necessary to develop new therapy strategies. After treatment of L-540 HL cells with 5’-azacytidine (5AC), we observed increased expression of the preferentially expressed antigen in melanoma (PRAME). In addition, we detected an increased resistance of 5AC-treated cells against cytotoxic drugs. We analyzed the influence of PRAME on cell survival of HL cells by knocking down PRAME in the chemotherapy resistant cell line L-428, a cell line that express PRAME at a high level. After knock-down of PRAME using vector based RNA interference we observed increased sensitivity for cisplatin, etoposide and retinoic acid. DNA microarray analysis of HL cells after PRAME knock-down indicated regulation of several genes including down-regulation of known anti-apoptotic factors. Increased retinoic acid signaling in these cells was revealed by increased expression of the retinoic acid metabolizing cytochrome P450 (CYP26B1), a transcriptional target of retinoic acid signaling. Our data suggest that PRAME inhibits retinoic acid signaling in HL cells and that the knock-down of PRAME might be an interesting option for the development of new therapy strategies for patients with chemo-resistant HL.
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[1043]
TÍTULO / TITLE: - TWIST interacts with endothelin-1/endothelin A receptor signaling in osteosarcoma cell survival against cisplatin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):857-861. Epub 2013 Jan 7.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1111
AUTORES / AUTHORS: - Zhou Y; Zang X; Huang Z; Zhang C
INSTITUCIÓN / INSTITUTION: - Department of Orthopaedics, The Third Xiangya Hospital, Central South University, Hunan, Changsha 410013, P.R. China.
RESUMEN / SUMMARY: - Both TWIST and the endothelin-1 (ET-1)/endothelin A receptor (ETAR) signaling are important in osteosarcoma (OS) progression. In the present study, the interaction between TWIST and ET-1/ETAR signaling in OS cells was investigated, and the impact of the functional interaction on OS cell survival against chemotherapy agent-induced apoptosis was assessed. TWIST was overexpressed and knocked down in Saos-2 and MG-63 OS cells, respectively. In Saos-2 cells, overexpression of TWIST significantly decreased ET-1 mRNA and protein expression levels, cell survival against cisplatin and phosphorylation of Akt at serine 473 (ser473), which was abolished by the selective phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, or the selective ETAR inhibitor, BQ123. In MG-63 cells, knockdown of TWIST significantly increased ET-1 expression, cell survival against cisplatin and phosphorylation of Akt at ser473. However, exogenous ET-1 only partially rescued cell survival against cisplatin-induced apoptosis in the cells in which TWIST had been knocked down in the presence of LY294002. In conclusion, we have demonstrated that TWIST significantly, although only partially, decreases OS cell survival against cisplatin by downregulating ET-1/ETAR signaling via inhibition of the PI3K/Akt pathway. To the best of our knowledge, the present study has provided the first evidence of a functional interaction between TWIST and ET-1/ETAR signaling in OS cells. This finding adds novel insights into the molecular mechanisms underlying OS progression, cell survival and chemoresistance.
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[1044]
TÍTULO / TITLE: - Mechanisms involved in the pro-apoptotic effect of melatonin in cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Mar 25;14(4):6597-613. doi: 10.3390/ijms14046597.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14046597
AUTORES / AUTHORS: - Rodriguez C; Martin V; Herrera F; Garcia-Santos G; Rodriguez-Blanco J; Casado-Zapico S; Sanchez-Sanchez AM; Suarez S; Puente-Moncada N; Anitua MJ; Antolin I
INSTITUCIÓN / INSTITUTION: - Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, c/Julian Claveria 6, 33006 Oviedo, España. carro@uniovi.es.
RESUMEN / SUMMARY: - It is well established that melatonin exerts antitumoral effects in many cancer types, mostly decreasing cell proliferation at low concentrations. On the other hand, induction of apoptosis by melatonin has been described in the last few years in some particular cancer types. The cytotoxic effect occurs after its administration at high concentrations, and the molecular pathways involved have been only partially determined. Moreover, a synergistic effect has been found in several cancer types when it is administered in combination with chemotherapeutic agents. In the present review, we will summarize published work on the pro-apoptotic effect of melatonin in cancer cells and the reported mechanisms involved in such action. We will also construct a hypothesis on how different cell signaling pathways may relate each other on account for such effect.
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[1045]
TÍTULO / TITLE: - Dose dependent activation of retinoic Acid-inducible gene-I promotes both proliferation and apoptosis signals in human head and neck squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58273. doi: 10.1371/journal.pone.0058273. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058273
AUTORES / AUTHORS: - Hu J; He Y; Yan M; Zhu C; Ye W; Zhu H; Chen W; Zhang C; Zhang Z
INSTITUCIÓN / INSTITUTION: - Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ; Shanghai Key Laboratory of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
RESUMEN / SUMMARY: - The retinoic-acid-inducible gene (RIG)-like receptor (RLR) family proteins are major pathogen reorganization receptors (PRR) responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC). RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5’-triphosphate RNA (3p-RNA) induces low levels of interferon and proinflammatory cytokines and promotes NF-kappaB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFalpha receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell surviral, whereas higher level of RIG-I activation leads to apopotosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC.
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[1046]
TÍTULO / TITLE: - Cladribine and bendamustine exhibit inhibitory activity in dexamethasone-sensitive and -resistant multiple myeloma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Transl Res. 2013;5(1):36-46. Epub 2013 Jan 21.
AUTORES / AUTHORS: - Cai B; Wang S; Huang J; Lee CK; Gao C; Liu B
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Chinese PLA General Hospital Beijing, China ; Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
RESUMEN / SUMMARY: - Cladribine (2-CDA) is a well-known purine nucleoside analog with activities against lymphoproliferative disorders such as hairy cell leukemia (HCL). Bendamustine, a hybrid molecule of purine analog and alkylator, induces apoptosis via DNA damage response and inhibition of mitotic checkpoint. Their therapeutic potential in patients with multiple myeloma (MM), particularly those become resistant to traditional chemotherapeutic agents, remains unclear. Here we study the effects of cladribine or bendamustine on dexamethasone-sensitive (MM1.S) and -resistant (MM1.R) MM cells. MTS-based proliferation assays showed that cladribine and bendamustine exhibited similar anti-proliferation/anti-survival effects on MM1.S and MM1.R cells in a dose-dependent manner. The IC50s of cladribine were approximately 35.3 nmol/L and 58 nmol/L for MM1.S and MM1.R cells, respectively. The IC50s of bendamustine were approximately 119.8 mumol/L (MM1.S) and 138 mumol/L (MM1.R). An apoptotic-ELISA and western blot assays of PARP cleavage and activation of caspase-8 and caspase-3 indicated that cladribine or bendamustine induced apoptosis in both cell lines. Similar results were obtained with flow cytometric analysis showing that cladribine or bendamustine increased the sub-G1 population. Treatment with bendamustine but not cladribine also resulted in cell cycle S-phase arrest. Either cladribine or bendamustine led to a remarkable increase of the phosphorylated H2A.X, CHK1 and CHK2 in both MM1.S and MM1.R cells, suggesting an induction of DNA damage response. Collectively, we demonstrate that cladribine and bendamustine exert potent inhibitory effects on dexamethasone-sensitive and -resistant MM cells in vitro. Our data suggest that MM patients, including those with dexamethasone resistance, may particularly benefit from cladribine or bendamustine.
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[1047]
TÍTULO / TITLE: - The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Amino Acids. 2013;2013:251398. doi: 10.1155/2013/251398. Epub 2013 Jan 16.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/251398
AUTORES / AUTHORS: - Fernandez Masso JR; Oliva Arguelles B; Tejeda Y; Astrada S; Garay H; Reyes O; Delgado-Roche L; Bollati-Fogolin M; Vallespi MG
INSTITUCIÓN / INSTITUTION: - Department of Genomic, Center for Genetic Engineering and Biotechnology, Cubanacan, P.O. Box 6162, 10600 Havana, Cuba.
RESUMEN / SUMMARY: - We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-kappaB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-kappaB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.
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[1048]
TÍTULO / TITLE: - Nanoscaled Poly(l-glutamic acid)/Doxorubicin-Amphiphile Complex as pH-responsive Drug Delivery System for Effective Treatment of Nonsmall Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ACS Appl Mater Interfaces. 2013 Mar 13;5(5):1781-92. doi: 10.1021/am303073u. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1021/am303073u
AUTORES / AUTHORS: - Li M; Song W; Tang Z; Lv S; Lin L; Sun H; Li Q; Yang Y; Hong H; Chen X
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
RESUMEN / SUMMARY: - Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Herein, we develop a polypeptide-based block ionomer complex formed by anionic methoxy poly(ethylene glycol)-b-poly(l-glutamic acid) (mPEG-b-PLG) and cationic anticancer drug doxorubicin hydrochloride (DOX.HCl) for NSCLC treatment. This complex spontaneously self-assembled into spherical nanoparticles (NPs) in aqueous solutions via electrostatic interaction and hydrophobic stack, with a high loading efficiency (almost 100%) and negative surface charge. DOX.HCl release from the drug-loaded micellar nanoparticles (mPEG-b-PLG-DOX.HCl) was slow at physiological pH, but obviously increased at the acidic pH mimicking the endosomal/lysosomal environment. In vitro cytotoxicity and hemolysis assays demonstrated that the block copolypeptide was cytocompatible and hemocompatible, and the presence of copolypeptide carrier could reduce the hemolysis ratio of DOX.HCl significantly. Cellular uptake and cytotoxicity studies suggested that mPEG-b-PLG-DOX.HCl was taken up by A549 cells via endocytosis, with a slightly slower cellular internalization and lower cytotoxicity compared with free DOX.HCl. The pharmacokinetics study in rats showed that DOX.HCl-loaded micellar NPs significantly prolonged the blood circulation time. Moreover, mPEG-b-PLG-DOX.HCl exhibited enhanced therapeutic efficacy, increased apoptosis in tumor tissues, and reduced systemic toxicity in nude mice bearing A549 lung cancer xenograft compared with free DOX.HCl, which were further confirmed by histological and immunohistochemical analyses. The results demonstrated that mPEG-b-PLG was a promising vector to deliver DOX.HCl into tumors and achieve improved pharmacokinetics, biodistribution and efficacy of DOX.HCl with reduced toxicity. These features strongly supported the interest of developing mPEG-b-PLG-DOX.HCl as a valid therapeutic modality in the therapy of human NSCLC and other solid tumors.
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[1049]
TÍTULO / TITLE: - Tumor-targeting and microenvironment-responsive smart nanoparticles for combination therapy of antiangiogenesis and apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ACS Nano. 2013 Mar 26;7(3):2860-71. doi: 10.1021/nn400548g. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1021/nn400548g
AUTORES / AUTHORS: - Huang S; Shao K; Liu Y; Kuang Y; Li J; An S; Guo Y; Ma H; Jiang C
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University , Shanghai 201203, China.
RESUMEN / SUMMARY: - Tumor microenvironment, such as the lowered tumor extracellular pH (pHe) and matrix metalloproteinase 2 (MMP2), has been extensively explored, which promotes the development of the microenvironment-responsive drug delivery system. Utilizing these unique features, an activatable cell-penetrating peptide (designated as dtACPP) that is dual-triggered by the lowered pHe and MMP2 has been constructed, and a smart nanoparticle system decorating with dtACPP has been successfully developed, which could dual-load gene drug and chemotherapeutics simultaneously. After systemic administration, dtACPP-modified nanoparticles possess passive tumor targetability via the enhanced permeability and retention effect. Then dtACPP would be activated to expose cell-penetrating peptide to drive the nanoparticles’ internalization into the intratumoral cells. As angiogenesis and tumor cells might be mutually improved in tumor growth, so combining antiangiogenesis and apoptosis is meaningful for oncotherapy. Vascular endothelial growth factor (VEGF) is significant in angiogenesis, and anti-VEGF therapy could decrease blood vessel density and delay tumor growth obviously. Chemotherapy using doxorubicin (DOX) could kill off tumor cells efficiently. Here, utilizing dtACPP-modified nanoparticles to co-deliver plasmid expressing interfering RNA targeting VEGF (shVEGF) and DOX (designated as dtACPPD/shVEGF-DOX) results in effective shutdown of blood vessels and cell apoptosis within the tumor. On the premise of effective drug delivery, dtACPPD/shVEGF-DOX has demonstrated good tumor targetability, little side effects after systemic administration, and ideal antitumor efficacy.
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[1050]
TÍTULO / TITLE: - Apoptosis of osteosarcoma cultures by the combination of the cyclin-dependent kinase inhibitor SCH727965 and a heat shock protein 90 inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 28;4:e566. doi: 10.1038/cddis.2013.101.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.101
AUTORES / AUTHORS: - Fu W; Sharma SS; Ma L; Chu B; Bui MM; Reed D; Pledger WJ
INSTITUCIÓN / INSTITUTION: - Department of Molecular Oncology, Gonzmart Research Laboratory, and the Sarcoma Research Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
RESUMEN / SUMMARY: - Osteosarcoma (OS) is an aggressive bone cancer typically observed in adolescents and young adults. Metastatic relapse accounts primarily for treatment failure, and obstacles to improving cure rates include a lack of efficacious agents. Our studies show apoptosis of OS cells prepared from localized and metastatic tumors by a novel drug combination: SCH727965 (SCH), a cyclin-dependent kinase inhibitor, and NVP-AUY922 (AUY) or other heat shock protein 90 inhibitor. SCH and AUY induced apoptosis when added simultaneously to cells and when AUY was added to and removed from cells before SCH addition. Sequential treatment was most effective when cells received AUY for approximately 12 h and when SCH was presented to cells immediately after AUY removal. The apoptotic protein Bax accumulated in mitochondria of cotreated cells but was primarily cytosolic in cells receiving either agent alone. Additional data show that SCH and AUY cooperatively induce the apoptosis of other sarcoma cell types but not of normal osteoblasts or fibroblasts, and that SCH and AUY individually inhibit cell cycle progression throughout the cell cycle. We suggest that the combination of SCH and AUY may be an effective new strategy for treatment of OS.
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[1051]
TÍTULO / TITLE: - Overexpression of wild-type but not C134W mutant FOXL2 enhances GnRH-induced cell apoptosis by increasing GnRH receptor expression in human granulosa cell tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55099. doi: 10.1371/journal.pone.0055099. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055099
AUTORES / AUTHORS: - Cheng JC; Klausen C; Leung PC
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
RESUMEN / SUMMARY: - The etiology of granulosa cell tumors (GCTs) is largely unknown. The primary mode of treatment is surgical, however not all women are cured by surgery alone. Thus, it is important to develop improved treatments through a greater understanding of the molecular mechanisms that contribute to this disease. Recently, it has been shown that a FOXL2 402C>G (C134W) mutation is present in 97% of human adult-type GCTs, suggesting an important role for this mutation in the development of GCTs. We have shown previously that gonadotropin-releasing hormone (GnRH)-I and -II induce apoptosis in cultured normal human granulosa cells. Moreover, it has been reported that FOXL2 can bind to the promoter of the mouse GnRH receptor gene and regulate its transcription. Thus, we hypothesized that C134W mutant FOXL2 could modulate the pro-apoptotic effects of GnRH via aberrant regulation of GnRH receptor levels. Using KGN cells, a human GCT-derived cell line which harbors the FOXL2 402C>G mutation, we show that treatment with GnRH-I and -II induces cell apoptosis, and that small interfering RNA-mediated depletion of GnRH receptor abolishes these effects. Overexpression of wild-type FOXL2 increases both mRNA and protein levels of GnRH receptor and consequently enhances GnRH-induced apoptosis. Importantly, neither the expression levels of GnRH receptor nor GnRH-induced apoptosis were affected by overexpression of the C134W mutant FOXL2. Interestingly, knockdown of endogenous FOXL2 down-regulates GnRHR expression in normal human granulosa cells with wild-type FOXL2, but not in KGN cells. These results suggest that the FOXL2 402C>G mutation may contribute to the development of human adult-type GCTs by reducing the expression of GnRH receptor, thus conferring resistance to GnRH-induced cell apoptosis.
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[1052]
TÍTULO / TITLE: - Profiling pathway-specific novel therapeutics in preclinical assessment for central nervous system atypical teratoid rhabdoid tumors (CNS ATRT): Favorable activity of targeting EGFR- ErbB2 signaling with lapatinib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Oncol. 2013 Jan 11. pii: S1574-7891(13)00012-4. doi: 10.1016/j.molonc.2013.01.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2013.01.001
AUTORES / AUTHORS: - Singh A; Lun X; Jayanthan A; Obaid H; Ruan Y; Strother D; Chi SN; Smith A; Forsyth P; Narendran A
INSTITUCIÓN / INSTITUTION: - Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC), Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada.
RESUMEN / SUMMARY: - Despite intensifying multimodal treatments, children with central nervous system atypical teratoid/rhabdoid tumor (CNS ATRT) continue to endure unacceptably high mortality rates. At present, concerted efforts are focusing on understanding the characteristic INI1 mutation and its implications for the growth and survival of these tumors. Additionally, pharmaceutical pipeline libraries constitute a significant source of potential agents that can be taken to clinical trials in a timely manner. However, this process requires efficient target validation and relevant preclinical studies. As an initial screening approach, a panel of 129 small molecule inhibitors from multiple pharmaceutical pipeline libraries was tested against three ATRT cell lines by in vitro cytotoxicity assays. Based on these data, agents that have strong activity and corresponding susceptible cellular pathways were identified. Target modulation, antibody array analysis, drug combination and in vivo xenograft studies were performed on one of the pathway inhibitors found in this screening. Approximately 20% of agents in the library showed activity with IC(50) values of 1 muM or less and many showed IC(50) values less than 0.05 muM. Intra cell line variability was also noted among some of the drugs. However, it was determined that agents capable of affecting pathways constituting ErbB2, mTOR, proteasomes, Hsp90, Polo like kinases and Aurora kinases were universally effective against the three ATRT cell lines. The first target selected for further analysis, the inhibition of ErbB2-EGFR pathway by the small molecule inhibitor lapatinib, indicated inhibition of cell migration properties and the initiation of apoptosis. Synergy between lapatinib and IGF-IR inhibition was also demonstrated by combination index (CI) values. Xenograft studies showed effective antitumor activity of lapatinib in vivo. We present an experimental approach to identifying agents and drug combinations for future clinical trials and provide evidence for the potential of lapatinib as an effective agent in the context of the biology and heterogeneity of its targets in ATRT.
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[1053]
TÍTULO / TITLE: - Patterns of cancer occurrence in different regions of West Bengal—a hospital based study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Indian Med Assoc. 2012 Jul;110(7):445-8.
AUTORES / AUTHORS: - Maiti PK; Jana U; Ray A; Karmakar R; Mitra TN; Ganguly S
INSTITUCIÓN / INSTITUTION: - Department of Radiotherapy, NRS Medical College, Kolkata 700014.
RESUMEN / SUMMARY: - The incidence of cancer has been rising steadily in the third world countries including India. The patterns of cancer incidence reflect the racial, cultural and pharmacogenomic diversity within populations and nowhere is this diversity more striking than in the Indian subcontinent. This article shows the diversity in patterns of incidence of major cancers across three medical college hospitals in the state of West Bengal in India. All the data were collected from the period between 2001 and 2005. The results show a striking variation of incidence of major cancers in the urban, semi-urban and rural parts of the same state. Indeed the differences of the patterns are explainable by the cultural and socioeconomic differences within the populations from which the study samples are drawn. This constitutes the largest single hospital based data collected from this part of the world till date and will help in re-evaluation of cancer control programmes promulgated by the health authorities of the region.
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[1054]
TÍTULO / TITLE: - Malignant hyperthermia in Brazil: analysis of hotline activity in 2009.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Rev Bras Anestesiol. 2013 Jan;63(1):13-26. doi: 10.1016/S0034-7094(13)70195-8.
●● Enlace al texto completo (gratuito o de pago) 1016/S0034-7094(13)70195-8
AUTORES / AUTHORS: - Almeida da Silva HC; Santos Almeida CD; Mendes Brandao JC; Nogueira E Silva CA; Pinto de Lorenzo ME; Duarte Ferreira CB; Resende AH; Barreira SR; de Almeida PA; Cunha Ferraro LH; Takeda A; de Oliveira KF; Lelis TG; Hortense A; Perez MV; Schmidt B; Bulle Oliveira AS; Gomes do Amaral JL
INSTITUCIÓN / INSTITUTION: - Department of Anesthesiology, Pain and Intensive Care, Escola Paulista de Medicina, Universidade Federal de Sao Paulo (Unifesp). Electronic address: halsilva@uol.com.br.
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVES: Malignant hyperthermia (MH) is a pharmacogenetic disease that causes abnormal hypermetabolic reaction to halogenated anesthetics and/or depolarizing muscle relaxants. In Brazil, there is a hotline telephone service for MH since 1991, available 24 hours a day in Sao Paulo. This article analyzes the activity of the Brazilian hotline service for MH in 2009. METHODS: Prospective analysis of all phone calls made to the Brazilian hotline service for MH from January to December 2009. RESULTS: Twenty-two phone calls were received: 21 from the South/Southeast region of Brazil and one from the North region. Fifteen calls were requests for general information about MH. Seven were about suspected MH acute episodes, two of which were not considered as MH. In five episodes compatible with MH, all patients received halogenated volatile anesthetics (2, isoflurane; 3, sevoflurane) and one also used succinylcholine; there were four men and one woman, with a mean age of 18 years (2-27). The problems described in the five MH episodes were tachycardia (5), increased expired carbon dioxide (4), hyperthermia (3), acidemia (1), rhabdomyolysis (1), and myoglobinuria (1). One patient received dantrolene. All five patients with MH episodes were follow-up in the intensive care unit and recovered without sequelae. Susceptibility to MH was later confirmed in two patients by in vitro muscle contracture test. CONCLUSIONS: The number of calls per year in the Brazilian hotline service for MH is still low. The characteristics of MH episode were similar to those reported in other countries. The knowledge of MH in Brazil needs to be increased.
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[1055]
TÍTULO / TITLE: - Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Mol Morphol. 2013 Mar 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s00795-013-0036-x
AUTORES / AUTHORS: - Teramoto M; Suzuki T; Satohisa S; Akashi Y; Matsuura M; Suzuki M; Tanaka R; Saito T
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Sapporo Medical University, S1, W16, Chuo-ku, Sapporo, 060-8543, Japan.
RESUMEN / SUMMARY: - Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.
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[1056]
TÍTULO / TITLE: - Effectiveness of the Histone Deacetylase Inhibitor (S)-2 against LNCaP and PC3 Human Prostate Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58267. doi: 10.1371/journal.pone.0058267. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058267
AUTORES / AUTHORS: - Laurenzana A; Balliu M; Cellai C; Romanelli MN; Paoletti F
INSTITUCIÓN / INSTITUTION: - Department of Experimental Pathology and Oncology, University of Florence, Firenze, Italy.
RESUMEN / SUMMARY: - Histone deacetylase inhibitors (HDACi) represent a promising class of epigenetic agents with anticancer properties. Here, we report that (S)-2, a novel hydroxamate-based HDACi, shown previously to be effective against acute myeloid leukemia cells, was also a potent inducer of apoptosis/differentiation in human prostate LNCaP and PC3 cancer cells. In LNCaP cells (S)-2 was capable of triggering H3/H4 histone acetylation, H2AX phosphorylation as a marker of DNA damage and producing G0/G1 cell cycle arrest. Consistently, (S)-2 led to enhanced expression of both the protein and mRNA p21 levels in LNCaP cells but, contrary to SAHA, not in normal non-tumorigenic prostate PNT1A cells. Mechanistic studies demonstrated that (S)-2-induced apoptosis in LNCaP cells developed through the cleavage of pro-caspase 9 and 3 and of poly(ADP-ribose)-polymerase accompanied by the dose-dependent loss of mitochondrial membrane potential. Indeed, the addition of the pan-caspase inhibitor Z-VAD-fmk greatly reduced drug-mediated apoptosis while the antioxidant N-acetyl-cysteine was virtually ineffective. Importantly, preliminary data with nude mice xenografted with LNCaP cells showed that (S)-2 prompted a decrease in the tumor volume and an increase in H2AX phosphorylation within the cancer cells. Moreover, the highly metastatic prostate cancer PC3 cells were also sensitive to (S)-2 that: i) induced growth arrest and moderate apoptosis; ii) steered cells towards differentiation and neutral lipid accumulation; iii) reduced cell invasiveness potential by decreasing the amount of MMP-9 activity and up-regulating TIMP-1 expression; and iv) inhibited cell motility and migration through the Matrigel. Overall, (S)-2 has proven to be a powerful HDACi capable of inducing growth arrest, cell death and/or differentiation of LNCaP and PC3 prostate cancer cells and, due to its low toxicity and efficacy in vivo, might also be of clinical interest to support conventional prostate cancer therapy.
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[1057]
TÍTULO / TITLE: - 5-Fluorouracil potentiates the anti-cancer effect of oxaliplatin on Colo320 colorectal adenocarcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointestin Liver Dis. 2013 Mar;22(1):37-43.
AUTORES / AUTHORS: - Berindan-Neagoe I; Braicu C; Pileczki V; Cojocneanu Petric R; Miron N; Balacescu O; Iancu D; Ciuleanu T
INSTITUCIÓN / INSTITUTION: - Department of Functional Genomics and Experimental Pathology, Oncological Institute Ion Chiricuta; Department of Immunology, University of Medicine and Pharmacy Iuliu Hatieganu; Cluj-Napoca, Romania; Email: braicucornelia@yahoo.com.
RESUMEN / SUMMARY: - BACKGROUND & AIMS. The present study was designed to examine the combined effects of Oxaliplatin (OXA) and 5-Fluorouracil (5-FU) in the Colo320 cell line. METHODS. The antiproliferative effects were evaluated using the MTT assay, apoptosis by flow cytometry, and RT-PCR-array technology was used to determine the major effects of the two chemotherapeutic drugs upon the most important genes involved in apoptosis. RESULTS. The antiproliferative effects of the therapeutic agents, as individual therapy or combined, proved to be dose and time-dependent, with increased efficiency for the combined treatment. Flow cytometry data revealed increased apoptotic processes in the case of the combined treatment at 24 hours after administration. The RT-PCR-array data indicated that at 24 hours after OXA treatment, 49 genes were differentially expressed, of which 45 were up-regulated and 4 down-regulated. In the case of the 5-FU treatment, 35 genes were down regulated and 2 up regulated. In the combined treatment of 5-FU and OXA, 19 genes were up-regulated and 15 down-regulated. CONCLUSIONS. This study proved that drug resistance could be counteracted by combining OXA with 5-FU to form a tandem that is capable of reducing cell proliferation and to stimulate extrinsic apoptosis pathway by targeting death receptors on the cell surface.
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[1058]
TÍTULO / TITLE: - The Effects of 5-Fluorouracil on the Proteome of Colon Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Proteome Res. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1021/pr400052p
AUTORES / AUTHORS: - Marin-Vicente C; Lyutvinskiy Y; Romans Fuertes P; Zubarev RA; Visa N
INSTITUCIÓN / INSTITUTION: - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
RESUMEN / SUMMARY: - The pyrimidine analogue 5-fluorouracil (5FU) is used as a treatment for solid tumors, but its mechanism of action is not fully understood. We have used mass spectrometry to study the mechanism of action of 5FU, and we have measured the effects of this drug on the composition and on the turnover of the proteome of RKO cancer cells. We have identified novel potential targets of 5FU that are affected after very short exposure times. We have also shown that 5FU has a massive effect on the proteins involved in RNA metabolism. After only 1 h of treatment, 5FU causes a post-transcriptional reduction in the abundance of components of the translation machinery (mostly ribosomal proteins), and this reduction is accompanied by a down-regulation of the translational capacity of the cells. Neither rapamycin nor raltitrexed, two drugs that also block cell proliferation, reduce the abundances of ribosomal proteins as 5FU does, which suggests that the down-regulation of ribosomal proteins is coupled to the mechanism of action of 5FU. Some of our observations conflict with previous reports based on RNA quantification. This shows how important it is to complement RNA profiling studies with analyses of drug toxicity at the protein level.
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[1059]
TÍTULO / TITLE: - Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57056. doi: 10.1371/journal.pone.0057056. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057056
AUTORES / AUTHORS: - Dong Y; Stephens C; Walpole C; Swedberg JE; Boyle GM; Parsons PG; McGuckin MA; Harris JM; Clements JA
INSTITUCIÓN / INSTITUTION: - Cancer Program, Institute of Health and Biomedical Innovation and Faculty of Sciences and Technology, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
RESUMEN / SUMMARY: - High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.
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[1060]
TÍTULO / TITLE: - Inhibition of NF- kappa B by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide and gamma -Radiation Cytotoxicity in Glioblastoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chemother Res Pract. 2013;2013:593020. doi: 10.1155/2013/593020. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/593020
AUTORES / AUTHORS: - Brassesco MS; Roberto GM; Morales AG; Oliveira JC; Delsin LE; Pezuk JA; Valera ET; Carlotti CG Jr; Rego EM; de Oliveira HF; Scrideli CA; Umezawa K; Tone LG
INSTITUCIÓN / INSTITUTION: - Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil ; Laboratorio de Pediatria, Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto (USP), Bloco G, Avenida Bandeirantes, 3900 Bairro Monte Alegre, 14048-900 Ribeirao Preto, SP, Brazil.
RESUMEN / SUMMARY: - Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF- kappa B is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF- kappa B inhibitor with antiproliferative properties in GBM. In the present study, the ability of DHMEQ to surmount tumor’s invasive nature and therapy resistance were further explored. Corroborating results showed that DHMEQ impaired cell growth in dose- and time-dependent manners with G2/M arrest when compared with control. Clonogenicity was also significantly diminished with increased apoptosis, though necrotic cell death was also observed at comparable levels. Notably, migration and invasion were inhibited accordingly with lowered expression of invasion-related genes. Moreover, concurrent combination with TMZ synergistically inhibited cell growth in all cell lines, as determined by proliferation and caspase-3 activation assays, though in those that express O(6)-methylguanine-DNA methyltransferase, the synergistic effects were schedule dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing radiation. Taken together, our results strengthen the potential usefulness of DHMEQ in future therapeutic strategies for tumors that do not respond to conventional approaches.
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[1061]
TÍTULO / TITLE: - Nelfinavir augments proteasome inhibition by bortezomib in myeloma cells and overcomes bortezomib and carfilzomib resistance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Blood Cancer J. 2013 Mar 1;3:e103. doi: 10.1038/bcj.2013.2.
●● Enlace al texto completo (gratuito o de pago) 1038/bcj.2013.2
AUTORES / AUTHORS: - Kraus M; Bader J; Overkleeft H; Driessen C
INSTITUCIÓN / INSTITUTION: - Department of Oncology and Hematology, Cantonal Hospital, St. Gallen, Switzerland.
RESUMEN / SUMMARY: - HIV protease inhibitors (HIV-PI) are oral drugs for HIV treatment. HIV-PI have antitumor activity via induction of ER-stress, inhibition of phospho-AKT (p-AKT) and the proteasome, suggesting antimyeloma activity. We characterize the effects of all approved HIV-PI on myeloma cells. HIV-PI were compared regarding cytotoxicity, proteasome activity, ER-stress induction and AKT phosphorylation using myeloma cells in vitro. Nelfinavir is the HIV-PI with highest cytotoxic activity against primary myeloma cells and with an IC near therapeutic drug blood levels (8-14 muM), irrespective of bortezomib sensitivity. Only nelfinavir inhibited intracellular proteasome activity in situ at drug concentrations <40 muM. Ritonavir, saquinavir and lopinavir inhibited p-AKT comparable to nelfinavir, and showed similar synergistic cytotoxicity with bortezomib against bortezomib-sensitive cells. Nelfinavir had superior synergistic activity with bortezomib/carfilzomib in particular against bortezomib/carfilzomib-resistant myeloma cells. It inhibited not only the proteasomal beta1/beta5 active sites, similar to bortezomib/carfilzomib, but in addition the beta2 proteasome activity not targeted by bortezomib/carfilzomib. Additional inhibition of beta2 proteasome activity is known to sensitize cells for bortezomib and carfilzomib. Nelfinavir has unique proteasome inhibiting activity in particular on the bortezomib/carfilzomib-insensitive tryptic (beta2) proteasome activity in intact myeloma cells, and is active against bortezomib/carfilzomib-resistant myeloma cells in vitro.
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[1062]
TÍTULO / TITLE: - Cetuximab conjugated O-carboxymethyl chitosan nanoparticles for targeting EGFR overexpressing cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carbohydr Polym. 2013 Apr 2;93(2):661-9. doi: 10.1016/j.carbpol.2012.12.032. Epub 2013 Jan 18.
●● Enlace al texto completo (gratuito o de pago) 1016/j.carbpol.2012.12.032
AUTORES / AUTHORS: - Maya S; Kumar LG; Sarmento B; Sanoj Rejinold N; Menon D; Nair SV; Jayakumar R
INSTITUCIÓN / INSTITUTION: - Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
RESUMEN / SUMMARY: - Nanoparticle mediated delivery of antineoplastic agents, functionalized with monoclonal antibodies has achieved extraordinary potential in cancer therapy. The objective of this study was to develop a drug delivery system comprising O-carboxymethyl chitosan (O-CMC) nanoparticles, surface-conjugated with Cetuximab (Cet) for targeted delivery of paclitaxel (PTXL) to Epidermal Growth Factor Receptor (EGFR) over-expressing cancer cells. Nanoparticles around 180+/-35nm and negatively charged were prepared through simple ionic gelation technique. The alamar blue assay indicated that these targeted nanoparticles displayed a superior anticancer activity compared to non-targeted nanoparticles. The nanoformulation triggered enhanced cell death (confirmed by flow cytometry) due to its higher cellular uptake. The selective uptake of Cet-PTXL-O-CMC nanoparticles by EGFR +VE cancer cells (A549, A431 and SKBR3) compared to EGFR -VE MIAPaCa-2 cells confirms the active targeting and delivery of PTXL via the targeted nanomedicine. Cet-PTXL-O-CMC nanoparticles can be used a promising candidate for the targeted therapy of EGFR over expressing cancers.
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[1063]
TÍTULO / TITLE: - Overexpression of CDCA2 in human squamous cell carcinoma: correlation with prevention of G1 phase arrest and apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56381. doi: 10.1371/journal.pone.0056381. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056381
AUTORES / AUTHORS: - Uchida F; Uzawa K; Kasamatsu A; Takatori H; Sakamoto Y; Ogawara K; Shiiba M; Bukawa H; Tanzawa H
INSTITUCIÓN / INSTITUTION: - Department of Oral and Maxillofacial Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
RESUMEN / SUMMARY: - Cell division cycle associated 2 (CDCA2) recruits protein phosphatase 1 to chromatin to antagonize activation of ataxia telangiectasia mutated (ATM)-dependent signal transduction. ATM kinase plays a critical role in the DNA damage response and its phosphorylation cascade to inhibit the p53-MDM2 interaction, which releases p53 to induce p21 and G1 cell-cycle arrest. However, the relevance of CDCA2 to human malignancy including oral squamous cell carcinoma (OSCC) is unknown. In the current study, we found that CDCA2 expression was up-regulated in OSCC cell lines. Functional studies with shRNA system showed that knockdown of CDCA2 significantly (P<0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase and up-regulating the cyclin-dependent kinase inhibitors (p21(Cip1), p27(Kip1), p15(INK4B), and p16(INK4A)). CDCA2 knockdown also promoted apoptosis after treatment with the DNA damage reagent, cisplatin. In clinical samples, the CDCA2 protein expression level in primary OSCCs was significantly (P<0.05) greater than in matched normal oral tissues (67/85, 79%). Furthermore, CDCA2-positive cases were correlated significantly (P<0.05) with high cancer progression. Our results showed for the first time that CDCA2 frequently is overexpressed in OSCCs and might be associated closely with OSCC progression by preventing cell-cycle arrest and apoptosis.
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[1064]
TÍTULO / TITLE: - Thioredoxin system: a model for determining novel lead molecules for breast cancer chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Avicenna J Med Biotechnol. 2012 Jul;4(3):121-30.
AUTORES / AUTHORS: - Jamil K; Mustafa SM
INSTITUCIÓN / INSTITUTION: - School of Life Sciences, Centre for Biotechnology and Bioinformatics (CBB), Jawaharlal Nehru Institute of Advanced Studies, Secunderabad, India.
RESUMEN / SUMMARY: - BACKGROUND: Thioredoxin reductase 1 (TXNRD1) and thioredoxin interacting protein (TXNIP) also known as thioredoxin binding protein 2 or vitamin D3-upregulated protein 1 are key players in oxidative stress control. Thioredoxin (TRX) is one of the major components of the thiol reducing system and plays multiple roles in cellular processes. Computational analyses of TXNRD1, TXNIP and TRX expressions have not been analyzed in relation to prognosis of breast cancer. High expression of TXNRD1 and low expression of TXNIP are associated with worst prognosis in breast cancer. METHODS: Using bioinformatics applications we studied sequence analysis, molecular modeling, template and fold recognition, docking and scoring of thioredoxin as a target. RESULTS: The resultant model obtained was validated based on the templates from I-TASSER server and binding site residues were predicted. The predicted model was used for Threading and Fold recognition and was optimized using GROMACS. The generated model was validated using programs such as Procheck, Ramachandran plot, verify-3d and Errat value from Saves server, and the results show that the model is reliable. Next we obtained small molecules from pubchem and chembank which are databases for selecting suitable ligands for our modeled target. These molecules were screened for docking, using GOLD and scoring was obtained using Chemscore as a scoring function. CONCLUSION: This study predicted the ligand interaction of four molecules with the minimized protein modeled structure and the best ligand with top scores from about 500 molecules screened. These were 3-hydroxy-2,3-diphenylbutanoic acid, 4-amino-3-pentadecylphenol, 3-(hydroxyimino)-2,4-diphenylbutanenitrile and 2-ethyl-1,2-diphenylbutyl carbamate, which are proposed as possible hit molecules for the drug discovery and development process.
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[1065]
TÍTULO / TITLE: - Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Oncol (Dordr). 2013 Apr;36(2):95-112. doi: 10.1007/s13402-013-0127-7. Epub 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s13402-013-0127-7
AUTORES / AUTHORS: - Hale MD; Hayden JD; Grabsch HI
INSTITUCIÓN / INSTITUTION: - Section of Pathology & Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK.
RESUMEN / SUMMARY: - BACKGROUND: Cytotoxic chemotherapy improves survival for some, but not all, cancer patients. Non-responders may experience unnecessary toxicity and cancer progression, thus creating an urgent need for biomarkers that can predict the response to chemotherapy. So far, the search for such biomarkers has primarily been focused on the cancer cells and less on their surrounding stroma. This stroma is known to act as a key regulator of tumour progression and, in addition, has been associated with drug delivery and drug efficacy. Fibroblasts represent the major cell type in cancer-associated stroma and they secrete extracellular matrix proteins as well as growth factors. This Medline-based literature review summarises the results from studies on epithelial cancers and aimed at investigating relationships between the quantity and quality of the intra-tumoral stroma, the cancer-associated fibroblasts, the proteins they produce and the concomitant response to chemotherapy. Biomarkers were selected for review that are known to affect cancer-related characteristics and patient prognosis. RESULTS: The current literature supports the hypothesis that biomarkers derived from the tumour stroma may be useful to predict response to chemotherapy. This notion appears to be related to the overall quantity and cellularity of the intra-tumoural stroma and the predominant constituents of the extracellular matrix. CONCLUSION: Increasing evidence is emerging showing that tumour-stroma interactions may not only affect tumour progression and patient prognosis, but also the response to chemotherapy. The tumour stroma-derived biomarkers that appear to be most appropriate to determine the patient’s response to chemotherapy vary by tumour origin and the availability of pre-treatment tissue. For patients scheduled for adjuvant chemotherapy, the most promising biomarker appears to be the PLAU: SERPINE complex, whereas for patients scheduled for neo-adjuvant chemotherapy the tumour stroma quantity appears to be most relevant.
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[1066]
TÍTULO / TITLE: - Lycopene-derived bioactive retinoic acid receptors/retinoid-X receptors-activating metabolites may be relevant for lycopene’s anti-cancer potential.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Nutr Food Res. 2013 Feb 4. doi: 10.1002/mnfr.201200548.
●● Enlace al texto completo (gratuito o de pago) 1002/mnfr.201200548
AUTORES / AUTHORS: - Aydemir G; Kasiri Y; Birta E; Beke G; Garcia AL; Bartok EM; Ruhl R
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
RESUMEN / SUMMARY: - Dietary consumption of tomato products and especially the red tomato pigment lycopene has been associated with lower risk of cancer. New evidence is emerging toward metabolic pathways mediating the anti-cancer activities of lycopene. In this review, we explore associations between tomatoes and lycopene intake and cancer and relate this to the metabolic activation pathways of lycopene via carotene oxygenases and further carotenoid/retinoid-metabolizing enzymes to apo-lycopenoids. Several of these apo-lycopenoids have already been identified but up to date no direct connection between lycopene metabolism and apo-lycopenoids mediated receptor activation pathways has been established. Retinoic acid receptors/retinoid-X receptors activation pathways in particular, may be mediated via lycopene metabolites that are related to retinoic acids. Various studies have shown an association between lower concentration of insulin-like growth factor-1 upon lycopene treatment, cancer incidences, and retinoid-mediated signaling. In this review, we interrelate tomato/lycopene ingestion and cancer incidence, with metabolic activation of lycopene and retinoid-mediated signaling. The aim is to discuss a potential mechanism to explain lycopene related anti-cancer activities by modulation of insulin-like growth factor-1 concentrations via lycopene metabolite activation of retinoid-mediated signaling.
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[1067]
TÍTULO / TITLE: - Histone de-acetylase inhibitors: a promising future for cancer treatment?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Infect Agent Cancer. 2013 Mar 11;8(1):10. doi: 10.1186/1750-9378-8-10.
●● Enlace al texto completo (gratuito o de pago) 1186/1750-9378-8-10
AUTORES / AUTHORS: - Khan RS; Hameed H; Bhutta RA; Kazi AN; Riaz H
INSTITUCIÓN / INSTITUTION: - Dow Medical College, Karachi, Pakistan. abdulnafey@hotmail.com.
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[1068]
TÍTULO / TITLE: - From Na+/K+-ATpase and Cardiac Glycosides to Cytotoxicity and Cancer Treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Agents Med Chem. 2013 Mar 27.
AUTORES / AUTHORS: - Babula P; Masarik M; Adam V; Provaznik I; Kizek R
INSTITUCIÓN / INSTITUTION: - Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic. kizek@sci.muni.cz.
RESUMEN / SUMMARY: - Cardiac glycosides represent group of compounds isolated from plants and some animals. They have been using in the therapy of heart failure for many years. In spite of the fact that cytotoxic effect of many cardiac glycosides has been demonstrated. The mechanism of the cytotoxic action is very complicated and complex, where Na+/K+-ATPase plays crucial role. On the other hand, Na+/K+-ATPase is regulated by many endogenous factors including hormones or FXYD proteins, which role in the regulation of cell cycle is intensively studied. This review focuses the role of Na+/K+-ATPase in the regulation of cell growth, cell cycle and cell proliferation and involvement of cardiac glycosides in the regulation of Na+/K+-ATPase. Cytotoxic effect of cardiac glycosides is discussed in the connection with possible apoptotic mechanisms induced by these compounds. Novel strategies in cancer therapy based on the cardiac glycosides as well as possibilities in the overcoming multidrug resistance by cardiac glycosides are discussed too. The goal of this review is to present cardiac glycosides as not only pharmaceuticals used in heart failure, but also as potent cytotoxic agents with possible involvement in cancer treatment.
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[1069]
TÍTULO / TITLE: - Direct Transformation of Lung Microenvironment by Interferon-alpha Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58913. doi: 10.1371/journal.pone.0058913. Epub 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058913
AUTORES / AUTHORS: - Zhuang PY; Shen J; Zhu XD; Zhang JB; Tang ZY; Qin LX; Sun HC
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China ; Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: Interferon (IFN)-alpha is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-alpha treatment in lung metastasis are not yet clear. METHODS: The effect of IFN-alpha treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-alpha before implantation of tumor was done to explore the effect of IFN-alpha on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry. RESULTS: IFN-alpha treatment did not decrease the number of CTCs (0.075%+/-0.020% versus 0.063%+/-0.018%, P = 0.574, IFN-alpha-treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75+/-1.0 versus 28.0+/-6.3, P = 0.008; size [pixels]: 116.8+/-72.2 versus 5226.4+/-1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%+/-0.04% versus 1.36%+/-0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1+/-1.7 versus 21.9+/-0.4, P<0.000) in the lung, which was independent of the primary tumor. CONCLUSION: IFN-alpha inhibited lung metastasis by directly modulating the lung microenvironment.
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[1070]
TÍTULO / TITLE: - Cell-based small-molecule compound screen identifies fenretinide as potential therapeutic for translocation-positive rhabdomyosarcoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55072. doi: 10.1371/journal.pone.0055072. Epub 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055072
AUTORES / AUTHORS: - Herrero Martin D; Boro A; Schafer BW
INSTITUCIÓN / INSTITUTION: - Department of Oncology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland.
RESUMEN / SUMMARY: - A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ss. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma.
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[1071]
TÍTULO / TITLE: - Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1006-4
AUTORES / AUTHORS: - Sanchez-Rovira P; Segui MA; Llombart A; Aranda E; Anton A; Sanchez A; Lomas M; Jaen A; Fernandez M; Porras I; Dalmau E; Morales S; de la Haba-Rodriguez J
INSTITUCIÓN / INSTITUTION: - Servicio de Oncologia Medica, Complejo Hospitalario de Jaen, Avda. del Ejercito Español, 10, 23007, Jaen, España, oncopsr@yahoo.es.
RESUMEN / SUMMARY: - PURPOSE: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. METHODS: Patients with HER-negative operable stage II-III BC >/=2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. RESULTS: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. CONCLUSION: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.
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[1072]
TÍTULO / TITLE: - Resistance after chronic application of the HDAC-inhibitor valproic acid is associated with elevated Akt activation in renal cell carcinoma in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e53100. doi: 10.1371/journal.pone.0053100. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053100
AUTORES / AUTHORS: - Juengel E; Makarevic J; Tsaur I; Bartsch G; Nelson K; Haferkamp A; Blaheta RA
INSTITUCIÓN / INSTITUTION: - Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
RESUMEN / SUMMARY: - Targeted drugs have significantly improved the therapeutic options for advanced renal cell carcinoma (RCC). However, resistance often develops, negating the benefit of these agents. In the present study, the molecular mechanisms of acquired resistance towards the histone deacetylase (HDAC) inhibitor valproic acid (VPA) in a RCC in vivo model were investigated. NMRI:nu/nu mice were transplanted with Caki-1 RCC cells and then treated with VPA (200 mg/kg/day). Controls remained untreated. Based on tumor growth dynamics, the mice were divided into “responders” and “non-responders” to VPA. Histone H3 and H4 acetylation and expression of cell signaling and cell cycle regulating proteins in the RCC mouse tumors were evaluated by Western blotting. Tumor growth of VPA responders was significantly diminished, whereas that of VPA non-responders even exceeded control values. Cdk1, 2 and 4 proteins were strongly enhanced in the non-responders. Importantly, Akt expression and activity were massively up-regulated in the tumors of the VPA non-responders. Chronic application (12 weeks) of VPA to Caki-1 cells in vitro evoked a distinct elevation of Akt activity and cancer cells no longer responded with cell growth reduction, compared to the short 2 week treatment. We assume that chronic use of an HDAC-inhibitor is associated with (re)-activation of Akt, which may be involved in resistance development. Consequently, combined blockade of both HDAC and Akt may delay or prevent drug resistance in RCC.
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[1073]
TÍTULO / TITLE: - Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Hepatobiliary Pancreat Sci. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s00534-012-0587-6
AUTORES / AUTHORS: - Ozaki N; Ohmuraya M; Ida S; Hashimoto D; Ikuta Y; Chikamoto A; Hirota M; Baba H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Serine protease inhibitor Kazal type 1 (SPINK1) is expressed in normal human pancreatic acinar cells and in a variety of tumors, and binds to the epidermal growth factor receptor (EGFR), mediating cell proliferation through the mitogen-activated protein kinase cascade in pancreatic cancer cell lines. Here, we aimed to assess SPINK1 and EGFR expression in various neoplastic lesions, including tissues demonstrating precancerous changes. METHODS: Surgical specimens of pancreatic ductal adenocarcinoma (n = 23), intraductal papillary mucinous neoplasm (IPMN; n = 21), pancreatic neoplasms other than ductal adenocarcinoma (n = 8), chronic pancreatitis (n = 11), and pancreatic intraepithelial neoplasia (PanIN) lesions within the resected specimens were analyzed immunohistochemically for SPINK1 and EGFR expression. RESULTS: Sixty-five PanIN-1A, 32 PanIN-1B, 17 PanIN-2, and 6 PanIN-3 were identified. Both SPINK1 and EGFR were expressed in almost all PanIN lesions. All tubular ductal adenocarcinoma, IPMN, and mucinous cystadenocarcinoma samples (neoplasms of ductal origin) expressed SPINK1, whereas acinar cell carcinoma, anaplastic carcinoma, adenosquamous carcinoma, insulinoma, and islet cell carcinoma did not. EGFR was expressed in 87 % of tubular adenocarcinoma and 48 % of IPMN lesions. Among IPMN lesions, malignant lesions (IPMC) expressed EGFR more often than benign lesions (IPMA) did. Scattered expression of EGFR was observed in normal pancreatic ducts and within the tubular complex within chronic pancreatitis lesions. CONCLUSIONS: These results indicate that SPINK1 plays a role as a growth factor, signaling through the EGFR pathway in pancreatic ductal adenocarcinoma and neoplasms, and that the EGFR is involved in the malignant transformation of IPMN.
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[1074]
TÍTULO / TITLE: - Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Zhejiang Univ Sci B. 2013 Mar;14(3):207-15. doi: 10.1631/jzus.B1200101.
●● Enlace al texto completo (gratuito o de pago) 1631/jzus.B1200101
AUTORES / AUTHORS: - Hong W; Wang K; Zhang YP; Kou JY; Hong D; Su D; Mao WM; Yu XM; Xie FJ; Wang XJ
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China; Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou 310022, China; Department of Respiratory Medicine, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, China; Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
RESUMEN / SUMMARY: - Objective: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. Results: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.
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[1075]
TÍTULO / TITLE: - Marine-derived angiogenesis inhibitors for cancer therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mar Drugs. 2013 Mar 15;11(3):903-33. doi: 10.3390/md11030903.
●● Enlace al texto completo (gratuito o de pago) 3390/md11030903
AUTORES / AUTHORS: - Wang YQ; Miao ZH
INSTITUCIÓN / INSTITUTION: - Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China. zhmiao@simm.ac.cn.
RESUMEN / SUMMARY: - Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.
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[1076]
TÍTULO / TITLE: - Dual Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor NVP-BEZ235 Has a Therapeutic Potential and Sensitizes Cisplatin in Nasopharyngeal Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59879. doi: 10.1371/journal.pone.0059879. Epub 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059879
AUTORES / AUTHORS: - Yang F; Qian XJ; Qin W; Deng R; Wu XQ; Qin J; Feng GK; Zhu XF
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, China ; Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
RESUMEN / SUMMARY: - Phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin inhibitor (mTOR) pathway is often constitutively activated in human tumor cells and thus has been considered as a promising drug target. To ascertain a therapeutical approach of nasopharyngeal carcinoma (NPC), we hypothesized NVP-BEZ235, a novel and potent imidazo[4,5-c] quinolone derivative, that dually inhibits both PI3K and mTOR kinases activities, had antitumor activity in NPC. Expectedly, we found that NVP-BEZ235 selectively inhibited proliferation of NPC cells rather than normal nasopharyngeal cells using MTT assay. In NPC cell lines, with the extended exposure, NVP-BEZ235 selectively inhibited proliferation of NPC cells harboring PIK3CA mutation, compared to cells with wild-type PIK3CA. Furthermore, exposure of NPC cells to NVP-BEZ235 resulted in G1 growth arrest by Propidium iodide uptake assay, reduction of cyclin D1and CDK4, and increased levels of P27 and P21 by Western blotting, but negligible apoptosis. Moreover, we found that cisplatin (CDDP) activated PI3K/AKT and mTORC1 pathways and NVP-BEZ235 alleviated the activation by CDDP through dually targeting PI3K and mTOR kinases. Also, NVP-BEZ235 combining with CDDP synergistically inhibited proliferation and induced apoptosis in NPC cells. In CNE2 and HONE1 nude mice xenograft models, orally NVP-BEZ235 efficiently attenuated tumor growth with no obvious toxicity. In combination with NVP-BEZ235 and CDDP, there was dramatic synergy in shrinking tumor volumes and inducing apoptosis through increasing Noxa, Bax and decreasing Mcl-1, Bcl-2. Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential as a monotherapy or in combination with CDDP for NPC treatment.
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[1077]
TÍTULO / TITLE: - High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):473-478. Epub 2012 Nov 16.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1032
AUTORES / AUTHORS: - Wei C; Wu S; Li X; Wang Y; Ren R; Lai Y; Ye J
INSTITUCIÓN / INSTITUTION: - Medical Department, The University of Hong Kong-Shenzhen Hospital;
RESUMEN / SUMMARY: - FER tyrosine kinase (FER) has been demonstrated to play a critical role in tumorigenesis and metastasis; however, its potential value as a novel prognostic marker for clear cell renal cell carcinoma (ccRCC) remains unclear. In 48 paired samples of ccRCCs and normal adjacent tissues (ADTs), real-time PCR was used to evaluate the expression of FER mRNA. The expression of FER protein was assessed in 87 ADTs and 206 samples of ccRCC using immunohistochemical methods. Statistical analysis was used to examine the correlations between the expression levels of FER and the clinical characteristics of ccRCC patients. A significant difference was identified between ccRCC tissues and ADTs in the mRNA levels of FER. Immunohistochemistry analyses revealed higher expression of FER protein in 87 ccRCC samples compared to the paired ADTs. In addition, FER protein expression in 206 ccRCC samples was significantly correlated with tumor size, T stage, N classification, metastasis, recurrence and Fuhrman grade, while associations with age and gender were not identifed. The Kaplan-Meier survival analysis showed that patients with high FER levels had a poorer survival outcome compared with those with lower levels. The log-rank test demonstrated that the cumulative survival rates were significantly different between the two groups. The Cox regression analysis indicated that FER expression, N stage and distant metastasis were independent prognostic factors for overall survival of ccRCC patients. Our results indicate that overexpression of FER in tumor tissues predicts a poor prognosis of patients with ccRCC, and FER may serve as a novel prognostic marker for ccRCC.
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[1078]
TÍTULO / TITLE: - Supplementation of fibrinogen concentrate in children with severe acquired hypofibrinogenaemia during chemotherapy for acute lymphoblastic leukaemia: our experience.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Blood Transfus. 2013 Mar 5:1-2. doi: 10.2450/2013.0228-12.
●● Enlace al texto completo (gratuito o de pago) 2450/2013.0228-12
AUTORES / AUTHORS: - Giordano P; Luciani M; Grassi M; De Leonardis F; Coletti V; Santoro N
INSTITUCIÓN / INSTITUTION: - Division of Paediatric Haematology-Oncology, University of Bari, Bari.
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[1079]
TÍTULO / TITLE: - Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57724. doi: 10.1371/journal.pone.0057724. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057724
AUTORES / AUTHORS: - Yamashita Y; Akatsuka S; Shinjo K; Yatabe Y; Kobayashi H; Seko H; Kajiyama H; Kikkawa F; Takahashi T; Toyokuni S
INSTITUCIÓN / INSTITUTION: - Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan ; Department of Pathology, Nagoya City University Hospital, Nagoya, Aichi, Japan.
RESUMEN / SUMMARY: - Clear cell adenocarcinoma of the ovary (OCC) is a chemo-resistant tumor with a relatively poor prognosis and is frequently associated with endometriosis. Although it is assumed that oxidative stress plays some role in the malignant transformation of this tumor, the characteristic molecular events leading to carcinogenesis remain unknown. In this study, an array-based comparative genomic hybridization (CGH) analysis revealed Met gene amplification in 4/13 OCC primary tumors and 2/8 OCC cell lines. Amplification of the AKT2 gene, which is a downstream component of the Met/PI3K signaling pathway, was also observed in 5/21 samples by array-based CGH analysis. In one patient, both the Met and AKT2 genes were amplified. These findings were confirmed using fluorescence in situ hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemistry. In total, 73 OCC cases were evaluated using real-time quantitative PCR; 37.0% demonstrated Met gene amplification (>4 copies), and 8.2% had AKT2 amplification. Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse survival than patients without Met gene amplification (p<0.05). Met knockdown by shRNA resulted in reduced viability of OCC cells with Met amplification due to increased apoptosis and cellular senescence, suggesting that the Met signaling pathway plays an important role in OCC carcinogenesis. Thus, we believe that targeted inhibition of the Met pathway may be a promising treatment for OCC.
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[1080]
TÍTULO / TITLE: - High MET gene copy number predicted poor prognosis in primary intestinal diffuse large B-cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Feb 4;8:16. doi: 10.1186/1746-1596-8-16.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-16
AUTORES / AUTHORS: - Huang WT; Chuang SS
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Chi-Mei Medical Center, Tainan, Taipei Medical University and National Taiwan University Hospital, Taipei, Taiwan. cmh5301@mail.chimei.org.tw.
RESUMEN / SUMMARY: - BACKGROUND: MET is a proto-oncogene with its copy number (CN) alterations been reported in some cancers, but not in primary intestinal diffuse large B-cell lymphoma (PI-DLBL) yet. METHODS: In this retrospective study, we performed histology and chart reviews, immunohistochemistry and quantitative polymerase chain reaction for MET CN alterations on 28 surgically resected PI-DLBLs. RESULTS: There were 12 men and 16 women with a median age of 70 and a mean follow-up of 32 months. The median MET CN was 2.20 (range, 1.04 to 3.35). CN gain was observed in 11 cases, including 5 with CN greater than 3. Nine patients (32%) had diploid CN and eight (29%) with CN loss. Patients with gain or diploid CN showed significantly worse prognosis (P = 0.046) than those with CN loss. Furthermore, MET CN greater than 3 was associated with an adverse outcome (P = 0.003). Intestinal perforation at presentation was the sole clinicopathological factor associated with a poor prognosis (P = 0.004) and perforation was correlated with CN greater than 3 (P = 0.002). CONCLUSIONS: Our finding of MET CN gain as a poor prognostic factor in PI-DLBL patients might serve as the rationale for targeting MET signaling pathway in the treatment of these patients.
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[1081]
TÍTULO / TITLE: - Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55934. doi: 10.1371/journal.pone.0055934. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055934
AUTORES / AUTHORS: - Yu J; Peng Y; Wu LC; Xie Z; Deng Y; Hughes T; He S; Mo X; Chiu M; Wang QE; He X; Liu S; Grever MR; Chan KK; Liu Z
INSTITUCIÓN / INSTITUTION: - Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America ; Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
RESUMEN / SUMMARY: - Bioactive components from dietary supplements such as curcumin may represent attractive agents for cancer prevention or treatment. DNA methylation plays a critical role in acute myeloid leukemia (AML) development, and presents an excellent target for treatment of this disease. However, it remains largely unknown how curcumin, a component of the popular Indian spice turmeric, plays a role in DNA hypomethylation to reactivate silenced tumor suppressor genes and to present a potential treatment option for AML. Here we show that curcumin down-regulates DNMT1 expression in AML cell lines, both in vitro and in vivo, and in primary AML cells ex vivo. Mechanistically, curcumin reduced the expression of positive regulators of DNMT1, p65 and Sp1, which correlated with a reduction in binding of these transcription factors to the DNMT1 promoter in AML cell lines. This curcumin-mediated down-regulation of DNMT1 expression was concomitant with p15(INK4B) tumor suppressor gene reactivation, hypomethylation of the p15(INK4B) promoter, G1 cell cycle arrest, and induction of tumor cell apoptosis in vitro. In mice implanted with the human AML MV4-11 cell line, administration of curcumin resulted in remarkable suppression of AML tumor growth. Collectively, our data indicate that curcumin shows promise as a potential treatment for AML, and our findings provide a basis for future studies to test the clinical efficacy of curcumin - whether used as a single agent or as an adjuvant - for AML treatment.
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[1082]
TÍTULO / TITLE: - Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioanalysis. 2013 Feb;5(3):369-91. doi: 10.4155/bio.12.325.
●● Enlace al texto completo (gratuito o de pago) 4155/bio.12.325
AUTORES / AUTHORS: - Cimino GD; Pan CX; Henderson PT
INSTITUCIÓN / INSTITUTION: - Accelerated Medical Diagnostics, Inc., 2121 Second Street, B101, Davis, CA 95618, USA.
RESUMEN / SUMMARY: - The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum-DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications.
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[1083]
TÍTULO / TITLE: - NADPH oxidase biology and the regulation of tyrosine kinase receptor signaling and cancer drug cytotoxicity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Feb 7;14(2):3683-704. doi: 10.3390/ijms14023683.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14023683
AUTORES / AUTHORS: - Paletta-Silva R; Rocco-Machado N; Meyer-Fernandes JR
INSTITUCIÓN / INSTITUTION: - Clinical Research Coordination, Nacional Institute of Cancer (INCA), Andre Cavalcanti Street, 37, Rio de Janeiro, RJ 20231-050, Brazil. rafael.paletta@hotmail.com.
RESUMEN / SUMMARY: - The outdated idea that reactive oxygen species (ROS) are only dangerous products of cellular metabolism, causing toxic and mutagenic effects on cellular components, is being replaced by the view that ROS have several important functions in cell signaling. In aerobic organisms, ROS can be generated from different sources, including the mitochondrial electron transport chain, xanthine oxidase, myeloperoxidase, and lipoxygenase, but the only enzyme family that produces ROS as its main product is the NADPH oxidase family (NOX enzymes). These transfer electrons from NADPH (converting it to NADP-) to oxygen to make O(2)*-. Due to their stability, the products of NADPH oxidase, hydrogen peroxide, and superoxide are considered the most favorable ROS to act as signaling molecules. Transcription factors that regulate gene expression involved in carcinogenesis are modulated by NADPH oxidase, and it has emerged as a promising target for cancer therapies. The present review discusses the mechanisms by which NADPH oxidase regulates signal transduction pathways in view of tyrosine kinase receptors, which are pivotal to regulating the hallmarks of cancer, and how ROS mediate the cytotoxicity of several cancer drugs employed in clinical practice.
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[1084]
TÍTULO / TITLE: - Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in lung cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Compr Canc Netw. 2013 Feb 1;11(2):161-9.
AUTORES / AUTHORS: - Yu HA; Riely GJ
INSTITUCIÓN / INSTITUTION: - Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
RESUMEN / SUMMARY: - EGFR mutations identify patients who are more likely to respond to treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) than cytotoxic chemotherapy. The distinct success of the first-generation EGFR TKIs erlotinib and gefitinib has been accompanied by the observation that acquired resistance to these treatments develops after a median of 1 year of treatment. Newer, second-generation EGFR TKIs have been developed with the intent to delay or overcome acquired resistance by the broader inhibition of kinases (eg, HER2 and vascular endothelial growth factor receptor) and/or altering the interactions with EGFR through irreversibly binding to the kinase domain. This article discusses many of these agents (including afatinib, dacomitinib, XL647, AP26113, and CO-1686) which have the potential for greater efficacy compared with first-generation EGFR TKIs, and may also have clinical activity against other oncogenic mutations within the EGFR family, including HER2.
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[1085]
TÍTULO / TITLE: - Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56234. doi: 10.1371/journal.pone.0056234. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056234
AUTORES / AUTHORS: - Reiner T; Parrondo R; de Las Pozas A; Palenzuela D; Perez-Stable C
INSTITUCIÓN / INSTITUTION: - Geriatric Research, Education, and Clinical Center and Research Service, Bruce W. Carter Veterans Affairs Medical Center, Miami, Florida, United States of America.
RESUMEN / SUMMARY: - Inhibition of the ubiquitin-proteasome system (UPS) of protein degradation is a valid anti-cancer strategy and has led to the approval of bortezomib for the treatment of multiple myeloma. However, the alternative approach of enhancing the degradation of oncoproteins that are frequently overexpressed in cancers is less developed. Betulinic acid (BA) is a plant-derived small molecule that can increase apoptosis specifically in cancer but not in normal cells, making it an attractive anti-cancer agent. Our results in prostate cancer suggested that BA inhibited multiple deubiquitinases (DUBs), which resulted in the accumulation of poly-ubiquitinated proteins, decreased levels of oncoproteins, and increased apoptotic cell death. In normal fibroblasts, however, BA did not inhibit DUB activity nor increased total poly-ubiquitinated proteins, which was associated with a lack of effect on cell death. In the TRAMP transgenic mouse model of prostate cancer, treatment with BA (10 mg/kg) inhibited primary tumors, increased apoptosis, decreased angiogenesis and proliferation, and lowered androgen receptor and cyclin D1 protein. BA treatment also inhibited DUB activity and increased ubiquitinated proteins in TRAMP prostate cancer but had no effect on apoptosis or ubiquitination in normal mouse tissues. Overall, our data suggests that BA-mediated inhibition of DUBs and induction of apoptotic cell death specifically in prostate cancer but not in normal cells and tissues may provide an effective non-toxic and clinically selective agent for chemotherapy.
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[1086]
TÍTULO / TITLE: - Pancreatic cancer and predictors of survival: comparing the CA 19-9/bilirubin ratio with the McGill Brisbane Symptom Score.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 22. doi: 10.1111/hpb.12085.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12085
AUTORES / AUTHORS: - Dumitra S; Jamal MH; Aboukhalil J; Doi SA; Chaudhury P; Hassanain M; Metrakos PP; Barkun JS
INSTITUCIÓN / INSTITUTION: - Department of Surgery, McGill University Health Center, Montreal, QC, Canada.
RESUMEN / SUMMARY: - INTRODUCTION: Few tools predict survival from pancreatic cancer (PAC). The McGill Brisbane Symptom Score (MBSS) based on symptoms at presentation (weight loss, pain, jaundice and smoking) was recently validated. The present study compares the ability of four strategies to predict 9-month survival: MBSS, carbohydrate antigen 19-9 (CA 19-9) alone, CA19-9-to-bilirubin ratio and a combination of MBSS and the CA19-9-to-bilirubin ratio. METHODOLOGY: A retrospective review of 133 patients diagnosed with PAC between 2005 and 2011 was performed. Survival was determined from the Quebec civil registry. Blood CA 19-9 and bilirubin values were collected (n = 52) at the time of diagnosis. Receiver-operating characteristic (ROC) curves were used to determine a cutoff for optimal test characteristics of CA 19-9 and CA19-9-to-total bilirubin ratio in predicting survival at 9 months. Predictive characteristics were then calculated for the four strategies. RESULTS: Of the four strategies, the one with the greatest negative predictive value was the MBSS: negative predictive value (NPV) was 90.2% (76.9-97.3%) and the positive likelihood ratio (LR) was the greatest. The ability of CA 19-9 levels alone, at baseline, to predict survival was low. For the CA19-9-to-bilirubin ratio, the test characteristics improved but remained non-significant. The best performing strategy according to likelihood ratios was the combined MBSS and CA19-9 to the bilirubin ratio. CONCLUSION: CA19-9 levels and the CA19-9-to-bilirubin ratio are poor predictors of survival for PAC, whereas the MBSS is a far better predictor, confirming its clinical value. By adding the CA19-9-to-bilirubin ratio to the MBSS the predictive characteristics improved.
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[1087]
TÍTULO / TITLE: - 5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Molecules. 2013 Mar 4;18(3):2924-33. doi: 10.3390/molecules18032924.
●● Enlace al texto completo (gratuito o de pago) 3390/molecules18032924
AUTORES / AUTHORS: - Huang KJ; Chen YC; El-Shazly M; Du YC; Su JH; Tsao CW; Yen WH; Chang WB; Su YD; Yeh YT; Lu MC
INSTITUCIÓN / INSTITUTION: - Department of Life Science, National Dong Hwa University, Hualien, 974, Taiwan. jinx6609@nmmba.gov.tw.
RESUMEN / SUMMARY: - 5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) apoptotic assay, indicated that the HL 60 cell line is the most sensitive one towards 5EPA. This diterpenoid led to caspases -3, -8, and -9 activation as well as PARP cleavage. It also induced ROS generation, calcium accumulation and disruption of mitochondrial membrane potential. Additionally, the expression levels of Hsp90 protein and several client proteins were downregulated in response to 5EPA treatment. These results suggest that 5EPA’s cytotoxic effect on HL 60 cells may be attributed to the inhibition of Hsp90 as well as the induction of mitochondrial stress which finally results in apoptotic cell death.
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[1088]
TÍTULO / TITLE: - Anti-Proliferative Activities and Apoptosis Induction by Triterpenes Derived from Eriobotrya japonica in Human Leukemia Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Feb 18;14(2):4106-20. doi: 10.3390/ijms14024106.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14024106
AUTORES / AUTHORS: - Uto T; Sakamoto A; Tung NH; Fujiki T; Kishihara K; Oiso S; Kariyazono H; Morinaga O; Shoyama Y
INSTITUCIÓN / INSTITUTION: - Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan. shoyama@niu.ac.jp.
RESUMEN / SUMMARY: - Eriobotrya japonica leaf is a traditional herbal medicine that contains numerous triterpenes, which have various pharmacological properties. In this study, we investigated the anti-proliferative activity of four triterpenes derived from E. japonica, including corosolic acid (CA), ursolic acid (UA), maslinic acid (MA) and oleanolic acid (OA), in human leukemia cell lines. CA showed the strongest anti-proliferative activity in all of the leukemia cell lines tested, but not in normal human skin fibroblast cell lines. To determine the mechanism underlying the anti-proliferative effect of CA, we examined the effect of CA on molecular events known as apoptosis induction. CA induced chromatin condensation, DNA fragmentation, sub-G(1) phase DNA, activation of caspase-3, -8 and -9 and the cleavage of PARP in HL-60. CA also activated Bid and Bax, leading to the loss of mitochondrial membrane potential (psi(m)) and cytochrome c release into the cytosol, whereas Bcl-2 and Bcl-xL were unaffected by CA. These results suggest that CA has an anti-proliferative effect on leukemia cells via the induction of apoptosis mediated by mitochondrial dysfunction and caspase activation. CA may be a potential chemotherapeutic agent for the treatment of human leukemia.
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[1089]
TÍTULO / TITLE: - The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Jan 31;13:42. doi: 10.1186/1471-2407-13-42.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-42
AUTORES / AUTHORS: - Zhang J; Jia Z; Ragaz J; Zhang YJ; Zhou M; Zhang YP; Li G; Wang BY; Wang ZH; Hu XC
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Department of Oncology, Fudan University Shanghai Cancer Center; Shanghai Medical College, Fudan University, Shanghai, China. huxicun@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. METHODS: 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. RESULTS: In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. CONCLUSIONS: SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype.
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[1090]
TÍTULO / TITLE: - Decreased expression of transcription elongation factor A-like 7 is associated with gastric adenocarcinoma prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54671. doi: 10.1371/journal.pone.0054671. Epub 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054671
AUTORES / AUTHORS: - Huang CY; Chen YM; Zhao JJ; Chen YB; Jiang SS; Yan SM; Zhao BW; Pan K; Wang DD; Lv L; Li YF; Wang W; Zhou ZW; Xia JC
INSTITUCIÓN / INSTITUTION: - Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: We sought to investigate the expression levels and prognosis value of TCEAL7 in primary gastric cancer. METHODS AND RESULTS: We investigated TCEAL7 and other homologous five members of the TCEAL family expression in normal gastricepithelial cell line and gastric cancer cell lines using real-time quantitative PCR. Furthermore, we examined the expression of TCEAL7 in 39 paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative PCR and western blotting. Moreover, we analyzed TCEAL7 expression in 406 gastric cancer patients using immunohistochemistry. The relationships between the TCEAL7 expression levels, the clinicopathological factors, and patient survival were investigated. RT- qPCR data showed that mRNA expression level of TCEAL7 was significantly lower in the gastric cancer cell lines comparing with the levels of other five members of the TCEAL family. Results also revealed decreased TCEAL7 mRNA (P = 0.025) and protein (P = 0.012) expression in tumor tissue samples compared with matched adjacent non-tumor tissue samples. Immunohistochemical staining data showed that TCEAL7 expression was significantly decreased in 43.3% of gastric adenocarcinoma cases. The result also showed that the low TCEAL7 expression was significantly correlated with female, larger tumor size, higher histological grade and worse nodal status. Kaplan-Meier survival curves revealed that the reduced expression of TCEAL7 was associated with a poor prognosis in gastric adenocarcinoma patients (P<0.001). Based on a univariate analysis that included all 406 patients, TCEAL7 expression was found to have statistically significant associations with overall survival (P<0.001). Multivariate analysis also demonstrated that TCEAL7 expression (P = 0.009), age, tumor size, histological grade, lymphovascular invasion, T stage, N stage and M stage were independent risk factors in the prognosis of gastric cancer patients. CONCLUSIONS: Our study suggests that TCEAL7 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.
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[1091]
TÍTULO / TITLE: - Apoptotic and inflammatory signaling via Fas and tumor necrosis factor receptor I contribute to the development of chest trauma-induced septic acute lung injury.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Trauma Acute Care Surg. 2013 Mar;74(3):792-800. doi: 10.1097/TA.0b013e31827a3655.
●● Enlace al texto completo (gratuito o de pago) 1097/TA.0b013e31827a3655
AUTORES / AUTHORS: - Weckbach S; Hohmann C; Denk S; Kellermann P; Huber-Lang MS; Baumann B; Wirth T; Gebhard F; Bachem M; Perl M
INSTITUCIÓN / INSTITUTION: - Department of Trauma, University of Ulm, Ulm, Germany.
RESUMEN / SUMMARY: - BACKGROUND: Direct acute lung injury (ALI) is still associated with a high mortality, whereas the underlying pathomechanisms are not yet fully understood. In this regard, epithelial cell death in the lungs has been attributed an important role in the pathogenesis of this clinical entity. Based on this background here, we hypothesized that signaling through Fas and tumor necrosis factor receptor 1 (TNFR-1) is involved in mediating apoptosis and inflammation in chest trauma induced septic ALI. METHODS: Male C57BL/6 mice (wild-type [WT]), male mutant mice expressing nonfunctional Fas receptor (B6.MRL-Faslpr/J [lpr]) (lpr) and male TNFR-1-deficient mice (TNFR-1(-/-)) were subjected to a model of direct ALI consisting of blunt chest trauma followed by cecal ligation and puncture.Cytokine/chemokine concentrations of plasma, bronchoalveolar lavage (BAL) fluids, and lung tissue were investigated as well as BAL protein and lung myeloperoxidase. Lung histology was assessed; lung caspase 3, TUNEL-positive cells, and apoptotic polymorphonuclear neutrophil were measured, followed by a survival study. RESULTS: Cytokine/chemokine levels in plasma, BAL, and lung tissue were markedly increased in WT animals following ALI, whereas lpr and TNFR-1((-/-) showed significantly decreased levels. BAL protein levels were substantially elevated following ALI, but lpr animals presented markedly diminished protein levels compared with WT and TNFR-1(-/-) animals. Lung myeloperoxidase level was only increased 12 hours after ALI in WT animals, whereas lung myeloperoxidase levels in lpr and TNFR-1(-/-) animals were not increased compared with sham. Lung histology revealed beneficial effects in lpr and TNFR-1(-/-). Lung active caspase 3 after ALI was substantially decreased in lpr and TNFR-1(-/-) mice compared with WT. Interestingly, an early but not persisting survival benefit was observed in lpr and TNFR-1 animals(-/-). CONCLUSION: Pathomechanistically, Fas and TNFR-1 signaling contributed to the apoptotic and inflammatory response in a clinically relevant double-hit model of trauma-induced septic ALI. Moreover, this was associated with a temporary survival benefit.
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[1092]
TÍTULO / TITLE: - Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in human acute myeloid leukemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:547430. doi: 10.1155/2013/547430. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/547430
AUTORES / AUTHORS: - Su YC; Li SC; Wu YC; Wang LM; Chao KS; Liao HF
INSTITUCIÓN / INSTITUTION: - Department of Medicine, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan ; Division of Hematology and Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi 62247, Taiwan.
RESUMEN / SUMMARY: - IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1 beta in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted.
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[1093]
TÍTULO / TITLE: - Knockdown of autophagy-related gene BECLIN1 promotes cell growth and inhibits apoptosis in the A549 human lung cancer cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 19. doi: 10.3892/mmr.2013.1379.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1379
AUTORES / AUTHORS: - Wang W; Fan H; Zhou Y; Duan P; Zhao G; Wu G
INSTITUCIÓN / INSTITUTION: - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China.
RESUMEN / SUMMARY: - The expression of BECLIN1 is significantly reduced in nonsmall cell lung cancer (NSCLC) compared with noncancerous tissue. However, the role of BECLIN1 in lung cancer is unclear. Using the RNA interference (RNAi) technique the present study investigated the effect of the knockdown of BECLIN1 on the cell growth and proliferation of the A549 human lung cancer cell line. The target site for the RNAi technique was designed and the lentivirus vector for the small interfering (si)RNA expression was constructed according to the encoding sequence of the mRNA for BECLIN1. The A549 cells were transfected with the siRNA virus against BECLIN1. BECLIN1 expression was detected by reverse transcription (RT)PCR and western blot analysis. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was applied to detect cell growth. Flow cytometry was used to determine cell apoptosis. The activity of caspase3 and caspase9 was also detected in the A549 cells with BECLIN1 knockdown. The results showed that siRNA virus transfection significantly decreased the mRNA and protein expression of BECLIN1 in the transfected A549 cells. The knockdown of BECLIN1 promoted cell growth and decreased apoptosis. Caspase3 and 9 activity in the A549 cells with BECLIN1 knockdown was significantly reduced. In conclusion, the siRNA expression vector effectively inhibited the expression of BECLIN1 in the A549 human lung cancer cell line and promote the growth and proliferation of the A549 cells.
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[1094]
TÍTULO / TITLE: - Activation of apoptosis in hepatocellular carcinoma by the Chinese traditional medicine Hu Qisan.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Mar;5(3):695-700. Epub 2012 Dec 18.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.862
AUTORES / AUTHORS: - Zeng X; Li X; Xue X; Shi ZM; Feng P; Wang P; Wang XJ
INSTITUCIÓN / INSTITUTION: - Pathophysiological Department, Capital Medical University, Beijing 100069;
RESUMEN / SUMMARY: - To investigate the effects of Hu Qisan (HQS) on apoptosis in diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC), a Solt-Farber two-step test model of precancerous liver lesions was established in rats using a previously described method. HQS (4 and 8 g/kg body weight/day) was administered for 4 weeks, after the majority of the liver was removed. HepG2 cells were used to detect the HtrA serine peptidase 2 (HtrA2/Omi) release from mitochondria and caspase-3 activation promoted by HQS. Exposure of the rats to DEN for 6 weeks induced hepatic carcinogenesis. HQS (4 and 8 g/kg body weight/day) markedly induced cell apoptosis. The protective effects against hepatic carcinogenesis were mediated by multiple mechanisms, including the reduction of DEN-induced gamma-GT-positive cell proliferation, mitochondrial morphological changes, HtrA2/Omi release from mitochondria and the activation of caspase-3. In conclusion, HQS is a potential anti-carcinogenic agent that may induce apoptosis by reducing the inhibitory effects of X-linked inhibitor of apoptosis protein (XIAP) on caspase-3. Thus, HQS should be further explored as a potentially promising new therapeutic agent against human hepatic cancer.
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[1095]
TÍTULO / TITLE: - High Expression of Lewis y Antigen and CD44 Is Correlated with Resistance to Chemotherapy in Epithelial Ovarian Cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57250. doi: 10.1371/journal.pone.0057250. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057250
AUTORES / AUTHORS: - Hu Z; Gao J; Zhang D; Liu Q; Yan L; Gao L; Liu J; Liu D; Zhang S; Lin B
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning Province, China.
RESUMEN / SUMMARY: - OBJECTIVES: To measure Lewis y antigen and CD44 antigen expression in epithelial ovarian carcinoma and to correlate the levels of these antigens with clinical response to chemotherapy. METHODS: The study cases included 34 cases of ovarian carcinoma with resistance to chemotherapeutic drugs, 6 partially drug-sensitive cases, and 52 drug-sensitive cases (92 total). RESULTS: The rates of expression of Lewis y antigen and CD44 antigen were significantly greater in the drug-resistant group than that in the partially-sensitive or sensitive groups. Surgical stage, residual tumor size and expression of CD44 and Lewis y antigen in ovarian carcinoma tissues were independent risk factors for chemotherapeutic drug resistance. CONCLUSIONS: Over-expression of Lewis y and CD44 antigen are strong risk factors for chemotherapeutic drug resistance in ovarian carcinoma patients.
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[1096]
TÍTULO / TITLE: - Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet J. 2013 Feb 4. pii: S1090-0233(12)00522-9. doi: 10.1016/j.tvjl.2012.11.018.
●● Enlace al texto completo (gratuito o de pago) 1016/j.tvjl.2012.11.018
AUTORES / AUTHORS: - Takeuchi Y; Fujino Y; Watanabe M; Takahashi M; Nakagawa T; Takeuchi A; Bonkobara M; Kobayashi T; Ohno K; Uchida K; Asano K; Nishimura R; Nakayama H; Sugano S; Ohashi Y; Tsujimoto H
INSTITUCIÓN / INSTITUTION: - Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
RESUMEN / SUMMARY: - The objective of this retrospective cohort study was to validate the prognostic value of histological grading of canine cutaneous mast cell tumours (MCTs) according to the Patnaik (grades I-III) and Kiupel (low, high) grading systems, and to confirm the prognostic significance of internal tandem duplications (ITDs) within exon 11 of the c-kit gene (ITD-Exon11). The baseline characteristics and outcome data from 47 dogs diagnosed with cutaneous MCTs were collected and reviewed. Tumours were graded according to both grading systems and the nucleotide sequence of c-kit was evaluated. Results were analyzed to evaluate predictive factors for overall survival (OS) and progression-free survival (PFS). Log-rank tests indicated that dogs with Patnaik grade III MCTs had significantly reduced OS and PFS compared to those with either grade I or II tumours. However, no significant difference in OS or PFS was observed between grade I and II tumours. The dogs with Kiupel high-grade MCTs had significantly shorter OS and PFS than dogs with low-grade MCTs. The presence of ITD-Exon11 was significantly associated with shorter PFS. The result of Cox regression analysis showed that the Kiupel grading system for OS and PFS, and lymph node metastasis for OS, independently predicted prognosis. Kappa statistics confirmed a significantly higher inter-observer consistency for the Kiupel compared to the Patnaik grading system. These findings demonstrate that the Kiupel grading system is a useful prognostic tool for canine cutaneous MCTs in predicting OS and PFS, while the occurrence of ITD-Exon11 appeared to be a useful predictor for PFS.
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[1097]
TÍTULO / TITLE: - Proteomic Analysis of Two Metabolic Proteins with Potential to Translocate to Plasma Membrane Associated with Tumor Metastasis Development and Drug Targets.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Proteome Res. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1021/pr301100r
AUTORES / AUTHORS: - Xue T; Zhang Y; Zhang L; Yao L; Hu X; Xu LX
INSTITUCIÓN / INSTITUTION: - School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University , Shanghai, China.
RESUMEN / SUMMARY: - Metastasis is the main cause for death of breast cancer patients. However, the underlying mechanism is still poorly understood. Plasma membrane (PM) proteins play a key role in various biological processes, especially for cell migration. In this study, we used a set of well-characterized mammary mouse cell lines, 67NR, 168FARN, 4T1, representing the metastatic progression, to study the differentially expressed membrane proteins. These proteins were analyzed by a linear ion trap tandem mass spectrometry (LTQ-MS/MS) following cell surface biotinylation and streptavidin purification. A total of 1667 membrane proteins were identified, out of which 472 were characterized as differentially expressed with at least 2-fold change and p-value < 0.01. Functional clustering of the 472 proteins revealed that 178 of them were metabolic proteins. Finally, we focused on two metabolic proteins, fatty acid synthase (FASN) and NAD(P)H steroid dehydrogenase-like protein (NSDHL), which were validated by Western blot and immunofluorescence. We found that FASN and NSDHL translocated to the plasma membrane from the intracellular compartment, and their expressions increased from 67NR to 4T1. This alteration of localization along with differential expressions might be necessary for metastasis development. Potentially, FASN and NSDHL could serve as drug targets in new antimetastasis therapy.
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[1098]
TÍTULO / TITLE: - Pre-treatment levels of C-reactive protein and squamous cell carcinoma antigen for predicting the aggressiveness of pharyngolaryngeal carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55327. doi: 10.1371/journal.pone.0055327. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055327
AUTORES / AUTHORS: - Chen HH; Wang HM; Fan KH; Lin CY; Yen TC; Liao CT; Chen IH; Kang CJ; Huang SF
INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China.
RESUMEN / SUMMARY: - The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level >/=2.0 ng/ml and a CRP level >/=5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (>/=8.6 mg/L) and lymph nodes (>/=5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC.
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[1099]
TÍTULO / TITLE: - A pilot study to investigate the role of thymidylate synthase as a marker of prognosis for neoadjuvant chemotherapy in gastric and gastro-oesophageal junction adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastroenterol Res Pract. 2013;2013:502153. doi: 10.1155/2013/502153. Epub 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/502153
AUTORES / AUTHORS: - Mirza A; Brown M; McNulty C; Valentine J; Annesley A; Galloway S; Welch I; West CM; Pritchard S
INSTITUCIÓN / INSTITUTION: - Departments of Gastrointestinal Surgery and Histopathology, University Hospital of South Manchester, Manchester M23 9LT, UK.
RESUMEN / SUMMARY: - Aims and Background. Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy. Our aim was to study the expression of thymidylate synthase (TS) enzyme in pre-treatment diagnostic biopsy specimens and investigate its clinical usefulness. Methods. A single-centre study was carried out in 45 patients with gastric and GOJ adenocarcinoma treated with neo-adjuvant chemotherapy according to the MAGIC protocol. TS expression was determined using immunohistochemistry. >10% tumour nuclei expression of TS was used as cut-off for positivity. Results. Forty-one (91%) of the 45 tumours expressed TS. There was no association between TS expression and lymph node status (P = 0.80), histological response (P = 0.30), and recurrence (P = 0.55). On univariate analysis, only N-stage (P = 0.02) and vascular invasion (P = 0.04) were associated with a poor prognosis. Patients with negative tumour TS expression had better outcome than those with positive expression. The overall 5-year survival rate was 100% in the TS negative versus 56% in TS positive group, but the difference was not statistically significant (P = 0.17). Conclusion. TS expression should be studied in a larger series of gastro-oesophageal cancers as a potential prognostic marker of prognosis to neo-adjuvant chemotherapy.
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[1100]
TÍTULO / TITLE: - Screening organometallic binuclear thiosemicarbazone ruthenium complexes as potential anti-tumour agents: cytotoxic activity and human serum albumin binding mechanism.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dalton Trans. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1039/c3dt00028a
AUTORES / AUTHORS: - Demoro B; de Almeida RF; Marques F; Matos CP; Otero L; Costa Pessoa J; Santos I; Rodriguez A; Moreno V; Lorenzo J; Gambino D; Tomaz AI
INSTITUCIÓN / INSTITUTION: - Catedra de Quimica Inorganica, Facultad de Quimica, Universidad de la Republica, 11800 Montevideo, Uruguay.
RESUMEN / SUMMARY: - Four complexes combining the {Ru(p-cym)} moiety (p-cym = para-cymene) with thiosemicarbazone (TSC) ligands containing the 5-nitrofuryl pharmacophore were investigated in vitro for their properties as prospective anti-tumour agents. The compounds are dimeric structures of general formula [Ru2(p-cym)2(L)2]X2 where X = Cl-, PF6- and L = deprotonated 5-nitrofuraldehyde TSC (), and the N-methyl (), N-ethyl () and N-phenyl () derivatives. The precursor [RuCl2(p-cym)]2, all TSC ligands and their corresponding complexes were screened in vitro for their cytotoxicity against a range of human cancer cell lines (HL-60 acute promyelocytic leukemia, A2780 ovarian adenocarcinoma, MCF7 breast adenocarcinoma and PC3 grade IV prostate carcinoma). While the precursor complex was found to be inactive and exhibited moderate activity only in the MCF7 cell line, the coordination of to the {Ru(p-cym)} moiety remarkably enhanced the activity of the whole complex. In fact, complex [Ru2(p-cym)2(L4)2]Cl2 was found to be the most active agent of the whole series, and was studied further (as well as complex for comparison). Concerning the mode of action, the mechanism of cell death for both and seemed to be related to apoptotic processes, and they strongly interacted with tubulin (involved in the cell cycle) and with integrin (involved in the cytoskeleton formation). As an approach to their pharmacokinetics, the interaction of and with human serum albumin (HSA) was assessed. A quantitative model for the binding of to HSA is proposed from Circular Dichroism data, and validated by fluorescence results. Models of Forster resonance energy transfer and fluorescence quenching afforded the distance of to the lone Trp214 residue. Importantly, HSA binding enhanced the cytotoxicity of and correlated well with the HSA binding data. Our results consistently indicate that [Ru2(p-cymene)2(L4)2]Cl2 is quite promising as a prospective metallodrug for cancer chemotherapy.
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[1101]
TÍTULO / TITLE: - Targeting early B-cell receptor signaling induces apoptosis in leukemic mantle cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Hematol. Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista medicinedirect.com/journal
●● Cita: Experimental Hematology: <> Oncol. 2013 Feb 19;2(1):4. doi: 10.1186/2162-3619-2-4.
●● Enlace al texto completo (gratuito o de pago) 1186/2162-3619-2-4
AUTORES / AUTHORS: - Boukhiar MA; Roger C; Tran J; Gressin R; Martin A; Ajchenbaum-Cymbalista F; Varin-Blank N; Ledoux D; Baran-Marszak F
INSTITUCIÓN / INSTITUTION: - INSERM, UMR U978, Adaptateur de Signalisation en Hematologie, F-93000, Bobigny, France. fanny.baran-marszak@avc.aphp.fr.
RESUMEN / SUMMARY: - BACKGROUND: We previously showed that B-cell receptor (BCR) signaling pathways are important for in vitro survival of mantle cell lymphoma (MCL) cells. To further identify early BCR-activated signaling pathways involved in MCL cell survival, we focused our study on BCR-proximal kinases such as LYN whose dysregulations could contribute to the aggressive course of MCL. METHODS: Primary MCL cells were isolated from 14 leukemic patients. Early BCR-induced genes were identified by qRT-PCR array. The basal and BCR-induced phosphorylation of LYN and JNK were evaluated by immunoblottting. Cell survival signals were evaluated by apoptosis using flow cytometry. RESULTS: We showed that LYN was constitutively phosphorylated in MCL cell lines and in 9/10 leukemic MCL cases. Treatment with dasatinib or with a specific inhibitor of Src kinases such as PP2 suppressed constitutive LYN activation and increased in vitro spontaneous apoptosis of primary MCL cells. BCR engagement resulted in an increase of LYN phosphorylation leading to activation of c-JUN NH2-terminal kinase (JNK) and over-expression of the early growth response gene-1 (EGR-1). Inhibition of JNK with SP600125 induced apoptosis and reduced level of basal and BCR-induced expression of EGR-1. Furthermore, decreasing EGR1 expression by siRNA reduced BCR-induced cell survival. Treatment with PP2 or with dasatinib suppressed BCR-induced LYN and JNK phosphorylation as well as EGR-1 upregulation and is associated with a decrease of cell survival in all cases analysed. CONCLUSIONS: This study highlights the importance of BCR signaling in MCL cell survival and points out to the efficiency of kinase inhibitors in suppressing proximal BCR signaling events and in inducing apoptosis.
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[1102]
TÍTULO / TITLE: - Tualang honey promotes apoptotic cell death induced by tamoxifen in breast cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:989841. doi: 10.1155/2013/989841. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/989841
AUTORES / AUTHORS: - Yaacob NS; Nengsih A; Norazmi MN
INSTITUCIÓN / INSTITUTION: - Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Malaysia Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.
RESUMEN / SUMMARY: - Tualang honey (TH) is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM), in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-)responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.
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[1103]
TÍTULO / TITLE: - Identification and Insilico Analysis of Retinoblastoma Serum microRNA Profile and Gene Targets Towards Prediction of Novel Serum Biomarkers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioinform Biol Insights. 2013;7:21-34. doi: 10.4137/BBI.S10501. Epub 2013 Jan 9.
●● Enlace al texto completo (gratuito o de pago) 4137/BBI.S10501
AUTORES / AUTHORS: - Beta M; Venkatesan N; Vasudevan M; Vetrivel U; Khetan V; Krishnakumar S
INSTITUCIÓN / INSTITUTION: - L & T Ocular Pathology Department, Kamalnayan Bajaj Research Institute, Vision Research Foundation, Sankara Nethralaya, Tamil Nadu, India. ; Shanmugha Arts, Science, Technology & Research Academy (SASTRA University), Tirumalaisamudram, Thanjavur, Tamil Nadu, India.
RESUMEN / SUMMARY: - Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient’s serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change </= -2.0, P </= 0.05) and 24 to be downregulated (fold change >/= +2.0, P </= 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway.
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[1104]
TÍTULO / TITLE: - Cost-utility analysis of nanoparticle albumin-bound paclitaxel versus paclitaxel in monotherapy in pretreated metastatic breast cancer in España.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Rev Pharmacoecon Outcomes Res. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1586/erp.13.18
AUTORES / AUTHORS: - Alba E; Ciruelos E; Lopez R; Lopez-Vega JM; Lluch A; Martin M; Munoz M; Sanchez-Rovira P; Segui MA; Liria MR; Perez-Alcantara F
INSTITUCIÓN / INSTITUTION: - Hospital Clinico Universitario Virgen de la Victoria, Malaga, España.
RESUMEN / SUMMARY: - Aim: The COSTABRAX study evaluated the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) versus polyethylated castor oil-based standard paclitaxel (sb-paclitaxel) in the treatment of patients with previously treated metastatic breast cancer in España. Materials & methods: Efficacy data were obtained from the CA012 trial (nab-paclitaxel administered every 3 weeks [q3w] and sb-paclitaxel q3w) and indirect comparison (sb-paclitaxel administered weekly), and were modeled to a time horizon of 5 years using a Markov model. The analysis was performed from the National Health Service perspective. Use of resources and key assumptions of the model were validated by a panel of 22 local oncologists. Results: Compared with sb-paclitaxel q3w, nab-paclitaxel q3w was cost effective, with a cost per life-year gained of euro11,088 and a cost per quality-adjusted life-year of euro17,808. Compared with sb-paclitaxel administered weekly, it showed savings of euro711 per patient. Conclusion: The COSTABRAX study showed that nab-paclitaxel q3w is a cost-effective alternative compared with sb-paclitaxel q3w and a cost-saving alternative to sb-paclitaxel administered weekly in España.
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[1105]
TÍTULO / TITLE: - Cancerous inhibitor of protein phosphatase 2A mediates bortezomib-induced autophagy in hepatocellular carcinoma independent of proteasome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55705. doi: 10.1371/journal.pone.0055705. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055705
AUTORES / AUTHORS: - Yu HC; Hou DR; Liu CY; Lin CS; Shiau CW; Cheng AL; Chen KF
INSTITUCIÓN / INSTITUTION: - Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
RESUMEN / SUMMARY: - Previously, we reported that cancerous inhibitor of protein phosphatase 2A (CIP2A) mediates the apoptotic effect of bortezomib in hepatocellular carcinoma (HCC). Here, we report a proteasome-independent mechanism by which bortezomib induces autophagy in HCC. Our data indicate that bortezomib activated autophagy in a dose- and time- dependent manner in HCC cell lines including Huh-7, Sk-Hep1, and Hep3B. Bortezomib downregulated CIP2A, phospho-Akt (P-Akt) and phospho-4EBP1 (P-4EBP1) in a dose- and time-dependent manner in all tested HCC cells. Ectopic expression of CIP2A abolished the effect of bortezomib on autophagy. Co-treatment of bortezomib and calyculin A, a PP2A inhibitor, reduced the effect of bortezomib on P-Akt, P-4EBP1, and autophagy. Increased phosphorylation of either Akt or 4EBP1 by ectopic overexpression protected cells from bortezomib-induced autophagy. Furthermore, we examined the effect of DeltaBtz, a bortezomib derivative that closely resembles bortezomib structurally but has no proteasome activity, in HCC. Interestingly, DeltaBtz demonstrated similar effects to bortezomib on autophagy, CIP2A, P-Akt and P-4EBP1, suggesting that the effect of bortezomib on autophagy is independent of proteasome inhibition. Moreover, our in vivo data showed that both bortezomib and DeltaBtz inhibited tumor growth, downregulated CIP2A, P-Akt and induced autophagy in Huh-7 tumors. In conclusion, bortezomib induces autophagy in HCC through a CIP2A-PP2A-Akt-4EBP1 pathway.
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[1106]
TÍTULO / TITLE: - Caveolin-1 expression level in cancer associated fibroblasts predicts outcome in gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59102. doi: 10.1371/journal.pone.0059102. Epub 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059102
AUTORES / AUTHORS: - Zhao X; He Y; Gao J; Fan L; Li Z; Yang G; Chen H
INSTITUCIÓN / INSTITUTION: - Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, P. R. China.
RESUMEN / SUMMARY: - AIMS: Altered expression of epithelial or stromal caveolin-1 (Cav-1) is observed in various types of human cancers. However, the clinical significance of Cav-1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of both tumor cells and cancer associated fibroblasts (CAFs) Cav-1 in GC. METHODS AND RESULTS: Quantum dots immunofluorescence histochemistry was performed to examine the expression of Cav-1 in 20 cases of gastritis without intestinal metaplasia (IM), 20 cases of gastritis with IM and 286 cases of GC. Positive rates of epithelial Cav-1 in gastritis without IM, gastritis with IM and GC showed a decreasing trend (P = 0.012). Low expression of Cav-1 in CAFs but not in tumor cells was an independent predictor of poor prognosis in GC patients (P = 0.034 and 0.005 respectively in disease free survival and overall survival). Cav-1 level in tumor cells and CAFs showed no significant correlation with classic clinicopathological features. CONCLUSIONS: Loss of epithelial Cav-1 may promote malignant progression and low CAFs Cav-1 level herald worse outcome of GC patient, suggesting CAFs Cav-1 may be a candidate therapeutic target and a useful prognostic marker of GC.
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[1107]
TÍTULO / TITLE: - Correlation between chemosensitivity to anticancer drugs and telomerase reverse transcriptase mRNA expression in gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Feb 22;8:33. doi: 10.1186/1746-1596-8-33.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-33
AUTORES / AUTHORS: - Wang L; Li PF; Geng M; Cao YC; Yin YC
INSTITUCIÓN / INSTITUTION: - Department of Pathology, General Hospital of Jinan Military Command, 250031, Jinan, Shandong Province, China. gm2227@sina.com.
RESUMEN / SUMMARY: - BACKGROUND: The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them. METHODS: The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization. RESULTS: Taxol, Cisplatin and 5-Fluorouracil were in general more effective than Adriamycin and Mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-Fluorouracil or Adriamycin in GC. CONCLUSIONS: These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/1793217009875483.
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[1108]
TÍTULO / TITLE: - Identification of Novel Breast Cancer Resistance Protein (BCRP) Inhibitors by Virtual Screening.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Pharm. 2013 Apr 1;10(4):1236-48. doi: 10.1021/mp300547h. Epub 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1021/mp300547h
AUTORES / AUTHORS: - Pan Y; Chothe PP; Swaan PW
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland , 20 Penn Street, Baltimore, Maryland 21201, United States.
RESUMEN / SUMMARY: - Breast cancer resistance protein (BCRP; ABCG2) is an efflux transporter that plays an important role in multidrug resistance to antineoplastic drugs. The identification of drugs as BCRP inhibitors could aid in designing better therapeutic strategies for cancer treatment and will be critical for identifying potential drug-drug interactions. In the present study, we applied ligand-based virtual screening combined with experimental testing for the identification of novel drugs that can possibly interact with BCRP. Bayesian and pharmacophore models generated with known BCRP inhibitors were validated with an external test set. The resulting models were applied to predict new potential drug candidates from a database with more than 2000 FDA-approved drugs. Thirty-three drugs were tested in vitro for their inhibitory effects on BCRP-mediated transport of [(3)H]-mitoxantrone in MCF-7/AdrVp cells. Nineteen drugs were identified with significant inhibitory effect on BCRP transport function. The combined strategy of computational and experimental approaches in this paper has suggested potential drug candidates and thus represents an effective tool for rational identification of modulators of other proteins.
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[1109]
TÍTULO / TITLE: - Silencing of human phosphatidylethanolamine-binding protein 4 enhances rituximab-induced death and chemosensitization in B-cell lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56829. doi: 10.1371/journal.pone.0056829. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056829
AUTORES / AUTHORS: - Wang K; Jiang Y; Zheng W; Liu Z; Li H; Lou J; Gu M; Wang X
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China.
RESUMEN / SUMMARY: - Rituximab is the first line drug to treat non Hodgkin’s lymphoma (B-NHL) alone or in combination with chemotherapy. However, 30-40% of B-NHL patients are unresponsive to rituximab or resistant after therapy. Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is a novel member of PEBP family and functions as an anti-apoptotic molecule. In this study, we found hPEBP4 to be expressed in up to 90% of B-cell lymphoma patients, but in only 16.7% of normal lymph nodes. Interestingly, hPEBP4 overexpression inhibited rituximab-mediated complement dependent cytotoxicity (R-CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in B-NHL cells while downregulation of hPEBP4 augmented the therapeutic efficacy of rituximab both in vitro and in vivo. Furthermore, hPEBP4 silencing sensitized the primary B-acute lymphocytic leukemia (B-ALL) cells to R-CDC. During rituximab-mediated complement dependent cytotoxicity, hPEBP4 was recruited to the cell membrane in a PE-binding domain dependent manner and inhibited R-CDC induced calcium flux and reactive oxygen species (ROS) generation. These events contributed to the decrease of cell death induced by R-CDC in B-cell lymphomas. Meanwhile, hPEBP4 knockdown potentiated the chemosensitization of the rituximab in B-cell lymphoma cells by regulating the expression of Bcl-xl, Cycline E, p21(waf/cip1) and p53 and the activation of caspase-3 and caspase-9. Considering that hPEBP4 conferred cellular resistance to rituximab treatment and was preferentially expressed in lymphoma tissue, it could be a potential valuable target for adjuvant therapy for B-cell lymphoma.
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[1110]
TÍTULO / TITLE: - Activity of the heat shock protein 90 inhibitor ganetespib in melanoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56134. doi: 10.1371/journal.pone.0056134. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056134
AUTORES / AUTHORS: - Wu X; Marmarelis ME; Hodi FS
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, United States of America.
RESUMEN / SUMMARY: - Heat shock protein 90 (HSP90) is involved in the regulation of diverse biological processes such as cell signaling, proliferation and survival, and has been recently recognized as a potential target for cancer therapy. Ganetespib is a potent ATP competitive inhibitor of HSP90. Ganetespib downregulated the expression of multiple signal transducing molecules including EGFR, IGF-1R, c-Met, Akt, B-RAF and C-RAF, resulting in pronounced decrease in phosphorylation of Akt and Erk1/2 in a panel of five cutaneous melanoma cell lines including those harboring B-RAF and N-RAS mutations. Ganetespib exhibited potent antiproliferative activity on all five of these cell lines, with IC50 values between 37.5 and 84 nM. Importantly, Ganetespib is active on B-RAF mutated melanoma cells that have acquired resistance to B-RAF inhibition. Ganetespib induced apoptosis and cell cycle arrest at G1 and/or G2/M phase. Ganetespib induced cell cycle arrest was accompanied by altered expression of cyclin-dependent kinase inhibitor (CDKI) p21(Cip1) and p27(Kip1), cyclins B1, D1 and E, and/or cyclin-dependent kinases 1, 2 and 4. HSP90 is functionally important for melanoma cells and HSP90 inhibitors such as ganetespib could potentially be effective therapeutics for melanoma with various genetic mutations and acquired resistance to B-RAF inhibition.
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[1111]
TÍTULO / TITLE: - Prognostic significance of annexin II expression in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1028-y
AUTORES / AUTHORS: - Luo CH; Liu QQ; Zhang PF; Li MY; Chen ZC; Liu YF
INSTITUCIÓN / INSTITUTION: - The Department of Pathology, The Traditional Chinese Medical Hospital of Xiamen, Xiamen, Fujian, People’s Republic of China.
RESUMEN / SUMMARY: - PURPOSE: To discover common metastasis-related and prognostic markers in lung squamous carcinoma (LSC) and lung adenocarcinoma (AdC), two forms of non-small cell lung cancer (NSCLC). METHODS: Quantitative proteomic analysis was performed between primary cancer tissues and matched lymph node metastatic tissues in LSC and AdC, respectively. Immunohistochemistry and statistic analysis were performed to investigate prognostic significance of metastasis-related protein annexin II expression in LSC and AdC. RESULTS: Both in LSC and AdC, elevated expression of annexin II was identified in lymph node metastatic lung cancers compared to corresponding primary lung cancers. Furthermore, immunohistochemical analysis of a bulk of clinical specimens indicated that annexin II over-expression was more frequently observed in matched lymph node metastatic tissues than corresponding primary cancer tissues. Statistical analysis showed that annexin II over-expression was significantly associated with advanced clinical stage (P < 0.05) and lymph node metastasis (P < 0.05) and increased relapse rate (P < 0.05) and decreased overall survival (P < 0.05) in both two subtypes of NSCLC. Cox regression analysis indicated that annexin II over-expression was an important prognostic factor in both LSC and AdC. CONCLUSION: Annexin II was identified as a common prognostic factor in both LSC and AdC.
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[1112]
TÍTULO / TITLE: - Concurrent targeting of EP1/EP4 receptors and COX-2 induces synergistic apoptosis in KSHV and EBV associated non-Hodgkin lymphoma cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Transl Res. 2013 Mar 20. pii: S1931-5244(13)00070-4. doi: 10.1016/j.trsl.2013.02.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.trsl.2013.02.008
AUTORES / AUTHORS: - Paul AG; Chandran B; Sharma-Walia N
INSTITUCIÓN / INSTITUTION: - H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Ill.
RESUMEN / SUMMARY: - The effective antitumorigenic potential of nonsteroidal anti-inflammatory drugs (NSAIDs) and eicosonoid (EP; EP1-4) receptor antagonists prompted us to test their efficacy in Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) related lymphomas. Our study demonstrated that (1) EP1-4 receptor protein levels vary among the various non-Hodgkin’s lymphoma (NHL) cell lines tested (BCBL-1:KSHV+/EBV-;BC-3: KSHV+/EBV-; Akata/EBV+: KSHV-/EBV+; and JSC-1 cells: KSHV+/EBV + cells); (2) 5.0 muM of EP1 antagonist (SC-51322) had a significant antiproliferative effect on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; (3) 50.0 muM of EP2 antagonist (AH6809) was required to induce a significant antiproliferative effect on BCBL-1, Akata/EBV+, and JSC-1 cells; (4) 5.0 muM of EP4 antagonist (GW 627368X) had a significant antiproliferative effect on BC-3, Akata/EBV+, and JSC-1 cells; (5) COX-2 selective inhibitor celecoxib (5.0 muM) had significant antiproliferative effects on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; and (6) a combination of 1.0 muM each of celecoxib, SC-51322 and GW 627368X could potentiate the proapoptotic properties of celecoxib or vice-versa. Overall, our studies identified the synergistic antiproliferative effect of NSAIDs and EP receptor blockers on KSHV and EBV related B cell malignancies.
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[1113]
TÍTULO / TITLE: - Carbenoxolone Enhances TRAIL-Induced Apoptosis Through the Upregulation of Death Receptor 5 and Inhibition of Gap Junction Intercellular Communication in Human Glioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Stem Cells. Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista stemcells.alphamedpress.org/
●● Cita: Stem Cells: <> Dev. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1089/scd.2012.0529
AUTORES / AUTHORS: - Yulyana Y; Endaya BB; Ng WH; Guo CM; Hui KM; Lam PY; Ho IA
INSTITUCIÓN / INSTITUTION: - 1 Laboratory of Cancer Gene Therapy, Cellular and Molecular Research Division, Humphrey Oei Institute of Cancer Research , National Cancer Centre of Singapore, Singapore, Singapore .
RESUMEN / SUMMARY: - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been used extensively in cancer therapy. However, more than half of glioblastoma multiforme are insensitive to the apoptotic effect of TRAIL. Improvement in therapeutic modalities that enhances the efficacy of TRAIL in glioma is much sought after. In this study, we combined the tumor selectivity of TRAIL and tumor-homing properties of mesenchymal stem cells (MSC) with gap junction (GJ) inhibitory effect of carbenoxolone (CBX) to target orthotopic glioma. MSC were engineered to express TRAIL (MSC-TRAIL) by incorporating the secretable trimeric form of TRAIL into a Herpes Simplex Virus (HSV) type I amplicon vector. Our results showed that combined treatment of MSC-TRAIL and CBX enhanced glioma cell death, especially in three primary human glioma isolates, of which two of those are marginally sensitive to TRAIL. CBX enhanced TRAIL-induced apoptosis through upregulation of death receptor 5, blockade of GJ intercellular communication, and downregulation of connexin 43. Dual arm therapy using TRAIL and CBX prolonged the survival of treated mice by approximately 27% when compared with the controls in an intracranial glioma model. The enhanced efficacy of TRAIL in combination with CBX coupled with the minimal cytotoxic nature of CBX suggested a favorable clinical usage of this treatment regimen.
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[1114]
TÍTULO / TITLE: - Expression of p53 upregulated modulator of apoptosis (PUMA) and C-myb in gallbladder adenocarcinoma and their pathological significance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1010-8
AUTORES / AUTHORS: - Cai W; Li Q; Yang Z; Miao X; Wen Y; Huang S; Ouyang J
INSTITUCIÓN / INSTITUTION: - Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Number 139, Renmin Road, Changsha, 410011, Hunan, People’s Republic of China, caiwenwu1986@sina.com.
RESUMEN / SUMMARY: - PURPOSE: An increasing number of studies have shown that PUMA and C-myb signaling pathways are involved in various human cancers including colon carcinomas. However, few studies have examined gallbladder cancer specimens, and little is known about the clinical and pathological significance signaling changes may have in gallbladder adenocarcinoma. This study has investigated the expression of PUMA and C-myb in benign and malignant lesions of gallbladder and its pathological significance. METHODS: Tissue specimens from 108 gallbladder adenocarcinoma patients, 46 adjacent tissues, 15 cases of adenomatous polyps, and 35 surgical specimens from chronic cholecystitis patients were routinely paraffin embedded and sectioned. PUMA and C-myb expressions were detected with EnVision immunohistochemistry. RESULTS: Positive rates of PUMA and C-myb are significantly higher in gallbladder adenocarcinoma tissues than that in the other three (P < 0.01). Gallbladder epithelial cells in PUMA and/or C-myb positive benign cases manifest moderate to severe atypical dysplasia. Positive rates of PUMA and C-myb in well-differentiated tumors with maximum diameter of <2 cm and with no lymph node metastasis and invasion of the surrounding tissues are significantly lower than that in those poorly differentiated cases with maximum diameter of >/=2 cm, lymph node metastasis, and invasion of the surrounding tissues (P < 0.05 or P < 0.01). The postoperative survival of patients whose tumor specimens are positive for PUMA and C-myb is significantly shorter than that of those who are negative for both markers (P < 0.05 or P < 0.01). CONCLUSIONS: Our results have demonstrated that PUMA and C-myb positive gallbladder tumors progress rapidly, are prone to metastasis, possess strong invasive ability, and have poor prognosis.
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[1115]
TÍTULO / TITLE: - Predictive factors for premature discontinuation of docetaxel-based systemic chemotherapy in men with castration-resistant prostate cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Urol. 2013 Mar;54(3):157-62. doi: 10.4111/kju.2013.54.3.157. Epub 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 4111/kju.2013.54.3.157
AUTORES / AUTHORS: - Park SC; Lee JW; Seo IY; Rim JS
INSTITUCIÓN / INSTITUTION: - Department of Urology, Institute of Wonkwang Medical Science, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
RESUMEN / SUMMARY: - PURPOSE: The objective was to determine predictive factors for premature discontinuation of docetaxel-based systemic chemotherapy in men with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of men who were treated with docetaxel-based systemic chemotherapy for CRPC in a single institution between May 2005 and April 2010. After being screened, 30 patients fit the eligibility criteria for inclusion in this study. Group 1 included 12 patients who were treated with five or fewer cycles of docetaxel chemotherapy for CRPC, and group 2 included 18 patients who were treated with six or more cycles of docetaxel chemotherapy for CRPC. The treatment consisted of 5 mg prednisolone twice daily and 75 mg/m(2) docetaxel once every 3 weeks. RESULTS: The median age was 72 years, and the median Eastern Cooperative Oncology Group (ECOG) performance status was 0. The median baseline prostate-specific antigen (PSA) level was 33.8 ng/mL. The median cycle of docetaxel-based chemotherapy was 5.8. Of 30 patients, 13 patients (48.2%) had a decline in PSA of >50% from baseline; 3 of 22 patients (13.6%) with measurable disease had achieved partial response on imaging. No differences in age, ECOG performance status, hemoglobin, serum creatinine, or PSA response were observed between the two groups. Body mass index was significantly lower (p=0.034) in group 1 (21.8 kg/m(2)) than in group 2 (23.6 kg/m(2)). Group 1 included more patients with prior systemic chemotherapy (p=0.039), and group 1 had a shorter overall survival rate (p=0.039). CONCLUSIONS: Premature discontinuation of docetaxel-based systemic chemotherapy is associated with lower body mass index and prior systemic chemotherapy. Premature discontinuation of docetaxel-based chemotherapy is associated with a shorter overall survival rate.
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[1116]
TÍTULO / TITLE: - Prediction of selective serotonin reuptake inhibitor response using diffusion-weighted MRI.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Psychiatry. 2013;4:5. doi: 10.3389/fpsyt.2013.00005. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 3389/fpsyt.2013.00005
AUTORES / AUTHORS: - Delorenzo C; Delaparte L; Thapa-Chhetry B; Miller JM; Mann JJ; Parsey RV
INSTITUCIÓN / INSTITUTION: - Department of Psychiatry and Behavioral Science, Stony Brook University Stony Brook, NY, USA ; Department of Psychiatry, Columbia University New York, NY, USA.
RESUMEN / SUMMARY: - Pre-treatment differences in serotonergic binding between those who remit to antidepressant treatment and those who do not have been found using Positron Emission Tomography (PET). To investigate these differences, an exploratory study was performed using a second imaging modality, diffusion-weighted MRI (DW-MRI). Eighteen antidepressant-free subjects with Major Depressive Disorder received a 25-direction DW-MRI scan prior to 8 weeks of selective serotonin reuptake inhibitor treatment. Probabilistic tractography was performed between the midbrain/raphe and two target regions implicated in depression pathophysiology (amygdala and hippocampus). Average fractional anisotropy (FA) within the derived tracts was compared between SSRI remitters and non-remitters, and correlation between pre-treatment FA values and SSRI treatment outcome was assessed. Results indicate that average FA in DW-MRI-derived tracts to the right amygdala was significantly lower in non-remitters (0.55 +/- 0.04) than remitters (0.61 +/- 0.04, p < 0.01). In addition, there was a significant correlation between average FA in tracts to the right amygdala and SSRI treatment response. These relationships were found at a trend level when using the left amygdala as a tractography target. No significant differences were observed when using the hippocampus as target. These regional differences, consistent with previous PET findings, suggest that the integrity and/or number of white matter fibers terminating in the right amygdala may be compromised in SSRI non-remitters. Further, this study points to the benefits of multimodal imaging and suggests that DW-MRI may provide a pre-treatment signature of SSRI depression remission at 8 weeks.
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[1117]
TÍTULO / TITLE: - Effects of the downregulation of SnoN expression on HepG2 cell proliferation and apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Apr;7(4):1324-8. doi: 10.3892/mmr.2013.1340. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1340
AUTORES / AUTHORS: - Wang W; Liu C; Wang Y; Cao L
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.
RESUMEN / SUMMARY: - Skinovel protein (SnoN) is a protooncogene that belongs to the Ski protein family and is involved in regulating processes such as cell proliferation and apoptosis. To investigate the role of SnoN in the proliferation and apoptosis of HepG2 cells, we downregulated its expression by the use of small interfering RNA (siRNA). Three fragments predicted to have RNAi capacity were designed and synthesized as the target siRNAs (siRNAA, B and C). Following transfection, inhibition efficiency was detected by reverse transcription PCR (RTPCR) and western blot analysis. The siRNA with the optimal inhibition efficiency was used for the cell proliferation and apoptosis analysis. Cell proliferation was analyzed by the Cell Counting Kit8 (CCK8) and cell apoptosis was investigated by flow cytometry. In our study, all three siRNAs efficiently inhibited SnoN expression, and siRNAC demonstrated the optimal inhibition efficiency. We found that following downregulation of SnoN expression, HepG2 cell proliferation was significantly inhibited (P<0.05), while HepG2 cell apoptosis was significantly increased (P<0.05). SnoNspecific siRNA is capable of effectively inhibiting the expression of SnoN in human HepG2 cells, and the downregulation of SnoN expression induces growth inhibition and apoptosis.
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[1118]
TÍTULO / TITLE: - The role of Type I interferons in immunoregulation of breast cancer metastasis to the bone.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncoimmunology. 2013 Jan 1;2(1):e22339.
●● Enlace al texto completo (gratuito o de pago) 4161/onci.22339
AUTORES / AUTHORS: - Slaney CY; Moller A; Hertzog PJ; Parker BS
INSTITUCIÓN / INSTITUTION: - Research Division; Peter MacCallum Cancer Centre; East Melbourne, Australia ; Sir Peter MacCallum Department of Oncology; The University of Melbourne; Parkville, Australia.
RESUMEN / SUMMARY: - Breast cancer spread to distant sites is often incurable. Our recent findings demonstrate that Type I interferons secreted by tumor cells induce anti-metastatic immune responses that prevent breast cancer metastasis to the bone. This provides novel insights into the importance of the crosstalk between neoplastic and immune cells in the metastatic process.
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[1119]
TÍTULO / TITLE: - Neoadjuvant interferon-based chemoradiation for borderline resectable and locally advanced pancreas cancer: a Phase II pilot study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 19. doi: 10.1111/hpb.12086.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12086
AUTORES / AUTHORS: - Jensen EH; Armstrong L; Lee C; Tuttle TM; Vickers SM; Sielaff T; Greeno EW
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA.
RESUMEN / SUMMARY: - OBJECTIVES: Neoadjuvant chemoradiotherapy (CRT) is a viable treatment strategy for patients with pancreatic cancer. This study was conducted to evaluate the Virginia Mason Protocol (5-fluorouracil, cisplatin, interferon-alpha and radiation) given in the neoadjuvant setting for the treatment of locally advanced pancreatic cancer. METHODS: A Phase II pilot study evaluating interferon-based neoadjuvant CRT in patients with locally advanced pancreatic cancer was performed. RESULTS: A total of 23 patients were enrolled. The mean age of the patients was 58.6 years. Of the 23 patients, seven (30.4%) completed all treatments. In the remaining 16 (69.6%) patients, treatment was interrupted as a result of toxicity. The most commonly reported effects of toxicity were leucopoenia/cytopoenia (n = 19, 82.6%) and gastrointestinal effects (n = 19, 82.6%). Surgical resection was successful in seven (30.4%) patients. Margins were negative in six (85.7%) of these seven patients. Positive lymph nodes were identified in three (42.9%) of seven patients. Overall survival was 11.5 months. Surgery provided improved survival (22.6 months) compared with CRT alone (8.8 months). Disease-free survival in resected patients was 17.2 months. CONCLUSIONS: Interferon-based neoadjuvant CRT may allow for resection of locally advanced pancreatic cancer, but with significant toxicity. In the absence of surgical resection, survival remains dismal.
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[1120]
TÍTULO / TITLE: - Imaging techniques as predictive and prognostic biomarkers in renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ther Adv Med Oncol. 2013 Mar;5(2):119-31. doi: 10.1177/1758834012463624.
●● Enlace al texto completo (gratuito o de pago) 1177_1758834012463624 [pii
●● Enlace al texto completo (gratuito o de pago) 1177/1758834012463624
AUTORES / AUTHORS: - Nathan P; Vinayan A
INSTITUCIÓN / INSTITUTION: - Mount Vernon Cancer Centre - Medical Oncology, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK.
RESUMEN / SUMMARY: - A number of imaging modalities are showing promise as predictive and prognostic biomarkers in advanced renal cell carcinoma. This review discusses progress to date in this exciting area and identifies areas of future promise.
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[1121]
TÍTULO / TITLE: - Serum APE1 Autoantibodies: A Novel Potential Tumor Marker and Predictor of Chemotherapeutic Efficacy in Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58001. doi: 10.1371/journal.pone.0058001. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058001
AUTORES / AUTHORS: - Dai N; Cao XJ; Li MX; Qing Y; Liao L; Lu XF; Zhang SH; Li Z; Yang YX; Wang D
INSTITUCIÓN / INSTITUTION: - Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China.
RESUMEN / SUMMARY: - Apurinic/apyrimidinic endonuclease 1 (APE1), which has the dual functions of both DNA repair and redox activity, has been reported to be highly expressed in non-small cell lung cancer (NSCLC), and this appears to be a characteristic related to chemotherapy resistance. In this study, we identified serum APE1 autoantibodies (APE1-AAbs) in NSCLC patients and healthy controls by immunoblotting and investigated the expression of APE1-AAbs by indirect ELISA from the serum of 292 NSCLC patients and 300 healthy controls. In addition, serum APE1-AAbs level alterations of 91 patients were monitored before and after chemotherapy. Our results showed that serum APE1-AAbs can be detected in both NSCLC patients and healthy controls. Serum APE1-AAbs were significantly higher than those of healthy controls and closely related to APE1 antigen levels both in tumor tissues and the peripheral blood. Moreover, the change in levels of serum APE1-AAbs in NSCLC is closely associated with the response to chemotherapy. These results suggest that APE1-AAbs is a potential tumor marker and predictor of therapeutic efficacy in NSCLC.
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[1122]
TÍTULO / TITLE: - Epidermal growth factor protects squamous cell carcinoma against cisplatin-induced cytotoxicity through increased interleukin-1beta expression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55795. doi: 10.1371/journal.pone.0055795. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055795
AUTORES / AUTHORS: - Ko SC; Huang CR; Shieh JM; Yang JH; Chang WC; Chen BK
INSTITUCIÓN / INSTITUTION: - Department of Chest Medicine, Chi Mei Medical Center, Tainan, Taiwan, Republic of China.
RESUMEN / SUMMARY: - The expression of cytokines, such as IL-1beta, and the activation of the epidermal growth factor receptor (EGFR) are crucial regulators in the process of carcinogenesis. The correlation between growth factor and activated cytokine signals in the control of tumor development is a critical issue to be clarified. In our study, we found that the IL-1beta gene and protein expression were induced by EGF in squamous cell carcinoma. To clarify the mechanism involved in EGF-regulated IL-1beta expression, we examined the transcriptional activity and mRNA stability of IL-1beta in EGF-treated cells. We found that EGF induced the expression of IL-1beta and was mediated through transcriptional activation, but not through mRNA stability. The involvement of Akt and NF-kappaB signaling pathways in the EGF-induced IL-1beta gene expression was confirmed by knockdown of RelA and Akt in cells or treating cells with Akt and NF-kappaB inhibitors, LY294002 and parthenolide, respectively. The expression of dominant negative IkappaB also repressed the activation of NF-kappaB and inhibited EGF-induced IL-1beta expression. Using immunofluorescence staining assay, the EGF-stimulated nuclear translocation of NF-kappaB (p65) was inhibited by pre-treating cells with LY294002 and parthenolide. Furthermore, EGF increased the binding of NF-kappaB to the NF-kappaB binding site of the IL-1beta promoter through the activation of the Akt/NF-kappaB pathway, which resulted in activating IL-1beta promoter activity. The expression and secretion of IL-1beta induced by EGF considerably reduced chemotherapeutic drug cisplatin-induced cell death. These results showed that EGF enhanced the expression of IL-1beta, which was mediated by the Akt/NF-kappaB pathway. The activation of EGF signaling and increase of IL-1beta contributed to chemotherapeutic resistance of cancer cells, suggesting that the expression of IL-1beta may be used as a biomarker to evaluate successful cancer treatment.
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[1123]
TÍTULO / TITLE: - Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Nanomedicine. 2013;8:983-93. doi: 10.2147/IJN.S42028. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 2147/IJN.S42028
AUTORES / AUTHORS: - Alarifi S; Ali D; Alkahtani S; Verma A; Ahamed M; Ahmed M; Alhadlaq HA
INSTITUCIÓN / INSTITUTION: - Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia.
RESUMEN / SUMMARY: - The widespread use of zinc oxide (ZnO) nanoparticles worldwide exposes humans to their adverse effects, so it is important to understand their biological effects and any associated risks. This study was designed to investigate the cytotoxicity, oxidative stress, and apoptosis caused by ZnO nanoparticles in human skin melanoma (A375) cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] and lactate dehydrogenase-based cell viability assays showed a significant decrease in cell viability after exposure to ZnO nanoparticles, and phase contrast images revealed that cells treated with these nanoparticles had a lower density and a rounded morphology. ZnO nanoparticles were also found to induce oxidative stress, evidenced by generation of reactive oxygen species and depletion of the antioxidant, glutathione. Induction of apoptosis was confirmed by chromosomal condensation assay and caspase-3 activation. Further, more DNA damage was observed in cells exposed to the highest concentration of ZnO nanoparticles. These results demonstrate that ZnO nanoparticles have genotoxic potential in A375 cells, which may be mediated via oxidative stress. Our short-term exposure study showing induction of a genotoxic and apoptotic response to ZnO nanoparticles needs further investigation to determine whether there may be consequences of long-term exposure to ZnO nanoparticles.
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[1124]
TÍTULO / TITLE: - Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Genomics. 2012 Sep;13(6):433-7. doi: 10.2174/138920212802510420.
●● Enlace al texto completo (gratuito o de pago) 2174/138920212802510420
AUTORES / AUTHORS: - Rumenapp C; Smida J; Gonzalez-Vasconcellos I; Baumhoer D; Malfoy B; Hadj-Hamou NS; Sanli-Bonazzi B; Nathrath M; Atkinson MJ; Rosemann M
INSTITUCIÓN / INSTITUTION: - Institute of Radiation Biology, Helmholtz-Center Munich, German Research Center for Environmental Health, Neuherberg, Germany ; Institute of Pathology, Helmholtz-Center Munich, German Research Center for Environmental Health, Neuherberg, Germany ; Current adress: Technische Universitat Munchen, Zentralinstitut fur Medizintechnik (IMETUM), Garching, Germany.
RESUMEN / SUMMARY: - Secondary bone tumours arising in the field of a preceding radiotherapy are a serious late effect, in particular considering the increasing survival times in patients treated for paediatric malignancies. In general, therapy associated tumours are known to show a more aggressive behaviour and a limited response to chemotherapy compared with their primary counterparts. It is not clear however whether this less favourable outcome is caused by inherent genetic factors of the tumour cells or by a general systemic condition of the patient. To elucidate this we analysed a series of bone sarcomas with a history of prior irradiation for the presence of genomic alterations and compared them with the alterations identified earlier in primary osteosarcomas. We analysed seven radiation induced bone sarcomas for genome-wide losses of heterozygosity (LOH) using Affymetrix 10K2 high-density single nucleotide polymorphism (SNP) arrays. Additionally, copy number changes were analysed at two distinct loci on 10q that were recently found to be of major prognostic significance in primary osteosarcomas. All the investigated tumours showed a LOH at 10q21.1 with 86% of cases (6/7) revealing a total genome-wide LOH score above 2400 and more than 24% of the genome being affected. Our results indicate similar genetic alterations in radiation induced sarcomas of bone and primary osteosarcomas with a poor prognosis. We speculate that the high degree of genomic instability found in these tumours causes the poor prognosis irrespective of the initiating event.
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[1125]
TÍTULO / TITLE: - Inhibition of cancer cell proliferation by 5-fluoro-2’-deoxycytidine, a DNA methylation inhibitor, through activation of DNA damage response pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Springerplus. 2012 Dec;1(1):65. Epub 2012 Dec 13.
●● Enlace al texto completo (gratuito o de pago) 1186/2193-1801-1-65
AUTORES / AUTHORS: - Zhao Q; Fan J; Hong W; Li L; Wu M
INSTITUCIÓN / INSTITUTION: - Hubei Clinical Centre & Key Laboratory of Intestinal and Colorectal Diseases, and College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China.
RESUMEN / SUMMARY: - Multiple epigenetic changes, including alterations in DNA methylation occur during tumorigenesis. Various inhibitors of DNA methylation have been developed to prevent proliferation of cancer cells. 5-fluoro-2(‘)-deoxycytidine (FCdR) is one such DNA methylation inhibitor, which is currently in phase II clinical trial. To investigate the molecular mechanism/s by which FCdR might mediate repression of tumor cell proliferation, we analyzed the toxicity of FCdR in various cell lines established from different sarcomas. We found HCT116, a colon cancer cell line, is much more sensitive to FCdR compared to others. FCdR treatment inhibited HCT116 cells at G2/M check point and up-regulated expression of multiple cancer-related genes, which could be due to its inhibitory activity towards DNA methylation. Furthermore, we found that FCdR activates DNA damage response pathway. Using an inhibitor for ATM and ATR kinases activity, which are required for amplifying the DNA damage repair signal, we show that FCdR induced inhibition of HCT116 cells at G2/M is mediated through activation of DNA damage response pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-1-65) contains supplementary material, which is available to authorized users.
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[1126]
TÍTULO / TITLE: - Expression of stem cell factor in gastrointestinal stromal tumors: Implications for proliferation and imatinib resistance.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):552-558. Epub 2012 Nov 9.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1019
AUTORES / AUTHORS: - Hou XW; Bai CG; Liu XH; Qiu C; Huang L; Xu JJ; Ma DL
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433; ; Department of Oncology, 401 Hospital of PLA, Qingdao, Shandong 266071;
RESUMEN / SUMMARY: - KIT autophosphorylation caused by mutation of KIT is considered to be a critical mechanism for the oncogenesis of gastrointestinal stromal tumors (GISTs). However, little is known regarding whether stem cell factor (SCF), the KIT ligand, is able to induce the proliferation of GIST cells by activating the wild-type KIT receptor in GISTs. Imatinib, a tyrosine kinase inhibitor, has been demonstrated to be effective as treatment for the majority of GISTs. However, primary resistance to imatinib in GISTs with wild-type KIT and acquired resistance in GISTs with mutant KIT are becoming increasingly significant problems. The aims of this study were to detect the expression and function of SCF in 68 GIST samples, and to explore the relationship between SCF activity and imatinib resistance using immunohistochemical staining and western blot analysis. Results showed abundant expression of SCF in GISTs and demonstrated that SCF is capable of enhancing GIST cell proliferation. Similar to its ineffectiveness in wild-type GISTs, imatinib also failed to inhibit SCF-induced KIT activation in GISTs with mutant KIT. We also found increased SCF expression in GIST cells treated with imatinib. Overall, our results indicated that SCF-induced KIT activation is a novel essential pathway for the proliferation of GISTs. Imatinib was not able to inhibit the activity of SCF, while it promoted the expression of SCF, which may have contributed to acquired imatinib resistance.
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[1127]
TÍTULO / TITLE: - Endometrial stromal tumors: immunohistochemical and molecular analysis of potential targets of tyrosine kinase inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Sarcoma Res. 2013 Mar 7;3(1):3. doi: 10.1186/2045-3329-3-3.
●● Enlace al texto completo (gratuito o de pago) 1186/2045-3329-3-3
AUTORES / AUTHORS: - Sardinha R; Hernandez T; Fraile S; Tresserra F; Vidal A; Gomez MC; Astudillo A; Hernandez N; Saenz de Santamaria J; Ordi J; Goncalves L; Ramos R; Balana C; de Alava E
INSTITUCIÓN / INSTITUTION: - Centro de Investigacion del Cancer-IBMCC USAL-CSIC, Salamanca, España. edealava@usal.es.
RESUMEN / SUMMARY: - BACKGROUND: The systemic treatment of malignant endometrial stromal tumors (EST) is not well established. A few reports describe objective responses to imatinib, which suggest a novel therapeutic strategy for these tumors. Due to these facts, we aimed to perform a retrospective analysis of possible molecular targets of tyrosine kinase inhibitors (TKI) in EST: KIT, PDGFRA and EGFR. METHODS: 52 endometrial stromal sarcomas and 13 undifferentiated endometrial sarcomas were examined and reviewed. Mutational analysis were performed for exons 9, 11, 13, and 17 of the KIT gene, exons 12 and 18 of the PDGFRA gene and exons 18, 19, 20 and 21 of the EGFR gene. The incidence and distribution of the KIT, PDGFRA, and EGFR expression were examined by immunohistochemistry, and EGFR amplification was assessed by fluorescence in situ hybridization. RESULTS: No mutations in KIT, PDGFRA and EGFR genes were detected. Overexpression of KIT, PDGFRA, EGFR, was detected in 2 (3%), 23 (35.4%), 7 (10.8%) cases respectively, whereas amplification of EGFR gene was not found. CONCLUSIONS: Absence of significant expression, amplification and activating mutations on these tyrosine kinase receptors suggest that it is unlikely that EST can benefit from therapies such as TKI on the systemic setting.
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[1128]
TÍTULO / TITLE: - Silencing mutated beta-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55743. doi: 10.1371/journal.pone.0055743. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055743
AUTORES / AUTHORS: - Gaujoux S; Hantel C; Launay P; Bonnet S; Perlemoine K; Lefevre L; Guillaud-Bataille M; Beuschlein F; Tissier F; Bertherat J; Rizk-Rabin M; Ragazzon B
INSTITUCIÓN / INSTITUTION: - Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France.
RESUMEN / SUMMARY: - CONTEXT: Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic options. Activating beta-catenin somatic mutations are found in ACC and have been associated with a poor clinical outcome. In fact, activation of the Wnt/beta-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might, thus, represent a promising therapeutic target. OBJECTIVE: Similar to patient tumor specimen the H295 cell line derived from an ACC harbors a natural activating beta-catenin mutation. We herein assess the in vitro and in vivo effect of beta-catenin inactivation using a doxycyclin (dox) inducible shRNA plasmid in H295R adrenocortical cancer cells line (clone named shbeta). RESULTS: Following dox treatment a profound reduction in beta-catenin expression was detectable in shbeta clones in comparison to control clones (Ctr). Accordingly, we observed a decrease in Wnt/betacatenin-dependent luciferase reporter activity as well as a decreased expression of AXIN2 representing an endogenous beta-catenin target gene. Concomitantly, beta-catenin silencing resulted in a decreased cell proliferation, cell cycle alterations with cell accumulation in the G1 phase and increased apoptosis in vitro. In vivo, on established tumor xenografts in athymic nude mice, 9 days of beta-catenin silencing resulted in a significant reduction of CTNNB1 and AXIN2 expression. Moreover, continous beta-catenin silencing, starting 3 days after tumor cell inoculation, was associated with a complete absence of tumor growth in the shbeta group while tumors were present in all animals of the control group. CONCLUSION: In summary, these experiments provide evidences that Wnt/beta-catenin pathway inhibition in ACC is a promising therapeutic target.
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[1129]
TÍTULO / TITLE: - The role of EGFR monoclonal antibodies (MoABs) cetuximab/panitumab, and BRAF inhibitors in BRAF mutated colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointest Oncol. 2013 Mar;4(1):72-81. doi: 10.3978/j.issn.2078-6891.2012.044.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.044
AUTORES / AUTHORS: - Muhammad S; Jiang Z; Liu Z; Kaur K; Wang X
INSTITUCIÓN / INSTITUTION: - Colorectal surgery department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; ; Colorectal Cancer Institute of Harbin Medical University, Harbin, China.
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[1130]
TÍTULO / TITLE: - Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0985-x
AUTORES / AUTHORS: - Afonso FJ; Anido U; Fernandez-Calvo O; Vazquez-Estevez S; Leon L; Lazaro M; Ramos M; Anton-Aparicio L
INSTITUCIÓN / INSTITUTION: - Complexo Hospitalario Arquitecto Marcide, Ferrol, España.
RESUMEN / SUMMARY: - We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC.
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[1131]
TÍTULO / TITLE: - N-Cadherin Expression Is Associated with Acquisition of EMT Phenotype and with Enhanced Invasion in Erlotinib-Resistant Lung Cancer Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57692. doi: 10.1371/journal.pone.0057692. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057692
AUTORES / AUTHORS: - Zhang X; Liu G; Kang Y; Dong Z; Qian Q; Ma X
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China.
RESUMEN / SUMMARY: - BACKGROUND: The epidermal growth-factor receptor tyrosine kinase inhibitors have been effective in non-small cell lung cancer patients. However, acquired resistance eventually develops in most patients despite an initial positive response. Emerging evidence suggests that there is a molecular connection between acquired resistance and the epithelial-mesenchymal transition (EMT). N-cadherin is involved in the EMT and in the metastasis of cancer cells. Here, we analyzed N-cadherin expression and function in erlotinib-resistant lung cancer cell lines. METHODS: H1650 cell lines were used to establish the subline resistant to erlotinib(H1650ER). Then, induction of the EMT was analyzed using immunostaining and western blots in H1650ER cells. N-cadherin expression in the resistant cells was examined using FACS and western blot. In addition, an invasion assay was performed to characterize the resistant cells. The effects of N-cadherin on cell proliferation and invasion were analyzed. The association of N-cadherin expression with the EMT phenotype was investigated using immunohistochemical analysis of 13 archived, lung adenocarcinoma tissues, before and after treatment with erlotinib. RESULTS: In H1650ER cells, N-cadherin expression was upregulated, paralleled by the reduced expression of E-cadherin. The marked histological change and the development of a spindle-like morphology suggest that H1650ER cells underwent an EMT, accompanied by a decrease in E-cadherin and an increase in vimentin. A change in the EMT status between pre-and post-treatment was observed in 11 out of 13 cases (79%). In biopsies of resistant cancers, N-cadherin expression was increased in 10 out of 13 cases. Induction of the EMT was consistent with aggressive characteristics. Inhibition of N-cadherin expression by siRNA was tested to reduce proliferation and invasion of H1650ER cells in vitro. CONCLUSIONS: Our data provide evidence that induction of the EMT contributes to the acquired resistance to EGFR-TKIs in lung cancer. It suggests that N-cadherin is a potential molecular target in the treatment of NSCLC.
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[1132]
TÍTULO / TITLE: - The differential expression of vascular endothelial growth inhibitor isoforms, VEGI251, VEGI174 and VEGI192 in human clear-cell renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Genomics Proteomics. 2013 Jan-Feb;10(1):47-53.
AUTORES / AUTHORS: - Zhang N; Wu P; Wu L; Shayiremu D; Shan H; Ye L; Jiang WG; Gong K; Yang Y
INSTITUCIÓN / INSTITUTION: - Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, PR China.
RESUMEN / SUMMARY: - Vascular endothelial growth inhibitor (VEGI) is a recently identified antiangiogenic cytokine that belongs to the tumour necrosis factor (TNF) superfamily, and may be essential for many physiological and pathological processes. However, the expression of VEGI and in particular its isoforms, VEGI251, VEGI192 and VEGI174, in clear-cell renal cell carcinoma (CCRCC) remain unknown. In the current study, we investigated the expression of the three isoforms of VEGI in CCRCC. The expression of VEGI was examined in paired human normal renal and CCRCC specimens (n=73). The transcripts of the three isoforms of VEGI were all detected in human renal normal and tumour tissues. Levels of VEGI174 and VEGI192 transcripts in normal renal specimens were higher than those in CCRCC (p=0.021 and p=0.038, respectively). Levels of VEGI251 were similar in normal and tumour specimens (p=0.67). The numbers of VEGI174 and VEGI192 transcripts in T1a+T1b tumours were higher than those in T2+T3 tumours (p=0.006 and p=0.018, respectively). Moreover, VEGI192 transcript levels were negatively correlated with pathological nuclear grade (r=-0.216, p=0.022). In immunohistochemical staining, VEGI192 staining in normal and CCRCC tissues differed significantly (100% vs. 39.7%, p<0.0001). VEGI192 staining intensity was also negatively correlated with pathological nuclear grade (r=-0.781, p=0.002). CONCLUSION: Transcripts of VEGI isoforms were detectable in normal and tumour renal tissues. VEGI192 and VEGI174 expressions markedly decreased in CCRCC and are linked to pathological grade and stage. VEGI192 and VEGI174 are more likely to be putative tumour suppressive factors and a potential therapeutic target in CCRCC.
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[1133]
TÍTULO / TITLE: - The Anti-Melanoma Activity of Dinaciclib, a Cyclin-Dependent Kinase Inhibitor, Is Dependent on p53 Signaling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59588. doi: 10.1371/journal.pone.0059588. Epub 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059588
AUTORES / AUTHORS: - Desai BM; Villanueva J; Nguyen TT; Lioni M; Xiao M; Kong J; Krepler C; Vultur A; Flaherty KT; Nathanson KL; Smalley KS; Herlyn M
INSTITUCIÓN / INSTITUTION: - The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
RESUMEN / SUMMARY: - Although cyclin dependent kinase (CDK)-2 is known to be dispensable for the growth of most tumors, it is thought to be important for the proliferation of melanoma cells, where its expression is controlled by the melanocyte-lineage specific transcription factor MITF. Treatment of a panel of melanoma cells with the CDK inhibitor dinaciclib led to a concentration-dependent inhibition of growth under both 2D adherent and 3D organotypic cell culture conditions. Dinaciclib targeted melanoma cell lines regardless of cdk2 or MITF levels. Inhibition of growth was associated with a rapid induction of G2/M cell arrest and apoptosis. Treatment of human melanoma mouse xenografts with dinaciclib led to tumor regression associated with reduced retinoblastoma protein phosphorylation and Bcl-2 expression. Further mechanistic studies revealed that dinaciclib induces p53 expression whilst simultaneously downregulating the expression of the anti-apoptotic factors Mcl-1 and XIAP. To clarify the role of p53 activation in the dinaciclib-induced cell death, we generated melanoma cell lines in which p53 expression was knocked down using a shRNA lentiviral vector. Knockdown of p53 completely abolished the induction of apoptosis seen following dinaciclib treatment as shown by a lack of annexin-V staining and caspase-3 cleavage. Altogether, these data show that dinaciclib induces apoptosis in a large panel of melanoma cell lines through a mechanism requiring p53 expression.
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[1134]
TÍTULO / TITLE: - Prognostic and predictive value of serum vascular endothelial growth factor (VEGF) in squamous cell carcinoma of the head and neck.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oral Maxillofac Surg. 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s10006-013-0402-9
AUTORES / AUTHORS: - Khademi B; Soleimanpour M; Ghaderi A; Mohammadianpanah M
INSTITUCIÓN / INSTITUTION: - Department of Otolaryngology, and Head and Neck Surgery, Khalili Hospital, Shiraz University of Medical Sciences, Shiraz, 71936-13511, Iran.
RESUMEN / SUMMARY: - INTRODUCTION: This study aimed to investigate the prognostic and predictive value of serum vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinoma (HNSCC). METHOD: Preoperative and 6-month postoperative serum VEGF levels were measured using a quantitative sandwich enzyme immunoassay technique in 55 consecutive patients with HNSCC and two control groups. The first control group included normal, healthy, age- and sex-matched individuals (n = 20), while the second control group included the patients who had history of HNSCC and were free of disease for at least 5 years (n = 25). RESULTS: The mean baseline serum VEGF concentrations of the 55 patients with HNSCC and the first and the second control groups were 437.86, 42.56, and 48.03 pg/ml, respectively (P < 0.001). After a median follow-up of 75 months, 15 patients of the study group developed recurrent disease and 40 patients remained free of disease. The mean preoperative and 6-month postoperative serum VEGF levels for the 40 patients who did not have recurrent disease were respectively 327.69 and 153.50 pg/ml compared to 731.72 and 692.96 pg/ml for the 15 patients with recurrent disease (P < 0.001). High (>/=540 pg/ml) serum VEGF level was associated with poor overall survival (P < 0.001). Moreover, multivariate analysis showed node stage (P < 0.001) and preoperative serum VEGF level (P = 0.020) as significant, independent prognostic factors for overall survival. CONCLUSION: Preoperative or postoperative elevated serum levels of VEGF are highly predictive for disease recurrence and are associated with poor disease-free and overall survival of patients with HNSCC.
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[1135]
TÍTULO / TITLE: - Signaling network of OSW1induced apoptosis and necroptosis in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 13. doi: 10.3892/mmr.2013.1366.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1366
AUTORES / AUTHORS: - Jin J; Jin X; Qian C; Ruan Y; Jiang H
INSTITUCIÓN / INSTITUTION: - Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, P.R. China.
RESUMEN / SUMMARY: - The compound 3beta, 16beta, 17alphatrihydroxycholest5en22one 16O(2O4methoxybenzoylbetaDxylopyranosyl) (1-->3)(2OacetylalphaLarabinopyranoside (OSW1) is a member of the cholestane saponin family that was created in the bulbs of Ornithogalum saudersiae. OSW1 has previously been shown as cytotoxic against numerous types of malignant cells, however, its antitumoral mechanisms remain unclear. The present study aimed to examine the potential changes in the gene expression of a hepatocellular carcinoma (HCC) cell line (Hep3B) incubated with OSW1 in vitro. The results showed that OSW1 inhibited tumors through invasiveness, angiogenesis, cell polarity and cell adhesion (as shown by Roche NimbleGen gene expression analysis), in addition to inducing apoptosis through the mitochondrial pathway. This affected the expression of a number of core genes in a number of signaling pathways, including WNT, MAPK, VEGF and P53. To the best of our knowledge, the present study is the first to report that OSW1, as a molecular compound, induces necroptotic death in hepatocellular carcinoma (HCC).
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[1136]
TÍTULO / TITLE: - Malignant solitary fibrous tumor of the kidney: report of the first case managed with interferon.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Oncol Med. 2013;2013:564980. doi: 10.1155/2013/564980. Epub 2013 Jan 15.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/564980
AUTORES / AUTHORS: - Cuello J; Bruges R
INSTITUCIÓN / INSTITUTION: - Clinical Oncology Group, Cancerology National Institute, E.S.E., Bogota, Colombia ; El Bosque University, Bogota, Colombia.
RESUMEN / SUMMARY: - Solitary fibrous tumors of the kidney are extremely rare tumors with unpredictable behavior. We describe a case of a patient with a solitary fibrous tumor of kidney with malignant findings with distant metastasis and nephrectomy managed with subcutaneous interferon achieving 23 months of progression-free survival. To date there is no prospective evaluation of any specific modality of treatment, but the surgical management and long-term followup are the only ones so far recommended strategies in the management of these patients. Studies are awaited with more patients to evaluate the different strategies of systemic therapy reported so far to allow adding survival benefit.
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[1137]
TÍTULO / TITLE: - Cortactin is a sensitive biomarker relative to the poor prognosis of human hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg Oncol. 2013 Mar 21;11(1):74.
●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-74
AUTORES / AUTHORS: - Zhao G; Huang ZM; Kong YL; Wen DQ; Li Y; Ren L; Zhang HY
RESUMEN / SUMMARY: - BACKGROUND: Cortactin is an important regulator involved in invasion and migration of hepatocellular carcinoma (HCC). The aim of this study was to elucidate the forecasting role of cortactin in resectable HCCs. METHODS: We compared the invasiveness and motility among liver epithelial cell line and HCC cell lines by using Transwell assay and wound healing assay. We further investigated the CTTN mRNA expression by real-time PCR. Next, 91 HCC and 20 normal liver tissue samples were detected by IHC and real-time PCR. Finally, we analyzed the clinicopathologic features and survival time of the HCC cases. RESULTS: We identified that HepG2, LM3, and SK-Hep-1 had more invasiveness and motility (P <0.05). Compared with liver epithelial cell line, CTTN expression was higher in LM3, HepG2, and MHCC97-L (P <0.01) and lower in SK-Hep-1 (P <0.05). IHC examination showed cortactin expression was closely relative to TNM stage (AJCC/UICC), cancer embolus, and metastasis (P <0.01). Cortactin overexpression indicated a longer survival time of 52 +/- 8.62 months and low expression of a shorter survival time of 20 +/- 4.95 months (P <0.01). Cortactin examination has more predictive power in patients with Child-Pugh grade A and BCLC stage 0-B. CONCLUSIONS: Overexpression of cortactin is closely associated with poor human HCCs prognosis that caused by cancer embolus and metastasis. Cortactin and CTTN should be used for differentiating varieties of survival for patients after HCC resection.
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[1138]
TÍTULO / TITLE: - Multifunctional Albumin Nanoparticles As Combination Drug Carriers for Intra-Tumoral Chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Adv Healthc Mater. 2013 Mar 12. doi: 10.1002/adhm.201200467.
●● Enlace al texto completo (gratuito o de pago) 1002/adhm.201200467
AUTORES / AUTHORS: - Cui M; Naczynski DJ; Zevon M; Griffith CK; Sheihet L; Poventud-Fuentes I; Chen S; Roth CM; Moghe PV
INSTITUCIÓN / INSTITUTION: - Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
RESUMEN / SUMMARY: - Current cancer therapies are challenged by weakly soluble drugs and by drug combinations that exhibit non-uniform biodistribution and poor bioavailability. In this study, we have presented a new platform of advanced healthcare materials based on albumin nanoparticles (ANPs) engineered as tumor penetrating, delivery vehicles of combinatorially applied factors to solid tumors. These materials were designed to overcome three sequential key barriers: tissue level transport across solid tumor matrix; uptake kinetics into individual cancer cells; therapeutic resistance to single chemotherapeutic drugs. The ANPs were designed to penetrate deeper into solid tumor matrices using collagenase decoration and evaluated using a three-dimensional multicellular melanoma tumor spheroid model. Collagenase modified ANPs exhibited 1-2 orders of magnitude greater tumor penetration than unmodified ANPs into the spheroid mass after 96 hours, and showed preferential uptake into individual cancer cells for smaller sized ANPs (<100 nm). For enhanced efficacy, collagenase coated ANPs were modified with two therapeutic agents, curcumin and riluzole, with complementary mechanisms of action for combined cell cycle arrest and apoptosis in melanoma. The collagenase coated, drug loaded nanoparticles induced significantly more cell death within 3-D tumor models than the unmodified, dual drug loaded ANP particles and the kinetics of cytotoxicity was further influenced by the ANP size. Thus, multifunctional nanoparticles can be imbued with complementary size and protease activity features that allow them to penetrate solid tumors and deliver combinatorial therapeutic payload with enhanced cancer cytotoxicity but minimal collateral damage to healthy primary cells.
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[1139]
TÍTULO / TITLE: - Sinusoidal obstruction syndrome (SOS) related to chemotherapy for colorectal liver metastases: factors predictive of severe SOS lesions and protective effect of bevacizumab.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Jan 18. doi: 10.1111/hpb.12047.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12047
AUTORES / AUTHORS: - Hubert C; Sempoux C; Humblet Y; van den Eynde M; Zech F; Leclercq I; Gigot JF
INSTITUCIÓN / INSTITUTION: - Division of Hepatobiliary and Pancreatic Surgery, Department of Abdominal Surgery and Transplantation, Saint-Luc University Hospital, Universite Catholique de Louvain, Brussels, Belgium.
RESUMEN / SUMMARY: - OBJECTIVES: The most frequent presentation of chemotherapy-related toxicity in colorectal liver metastases (CRLM) is sinusoidal obstruction syndrome (SOS). The purpose of the present study was to identify preoperative factors predictive of SOS and to establish associations between type of chemotherapy and severity of SOS. METHODS: A retrospective study was carried out in a tertiary academic referral hospital. Patients suffering from CRLM who had undergone resection of at least one liver segment were included. Grading of SOS on the non-tumoral liver parenchyma was accomplished according to the Rubbia-Brandt criteria. A total of 151 patients were enrolled and divided into four groups according to the severity of SOS (grades 0-3). RESULTS: Multivariate analysis identified oxaliplatin and 5-fluorouracil as chemotherapeutic agents responsible for severe SOS lesions (P < 0.001 and P = 0.005, respectively). Bevacizumab was identified as having a protective effect against the occurrence of SOS lesions (P = 0.005). Univariate analysis identified the score on the aspartate aminotransferase : platelets ratio index (APRI) as the most significant biological factor predictive of severe SOS lesions. Splenomegaly is also significantly associated with the occurrence of severe SOS lesions. CONCLUSIONS: The APRI score and splenomegaly are effective as factors predictive of SOS. Bevacizumab has a protective effect against SOS.
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[1140]
TÍTULO / TITLE: - Afatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onco Targets Ther. 2013;6:135-43. doi: 10.2147/OTT.S23165. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S23165
AUTORES / AUTHORS: - Nelson V; Ziehr J; Agulnik M; Johnson M
INSTITUCIÓN / INSTITUTION: - Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
RESUMEN / SUMMARY: - The discovery of epidermal growth-factor receptor (EGFR)-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs) have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.
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[1141]
TÍTULO / TITLE: - Antrodia camphorata Grown on Germinated Brown Rice Suppresses Melanoma Cell Proliferation by Inducing Apoptosis and Cell Differentiation and Tumor Growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:321096. doi: 10.1155/2013/321096. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/321096
AUTORES / AUTHORS: - Song M; Park DK; Park HJ
INSTITUCIÓN / INSTITUTION: - Department of Bioscience and Biotechnology, Konkuk University, Gwangjin-gu, Achasan-ro 263, Seoul 143-701, Republic of Korea.
RESUMEN / SUMMARY: - Antrodia camphorata grown on germinated brown rice (CBR) was prepared to suppress melanoma development. CBR extracts were divided into hexane, EtOAc, BuOH, and water fractions. Among all the fractions, EtOAc fraction showed the best suppressive effect on B16F10 melanoma cell proliferation by CCK-8 assay. It also showed the increased cell death and the changed cellular morphology after CBR treatment. Annexin V-FITC/PI, flow cytometry, and western blotting were performed to elucidate anticancer activity of CBR. The results showed that CBR induced p53-mediated apoptotic cell death of B16F10. CBR EtOAc treatment increased melanin content and melanogenesis-related proteins of MITF and TRP-1 expressions, which supports its anticancer activity. Its potential as an anticancer agent was further investigated in tumor-xenografted mouse model. In melanoma-xenografted mouse model, melanoma tumor growth was significantly suppressed under CBR EtOAc fraction treatment. HPLC analysis of CBR extract showed peak of adenosine. In conclusion, CBR extracts notably inhibited B16F10 melanoma cell proliferation through the p53-mediated apoptosis induction and increased melanogenesis. These findings suggest that CBR EtOAc fraction can act as an effective anticancer agent to treat melanoma.
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[1142]
TÍTULO / TITLE: - Cytotoxic Effect of Ethanol Extract of Microalga, Chaetoceros calcitrans, and Its Mechanisms in Inducing Apoptosis in Human Breast Cancer Cell Line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:783690. doi: 10.1155/2013/783690. Epub 2012 Dec 30.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/783690
AUTORES / AUTHORS: - Ebrahimi Nigjeh S; Yusoff FM; Mohamed Alitheen NB; Rasoli M; Keong YS; Omar AR
INSTITUCIÓN / INSTITUTION: - Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
RESUMEN / SUMMARY: - Marine microalgae have been prominently featured in cancer research. Here, we examined cytotoxic effect and apoptosis mechanism of crude ethanol extracts of an indigenous microalga, Chaetoceros calcitrans (UPMAAHU10) on human breast cell lines. MCF-7 was more sensitive than MCF-10A with IC50 value of 3.00 +/- 0.65, whilst the IC50 value of Tamoxifen against MCF-7 was 12.00 +/- 0.52 mu g/mL after 24 hour incubation. Based on Annexin V/Propidium iodide and cell cycle flow cytometry analysis, it was found that inhibition of cell growth by EEC on MCF-7 cells was through the induction of apoptosis without cell cycle arrest. The apoptotic cells at subG0/G1 phase in treated MCF-7 cells at 48 and 72 hours showed 34 and 16 folds increased compared to extract treated MCF-10A cells which showed only 6 and 7 folds increased at the same time points, respectively. Based on GeXP study, EEC induced apoptosis on MCF-7 cells via modulation of CDK2, MDM2, p21Cip1, Cyclin A2, Bax and Bcl-2. The EEC treated MCF-7 cells also showed an increase in Bax/Bcl-2 ratio that in turn activated the caspase-dependent pathways by activating caspase 7. Thus, marine microalga, Chaetoceros calcitrans may be considered a good candidate to be developed as a new anti-breast cancer drug.
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[1143]
TÍTULO / TITLE: - A multibody atomic statistical potential for the prediction of enzyme-inhibitor binding energy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Conf Proc IEEE Eng Med Biol Soc. 2012;2012:5526-9. doi: 10.1109/EMBC.2012.6347246.
●● Enlace al texto completo (gratuito o de pago) 1109/EMBC.2012.6347246
AUTORES / AUTHORS: - Masso M
INSTITUCIÓN / INSTITUTION: - Laboratory for Structural Bioinformatics, School of Systems Biology, George Mason University, Manassas, VA 20110, USA. mmasso@ gmu.edu
RESUMEN / SUMMARY: - Accurate prediction of enzyme-inhibitor binding energy has the capacity to speed drug design and chemical genomics efforts by helping to narrow the focus of experiments. Here a non-redundant set of three hundred high-resolution crystallographic enzyme-inhibitor structures was compiled for analysis, complexes with known binding energies (DeltaG) based on the availability of experimentally determined inhibition constants (ki). Additionally, a separate set of over 1400 diverse high-resolution macromolecular crystal structures was collected for the purpose of creating an all-atom knowledge-based statistical potential, via application of the Delaunay tessellation computational geometry technique. Next, two hundred of the enzyme-inhibitor complexes were randomly selected to develop a model for predicting binding energy, first by tessellating structures of the complexes as well as the enzymes without their bound inhibitors, then by using the statistical potential to calculate a topological score for each structure tessellation. We derived as a predictor of binding energy an empirical linear function of the difference between topological scores for a complex and its isolated enzyme. A correlation coefficient ® of 0.79 was obtained for the experimental and calculated DeltaG values, with a standard error of 2.34 kcal/mol. Lastly, the model was evaluated with the held-out set of one hundred complexes, for which structure tessellations were performed in order to calculate topological score differences, and binding energy predictions were generated from the derived linear function. Calculated binding energies for the test data also compared well with their experimental counterparts, displaying a correlation coefficient of r= 0.77 with a standard error of 2.50 kcal/mol.
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[1144]
TÍTULO / TITLE: - Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF mutant thyroid carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0531
AUTORES / AUTHORS: - Montero-Conde C; Ruiz-Llorente S; Dominguez JM; Knauf JA; Viale A; Sherman EJ; Ryder M; Ghossein RA; Rosen N; Fagin JA
INSTITUCIÓN / INSTITUTION: - 1Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center.
RESUMEN / SUMMARY: - The RAF inhibitor vemurafenib (PLX4032) increases survival in patients with BRAF-mutant metastatic melanoma, but has limited efficacy in patients with colorectal cancers. Thyroid cancer cells are also comparatively refractory to RAF inhibitors. By contrast to melanomas, inhibition of MAPK signaling by vemurafenib is transient in thyroid and colorectal cancer cells. The rebound in ERK in thyroid cells is accompanied by increased HER3 signaling caused by induction of HER3 transcription through decreased promoter occupancy by the transcriptional repressors CtBP1 and 2, and by autocrine secretion of neuregulin-1. The HER kinase inhibitor lapatinib prevents MAPK rebound and sensitizes BRAF-mutant thyroid cancer cells to RAF or MEK inhibitors. This provides a rationale for combining ERK pathway antagonists with inhibitors of feedback-reactivated HER signaling in this disease. The determinants of primary resistance to MAPK inhibitors vary between cancer types, due to preferential upregulation of specific RTKs, and the abundance of their respective ligands.
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[1145]
TÍTULO / TITLE: - 14-3-3epsilon mediates the cell fate decision-making pathways in response of hepatocellular carcinoma to bleomycin-induced DNA damage.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e55268. doi: 10.1371/journal.pone.0055268. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055268
AUTORES / AUTHORS: - Tang S; Bao H; Zhang Y; Yao J; Yang P; Chen X
INSTITUCIÓN / INSTITUTION: - Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - BACKGROUND: Lack of understanding of the response of hepatocellular carcinoma (HCC) to anticancer drugs causes the high mortality of HCC patients. Bleomycin (BLM) that induces DNA damage is clinically used for cancer therapy, while the mechanism underlying BLM-induced DNA damage response (DDR) in HCC cells remains ambiguous. Given that 14-3-3 proteins are broadly involved in regulation of diverse biological processes (BPs)/pathways, we investigate how a 14-3-3 isoform coordinates particular BPs/pathways in BLM-induced DDR in HCC. METHODOLOGYPRINCIPAL FINDINGS: Using dual-tagging quantitative proteomic approach, we dissected the 14-3-3epsilon interactome formed during BLM-induced DDR, which revealed that 14-3-3epsilon via its associations with multiple pathway-specific proteins coordinates multiple pathways including chromosome remodeling, DNA/RNA binding/processing, DNA repair, protein ubiquitination/degradation, cell cycle arrest, signal transduction and apoptosis. Further, “zoom-in” investigation of the 14-3-3epsilon interacting network indicated that the BLM-induced interaction between 14-3-3epsilon and a MAP kinase TAK1 plays a critical role in determining cell propensity of apoptosis. Functional characterization of this interaction further revealed that BLM triggers site-specific phosphorylations in the kinase domain of TAK1. These BLM-induced changes of phosphorylations directly correlate to the strength of the TAK1 binding to 14-3-3epsilon, which govern the phosphorylation-dependent TAK1 activation. The enhanced 14-3-3epsilon-TAK1 association then inhibits the anti-apoptotic activity of TAK1, which ultimately promotes BLM-induced apoptosis in HCC cells. In a data-dependent manner, we then derived a mechanistic model where 14-3-3epsilon plays the pivotal role in integrating diverse biological pathways for cellular DDR to BLM in HCC. CONCLUSIONS: Our data demonstrated on a systems view that 14-3-3epsilon coordinates multiple biological pathways involved in BLM-induced DDR in HCC cells. Specifically, 14-3-3epsilon associates with TAK1 in a phosphorylation-dependent manner to determine the cell fate of BLM-treated HCC cells. Not only individual proteins but also those critical links in the network could be the potential targets for BLM-mediated therapeutic intervention of HCC.
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[1146]
TÍTULO / TITLE: - Neuro-oncology: Optimizing the potential of MGMT as a prognostic biomarker in glioblastoma multiforme.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Neurol. 2013 Mar;9(3):121. doi: 10.1038/nrneurol.2013.20. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1038/nrneurol.2013.20
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[1147]
TÍTULO / TITLE: - A prognostic biomarker for gastric cancer with lymph node metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anat Rec (Hoboken). 2013 Apr;296(4):590-4. doi: 10.1002/ar.22642. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1002/ar.22642
AUTORES / AUTHORS: - Zhang MH; Xu XH; Wang Y; Linq QX; Bi YT; Miao XJ; Ye CF; Gao SX; Gong CY; Xiang H; Dong MS
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, 310003, China.
RESUMEN / SUMMARY: - Gastric cancer is one of the leading causes of tumor-related deaths in China. The tumor, node, metastasis (TNM) classification system is useful for predicting clinical prognosis of patients with gastric cancer. However, determining the presence of lymph node involvement in the early stages of gastric cancer is difficult without biopsy. Therefore, it is necessary to identify novel serum biomarkers for TNM cancer staging and prognostic follow-up. In this study, we have reported fibrinopeptide-A (FPA) with alanine truncation at the N-terminal as a novel biomarker to differentiate gastric cancer with and without lymph node metastases. We analyzed 369 individual serum samples including gastric cancer patients without lymph node metastases (n = 33), gastric cancer patients with lymph node metastases (n = 157; confirmed by pathology), and age- and sex-matched healthy individuals (n = 179). The data showed that 85.4% of patients with lymph node metastases were positive for FPA with alanine truncation at the N-terminal (degAla-FPA, 1,465.63 Da), as determined by tandem mass spectrometry (MS). Using degAla-FPA as the biomarker, the sensitivity was 85.4% for gastric cancer patients with lymph node metastases, and the specificity was 100% for gastric cancer patients without lymph node metastases. The high sensitivity and specificity achieved with serum degAla-FPA levels indicated that MS technology could facilitate the discovery of a novel and quantitative prognostic biomarker for gastric cancer with lymph node involvement. Anat Rec, 296:590-594, 2013. © 2013 Wiley Periodicals, Inc.
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[1148]
TÍTULO / TITLE: - Alteration of the E-Cadherin/beta-Catenin Complex Is an Independent Poor Prognostic Factor in Lung Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Pathol. 2013 Feb;47(1):44-51. doi: 10.4132/KoreanJPathol.2013.47.1.44. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 4132/KoreanJPathol.2013.47.1.44
AUTORES / AUTHORS: - Kim H; Yoo SB; Sun P; Jin Y; Jheon S; Lee CT; Chung JH
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUND: Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells. METHODS: To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, beta-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival. RESULTS: The loss of E-cadherin expression and aberrant beta-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/beta-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/beta-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314). CONCLUSIONS: The alteration of the expression of the E-cadherin/beta-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.
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[1149]
TÍTULO / TITLE: - Tumor Stress-Induced Phosphoprotein1 (STIP1) as a Prognostic Biomarker in Ovarian Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57084. doi: 10.1371/journal.pone.0057084. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057084
AUTORES / AUTHORS: - Chao A; Lai CH; Tsai CL; Hsueh S; Hsueh C; Lin CY; Chou HH; Lin YJ; Chen HW; Chang TC; Wang TH
INSTITUCIÓN / INSTITUTION: - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
RESUMEN / SUMMARY: - Stress-induced phosphoprotein 1 (STIP1) has been recently identified as a released biomarker in human ovarian cancer. In addition, STIP1 secreted by human ovarian cancer cells has been shown to promote tumor cell proliferation by binding to ALK2 (activin A receptor, type II-like kinase 2) and activating the SMAD-ID3 signaling pathways. In this study, a total of 330 ovarian cancer tumor samples were evaluated for STIP1 expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. The quantification of immunoreactivity was accomplished by applying an immunohistochemical scoring system (histoscore). Patients with high-level STIP1 expression (histoscore >/=169) had a significantly worse survival (high STIP1, mean survival time = 76 months; low STIP1, mean survival time = 112 months; P<0.0001). Moreover, STIP1 histoscores were significantly higher in high-grade tumors (grade 3) than in low-grade (grade 1-2) malignancies (P<0.0001), suggesting that STIP1 may be a proxy for tumor aggressiveness. The results of multivariable analysis revealed that high STIP1 histoscores, advanced stages, histologic types, and the presence of residual disease (>/=2 cm) were independent predictors of poor prognosis. The addition of STIP1 histoscores improved the prediction of overall and progression-free survival rates in the multivariable Cox proportional hazard model. The treatment of ovarian cancer cells with recombinant STIP1 stimulated cell proliferation and migration, but co-treatment with anti-STIP1 antibodies abrogated this effect. Our findings suggest that STIP1 expression may be related to prognosis and that the STIP1 pathway may represent a novel therapeutic target for human ovarian cancer.
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[1150]
TÍTULO / TITLE: - Prognostic and predictive biomarkers in gastroenteropancreatic neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):155-7. doi: 10.6092/1590-8577/1472.
AUTORES / AUTHORS: - Stevenson R; Libutti SK; Saif MW
INSTITUCIÓN / INSTITUTION: - Tufts University School of Medicine. Boston, MA, USA. rstevenson@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Neuroendocrine tumors (NET) are a diverse group of tumors that derive from epithelial cells with neuroendocrine differentiation. Gastroenteropancreatic NETs are a subset of NET that arise from the gastrointestinal tract. The natural history and prognosis varies widely between different gastroenteropancreatic NETs, highlighting the importance of identifying accurate prognostic and predictive biomarkers. At the 2013 ASCO Gastrointestinal Cancers Symposium, De Braud et al. (Abstract #186) and Bellister et al. (Abstract #163) present data on two new possible biomarkers.
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[1151]
TÍTULO / TITLE: - The Polo-Like Kinase 1 (PLK1) Inhibitor NMS-P937 Is Effective in a New Model of Disseminated Primary CD56(+) Acute Monoblastic Leukaemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58424. doi: 10.1371/journal.pone.0058424. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058424
AUTORES / AUTHORS: - Casolaro A; Golay J; Albanese C; Ceruti R; Patton V; Cribioli S; Pezzoni A; Losa M; Texido G; Giussani U; Marchesi F; Amboldi N; Valsasina B; Bungaro S; Cazzaniga G; Rambaldi A; Introna M; Pesenti E; Alzani R
INSTITUCIÓN / INSTITUTION: - Oncology, Nerviano Medical Sciences, Nerviano, Milano, Italy.
RESUMEN / SUMMARY: - CD56 is expressed in 15-20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56(+) monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56(+) AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.
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[1152]
TÍTULO / TITLE: - Targeting SRC family kinases inhibits bevacizumab-induced glioma cell invasion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56505. doi: 10.1371/journal.pone.0056505. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056505
AUTORES / AUTHORS: - Huveldt D; Lewis-Tuffin LJ; Carlson BL; Schroeder MA; Rodriguez F; Giannini C; Galanis E; Sarkaria JN; Anastasiadis PZ
INSTITUCIÓN / INSTITUTION: - Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
RESUMEN / SUMMARY: - Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients with recurrent glioblastoma multiforme (GBM). Unfortunately, progression on bevacizumab therapy is often associated with a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there is an urgent need to understand bevacizumab’s influence on glioma biology and block it’s actions towards cell invasion.To explore the mechanism(s) of GBM cell invasion we have examined a panel of serially transplanted human GBM lines grown either in short-term culture, as xenografts in mouse flank, or injected orthotopically in mouse brain. Using an orthotopic xenograft model that exhibits increased invasiveness upon bevacizumab treatment, we also tested the effect of dasatinib, a broad spectrum SFK inhibitor, on bevacizumab-induced invasion.We show that 1) activation of Src family kinases (SFKs) is common in GBM, 2) the relative invasiveness of 17 serially transplanted GBM xenografts correlates strongly with p120 catenin phosphorylation at Y228, a Src kinase site, and 3) SFK activation assessed immunohistochemically in orthotopic xenografts, as well as the phosphorylation of downstream substrates occurs specifically at the invasive tumor edge. Further, we show that SFK signaling is markedly elevated at the invasive tumor front upon bevacizumab administration, and that dasatinib treatment effectively blocked the increased invasion induced by bevacizumab.Our data are consistent with the hypothesis that the increased invasiveness associated with anti-VEGF therapy is due to increased SFK signaling, and support testing the combination of dasatinib with bevacizumab in the clinic.
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[1153]
TÍTULO / TITLE: - Occludin is involved in adhesion, apoptosis, differentiation and Ca2+-homeostasis of human keratinocytes: implications for tumorigenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55116. doi: 10.1371/journal.pone.0055116. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055116
AUTORES / AUTHORS: - Rachow S; Zorn-Kruppa M; Ohnemus U; Kirschner N; Vidal-y-Sy S; von den Driesch P; Bornchen C; Eberle J; Mildner M; Vettorazzi E; Rosenthal R; Moll I; Brandner JM
INSTITUCIÓN / INSTITUTION: - Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
RESUMEN / SUMMARY: - Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca(2+)-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.
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[1154]
TÍTULO / TITLE: - Novel biomarkers for the prediction of metastasis in colorectal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Med Diagn. 2013 Mar;7(2):137-46. doi: 10.1517/17530059.2013.753054. Epub 2012 Dec 14.
●● Enlace al texto completo (gratuito o de pago) 1517/17530059.2013.753054
AUTORES / AUTHORS: - Zlobec I
INSTITUCIÓN / INSTITUTION: - University of Bern, Institute of Pathology L414, Translational Research Unit (TRU) , Murtenstrasse 31, 3010 Bern , Switzerland +41 031 632 8755 ; +41 031 632 9775 ; inti.zlobec@pathology.unibe.ch.
RESUMEN / SUMMARY: - Introduction: In patients with metastatic colorectal cancers, multimodal management and the use of biological agents such as monoclonal antibodies have had major positive effects on survival. The ability to predict which patients may be at ‘high risk’ of distant metastasis could have major implications on patient management. Histomorphological, immunohistochemical or molecular biomarkers are currently being investigated in order to test their potential value as predictors of metastasis. Areas covered: Here, the author reviews the clinical and functional data supporting the investigation of three novel promising biomarkers for the prediction of metastasis in patients with colorectal cancer: tumor budding, Raf1 kinase inhibitor protein (RKIP) and metastasis-associated in colon cancer-1 (MACC1). Expert opinion: The lifespan of most potential biomarkers is short as evidenced by the rare cases that have successfully made their way into daily practice such as KRAS or microsatellite instability (MSI) status. Although the three biomarkers reviewed herein have the potential to become important predictive biomarkers of metastasis, they have similar hurdles to overcome before they can be implemented into clinical management: standardization and validation in prospective patient cohorts.
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[1155]
TÍTULO / TITLE: - Association of Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) with Central Adiposity and Low-Density Lipoprotein Cholesterol.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58225. doi: 10.1371/journal.pone.0058225. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058225
AUTORES / AUTHORS: - Brombo G; Volpato S; Secchiero P; Passaro A; Bosi C; Zuliani G; Zauli G
INSTITUCIÓN / INSTITUTION: - Department of Clinical and Experimental Medicine, Section of Internal Medicine, Gerontology and Clinical Nutrition, University of Ferrara, Ferrara, Italy.
RESUMEN / SUMMARY: - OBJECTIVE: Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), in addition to having a prognostic value in patients with cardiovascular disease, seems to interact with adiposity, insulin resistance and other cardiovascular risk factors. However, the results of previous clinical studies, focused on the association of TRAIL with selected metabolic or anthropometric indices were inconclusive. The aim of this study was to further investigate how soluble TRAIL concentrations independently correlate with major cardiovascular risk factors, including lipid, glycemic and anthropometric features. MATERIALSMETHODS: We examined the associations between serum soluble TRAIL concentrations, measured by ELISA, and lipid, glycemic and anthropometric features in 199 subjects recruited at our Metabolic Outpatient Clinic. RESULTS: Soluble TRAIL concentrations had a significant and direct correlation with total cholesterol (p = 0.046), LDL-cholesterol (p = 0.032), triglycerides (p = 0.01), body mass index (p = 0.046), waist circumference (p = 0.008), fat mass (p = 0.056) and insulin (p = 0.046) and an inverse correlation with HDL-cholesterol (p = 0.02). In multivariable regression analyses adjusted for potential confounders (age, gender, C-reactive protein, HDL-cholesterol, triglycerides, waist circumference, and insulin), TRAIL levels continued to have an independent correlation with LDL-cholesterol and waist circumference (r(2) = 0.04). CONCLUSIONS: Serum TRAIL levels were weakly but significantly and independently associated with waist circumference, a marker of visceral adiposity, and with LDL-cholesterol. Further studies are needed to clarify the biological basis of these relationships.
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[1156]
TÍTULO / TITLE: - Inhibition of Growth and Induction of Apoptosis in Fibrosarcoma Cell Lines by Echinophora platyloba DC: In Vitro Analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Adv Pharmacol Sci. 2013;2013:512931. doi: 10.1155/2013/512931. Epub 2013 Jan 14.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/512931
AUTORES / AUTHORS: - Shahneh FZ; Valiyari S; Azadmehr A; Hajiaghaee R; Yaripour S; Bandehagh A; Baradaran B
INSTITUCIÓN / INSTITUTION: - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
RESUMEN / SUMMARY: - Echinophora platyloba DC plant (Khousharizeh) is one of the indigenous medicinal plants which is used as a food seasoning and medicine in Iran. The objective of this study was to examine the in vitro cytotoxic activity and the mechanism of cell death of crude methanolic extracts prepared from Echinophora platyloba DC, on mouse fibrosarcoma cell line (WEHI-164). Cytotoxicity and viability of methanolic extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Cell death ELISA was employed to quantify the nucleosome production result from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP nick end labeling (TUNEL) assay. Our results demonstrated that the extract decreased cell viability, suppressed cell proliferation, and induced cell death in a time- and dose-dependent manner in WEHI-164 cells (IC50 = 196.673 +/- 12.4 mug/mL) when compared with a chemotherapeutic anticancer drug, Toxol. Observation proved that apoptosis was the major mechanism of cell death. So the Echinophora platyloba DC extract was found to time- and dose-dependently inhibit the proliferation of fibrosarcoma cell possibly via an apoptosis-dependent pathway.
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[1157]
TÍTULO / TITLE: - Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Prod Commun. 2013 Feb;8(2):213-6.
AUTORES / AUTHORS: - Hasan TN; Shafi G; Syed NA; Alfawaz MA; Alsaif MA; Munshi A; Lei KY; Alshatwi AA
INSTITUCIÓN / INSTITUTION: - Molecular Cancer Biology Research Lab, Dept. of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Saudi Arabia.
RESUMEN / SUMMARY: - Nigella sativa (NS), also known as black cumin, has long been used in traditional medicine for treating various cancer conditions. In this study, we sought to investigate the potential anti-cancer effects of NS extract using SiHa human cervical cancer cells. NS showed an 88.3% inhibition of proliferation of SiHa human cervical cancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy.
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[1158]
TÍTULO / TITLE: - Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 26;13(1):154.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-154
AUTORES / AUTHORS: - Ohlund D; Franklin O; Lundberg E; Lundin C; Sund M
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized. METHODS: The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule. RESULTS: We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis. CONCLUSION: We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.
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[1159]
TÍTULO / TITLE: - Docetaxel for non-small-cell lung cancer harboring the activated EGFR mutation with T790M at initial presentation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onco Targets Ther. 2013;6:155-60. doi: 10.2147/OTT.S41797. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S41797
AUTORES / AUTHORS: - Yamane H; Ochi N; Yasugi M; Tabayashi T; Yamagishi T; Monobe Y; Hisamoto A; Kiura K; Takigawa N
INSTITUCIÓN / INSTITUTION: - Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
RESUMEN / SUMMARY: - A 72-year-old woman was referred to our hospital with Stage IV non-small-cell lung cancer (NSCLC). Chest computed tomography revealed a mass in the upper lobe of the right lung, with pleural effusion. Cytologic examination identified adenocarcinoma cells in the right pleural effusion. Furthermore, both a deletion mutation in exon 19 and a threonine-methionine substitution mutation at position 790 in exon 20 (T790M) were detected in the epidermal growth factor receptors (EGFR) in the malignant cells. As systemic chemotherapy consisting of carboplatin and pemetrexed or erlotinib proved ineffective, docetaxel monotherapy was initiated as a third-line treatment. Following salvage chemotherapy, her Eastern Cooperative Oncology Group performance status improved from 3 to 1, with tumor regression over 5 months. To the best of our knowledge, this is the first report of successful docetaxel treatment for a patient with NSCLC harboring the T790M EGFR-activating mutation identified before treatment with EGFR tyrosine kinase inhibitors.
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[1160]
TÍTULO / TITLE: - 3-D DNA methylation phenotypes correlate with cytotoxicity levels in prostate and liver cancer cell models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Pharmacol Toxicol. 2013 Feb 11;14:11. doi: 10.1186/2050-6511-14-11.
●● Enlace al texto completo (gratuito o de pago) 1186/2050-6511-14-11
AUTORES / AUTHORS: - Gertych A; Oh JH; Wawrowsky KA; Weisenberger DJ; Tajbakhsh J
INSTITUCIÓN / INSTITUTION: - Translational Cytomics Group, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. tajbakhshj@cshs.org.
RESUMEN / SUMMARY: - BACKGROUND: The spatial organization of the genome is being evaluated as a novel indicator of toxicity in conjunction with drug-induced global DNA hypomethylation and concurrent chromatin reorganization. 3D quantitative DNA methylation imaging (3D-qDMI) was applied as a cell-by-cell high-throughput approach to investigate this matter by assessing genome topology through represented immunofluorescent nuclear distribution patterns of 5-methylcytosine (MeC) and global DNA (4,6-diamidino-2-phenylindole = DAPI) in labeled nuclei. METHODS: Differential progression of global DNA hypomethylation was studied by comparatively dosing zebularine (ZEB) and 5-azacytidine (AZA). Treated and untreated (control) human prostate and liver cancer cells were subjected to confocal scanning microscopy and dedicated 3D image analysis for the following features: differential nuclear MeC/DAPI load and codistribution patterns, cell similarity based on these patterns, and corresponding differences in the topology of low-intensity MeC (LIM) and low in intensity DAPI (LID) sites. RESULTS: Both agents generated a high fraction of similar MeC phenotypes across applied concentrations. ZEB exerted similar effects at 10-100-fold higher drug concentrations than its AZA analogue: concentration-dependent progression of global cytosine demethylation, validated by measuring differential MeC levels in repeat sequences using MethyLight, and the concurrent increase in nuclear LIM densities correlated with cellular growth reduction and cytotoxicity. CONCLUSIONS: 3D-qDMI demonstrated the capability of quantitating dose-dependent drug-induced spatial progression of DNA demethylation in cell nuclei, independent from interphase cell-cycle stages and in conjunction with cytotoxicity. The results support the notion of DNA methylation topology being considered as a potential indicator of causal impacts on chromatin distribution with a conceivable application in epigenetic drug toxicology.
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[1161]
TÍTULO / TITLE: - HDAC inhibitors induce tumor-cell-selective pro-apoptotic transcriptional responses.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Feb 28;4:e519. doi: 10.1038/cddis.2013.9.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.9
AUTORES / AUTHORS: - Bolden JE; Shi W; Jankowski K; Kan CY; Cluse L; Martin BP; Mackenzie KL; Smyth GK; Johnstone RW
INSTITUCIÓN / INSTITUTION: - Cancer Therapeutics Program, Gene Regulation Laboratory, The Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne 3002, Victoria, Australia.
RESUMEN / SUMMARY: - The identification of recurrent somatic mutations in genes encoding epigenetic enzymes has provided a strong rationale for the development of compounds that target the epigenome for the treatment of cancer. This notion is supported by biochemical studies demonstrating aberrant recruitment of epigenetic enzymes such as histone deacetylases (HDACs) and histone methyltransferases to promoter regions through association with oncogenic fusion proteins such as PML-RARalpha and AML1-ETO. HDAC inhibitors (HDACi) are potent inducers of tumor cell apoptosis; however, it remains unclear why tumor cells are more sensitive to HDACi-induced cell death than normal cells. Herein, we assessed the biological and molecular responses of isogenic normal and transformed cells to the FDA-approved HDACi vorinostat and romidepsin. Both HDACi selectively killed cells of diverse tissue origin that had been transformed through the serial introduction of different oncogenes. Time-course microarray expression profiling revealed that normal and transformed cells transcriptionally responded to vorinostat treatment. Over 4200 genes responded differently to vorinostat in normal and transformed cells and gene ontology and pathway analyses identified a tumor-cell-selective pro-apoptotic gene-expression signature that consisted of BCL2 family genes. In particular, HDACi induced tumor-cell-selective upregulation of the pro-apoptotic gene BMF and downregulation of the pro-survival gene BCL2A1 encoding BFL-1. Maintenance of BFL-1 levels in transformed cells through forced expression conferred vorinostat resistance, indicating that specific and selective engagement of the intrinsic apoptotic pathway underlies the tumor-cell-selective apoptotic activities of these agents. The ability of HDACi to affect the growth and survival of tumor cells whilst leaving normal cells relatively unharmed is fundamental to their successful clinical application. This study provides new insight into the transcriptional effects of HDACi in human donor-matched normal and transformed cells, and implicates specific molecules and pathways in the tumor-selective cytotoxic activity of these compounds.
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[1162]
TÍTULO / TITLE: - Epigenetic regulation of the Wnt signaling inhibitor DACT2 in human hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Epigenetics. 2013 Feb 28;8(4).
AUTORES / AUTHORS: - Zhang X; Yang Y; Liu X; Herman JG; Brock MV; Licchesi JD; Yue W; Pei X; Guo M
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology & Hepatology; Chinese PLA General Hospital; Beijing, China.
RESUMEN / SUMMARY: - DACT2 (Dapper, Dishevelled-associated antagonist of beta-catenin homolog 2) is a member of the DACT family involved in the regulation of embryonic development. Human DACT2 is localized on 6q27, a region of frequent loss of heterozygosity in human cancers. However, the regulation of DACT2 expression and function in hepatocellular carcinoma (HCC) remains unclear. In this study, genetic and epigenetic changes of DACT2 were analyzed in HCC cell lines and primary cancer. We found no single-nucleotide polymorphism (SNP) associated with HCC. Promoter region methylation was correlated with loss or reduction of DACT2 expression, and restoration of DACT2 expression was induced by 5-aza-2’-deoxycytidine (5-AZA) in HCC cell lines. Promoter region methylation was found in 54.84% of primary HCC. Reduction of DACT2 expression was associated with promoter hypermethylation, and expression of DACT2 was inversely related to beta-catenin expression in primary HCC. DACT2 suppressed cell proliferation, induced G 2-M arrest in cell lines and inhibited tumor growth in xenograft nude mice. The transcriptional activity of TCF-4 and the expression of Wnt signaling downstream genes were suppressed by DACT2 re-expression and reactivated by depletion of DACT2. In conclusion, DACT2 is frequently methylated in HCC and its expression is regulated by promoter hypermethylation. DACT2 suppresses HCC by inhibiting Wnt signaling in human HCC.
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[1163]
TÍTULO / TITLE: - Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Molecules. 2013 Mar 19;18(3):3543-61. doi: 10.3390/molecules18033543.
●● Enlace al texto completo (gratuito o de pago) 3390/molecules18033543
AUTORES / AUTHORS: - Mathieu V; Wauthoz N; Lefranc F; Niemann H; Amighi K; Kiss R; Proksch P
INSTITUCIÓN / INSTITUTION: - Laboratoire de Toxicologie, Faculte de Pharmacie, Universite Libre de Bruxelles (ULB), Campus de la Plaine, Boulevard du Triomphe, 1050 Brussels, Belgium. vemathie@ulb.ac.be.
RESUMEN / SUMMARY: - Bastadins-6, -9 and -16 isolated from the marine sponge Ianthella basta displayed in vitro cytostatic and/or cytotoxic effects in six human and mouse cancer cell lines. The in vitro growth inhibitory effects of these bastadins were similar in cancer cell lines sensitive to pro-apoptotic stimuli versus cancer cell lines displaying various levels of resistance to pro-apoptotic stimuli. While about ten times less toxic than the natural cyclic bastadins, the synthetically derived 5,5’-dibromohemibastadin-1 (DBHB) displayed not only in vitro growth inhibitory activity in cancer cells but also anti-angiogenic properties. At a concentration of one tenth of its in vitro growth inhibitory concentration, DBHB displayed actual antimigratory effects in mouse B16F10 melanoma cells without any sign of cytotoxicity and/or growth inhibition. The serum concentration used in the cell culture media markedly influenced the DBHB-induced antimigratory effects in the B16F10 melanoma cell population. We are currently developing a specific inhalation formulation for DBHB enabling this compound to avoid plasmatic albumin binding through its direct delivery to the lungs to combat primary as well as secondary (metastases) tumors.
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[1164]
TÍTULO / TITLE: - ICAD Deficiency in Human Colon Cancer and Predisposition to Colon Tumorigenesis: Linkage to Apoptosis Resistance and Genomic Instability.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57871. doi: 10.1371/journal.pone.0057871. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057871
AUTORES / AUTHORS: - Errami Y; Brim H; Oumouna-Benachour K; Oumouna M; Naura AS; Kim H; Ju J; Davis CJ; Kim JG; Ashktorab H; Fallon K; Xu M; Zhang J; Valle LD; Boulares AH
INSTITUCIÓN / INSTITUTION: - The Stanley Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
RESUMEN / SUMMARY: - We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency may be associated with colon malignancy in humans. Indeed, an examination of ICAD expression using immunohistochemistry in an array of both colon cancer and normal tissues revealed that ICAD expression levels were severely compromised in the cancerous tissues. Upon DNA damage caused by a low dose of irradiation, ICAD cells acquire a tumorigenic phenotype. Colon epithelial cells derived from ICAD mice showed a significant resistance to death induced by the colon carcinogen dimethylhydrazine in vitro and in mice. Such resistance was associated with a decrease in PARP-1 activation. In an animal model of dimethylhydrazine-induced colon tumorigenesis, ICAD(-/-) mice developed significantly higher numbers of tumors with markedly larger sizes than the wild-type counterparts. Interestingly, the phenotype of the ICAD(-/-) mice was not associated with a significant increase in the precancerous aberrant crypt foci suggesting a potential link to tumor progression rather than initiation. More importantly, ICAD deficiency was associated with severe genomic instability as assessed by array comparative genomic hybridization. Such genomic instability consisted most prominently of amplifications but with sizable deletions as compared to the wild-type counterparts affecting several cancer-related genes including RAF-1, GSN, LMO3, and Fzd6 independently of p53. Altogether, our results present a viable case for the involvement of ICAD deficiency in colon carcinogenesis and show that apoptosis and genomic instability may comprise the means by which such deficiency may contribute to the process of increasing susceptibility to carcinogen-induced tumorigenesis.
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[1165]
TÍTULO / TITLE: - Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 1;13:96. doi: 10.1186/1471-2407-13-96.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-96
AUTORES / AUTHORS: - Bruchmann A; Roller C; Walther TV; Schafer G; Lehmusvaara S; Visakorpi T; Klocker H; Cato AC; Maddalo D
INSTITUCIÓN / INSTITUTION: - Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann-von-Helmholtz Platz 1, Eggenstein-Leopoldshafen 76344, Germany. danilo.maddalo@kit.edu.
RESUMEN / SUMMARY: - BACKGROUND: The Bag (Bcl-2 associated athanogene) family of proteins consists of 6 members sharing a common, single-copied Bag domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in the Bag family since it consists of 5 Bag domains covering the whole protein. Bag proteins like Bag1 and Bag3 have been implicated in tumor growth and survival but it is not known whether Bag5 also exhibits this function. METHODS: Bag5 mRNA and protein expression levels were investigated in prostate cancer patient samples using real-time PCR and immunoblot analyses. In addition immunohistological studies were carried out to determine the expression of Bag5 in tissue arrays. Analysis of Bag5 gene expression was carried out using one-way ANOVA and Bonferroni’s Multiple Comparison test. The mean values of the Bag5 stained cells in the tissue array was analyzed by Mann-Whitney test. Functional studies of the role of Bag5 in prostate cancer cell lines was performed using overexpression and RNA interference analyses. RESULTS: Our results show that Bag5 is overexpressed in malignant prostate tissue compared to benign samples. In addition we could show that Bag5 levels are increased following endoplasmic reticulum (ER)-stress induction, and Bag5 relocates from the cytoplasm to the ER during this process. We also demonstrate that Bag5 interacts with the ER-resident chaperone GRP78/BiP and enhances its ATPase activity. Bag5 overexpression in 22Rv.1 prostate cancer cells inhibited ER-stress induced apoptosis in the unfolded protein response by suppressing PERK-eIF2-ATF4 activity while enhancing the IRE1-Xbp1 axis of this pathway. Cells expressing high levels of Bag5 showed reduced sensitivity to apoptosis induced by different agents while Bag5 downregulation resulted in increased stress-induced cell death. CONCLUSIONS: We have therefore shown that Bag5 is overexpressed in prostate cancer and plays a role in ER-stress induced apoptosis. Furthermore we have identified GRP78/BiP as a novel interaction partner of Bag5.
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[1166]
TÍTULO / TITLE: - MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ISRN Hematol. 2013;2013:348212. doi: 10.1155/2013/348212. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/348212
AUTORES / AUTHORS: - Sionov RV
INSTITUCIÓN / INSTITUTION: - The Department of Biochemistry and Molecular Biology, The Institute for Medical Research-Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, Ein-Kerem, 91120 Jerusalem, Israel.
RESUMEN / SUMMARY: - The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance.
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[1167]
TÍTULO / TITLE: - Effects of combining Taxol and cyclooxygenase inhibitors on the angiogenesis and apoptosis in human ovarian cancer xenografts.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):923-928. Epub 2012 Dec 19.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1086
AUTORES / AUTHORS: - Li W; Tang YX; Wan L; Cai JH; Zhang J
INSTITUCIÓN / INSTITUTION: - Department of Gynecology, Nanjing Medical University of Hangzhou Hospital, Hangzhou, Zhejiang 310006, P.R. China.
RESUMEN / SUMMARY: - The present study aimed to investigate the combined effects of Taxol and cyclooxygenase (COX) inhibitors on angiogenesis and cell apoptosis of SKOV-3 human ovarian carcinoma cell xenograft-bearing mice. The experiments were continued for 28 days. Animals were treated with 3 mg/kg SC-560 (a COX-1-selective inhibitor) alone, 100 mg/kg celecoxib (a COX-2-selective inhibitor) alone or SC-560/celecoxib by gavage twice a day, 20 mg/kg Taxol alone intraperitoneally once a week or in combination with SC-560 or celecoxib or SC-560/celecoxib/Taxol for three weeks. The mRNA levels of vascular endothelial growth factor (VEGF) was determined by reverse transcription-polymerase chain reaction (RT-PCR). The microvessel density (MVD) of ovarian carcinoma was determined by immunohistochemistry with anti-CD(34) as the label. The apoptotic index was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. The MVD value and apoptotic index in the SC-560/Taxol group were notably inhibited compared with the Taxol group (P<0.001). Moreover, the VEGF mRNA levels, MVD value and apoptotic index in the SC-560/Taxol group were significantly different from the celecoxib/Taxol group (P<0.05, P<0.05 and P<0.001, respectively). The present study demonstrated that SC-560 enhances the anti-angiogenic and pro-apoptotic effects of Taxol and these effects are better than with celecoxib.
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[1168]
TÍTULO / TITLE: - Nutrient availability alters the effect of autophagy on sulindac sulfide-induced colon cancer cell apoptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastroenterol Res Pract. 2012;2012:897678. doi: 10.1155/2012/897678. Epub 2012 Dec 9.
●● Enlace al texto completo (gratuito o de pago) 1155/2012/897678
AUTORES / AUTHORS: - Chiou SK; Hoa N; Ge L; Jadus MR
INSTITUCIÓN / INSTITUTION: - Research Division, Veterans Affairs Medical Center, 5901 E 7th Street, Long Beach, CA 90822, USA ; Department of Medicine, University of California, 101 The City Drive, Irvine, Orange, CA 92868, USA.
RESUMEN / SUMMARY: - Autophagy is a catabolic process by which a cell degrades its intracellular materials to replenish itself. Induction of autophagy under various cellular stress stimuli can lead to either cell survival or cell death via apoptotic and/or autophagic (nonapoptotic) pathways. The NSAID sulindac sulfide induces apoptosis in colon cancer cells. Here, we show that inhibition of autophagy under serum-deprived conditions resulted in significant reductions of sulindac sulfide-induced apoptosis in HT-29 colon cancer cells. In contrast, inhibition of autophagy under conditions where serum is available significantly increased sulindac sulfide-induced apoptosis in HT-29 cells. We previously showed that the apoptosis inhibitor, survivin, plays a role in regulating NSAID-induced apoptosis and autophagic cell death. Here, we show that survivin protein half-life is increased in the presence of autophagy inhibitors under serum-deprived conditions, but not under conditions when serum is available. Thus, the increased levels of survivin may be a factor contributing to inhibition of sulindac sulfide-induced apoptosis under serum-deprived conditions. These results suggest that whether a cell lives or dies due to autophagy induction depends on the balance of factors that regulate both autophagic and apoptotic processes.
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[1169]
TÍTULO / TITLE: - Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chem Biodivers. 2013 Feb;10(2):177-88. doi: 10.1002/cbdv.201200406.
●● Enlace al texto completo (gratuito o de pago) 1002/cbdv.201200406
AUTORES / AUTHORS: - Ukiya M; Sawada S; Kikuchi T; Kushi Y; Fukatsu M; Akihisa T
INSTITUCIÓN / INSTITUTION: - College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Tokyo 101-8308, Japan. ukiya.motohiko@nihon-u.ac.jp
RESUMEN / SUMMARY: - Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4’,4’,4’-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 muM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity.
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[1170]
TÍTULO / TITLE: - Induction of selective cytotoxicity and apoptosis in human T4-lymphoblastoid cell line (CEMss) by boesenbergin a isolated from boesenbergia rotunda rhizomes involves mitochondrial pathway, activation of caspase 3 and G2/M phase cell cycle arrest.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Complement Altern Med. 2013 Feb 22;13:41. doi: 10.1186/1472-6882-13-41.
●● Enlace al texto completo (gratuito o de pago) 1186/1472-6882-13-41
AUTORES / AUTHORS: - Ng KB; Bustamam A; Sukari MA; Abdelwahab SI; Mohan S; Buckle MJ; Kamalidehghan B; Nadzri NM; Anasamy T; A Hadi AH; Rahman HS
INSTITUCIÓN / INSTITUTION: - UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. ahmadbstmm@yahoo.com.
RESUMEN / SUMMARY: - BACKGROUND: Boesenbergia rotunda (Roxb.) Schlecht (family zingiberaceae) is a rhizomatous herb that is distributed from north-eastern India to south-east Asia, especially in Indonesia, Thailand and Malaysia. Previous research has shown that the crude extract of this plant has cytotoxic properties. The current study examines the cytotoxic properties of boesenbergin A isolated from Boesenbergia rotunda. METHODS: MTT assay was used to check the cytotoxicity of boesenbergin A. The morphological assessment of apoptosis was monitored using normal and fluorescence microscopy. The early and late phase of apoptosis was investigated using annexin V and DNA laddering assays, respectively. The mitochondrial membrane potential (MMP) was assessed by fluorescence microscopy. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition, the protein levels of Bax, Bcl2 and HSP 70 were also analyzed using western blot. Assays of caspase =-3/7, -8 and =-9 were carried out in order to test for induction during treatment. Lastly, cell cycle progression was analyzed using flow cytometry. RESULTS: Boesenbergin A was found to have the highest toxicity towards CEMss cancer cells (IC50 = 8 mug/ml). The morphology of CEMss cells after treatment showed evidence of apoptosis that included blebbing and chromatin condensation. The annexin V assay revealed that early apoptosis is induced after treatment. The DNA laddering assay confirmed that DNA fragmentation had occurred during late apoptosis. The cell cycle analysis indicated that boesenbergin A was able to induce G2/M phase arrest in CEMss cells. The activity of caspases -3/7, -8 and -9 was increased after treatment which indicates both intrinsic and extrinsic pathways are induced during apoptosis. The involvement of mitochondria was established by increased mitochondrial membrane potential and up and down regulation of Bcl2 and Bax proteins as well as HSP70. CONCLUSION: In conclusion, the results demonstrated that boesenbergin A induced apoptosis of CEMss cells through Bcl2/Bax signaling pathways with the involvement of caspases and G2/M phase cell cycle arrest. The current findings warrant further research on boesenbergin A as a novel chemotherapeutic agent for leukemia intervention including studies in animal models.
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[1171]
TÍTULO / TITLE: - Inecalcitol, an analog of 1,25D(3), displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Mar 1;12(5):743-52. doi: 10.4161/cc.23846. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 4161/cc.23846
AUTORES / AUTHORS: - Ma Y; Yu WD; Hidalgo AA; Luo W; Delansorne R; Johnson CS; Trump DL
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology and Therapeutics; Roswell Park Cancer Institute; Buffalo, NY USA.
RESUMEN / SUMMARY: - Epidemiological data suggest an important role of vitamin D signaling in cancer development and progression, and experimental studies demonstrate that the active vitamin D metabolite 1alpha, 25-dihydroxyvitamin D(3) (1,25D(3)) has broad spectrum antitumor activity. Hypercalcemia has often been suggested to limit the clinical application of these data. The 14-epi-analog of 1,25D(3), inecalcitol [19-nor-14-epi-23-yne-1,25-(OH)(2)D(3); TX522], was developed to have superagonistic antitumor activities but low hypercalcemia potential. We examined the antitumor activity of inecalcitol and the underlying mechanisms in a murine squamous cell carcinoma (SCC) model system. In vitro, compared with 1,25D(3), inecalcitol showed enhanced vitamin D receptor (VDR)-mediated transcriptional activity. Inecalcitol suppressed SCC cell proliferation in a dose-dependent manner with an IC(5)(0) value 30 times lower than that of 1,25D(3). Both inecalcitol and 1,25D(3) induced a comparable level of G(0)/G(1) cell cycle arrest in SCC cells. The level of apoptosis induced by inecalcitol was markedly higher than that of 1,25D(3). Apoptosis was mediated through the activation of the caspase 8/10- caspase 3 pathway. Further, inecalcitol markedly inhibited the mRNA and protein expression of c-IAP1 and XIAP compared with 1,25D(3). In vivo, inecalcitol inhibits SCC tumor growth in a dose-dependent fashion. Notably, inecalcitol induced a significantly higher level of apoptosis in the SCC xenograft model. While in vitro inecalcitol demonstrates apparent enhanced VDR binding and antiproliferative effects compared to 1,25D(3), in vivo these advantages disappear; at doses of inecalcitol that have equivalent antitumor effects, similar hypercalcemia is seen. This may be explained by the pharmacokinetics of 1,25D(3) vs. inecalcitol and attributed to the much shorter serum half-life of inecalcitol.We show that inecalcitol has potent antitumor activity in the SCC model system, and this is associated with a strong induction of apoptosis. These findings support the further development of inecalcitol in cancer treatment.
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[1172]
TÍTULO / TITLE: - Silver nanoparticles of Albizia adianthifolia: the induction of apoptosis in human lung carcinoma cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Nanobiotechnology. 2013 Feb 18;11:5. doi: 10.1186/1477-3155-11-5.
●● Enlace al texto completo (gratuito o de pago) 1186/1477-3155-11-5
AUTORES / AUTHORS: - Govender R; Phulukdaree A; Gengan RM; Anand K; Chuturgoon AA
INSTITUCIÓN / INSTITUTION: - Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Private Bag 7, Congella, Durban, 4013, South Africa. chutur@ukzn.ac.za.
RESUMEN / SUMMARY: - BACKGROUND: Silver nanoparticles (AgNP), the most popular nano-compounds, possess unique properties. Albizia adianthifolia (AA) is a plant of the Fabaceae family that is rich in saponins. The biological properties of a novel AgNP, synthesized from an aqueous leaf extract of AA (AAAgNP), were investigated on A549 lung cells. Cell viability was determined by the MTT assay. Cellular oxidative status (lipid peroxidation and glutathione (GSH) levels), ATP concentration, caspase-3/-7, -8 and -9 activities were determined. Apoptosis, mitochondrial (mt) membrane depolarization (flow cytometry) and DNA fragmentation (comet assay) were assessed. The expression of CD95 receptors, p53, bax, PARP-1 and smac/DIABLO was evaluated by flow cytometry and/or western blotting. RESULTS: Silver nanoparticles of AA caused a dose-dependent decrease in cell viability with a significant increase in lipid peroxidation (5-fold vs. control; p = 0.0098) and decreased intracellular GSH (p = 0.1184). A significant 2.5-fold decrease in cellular ATP was observed upon AAAgNP exposure (p = 0.0040) with a highly significant elevation in mt depolarization (3.3-fold vs. control; p < 0.0001). Apoptosis was also significantly higher (1.5-fold) in AAAgNP treated cells (p < 0.0001) with a significant decline in expression of CD95 receptors (p = 0.0416). Silver nanoparticles of AA caused a significant 2.5-fold reduction in caspase-8 activity (p = 0.0024) with contrasting increases in caspase-3/-7 (1.7-fold vs. control; p = 0.0180) and -9 activity (1.4-fold vs. control; p = 0.0117). Western blots showed increased expression of smac/DIABLO (4.1-fold) in treated cells (p = 0.0033). Furthermore, AAAgNP significantly increased the expression of p53, bax and PARP-1 (1.2-fold; p = 0.0498, 1.6-fold; p = 0.0083 and 1.1-fold; p = 0.0359 respectively). CONCLUSION: Data suggests that AAAgNP induces cell death in the A549 lung cells via the mt mediated intrinsic apoptotic program. Further investigation is required to potentiate the use of this novel compound in cancer therapy trials.
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[1173]
TÍTULO / TITLE: - Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):805-812. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1118
AUTORES / AUTHORS: - Zhao X; Zhang GB; Gan WJ; Xiong F; Li Z; Zhao H; Zhu DM; Zhang B; Zhang XG; Li DC
INSTITUCIÓN / INSTITUTION: - Departments of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
RESUMEN / SUMMARY: - In numerous types of cancer, the expression of a novel member of the B7 ligand family, the B7-H3 immunoregulatory protein, has been correlated with a poor prognosis. In the present study, we investigated the role of B7-H3 in chemoresistance in pancreatic carcinoma. Silencing of B7-H3, through lentivirus-mediated delivery of stable short hairpin RNA, was observed to increase the sensitivity of the human pancreatic carcinoma cell line Patu8988 to gemcitabine as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 caused the cancer cells to be more resistant to the drug. Subsequently, we investigated the underlying mechanisms of B7-H3-mediated gemcitabine resistance, and found that the levels of survivin decreased in cells in which B7-H3 had been knocked down. In vivo animal experiments demonstrated that tumors in which B7-H3 had been knocked down displayed a slower growth rate compared with the control xenografts. Notably, gemcitabine treatment led to a strong antitumor activity in mice with tumors in which B7-H3 had been knocked down; however, this effect was only marginal in the control group. Furthermore, survivin expression was weak in gemcitabine-treated tumors in which B7-H3 had been knocked down and apoptosis was increased, as revealed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining. In summary, the present study demonstrated that B7-H3 induces gemcitabine resistance in pancreatic carcinoma cells, at least partially by downregulating survivin expression. These results provide novel insights into the function of B7-H3 and encourage the design and investigation of approaches targeting this protein in treating pancreatic carcinoma.
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[1174]
TÍTULO / TITLE: - Induction of tumor cell apoptosis via Fas/DR5.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Mol Immunol. 2013 Mar;10(2):184. doi: 10.1038/cmi.2012.76.
●● Enlace al texto completo (gratuito o de pago) 1038/cmi.2012.76.
AUTORES / AUTHORS: - Li W; Wang S; Chen C; Zhuang G
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[1175]
TÍTULO / TITLE: - RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Mol Immunol. 2013 Mar;10(2):183. doi: 10.1038/cmi.2012.75.
●● Enlace al texto completo (gratuito o de pago) 1038/cmi.2012.75
AUTORES / AUTHORS: - Liu Z; Wang J; Yin P; Qiu J; Liu R; Li W; Fan X; Cheng X; Chen C; Zhang J; Zhuang G
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[1176]
TÍTULO / TITLE: - Genomics and proteomics approaches for biomarker discovery in sporadic colorectal cancer with metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Genomics Proteomics. 2013 Jan-Feb;10(1):19-25.
AUTORES / AUTHORS: - Gonzalez-Gonzalez M; Garcia JG; Montero JA; Fernandez LM; Bengoechea O; Munez OB; Orfao A; Sayagues JM; Fuentes M
INSTITUCIÓN / INSTITUTION: - Servicio General de Citometria, Departamento de Medicina and Centro de Investigacion del Cancer, Salamanca, España.
RESUMEN / SUMMARY: - Sporadic colorectal cancer (sCRC) is one of the most frequent types of cancer in Europe. Despite understanding of its tumorigenesis, the metastatic process is not yet clear. In this article, we review the most significant genetic and proteomic advances that have been made in regards to research of the sCRC metastatic process, and the new biomarkers that are able to predict disease prognosis or response to treatments, in order to define personalized medicine.
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[1177]
TÍTULO / TITLE: - Cancer Stem-like Cell Properties are Regulated by EGFR/AKT/beta-catenin Signaling and Preferentially Inhibited by Gefitinib in Nasopharyngeal Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS J. 2013 Mar 5. doi: 10.1111/febs.12226.
●● Enlace al texto completo (gratuito o de pago) 1111/febs.12226
AUTORES / AUTHORS: - Ma L; Zhang G; Miao XB; Deng XB; Wu Y; Liu Y; Jin ZR; Li XQ; Liu QZ; Sun DX; Testa JR; Yao KT; Xiao GH
INSTITUCIÓN / INSTITUTION: - Cancer Institute, Southern Medical University, Guangzhou, China.
RESUMEN / SUMMARY: - We report that the EGFR pathway plays a critical role in regulating cancer stem-like cells (CSCs) in nasopharyngeal carcinoma (NPC), one of the most common malignant tumors in Southeast Asia. Effects of EGFR on maintaining CSCs are mainly mediated by AKT signaling, and beta-catenin is responsible for governing CSC properties in response to EGFR/AKT activation. Significantly, CSCs are enriched by cisplatin and decreased by gefitinib in NPC xenograft models. Upon reimplantation in secondary mice, tumor cells derived from cisplatin-treated mice grew rapidly, whereas regrowth of tumor cells from gefitinib-treated mice was severely diminished. We further demonstrate that expression of EGFR correlates with expression of beta-catenin and Nanog in primary tumor specimens from NPC patients. These findings provide mechanistic and preclinical evidence supporting the use of gefitinib alone or in combination with a chemotherapeutic agent in first-line therapy for patients with NPC. In addition, our results suggest that targeting beta-catenin represents a rational clinical modality for patients whose tumors harbor activated EGFR or AKT. © 2013 The Authors Journal compilation © 2013 FEBS.
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[1178]
TÍTULO / TITLE: - Are the Serum Biomarkers Pepsinogen I and II Good Predictors for the Detection of Subjects with Atrophic Gastritis in Areas that have Different Gastric Cancer Incidence?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Iran Med. 2013 Apr;16(4):208-12. doi: 013164/AIM.003.
AUTORES / AUTHORS: - Mohamadkhani A; Darvish Moghaddam S; Salmanroghani H; Allafsghari A; Yazdanbod A; Mirzaei M; Haj-Sheykholeslami A; Bashiri J; Sadjadi A; Massarrat S
INSTITUCIÓN / INSTITUTION: - Digestive Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.massarrat@ams.ac.ir.
RESUMEN / SUMMARY: - BACKGROUND: Northern Iran (Ardabil) is characterized by a high gastric cancer (GC) rate, whereas Southern Iran (Kerman and Yazd) has a low GC rate. The aim of this study is to verify the potential for pepsinogen I and II to detect atrophic gastritis (AG) in both high and low risk populations for GC. METHODS: Sera of blood donors and patients with GC from Ardebil, Kerman and Yazd were used to measure levels of pepsinogen I, II and H. pylori IgG antibody. GC rates in these cities were determined according to the Cancer Registry and upper gastrointestinal (GI) endoscopy results. RESULTS: There were 449 subjects with an average age of 45 +/- 15 years. The GC rate in the endoscopy units of the hospital in Ardabil was four times higher than Kerman or Yazd. The mean serum pepsinogen I levels did not differ between Ardabil (102 +/- 42.6 microg/mL), Kerman (103.3 +/- 49.8 microg/mL), and Yazd (111.7 +/- 39 microg/mL). Pepsinogen II levels were: 8.1 +/- 4.7 microg/mL (Ardabil), 7.5 +/- 5.3 microg/mL (Kerman), and 7.6 +/- 4.4 microg/mL (Yazd), which were not different. The H. pylori infection rates were: Ardabil (61%), Kerman (55%), and Yazd (73%). A low ratio of pepsinogen I to II (</=3) was seen in Ardabil (1.3%), Kerman (1.9%), and Yazd (0.0%), which was not significant. A total of 51.9% of GC patients from Ardabil had normal pepsinogen I (>/=70 microg/mL) levels and pepsinogen I/II ratios that were >5. CONCLUSION: Serum biomarkers pepsinogen I and II and their ratios are probably not sensitive predictors of AG in areas that have either a high or low GC prevalence. This finding is likely related to the lack of an association between GC and advanced AG.
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[1179]
TÍTULO / TITLE: - Dendritic cell-based immunotherapy for colon cancer using an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope from tumor-associated antigen 90K.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Mol Immunol. 2013 Mar 25. doi: 10.1038/cmi.2012.74.
●● Enlace al texto completo (gratuito o de pago) 1038/cmi.2012.74
AUTORES / AUTHORS: - Hee Lee J; Park MS; Hwang JE; Cho SH; Bae WK; Shim HJ; Kim DE; Chung IJ
INSTITUCIÓN / INSTITUTION: - Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.
RESUMEN / SUMMARY: - Tumor-associated antigen 90K is implicated in cell-cell and cell-extracellular matrix adhesion through its interaction with galectin-3 and integrin-beta1 and is highly expressed in malignant tissues, making it a novel target for the development of new immunotherapies. We investigated a potential immunotherapy treatment for colon cancer using 90K-specific cytotoxic T lymphocytes induced by autologous dendritic cells and pulsed with 90K peptides. We selected three peptides (90K351, 90K5 and 90K523) that bind to HLA-A*0201 molecules on the basis of their binding affinity, as determined by a peptide-T2 binding assay. Dendritic cells pulsed with 90K peptides resulted in the efficient generation of mature dendritic cells and exhibited enhanced T-cell stimulation and polarization of naive T cells toward Th1. Dendritic cells pulsed with 90K peptides generated potent cytotoxic T-lymphocytes that lysed T2 cells loaded with each 90K peptide, and 90K+/HLA-A2+ colon cancer cell lines, including HCT116 and SW480, in a dose-dependent and HLA-A*0201-restricted manner. No killing was observed in 90K+/HLA-A2- DLD1 or 90K-/HLA-A2- K562 cells. Therefore, we believe that cytotoxic T-lymphocytes stimulated by 90K peptide-pulsed dendritic cells naturally recognize the 90K peptide presented by colon cancer cells in the context of HLA-A2, and kill 90K-positive tumor cells. Dendritic cells pulsed with 90K peptides led to the induction of granzyme B and perforin positive CD8+ T cells against HCT116 and SW480 cells, but not DLD1 cells. In conclusion, 90K-specific cytotoxic T lymphocytes, generated by stimulating T cells with 90K peptide-pulsed dendritic cells, could be useful effector cells for the immunotherapy treatment of colon cancer.Cellular & Molecular Immunology advance online publication, 25 March 2013; doi:10.1038/cmi.2012.74.
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[1180]
TÍTULO / TITLE: - Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 19;8(1):65.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-65
AUTORES / AUTHORS: - Barazzuol L; Jena R; Burnet NG; Meira LB; Jeynes JC; Kirkby KJ; Kirkby NF
RESUMEN / SUMMARY: - BACKGROUND: The cytotoxicity of radiotherapy and chemotherapy can be enhanced by modulating DNA repair. PARP is a family of enzymes required for an efficient base-excision repair of DNA single-strand breaks and inhibition of PARP can prevent the repair of these lesions. The current study investigates the trimodal combination of ABT-888, a potent inhibitor of PARP1-2, ionizing radiation and temozolomide(TMZ)-based chemotherapy in glioblastoma (GBM) cells. METHODS: Four human GBM cell lines were treated for 5 h with 5 muM ABT-888 before being exposed to X-rays concurrently with TMZ at doses of 5 or 10 muM for 2 h. ABT-888[prime]s PARP inhibition was measured using immunodetection of poly(ADP-ribose) (pADPr). Cell survival and the different cell death pathways were examined via clonogenic assay and morphological characterization of the cell and cell nucleus. RESULTS: Combining ABT-888 with radiation yielded enhanced cell killing in all four cell lines, as demonstrated by a sensitizer enhancement ratio at 50% survival (SER50) ranging between 1.12 and 1.37. Radio- and chemo-sensitization was further enhanced when ABT-888 was combined with both X-rays and TMZ in the O6-methylguanine-DNA-methyltransferase (MGMT)-methylated cell lines with a SER50 up to 1.44. This effect was also measured in one of the MGMT-unmethylated cell lines with a SER50 value of 1.30. Apoptosis induction by ABT-888, TMZ and X-rays was also considered and the effect of ABT-888 on the number of apoptotic cells was noticeable at later time points. In addition, this work showed that ABT-888 mediated sensitization is replication dependent, thus demonstrating that this effect might be more pronounced in tumour cells in which endogenous replication lesions are present in a larger proportion than in normal cells. CONCLUSIONS: This study suggests that ABT-888 has the clinical potential to enhance the current standard treatment for GBM, in combination with conventional chemo-radiotherapy. Interestingly, our results suggest that the use of PARP inhibitors might be clinically significant in those patients whose tumour is MGMT-unmethylated and currently derive less benefit from TMZ.
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[1181]
TÍTULO / TITLE: - A novel angiopoietin-2 selective fully human antibody with potent anti-tumoral and anti-angiogenic efficacy and superior side effect profile compared to Pan-Angiopoietin-1/-2 inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e54923. doi: 10.1371/journal.pone.0054923. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054923
AUTORES / AUTHORS: - Thomas M; Kienast Y; Scheuer W; Bahner M; Kaluza K; Gassner C; Herting F; Brinkmann U; Seeber S; Kavlie A; Welschof M; Ries S; Weidner KM; Regula JT; Klein C
INSTITUCIÓN / INSTITUTION: - Discovery Oncology, Pharma Research and Early Development, Roche Diagnostics GmbH, Penzberg, Germany. markus.thomas@roche.com
RESUMEN / SUMMARY: - There is increasing experimental evidence for an important role of Angiopoietin-2 (Ang-2) in tumor angiogenesis and progression. In addition, Ang-2 is up-regulated in many cancer types and correlated with poor prognosis. To investigate the functional role of Ang-2 inhibition in tumor development and progression, we generated novel fully human antibodies that neutralize specifically the binding of Ang-2 to its receptor Tie2. The selected antibodies LC06 and LC08 recognize both rodent and human Ang-2 with high affinity, but LC06 shows a higher selectivity for Ang-2 over Ang-1 compared to LC08 which can be considered an Ang-2/Ang-1 cross-reactive antibody. Our data demonstrate that Ang-2 blockade results in potent tumor growth inhibition and pronounced tumor necrosis in subcutaneous and orthotopic tumor models. These effects are attended with a reduction of intratumoral microvessel density and tumor vessels characterized by fewer branches and increased pericyte coverage. Furthermore, anti-Ang-2 treatment strongly inhibits the dissemination of tumor cells to the lungs. Interestingly, in contrast to the Ang-2/Ang-1 cross-reactive antibody LC08 that leads to a regression of physiological vessels in the mouse trachea, the inhibition with the selective anti-Ang-2 antibody LC06 appears to be largely restricted to tumor vasculature without obvious effects on normal vasculature. Taken together, these data provide strong evidence for the selective Ang-2 antibody LC06 as promising new therapeutic agent for the treatment of various cancers.
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[1182]
TÍTULO / TITLE: - Activity of the mTOR inhibitor RAD001, the dual mTOR and PI3-kinase inhibitor BEZ235 and the PI3-kinase inhibitor BKM120 in hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Liver Int. 2013 Jan 25. doi: 10.1111/liv.12126.
●● Enlace al texto completo (gratuito o de pago) 1111/liv.12126
AUTORES / AUTHORS: - Kirstein MM; Boukouris AE; Pothiraju D; Buitrago-Molina LE; Marhenke S; Schutt J; Orlik J; Kuhnel F; Hegermann J; Manns MP; Vogel A
INSTITUCIÓN / INSTITUTION: - Department of Hepatology, Gastroenterology and Endocrinology, Hannover Medical School, Hannover, Germany.
RESUMEN / SUMMARY: - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide with only few therapeutic options for patients with advanced disease. There is growing evidence indicating that activation of the PI3K/Akt/mTOR pathway plays an important role in HCC and therefore represents a promising target for novel therapeutic approaches. The aim of this study was to evaluate and compare the antitumour activity of the mTOR inhibitor RAD001, the dual mTOR and PI3-kinase inhibitor BEZ235 and the PI3-kinase inhibitor BKM120 in vitro and in vivo. EXPERIMENTAL DESIGN: The antitumour effects of RAD001, BEZ235 and BKM120 were analysed in seven hepatoma cell lines as mono and combination therapy with Doxorubicin, Cisplatin, Irinotecan or 5-Flourouracil in vitro and in xenografts. Cell-cycle progression, apoptosis, and autophagy were analysed. Furthermore, effects on mitochondrial respiration and glycolysis were assessed. RESULTS: Treatment with RAD001, BEZ235 and BKM120 markedly reduced tumour cell viability. Combination of PI3K inhibitors with chemotherapy was most effective. RAD001, BEZ235 and BKM120 reduced tumour growth mainly by inhibiting cell-cycle progression rather than by inducing apoptosis. Interestingly, the antitumour effects were strongly associated with a reduction of mitochondrial respiration. BKM120, which exhibited the strongest antiproliferative effect, most strongly impaired oxidative phosphorylation compared with the other drugs. CONCLUSIONS: In this study, BKM120 showed the strongest antitumour activity. Our findings suggest impairment of mitochondrial function as a relevant mechanism of BKM120. Moreover, combination of PI3K and mTOR inhibitors with cytotoxic agents could be promising option for non-cirrhotic HCC patients.
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[1183]
TÍTULO / TITLE: - Pancreatic cancer: updates on translational research and future applications.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):145-8. doi: 10.6092/1590-8577/1466.
AUTORES / AUTHORS: - Sarris EG; Syrigos KN; Saif MW
INSTITUCIÓN / INSTITUTION: - Department of Medicine and Cancer Center, Tufts Medical Center. Boston, MA, USA. wsaif@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Pancreatic cancer is one of the most lethal malignancies with a mortality rate almost equal to its incidence. It is ranked as the fourth leading cause of cancer-related deaths in the United States, and despite intensive basic and clinical research over the last few years, the survival benefit for the majority of patients with pancreatic cancer is still disappointing. Due to the absence of specific symptoms and the lack of early detection tests, pancreatic cancer is usually diagnosed at an advanced inoperrable stage and palliative chemotherapy with the purine analogue gemcitabine in combination with the targeted agent erlotinib, remains the mainstay method in the management of these patients. Therefore, there is an imperative need for new findings in the translational research field with prognostic, predictive and therapeutic value. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #141 which investigates the interaction between liver and pancreatic organ damage in patients with pancreatic cancer and the potential contribution of the patatin-like phospholipase domain containing 3 (PNPLA3) gene variation in pancreatic cancer development and on Abstract #149, in which, the prognostic and predictive role of SWI/SNF complex, a chromatin-remodeling complex, is examined. The key role of pharmacogenomics, in terms of predicting response and resistance to chemotherapy in pancreatic cancer patients, is analyzed in Abstract #142 and the contribution of circulating tumor cell detection in the early diagnosis of pancreatic cancer, allowing the avoidance of more invasive procedures like EUS-FNA, is discussed in Abstract #157. Lastly, in Abstract #164, the diagnostic utility of YKL-40 and IL-6 in pancreatic cancer patients is investigated.
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[1184]
TÍTULO / TITLE: - Synergistic interaction between sorafenib and gemcitabine in EGFR-TKI-sensitive and EGFR-TKI-resistant human lung cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):440-446. Epub 2012 Nov 7.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1017
AUTORES / AUTHORS: - Li J; Pan YY; Zhang Y
INSTITUCIÓN / INSTITUTION: - Department of Geriatrics, The Third Affiliated Hospital of Anhui Medical University, Hefei 230061;
RESUMEN / SUMMARY: - Sorafenib is a highly selective multi-targeted agent and has been reported to have potent antitumor effects against various tumors, including human non-small cell lung cancer (NSCLC). In the present study, we explored the antitumor effect and associated molecular mechanisms of sorafenib against human lung cancer cell lines in vitro. We also investigated the efficacy of concurrent and sequential administration of sorafenib and gemcitabine in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-sensitive and EGFR-TKI-resistant NSCLC cell lines. The PC-9 (EGFR-TKI-sensitive, EGFR-mutated) and A549 (EGFR-TKI-resistant, K-Ras-mutated) NSCLC cell lines were treated with sorafenib and gemcitabine, alone, in combination or with different schedules. Cytotoxicity was assessed by MTT assay, cell cycle distribution was analyzed by flow cytometry and alterations in signaling pathways were analyzed by western blotting. We found that sorafenib exhibited dose-dependent growth inhibition in the EGFR-TKI-sensitive and EGFR-TKI-resistant NSCLC cell lines, and the sequence gemcitabine-->sorafenib exhibited the strongest synergism. Sorafenib arrested the cell cycle at G1 phase, whereas gemcitabine caused arrest at S phase. The molecular mechanism of this synergism is that the downstream signaling pathways that were initially activated by gemcitabine exposure were efficiently suppressed by the subsequent exposure to sorafenib. By contrast, the reverse of this sequential administration resulted in antagonism, which may be due to differential effects on cell cycle arrest. The results suggest that sorafenib as a single agent exhibits anti-proliferative effects in vitro in NSCLC cell lines with EGFR and K-Ras mutations and that the sequential administration of gemcitabine followed by sorafenib is superior to sorafenib followed by gemcitabine and concurrent administration.
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[1185]
TÍTULO / TITLE: - Curcumin-targeting Pericellular Serine Protease Matriptase Role in Suppression of Prostate Cancer Cell Invasion, Tumor Growth and Metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Prev Res (Phila). 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0293-T
AUTORES / AUTHORS: - Cheng TS; Chen WC; Lin YY; Tsai CH; Liao CI; Shyu HY; Ko CJ; Tzeng SF; Huang CY; Yang PC; Hsiao PW; Lee MS
INSTITUCIÓN / INSTITUTION: - 1Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University.
RESUMEN / SUMMARY: - Curcumin has been shown to possess potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism involved in curcumin’s ability to suppress prostate cancer cell invasion, tumor growth and metastasis is not yet well understood. In this study, we showed that curcumin can suppress EGF- and heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment significantly resulted in reduced MMP-9 activity and down-regulation of cellular matriptase, a membrane-anchored serine protease with oncogenic roles in tumor formation and invasion. Our data further show that curcumin is able to inhibit the induction effects of androgens and EGF on matriptase activation, as well as to reduce the activated levels of matriptase after its overexpression, thus suggesting that curcumin may interrupt diverse signal pathways to block the protease. Furthermore, the reduction of activated matriptase in cells by curcumin was also partly due to curcumin’s effect on promoting the shedding of matriptase into an extracellular environment, but not via altering matriptase gene expression. Additionally, curcumin significantly suppressed the invasive ability of PCa cells induced by matriptase overexpression. In xenograft model, curcumin not only inhibits PCa tumor growth and metastasis but also down-regulates matriptase activity in vivo. Overall, the data indicate that curcumin exhibits a suppressive effect on prostate cancer cell invasion, tumor growth and metastasis, at least in part via down-regulating matriptase function.
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[1186]
TÍTULO / TITLE: - Superior antitumor activity of nanoparticle albumin-bound Paclitaxel in experimental gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e58037. doi: 10.1371/journal.pone.0058037. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058037
AUTORES / AUTHORS: - Zhang C; Awasthi N; Schwarz MA; Hinz S; Schwarz RE
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America ; Hamon Center for Therapeutic Oncology Research, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America ; Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
RESUMEN / SUMMARY: - Gastric cancer is the second common cause of cancer related death worldwide and lacks highly effective treatment for advanced disease. Nab-paclitaxel is a novel microtubule-inhibitory cytotoxic agent that has not been tested in gastric cancer as of yet. In this study, human gastric cancer cell lines AGS, NCI-N87 and SNU16 were studied. Nab-paclitaxel inhibited cell proliferation with an IC50 of 5 nM in SNU16, 23 nM in AGS and 49 nM in NCI-N87 cells after 72-hour treatment, which was lower than that of oxaliplatin (1.05 muM to 1.51 muM) and epirubicin (0.12 muM to 0.25 muM). Nab-paclitaxel treatment increased expression of the mitotic-spindle associated phospho-stathmin irrespective of the baseline total or phosphorylated stathmin level, and induced mitotic cell death as confirmed through increased expression of cleaved-PARP and caspase-3. After a two-week nab-paclitaxel, oxaliplatin or epirubicin treatment, the average in vivo local tumor growth inhibition rate was 77, 17.2 and 21.4 percent, respectively (p = 0.002). Effects of therapy on tumoral proliferative and apoptotic indices corresponded with tumor growth inhibition data, while expression of phospho-stathmin also increased in tissues. There was an increase in median animal survival after nab-paclitaxel treatment (93 days) compared to controls (31 days, p = 0.0007), oxaliplatin (40 days, p = 0.0007) or to docetaxel therapy (81 days, p = 0.0416). The strong antitumor activity of nab-paclitaxel in experimental gastric cancer supports such microtubule-inhibitory strategy for clinical application. Nab-paclitaxel benefits were observed independent from phosphorylated stathmin expression at baseline, putting into question the consideration of nab-paclitaxel use in gastric cancer based on this putative biomarker.
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[1187]
TÍTULO / TITLE: - The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56661. doi: 10.1371/journal.pone.0056661. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056661
AUTORES / AUTHORS: - Yeh CB; Hsieh MJ; Lin CW; Chiou HL; Lin PY; Chen TY; Yang SF
INSTITUCIÓN / INSTITUTION: - School of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Emergency Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
RESUMEN / SUMMARY: - BACKGROUND: The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion. METHODOLOGY AND PRINCIPAL FINDINGS: Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 microM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol. CONCLUSIONS: Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways.
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[1188]
TÍTULO / TITLE: - Synstatin: a selective inhibitor of the syndecan-1-coupled IGF1R-alphavbeta3 integrin complex in tumorigenesis and angiogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS J. 2013 Feb 1. doi: 10.1111/febs.12160.
●● Enlace al texto completo (gratuito o de pago) 1111/febs.12160
AUTORES / AUTHORS: - Rapraeger AC
INSTITUCIÓN / INSTITUTION: - Department of Human Oncology, Carbone Comprehensive Cancer Center, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, WI, USA.
RESUMEN / SUMMARY: - The syndecans are a family of heparan sulfate-decorated cell-surface proteoglycans: matrix receptors with roles in cell adhesion and growth factor signaling. Their heparan sulfate chains recognize ‘heparin-binding’ motifs that are ubiquitously present in the extracellular matrix, providing the means for syndecans to constitutively bind and cluster to sites of cell-matrix adhesion. Emerging evidence suggests that specialized docking sites in the syndecan extracellular domains may serve to localize other receptors to these sites as well, including integrins and growth factor receptor tyrosine kinases. A prototype of this mechanism is capture of the alphavbeta3 integrin and insulin-like growth factor 1 receptor (IGF1R) by syndecan-1 (Sdc1), forming a ternary receptor complex in which signaling downstream of IGF1R activates the integrin. This Sdc1-coupled ternary receptor complex is especially prevalent on tumor cells and activated endothelial cells undergoing angiogenesis, reflecting the up-regulated expression of alphavbeta3 integrin in such cells. As such, much effort has focused on developing therapeutic agents that target this integrin in various cancers. Along these lines, the site in the Sdc1 ectodomain that is responsible for capture and activation of the alphavbeta3 or alphavbeta5 integrins by IGF1R can be mimicked by a short peptide called ‘synstatin’, which competitively displaces the integrin and IGF1R kinase from the syndecan and inactivates the complex. This review summarizes our current knowledge of the Sdc1-coupled ternary receptor complex and the efficacy of synstatin as an emerging therapeutic agent to target this signaling mechanism.
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[1189]
TÍTULO / TITLE: - Type I interferons induce autophagy in certain human cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Autophagy. 2013 Feb 18;9(5).
AUTORES / AUTHORS: - Schmeisser H; Fey SB; Horowitz J; Fischer ER; Balinsky CA; Miyake K; Bekisz J; Snow AL; Zoon KC
INSTITUCIÓN / INSTITUTION: - National Institutes of Health; National Institute of Allergy and Infectious Disease; Cytokine Biology Section; Bethesda, MD USA.
RESUMEN / SUMMARY: - Autophagy is an evolutionarily conserved cellular recycling mechanism that occurs at a basal level in all cells. It can be further induced by various stimuli including starvation, hypoxia, and treatment with cytokines such as IFNG/IFNgamma and TGFB/TGFbeta. Type I IFNs are proteins that induce an antiviral state in cells. They also have antiproliferative, proapoptotic and immunomodulatory activities. We investigated whether type I IFN can also induce autophagy in multiple human cell lines. We found that treatment with IFNA2c/IFNalpha2c and IFNB/IFNbeta induces autophagy by 24 h in Daudi B cells, as indicated by an increase of autophagy markers MAP1LC3-II, ATG12-ATG5 complexes, and a decrease of SQSTM1 expression. An increase of MAP1LC3-II was also detected 48 h post-IFNA2c treatment in HeLa S3, MDA-MB-231, T98G and A549 cell lines. The presence of autophagosomes in selected cell lines exposed to type I IFN was confirmed by electron microscopy analysis. Increased expression of autophagy markers correlated with inhibition of MTORC1 in Daudi cells, as well as inhibition of cancer cell proliferation and changes in cell cycle progression. Concomitant blockade of either MTOR or PI3K-AKT signaling in Daudi and T98G cells treated with IFNA2c increased the level of MAP1LC3-II, indicating that the PI3K-AKT-MTORC1 signaling pathway may modulate IFN-induced autophagy in these cells. Taken together, our findings demonstrated a novel function of type I IFN as an inducer of autophagy in multiple cell lines.
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[1190]
TÍTULO / TITLE: - Specific Biomarkers Are Associated with Docetaxeland Gemcitabine-Resistant NSCLC Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Transl Oncol. 2012 Dec;5(6):461-8. Epub 2012 Dec 1.
AUTORES / AUTHORS: - Pasini A; Paganelli G; Tesei A; Zoli W; Giordano E; Calistri D
INSTITUCIÓN / INSTITUTION: - Laboratory of Cellular and Molecular Engineering “S. Cavalcanti”, School of Engineering, University of Bologna, Campus of Cesena, Cesena, Italy.
RESUMEN / SUMMARY: - Five-year survival rate for lung cancer is limited to 10% to 15%. Therefore, the identification of novel therapeutic prognostic factors is an urgent requirement. The aim of this study is thus to highlight specific biomarkers in chemoresistant non-small cell lung cancer cell lines. Therefore, we checked-in the control condition as well as after short-term pharmacological treatment with either docetaxel or gemcitabine-the expression of genes such as tumor suppressor genes (CDKN2A, DAPK, FHIT, GSTP1, MGMT, RARbeta2, RASSF1A, and TIMP3), genes associated with drug resistance (BRCA1, COX2, ERCC1, IGFBP3, RRM1, and TUBB3), and stemness-related genes (CD133, OCT4, and SLUG) in two cellular models of squamous carcinoma (CAEP) and adenocarcinoma (RAL) of the lung originally established. Their promoter methylation profile was also evaluated. Drug-related genes were upregulated. Cisplatin resistance matched with high levels of BRCA1 and ERCC1 in both cell lines; docetaxel sensitivity of CAEP cells was associated to levels of TUBB3 lower than RAL cells. Although CAEP cells were more sensitive to gemcitabine, both cell lines showed high levels of RRM1. Stemness-related genes were downregulated in the control condition but became upregulated in docetaxel-resistant cells, indicating the selection of a population with stemness features. We did not find an unequivocal correspondence between gene expression and respective DNA promoter methylation status, suggesting the involvement of additional mechanisms of gene expression regulation. These results highlight specific biomarkers consistent with the different responses of the two cell lines to standard pharmacological treatments and indicate specific molecular traits for their chemoresistance.
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[1191]
TÍTULO / TITLE: - Inhibition of U-87 MG glioblastoma by AN-152 (AEZS-108), a targeted cytotoxic analog of luteinizing hormone-releasing hormone.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncotarget. 2013 Mar 7.
AUTORES / AUTHORS: - Jaszberenyi M; Schally AV; Block NL; Nadji M; Vidaurre I; Szalontay L; Rick FG
INSTITUCIÓN / INSTITUTION: - Veterans Affairs Medical Center, Miami, FL.
RESUMEN / SUMMARY: - Glioblastoma multiforme is the most frequent tumor of the central nervous system in adults and has a dismal clinical outcome, which necessitates the development of new therapeutic approaches. We investigated in vivo the action of the targeted cytotoxic analog of luteinizing hormone releasing hormone, AN-152 (AEZS-108) in nude mice (Ncr nu/nu strain) bearing xenotransplanted U-87 MG glioblastoma tumors. We evaluated in vitro the expression of LHRH receptors, proliferation, apoptosis and the release of oncogenic and tumor suppressor cytokines. Clinical and U-87 MG samples of glioblastoma tumors expressed LHRH receptors. Treatment of nude mice with AN-152, once a week at an intravenous dose of 413 nmol/20g, for six weeks resulted in 76 % reduction in tumor growth. AN-152 nearly completely abolished tumor progression and elicited remarkable apoptosis in vitro. Genomic (RT-PCR) and proteomic (ELISA, Western blot) studies revealed that AN-152 activated apoptosis, as reflected by the changes in p53 and its regulators and substrates, inhibited cell growth, and elicited changes in intermediary filament pattern. AN-152 similarly reestablished contact regulation as demonstrated by expression of adhesion molecules and inhibited vascularization, as reflected by the transcription of angiogenic factors. Our findings suggest that targeted cytotoxic analog AN-152 (AEZS-108) should be considered for a treatment of glioblastomas.
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[1192]
TÍTULO / TITLE: - Association of integrin beta1 and c-MET in mediating EGFR TKI gefitinib resistance in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 13;13(1):15. doi: 10.1186/1475-2867-13-15.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-15
AUTORES / AUTHORS: - Ju L; Zhou C
INSTITUCIÓN / INSTITUTION: - Cancer Institute, Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Medical School, 507 Zhengmin Road, Shanghai, 200433, China. caicunzhou@yahoo.com.cn.
RESUMEN / SUMMARY: - Although some patients are initially sensitive to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), resistance invariably develops. Therefore, it’s very important to study the molecular mechanism of this resistance. In our previous study we found that integrin beta1 can induce EGFR TKIs resistance in non-small cell lung cancer (NSCLC) cells. Here we analyzed the association of integrin beta1 and c-MET that is a recognized mechanism of EGFR TKIs resistance in NSCLC to demonstrate the mechanism of integrin beta1 related EGFR TKIs resistance. We found that the ligands of integrin beta1 and c-MET could synergistically promote cell proliferation and their inhibitors could synergistically improve the sensitivity to gfitinib, increase apoptosis, and inhibit the downstream signal transduction: focal adhesion kinase (FAK) and AKT. On the other hand, ligand-dependent activation of integrin beta1 could induce EGFR TKIs resistance through activating c-MET and its downstream signals. Thus, it can be concluded that there is crosstalk between integrin beta1 and c-MET and integrin beta1 mediates EGFR TKI resistance associating with c-MET signaling pathway in non-small cell lung cancer.
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