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Artículos originales (todos) *** Original articles (all)
RESPIRATORY TRACT TUMORS
(Conceptos / Keywords: NSCLC; SCLC, Mesotheliomas; Tracheal tumors; Bronchial tumors; etc).
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: - Elderly patients with advanced NSCLC in phase III clinical trials: are the elderly excluded from practice-changing trials in advanced NSCLC?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):366-8. doi: 10.1097/JTO.0b013e31827e2145.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827e2145
AUTORES / AUTHORS: - Sacher AG; Le LW; Leighl NB; Coate LE
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology & Hematology, Princess Margaret Hospital & University Health Network, University of Toronto, Ontario, Canada. adrian.sacher@mail.utoronto.ca
RESUMEN / SUMMARY: - INTRODUCTION: Elderly patients constitute the majority of patients with advanced non-small-cell lung cancer (NSCLC). The median age of newly diagnosed patients with lung cancer in the United States is approximately 70 years. Despite this, the elderly are significantly underrepresented in clinical trials. This has led to increasing uncertainty as to their optimal treatment. Here, we seek to determine the proportion of elderly patients in key phase III clinical trials in advanced NSCLC. METHODS: A literature search for all phase III trials of systemic therapy for advanced NSCLC between 1980 and 2010 was performed using PubMed. The 100 most highly cited trials were then determined using the “Web of Science” application. The inclusion criteria and results of each of these studies were examined for the exclusion of elderly patients, median patient age, and age range. RESULTS: A total of 248 trials were reviewed. Among the 100 most cited trials, 33% specifically excluded elderly patients in their trial design (age exclusion ranged from >65 to >75 years of age). The average-reported patient median age in these trials was 60.9 years. The average age for trials that did not exclude elderly patients was not significantly different at 61.0 (p = 0.97). The average median age of patients was 61 years (95% confidence interval (CI): 60.4-61.6) in all trials. CONCLUSION: Elderly patients are significantly underrepresented in these recent key practice-defining trials. Greater representation of elderly patients in phase III trials is required to better define evidence-based treatment paradigms in the increasingly elderly NSCLC population.
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[3]
TÍTULO / TITLE: - A Retrospective Analysis of VeriStrat Status on Outcome of a Randomized Phase II Trial of First-Line Therapy with Gemcitabine, Erlotinib, or the Combination in Elderly Patients (Age 70 Years or Older) with Stage IIIB/IV Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):443-51. doi: 10.1097/JTO.0b013e3182835577.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182835577
AUTORES / AUTHORS: - Stinchcombe TE; Roder J; Peterman AH; Grigorieva J; Lee CB; Moore DT; Socinski MA
INSTITUCIÓN / INSTITUTION: - *Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; daggerBiodesix, Inc. Boulder, CO; double daggerDepartment of Psychology, University of North Carolina at Charlotte, Charlotte, NC; section signDivision of Biostatistics and Data Management, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; and ||Division of Hematology and Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
RESUMEN / SUMMARY: - PURPOSE: : In a multicenter randomized phase II trial of gemcitabine (arm A), erlotinib (arm B), and gemcitabine and erlotinib (arm C), similar progression-free survival (PFS) and overall survival (OS) were observed in all arms. We performed an exploratory, blinded, retrospective analysis of plasma or serum samples collected as part of the trial to investigate the ability of VeriStrat (VS) to predict treatment outcomes. METHODS: : Ninety-eight patients were assessable, and the majority had stage IV disease (81%), adenocarcinoma histology (63%), reported current or previous tobacco use (84%), and 26% had a performance status (PS) of 2. RESULTS: : In arm A, patients with VS Good (n = 20) compared with VS Poor status (n = 8) had similar PFS (hazard ratio [HR]: 1.21; p = 0.67) and OS (HR: 0.82; p = 0.64). In arm B, patients with VS Good (n = 26) compared with VS Poor (n = 12) had a statistically significantly superior PFS (HR: 0.33; p = 0.002) and OS (HR: 0.40; p = 0.014). In arm C, patients with VS Good (n = 17) compared with Poor (n = 1 5) had a superior PFS (HR: 0.42; p = 0.027) and a trend toward superior OS (HR: 0.48; p = 0.051). In the multivariate analysis for PFS, VS status was statistically significant (p = 0.011); for OS, VS status (p = 0.017) and PS (p = 0.005) were statistically significant. A statistically significant VS and treatment interaction (gemcitabine versus erlotinib) was observed for PFS and OS. CONCLUSIONS: : Gemcitabine is the superior treatment for elderly patients with VS Poor status. First-line erlotinib for elderly patients with VS Good status may warrant further investigation.
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[4]
TÍTULO / TITLE: - New pathologic classification of lung cancer: relevance for clinical practice and clinical trials.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):992-1001. doi: 10.1200/JCO.2012.46.9270. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.46.9270
AUTORES / AUTHORS: - Travis WD; Brambilla E; Riely GJ
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; travisw@mskcc.org.
RESUMEN / SUMMARY: - We summarize significant changes in pathologic classification of lung cancer resulting from the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. The classification was developed by an international core panel of experts representing IASLC, ATS, and ERS with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. Because 70% of patients with lung cancer present with advanced stages, a new approach to small biopsies and cytology with specific terminology and criteria focused on the need for distinguishing squamous cell carcinoma from adenocarcinoma and on molecular testing for EGFR mutations and ALK rearrangement. Tumors previously classified as non-small-cell carcinoma, not otherwise specified, because of the lack of clear squamous or adenocarcinoma morphology should be classified further by using a limited immunohistochemical workup to preserve tissue for molecular testing. The terms “bronchioloalveolar carcinoma” and “mixed subtype adenocarcinoma” have been discontinued. For resected adenocarcinomas, new concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma define patients who, if they undergo complete resection, will have 100% disease-free survival. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic, acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype with poor prognosis. Former mucinous bronchioloalveolar carcinomas are now called “invasive mucinous adenocarcinoma.” Because the lung cancer field is now rapidly evolving with new advances occurring on a frequent basis, particularly in the molecular arena, this classification provides a much needed standard for pathologic diagnosis not only for patient care but also for clinical trials and TNM classification.
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[5]
TÍTULO / TITLE: - Phase II randomized trial of carboplatin and gemcitabine with or without dexamethasone pre-treatment in patients with Stage IV non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2111-3
AUTORES / AUTHORS: - Rinehart J; Arnold S; Kloecker G; Lim A; Zaydan MA; Baeker T; Maheshwari JG; Carloss H; Slone S; Shelton B; Croley J; Kvale E; Brooks M; Leggas M
INSTITUCIÓN / INSTITUTION: - Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, KY, 40536, USA, john.rinehart@uky.edu.
RESUMEN / SUMMARY: - PURPOSE: Pre-clinical and early-phase clinical studies have demonstrated that dexamethasone (DEX) administration prior to chemotherapy reduces toxicity and enhances efficacy in the treatment of cancer. We undertook a randomized, phase II multi-institutional trial to evaluate these effects in patients with Stage IV non-small cell lung cancer. METHODS: Patients were treated with carboplatin on day 1 and gemcitabine on days 1 and 8 every 21 days, for up to 6 cycles. Patients were randomized not to receive (Arm 1, n = 25) or to receive (Arm 2, n = 31) DEX orally for 4 days prior to chemotherapy on days 1 and 8. The primary endpoint was the incidence/course of grade 3 and 4 hematologic toxicity. Secondary endpoints included efficacy [response and overall survival (OS)] and evaluation of the Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, to predict survival and toxicity. RESULTS: The incidence/course of grade 3 and 4 hematologic toxicity was significantly reduced in Arm 2 (DEX) versus Arm 1 (no DEX): neutrophils = 13 versus 40 % (p = 0.009) and platelets = 23 versus 44 % (p = 0.03). Response rates and OS were higher in Arm 2 versus Arm 1: 8/31 versus 2/25 (partial response, p = ns) and 378 versus 291 days (p = ns). The GPS significantly predicted survival OS (p = 0.04) but not toxicity. CONCLUSIONS: Pre-treating patients with DEX is a safe, effective, and economic method of reducing the hematologic toxicity of carboplatin and gemcitabine. Our data suggest efficacy may also be enhanced by DEX pre-treatment.
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[6]
TÍTULO / TITLE: - Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): A phase II trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 20. pii: S0169-5002(13)00016-0. doi: 10.1016/j.lungcan.2013.01.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.008
AUTORES / AUTHORS: - Gervais R; Robinet G; Clement-Duchene C; Denis F; Kouri CE; Martin P; Chouaki N; Bourayou N; Morere JF
INSTITUCIÓN / INSTITUTION: - Oncology Department, Centre Francois Baclesse, Caen, France.
RESUMEN / SUMMARY: - The synergistic activity of pemetrexed with platinum agents in non-small cell lung cancer (NSCLC) and the renal safety of carboplatin suggest a balanced benefit/risk profile for this combination in elderly patients. This multicenter, single-arm, phase II study included 62 patients (>/=70 years) with chemonaive advanced NSCLC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and assigned to receive 6 cycles of 3-weekly pemetrexed 500mg/m(2) and carboplatin AUC 5. The primary endpoint was objective tumor response rate (ORR). Sixty-two patients received at least one dose of chemotherapy. Median age was 76.4 years [70.2-86] and all patients had PS 0 (16.1%) or PS 1 (83.9%). Stage IIIb disease in 21% patients and stage IV in 79% patients. Non-squamous cell carcinoma in 66.1% patients (adenocarcinoma 51.6%, large cell carcinoma 8.1%, other 6.5%) and squamous cell carcinoma in 33.9% patients. ORR was 28.6% (95% confidence interval [CI], 16.58-43.26), all were partial responses. Stable disease rate was 42.9%. Grade ¾ toxicities related to study drugs were: asthenia 16.1%, anorexia 4.8%, diarrhea 3.2%, neutropenia 51.6%, leucopenia 30.7%, thrombocytopenia 29%, anemia 19.4%. One related fatal septic shock occurred. In advanced NSCLC, pemetrexed use is restricted to non-squamous histology. The combination pemetrexed-carboplatin could be a valuable treatment option in elderly patients. Neutropenia was the most common toxicity. The ORR is within the range of data reported for pemetrexed-carboplatin in the general NSCLC population (24-31%).
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[7]
TÍTULO / TITLE: - Coregistered whole body magnetic resonance imaging-positron emission tomography (MRI-PET) versus PET-computed tomography plus brain MRI in staging resectable lung cancer: Comparisons of clinical effectiveness in a randomized trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Feb 19. doi: 10.1002/cncr.28000.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.28000
AUTORES / AUTHORS: - Yi CA; Lee KS; Lee HY; Kim S; Kwon OJ; Kim H; Choi JY; Kim BT; Hwang HS; Shim YM
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUND: The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging-positron emission tomography (MRI-PET) would increase the number of correctly upstaged patients compared with WB PET-computed tomography (PET-CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC). METHODS: From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI-PET or WB PET-CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging. RESULTS: Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI-PET group and in 26 of 120 patients (21.7%) in the PET-CT plus brain MRI group (4.2% difference; 95% confidence interval, -6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI-PET group and in 7 of 120 patients (5.8%) in the PET-CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%-20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (-10.7% difference; 95% confidence interval, -20.1% to -1.4%; P = .022). CONCLUSIONS: Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI-PET did not appear to help identify significantly more correctly upstaged patients than PET-CT plus brain MRI in patients with NSCLC. 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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[8]
TÍTULO / TITLE: - Pemetrexed and cisplatin combination with concurrent whole brain radiotherapy in patients with brain metastases of lung adenocarcinoma: a single-arm phase II clinical trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Neurooncol. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s11060-013-1079-5
AUTORES / AUTHORS: - Dinglin XX; Huang Y; Liu H; Zeng YD; Hou X; Chen LK
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Guangzhou, China.
RESUMEN / SUMMARY: - Pemetrexed-based chemotherapy presented about 40 % response rate (RR) on brain lesions of non-small cell lung cancer (NSCLC). But whole brain radiotherapy (WBRT) is still the standard treatment when surgery or radio-surgery is not feasible. This trial evaluated the efficacy and safety and efficacy of pemetrexed-cisplatin plus concurrent WBRT in this population. Forty-two patients were enrolled this study. Patients with newly diagnosed NSCLC with brain metastasis (BM) and performance status (PS) 0-2 were eligible for WBRT. Patients received up to six cycles of cisplatin and pemetrexed (75 and 500 mg/m(2), respectively) every 3 weeks. On day 1-12 during the first cycle of chemotherapy, patients received WBRT 30 Gy/10 fx/12 days. Primary end point was objective RR and progression free survival (PFS) on BM. Secondary end points included extracerebral and overall RR, survival and safety profile. Forty-one were evaluable for response. The histology was all adenocarcinoma. The objective cerebral RR (complete and partial response) in the intent-to-treat population was 68.3 % (28 of 41 patients). Extracerebral and overall RR was 34.1 and 36.6 %, respectively. Progression free survival of BM was 10.6 months, and median overall survival was 12.6 months. The combined treatment with pemetrexed-cisplatin and concurrent WBRT are effective in patients with NSCLC with newly diagnosed BM. This modality of treatment appears to be particularly favorable in RR and progression free survival of BM. Further clinical studies are warranted.
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[9]
TÍTULO / TITLE: - Selection criteria for lung-cancer screening.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - N Engl J Med. 2013 Feb 21;368(8):728-36. doi: 10.1056/NEJMoa1211776.
●● Enlace al texto completo (gratuito o de pago) 1056/NEJMoa1211776
AUTORES / AUTHORS: - Tammemagi MC; Katki HA; Hocking WG; Church TR; Caporaso N; Kvale PA; Chaturvedi AK; Silvestri GA; Riley TL; Commins J; Berg CD
INSTITUCIÓN / INSTITUTION: - Department of Community Health Sciences, Brock University, St. Catharines, ON, Canada. martin.tammemagi@brocku.ca
RESUMEN / SUMMARY: - BACKGROUND: The National Lung Screening Trial (NLST) used risk factors for lung cancer (e.g., >/=30 pack-years of smoking and <15 years since quitting) as selection criteria for lung-cancer screening. Use of an accurate model that incorporates additional risk factors to select persons for screening may identify more persons who have lung cancer or in whom lung cancer will develop. METHODS: We modified the 2011 lung-cancer risk-prediction model from our Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to ensure applicability to NLST data; risk was the probability of a diagnosis of lung cancer during the 6-year study period. We developed and validated the model (PLCO(M2012)) with data from the 80,375 persons in the PLCO control and intervention groups who had ever smoked. Discrimination (area under the receiver-operating-characteristic curve [AUC]) and calibration were assessed. In the validation data set, 14,144 of 37,332 persons (37.9%) met NLST criteria. For comparison, 14,144 highest-risk persons were considered positive (eligible for screening) according to PLCO(M2012) criteria. We compared the accuracy of PLCO(M2012) criteria with NLST criteria to detect lung cancer. Cox models were used to evaluate whether the reduction in mortality among 53,202 persons undergoing low-dose computed tomographic screening in the NLST differed according to risk. RESULTS: The AUC was 0.803 in the development data set and 0.797 in the validation data set. As compared with NLST criteria, PLCO(M2012) criteria had improved sensitivity (83.0% vs. 71.1%, P<0.001) and positive predictive value (4.0% vs. 3.4%, P=0.01), without loss of specificity (62.9% and. 62.7%, respectively; P=0.54); 41.3% fewer lung cancers were missed. The NLST screening effect did not vary according to PLCO(M2012) risk (P=0.61 for interaction). CONCLUSIONS: The use of the PLCO(M2012) model was more sensitive than the NLST criteria for lung-cancer detection.
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[10]
TÍTULO / TITLE: - MicroRNA-Related Genetic Variants Associated with Clinical Outcomes in Early-Stage Non-Small Cell Lung Cancer Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 15;73(6):1867-75. doi: 10.1158/0008-5472.CAN-12-0873. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-0873
AUTORES / AUTHORS: - Pu X; Roth JA; Hildebrandt MA; Ye Y; Wei H; Minna JD; Lippman SM; Wu X
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Epidemiology, Thoracic and Cardiovascular Surgery, and Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, Texas; and Moores Cancer Center, University of California, San Diego, California.
RESUMEN / SUMMARY: - Given the density of single-nucleotide polymorphisms (SNP) in the human genome and the sensitivity of single-nucleotide changes in microRNA (miRNA) functionality and processing, we asked whether polymorphisms within miRNA processing pathways and binding sites may influence non-small cell lung cancer (NSCLC) patients’ prognosis. We genotyped 240 miRNA-related SNPs in 535 patients with stage I and II NSCLCs to determine associations with overall recurrence and survival as well as effect in specific treatment subgroups. After correcting for multiple comparisons, the G allele of FZD4:rs713065 displayed a significant association with decreased risk of death in surgery-only patients [HR, 0.46; 95% confidence interval (CI), 0.32-0.65]. DROSHA:rs6886834 variant A allele (HR, 6.38; 95% CI, 2.49-16.31) remained significant for increased risk of recurrence in the overall and surgery-only populations, respectively. FAS:rs2234978 G allele remained significantly associated with survival in all patients (HR, 0.59; 95% CI, 0.44-0.77), whereas borderline significant in subgroups (surgery-only: HR, 0.59; 95% CI, 0.42-0.84; surgery plus chemo: HR, 0.19; 95% CI, 0.07-0.46). Luciferase assays showed that the FAS SNP created a miR-651 functional binding site. Survival tree analysis was conducted to classify patients into distinct risk subgroups based on their risk genotype combinations. These results indicate that miRNA-related polymorphisms may be associated with NSCLC patients’ clinical outcomes through altered miRNA regulation of target genes. Cancer Res; 73(6); 1867-75. ©2013 AACR.
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[11]
TÍTULO / TITLE: - Prospective, multicenter, randomized, independent-group, open-label phase II study to investigate the efficacy and safety of three regimens with two doses of sagopilone as second-line therapy in patients with stage IIIB or IV non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 19. pii: S0169-5002(13)00066-4. doi: 10.1016/j.lungcan.2013.02.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.007
AUTORES / AUTHORS: - Heigener DF; von Pawel J; Eschbach C; Brune A; Schmittel A; Schmelter T; Reck M; Fischer JR
INSTITUCIÓN / INSTITUTION: - Lungen Clinic Grosshansdorf, Wohrendamm 80, 22927 Grosshansdorf, Germany. Electronic address: d.heigener@lungenclinic.de.
RESUMEN / SUMMARY: - INTRODUCTION: Sagopilone is the first fully synthetic epothilone in clinical development and has proven preclinical activity in tumor models. This multicenter, randomized, open-label, phase II study examined the efficacy and safety of three regimens with two doses and two infusion durations of second-line sagopilone in pretreated patients with stage IIIB or IV non-small-cell lung cancer. METHODS: Eligibility criteria included: at least one measurable lesion by modified response evaluation criteria in solid tumors; World Health Organization performance status of 0 or 1; and failure of previous platinum-based chemotherapy. Patients were randomized to receive: 16mg/m2 sagopilone over 3h (treatment arm A); 22mg/m2 sagopilone over 0.5h (treatment arm B); or 22mg/m2 sagopilone over 3h (treatment arm C). Treatment duration was two to six courses every 3 weeks; more than six treatment courses were permitted if there was sustained clinical benefit. The primary efficacy endpoint was best overall response after six courses; at least five confirmed responders per arm indicated a successful outcome. RESULTS: In total, 128 patients (44, arm A; 41, arm B; 43, arm C) were randomized; 127 received at least one infusion of sagopilone. Baseline demographic data were similar across all arms. Eight patients across all arms had a confirmed partial response; the primary endpoint was not achieved. The most frequently reported adverse event (AE) was peripheral sensory neuropathy (75%). Most hematologic AEs were grade 1 or 2. CONCLUSION: As fewer than five patients per arm responded after six treatment courses, the primary endpoint was not met. Sagopilone was only moderately tolerated. Most AEs, including peripheral neuropathy, were grade 1 or 2; hematologic toxicities were rare.
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[12]
TÍTULO / TITLE: - A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1312-8. doi: 10.1016/j.ijrobp.2012.11.042. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.042
AUTORES / AUTHORS: - Sperduto PW; Wang M; Robins HI; Schell MC; Werner-Wasik M; Komaki R; Souhami L; Buyyounouski MK; Khuntia D; Demas W; Shah SA; Nedzi LA; Perry G; Suh JH; Mehta MP
INSTITUCIÓN / INSTITUTION: - Metro MN CCOP, Minneapolis, Minnesota. Electronic address: psperduto@mropa.com.
RESUMEN / SUMMARY: - BACKGROUND: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. METHODS AND MATERIALS: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy x 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day x 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day x 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. RESULTS: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). CONCLUSION: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.
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[13]
TÍTULO / TITLE: - Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genes Dev. 2013 Mar 1;27(5):504-13. doi: 10.1101/gad.205542.112.
●● Enlace al texto completo (gratuito o de pago) 1101/gad.205542.112
AUTORES / AUTHORS: - Soucek L; Whitfield JR; Sodir NM; Masso-Valles D; Serrano E; Karnezis AN; Swigart LB; Evan GI
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143-0502, USA;
RESUMEN / SUMMARY: - The principal reason for failure of targeted cancer therapies is the emergence of resistant clones that regenerate the tumor. Therapeutic efficacy therefore depends on not only how effectively a drug inhibits its target, but also the innate or adaptive functional redundancy of that target and its attendant pathway. In this regard, the Myc transcription factors are intriguing therapeutic targets because they serve the unique and irreplaceable role of coordinating expression of the many diverse genes that, together, are required for somatic cell proliferation. Furthermore, Myc expression is deregulated in most-perhaps all-cancers, underscoring its irreplaceable role in proliferation. We previously showed in a preclinical mouse model of non-small-cell lung cancer that systemic Myc inhibition using the dominant-negative Myc mutant Omomyc exerts a dramatic therapeutic impact, triggering rapid regression of tumors with only mild and fully reversible side effects. Using protracted episodic expression of Omomyc, we now demonstrate that metronomic Myc inhibition not only contains Ras-driven lung tumors indefinitely, but also leads to their progressive eradication. Hence, Myc does indeed serve a unique and nondegenerate role in lung tumor maintenance that cannot be complemented by any adaptive mechanism, even in the most aggressive p53-deficient tumors. These data endorse Myc as a compelling cancer drug target.
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[14]
TÍTULO / TITLE: - Nkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell. 2013 Mar 19. pii: S1097-2765(13)00174-3. doi: 10.1016/j.molcel.2013.02.018.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molcel.2013.02.018
AUTORES / AUTHORS: - Snyder EL; Watanabe H; Magendantz M; Hoersch S; Chen TA; Wang DG; Crowley D; Whittaker CA; Meyerson M; Kimura S; Jacks T
INSTITUCIÓN / INSTITUTION: - Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA.
RESUMEN / SUMMARY: - Tissue-specific differentiation programs become dysregulated during cancer evolution. The transcription factor Nkx2-1 is a master regulator of pulmonary differentiation that is downregulated in poorly differentiated lung adenocarcinoma. Here we use conditional murine genetics to determine how the identity of lung epithelial cells changes upon loss of their master cell-fate regulator. Nkx2-1 deletion in normal and neoplastic lungs causes not only loss of pulmonary identity but also conversion to a gastric lineage. Nkx2-1 is likely to maintain pulmonary identity by recruiting transcription factors Foxa1 and Foxa2 to lung-specific loci, thus preventing them from binding gastrointestinal targets. Nkx2-1-negative murine lung tumors mimic mucinous human lung adenocarcinomas, which express gastric markers. Loss of the gastrointestinal transcription factor Hnf4alpha leads to derepression of the embryonal proto-oncogene Hmga2 in Nkx2-1-negative tumors. These observations suggest that loss of both active and latent differentiation programs is required for tumors to reach a primitive, poorly differentiated state.
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[15]
TÍTULO / TITLE: - Computed tomography screening for lung cancer: has it finally arrived? Implications of the national lung screening trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1002-8. doi: 10.1200/JCO.2012.43.3110. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.3110
AUTORES / AUTHORS: - Aberle DR; Abtin F; Brown K
INSTITUCIÓN / INSTITUTION: - David Geffen School of Medicine at University of California, Los Angeles, 924 Westwood Blvd, Ste 420, Los Angeles, CA 90024; daberle@mednet.ucla.edu.
RESUMEN / SUMMARY: - The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
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[16]
TÍTULO / TITLE: - The addition of amifostine to carboplatin and paclitaxel based chemoradiation in locally advanced non-small cell lung cancer: Long-term follow-up of Radiation Therapy Oncology Group (RTOG) randomized trial 9801.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 7. pii: S0169-5002(13)00067-6. doi: 10.1016/j.lungcan.2013.02.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.008
AUTORES / AUTHORS: - Lawrence YR; Paulus R; Langer C; Werner-Wasik M; Buyyounouski MK; Komaki R; Machtay M; Smith C; Axelrod RS; Wasserman T; Bradley JD; Movsas B
INSTITUCIÓN / INSTITUTION: - Sheba Medical Center, Tel HaShomer, Israel; Thomas Jefferson University Hospital, Philadelphia, PA, United States. Electronic address: yaacov.lawrence@sheba.health.gov.il.
RESUMEN / SUMMARY: - INTRODUCTION: We report the long-term results of RTOG 9801, a randomized trial investigating the ability of amifostine, a radioprotector, to reduce chemoradiation-induced esophagitis. METHODS: Patients with stages II and IIIA/B non-small-cell lung cancer received induction paclitaxel 225mg/m2 intravenously (IV) and carboplatin area under the curve (AUC) 6 both days 1 and 22, followed by concurrent weekly paclitaxel (50mg/m2) and carboplatin (AUC 2), with hyperfractionated radiation therapy (69.6Gy at 1.2Gy BID). Patients were randomly assigned to amifostine (AM) 500mg IV four times per week or no-AM during chemoradiotherapy. Stratification factors included age (<70 vs. >/=70years), stage and performance status. RESULTS: 243 patients (pts) were enrolled; 120 received AM, 123 received no-AM. Two pts on each arm were found ineligible. Overall, 85% of patients were </=70years; 75% had a KPS >/=90. 34% had squamous histology. With median follow-up of 96.3months (for patients still alive), overall survival was identical (hazard ratio 1.03 (0.79-1.34), NS): five-year survival 17% in both arms. The incidence of late grade 3-5 toxicities was 16% in the AM arm and 19% in the control arm (hazard ratio 1.24 (0.66-2.32), NS). There was no significant difference between the arms regarding overall survival, disease-free survival or long-term toxicity. CONCLUSION: The chemoradiation regimen of carboplatin and paclitaxel produced long-term results in the multi-institutional setting comparable to other regimens. Amifostine did not appear to compromise survival. As done in RTOG 9801, more consistent reporting of long term toxicity is needed for comparison of different chemoradiation regimens.
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[17]
TÍTULO / TITLE: - A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):981-90. doi: 10.1007/s00280-013-2091-3. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2091-3
AUTORES / AUTHORS: - Park SR; Speranza G; Piekarz R; Wright JJ; Kinders RJ; Wang L; Pfister T; Trepel JB; Lee MJ; Alarcon S; Steinberg SM; Collins J; Doroshow JH; Kummar S
INSTITUCIÓN / INSTITUTION: - Division of Cancer Treatment and Diagnosis, National Cancer Institute, 31 Center Drive, 3A44, Bethesda, MD, 20892, USA.
RESUMEN / SUMMARY: - PURPOSE: A multi-cohort phase II study of fostamatinib, an oral multi-kinase inhibitor, was conducted to determine the response rate in patients with advanced colorectal (CRC), thyroid, non-small cell lung, head and neck, and renal cell carcinomas, and pheochromocytomas. METHODS: Patients received 200 mg fostamatinib BID in 4-week cycles with response assessed every 2 cycles. Blood was collected for pharmacokinetic analysis and measurements of circulating tumor cells and circulating endothelial (progenitor) cells (CE(P)Cs). RESULTS: A total of 37 patients (22 CRC), median of 4 prior therapies, were enrolled. Due to toxicities in four of the first five patients, the study was amended to incorporate a dose escalation phase for each histology. The maximum-tolerated dose was established at 50 mg BID in CRC but was not established for the other cancers. Common grade ¾ toxicities included transaminitis, hyperbilirubinemia, and hypertension. Pharmacokinetic profile was similar to previous reports. Seventy-three percent of CRC patients had liver involvement and 91 % had prior anti-angiogenic therapy. Patients with abnormal liver tests at baseline were more likely to experience grade >/=2 hepatotoxicity than those with normal tests (44 vs. 0 %). No responses were observed; disease stabilization rate was 27 % in CRC. Reduction in CECs following treatment was associated with a better disease stabilization rate (75 vs. 0 %) in CRC. CONCLUSION: Fostamatinib had limited anti-tumor activity in this first clinical trial in patients with advanced refractory solid tumors; reduction in CECs and CEPs was indicative of anti-angiogenic effects. Abnormal liver testing at baseline appeared to influence drug tolerability.
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[18]
TÍTULO / TITLE: - Unilateral proptosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JAMA. 2013 Feb 13;309(6):605-6. doi: 10.1001/jama.2013.233.
●● Enlace al texto completo (gratuito o de pago) 1001/jama.2013.233
AUTORES / AUTHORS: - Munoz J; Kurzrock R
INSTITUCIÓN / INSTITUTION: - Investigational Cancer Therapeutics (Phase I Clinical Trials Program), MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 455, Houston, TX 77030, USA. jlmunoz@mdanderson.org
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[19]
TÍTULO / TITLE: - Survival of Patients with Non-Small Cell Lung Cancer According to Lymph Node Disease: Single pN1 vs Multiple pN1 vs Single Unsuspected pN2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Feb 2.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2865-6
AUTORES / AUTHORS: - Macia I; Ramos R; Moya J; Rivas F; Urena A; Banque M; Escobar I; Rosado G; Rodriguez-Taboada P
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery and University of Barcelona, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, España, imacia@bellvitgehospital.cat.
RESUMEN / SUMMARY: - PURPOSE: This study was designed to describe the characteristics and survival of NSCLC patients treated with surgery and single pN1 disease, multiple pN1, and single unsuspected pN2. METHODS: In 2005-2009, we treated 378 lung cancer patients with surgery with radical intent; 152 cases were pN1 or pN2. We excluded patients with neoadjuvant treatment, incomplete resection, incomplete lymph node dissection, metastasis, cN2 disease, multiple pN2, SCLC, and lack of PET-CT. All patients were staged with TNM 2010. We included 72 patients: 21 single pN1, 26 multiple pN1, and 25 single unsuspected pN2. Statistical analysis included descriptive statistics, chi-square test, Kaplan-Meier, log-rank test, and Cox proportional hazard model. RESULTS: The sample included 62 men (86 %) and 10 women (14 %), mean age 64 +/- 9 years. The three subgroups did not show statistically significant differences in the main characteristics. Adjuvant treatment was performed in 56 patients (78 %). The 5 year overall survival (OS) for single pN1 was 73 %; for multiple pN1, 34 %; and for single unsuspected pN2, 25 % (P = 0.15). The mean OS for single pN1 was 63 +/- 6 months; median OS for multiple pN1 was 45 (range, 42-48) months and for single pN2 was 54 (range, 32-77) months. Multivariate analysis found the following negative prognostic factors of OS: for single pN1, age, female sex, and microscopic intratumoral lymphatic and vascular invasion; for multiple pN1, </=10 lymph nodes resected. CONCLUSIONS: Patients with single pN1 had better OS than patients with multiple pN1. Patients with single unsuspected pN2 had OS similar to that of multiple pN1.
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[20]
TÍTULO / TITLE: - Phase II study of pemetrexed as first-line treatment in elderly (>/=75) non-squamous non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0901.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2142-9
AUTORES / AUTHORS: - Kim YH; Hirabayashi M; Kosaka S; Nikaidoh J; Yamamoto Y; Shimada M; Toyazaki T; Nagai H; Sakamori Y; Mishima M
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan, ekim@kuhp.kyoto-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: Single-agent chemotherapy with third-generation non-platinum agents, such as docetaxel, vinorelbine, is a standard therapeutic option for elderly patients with non-small-cell lung cancer (NSCLC). Subset analysis of a previous phase III study comparing pemetrexed with docetaxel in the second-line setting showed the superiority of pemetrexed in an elderly (>/=70) population in both efficacy and toxicity. PATIENTS AND METHODS: This was a single-arm phase II study of pemetrexed in elderly (>/=75) Japanese patients with advanced non-squamous NSCLC. Patients received four cycles of pemetrexed (500 mg/m2) every 3 weeks. The primary endpoint was the response rate, and secondary endpoints were safety and survival. RESULTS: Twenty-eight patients were enrolled between January 2010 and April 2012. The median age of the patients was 77 years (range 75-88). All but one patient had adenocarcinoma histology. The median number of chemotherapy cycles administered was 4 (range, 1-12). Seventeen (60 %) patients completed four cycles of chemotherapy. Partial response was achieved in 7 patients (response rate: 25 %) and stable disease in 11 patients (disease control rate: 64 %). Median progression-free survival and overall survival were 3.3 and 17.5 months, respectively. Grade ¾ neutropenia and thrombocytopenia were observed in 8 patients (29 %) and 2 (7 %), respectively. Non-hematologic toxicities were generally mild, and there were no treatment-related deaths. CONCLUSIONS: Although this study did not meet our primary endpoint, pemetrexed showed favorable antitumor activity with mild toxicity in elderly patients with non-squamous NSCLC. Further investigations of pemetrexed in this population are warranted (UMIN-CTR number, 000002452).
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[21]
TÍTULO / TITLE: - Association between single nucleotide polymorphisms of the transforming growth factor-beta1 gene and overall survival in unresectable locally advanced non-small-cell lung cancer patients treated with radio(chemo)therapy in a Chinese population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):512. doi: 10.1007/s12032-013-0512-0. Epub 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0512-0
AUTORES / AUTHORS: - Xue SL; Zheng YH; Su HF; Deng X; Zhang XB; Zou CL; Hu ML; Xie CY
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical College, 2 Fuxuexiang Road, Wenzhou 325002, Zhejiang, People’s Republic of China.
RESUMEN / SUMMARY: - The outcome is variable for unresectable locally advanced non-small-cell lung cancer (ULANSCLC) patients treated with radio(chemo)therapy. The aim of this study is to investigate whether single-nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 (TGF-beta1) gene are associated with overall survival (OS) in ULANSCLC patients treated with definitive radio(chemo)therapy. A total of 109 patients who had available blood samples and complete clinical and follow-up information were enrolled. DNA from blood was genotyped for two SNPs: TGF-beta1 C-509T and T+869C. Kaplan-Meier survival analysis, log-rank test, and Cox’s proportional hazard model were used to evaluate associations between genotypes and OS. Log-rank test showed that TGF-beta1 C-509T significantly correlated with OS (pooled P = 0.017). Both univariate and multivariate analyses showed that TGF-beta1 C-509T CC genotype was significantly associated with better OS than CT or TT genotypes. These results indicate that TGF-beta1 C-509T CC genotype is significantly associated with better OS in ULANSCLC patients treated with radio(chemo)therapy as a potential independent survival predictor.
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[22]
TÍTULO / TITLE: - Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surgery. 2013 Mar 8. pii: S0039-6060(13)00002-0. doi: 10.1016/j.surg.2013.01.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2013.01.001
AUTORES / AUTHORS: - Alexander HR Jr; Bartlett DL; Pingpank JF; Libutti SK; Royal R; Hughes MS; Holtzman M; Hanna N; Turner K; Beresneva T; Zhu Y
INSTITUCIÓN / INSTITUTION: - Divisions of General and Oncologic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD. Electronic address: HRAlexander@smail.umaryland.edu.
RESUMEN / SUMMARY: - OBJECTIVES: Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum. Morbidity and mortality are almost invariably owing to locoregional progression. Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome. METHODS: Between January 1992 and 2010, 211 patients with MPM treated at 3 major referral centers with operative CRS and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were analyzed. RESULTS: The median, actuarial overall survival was 38.4 months; the actuarial 5- and 10-year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were younger age <60 years (P < .01), complete or near complete (R0-1) versus incomplete (R2-3) resection (P < .02), low versus high histologic grade (P < .01), and the use of cisplatin versus mitomycin-C during HIPEC (P < .01). There was a trend toward female sex and improved survival (male hazard ratio, 1.46; 95% confidence interval, 0.89-2.41; P = .13). CONCLUSION: Operative CRS with HIPEC is associated with prolonged survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM.
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[23]
TÍTULO / TITLE: - Preexisting interstitial lung disease is inversely correlated to tumor epidermal growth factor receptor mutation in patients with lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 15. pii: S0169-5002(13)00053-6. doi: 10.1016/j.lungcan.2013.01.017.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.017
AUTORES / AUTHORS: - Fujimoto D; Tomii K; Otoshi T; Kawamura T; Tamai K; Takeshita J; Tanaka K; Matsumoto T; Monden K; Nagata K; Otsuka K; Nakagawa A; Hata A; Tachikawa R; Otsuka K; Hamakawa H; Katakami N; Takahashi Y; Imai Y
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: daichi@kcho.jp.
RESUMEN / SUMMARY: - INTRODUCTION: Interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis, has been shown to be associated with lung carcinogenesis. However, an association between epidermal growth factor receptor (EGFR) mutation status and preexisting ILD in patients with lung adenocarcinoma is unknown. METHODS: Between January 2008 and April 2012, we analyzed 602 patients with lung adenocarcinoma. EGFR mutation status was analyzed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method, and preexisting ILD was diagnosed based on clinical features, chest high-resolution computed tomography (HRCT) findings, and histological findings. RESULTS: There were 555 patients with pulmonary adenocarcinoma with tumor EGFR mutation data available for analysis. Of them, 31 patients (6%) had preexisting ILD, and EGFR mutations were detected in 246 of the 555 patients (46%). In the comparison between patients with EGFR mutations and those with wild-type EGFR, there was a significant inverse association between occurrence of tumors with EGFR mutations and ILD (1/246 vs. 30/309, P<0.001). Based on the multivariate analysis of age, gender, smoking status, Eastern Cooperative Oncology Group Performance Status, stage, and ILD, EGFR mutations were found to be independently associated with females (OR, 1.58; 95% CI, 1.01-2.46; P=0.048), never-smokers (OR, 3.31; 95% CI, 2.12-5.20; P<0.001), and the absence of ILD (OR, 17.41; 95% CI, 3.54-315.34; P<0.001). CONCLUSIONS: This study showed that patients with pulmonary adenocarcinoma and ILD had a lower probability of carrying tumor EGFR mutations.
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[24]
TÍTULO / TITLE: - Prognostic value of patient-reported symptom interference in patients with late-stage lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Qual Life Res. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1007/s11136-013-0356-2
AUTORES / AUTHORS: - Barney BJ; Wang XS; Lu C; Liao Z; Johnson VE; Cleeland CS; Mendoza TR
INSTITUCIÓN / INSTITUTION: - Department of Mathematics and Statistics, Kennesaw State University, Kennesaw, Georgia.
RESUMEN / SUMMARY: - PURPOSE: Patient-reported outcomes (PROs) have been found to be significant predictors of clinical outcomes such as overall survival (OS), but the effect of demographic and clinical factors on the prognostic ability of PROs is less understood. Several PROs derived from the 12-item Short-Form Health Survey (SF-12) and M. D. Anderson Symptom Inventory (MDASI) were investigated for association with OS, with adjustments for other factors, including performance status. METHODS: A retrospective analysis was performed on data from 90 patients with stage IV non-small cell lung cancer. Several baseline PROs were added to a base Cox proportional hazards model to examine the marginal significance and improvement in model fit attributable to the PRO: mean MDASI symptom interference level; mean MDASI symptom severity level for five selected symptoms; SF-12 physical and mental component summaries; and the SF-12 general health item. Bootstrap resampling was used to assess the robustness of the findings. RESULTS: The MDASI mean interference level had a significant effect on OS (p = 0.007) when the model was not adjusted for interactions with other prognostic factors. Further exploration suggested the significance was due to an interaction with performance status (p = 0.001). The MDASI mean symptom severity level and the SF-12 physical component summary, mental component summary, and general health item did not have a significant effect on OS. CONCLUSIONS: Symptom interference adds prognostic information for OS in advanced lung cancer patients with poor performance status, even when demographic and clinical prognostic factors are accounted for.
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[25]
TÍTULO / TITLE: - Safety and Efficacy of Platinum Agents plus Etoposide for Patients with Small Cell Lung Cancer with Interstitial Lung Disease.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1175-9.
AUTORES / AUTHORS: - Yoshida T; Yoh K; Goto K; Niho S; Umemura S; Ohmatsu H; Ohe Y
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. tatyoshi@east.ncc.go.jp.
RESUMEN / SUMMARY: - BACKGROUND: The safety and efficacy of combination of platinum agents plus etoposide for patients with small cell lung cancer (SCLC) with pre-existing interstitial lung disease (ILD) is uncertain. PATIENTS AND METHODS: Fifty-two patients received platinum agents plus etoposide as first-line chemotherapy for SCLC with pre-existing ILD. The clinical characteristics, treatment outcome and survival of these patients were retrospectively reviewed. RESULTS: During first-line chemotherapy, only one (2%) out of the 52 patients developed an acute exacerbation of ILD. The median number of treatment cycles was four. The overall response rate was 69%. The median progression-free survival period was 4.5 months. The median survival time was 9.4 months. Thirty-three patients (63%) received at least one subsequent chemotherapy regimen, and five of these patients developed acute exacerbation of ILD. CONCLUSION: The combination of platinum agents plus etoposide is feasible and effective in SCLC patients with pre-existing ILD, compared with regimens after second-line chemotherapy.
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[26]
TÍTULO / TITLE: - Post-thoracotomy pain and long-term survival associated with video-assisted thoracic surgery lobectomy methods for clinical T1N0 lung cancer: a patient-oriented, prospective cohort study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cardiothorac Surg. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt107
AUTORES / AUTHORS: - Yamashita Y; Mukaida H; Harada H; Tsubokawa N
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Kure Medical Center/Chugoku Cancer Center, Hiroshima, Kure, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: To provide a less-invasive procedure for video-assisted thoracic surgery (VATS), we prospectively evaluated the feasibility of two existing VATS approaches. METHODS: We conducted a prospective cohort study to determine the feasibility of two strictly defined types of VATS lobectomy. Based on free decisions made by patients after hearing similar preoperative explanations using the same table, either one modality was adopted. The perioperative variables, including operation time, blood loss, morbidity, mortality and particularly post-thoracotomy pain and long-term survival, were evaluated for the assisted VATS and the complete VATS groups. RESULTS: We reviewed 104 consecutive patients who had clinical T1N0M0 non-small-cell lung cancer. Twenty-six patients (ASSIST group) chose lobectomy performed via an anterolateral small thoracotomy by using a rib spreader with a combination of thoracoscopic and direct views. Seventy-eight patients (PURE group) chose complete VATS in which only a monitor was used during smaller-access thoracotomy without a rib spreader. All clinical parameters that were scheduled to be measured during the perioperative period were found to be acceptable using both approaches. The ASSIST group had a significantly high odds ratio of using additional painkillers except epidural anaesthesia when compared with the PURE group, as shown by multivariate logistic regression analysis. Patients in the PURE group exhibited early recovery from surgery, but their operation time was longer. Disease-free and overall 5-year survival rates were equivalent between the two groups. CONCLUSIONS: Both procedures are feasible with regard to perioperative factors and long-term survival rates. Patients undergoing complete VATS required less medication than those undergoing assisted VATS.
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[27]
TÍTULO / TITLE: - The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Apr;20(4):1093-100. doi: 10.1245/s10434-012-2845-x. Epub 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-012-2845-x
AUTORES / AUTHORS: - Deraco M; Baratti D; Hutanu I; Bertuli R; Kusamura S
INSTITUCIÓN / INSTITUTION: - Peritoneal Surface Malignancy Program, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy, marcello.deraco@istitutotumori.mi.it.
RESUMEN / SUMMARY: - BACKGROUND: The aim of this study was to evaluate the effects of perioperative systemic chemotherapy (CT) on short-term surgical and long-term oncologic results in diffuse malignant peritoneal mesothelioma (DMPM) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: We retrospectively analyzed data obtained from an institutional prospective database at NCI of Milan. The study group comprised 116 DMPM patients treated with CRS + HIPEC from August 1995 to October 2011. A total of 60 cases underwent preoperative CT (PRECT), 30 underwent postoperative CT (POSTCT), and 26 did not undergo any CT (NOCT). Also, 55 cases used the perioperative combination of platinum and pemetrexed. We tested whether covariates related to clinical, histologic, PRECT, and surgical treatment were correlated with completeness of cytoreduction (CC), postoperative G3-5 morbidity, and progression-free survival and overall survival (OS). Univariate and multivariate analyses were performed. RESULTS: Factors independently associated with CC were ECOG performance status (PF) of 0, and PCI <20. Factors independently associated with postoperative G3-5 morbidity were ECOG >1, bowel anastomosis, and number of peritonectomy procedures. Preoperative platelet count >400 x 103/mm(3), histological subtype (biphasic and sarcomatoid vs epithelial), CC, and G3-5 morbidity were independent prognostic factors. PRECT was not associated with CC or G3-5 morbidity. There was no significant difference in terms of survival between the PRECT, POSTCT, and NOCT groups. CONCLUSIONS: The CC, G3-5, and OS were not influenced by aspects related to perioperative CT. The present data warrants confirmation reconducting the comparative analysis in a larger multi-institutional series preferably using matching control techniques.
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[28]
TÍTULO / TITLE: - Needs regarding care and factors associated with unmet needs in disease-free survivors of surgically treated lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt032
AUTORES / AUTHORS: - Yun YH; Shon EJ; Yang AJ; Kim SH; Kim YA; Chang YJ; Lee J; Kim MS; Lee HS; Zo JI; Kim J; Choi YS; Shim YM
INSTITUCIÓN / INSTITUTION: - Seoul National University College of Medicine, Seoul.
RESUMEN / SUMMARY: - BackgroundTo evaluate the long-term needs of lung cancer survivors and to explore factors associated with unmet need.Patients and methodsWe recruited lung patients treated with curative surgery from 2001 through 2006 at two centers in Korea. Needs in the domains of information, supportive care, education and counseling, and socioeconomic support were measured. We selected the four most frequently reported items of unmet need among 19 items in four domains.ResultsThe most frequently reported unmet needs were Complementary and alternative medicine (CAM) and folk remedies (59.8%) in the Information domain, Counseling and treatment of depression and anxiety (63.5%) in the Supportive care domain, diet, exercise and weight control (55.1%) in the Education and counseling domain and Financial support (90.4%) in the socioeconomic support domain. Unmet needs for psychological treatment was significantly greater in participants who were employed (adjusted odds ratio [aOR], 2.25; 95% confidential interval [CI], 1.12 to 4.53). Unmet needs for diet, exercise and weight control were significantly greater in participants who had not received chemotherapy (aOR, 1.76; 95% CI, 1.09 to 2.85). Unmet need for financial support was greater in participants who were married (aOR, 4.14, 95%CI, 1.12 to 15.22) and those who had not received chemotherapy (aOR, 5.91, 95%CI, 1.91 to 18.31).ConclusionThere were substantial unmet needs for information regarding psychological support, education for diet and exercise, and financial support among lung cancer survivors.
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[29]
TÍTULO / TITLE: - Treatment-related Acute Esophagitis For Patients With Locoregionally Advanced Non-Small Cell Lung Cancer Treated With Involved-field Radiotherapy and Concurrent Chemotherapy.
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.0b013e31827de7a2
AUTORES / AUTHORS: - Bar-Ad V; Leiby B; Witek M; Xiao Y; Cui Y; Dai Y; Cao J; Axelrod R; Campling B; Both S; Werner-Wasik M
INSTITUCIÓN / INSTITUTION: - Departments of *Radiation Oncology daggerBiostatistics double daggerMedical Oncology, Thomas Jefferson University section signDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
RESUMEN / SUMMARY: - PURPOSE:: To explore the incidence and risk factors for treatment-related acute esophagitis associated with involved-field radiation therapy (RT) delivered concurrently with chemotherapy for patients with locoregionally advanced non-small cell lung cancer. MATERIALS AND METHODS:: Forty-nine consecutive patients diagnosed with locoregionally advanced non-small cell lung cancer were treated using involved-field RT. Radiotherapy target volumes included the primary lung tumor and involved mediastinal lymphadenopathy as defined on imaging studies including computed tomography of the chest and fluorodeoxyglucose-positron emission tomography/computed tomography. The patients were treated to a median total dose of 63 Gy (range, 55.8 to 74 Gy) using daily fractions of 1.8 or 2.0 Gy. No elective radiotherapy of mediastinal lymph nodes was used. Concurrent platinum-based chemotherapy was delivered to all patients. Treatment-related toxicity was evaluated during the course of RT and subsequent follow-up visits. RESULTS:: Thirty-one (63%) patients were female and 18 (37%) were male. Median age at the time of diagnosis was 68 years (range, 36 to 83 y). Thirty-one patients (63%) developed treatment-related acute esophagitis: 24 patients (49%) grade 2 and 7 (14%) patients grade 3 esophagitis, with the peak occurring during the seventh week of radiotherapy. No grade >/=4 esophagitis was seen in this cohort. Eighteen patients (37%) did not develop radiation-induced esophagitis associated with their course of chemoradiotherapy. In the univariate analysis, age at the time of diagnosis, radiation dose per fraction, and total volume of the esophagus were significantly associated with the risk of acute esophagitis. Increasing age reduced the risk of acute esophagitis [odds ratio (OR) for 10-y increase=0.40] as did increasing total esophagus volume (OR for 10-U increase=0.27). Dose per fraction of 1.8 Gy was associated with lower risk of acute esophagitis when compared with dose per fraction of 2 Gy (OR=0.19). Marginal associations were observed for all of the volume variables. Higher volume variable values had a nonsignificant association with an increase in risk of acute esophagitis. However, only the total volume of the esophagus (P=0.0032) and larger dose per fraction (2 vs. 1.8 Gy) (P=0.011) remained significantly associated with higher risk of developing grade >/=2 acute esophagitis in the multivariate analysis. CONCLUSIONS:: Higher risk of grade >/=2 treatment-related esophagitis was associated with lower total esophageal volume and higher radiotherapy dose per fraction and should be taken into consideration during patient treatment planning. Inclusion of total esophageal volume and dose per fraction into future clinical protocols may further help our understanding of treatment-related esophagitis and enable the development of novel preventative approaches.
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[30]
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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[31]
TÍTULO / TITLE: - Analysis of Mechanisms of Acquired Resistance to EGFR TKI therapy in 155 patients with EGFR-mutant Lung Cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2246
AUTORES / AUTHORS: - Yu H; Arcila ME; Rekhtman N; Sima CS; Zakowski MF; Pao W; Kris MG; Miller VA; Ladanyi M; Riely GJ
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Memorial Sloan Kettering Cancer Center.
RESUMEN / SUMMARY: - PURPOSE: All patients with EGFR mutant lung cancers eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Smaller series have identified various mechanisms of resistance, but systematic evaluation of a large number of patients to definitively establish the frequency of various mechanisms has not been performed. EXPERIMENTAL DESIGN: Patients with lung adenocarcinomas and acquired resistance to erlotinib or gefitinib enrolled onto a prospective biopsy protocol and underwent a re-biopsy after the development of acquired resistance. Histology was reviewed. Samples underwent genotyping for mutations in EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS and PIK3CA, and FISH for MET and HER2. RESULTS: Adequate tumor samples for molecular analysis were obtained in 155 patients. Ninety-eight had second-site EGFR T790M mutations (63%, 95% CI 55-70%) and four had small cell transformation (3%, 95% CI 0-6%). MET amplification was seen in 4/75 (5%, 95% CI 1-13%). HER2 amplification was seen in 3/24 (13%, 95% CI 3-32%). We did not detect any acquired mutations in PIK3CA, AKT1, BRAF, ERBB2, KRAS, MEK1, or NRAS. (0/88, 0%, 95% CI 0-4%). Overlap among mechanisms of acquired resistance was seen in 4%. CONCLUSIONS: This is the largest series reporting mechanisms of acquired resistance to EGFR TKI therapy. We identified EGFR T790M as the most common mechanism of acquired resistance, while MET amplification, HER2 amplification, and small cell histologic transformation occur less frequently. More comprehensive methods to characterize molecular alterations in this setting are needed to improve our understanding of acquired resistance to EGFR TKIs.
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[32]
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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[33]
TÍTULO / TITLE: - Prospective analysis of quality of life in elderly patients treated with adjuvant chemotherapy for non-small-cell lung cancer.
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/mds649
AUTORES / AUTHORS: - Park S; Kim IR; Baek KK; Lee SJ; Chang WJ; Maeng CH; Hong JY; Choi MK; Kim YS; Sun JM; Ahn JS; Park K; Jo J; Jung SH; Ahn MJ
INSTITUCIÓN / INSTITUTION: - Division of Hematology-Oncology, Department of Medicine.
RESUMEN / SUMMARY: - BackgroundGiven the more comorbidities with a decline in physiologic reserve, it can be challenging to make appropriate treatment decisions in the elderly.Patients and methodsHere, we prospectively evaluated and compared the health-related quality of life (HRQOL) of patients aged >/=65 with aged <65 who were treated with a postoperative chemotherapy for completely resected stage Ib, II or IIIa non-small-cell lung cancer (NSCLC). Either four cycles of paclitaxel (Taxol)-carboplatin (PC) or vinorelbine-cisplatin (NP) was used. The HRQOL was assessed with EORTC QLQ-C30 and EORTC QLQ-LC13.ResultsBetween October 2008 and October 2011, a total of 139 patients (aged <65, n = 73; >/=65, n = 66) were enrolled, and 127 (91.4%) completed the questionnaire. Overall, the quality of life (QOL) in elderly patients did not significantly deteriorate with adjuvant chemotherapy and the time trend of QOL in elderly patients was similar to that of younger patients. Although the elderly suffered from increased treatment-related adverse events involving sore mouth, peripheral neuropathy and alopecia compared with the baseline, the same time trends were also observed in younger group. The mean dose intensities (MDIs) for PC and NP regimen were not significantly different between the two age groups.ConclusionsPostoperative chemotherapy did not substantially reduce HRQOL in elderly NSCLC patients, and HRQOL during and after adjuvant chemotherapy did not significantly differ by age.
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[34]
TÍTULO / TITLE: - Review of Ongoing Clinical Trials in Non-Small-Cell Lung Cancer: A Status Report for 2012 from the ClinicalTrials.gov Web Site.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318287c562
AUTORES / AUTHORS: - Subramanian J; Regenbogen T; Nagaraj G; Lane A; Devarakonda S; Zhou G; Govindan R
INSTITUCIÓN / INSTITUTION: - *Department of Medicine, University of Tennessee Medical Center, Knoxville, Tennessee; daggerDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri; double daggerDepartment of Medicine, Division of Hematology and Oncology, Loma Linda University, Loma Linda, California; section signDepartment of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis, Missouri; ||Department of Medicine, St. Lukes Hospital, St. Louis, Missouri; paragraph signDivision of Biostatistics, Washington University School of Medicine in St. Louis, Missouri; and #Alvin J. Siteman Cancer Center.
RESUMEN / SUMMARY: - INTRODUCTION:: Clinical research in non-small-cell lung cancer (NSCLC) is a rapidly evolving field. In an effort to identify the current trends in lung cancer clinical research, we reviewed ongoing clinical trials in NSCLC listed in the ClinicalTrials.gov registry in 2012, and we also compared this data to a similar survey conducted by us in 2009. METHODS:: The Web site’s advanced search function was used to search for the term “non-small cell lung cancer.” The search was further refined by using the following options from the search page drop-down menu, “open studies” and “interventional.” Studies with non-NSCLC tumor histologies and pediatric studies were excluded. RESULTS:: Of the 477 trials included in the analysis, 105 (22.0%) were phase I, 223 phase II (46.8%), and 63 phase III trials (13.2%). When compared with data from 2009, university-sponsored trials decreased in number (45.4%-34.2%; p < 0.001) whereas industry-sponsored trials remained almost the same. There was a significant increase in trials conducted exclusively outside of the United States (35.9%-48.8%; p = 0.001). The number of studies with locations in China (61, 12.8%) was second only to that in the United States (244, 51.2%). Studies reporting biomarker analysis increased significantly from 37.5% to 49.1% in 2012 (p < 0.001). Biomarker-based patient selection also increased significantly from 7.9% to 25.8% (p < 0.001). Targeted therapies were evaluated in 70.6% of phase I/II and II trials, and the most common class of targeted agent studied was epidermal growth factor receptor tyrosine kinase inhibitors (38.0%). Prespecified accrual times were observed to increase when compared with data reported in 2009, especially among industry-sponsored studies. CONCLUSIONS:: Our survey identified major changes in lung cancer clinical research since 2009. Almost half of all studies registered at the ClinicalTrials.gov Web site are being conducted outside the United States, and several novel molecularly targeted agents are being evaluated in the treatment of patients with NSCLC. More importantly, we identified a threefold increase in the number of studies that perform biomarker testing to determine patient selection over the last 3 years.
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[35]
TÍTULO / TITLE: - Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Arch Otorhinolaryngol. 2013 Feb 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s00405-013-2358-7
AUTORES / AUTHORS: - Tjon Pian Gi RE; Ilmarinen T; van den Heuvel ER; Aaltonen LM; Andersen J; Brunings JW; Chirila M; Dietz A; Ferran Vila F; Friedrich G; de Gier HH; Golusinski W; Graupp M; Hantzakos A; Horcasitas R; Jackowska J; Koelmel JC; Lawson G; Lindner F; Remacle M; Sittel C; Weichbold V; Wierzbicka M; Dikkers FG
INSTITUCIÓN / INSTITUTION: - Department of Otorhinolaryngology Head and Neck Surgery, University of Groningen, University Medical Center Groningen, P.O. box 30001, 9700, RB, Groningen, The Netherlands, r.e.a.tjonpiangi@umcg.nl.
RESUMEN / SUMMARY: - Intralesional use of cidofovir (Vistide(®)) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.
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[36]
TÍTULO / TITLE: - Gene expression profiling and molecular pathway analysis for the identification of early-stage lung adenocarcinoma patients at risk for early recurrence.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 6. doi: 10.3892/or.2013.2332.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2332
AUTORES / AUTHORS: - Saji H; Tsuboi M; Shimada Y; Kato Y; Hamanaka W; Kudo Y; Yoshida K; Matsubayashi J; Usuda J; Ohira T; Ikeda N
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Surgery, Department of Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan.
RESUMEN / SUMMARY: - Clinicohistopathological staging is insufficient to predict disease progression and clinical outcome in lung carcinoma. Based on the results of the principal component analysis of 24 samples of early-stage lung adenocarcinoma, two subgroups were identified within the early-relapse group. The histological classification of all samples of group A was poorly differentiated, whereas one out of three in group B was poorly differentiated. DAVID functional annotation analysis revealed that the molecular pathways enriched in group A included those associated with cell adhesion molecules (CAMs), cell cycle and antigen processing and presentation, whereas those in group B included CAMs, T cell receptor signaling, cytokine-cytokine receptor interaction, toll-like receptor signaling, chemokine signaling, primary immunodeficiency and natural killer cell-mediated cytotoxicity. The CAM pathway was enriched in both groups. This comprehensive gene expression and functional pathway analysis identified a distinct molecular pathway, CAMs, that correlated with the early relapse of patients with early-stage lung adenocarcinoma.
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[37]
TÍTULO / TITLE: - Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Invest. 2013 Mar 1;123(3):1241-61. doi: 10.1172/JCI61271. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1172/JCI61271
AUTORES / AUTHORS: - Xi S; Xu H; Shan J; Tao Y; Hong JA; Inchauste S; Zhang M; Kunst TF; Mercedes L; Schrump DS
RESUMEN / SUMMARY: - MicroRNAs are critical mediators of stem cell pluripotency, differentiation, and malignancy. Limited information exists regarding microRNA alterations that facilitate initiation and progression of human lung cancers. In this study, array techniques were used to evaluate microRNA expression in normal human respiratory epithelia and lung cancer cells cultured in the presence or absence of cigarette smoke condensate (CSC). Under relevant exposure conditions, CSC significantly repressed miR-487b. Subsequent experiments demonstrated that miR-487b directly targeted SUZ12, BMI1, WNT5A, MYC, and KRAS. Repression of miR-487b correlated with overexpression of these targets in primary lung cancers and coincided with DNA methylation, de novo nucleosome occupancy, and decreased H2AZ and TCF1 levels within the miR-487b genomic locus. Deoxy-azacytidine derepressed miR-487b and attenuated CSC-mediated silencing of miR-487b. Constitutive expression of miR-487b abrogated Wnt signaling, inhibited in vitro proliferation and invasion of lung cancer cells mediated by CSC or overexpression of miR-487b targets, and decreased growth and metastatic potential of lung cancer cells in vivo. Collectively, these findings indicate that miR-487b is a tumor suppressor microRNA silenced by epigenetic mechanisms during tobacco-induced pulmonary carcinogenesis and suggest that DNA demethylating agents may be useful for activating miR-487b for lung cancer therapy.
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[38]
TÍTULO / TITLE: - Deuterium depleted water effects on survival of lung cancer patients and expression of kras, bcl2, and myc genes in mouse lung.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Feb;65(2):240-6. doi: 10.1080/01635581.2013.756533.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.756533
AUTORES / AUTHORS: - Gyongyi Z; Budan F; Szabo I; Ember I; Kiss I; Krempels K; Somlyai I; Somlyai G
INSTITUCIÓN / INSTITUTION: - a Department of Public Health , Medical School, University of Pecs , Pecs , Hungary.
RESUMEN / SUMMARY: - Although advances in cancer therapies continue to develop, the shortness of the survival of lung cancer patients is still disappointing. Therefore, finding new adjuvant strategies is within the focus of cancer cure. Based on observations that deuterium depletion inhibits the growth of cancer cell lines and suppresses certain proto-oncogenes, we have conducted a clinical study in 129 patients with small cell and nonsmall cell lung cancers who consumed deuterium-depleted drinking water (DDW) as a nontoxic agent in addition to conventional chemotherapy and radiotherapy. Median survival time (MST) was 25.9 mo in males and 74.1 mo in female patients; the difference between genders was statistically significant (p < 0.05). Median survival of subjects with brain metastasis was 27.1 mo. Cumulative 5-yr survival probabilities were 19%, 52%, and 33% in males, females, and all patients with brain metastasis, respectively. Gene expression analysis in mouse lung indicated that DDW attenuates 7,12-dimethylbenz(a)anthracene (DMBA)-induced expression of Bcl2, Kras, and Myc in females. In conclusion, DDW counteracts the DMBA-induced overexpression of Bcl2, Kras and Myc genes in mouse lung, and it may extend survival of lung cancer patients as a nontoxic anticancer dietary supplement, especially for women with tumors overexpressing cancer-related genes, because MST of DDW-consuming group was 2-4 times longer than it is generally observed in lung cancer patients.
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[39]
TÍTULO / TITLE: - Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Invest. 2013 Mar 1. pii: 65385. doi: 10.1172/JCI65385.
●● Enlace al texto completo (gratuito o de pago) 1172/JCI65385
AUTORES / AUTHORS: - Chatterjee S; Heukamp LC; Siobal M; Schottle J; Wieczorek C; Peifer M; Frasca D; Koker M; Konig K; Meder L; Rauh D; Buettner R; Wolf J; Brekken RA; Neumaier B; Christofori G; Thomas RK; Ullrich RT
RESUMEN / SUMMARY: - The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. This disruption was sufficient to prevent tumor growth in vivo. In patients with lung cancer, we found that this VEGF:VEGFR2 feed-forward loop was active, as the level of VEGF/VEGFR2 binding in tumor cells was highly correlated to tumor angiogenesis. We further demonstrated that inhibition of tumor cell VEGFR2 induces feedback activation of the IRS/MAPK signaling cascade. Most strikingly, combined pharmacological inhibition of VEGFR2 (ZD6474) and MEK (PD0325901) in tumor cells resulted in dramatic tumor shrinkage, whereas monotherapy only modestly slowed tumor growth. Thus, a tumor cell-autonomous VEGF:VEGFR2 feed-forward loop provides signal amplification required for the establishment of fully angiogenic tumors in lung cancer. Interrupting this feed-forward loop switches tumor cells from an angiogenic to a proliferative phenotype that sensitizes tumor cells to MAPK inhibition.
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[40]
TÍTULO / TITLE: - Real world impact of epidermal growth factor receptor mutation status on treatment patterns in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 2. pii: S0169-5002(13)00019-6. doi: 10.1016/j.lungcan.2013.01.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.009
AUTORES / AUTHORS: - Sun JM; Rampal S; Lee G; Lee J; Choi YL; Parasuraman B; Guallar E; Cho J; Shim YM
INSTITUCIÓN / INSTITUTION: - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation status is an important predictor of the efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy in patients with non-small cell lung cancer (NSCLC). We evaluated the real impact of EGFR mutation status on chemotherapy patterns of NSCLC patients. PATIENTS AND METHODS: This is a retrospective cohort study of consecutive advanced NSCLC patients attended at the Samsung Medical Centre in Seoul, Korea, from January 2007 through July 2010. EGFR mutation was analyzed by direct sequencing testing. RESULTS: Among 1164 patients treated during the study period, 166 (14.3%) were EGFR mutation positive, 275 (23.6%) were mutation negative, and 723 (62.1%) had mutation status unknown. Overall, 605 (52%) received TKI therapy as a first-, second-, or third-line therapy. The proportions of patients receiving TKI therapy among those with positive, negative and unknown EGFR mutation status were 88.0, 46.5, and 45.8%, respectively. After adjustment for other factors, patients with a positive EGFR mutation status (odds ratio [OR] 7.88, 95% CI 4.58, 13.57), and those who were female (OR 2.83, 95% CI 2.04, 3.92) or had poor performance status (OR 1.58, 95% CI 1.13, 2.22) were significantly more likely to receive TKI treatment. Furthermore, the temporal relationship between EGFR mutation reporting and initiation of TKI therapy significantly differed by EGFR mutation status. CONCLUSION: EGFR mutation status significantly affected the chemotherapy patterns in advanced NSCLC. More widespread EGFR testing and the use of faster and more sensitive mutation tests will result in more timely and appropriate use of TKI therapy in advanced NSCLC.
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[41]
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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[42]
TÍTULO / TITLE: - Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):751-5. doi: 10.1700/1217.13499.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13499
AUTORES / AUTHORS: - Chen YB; Mu CY; Huang JA
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine and Jiangsu Institute of Clinical Immunology, First Affiliated Hospital of Soochow University, Suzhou, China.
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: The programmed death-1-ligand 1 (PD-L1) has been recently suggested to play a pivotal role in the immune evasion of tumors from host immune system. In the study, we tried to reveal the clinical significance of PD-L1 in patients with non-small cell lung cancer (NSCLC), which is one of the most aggressive and intractable malignant tumors. METHODS AND STUDY DESIGN: PD-L1 expression in 120 NSCLC tissue specimens and 10 benign control samples embedded with wax were retrospectively detected by immunohistochemistry. RESULTS: No PD-L1 was detected in the 10 benign controls, whereas 57.5% of NSCLC tissue specimens showed PD-L1 expression. There was no relationship between PD-L1 expression and patient age, gender or histopathological type. However, PD-L1 expression was significantly correlated to the degree of tumor cell differentiation, stage of tumor node metastasis (TNM) and patient survival. Poor tumor cell differentiation and advanced TNM stage were related to higher PD-L1 expression. PD-L1-negative NSCLC patients had longer overall 5-year survival than PD-L1-positive patients ( P <0.0001). PD-L1 status was a significant independent prognostic factor of NSCLC (chi2 = 18.153, RR = 2.946, P <0.001). CONCLUSIONS: Up-regulated PD-L1 expression in NSCLC is related to the degree of tumor cell differentiation and TNM stage. PD-L1 status may be a new predictor of prognosis for patients with NSCLC.
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[43]
TÍTULO / TITLE: - Mechanistic links between COPD and lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Cancer. 2013 Apr;13(4):233-45. doi: 10.1038/nrc3477. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1038/nrc3477
AUTORES / AUTHORS: - Houghton AM
INSTITUCIÓN / INSTITUTION: - Clinical Research Division, Fred Hutchinson Cancer Research Center and Division of Pulmonary and Critical Care, University of Washington, Seattle, Washington 98109, USA.
RESUMEN / SUMMARY: - Numerous epidemiological studies have consistently linked the presence of chronic obstructive pulmonary disease (COPD) to the development of lung cancer, independently of cigarette smoking dosage. The mechanistic explanation for this remains poorly understood. Progress towards uncovering this link has been hampered by the heterogeneous nature of the two disorders: each is characterized by multiple sub-phenotypes of disease. In this Review, I discuss the nature of the link between the two diseases and consider specific mechanisms that operate in both COPD and lung cancer, some of which might represent either chemopreventive or chemotherapeutic targets.
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[44]
TÍTULO / TITLE: - Comment on: Smiechowski et al. The Use of Metformin and the Incidence of Lung Cancer in Patients With Type 2 Diabetes. Diabetes Care 2013;36:124-129.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diabetes Care. 2013 Mar;36(3):e40. doi: 10.2337/dc12-1978.
●● Enlace al texto completo (gratuito o de pago) 2337/dc12-1978
AUTORES / AUTHORS: - Lai SW; Liao KF
INSTITUCIÓN / INSTITUTION: - Corresponding author: Kuan-Fu Liao, kuanfuliao@yahoo.com.tw.
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[45]
TÍTULO / TITLE: - Response to Comment on: Smiechowski et al. The Use of Metformin and the Incidence of Lung Cancer in Patients With Type 2 Diabetes. Diabetes Care 2013;36:124-129.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diabetes Care. 2013 Mar;36(3):e41. doi: 10.2337/dc12-2262.
●● Enlace al texto completo (gratuito o de pago) 2337/dc12-2262
AUTORES / AUTHORS: - Suissa S; Azoulay L
INSTITUCIÓN / INSTITUTION: - Corresponding author: Samy Suissa, samy.suissa@mcgill.ca.
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[46]
TÍTULO / TITLE: - Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Apr;145(4):955-63. doi: 10.1016/j.jtcvs.2012.12.037. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2012.12.037
AUTORES / AUTHORS: - Sugarbaker DJ; Gill RR; Yeap BY; Wolf AS; Dasilva MC; Baldini EH; Bueno R; Richards WG
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass. Electronic address: dsugarbaker@partners.org.
RESUMEN / SUMMARY: - OBJECTIVE: Local recurrence limits long-term survival in patients with malignant pleural mesothelioma. We investigated whether hyperthermic intraoperative cisplatin chemotherapy lavage affects the interval to recurrence and overall survival among patients with favorable prognostic factors. METHODS: Using a preoperative risk assessment algorithm we had previously developed and validated, we retrospectively identified a cohort of patients treated with cytoreductive surgery from 2001 to 2009. The patients had epithelial histologic findings on biopsy and were characterized as having a low risk of early recurrence and death (ie, tumor volume </=500 cm(3) and were either men with a hemoglobin level of >/=13 g/dL or were women). Those patients who had received hyperthermic intraoperative cisplatin chemotherapy were compared with a comparison group of those who had not. Fisher’s exact test was used to determine the balance of prognostic factors. The Kaplan-Meier method and log-rank tests were used to estimate and compare the interval to recurrence and overall survival. Cox proportional hazards regression was used for multivariate analysis. RESULTS: The cohort criteria identified 103 patients: 72 who received hyperthermic intraoperative cisplatin chemotherapy and 31 who did not. The groups were balanced for prognostic factors, except for the use of neoadjuvant chemotherapy (more common in the comparison group). The hyperthermic intraoperative cisplatin chemotherapy group exhibited a significantly longer interval to recurrence (27.1 vs 12.8 months) and overall survival (35.3 vs 22.8 months) than the comparison group. The improved interval to recurrence and overall survival for the hyperthermic intraoperative cisplatin chemotherapy group were particularly evident among the subgroups of patients who had not received hemithoracic radiotherapy and who had pathologic stage N1 or N2 lymph node metastases. CONCLUSIONS: A favorable outcome and minimal incremental morbidity support the incorporation of hyperthermic intraoperative cisplatin chemotherapy into multimodality treatment strategies for patients with low-risk epithelial malignant pleural mesothelioma.
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[47]
TÍTULO / TITLE: - Motion Interplay as a Function of Patient Parameters and Spot Size in Spot Scanning Proton Therapy for Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Feb 22. pii: S0360-3016(13)00088-6. doi: 10.1016/j.ijrobp.2013.01.024.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.01.024
AUTORES / AUTHORS: - Grassberger C; Dowdell S; Lomax A; Sharp G; Shackleford J; Choi N; Willers H; Paganetti H
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Center for Proton Radiotherapy, Paul Scherrer Institute, Villigen, Switzerland. Electronic address: Grassberger.Clemens@mgh.harvard.edu.
RESUMEN / SUMMARY: - PURPOSE: To quantify the impact of respiratory motion on the treatment of lung tumors with spot scanning proton therapy. METHODS AND MATERIALS: Four-dimensional Monte Carlo simulations were used to assess the interplay effect, which results from relative motion of the tumor and the proton beam, on the dose distribution in the patient. Ten patients with varying tumor sizes (2.6-82.3 cc) and motion amplitudes (3-30 mm) were included in the study. We investigated the impact of the spot size, which varies between proton facilities, and studied single fractions and conventionally fractionated treatments. The following metrics were used in the analysis: minimum/maximum/mean dose, target dose homogeneity, and 2-year local control rate (2y-LC). RESULTS: Respiratory motion reduces the target dose homogeneity, with the largest effects observed for the highest motion amplitudes. Smaller spot sizes (sigma approximately 3 mm) are inherently more sensitive to motion, decreasing target dose homogeneity on average by a factor 2.8 compared with a larger spot size (sigma approximately 13 mm). Using a smaller spot size to treat a tumor with 30-mm motion amplitude reduces the minimum dose to 44.7% of the prescribed dose, decreasing modeled 2y-LC from 87.0% to 2.7%, assuming a single fraction. Conventional fractionation partly mitigates this reduction, yielding a 2y-LC of 71.6%. For the large spot size, conventional fractionation increases target dose homogeneity and prevents a deterioration of 2y-LC for all patients. No correlation with tumor volume is observed. The effect on the normal lung dose distribution is minimal: observed changes in mean lung dose and lung V20 are <0.6 Gy(RBE) and <1.7%, respectively. CONCLUSIONS: For the patients in this study, 2y-LC could be preserved in the presence of interplay using a large spot size and conventional fractionation. For treatments using smaller spot sizes and/or in the delivery of single fractions, interplay effects can lead to significant deterioration of the dose distribution and lower 2y-LC.
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[48]
TÍTULO / TITLE: - Thromboxane A receptor-mediated release of matrix metalloproteinase-1 (MMP-1) induces expression of monocyte chemoattractant protein-1 (MCP-1) by activation of protease-activated receptor 2 (PAR2) in A549 human lung adenocarcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Carcinog. 2013 Mar 8. doi: 10.1002/mc.22020.
●● Enlace al texto completo (gratuito o de pago) 1002/mc.22020
AUTORES / AUTHORS: - Li X; Tai HH
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky.
RESUMEN / SUMMARY: - Matrix metalloproteinases (MMPs) and monocyte chemoattractant protein-1 (MCP-1, CCL2) are known to be upregulated in many tumors. Their roles in tumor invasion and metastasis are being uncovered. How they are related to each other and involved in tumor progression remains to be determined. Earlier it was reported that I-BOP-initiated activation of thromboxane A2 receptor (TP) induced the release of MMP-1, MMP-3, and MMP-9 from lung cancer A549 cells overexpressing TPalpha (A549-TPalpha). Herein it was found that MMP-1, but not MMP-3 or MMP-9, induced the expression of MCP-1 in A549 cells. Conditioned medium (CM) from I-BOP activated, MMP-1 siRNA pretreated A549-TPalpha cells induced greatly attenuated expression of MCP-1 in A549 cells indicating that MMP-1 in the CM contributed significantly to the expression of MCP-1. MMP-1 was shown to activate protease-activated receptor 2 (PAR2) instead of commonly assumed PAR1 to increase the expression of MCP-1 in A549 cells. This conclusion was reached from the following findings: (1) expression of MCP-1 induced by trypsin, a PAR2 agonist, and also PAR2 agonist peptide, was inhibited by a PAR2 antagonist; (2) expression of MCP-1 induced by MMP-1 and by CM from I-BOP activated A549-TPalpha cells was blocked by a PAR2 antagonist but not by other PAR antagonists; (3) expression of MCP-1 induced by MMP-1 and by CM from I-BOP activated A549-TPalpha cells was attenuated significantly by pretreatment of cells with PAR2-siRNA. These results suggest that PAR2 is a novel MMP-1 target mediating MMP-1-induced signals in A549 lung cancer cells. © 2013 Wiley Periodicals, Inc.
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[49]
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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[50]
TÍTULO / TITLE: - Effects of erlotinib first-line maintenance therapy versus placebo on the health-related quality of life of patients with metastatic non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Apr;49(6):1205-15. doi: 10.1016/j.ejca.2012.11.006. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2012.11.006
AUTORES / AUTHORS: - Juhasz E; Kim JH; Klingelschmitt G; Walzer S
INSTITUCIÓN / INSTITUTION: - Koranyi National Institute for TB and Pulmonology, Budapest, Hungary. Electronic address: juhasz@koranyi.hu.
RESUMEN / SUMMARY: - INTRODUCTION: Maintenance therapy can delay progression and prolong survival in metastatic non-small-cell lung cancer (mNSCLC). As treatment for mNSCLC is non-curative, its impact on patient health-related quality of life (HRQoL) is an important consideration. SATURN (Sequential Tarceva in Unresectable NSCLC) was a randomised, double-blind, placebo-controlled, multicentre study investigating the impact of erlotinib maintenance therapy on HRQoL in patients with locally advanced or recurrent NSCLC. PATIENTS AND METHODS: Eligible patients who had previously completed four cycles of platinum-based chemotherapy were randomised 1:1 to receive erlotinib 150mg/day or placebo until disease progression, unacceptable toxicity or death. Patient HRQoL was assessed using the Functional Assessment of Cancer Therapy-Lung questionnaire, in terms of time to symptom progression (TSP), time to deterioration (TTD) in Trial Outcome Index (TOI) and TTD. Exploratory analysis was based on time to analgesia and appearance of key symptoms (pain, cough and dyspnoea). RESULTS: Compared with placebo, erlotinib maintenance therapy prolonged progression-free and overall survival by 41% and 23%, respectively. At baseline, HRQoL measures were comparable between the two treatment groups. Maintenance therapy with erlotinib did not impact on deterioration in HRQoL: TSP (hazard ratio [HR]=0.91 [95% confidence interval (CI) 0.74-1.12]; n=785), TTD in TOI (HR=1.06 [95% CI 0.87-1.31]; n=781) and TTD in HRQoL (HR=0.96 [95% CI 0.79-1.16]; n=776). Time to pain and time to analgesic use were significantly delayed in patients receiving erlotinib compared with placebo (HR=0.61 [95% CI 0.42-0.88]; p=0.0080 and HR=0.66 [95% CI 0.46-0.94]; p=0.0199, respectively). A non-significant trend towards delayed time to cough and time to dyspnoea (HR=0.77 [95% CI 0.49-1.21] and HR=0.75 [95% CI 0.48-1.17], respectively) was also observed. CONCLUSIONS: Erlotinib maintenance therapy significantly extends progression-free survival without compromising patient HRQoL in comparison with placebo, with some improvement in symptoms.
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[51]
- CASTELLANO -
TÍTULO / TITLE:Carcinoma broncogenico no microcitico resecado, estadio pIIIA-N2.¿En que pacientes la adyuvancia ofrece mayor beneficio?
TÍTULO / TITLE: - Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cir Esp. 2013 Feb 28. pii: S0009-739X(13)00036-5. doi: 10.1016/j.ciresp.2012.11.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ciresp.2012.11.014
AUTORES / AUTHORS: - Gomez AM; Jarabo JR; Fernandez C; Calatayud J; Fernandez E; Torres AJ; Balibrea JL; Hernando F
INSTITUCIÓN / INSTITUTION: - Servicio de Cirugia General II y Cirugia Toracica, Hospital Clinico San Carlos, Madrid, España. Electronic address: agm912@hotmail.com.
RESUMEN / SUMMARY: - BACKGROUND: Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. METHODS: A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. RESULTS: The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). CONCLUSIONS: Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma.
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[52]
TÍTULO / TITLE: - Diagnosis, clinicopathologic features, treatment, and prognosis of small cell carcinoma of the uterine cervix; Kansai Clinical Oncology Group/Intergroup study in Japan.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gynecol Oncol. 2013 Feb 26. pii: S0090-8258(13)00096-6. doi: 10.1016/j.ygyno.2013.02.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ygyno.2013.02.025
AUTORES / AUTHORS: - Kuji S; Hirashima Y; Nakayama H; Nishio S; Otsuki T; Nagamitsu Y; Tanaka N; Ito K; Teramoto N; Yamada T
INSTITUCIÓN / INSTITUTION: - Division of gynecology, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka, Japan. Electronic address: s.kuji@scchr.jp.
RESUMEN / SUMMARY: - OBJECTIVES: This is a multicenter, collaborative study to accumulate cases of small cell carcinoma of the uterine cervix (SmCC), to clarify its clinical and clinicopathologic features and prognosis, and to obtain findings to establish future individualized treatment. METHODS: At medical centers participating in the Kansai Clinical Oncology Group/Intergroup, patients diagnosed with SmCC between 1997 and 2007 were enrolled. Clinicopathologic features and prognosis were retrospectively evaluated in patients with SmCC diagnosed at a central pathologic review. RESULTS: A total of 71 patients were registered at 25 medical centers in Japan. Of these, 52 patients (73%) were diagnosed with SmCC based on a pathological review. These 52 patients diagnosed with SmCC were analyzed. The median follow-up period was 57months. The 4-year progression-free survival (PFS) was: IB1, 59%; IB2, 68%; IIB, 13%; and IIIB, 17%. The 4-year overall survival (OS) was: IB1, 63%; IB2, 67%; IIB, 30%; IIIB, 29%; and IVB, 25%. For postoperative adjuvant therapy, postoperative chemotherapy (a platinum drug in all cases) was compared to non-chemotherapy. The 4-year PFS was 65% and 14%, and the 4-year OS was 65% and 29%. PFS was significantly better (p=0.002), and the OS tended to be better (p=0.073) in the group with postoperative chemotherapy. CONCLUSION: Even in patients with early stage SmCC, the prognosis is poor. However, in early stage patients, by adding postoperative chemotherapy, the prognosis may improve. Currently, various treatment protocols are used at each medical center, but in the future, a standardized treatment protocol for SmCC will hopefully be established.
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[53]
TÍTULO / TITLE: - TPL2 kinase is a suppressor of lung carcinogenesis.
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.1215938110
AUTORES / AUTHORS: - Gkirtzimanaki K; Gkouskou KK; Oleksiewicz U; Nikolaidis G; Vyrla D; Liontos M; Pelekanou V; Kanellis DC; Evangelou K; Stathopoulos EN; Field JK; Tsichlis PN; Gorgoulis V; Liloglou T; Eliopoulos AG
INSTITUCIÓN / INSTITUTION: - Molecular and Cellular Biology Laboratory, Division of Basic Sciences and Department of Pathology, University of Crete Medical School, 710 03 Heraklion, Greece.
RESUMEN / SUMMARY: - Lung cancer is a heterogeneous disease at both clinical and molecular levels, posing conceptual and practical bottlenecks in defining key pathways affecting its initiation and progression. Molecules with a central role in lung carcinogenesis are likely to be targeted by multiple deregulated pathways and may have prognostic, predictive, and/or therapeutic value. Here, we report that Tumor Progression Locus 2 (TPL2), a kinase implicated in the regulation of innate and adaptive immune responses, fulfils a role as a suppressor of lung carcinogenesis and is subject to diverse genetic and epigenetic aberrations in lung cancer patients. We show that allelic imbalance at the TPL2 locus, up-regulation of microRNA-370, which targets TPL2 transcripts, and activated RAS (rat sarcoma) signaling may result in down-regulation of TPL2 expression. Low TPL2 levels correlate with reduced lung cancer patient survival and accelerated onset and multiplicity of urethane-induced lung tumors in mice. Mechanistically, TPL2 was found to antagonize oncogene-induced cell transformation and survival through a pathway involving p53 downstream of cJun N-terminal kinase (JNK) and be required for optimal p53 response to genotoxic stress. These results identify multiple oncogenic pathways leading to TPL2 deregulation and highlight its major tumor-suppressing function in the lung.
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[54]
TÍTULO / TITLE: - Association of p53 Codon 72 Genotypes and Clinical Outcome in Human Papillomavirus-Infected Lung Cancer Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Apr;95(4):1196-203. doi: 10.1016/j.athoracsur.2012.12.059.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.12.059
AUTORES / AUTHORS: - Chen SP; Hsu NY; Wu JY; Chen CY; Chou MC; Lee H; Cheng YW
INSTITUCIÓN / INSTITUTION: - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China; Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: We recently reported that high-risk human papillomavirus (HPV) 16/18 E6 protein was associated with p53 protein degradation in lung cancer. The present study addressed the relationship between the different p53 genotypes and HPV oncoprotein expression with respect to p53 protein degradation and clinical outcome in primary lung cancer patients. METHODS: We examined whether p53 codon 72 polymorphism and HPV oncoprotein expression could be associated with patients’ outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine p53 codon 72 polymorphisms, HPV 16/18 infection, and HPV 16/18 E6 and p53 protein expression by polymerase chain reaction (PCR)-restriction fragment length polymorphism, nested-PCR, and immunohistochemical analysis. RESULTS: The presence of HPV 16/18 DNA and E6 protein was inversely associated with p53 expression. The frequency of p53 protein degradation was also much higher in HPV 16/18 E6-positive/Arg/Arg lung tumors than in the other 3 groups. After adjusting gender and tumor type, the major contributors to p53 degradation in lung cancer patients were determined to be p53 codon72 polymorphism and HPV 16/18 E6 oncoprotein expression. This association was not found for HPV 16/18 DNA infection. Survival was significantly longer in patients with HPV 16/18 E6-negative/Arg/Arg tumors (median 32.7 months) than in patients with HPV-positive and p53 genetic variant tumors (p = 0.008). CONCLUSIONS: The HPV 16/18 E6 protein, which is involved in the p53 inactivation that contributes to HPV-infected lung tumorigenesis, is associated with the p53 codon 72 genotype. The combination of HPV 16/18 E6 status and p53 codon72 polymorphism in lung tumors is an important biologic and prognostic parameter.
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[55]
TÍTULO / TITLE: - Harnessing the immune system for the treatment of non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1021-8. doi: 10.1200/JCO.2012.45.8703. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.45.8703
AUTORES / AUTHORS: - Brahmer JR
INSTITUCIÓN / INSTITUTION: - MSc, The Bunting-Blaustein Cancer Research Bldg, 1650 Orleans St, Room G-94, Baltimore, MD 21287-0013; brahmju@jhmi.edu.
RESUMEN / SUMMARY: - Over the last several years, new therapeutic targets have emerged in immunotherapy, particularly the immune checkpoint pathways. Blocking inhibitory pathways via monoclonal antibodies, such as the anti-cytotoxic T-lymphocyte antigen-4 antibody (ipilimumab), anti-programmed cell death-1 antibody (BMS-936558), and anti-programmed cell death-1 ligand antibody (BMS-936559), has the ability to break down the shield that tumors co-opt for their defense. Vaccines are able to help the immune system develop immune memory that can have long-lasting, tumor-specific effects. Newer vaccines, particularly the tumor cell vaccine, belagenpumatucel-L, and the antigen-specific vaccines, melanoma-associated antigen-A3, liposomal BLP-25, TG4010, and recombinant human epidermal growth factor, are being evaluated in some of the largest trials ever attempted in lung cancer therapy. These therapies alone or in combination may hold the key to making immunotherapy a reality in the treatment of lung cancer.
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[56]
TÍTULO / TITLE: - A Cancer Stem Cell Model for Studying Brain Metastases From Primary Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Cancer Inst. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djt022
AUTORES / AUTHORS: - Nolte SM; Venugopal C; McFarlane N; Morozova O; Hallett RM; O’Farrell E; Manoranjan B; Murty NK; Klurfan P; Kachur E; Provias JP; Farrokhyar F; Hassell JA; Marra M; Singh SK
INSTITUCIÓN / INSTITUTION: - Affiliations of authors: Department of Biochemistry and Biomedical Sciences (SMN, CV, RMH, BM, JAH, SKS), Department of Neuroscience (EO, SKS), Department of Surgery (NKM, PK, EK, SKS), Department of Pathology and Molecular Medicine (JPP), Department of Health Research Methodology (FF), and Department of Pediatrics (SKS), Faculty of Health Sciences, McMaster Stem Cell and Cancer Research Institute (SMN, CV, NM, EO, BM, SKS) , and McMaster Centre of Functional Genomics (RMH, JAH), McMaster University, Hamilton, ON, Canada; Genome Sciences Centre, BC Cancer Agency (OM, MM) , and Department of Medical Genetics, University of British Columbia (MM), Vancouver, BC, Canada.
RESUMEN / SUMMARY: - BackgroundBrain metastases are most common in adults with lung cancer, predicting uniformly poor patient outcome, with a median survival of only months. Despite their frequency and severity, very little is known about tumorigenesis in brain metastases.MethodsWe applied previously developed primary solid tumor-initiating cell models to the study of brain metastases from the lung to evaluate the presence of a cancer stem cell population. Patient-derived brain metastases (n = 20) and the NCI-H1915 cell line were cultured as stem-enriching tumorspheres. We used in vitro limiting-dilution and sphere-forming assays, as well as intracranial human-mouse xenograft models. To determine genes overexpressed in brain metastasis tumorspheres, we performed comparative transcriptome analysis. All statistical analyses were two-sided.ResultsPatient-derived brain metastasis tumorspheres had a mean sphere-forming capacity of 33 spheres/2000 cells (SD = 33.40) and median stem-cell frequency of 1/60 (range = 0-1/141), comparable to that of primary brain tumorspheres (P = .53 and P = .20, respectively). Brain metastases also expressed CD15 and CD133, markers suggestive of a stemlike population. Through intracranial xenotransplantation, brain metastasis tumorspheres were found to recapitulate the original patient tumor heterogeneity. We also identified several genes overexpressed in brain metastasis tumorspheres as statistically significant predictors of poor survival in primary lung cancer.ConclusionsFor the first time, we demonstrate the presence of a stemlike population in brain metastases from the lung. We also show that NCI-H1915 tumorspheres could be useful in studying self-renewal and tumor initiation in brain metastases. Our candidate genes may be essential to metastatic stem cell populations, where pathway interference may be able to transform a uniformly fatal disease into a more localized and treatable one.
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[57]
TÍTULO / TITLE: - Researchers explore possible link between mesothelioma and dust emissions in southern nevada.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Cancer Inst. 2013 Mar 6;105(5):312-4. doi: 10.1093/jnci/djt033. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1093/jnci/djt033
AUTORES / AUTHORS: - O’Hanlon LH
INSTITUCIÓN / INSTITUTION: - kristine.crane@oup.com.
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[58]
TÍTULO / TITLE: - CD4/CD8 co-expression shows independent prognostic impact in resected non-small cell lung cancer patients treated with adjuvant radiotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 2. pii: S0169-5002(13)00018-4. doi: 10.1016/j.lungcan.2012.12.026.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.026
AUTORES / AUTHORS: - Hald SM; Bremnes RM; Al-Shibli K; Al-Saad S; Andersen S; Stenvold H; Busund LT; Donnem T
INSTITUCIÓN / INSTITUTION: - Department of Clinical Medicine, University of Tromso, Norway. Electronic address: sigurd.hald@uit.no.
RESUMEN / SUMMARY: - BACKGROUND: Though traditionally regarded as immunosuppressive, radiotherapy may also stimulate immune cells and facilitate an anti-tumor immune response. We therefore aimed to explore the prognostic significance of immune cell markers in non-small cell lung cancer (NSCLC) patients treated with postoperative radiotherapy (PORT). METHODS: In addition to demographic and clinicopathological information, tumor tissue samples were collected and tissue microarrays (TMAs) were constructed from 55 patients with stage I-IIIA NSCLC who received PORT. Tumor and stromal expression of CD1a+, CD3+, CD4+, CD8+, CD20+, CD56+, CD68+, CD117+ and CD138+ cells, as well as M-CSF and CSF-1R, was assessed by immunohistochemistry. RESULTS: In univariate analysis, high co-expression of CD4+ and CD8+ T lymphocytes as well as high expression of CD1a+ dendritic cells in the tumor stroma correlated with improved disease-specific survival (DSS). In multivariate analysis patients with stromal downward arrowCD4/ downward arrowCD8 expression had a hazard ratio of 21.1 (CI95% 3.9-115.6, P<0.001) when compared to those with upward arrowCD4/ upward arrowCD8 expression. CONCLUSIONS: Stromal downward arrowCD4/ downward arrowCD8 expression was an independent negative prognostic factor for survival in NSCLC patients receiving PORT, indicating a highly detrimental prognosis.
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[59]
TÍTULO / TITLE: - Clinical significance of RUNX2 expression in patients with nonsmall cell lung cancer: a 5-year follow-up study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0720-4
AUTORES / AUTHORS: - Li H; Zhou RJ; Zhang GQ; Xu JP
INSTITUCIÓN / INSTITUTION: - Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, No. 183, Xinqiaozheng Rd, Chongqing, 400037, China.
RESUMEN / SUMMARY: - This study was designed to evaluate expression and prognostic significance of runt-related transcription factor (RUNX)-2 in human nonsmall cell lung cancer (NSCLC). RUNX2 expression was examined at mRNA and protein levels by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot in NSCLC tissues and adjacent normal tissues. In addition, RUNX2 expression was analyzed by immunohistochemistry in 121 clinicopathologically characterized NSCLC cases. The relationship between the expression of RUNX2 and clinicopathological characteristics and prognosis was statistically analyzed. Both qRT-PCR and Western blot demonstrated that RUNX2 mRNA and protein levels were significantly higher in NSCLC tissues compared to the adjacent normal tissues from the same individual. Immunohistochemistry analysis showed that RUNX2 expression was significantly correlated with tumor size, tumor stage, and lymph node metastasis. Higher RUNX2 expression was associated with shorter postoperative survival time of NSCLC patients by Kaplan-Meier method and was found to be an independent risk factor that influences the postoperative survival time of NSCLC patients by Cox regression analysis. In conclusion, these data showed that RUNX2 may play an important role in NSCLC tumorigenesis, and RUNX2 might serve as a novel prognostic marker in NSCLC.
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[60]
TÍTULO / TITLE: - Endothelial Cell Protein C Receptor Opposes Mesothelioma Growth Driven by Tissue Factor.
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-12-1690
AUTORES / AUTHORS: - Keshava S; Sahoo S; Tucker TA; Idell S; Rao LV; Pendurthi UR
INSTITUCIÓN / INSTITUTION: - Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler.
RESUMEN / SUMMARY: - The pro-coagulant protein Tissue Factor (TF, F3) is a powerful growth promoter in many tumors but its mechanism of action is not well understood. More generally, it is unknown whether hemostatic factors expressed on tumor cells influence TF-mediated effects on cancer progression. In this study, we investigated the influence of TF, endothelial cell protein C receptor (EPCR, PROCR) and protease activated receptor-1 (PAR1, F2R) on the growth of malignant pleural mesothelioma (MPM), using human MPM cells that lack or express TF, EPCR or PAR1 and an orthotopic nude mouse model of MPM. Intrapleural administration of MPM cells expressing TF and PAR1 but lacking EPCR and PAR2 (F2RL1) generated large tumors in the pleural cavity. Suppression of TF or PAR1 expression in these cells markedly reduced tumor growth. In contrast, TF overexpression in non-aggressive MPM cells that expressed EPCR and PAR1 with minimal levels of TF did not increase their limited tumorigenicity. More importantly, ectopic expression of EPCR in aggressive MPM cells attenuated their growth potential, whereas EPCR silencing in non-aggressive MPM cells engineered to overexpress TF increased their tumorigenicity. Immunohistochemical analyses revealed that EPCR expression in tumor cells reduced tumor cell proliferation and enhanced apoptosis. Overall, our results enlighten the mechanism by which TF promotes tumor growth through PAR1, and they show how EPCR can attenuate the growth of TF-expressing tumor cells.
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[61]
TÍTULO / TITLE: - Prediagnosis Soy Food Consumption and Lung Cancer Survival in Women.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.0942
AUTORES / AUTHORS: - Yang G; Shu XO; Li HL; Chow WH; Wen W; Xiang YB; Zhang X; Cai H; Ji BT; Gao YT; Zheng W
INSTITUCIÓN / INSTITUTION: - Gong Yang, Xiao-Ou Shu, Wanqing Wen, Xianglan Zhang, Hui Cai, and Wei Zheng, Vanderbilt University Medical Center, Nashville, TN; Hong-Lan Li, Yong-Bing Xiang, and Yu-Tang Gao, Shanghai Cancer Institute, Shanghai, China; and Wong-Ho Chow and Bu-Tian Ji, National Cancer Institute, National Institutes of Health, Bethesda, MD.
RESUMEN / SUMMARY: - PURPOSEWe recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer. PATIENTS AND METHODSThis analysis included 444 women with incident lung cancer identified from the Shanghai Women’s Health Study. Prediagnosis soy food intake was assessed at enrollment and reassessed 2 years later. Proportional hazards models were used to evaluate the association between soy food intake and overall survival.ResultsOf the 444 patients with lung cancer, 318 died during follow-up. Initial analyses including all patients showed that higher intake of soy food was associated with better overall survival after adjusting for demographic and lifestyle characteristics and other nonclinical factors. Larger effect sizes for the association were found after additional adjustment for tumor stage and treatment in analyses including 301 patients with data available on these clinical factors. Compared with the median intake of soy food, fully adjusted hazard ratios for total mortality associated with the 10th, 30th, 70th, and 90th percentiles of intake were 1.81 (95% CI, 1.26 to 2.59), 1.25 (95% CI, 1.09 to 1.42), 0.88 (95% CI, 0.80 to 0.97), and 0.89 (95% CI, 0.68 to 1.16), respectively. Similar inverse associations were observed for dietary isoflavone intake. CONCLUSIONThis study suggests, to the best of our knowledge for the first time, that, among women with lung cancer, prediagnosis intake of soy food is associated with better overall survival.
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[62]
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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[63]
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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[64]
TÍTULO / TITLE: - Neuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 21. doi: 10.1038/bjc.2013.112.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.112
AUTORES / AUTHORS: - Stovold R; Meredith SL; Bryant JL; Babur M; Williams KJ; Dean EJ; Dive C; Blackhall FH; White A
INSTITUCIÓN / INSTITUTION: - 1] Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, 3.016 AV Hill Building, Manchester M13 9PT, UK [2] Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, UK.
RESUMEN / SUMMARY: - Background:Small-cell lung cancer (SCLC) has a very aggressive clinical course with early metastasis. This study investigated how the distinctive neuroendocrine characteristics contribute to disease progression and invasion in human SCLC.Methods:The neuroendocrine phenotype (pro-opiomelanocortin (POMC)) was quantified by ELISA in blood samples from 43 SCLC patients. The neuroendocrine (POMC, chromogranin A, neuron-specific enolase, NCAM) and epithelial (cytokeratin and E-cadherin) phenotypes were investigated, using ELISA and immunocytochemistry/immunohistochemistry.Results:In SCLC patients, 16% had elevated circulating POMC, which was associated with significantly worse survival (P=0.02) and liver metastases (P=0.004). In addition, POMC correlated with epithelial-positive circulating tumour cells (P=0.0002). In a panel of SCLC cell lines, all POMC-secreting cell lines expressed cytokeratin (40% of total). Even after cloning, DMS 79 cells expressed both neuroendocrine and epithelial markers. DMS 79 xenografts secreted POMC into the blood, which mirrored the tumour volume. These xenografts expressed both neuroendocrine and epithelial phenotypes in all tumours, with both phenotypes prevalent in cells invading the surrounding tissue.Conclusion:Both neuroendocrine and epithelial phenotypes coexist in human SCLC tumours in vitro and in vivo and this persists in invading tumour cells. In patients, POMC secretion predicts poor survival and liver metastases, suggesting a crucial role of the neuroendocrine phenotype.British Journal of Cancer advance online publication, 21 March 2013; doi:10.1038/bjc.2013.112 www.bjcancer.com.
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[65]
TÍTULO / TITLE: - Analysis of Treatment Outcomes of Intraventricular Chemotherapy in 105 Patients for Leptomeningeal Carcinomatosis from Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318287c943
AUTORES / AUTHORS: - Gwak HS; Joo J; Kim S; Yoo H; Shin SH; Han JY; Kim HT; Lee JS; Lee SH
INSTITUCIÓN / INSTITUTION: - *Neuro-Oncology Clinic, daggerBiometric Research branch, and double daggerCenter for Lung Cancer, National Cancer Center, Goyang, Korea.
RESUMEN / SUMMARY: - INTRODUCTION:: Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non-small-cell lung cancer. METHODS:: Medical records of 105 patients were retrieved and retrospectively analyzed to find the prognostic factors of patients’ survival and symptom responses, including intracranial pressure (ICP) control. RESULTS:: There were 44 men and 61 women, with a median age of 56 years (range, 31-75 years). Patients received a median five rounds of intraventricular chemotherapy (range, 1-49 rounds). The most common presenting symptom was headache (77%) with nausea or vomiting, which showed the highest response rate of 42%. Altered mentality (36%), cranial neuropathy (15%), and cauda equina symptoms (12%) revealed 10% or less of symptom response. Only eight patients (7.6%) showed negative conversion of cerebrospinal fluid cytology. Median overall survival was 3.0 months (range, 0.5-21.5 months). Age (>/=60 years), poor Karnofsky performance score (< 70), and uncontrolled ICP were found to be unfavorable prognostic factors for patient survival. A greater amount of intraventricular chemotherapy, which was evaluated as time-dependent covariate, and concurrent systemic chemotherapy significantly improved overall survival in the multivariable analysis. CONCLUSION:: Intraventricular chemotherapy for patients with LMC from non-small-cell lung cancer could palliate associated symptoms and prolong patients’ survival. Careful selection of patients for intraventricular chemotherapy is recommended with aggressive ICP control and concurrent systemic chemotherapy.
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[66]
TÍTULO / TITLE: - Dachshund Binds p53 To Block The Growth of Lung Adenocarcinoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3191
AUTORES / AUTHORS: - Chen K; Wu K; Cai S; Zhang W; Zhou J; Wang J; Ertel A; Li Z; Rui H; Quong A; Lisanti MP; Tozeren A; Tanes C; Addya S; Wang C; McMahon SB; Pestell RG
INSTITUCIÓN / INSTITUTION: - Dept of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University.
RESUMEN / SUMMARY: - Hyperactive EGFR and mutant p53 are common genetic abnormalities driving the progression of non-small cell lung cancer (NSCLC), the leading cause of cancer deaths in the world. The Drosophila gene Dachshund (Dac) was originally cloned as an inhibitor of hyperactive EGFR alleles. Given the importance of EGFR signaling in lung cancer etiology, we examined the role of DACH1 expression in lung cancer development. DACH1 protein and mRNA expression was reduced in human NSCLC. Re-expression of DACH1 reduced NSCLC colony formation and tumor growth in vivo via p53. Endogenous DACH1 co-localized with p53 in a nuclear, extranucleolar location, and shared occupancy of -15% of p53 bound genes in ChIP Seq. The C-terminus of DACH1 was necessary for direct p53 binding, contributing to the inhibition of colony formation and cell cycle arrest. Expression of the stem cell factor SOX2 was repressed by DACH1, and SOX2 expression was inversely correlated with DACH1 in NSCLC. We conclude that DACH1 binds p53 to inhibit NSCLC cellular growth.
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[67]
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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[68]
TÍTULO / TITLE: - Treatment-related Lymphopenia in Patients With Stage III Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Invest. 2013 Mar;31(3):183-8. doi: 10.3109/07357907.2013.767342. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2013.767342
AUTORES / AUTHORS: - Campian JL; Ye X; Brock M; Grossman SA
INSTITUCIÓN / INSTITUTION: - Departments of Oncology, The Johns Hopkins University School of Medicine, Baltimore , Maryland , USA1.
RESUMEN / SUMMARY: - Background: This study sought to estimate the severity, etiology, and clinical importance of treatment-related lymphopenia in patients with stage III non-small-cell lung cancer. Methods: Serial lymphocyte counts and survival were analyzed retrospectively in 47 patients accounting for known prognostic factors. Results: Total lymphocyte counts (TLCs) were normal before therapy and did not change following neoadjuvant chemotherapy. Following radiation, TLC fell by 67% (median 500 cells/mm, p <.00001). Multivariate analysis revealed an association between severe TLC and survival (HR 1.70, 95% CI: 0.8-3.6). Conclusions: Rapid and severe lymphopenia occurred in 50% of patients following radiation which was associated with reduced survival.
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[69]
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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[70]
TÍTULO / TITLE: - Oncologic outcomes of segmentectomy compared with lobectomy for clinical stage IA lung adenocarcinoma: Propensity score-matched analysis in a multicenter study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Mar 8. pii: S0022-5223(13)00158-X. doi: 10.1016/j.jtcvs.2013.02.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2013.02.008
AUTORES / AUTHORS: - Tsutani Y; Miyata Y; Nakayama H; Okumura S; Adachi S; Yoshimura M; Okada M
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
RESUMEN / SUMMARY: - OBJECTIVE: Our objective was to compare the oncologic outcomes of lobectomy and segmentectomy for clinical stage IA lung adenocarcinoma. METHODS: We examined 481 of 618 consecutive patients with clinical stage IA lung adenocarcinoma who underwent lobectomy or segmentectomy after preoperative high-resolution computed tomography and F-18-fluorodeoxyglucose positron emission tomography/computed tomography. Patients (n = 137) who underwent wedge resection were excluded. Lobectomy (n = 383) and segmentectomy (n = 98) as well as surgical results were analyzed for all patients and their propensity score-matched pairs. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between patients undergoing lobectomy (3-year RFS, 87.3%; 3-year OS, 94.1%) and segmentectomy (3-year RFS, 91.4%; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.27-1.20; P = .14; 3-year OS, 96.9%; HR, 0.49; 95% CI, 0.17-1.38; P = .18). Significant differences in clinical factors such as solid tumor size (P < .001), maximum standardized uptake value (SUVmax) (P < .001), and tumor location (side, P = .005; lobe, P = .001) were observed between both treatment groups. In 81 propensity score-matched pairs including variables such as age, gender, solid tumor size, SUVmax, side, and lobe, RFS and OS were similar between patients undergoing lobectomy (3-year RFS, 92.9%, 3-year OS, 93.2%) and segmentectomy (3-year RFS, 90.9%, 3-year OS, 95.7%). CONCLUSIONS: Segmentectomy is suitable for clinical stage IA lung adenocarcinoma, with survivals equivalent to those of standard lobectomy.
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[71]
TÍTULO / TITLE: - Erlotinib versus Pemetrexed for Pretreated Non-Squamous Non-Small Cell Lung Cancer Patients in Clinical Practice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncology. 2013 Feb 20;84(5):255-264.
●● Enlace al texto completo (gratuito o de pago) 1159/000346534
AUTORES / AUTHORS: - Zugazagoitia J; Puente J; Gonzalez-Larriba JL; Manzano A; Sotelo M; Hernandez S; Sanz J; Perez P; Diaz-Rubio E
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Hospital Clinico San Carlos, Madrid, España.
RESUMEN / SUMMARY: - Background/Aim: Erlotinib and chemotherapy have shown similar efficacy for pretreated non-small cell lung cancer (NSCLC) patients, but none of the large studies have selected patients based on histology. We present a retrospective single-center series of advanced non-squamous NSCLC patients treated with erlotinib or pemetrexed as second-line therapy. Our aim was to compare the efficacy and safety data under clinical practice conditions and to identify subgroups of patients who could benefit more from these therapies. Methods: A total of 88 patients were included. Squamous histology was our main exclusion criterion. EGFR mutation status was known for 54.5% of the patients; 6 patients treated with erlotinib and 2 with pemetrexed had EGFR-mutated tumors. Smoking history was analyzed as possible predictive factor of efficacy. Results: No significant differences in progression-free survival (PFS; 3 vs. 2.5 months, p = 0.06) or overall survival (OS; 4.9 vs. 7.4 months, p = 0.733) between the erlotinib and pemetrexed groups were found in the overall population. EGFR wild-type patients had a similar median PFS with erlotinib compared to pemetrexed (2.7 vs. 2.3 months, p = 0.42), with no statistical differences in OS. Statistically significant differences in OS in favor of pemetrexed for current smokers (3 vs. 7.1 months, p = 0.017) were found, while erlotinib achieved significantly better PFS in never-smokers compared to former smokers (3.5 vs. 2.7 months, p = 0.005). Serious adverse events were uncommon but more frequent with pemetrexed, and were mainly related to hematologic toxicity. Conclusions: Erlotinib should be considered as another equal option in second-line treatment for EGFR wild-type patients as well as for subpopulations with unknown mutational status. Smoking history could be a useful clinical marker to choose a second-line treatment.
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[72]
TÍTULO / TITLE: - Effects of Patient-Provider Race Concordance and Smoking Status on Lung Cancer Risk Perception Accuracy Among African-Americans.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Behav Med. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1007/s12160-013-9475-9
AUTORES / AUTHORS: - Persky S; Kaphingst KA; Allen VC Jr; Senay I
INSTITUCIÓN / INSTITUTION: - Social and Behavioral Research Branch, National Human Genome Research Institute, 31 Center Drive, Rm. B1B36, Bethesda, MD, 20892, USA, perskys@mail.nih.gov.
RESUMEN / SUMMARY: - BACKGROUND: Communication of lung cancer risk information between providers and African-American patients occurs in a context marked by race-based health disparities. PURPOSE: A controlled experiment assessed whether perceived physician race influenced African-American patients’ (n = 127) risk perception accuracy following the provision of objective lung cancer risk information. METHODS: Participants interacted with a virtual reality-based, simulated physician who provided personalized cancer risk information. RESULTS: Participants who interacted with a racially discordant virtual doctor were less accurate in their risk perceptions at post-test than those who interacted with a concordant virtual doctor, F(1,94) = 4.02, p = .048. This effect was amplified among current smokers. Effects were not mediated by trust in the provider, engagement with the health care system, or attention during the encounter. CONCLUSIONS: The current study demonstrates that African-American patients’ perceptions of a doctor’s race are sufficient to independently impact their processing of lung cancer risk information.
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[73]
TÍTULO / TITLE: - ADAM17 is overexpressed in non-small cell lung cancer and its expression correlates with poor patient survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0721-3
AUTORES / AUTHORS: - Ni SS; Zhang J; Zhao WL; Dong XC; Wang JL
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai, 200003, China.
RESUMEN / SUMMARY: - The purpose of this study was to assess ADAM17 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcriptase-polymerase chain reaction was conducted to detect ADAM17 mRNA expression. In addition, ADAM17 expression was analyzed by immunohistochemistry in 124 clinicopathologically characterized NSCLC cases. The correlation of ADAM17 expression with patients’ survival rate was assessed by Kaplan-Meier and Cox regression. The expression levels of ADAM17 mRNA and protein in NSCLC tissues were both significantly higher than those in non-cancerous tissues. In addition, high expression of ADAM17 was significantly correlated with tumor grade (P = 0.026), tumor size (P = 0.001), clinical stage (P = 0.016), and lymph node metastases (P < 0.001). Furthermore, multivariate analysis suggested that tumor grade, tumor size, clinical stage, lymph node metastases, and ADAM17 expression were independent prognostic indicators for NSCLC. Our data suggest for the first time that the increased expression of ADAM17 in NSCLC is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of NSCLC.
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[74]
TÍTULO / TITLE: - Expression of p114RhoGEF predicts lymph node metastasis and poor survival of squamous-cell lung carcinoma patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0737-8
AUTORES / AUTHORS: - Song C; Gao Y; Tian Y; Han X; Chen Y; Tian DL
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Fourth Affiliated Hospital of China Medical University, No. 4 Chong-Shan East Road, Shenyang, 110032, China.
RESUMEN / SUMMARY: - The Rho-specific guanine nucleotide exchanging factor p114RhoGEF is involved in RhoA activation and cell motility. Previous studies suggest that altered expression of p114RhoGEF could contribute to cancer progression. We investigated an association of p114RhoGEF expression with progression and prognosis of non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to detect p114RhoGEF expression in 105 NSCLC (34 adenocarcinoma and 71 squamous-cell carcinoma) and 32 normal lung tissues. We found that p114RhoGEF expression was upregulated in squamous-cell lung carcinoma and that p114RhoGEF expression was significantly higher in squamous-cell carcinoma than in adenocarcinoma or normal tissues (P < 0.05, both). Expression of p114RhoGEF protein was significantly associated with lymph node metastasis of lung cancer (P < 0.05), but not with patients’ age, gender, tumor size, differentiation, or stage. Expression of p114RhoGEF protein was also associated with poor overall and event-free survival of squamous-cell lung carcinoma patients (P < 0.05). Taken together, p114RhoGEF expression may be useful in predicting progression and survival of squamous-cell lung carcinoma patients. A future study will investigate whether p114RhoGEF can serve as a novel therapeutic target in squamous-cell lung cancer.
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[75]
TÍTULO / TITLE: - Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Ther. 2013 Apr;21(4):816-24. doi: 10.1038/mt.2013.10. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1038/mt.2013.10
AUTORES / AUTHORS: - Shim G; Choi HW; Lee S; Choi J; Yu YH; Park DE; Choi Y; Kim CW; Oh YK
INSTITUCIÓN / INSTITUTION: - College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
RESUMEN / SUMMARY: - Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.
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[76]
TÍTULO / TITLE: - Counterpoint: should epidermal growth factor receptor mutations be routinely tested for in patients with lung cancer? No.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chest. 2013 Mar 1;143(3):600-2. doi: 10.1378/chest.12-2548.
●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-2548
AUTORES / AUTHORS: - Lam DC
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[77]
TÍTULO / TITLE: - Point: should epidermal growth factor receptor mutations be routinely tested for in patients with lung cancer? Yes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chest. 2013 Mar 1;143(3):597-600. doi: 10.1378/chest.12-2546.
●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-2546
AUTORES / AUTHORS: - Sterman DH
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[78]
TÍTULO / TITLE: - Randomized phase II study of cetuximab and bevacizumab in combination with two regimens of paclitaxel and carboplatin in chemonaive patients with stage IIIB/IV non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):338-45. doi: 10.1097/JTO.0b013e318282ded5.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318282ded5
AUTORES / AUTHORS: - Bonomi PD; Mace J; Mandanas RA; Min M; Olsen M; Youssoufian H; Katz TL; Sheth G; Lee HJ
INSTITUCIÓN / INSTITUTION: - Rush University Medical Center, 1725 W Harrison St, Chicago, IL 60612, USA. philip_bonomi@rush.edu
RESUMEN / SUMMARY: - INTRODUCTION: We conducted a phase II study of dual-agent monoclonal antibody therapy consisting of cetuximab and bevacizumab in combination with paclitaxel and carboplatin chemotherapy in non-small-cell lung cancer. METHODS: Patients with stage IIIB/IV nonsquamous non-small-cell lung cancer randomly received cetuximab (400 mg/m initially, 250 mg/m weekly thereafter) plus bevacizumab (15 mg/kg) for six cycles combined with paclitaxel (200 mg/m) and carboplatin (area under the curve 6) for either six cycles (six-cycle arm) or the first three cycles (three-cycle arm) (one cycle = 3 weeks). The primary objective was progression-free survival (PFS), estimated separately for each treatment arm. RESULTS: In 121 patients, the median PFS was 6.05 months (95% confidence interval [CI]: 5.65, 7.03) in the six-cycle arm and 4.50 months (95% CI: 4.01, 5.42) in the three-cycle arm. Respective median overall survival times were 12.06 months (95% CI: 9.40, 19.25) and 11.63 months (95% CI: 6.64, 17.61). The tumor response rate was 51.7% (95% CI: 39.0%, 64.3%) and 44.3% (95% CI: 31.8%, 56.7%) in the six-cycle and three-cycle arms, respectively, with corresponding median response durations of 4.86 months (95% CI: 4.30, 7.16) and 3.94 months (95% CI: 2.92, 4.47). Quality of life was consistent across arms. Cetuximab-related grade ¾ events in greater than 5% of patients (six-cycle arm, three-cycle arm) were dermatitis acneiform (6.9%; 8.6%) and fatigue (13.8%; 5.2%). Three patients died during the study from drug-related adverse events (one in the six-cycle arm and two in the three-cycle arm). CONCLUSIONS: Both the regimens showed expected PFS and numerically comparable overall survival. Quality of life was similar in the two arms, and both the regimens were well tolerated.
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[79]
TÍTULO / TITLE: - Successful treatment with erlotinib of severe neutropenia induced by gefitinib in a patient with advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 8. pii: S0169-5002(13)00073-1. doi: 10.1016/j.lungcan.2013.02.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.014
AUTORES / AUTHORS: - Araya T; Kasahara K; Demura Y; Matsuoka H; Nishitsuji M; Nishi K
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Ishikawa Prefectural Central Hospital, 2-1 Kuratsuki-Higashi, Kanazawa 920-8530, Japan. Electronic address: komatsu_alone@yahoo.co.jp.
RESUMEN / SUMMARY: - Neutropenia is a rare side effect of gefitinib and was scarcely reported in many large-scale randomized phase III trials using gefitinib monotherapy as first-line treatment. A 77-year-old female was referred to our institution due to abnormal shadow of the right lung, diagnosed by CT scan and biopsy histopathology as adenocarcinoma of the lung (cT3N1M1b). Mutation analysis with PCR-Invader assay of tumor DNA samples revealed short in-frame deletion in exon 19. Based on the diagnosis, first-line treatment was initiated using oral gefitinib (250mg, daily). During the initial 27 days of gefitinib therapy, the only side effect was a mild skin rash. After 28 days, there was marked tumor shrinkage, indicative of a partial response to gefitinib; however, grade 4 neutropenia was also detected. The patient was switched to the oral erlotinib monotherapy (150mg/day) as second-line chemotherapy with careful monitoring of neutropenia. Discontinuation of the gefitinib, without the need for granulocyte colony-stimulating factor support, was successful in allowing the neutrophils and leukocytes counts to recover to normal by day 47. The patient continued oral erlotinib for more than 9 months and there has been no evidence of neutropenia, leukopenia, or disease progression. Clinicians should be aware that gefitinib-induced neutropenia in patients with non-small cell lung cancer can be treated successful by switching to erlotinib.
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[80]
TÍTULO / TITLE: - Predictors of nursing home admission, severe functional impairment, or death one year after surgery for non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Mar;257(3):555-63. doi: 10.1097/SLA.0b013e31828353af.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e31828353af
AUTORES / AUTHORS: - Billmeier SE; Ayanian JZ; He Y; Jaklitsch MT; Rogers SO
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Brigham and Women’s Hospital, Boston, MA 02115, USA. sbillmeier@partners.org
RESUMEN / SUMMARY: - OBJECTIVE: To assess factors associated with nursing home admission, severe functional impairment, or death 1 year after surgery for stage I-IIIa non-small cell lung cancer. BACKGROUND: Patients perceive long-term disability to be one of the most undesirable complications of lung cancer treatment. METHODS: A multiregional cohort was surveyed 12 months after surgery. Logistic regression was used to determine adjusted predictors of long-term disability. Recursive partitioning was used to create a risk index based on preoperative factors. RESULTS: Of the 1007 patients, 146 (15%) were admitted to a nursing home or died by 1 year after surgery, with higher risk among patients 80 years or older, those with severe comorbidities, and those with stage II-IIIa disease (all Ps </= 0.01). Among 759 survivors who completed the follow-up survey, 51 (7%) were admitted to a nursing home or reported inability to get out of bed, dress or wash themselves, or perform usual activities. Patients with moderate comorbidities (P < 0.001) or lack of high school diploma (P = 0.03) were more likely to experience nursing home admission or severe functional impairment. The risk of nursing home admission, severe functional impairment, or death was low (16%) for patients younger than 75 years and for those 75 years or older with stage I disease, intermediate (33%) for patients 75 years or older with stage II-IIIa disease and no or mild comorbidities, and high (60%) for those 75 years or older with stage II-IIIa disease and moderate or severe comorbidities. CONCLUSIONS: Patients’ risk of long-term disability should be incorporated in preoperative counseling.
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[81]
TÍTULO / TITLE: - DNA Adducts in Aldehyde Dehydrogenase-Positive Lung Stem Cells of A/J Mice Treated with the Tobacco Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chem Res Toxicol. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1021/tx400054s
AUTORES / AUTHORS: - Balbo S; Upadhyaya P; Villalta PW; Qian X; Kassie F
INSTITUCIÓN / INSTITUTION: - The Masonic Cancer Center, University of Minnesota , MMC 806, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, United States.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer death in the world. Evidence suggests that lung cancer could originate from mutations accumulating in a subpopulation of self-renewing cells, lung stem cells. Aldehyde dehydrogenase (ALDH) is a marker of stem cells. To investigate the presence of DNA modifications in these cells, we isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Using LC-NSI-HRMS/MS-PRM, O6-methyl-G, 7-POB-G, and O2-POB-dT were positively identified in ALDH-positive cell DNA. This is the first example of detection of carcinogen-DNA adducts in lung stem cells, supporting the hypothesis of their role in lung carcinogenesis.
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[82]
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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[83]
TÍTULO / TITLE: - Use of cancer therapy at the end of life in patients with malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Support Care Cancer. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1753-3
AUTORES / AUTHORS: - Kao SC; van Zandwijk N; Corte P; Clarke C; Clarke S; Vardy J
INSTITUCIÓN / INSTITUTION: - Asbestos Diseases Research Institute, Rhodes, Australia.
RESUMEN / SUMMARY: - PURPOSE: Malignant pleural mesothelioma (MPM) is considered a treatment-resistant disease. We determined the proportion of patients who received treatment in the last month of life and potential factors associated with use of chemotherapy at the end of life. METHODS: Consenting MPM patients compensated by the Dust Diseases Board (DDB) were included. Patient, treatment and outcome details were obtained through the DDB, treating physicians and Medicare Australia. The association between potential factors (age, gender, geographical location, disease stage, histological subtype, palliative care referral, length of first line chemotherapy and lines of treatment) and chemotherapy use in the last month of life was determined. RESULTS: A total of 147 MPM patients were included in the analysis: 78 received chemotherapy, 50 had radiotherapy and 116 had surgery (77 received more than one treatment modality whilst 56 received one treatment modality). Twenty-one patients received treatment in their last month of life: nine received chemotherapy; six, radiotherapy and six had surgery. Those who were treated with second or subsequent lines of chemotherapy were more at risk of receiving chemotherapy until the end of life (six of 19 patients, i.e., 32 %) compared to those who were only treated with first-line therapy (three of 59 patients, i.e., 5 %; p < 0.01). Patients who received chemotherapy at the end of life had shorter survival compared to those who did not receive chemotherapy at the end of life (5.3 vs. 12.5 months, respectively; p = 0.01). CONCLUSIONS: Chemotherapy utilisation in the last month of life is not uncommon in this series of MPM patients. Patients who failed previous chemotherapy were more likely to receive chemotherapy near the end of life. More careful consideration of when to cease chemotherapy needs to be made as patients who received chemotherapy at the end of life had poorer survival outcome.
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[84]
TÍTULO / TITLE: - The impact of time between staging PET/CT and definitive chemo-radiation on target volumes and survival in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiother Oncol. 2013 Mar 12. pii: S0167-8140(13)00062-5. doi: 10.1016/j.radonc.2013.02.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.radonc.2013.02.010
AUTORES / AUTHORS: - Everitt S; Plumridge N; Herschtal A; Bressel M; Ball D; Callahan J; Kron T; Schneider-Kolsky M; Binns D; Hicks RJ; Mac Manus M
INSTITUCIÓN / INSTITUTION: - Radiation Therapy Services, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, Victoria, Australia; Sir Peter MacCallum Department of Oncology, Melbourne University, Victoria, Australia. Electronic address: sarah.everitt@petermac.org.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: To investigate the impact of treatment delays on radiation therapy (RT) target volumes and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who underwent two baseline FDG PET/CT scans. MATERIAL AND METHODS: Patients underwent a staging (PET1) and RT planning (PET2) FDG PET/CT scan. At PET1 all patients were eligible for radical chemo-RT. OS and progression-free survival (PFS) were compared for patients remaining eligible for radical RT and those treated palliatively because PET2 showed progression. RT target volumes were contoured using PET1 and PET2. Normal tissue doses were compared for patients remaining eligible for radical RT. RESULTS: Eighty-two patients underwent PET2 scans between October 2004 and February 2007. Of these, 21 had a prior PET1 scan, median 23days apart (range 8-176days). Six patients (29%) were unsuitable for radical RT after PET2; five received palliative treatment and one received no treatment. Patients treated palliatively had significantly worse OS and PFS than patients treated radically p<0.001. Mean RT tumour volume increased from 105cc to 198cc (p<0.005) between scans. CONCLUSIONS: Disease progression while awaiting initiation of curative RT in NSCLC is associated with larger treatment volumes and worse survival.
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[85]
TÍTULO / TITLE: - KIF5B-RET fusions in Chinese patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Feb 1. doi: 10.1002/cncr.27940.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27940
AUTORES / AUTHORS: - Cai W; Su C; Li X; Fan L; Zheng L; Fei K; Zhou C
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: It has been established that “ret proto-oncogene” (RET) fusions are oncogenic drivers in non-small cell lung cancer (NSCLC). The prevalence and clinicopathologic characteristics of RET fusions in Chinese patients with NSCLC remain unclear. The objective of the current study was to determine the prevalence and clinicopathologic characteristics of KIF5B-RET fusions (fusions of the RET and kinesin family member 5B [KIF5B] genes) in Chinese patients with NSCLC. METHODS: The authors screened for KIF5B-RET fusions in 392 patients with NSCLC using multiplex real-time polymerase chain reaction assay and validated all positive samples using direct sequencing. The relations between KIF5B-RET fusions and clinicopathologic characteristics were analyzed. RESULTS: In total, 6 patients (1.5%) were identified who harbored KIF5B-RET fusions. Of these, 4 had adenocarcinoma, 1 had a malignant neuroendocrine tumor, and 1 had squamous cell carcinoma. All patients who were positive for a KIF5B-RET fusion were never-smokers. There was no statistically significant difference in age, sex, smoking status, pathologic stage, or histologic type between patients with and without KIF5B-RET fusions. Patients without KIF5B-RET fusions had a better prognosis than those with KIF5B-RET fusions (median survival, 52.6 months vs 21.0 months; P = .06), with a hazard ratio of 2.398 (95% confidence interval, 0.982-5.856; P = .055) on multivariate analysis. Disease stage (hazard ratio, 2.879) and younger age (<65 years; hazard ratio, 1.485) were identified as independent prognostic factors for better survival. CONCLUSIONS: KIF5B-RET fusions were quite rare, with a prevalence of approximately 1.5% in Chinese patients with NSCLC, and they were a little more common in patients with adenocarcinoma than in those with squamous carcinoma (1.73% vs 0.84%). In addition, KIF5B-RET fusions also existed in patients with low-grade malignant neuroendocrine tumors. 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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[86]
TÍTULO / TITLE: - Cost and effectiveness of radiofrequency ablation versus limited surgical resection for stage I non-small-cell lung cancer in elderly patients: is less more?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Vasc Interv Radiol. 2013 Apr;24(4):476-82. doi: 10.1016/j.jvir.2012.12.016. Epub 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jvir.2012.12.016
AUTORES / AUTHORS: - Alexander ES; Machan JT; Ng T; Breen LD; Dipetrillo TA; Dupuy DE
INSTITUCIÓN / INSTITUTION: - Department of Diagnostic Imaging, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy St., Providence, RI 02903.
RESUMEN / SUMMARY: - PURPOSE: To retrospectively evaluate cost and mortality in 84 patients older than 65 years of age with stage IA or IB non-small-cell lung cancer treated with radiofrequency (RF) ablation or limited surgical resection (ie, wedge resection or segmentectomy) from the perspective of the payer, Medicare. MATERIALS AND METHODS: From August 2000 to November 2009, 56 patients were treated with RF ablation and 28 with surgery who met the inclusion criteria. Patient health histories and billing charges from initial treatment to the study endpoint were collected. Charges were converted to 2009 Medicare reimbursement fees and cumulated by month. Time-event data were analyzed by using the Kaplan-Meier method. Survival functions and median survival estimates were reported with standard errors. Patient cohorts’ survival functions were compared based on the Wilcoxon weighted chi(2) statistic. RESULTS: Group demographics were comparable with the exception of age, with patients treated with RF ablation an average of 4 years older (95% confidence interval, 0.85-6.76). The overall mortality rate was lower in patients treated with surgery than in those treated with RF ablation (chi(2) = 8.0225, P = .0046), with a median cost per month lived for RF ablation recipients of $620.74, versus $1,195.92 for those treated with surgery (P = .0002, Wilcoxon rank-sum test). CONCLUSIONS: Patients treated with surgery showed a significant increase in survival; however, those treated with RF ablation were significantly older. For patients who are not surgical candidates, RF ablation provides an alternative treatment option at a significantly lower cost.
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[87]
TÍTULO / TITLE: - Radiofrequency Ablation and Immunostimulant OK-432: Combination Therapy Enhances Systemic Antitumor Immunity for Treatment of VX2 Lung Tumors in Rabbits.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiology. 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13120249
AUTORES / AUTHORS: - Hamamoto S; Okuma T; Yamamoto A; Kageyama K; Takeshita T; Sakai Y; Nishida N; Matsuoka T; Miki Y
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
RESUMEN / SUMMARY: - Purpose:To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432.Materials and Methods:Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test.Results:The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased.Conclusion:Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.© RSNA, 2013.
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[88]
TÍTULO / TITLE: - Screening for brain metastases in patients with stage III non-small cell lung cancer: Is there additive value of magnetic resonance imaging above a contrast-enhanced computed tomography of the brain?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 18. pii: S0169-5002(13)00065-2. doi: 10.1016/j.lungcan.2013.02.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.006
AUTORES / AUTHORS: - Hendriks LE; Bootsma GP; de Ruysscher DK; Scheppers NA; Hofman PA; Brans BT; Dingemans AM
INSTITUCIÓN / INSTITUTION: - Department of Pulmonology, Atrium Medical Centre, H. Dunantstraat 5, 6401 CX, Heerlen, The Netherlands; Department of Pulmonology, Maastricht University Medical Centre+, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: lizza.hendriks@mumc.nl.
RESUMEN / SUMMARY: - INTRODUCTION: Stage III NSCLC patients are candidates for treatment with curative intent. Current guidelines advise post contrast magnetic resonance imaging (MRI) or contrast enhanced computed tomography (CE-CT) of the brain in these patients to exclude brain metastases (BM). In previous small studies MRI was reported to be superior to CE-CT. However, CT and MR technology have evolved and 18F-deoxyglucose-positron-emission-tomography (18FDG-PET) has been implemented in staging of NSCLC. If CE-CT, performed together with 18FDG-PET-CT shows the same yield of BM detection as an additionally performed MRI, substantial gain in time and resources is expected. METHODS: All NSCLC patients who underwent a staging 18FDG-PET-CT between January 2008 and September 2011 were reviewed. Neurological asymptomatic patients with stage III NSCLC who were eligible for treatment with curative intent were selected, without taking into account the results of brain MRI. CT was compared to MRI to investigate whether additional BM were detected on MRI. Development of BM within a year after negative MRI was recorded. RESULTS: 97/429 NSCLC patients who underwent a PET-CT had stage III disease. Three otherwise stage III patients already had occult BM on CE-CT. 77/97 (79%) patients underwent MRI, 45/77 (58%) CE-CT and 32/77 (42%) LD-CT. In none of the CE-CT, but in 5/32 (16%) LD-CT patients BM were detected on MRI. 9/72 patients (13%) without BM on MRI at diagnosis developed BM within a year. CONCLUSIONS: This retrospective study suggests that there is no additive value of MRI to 18FDG-PET-CT with CE-CT in screening for BM in neurological asymptomatic patients with stage III NSCLC.
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[89]
TÍTULO / TITLE: - Pemetrexed and carboplatin followed by pemetrexed maintenance therapy in chemo-naive patients with advanced nonsquamous non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Invest New Drugs. 2013 Mar 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s10637-013-9941-z
AUTORES / AUTHORS: - Okamoto I; Aoe K; Kato T; Hosomi Y; Yokoyama A; Imamura F; Kiura K; Hirashima T; Nishio M; Nogami N; Okamoto H; Saka H; Yamamoto N; Yoshizuka N; Sekiguchi R; Kiyosawa K; Nakagawa K; Tamura T
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan, chi-okamoto@dotd.med.kindai.ac.jp.
RESUMEN / SUMMARY: - Introduction This study prospectively evaluated the efficacy and safety of pemetrexed and carboplatin followed by maintenance pemetrexed in chemo-naive patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Methods A total of 109 patients received pemetrexed (500 mg/m2) and carboplatin (area under the curve = 6 mg/mL.min) every 21 days. For patients without disease progression after 4 cycles, pemetrexed was continued until disease progression or unacceptable toxicity. Pre-planned subgroup analysis results based on the presence of epidermal growth factor receptor (EGFR) mutations are also presented. Results The median number of treatment cycles was 5 (range: 1-30) in the entire study period. Most of the grade >/=3 toxicities observed were hematologic in nature, with no increase in the relative incidence associated with continuation maintenance therapy with pemetrexed. Among the 106 total patients assessable for efficacy, the objective response rate was 35.8 %, median progression free survival (PFS) 5.7 months, and median overall survival (OS) 20.2 months. Sixty patients received maintenance pemetrexed (median: 4 cycles, range: 1-26 cycles); median PFS from the beginning of induction treatment was 7.5 months. From the subgroup analysis for EGFR mutation status, the median OS of EGFR wild-type patients (n = 61) was 20.2 months. Conclusions Pemetrexed/carboplatin followed by pemetrexed was well tolerated and active for front-line treatment of advanced nonsquamous NSCLC. Encouraging survival outcomes were observed even in EGFR-wild type patients.
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[90]
TÍTULO / TITLE: - PET-based primary tumor volumetric parameters and survival of patients with non-small cell lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - AJR Am J Roentgenol. 2013 Mar;200(3):635-40. doi: 10.2214/AJR.12.9138.
●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.9138
AUTORES / AUTHORS: - Davison J; Mercier G; Russo G; Subramaniam RM
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Boston University School of Medicine, Boston, MA, USA.
RESUMEN / SUMMARY: - OBJECTIVE: The purpose of the study was to assess metabolic tumor volume and total glycolytic activity of the primary tumor as prognostic parameters for outcome in patients with non-small cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Thirty-nine patients who had undergone a baseline staging PET/CT examination at our institution for the diagnosis of NSCLC were retrospectively identified. The maximum standardized uptake value (SUV(max)), metabolic tumor volume, and total glycolytic activity were segmented from PET using the gradient method; 12-month survival and overall survival at the end of follow-up were used as outcome measures. Multivariate logistic regression, receiver operating characteristic curve analysis, and Kaplan-Meier curves for survival analysis were generated and compared using the Mantel-Cox log-rank test. RESULTS: The mean gradient-based metabolic tumor volume and gradient-based total glycolytic activity were significantly greater in the patients who died (93.3 mL and 597.5 g) than in those who survived (19.3 mL and 193.9 g, respectively) (p < 0.003 and p < 0.031). There was no statistically significant difference in the mean SUV(max) between the patients who survived (12.7) at 12 months and those who had died (13.1) (p = 0.85). On multivariate analysis, gradient-based metabolic tumor volume was the only variable associated with 12-month mortality when adjusted for all other factors.(.) The area under the curve (AUC) for gradient-based metabolic tumor volume was 0.77 (p < 0.006). A significant difference in the time to survival was observed between high and low gradient-based metabolic tumor volume (log-rank p < 0.05) cohorts using the median gradient-based metabolic tumor volume (9.7 mL) as the cut point. CONCLUSION: PET-based volumetric imaging parameters are potential prognostic markers of outcome in patients with NSCLC.
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[91]
TÍTULO / TITLE: - Phase II study of camtobell inj. (belotecan) in combination with cisplatin in patients with previously untreated, extensive stage small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 16. pii: S0169-5002(13)00068-8. doi: 10.1016/j.lungcan.2013.02.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.009
AUTORES / AUTHORS: - Lim S; Cho BC; Jung JY; Kim GM; Kim SH; Kim HR; Kim HS; Lim SM; Park JS; Lee JH; Kim D; Kim EY; Park MS; Kim YS; Kim SK; Chang J; Kim JH
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - The aim of this study was to investigate the efficacy and safety of belotecan in combination with cisplatin in patients with previously non-treated extensive stage small cell lung cancer. A total of 42 patients were enrolled and treated with combination of belotecan 0.5mg/m2 on daily basis throughout day 1-4 and cisplatin 60mg/m2 on day 1 of a 3-week cycle, up to 6 cycles. Treatment was continued until the completion of 6 cycles of the chemotherapy, disease progression, detection of unacceptable toxicity, withdrawal of the consent, or death of the patient. Response was assessed every 2 cycles of chemotherapy by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0. The overall response rate was 73.8% in an intention to treat population and 83.9% in the evaluable patients. With the median follow up of 9.9 months, the median progression free survival was 6.9 months (95% CI, 6.6-7.2 months), and median overall survival was 11.2 months (95% CI, 9.9-12.5 months). The frequently reported grade>/=3 toxicities were neutropenia (90.2%), thrombocytopenia (63.4%), and anemia (34.1%). Febrile neutropenia was reported in 16 patients (39.0%). Although most of non-hematologic toxicities were grade 1 or 2, there were 4 patient deaths caused by pneumonia complicated by septic shock. Belotecan and cisplatin combination chemotherapy demonstrated a promising efficacy in ED SCLC patients. But, the hematologic toxicity of this regimen requires considerable amount of attention.
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[92]
TÍTULO / TITLE: - Epidemic of lung cancer in patients with HIV infection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chest. 2013 Feb 1;143(2):305-14. doi: 10.1378/chest.12-1699.
●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-1699
AUTORES / AUTHORS: - Winstone TA; Man SF; Hull M; Montaner JS; Sin DD
INSTITUCIÓN / INSTITUTION: - Division of Respiratory Medicine, University of British Columbia, BC, Canada.
RESUMEN / SUMMARY: - The survival of patients with HIV infection has improved dramatically over the past 20 years, largely owing to a significant reduction in opportunistic infections and AIDs-defining malignancies, such as lymphoma and Kaposi sarcoma. However, with improved survival, patients with HIV are experiencing morbidity and mortality from other (non-AIDs-defining) complications, such as solid organ malignancies. Of these, the leading cause of mortality in the HIV-infected population is lung cancer, accounting for nearly 30% of all cancer deaths and 10% of all non-HIV-related deaths. Importantly, the average age of onset of lung cancer in the HIV-infected population is 25 to 30 years earlier than that in the general population and at lower exposure to cigarette smoke. This article provides an overview of the epidemiology of lung cancer in the HIV-infected population and discusses some of the important risk factors and pathways that may enhance the risk of lung cancer in this population.
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[93]
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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[94]
TÍTULO / TITLE: - Long-term clinical experience of high-dose ablative lung radiotherapy: High pre-treatment [18F]Fluorodeoxyglucose-positron emission tomography maximal standardized uptake value of the primary tumor adversely affects treatment outcome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 8. pii: S0169-5002(13)00006-8. doi: 10.1016/j.lungcan.2012.12.023.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.023
AUTORES / AUTHORS: - Lee DS; Kim YS; Yoo IR; Kang YN; Kim SJ; Oh JK; Kim YK; Wang YP; Park JG; Kang JH; Han DH; Ahn MI; Lee KY
INSTITUCIÓN / INSTITUTION: - Multidisciplinary Team of Lung Cancer in Seoul St. Mary’s Hospital, Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
RESUMEN / SUMMARY: - PURPOSE: The aim of this study was to report the long-term clinical experience with lung stereotactic ablative radiotherapy (SABR). METHODS: Between April 2004 and December 2011, 58 of 92 consecutive lung SABR cases were treated with a curative purpose and were eligible for inclusion. Forty patients were treated for primary lung cancer, and eighteen were treated for locally confined recurrent tumors. The majority of the cases were medically inoperable (65.5%). A median five fractions with a total dose of 30-60Gy were prescribed to the planned target volume. We routinely performed an image-guided respiratory gating technique or four-dimensional computed tomography to minimize set-up errors and accurately determine target volumes. RESULTS: The median follow-up was 23.8 (range, 1.5-77.2) months. The median age of the entire cohort was 73 (range, 48-90) years. The median gross tumor volume and maximal tumor diameter were 20 (range, 0.5-189.7) ml and 2.2 (range, 0.7-5.9) cm, respectively. The two-year local control (LC) rate was 92.1%, and the major pattern of failure was distant metastasis (25.9%). A high pre-treatment maximal standardized uptake value (mSUV) of the primary tumor significantly and adversely affected LC, local relapse-free survival, distant metastasis-free survival, cause-specific survival and overall survival. The toxicity rates (>/=grade 2) were 34.5% and 35% for the central and peripheral tumors, respectively, and one grade 5 toxic event (death due to massive hemoptysis) occurred in a centrally located tumor at 16.7 months post-SABR. CONCLUSIONS: Lung SABR remains an effective and safe local treatment modality. Pre-treatment mSUV may be a helpful parameter to select patients requiring higher radiation doses and adjuvant systemic therapy for lung SABR.
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[95]
TÍTULO / TITLE: - Maintenance chemotherapy for advanced non-small-cell lung cancer: new life for an old idea.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1009-20. doi: 10.1200/JCO.2012.43.7459. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.7459
AUTORES / AUTHORS: - Gerber DE; Schiller JH
INSTITUCIÓN / INSTITUTION: - Division of Hematology-Oncology, Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Mail Code 8852, Dallas, TX 75390-8852; joan.schiller@utsouthwestern.com.
RESUMEN / SUMMARY: - Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non-small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non-cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting.
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[96]
TÍTULO / TITLE: - Relationships between hepatitis B infection status and liver dysfunction after chemotherapy of lung cancer patients in mainland China.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Support Care Cancer. 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1738-2
AUTORES / AUTHORS: - Ruofan H; Qiong Z; Xinli Z; Zhaohui C; Jingwei J; Xiaohua L
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Huashan Hospital, Fudan University, 200040, Shanghai, China.
RESUMEN / SUMMARY: - PURPOSE: A preliminary analysis on the risk factors of liver dysfunction was made after the investigation of hepatitis B prevalence and chemotherapy-related hepatic dysfunction occurrence for patients with lung cancer. PATIENTS AND METHODS: Consecutively diagnosed 950 lung cancer patients treated in Huashan Hospital, Fudan University from 1999 to 2009 were enrolled in the study. We investigated hepatitis B (HB) prevalence and analyzed chemotherapy-related hepatic dysfunction occurrence and its influencing factors. Liver dysfunction was considered when alanine transaminase, aspartate aminotransferase, and serum bilirubin levels exceeded at least 1.25-fold of normal levels, and HB statuses were categorized into diagnosed HB, previous HB infection, HB immunity, and no HB infection. RESULTS: Among the 950 lung cancer patients, 632 accepted the HB serum marker tests: 8.4 % (53/632) were HB surface antigen positive, and 37.2 % (235/632) were HB core antibody positive. A number of 281 patients received liver function follow-up examinations after they underwent a total of 774 chemotherapy courses, and 34 liver dysfunctions were detected. A logistic regression analysis showed that younger age at diagnosis (</=60 years; P = 0.029) and abnormal liver function before chemotherapy (P = 0.000) were the risk factors for liver dysfunctions after chemotherapy, but HB status had no influence. CONCLUSIONS: The screening rates for serum HB marker and HB prevalence in patients with lung cancer were high in mainland China. Lung cancer patients with abnormal liver function before chemotherapy and in younger ages had higher risks for liver dysfunctions after chemotherapies, whereas HB status before the first chemotherapy is not an independent impact factor for post-treatment liver dysfunctions.
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[97]
TÍTULO / TITLE: - SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Exp Clin Cancer Res. 2013 Feb 5;32(1):7.
●● Enlace al texto completo (gratuito o de pago) 1186/1756-9966-32-7
AUTORES / AUTHORS: - Zhang Y; He J; Zhang F; Li H; Yue D; Wang C; Jablons DM; He B; Lui N
RESUMEN / SUMMARY: - ABSTRACT: BACKGROUND: Malignant mesothelioma is an aggressive, treatment-resistant tumor arising from mesothelium of pleura, peritoneum and pericardium. Despite current combined regimen, its prognosis remains dismal, calling for more effective targeted therapies. We investigated whether aberrant Hh activation may play a role in mesothelioma. METHODS: SMO and SHH expression levels were analyzed in 46 mesothelioma tissue specimens with real-time RT-PCR, and correlation with survival was analyzed with univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. We also examined multiple mesothelioma cell lines for SMO expression and the effect of Hh inhibition by a specific SMO antagonist on cell proliferation by MTS assay. RESULTS: We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival. Remarkably, Hh inhibition by a specific SMO inhibitor significantly suppressed cell proliferation in the mesothelioma cell lines examined. CONCLUSION: Our data strongly support that Hh signaling deregulation plays critical roles in proliferation of mesothelioma, and consistently exerts significant impact on prognosis of the disease. Therefore our findings revealed the hitherto unappreciated role of Hh activation in mesothelioma, and pinpointed Hh signaling antagonist as a potential new therapy against this devastating disease.
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[98]
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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[99]
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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[100]
TÍTULO / TITLE: - Influence of Postoperative Infectious Complications on Long-Term Survival of Lung Cancer Patients: A Population-Based Cohort Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182862e7e
AUTORES / AUTHORS: - Andalib A; Ramana-Kumar AV; Bartlett G; Franco EL; Ferri LE
INSTITUCIÓN / INSTITUTION: - *Department of Surgery, McGill University, Montreal, QC, Canada; daggerDepartment of Oncology, McGill University, Montreal, QC, Canada; double daggerDepartment of Family Medicine, McGill University, Montreal, QC, Canada; section signDivision of Thoracic Surgery, McGill University, Montreal, QC, Canada; and ||Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
RESUMEN / SUMMARY: - INTRODUCTION:: Surgery is essential to any curative plan for lung cancer, but is associated with a high complication rate. We sought to determine the impact of complications on long-term survival after a curative surgery for lung cancer, independent of the effect on early postoperative mortality. METHODS:: We studied a population-based cohort of patients with lung cancer who underwent curative-intent surgery in the province of Quebec, Canada, from 2000 to 2005. Kaplan-Meier survival analysis was used to compare unadjusted overall survival (OS) beyond postoperative day 90 for patients with and without complications. Cox regression was used to determine the prognostic impact of 30-day postoperative complications on the OS after adjusting for several confounders. RESULTS:: The overall 30-day postoperative complication rate was 58.2% among 4033 eligible patients. A major infectious complication (pneumonia, empyema, or mediastinitis) occurred in 378 patients. The 5-year OS was lower for those with any postoperative complication (62.8%) than those without (73.8%; p < 0.001). Those with major infectious complications had the lowest OS (56.3%; p < 0.001). Postoperative complication was an independent prognostic factor after adjusting for several patient and treatment factors (hazard ratio = 1.37; 95% confidence interval, 1.21-1.54). Adjusted hazard ratio for major infectious complications was 1.67 (95% confidence interval, 1.39-2.01). CONCLUSIONS:: Postoperative complications, particularly of a major infectious type, are strong negative predictors of long-term survival in lung cancer patients. The strong association between major infectious complications and survival may also open the door to investigational therapies targeting bacterial antigens in the perioperative period in patients who undergo lung cancer surgery.
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[101]
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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[102]
TÍTULO / TITLE: - Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-0370
AUTORES / AUTHORS: - Hassan KA; Wang L; Korkaya H; Chen G; Maillard I; Beer DG; Kalemkerian GP; Wicha MS
INSTITUCIÓN / INSTITUTION: - Internal Medicine, University of Michigan.
RESUMEN / SUMMARY: - PURPOSE: The cancer stem cell theory postulates that tumors contain a subset of cells with stem cell properties of self-renewal, differentiation and tumor-initiation. The purpose of this study is to determine the role of Notch activity in identifying lung cancer stem cells. EXPERIMENTAL DESIGN: We investigated the role of Notch activity in lung adenocarcinoma utilizing a Notch GFP-reporter construct and a gamma-secretase inhibitor (GSI), which inhibits Notch pathway activity. RESULTS: Transduction of lung cancer cells with Notch GFP-reporter construct identified a subset of cells with high Notch activity (GFP-bright). GFP-bright cells had the ability to form more tumor spheres in serum-free media, and were able to generate both GFP-bright and GFP-dim (lower Notch activity) cell populations. GFP-bright cells were resistant to chemotherapy and were tumorigenic in serial xenotransplantation assays. Tumor xenografts of mice treated with GSI had decreased expression of downstream effectors of Notch pathway and failed to regenerate tumors upon reimplantation in NOD/SCID mice. Using multivariate analysis, we detected a statistically significant correlation between poor clinical outcome and Notch activity (reflected in increased Notch ligand expression or decreased expression of the negative modulators), in a group of 441 lung adenocarcinoma patients. This correlation was further confirmed in an independent group of 89 adenocarcinoma patients where Hes-1 overexpression correlated with poor overall survival. CONCLUSIONS: Notch activity can identify lung cancer stem cell-like population and its inhibition may be an appropriate target for treating lung adenocarcinoma.
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[103]
TÍTULO / TITLE: - Thymidylate Synthase and Folyl-Polyglutamate Synthase Are Not Clinically Useful Markers of Response to Pemetrexed in Patients with Malignant Pleural Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):469-477.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318283da3e
AUTORES / AUTHORS: - Lustgarten DE; Deshpande C; Aggarwal C; Wang LC; Saloura V; Vachani A; Wang LP; Litzky L; Feldman M; Creaney J; Nowak AK; Langer C; Inghilleri S; Stella G; Albelda SM
INSTITUCIÓN / INSTITUTION: - *Pulmonary Associates, Lehigh Valley Health Network, Allentown, PA; daggerUniversity of Pennsylvania, Philadelphia, PA; double daggerHematology-Oncology, University of Chicago, Chicago, IL; section signSchool of Medicine and Pharmacology, University of Western Australia, Perth, Australia; ||Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia; paragraph signDepartment of Molecular Medicine; Division of Pneumology, Laboratory of Biochemistry & Genetics, University and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; #Institute for Cancer Research at Candiolo (IRCC), Candiolo, Italy.
RESUMEN / SUMMARY: - PURPOSE:: Thymidylate synthase (TS) is a potential predictor of outcome after pemetrexed (Pem) in patients with malignant pleural mesothelioma (MPM), and assays measuring TS levels are commercially marketed. The goal of this study was to further evaluate the value of TS and to study another potential biomarker of response, the enzyme, folyl-polyglutamate synthase (FPGS), which activates Pem intracellularly. METHODS:: Levels of TS and FPGS were semi-quantitatively determined immunohistochemically using H-scores on tissue samples from 85 MPM patients receiving Pem as primary therapy. H-score was correlated with radiographic disease control rate (DCR), time to progression (TTP) and overall survival (OS). In addition, expression levels of TS and FPGS in MPM cell lines were determined using immunoblotting and correlated with their sensitivity to Pem-induced cell death. RESULTS:: H-scores from patients with disease control versus progressive disease showed extensive overlap. There were no significant correlations of DCR, TTP, or OS to either TS levels (p = 0.73, 0.93, and 0.59, respectively), FPGS levels (p = 0.95, 0.77, and 0.43, respectively) or the ratio of FPGS/TS using the median scores of each test as cutoffs. There was no correlation between TS or FPGS expression and chemosensitivity of mesothelioma cells to Pem in vitro. CONCLUSIONS:: Although previous retrospective data suggest that TS and FPGS expression might be potential markers of Pem efficacy in MPM, our data indicate these markers lack sufficient predictive value in individual patients and should not be used to guide therapeutic decisions in the absence of prospective studies.
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[104]
TÍTULO / TITLE: - Prevalence of underlying lung disease in smokers with epidermal growth factor receptor-mutant lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 1. doi: 10.3892/or.2013.2320.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2320
AUTORES / AUTHORS: - Sekine A; Tamura K; Satoh H; Tanaka T; Tsunoda Y; Tanaka T; Takoi H; Lin SY; Yatagai Y; Hashizume T; Hayasihara K; Saito T
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, National Hospital Organization, Ibarakihigashi National Hospital, Naka-gun, Ibaraki 319-1113, Japan.
RESUMEN / SUMMARY: - The prevalence of underlying lung diseases, such as emphysema and interstitial lung disease in smokers with epidermal growth factor receptor (EGFR)-mutant lung cancer remains unclear. This study aimed to clarify the correlation between the EGFR mutation status and the prevalence of underlying lung disease in smokers with lung cancer. A total of 88 consecutive smokers with non-small cell or non-squamous cell lung cancer who underwent surgical resection at our hospital from January 2007 through December 2010 were included in this study. The patients were divided into two groups on the basis of the EGFR mutation status: the mutation-positive group (n=19) and the wild-type group (n=69). The results of radiographic assessment via computed tomography (CT) and pulmonary function analysis were compared between the two groups. In the radiological evaluation, CT images at three levels were evaluated by two reviewers. Radiographic assessment revealed that the mutation-positive group tended to have milder emphysematous changes and a lower prevalence of interstitial changes compared with the wild-type group (P=0.13, 0.06). When the analysis was limited to the ipsilateral lung at the nearest CT level to the tumor, emphysematous changes were found to be less common in the mutation-positive group (P=0.02). The prevalence of the emphysematous and/or interstitial changes in the ipsilateral lung at the nearest CT level to the tumor was lower in the mutation-positive group compared to the wild-type group (P=0.005). In the pulmonary function test, the results were comparable between the two groups. In conclusion, according to our results, EGFR-mutant lung cancer was commonly observed in the areas where emphysematous and interstitial changes were absent. EGFR-mutant lung cancer may develop in radiographically normal areas of the lungs, even in smokers. It would be of importance to evaluate the EGFR mutation status in patients with no emphysematous or interstitial changes in the ipsilateral lung near the tumor, regardless of their smoking history. These results should be confirmed in a future prospective study.
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[105]
TÍTULO / TITLE: - Correlation of Mutation Status and Survival with Predominant Histologic Subtype According to the New IASLC/ATS/ERS Lung Adenocarcinoma Classification in Stage III (N2) Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):461-468.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182828fb8
AUTORES / AUTHORS: - Russell PA; Barnett SA; Walkiewicz M; Wainer Z; Conron M; Wright GM; Gooi J; Knight S; Wynne R; Liew D; John T
INSTITUCIÓN / INSTITUTION: - *Department of Anatomical Pathology, St Vincent’s Hospital, The University of Melbourne, Melbourne, Australia; daggerDepartment of Thoracic Surgery, Austin Health, The University of Melbourne, Melbourne, Australia; double daggerLudwig Institute for Cancer Research, Austin Health, The University of Melbourne, Melbourne, Australia; section signThe University of Melbourne, Department of Surgery, St Vincent’s Hospital, Melbourne, Australia; ||Department of Respiratory and Sleep Medicine, St. Vincent’s Hospital, The University of Melbourne, Melbourne, Australia; paragraph signDepartment of Thoracic Surgery, St Vincent’s Hospital, The University of Melbourne, Melbourne, Australia; #Melbourne School of Health Sciences, The University of Melbourne, Melbourne, Australia; and **Melbourne EpiCentre, The University of Melbourne and Melbourne Health, Melbourne, Australia.
RESUMEN / SUMMARY: - INTRODUCTION:: We investigated the relationship between predominant subtype, according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification; mutation status; and patient outcome in stage III (N2) lung adenocarcinoma. METHODS:: We identified 69 patients with stage III (N2) lung adenocarcinoma operated on with curative intent between 1993 and 2011 who had adequate tumor tissue for molecular analysis and adequate follow-up time for survival analysis. DNA was isolated and tested for mutations using Sequenom’s OncoCarta Panel (v1.0; Sequenom, San Diego, CA). RESULTS:: The majority of tumors were acinar (26 of 69 tumors; 38%), solid (24 of 69 tumors; 35%), and micropapillary predominant (13 of 69 tumors; 19%) subtypes. EGFR and KRAS mutations were identified in 17 of 59 tumors (29%) and 13 of 59 tumors (22%), respectively. EGFR mutations occurred most often in acinar (11 of 25 tumors; 44%) and micropapillary predominant tumors (five of 13 tumors; 38%) (p = 0.009), whereas KRAS mutations occurred most often in solid predominant tumors (nine of 21 tumors; 43%) (p = 0.016). Patients with acinar predominant tumors had significantly improved overall survival compared with those with non-acinar predominant tumors (hazard ratio: 0.45; 95% confidence interval: 0.22-0.91; p = 0.026), which remained significant after adjustment for EGFR status, T-stage, sex, and age. Patients with EGFR-mutant micropapillary predominant tumors had similar survival to those with EGFR-mutant acinar predominant tumors. The predominant subtype in the primary tumor was most often seen in the N2 node in micropapillary and solid predominant tumors but not in acinar predominant tumors. CONCLUSIONS:: The predominant subtype in the primary tumor was associated with overall survival in resected stage III (N2) lung adenocarcinoma and was independent of mutation status. Histologic subtyping provides important prognostic information and potentially molecular correlates.
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[106]
TÍTULO / TITLE: - Identification of risk factors and characteristics of supraclavicular lymph node metastasis in patients with small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Mar;30(1):493. doi: 10.1007/s12032-013-0493-z. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0493-z
AUTORES / AUTHORS: - Feng ZX; Zhao LJ; Guan Y; Sun Y; Meng MB; Ji K; Wang P
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Cancer Prevention and Therapy, Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
RESUMEN / SUMMARY: - Thoracic radiotherapy provides a survival benefit in patients with limited-stage disease of small cell lung cancer (LS-SCLC), but inclusion and exclusion of prophylactic irradiation of the supraclavicular area are still controversial. This study analyses the risk factors and characteristics of lymph node metastases in the supraclavicular area of LS-SCLC patients, which could help in developing a better radiotherapy for the patients. A total of 239 patients with LS-SCLC were included in this retrospective analysis. Clinical characteristics and mediastinal lymph node metastasis were analyzed for association with SCM, and the SCM pattern was further analyzed based on the treatment planning CT scans. The SCM incidence was 34.7 % (83 of 239). The multivariate analysis showed that only the mediastinal level 2 (OR = 16.101, P = 0.000) and level 3 (OR = 5.597, P = 0.000) lymph node metastases were significantly associated with SCM. As the most frequently involved region, supraclavicular level I lymph node metastases were identified in 61 of 83 patients (73.5 %), followed by level III, level IV, level V, and level II lymph node metastases, accounting a total of 95.2 % for level I and/or III lymph node metastases, whereas the incidence of skip metastasis was only 4.8 %. SCLC patients with mediastinal level 2 and level 3 lymph node metastasis were at high risk of SCM. If prophylactic irradiation therapy is considered, the nodal clinical target volume of irradiation should include bilateral lower para-recurrent laryngeal neural region (level I) and the para-internal jugular venous region (level III).
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[107]
TÍTULO / TITLE: - Surfactant Protein A Suppresses Lung Cancer Progression by Regulating the Polarization of Tumor-Associated Macrophages.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Pathol. 2013 Mar 14. pii: S0002-9440(13)00116-8. doi: 10.1016/j.ajpath.2013.01.030.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2013.01.030
AUTORES / AUTHORS: - Mitsuhashi A; Goto H; Kuramoto T; Tabata S; Yukishige S; Abe S; Hanibuchi M; Kakiuchi S; Saijo A; Aono Y; Uehara H; Yano S; Ledford JG; Sone S; Nishioka Y
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
RESUMEN / SUMMARY: - Surfactant protein A (SP-A) is a large multimeric protein found in the lungs. In addition to its immunoregulatory function in infectious respiratory diseases, SP-A is also used as a marker of lung adenocarcinoma. Despite the finding that SP-A expression levels in cancer cells has a relationship with patient prognosis, the function of SP-A in lung cancer progression is unknown. We investigated the role of SP-A in lung cancer progression by introducing the SP-A gene into human lung adenocarcinoma cell lines. SP-A gene transduction suppressed the progression of tumor in subcutaneous xenograft or lung metastasis mouse models. Immunohistochemical analysis showed that the number of M1 antitumor tumor-associated macrophages (TAMs) was increased and the number of M2 tumor-promoting TAMs was not changed in the tumor tissue produced by SP-A-expressing cells. In addition, natural killer (NK) cells were also increased and activated in the SP-A-expressing tumor. Moreover, SP-A did not inhibit tumor progression in mice depleted of NK cells. Taking into account that SP-A did not directly activate NK cells, these results suggest that SP-A inhibited lung cancer progression by recruiting and activating NK cells via controlling the polarization of TAMs.
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[108]
TÍTULO / TITLE: - Are women who smoke at higher risk for lung cancer than men who smoke?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Epidemiol. 2013 Apr 1;177(7):601-12. doi: 10.1093/aje/kws445. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1093/aje/kws445
AUTORES / AUTHORS: - De Matteis S; Consonni D; Pesatori AC; Bergen AW; Bertazzi PA; Caporaso NE; Lubin JH; Wacholder S; Landi MT
RESUMEN / SUMMARY: - Worldwide lung cancer incidence is decreasing or leveling off among men, but rising among women. Sex differences in associations of tobacco carcinogens with lung cancer risk have been hypothesized, but the epidemiologic evidence is conflicting. We tested sex-smoking interaction in association with lung cancer risk within a population-based case-control study, the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study (Lombardy, Italy, 2002-2005). Detailed lifetime smoking histories were collected by personal interview in 2,100 cases with incident lung cancer and 2,120 controls. Odds ratios and 95% confidence intervals for pack-years of cigarette smoking were estimated by logistic regression, adjusted for age, residence area, and time since quitting smoking. To assess sex-smoking interaction, we compared the slopes of odds ratios for logarithm of pack-years in a model for men and women combined. Overall, the slope for pack-years was steeper in men (odds ratio for female-smoking interaction = 0.39, 95% confidence interval: 0.24, 0.62; P < 0.0001); after restriction to ever smokers, the difference in slopes was much smaller (odds ratio for interaction = 0.63, 95% confidence interval: 0.29, 1.37; P = 0.24). Similar results were found by histological type. Results were unchanged when additional confounders were evaluated (e.g., tobacco type, inhalation depth, Fagerstrom-assessed nicotine dependence). These findings do not support a higher female susceptibility to tobacco-related lung cancer.
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[109]
TÍTULO / TITLE: - Histology-Related Associations of ERCC1, RRM1, and TS Biomarkers in Patients with Non-Small-Cell Lung Cancer: Implications for Therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318287c3c5
AUTORES / AUTHORS: - Maus MK; Mack PC; Astrow SH; Stephens CL; Zeger GD; Grimminger PP; Hsiang JH; Huang E; Li T; Lara PN; Danenberg KD; Gandara DR
INSTITUCIÓN / INSTITUTION: - *Department of General, Visceral and Tumor Surgery, University of Cologne, Germany; daggerResponse Genetics Inc., Los Angeles, California; double daggerDepartment of Internal Medicine, University of California Davis Comprehensive Cancer Center, University of California, Davis, Sacramento, California; section signDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California.
RESUMEN / SUMMARY: - INTRODUCTION:: On the basis of the results of recent clinical trials, histology-based decision-making for therapy of non-small-cell lung cancer has been advocated. We hypothesized associations of the biomarkers excision repair cross-complementing 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and thymidylate synthase (TS) with histology as a contributing factor to reported differences in chemotherapy outcomes between squamous cell carcinoma (SCCA) and adenocarcinoma (AC) subtypes. Here, we report analysis of the Response Genetics Inc., database and implications for histology-based therapy. METHODS:: RNA from microdissected formalin-fixed paraffin-embedded tumors was extracted and analyzed as previously described. Specimens from 2540 individual non-small-cell lung cancer patients were analyzed for one or more biomarkers, of which 1457 were categorized as AC or SCCA. RESULTS:: For each biomarker, gene expression was lower in AC compared with SCCA (<0.001), although there was a wide range between individual patients. Gene expression was higher in men versus women: ERCC1: 2.51 versus 2.22 (p = 0.005); RRM1: 1.41 versus 1.24 (p = 0.004); TS: 3.23 versus 2.83 (p < 0.001). However, SCCA was more frequent in men versus women (30%/19%; p < 0.001). When AC and SCCA were assessed separately, the statistical significance between gene expression and sex was lost (in SCCA: ERCC1, p = 0.14; RRM1, p = 0.26; TS, p = 0.11). CONCLUSIONS:: This analysis represents the largest data set for gene expression of these biomarkers reported so far. Significant histology-related associations for ERCC1, RRM1, and TS are seen. However, marked heterogeneity exists in individual patient tumor expression levels. Randomized phase III trials assessing the predictive value of these chemotherapy-related biomarkers are warranted.
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[110]
TÍTULO / TITLE: - New radiotherapy and chemoradiotherapy approaches for non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1029-38. doi: 10.1200/JCO.2012.44.5064. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.5064
AUTORES / AUTHORS: - Salama JK; Vokes EE
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637; evokes@medicine.bsd.uchicago.edu.
RESUMEN / SUMMARY: - Recent advances in systemic cytotoxic and molecularly targeted therapies coupled with technologic strides in radiotherapy have the potential to improve outcomes for patients with non-small-cell lung cancer (NSCLC). Investigations are ongoing to identify optimal cytotoxin-based chemoradiotherapy platforms. The influence of specific histologic and molecular mutation status on the combination of targeted therapies and radiotherapy is also being actively studied. Although there are no convincing randomized phase III data to date supporting a survival advantage for combining molecularly targeted agents with radiation or chemoradiotherapy in the setting of locally advanced NSCLC, phase II and III studies targeted to elderly patients and those with poor performance status are elucidating preferred chemoradiotherapy strategies. Radiotherapy dose escalation did not improve chemoradiotherapy outcomes, although increasing radiation dose-intensity with modern techniques is being actively studied. As modern radiotherapy techniques have been shown to improve outcomes of some patients with limited metastatic disease, investigations are ongoing regarding how to optimally integrate them with standard chemotherapy platforms.
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[111]
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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[112]
TÍTULO / TITLE: - Chronic Obstructive Pulmonary Disease and Risk of Lung Cancer: The Importance of Smoking and Timing of Diagnosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):e34-e35.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31828950e3
AUTORES / AUTHORS: - Powell HA; Iyen-Omofoman B; Baldwin DR; Hubbard RB; Tata LJ
INSTITUCIÓN / INSTITUTION: - Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom Respiratory Medicine, Nottingham University Hospitals, NHS Trust, Nottingham, United Kingdom Division of Epidemiology & Public Health and, Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom.
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[113]
TÍTULO / TITLE: - Chronic obstructive pulmonary disease and risk of lung cancer: the importance of smoking and timing of diagnosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):e34. doi: 10.1097/JTO.0b013e318286c1c1.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318286c1c1
AUTORES / AUTHORS: - Molins L; Agusti A
INSTITUCIÓN / INSTITUTION: - Thoracic Service, Thorax Institute, Hospital Clinic, University of Barcelona, Barcelona, España.
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[114]
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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[115]
TÍTULO / TITLE: - ROS1 fusions in Chinese patients with non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt071
AUTORES / AUTHORS: - Cai W; Li X; Su C; Fan L; Zheng L; Fei K; Zhou C; Manegold C; Schmid-Bindert G
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai.
RESUMEN / SUMMARY: - BackgroundTo determine the prevalence and clinicopathological features of ROS1 fusions in Chinese patients with non-small-cell lung cancer (NSCLC).MethodsFormalin-fixed and paraffin-embedded (FFPE) tissue sections from 392 patients with NSCLC were screened for ROS1 fusions by multiplex RT-PCR and all ROS1 fusions were validated by direct sequencing. The relationship between ROS1 fusions and clinicopathological features and the prognostic effect of the ROS1 fusion status on survival were analyzed.ResultsIn this study, 8 of 392 (2.0%) evaluable samples were found to harbor ROS1 fusions. Of the ROS1-positive patients, seven presented with adenocarcinoma, and one with adenosquamous carcinoma. The ratio of female to male and never smoker to smokers in a ROS1 fusion-positive group was 5:3. There was no statistically significant difference in age, sex, smoking history, histological type and pathological stage between ROS1 fusion-positive and ROS1 fusion-negative patients. ROS1 fusion-negative patients had a significantly longer survival when compared with ROS1 fusion-positive patients (P = 0.041). Lower pathological stage, younger age and ROS1 fusion-negative status were significantly associated with better prognosis on multivariate analysis.ConclusionsROS1 fusions occurred in approximately 2.0% of Chinese patients with NSCLC and had no specific clinicopathological feature. ROS1 fusion-negative patients may have a better survival than ROS1 fusion-positive patients.
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[116]
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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[117]
TÍTULO / TITLE: - Non-small-cell lung cancer: then and now.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):981-3. doi: 10.1200/JCO.2012.47.5772. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.47.5772
AUTORES / AUTHORS: - Schiller JH; Gandara DR; Goss GD; Vokes EE
INSTITUCIÓN / INSTITUTION: - Division of Hematology/Oncology, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX 75390-8852; joan.schiller@utsouthwestern.edu.
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[118]
TÍTULO / TITLE: - MET As a Possible Target for Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1089-96. doi: 10.1200/JCO.2012.43.9422. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.43.9422
AUTORES / AUTHORS: - Sadiq AA; Salgia R
INSTITUCIÓN / INSTITUTION: - 5841 S Maryland Ave, MC 2115, Chicago, IL 60637-1470; rsalgia@medicine.bsd.uchicago.edu.
RESUMEN / SUMMARY: - Lung cancer is a heterogeneous group of disorders that is now being subdivided into molecular subtypes with dedicated targeted therapies. The MET receptor tyrosine kinase has been identified as aberrantly overexpressed, potentially having activating mutations, and amplified in certain subsets of lung cancers. The ligand hepatocyte growth factor (HGF) can also be overexpressed in lung cancer or expressed in stroma, and both the MET receptor and the HGF ligand can be targets for therapeutics, especially in lung cancer. Activation of MET leads to a plethora of biochemical and biologic changes both in normal and cancerous cells. Preclinically, it has been shown that silencing or inactivating MET leads to decreased viability of cancer cells. There are a number of compounds against MET/HGF in clinical trials that have been shown to be active in lung cancers. This review will summarize the biology of MET as well as its therapeutic inhibition in lung cancer.
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[119]
TÍTULO / TITLE: - ALK in Lung Cancer: Past, Present, and Future.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1105-11. doi: 10.1200/JCO.2012.44.5353. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.5353
AUTORES / AUTHORS: - Shaw AT; Engelman JA
INSTITUCIÓN / INSTITUTION: - Massachusetts General Hospital Cancer Center, Yawkey 7B, 32 Fruit St, Boston, MA 02114; ashaw1@partners.org.
RESUMEN / SUMMARY: - In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers.
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[120]
TÍTULO / TITLE: - New targetable oncogenes in non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 10;31(8):1097-104. doi: 10.1200/JCO.2012.42.9829. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.42.9829
AUTORES / AUTHORS: - Oxnard GR; Binder A; Janne PA
INSTITUCIÓN / INSTITUTION: - Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, HIM223, Boston, MA 02215; pasi_janne@dfci.harvard.edu.
RESUMEN / SUMMARY: - The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non-small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development.
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[121]
TÍTULO / TITLE: - alpha-Fetoprotein Secreting Extrapulmonary Small-Cell Carcinoma of the Liver.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Apr 1;31(10):e152-4. doi: 10.1200/JCO.2012.44.7771. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.44.7771
AUTORES / AUTHORS: - Walshauser MA; Ishii K; Murugappan K; Masoom S; Yong S; Bhoopalam N
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Division of Hematology and Oncology, Cardinal Bernardin Cancer Center, 2160 S First Ave, Maywood, IL 60153; mwalshauser@lumc.edu.
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[122]
TÍTULO / TITLE: - K-ras 4A and 4B mRNA levels correlate with superoxide in lung adenocarcinoma cells, while at the protein level, only mutant K-ras 4A protein correlates with superoxide.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 6. pii: S0169-5002(13)00058-5. doi: 10.1016/j.lungcan.2013.01.022.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.022
AUTORES / AUTHORS: - Calvert RJ; Gupta M; Maciag A; Shiao YH; Anderson LM
INSTITUCIÓN / INSTITUTION: - U.S. Food and Drug Administration, MOD-1 Laboratory, 8301 Muirkirk Road, Laurel, MD 20708, United States. Electronic address: richard.calvert@fda.hhs.gov.
RESUMEN / SUMMARY: - The K-ras gene is frequently mutated in lung and other cancers. K-ras protein includes two splice variants, K-ras 4A and 4B. While K-ras 4B is more widely expressed, recent evidence implicates K-ras 4A in lung tumorigenesis. We found that K-ras 4A protein has a wide range of expression in a large panel of human lung adenocarcinoma cell lines. In cell lines with mutant K-ras, but not those with wildtype K-ras, the K-ras 4A protein had a strong positive correlation with levels of cellular superoxide. We investigated whether K-ras 4A protein was involved in superoxide production, or alternatively was modulated by elevated superoxide. Experiments with small interfering RNA targeting K-ras 4A did not confirm its role in superoxide generation. However, decreasing cellular superoxide with the scavenger Tiron tended to reduce levels of K-ras 4A protein. K-ras 4A and 4B mRNA were also quantified in a number of NSCLC cell lines. 4A mRNA correlated with 4A protein only in K-ras-mutant cells. K-ras 4A mRNA also correlated with superoxide, but with no difference between cell lines with mutant or wildtype K-ras. K-ras 4B mRNA correlated with 4A mRNA and with superoxide, in both K-ras mutant and wildtype cells. The results are consistent with superoxide directly or indirectly up-regulating expression of all K-ras genes, and also increasing the stability of K-ras 4A mutant protein selectively.
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[123]
TÍTULO / TITLE: - Phototoxic effect of photodynamic therapy on lung cancer cells grown as a monolayer and three dimensional multicellular spheroids.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lasers Surg Med. 2013 Mar;45(3):186-94. doi: 10.1002/lsm.22121. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1002/lsm.22121
AUTORES / AUTHORS: - Manoto SL; Houreld NN; Abrahamse H
INSTITUCIÓN / INSTITUTION: - Faculty of Health Sciences, Laser Research Centre, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is a minimally invasive therapeutic modality for the treatment of neoplastic and non-neoplastic diseases. The photochemical interaction of light, photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces cell death. The effectiveness of zinc sulfophthalocyanine (ZnPcSmix ) has been shown on A549 monolayers and not on MCTS. The objective of this study was to investigate whether the same pattern of cell death would be induced in lung cancer cells (A549) grown as monolayer cells compared to three dimensional multicellular tumor spheroids (MCTS) using the same laser parameters. MATERIALS AND METHODS: Commercially purchased A549 cells used in this study were cultured as monolayers and as MCTS. ZnPcSmix at different concentrations [0, 5, 10, 20, and 40 microM] was used and activated at a wavelength of 680 nm with 5 J/cm(2) . Lysosomal and mitochondrial damage after PDT and reactive oxygen species (ROS) production were determined by fluorescent microscopy. Changes in cellular responses were evaluated using cell morphology, viability, proliferation, cytotoxicity, and cell death analysis. RESULTS: Cells exposed to neither laser light nor PS, showed no changes in cell morphology, proliferation, cytotoxicity, and ROS production. However, cells treated with light activated ZnPcSmix resulted in a significant production of ROS and a dose dependant decrease in viability and proliferation as well as an increase in cell membrane damage in both monolayer and MCTSs. CONCLUSION: ZnPcSmix PS used in this study induced damage to vital organelles and was effective in inducing apoptosis in lung cancer cells grown as a monolayer and MTCS through ROS production. Lasers Surg. Med. 45: 186-194, 2013. © 2013 Wiley Periodicals, Inc.
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[124]
TÍTULO / TITLE: - Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Mar 22;432(4):689-94. doi: 10.1016/j.bbrc.2013.01.131. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.01.131
AUTORES / AUTHORS: - Omura T; Asari M; Yamamoto J; Oka K; Hoshina C; Maseda C; Awaya T; Tasaki Y; Shiono H; Yonezawa A; Masuda S; Matsubara K; Shimizu K
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
RESUMEN / SUMMARY: - Paraquat is a commonly used herbicide; however, it is highly toxic to humans and animals. Exposure to paraquat causes severe lung damage, leading to pulmonary fibrosis. However, it has not been well clarified as how paraquat causes cellular damage, and there is no established standard therapy for paraquat poisoning. Meanwhile, endoplasmic reticulum stress (ERS) is reported to be one of the causative factors in many diseases, although mammalian cells have a defense mechanism against ERS-induced apoptosis (unfolded protein response). Here, we demonstrated that paraquat changed the expression levels of unfolded protein response-related molecules, resulting in ERS-related cell death in human lung epithelial A549 cells. Moreover, treatment with sodium tauroursodeoxycholate (TUDCA), a chemical chaperone, crucially rescued cells from death caused by exposure to paraquat. These results indicate that paraquat toxicity may be associated with ERS-related molecules/events. Through chemical chaperone activity, treatment with TUDCA reduced paraquat-induced ERS and mildly suppressed cell death. Our findings also suggest that TUDCA treatment represses the onset of pulmonary fibrosis caused by paraquat, and therefore chemical chaperones may have novel therapeutic potential for the treatment of paraquat poisoning.
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[125]
TÍTULO / TITLE: - Gene therapy for malignant mesothelioma: Current prospects and challenges.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar;20(3):150-6. doi: 10.1038/cgt.2013.1. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.1
AUTORES / AUTHORS: - Tagawa M; Tada Y; Shimada H; Hiroshima K
INSTITUCIÓN / INSTITUTION: - 1] Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan [2] Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
RESUMEN / SUMMARY: - Malignant mesothelioma, developed in the thoracic cavity, is resistant to current treatments. Suppression of the local tumor growth is beneficial to the patients since mesothelioma infrequently metastasizes to extrapleural organs. A majority of the tumors have a homologous genetic deletion at the INK4A/ARF locus that includes the p14(ARF) and the p16(INK4A) genes, and the genetic defect results in an inactivation of the p53-mediated pathways and in progression of cell cycle through pRb phosphorylation. Preclinical studies targeting the genetic abnormality with adenoviruses showed that restoration of the p53 pathways induced pRb dephosphorylation and subsequently produced anti-tumor effects. A number of preclinical studies with different genes and vector systems demonstrated the therapeutic efficacy and raised the possibility of gene therapy in clinical settings. An intrapleural administration of vectors has several advantages in transducing pleural mesothelioma but activates rapid antibody production which impedes further gene expression. There have been several clinical studies conducted for mesothelioma and these trials showed the feasibility of intrapleural administrations of adenovirus vectors. In this review we summarize major preclinical and clinical gene therapy for mesothelioma, and discuss the advantages of gene therapy in the context of stimulating host immune systems. Accumulating clinical data suggest that an intrapleural administration of viral vectors has distinct aspects which are not observed in other administration routes.
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[126]
TÍTULO / TITLE: - Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Respir Med. 2013 Mar 16. pii: S0954-6111(13)00056-5. doi: 10.1016/j.rmed.2013.02.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.rmed.2013.02.007
AUTORES / AUTHORS: - Yang Ai SS; Hsu K; Herbert C; Cheng Z; Hunt J; Lewis CR; Thomas PS
INSTITUCIÓN / INSTITUTION: - Inflammation and Infection Research Centre, Faculty of Medicine, University of New South Wales, Australia.
RESUMEN / SUMMARY: - INTRODUCTION: Lung cancer is a leading cause of cancer mortality worldwide. Non-invasively collected biofluids such as exhaled breath condensate (EBC) present a potential sampling medium to detect and study pathological changes implicated in tumourigenesis. Mitochondrial DNA changes have been implicated in the carcinogenesis process. Consequently, the detection of mitochondrial changes in EBC could expand our understanding of lung carcinogenesis as well as identifying specific markers for future studies. METHODS: EBC and saliva was collected from newly diagnosed subjects with lung cancer and control subjects in a cross-sectional study. The EBC and saliva was analysed for mitochondrial DNA D-loop changes using a PCR sequencing approach. The sequences obtained were compared to paired salivary DNA and the revised Cambridge Reference Sequence (rCRS) to identify somatic mutations, and quantitative and qualitative differences in mutations were analysed between groups. RESULTS: A total of 25 subjects (9 NSCLC patients, 10 smokers/ex-smokers and 6 non-smokers) were recruited. A significantly elevated D-loop mutation rate in the lung cancer group compared to the control groups was present (7 vs 3.5 for smokers/ex-smokers, and 7 vs. 4 for non-smokers, p = 0.034). The recognised mutation T16217C showed specificity for lung cancer. CONCLUSIONS: Mitochondrial DNA mutations are more common in the EBC of patients with lung cancer. This suggests that these processes are associated with the carcinogenesis of lung cancer and may be a marker of the disease.
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[127]
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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[128]
TÍTULO / TITLE: - Expression of Metallothionein-III in Patients with Non-small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):965-74.
AUTORES / AUTHORS: - Werynska B; Pula B; Muszczynska-Bernhard B; Gomulkiewicz A; Jethon A; Podhorska-Okolow M; Jankowska R; Dziegiel P
INSTITUCIÓN / INSTITUTION: - Department of Histology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland. piotr.dziegiel@umed.wroc.pl.
RESUMEN / SUMMARY: - BACKGROUND: Currently, there is little knowledge concerning expression of metallothionein-III (MT-III), also known as growth-inhibitory factor, in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this study, we evaluated MT-III expression in 184 patients using immunohistochemistry and in 61 cases using real-time polymerase chain reaction. RESULTS: MT-III mRNA expression was significantly higher in NSCLC as compared to non-malignant lung tissues (NMLT; p<0.0086). MT-III expression was noted in the cytoplasm and nucleus of cancer cells. Significantly lower nuclear MT-III (p<0.0001) expression and significantly higher cytoplasmic MT-III (p=0.0068) expression was noted in the pneumocytes of NMLT, as compared to NSCLC. Nuclear MT-III expression was significantly higher in G1 cases as compared to G2 (p=0.0308) and G3 (p=0.0194) cases. Low cytoplasmic MT-III expression was associated with larger primary tumour size (p=0.0378). Lower MT-III mRNA and cytoplasmic MT-III expression was associated with poor patient outcome (p=0.0410 and p=0.0347, respectively). CONCLUSION: MT-III expression may have an impact on the pathogenesis of NSCLC.
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[129]
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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[130]
TÍTULO / TITLE: - A patient with concurrent primary lung cancer and lymphoma diagnosed using endobronchial ultrasound.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - QJM. 2013 Apr;106(4):389-90. doi: 10.1093/qjmed/hct045. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1093/qjmed/hct045
AUTORES / AUTHORS: - Marshall AD; Miller DR; Smith LJ; Chetty M; Currie GP
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[131]
TÍTULO / TITLE: - Genetic polymorphisms of TERT and CLPTM1L and risk of lung cancer-A case-control study in a Chinese population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 19. pii: S0169-5002(13)00057-3. doi: 10.1016/j.lungcan.2013.01.021.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.021
AUTORES / AUTHORS: - Myneni AA; Chang SC; Niu R; Liu L; Ochs-Balcom HM; Li Y; Zhang C; Zhao B; Shi J; Han X; Li J; Su J; Cai L; Yu S; Zhang ZF; Mu L
INSTITUCIÓN / INSTITUTION: - Department of Social and Preventive, School of Public Health and Health Professions, State University of New York (SUNY) at Buffalo, Buffalo, NY 14221, USA.
RESUMEN / SUMMARY: - BACKGROUND/OBJECTIVES: Genetic variants of telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes in chromosome 5p15.33 region were previously identified to influence the susceptibility to lung cancer. We examined the association of single nucleotide polymorphisms (SNPs) in TERT and CLPTM1L genes with lung cancer and explored their potential modifying effects on the relationship between environmental risk factors and lung cancer in a Chinese population. METHODS: We genotyped rs2736100 (TERT) and rs401681 (CLPTM1L) SNPs in a case-control study with 399 lung cancer cases and 466 controls form Taiyuan, China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. Potential confounders were controlled for in the adjusted models. RESULTS: We found that the GG genotype of TERT was positively associated with lung cancer (OR=1.47, 95% CI: 1.00-2.16). The association was stronger in participants older than 60years, exposed to low indoor air pollution and adenocarcinoma and squamous cell carcinoma (SCC) in recessive model analysis. The GA genotype of CLPTM1L was inversely associated with lung cancer (OR=0.72, 95% CI: 0.54-0.97). The association was stronger in participants 60 years old or younger, males, heavy smokers, exposed to low indoor air pollution and SCC in dominant model analysis. Individuals carrying both TERT and CLPTM1L risk genotypes had higher risk of lung cancer (OR=1.80, 95% CI: 1.15-2.82). Significant interaction was observed between CLPTM1L and indoor air pollution in association with lung cancer. CONCLUSIONS: Our results reiterate that genetic variants of TERT and CLPTM1L contribute to lung cancer susceptibility in Chinese population. These associations need to be verified in larger and different populations.
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[132]
TÍTULO / TITLE: - Exploring the impact of screening with low-dose CT on lung cancer mortality in mild to moderate COPD patients: A pilot study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Respir Med. 2013 Mar 7. pii: S0954-6111(13)00039-5. doi: 10.1016/j.rmed.2013.01.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.rmed.2013.01.013
AUTORES / AUTHORS: - de-Torres JP; Casanova C; Marin JM; Zagaceta J; Alcaide AB; Seijo LM; Campo A; Carrizo S; Montes U; Cordoba-Lanus E; Baz-Davila R; Aguirre-Jaime A; Celli BR; Zulueta JJ
INSTITUCIÓN / INSTITUTION: - Pulmonary Department, Clinica Universidad de Navarra, Pamplona 31200, España. Electronic address: jpdetorres@unav.es.
RESUMEN / SUMMARY: - BACKGROUND: COPD is an independent risk factor for lung cancer, especially in patients with mild to moderate disease. OBJECTIVE: To determine if performing lung cancer screening in GOLD 1 and 2 COPD patients, results in reduced lung cancer mortality. METHODS: This study compared patients with mild to moderate COPD from 2 cohorts matched for age, gender, BMI, FEV1%, pack-yrs history and smoking status. The screening group (SG) had an annual low dose computed tomography (LDCT). The control group (CG) was prospectively followed with usual care. Lung cancer incidence and mortality densities were compared between groups. RESULTS: From an initial sample of 410 (SG) and 735 (CG) patients we were able to match 333 patients from each group. At the same follow-up time lung cancer incidence density was 1.79/100 person-years in the SG and 4.14/100 person-years in the CG (p = 0.004). The most frequent histological type was adenocarcinoma in both SG and CG (65% and 46%, respectively), followed by squamous cell carcinoma (25% and 37%, respectively). Eighty percent of lung cancers in the SG (16/20) were diagnosed in stage I, and all of CG cancers (35/35) were in stage III or IV. Mortality incidence density from lung cancer (0.08 vs. 2.48/100 person-years, p < 0.001) was lower in the SG. CONCLUSIONS: This pilot study in patients with mild to moderate COPD suggests that screening with LDCT detects lung cancer in early stages, and could decrease lung cancer mortality in that high risk group. Appropriately designed studies should confirm these important findings.
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[133]
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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[134]
TÍTULO / TITLE: - ROS1-Rearranged Lung Cancer: A Clinicopathologic and Molecular Study of 15 Surgical Cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Surg Pathol. 2013 Apr;37(4):554-62. doi: 10.1097/PAS.0b013e3182758fe6.
●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e3182758fe6
AUTORES / AUTHORS: - Yoshida A; Kohno T; Tsuta K; Wakai S; Arai Y; Shimada Y; Asamura H; Furuta K; Shibata T; Tsuda H
INSTITUCIÓN / INSTITUTION: - *Division of Pathology and Clinical Laboratories section signDivision of Thoracic Surgery, National Cancer Center Hospital daggerDivision of Genome Biology double daggerDivision of Cancer Genomics, Center for Medical Genomics, National Cancer Center Research Institute, Tokyo, Japan.
RESUMEN / SUMMARY: - Recent discovery of ROS1 gene fusion in a subset of lung cancers has raised clinical interest, because ROS1 fusion-positive cancers are reportedly sensitive to kinase inhibitors. To better understand these tumors, we examined 799 surgically resected non-small cell lung cancers by reverse transcriptase polymerase chain reaction and identified 15 tumors harboring ROS1 fusion transcripts (2.5% of adenocarcinomas). The most frequent fusion partner was CD74 followed by EZR. The affected patients were often younger nonsmoking female individuals, and they had overall survival rates similar to those of the ROS1 fusion-negative cancer patients. All the ROS1 fusion-positive tumors were adenocarcinomas except 1, which was an adenosquamous carcinoma. Histologic examination identified an at least focal presence of either solid growth with signet-ring cells or cribriform architecture with abundant extracellular mucus in 53% of the cases. These 2 patterns are reportedly also characteristic of anaplastic lymphoma kinase (ALK)-rearranged lung cancers, and our data suggest a phenotypic resemblance between the ROS1-rearranged and ALK-rearranged tumors. All tumors except 1 were immunoreactive to thyroid transcription factor-1. Fluorescence in situ hybridization using ROS1 break-apart probes revealed positive rearrangement signals in 23% to 93% of the tumor cells in ROS1 fusion-positive cancers, which were readily distinguished using a 15% cutoff value from 50 ROS1 fusion-negative tumors tested, which showed 0% to 6% rearrangement signals. However, this perfect test performance was achieved only when isolated 3’ signals were included along with classic split signals in the definition of rearrangement positivity. Fluorescence in situ hybridization signal patterns were unrelated to 5’ fusion partner genes. All ROS1 fusion-positive tumors lacked alteration of EGFR, KRAS, HER2, ALK, and RET genes.
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[135]
TÍTULO / TITLE: - Prognosis of lung cancer resection in patients with previous extra-respiratory solid malignancies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cardiothorac Surg. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt031
AUTORES / AUTHORS: - Pages PB; Mordant P; Cazes A; Grand B; Foucault C; Dujon A; Le Pimpec Barthes F; Riquet M
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Georges Pompidou European Hospital, Paris-Descartes-University, Paris, France.
RESUMEN / SUMMARY: - OBJECTIVES: Non-small-cell lung cancer (NSCLC) following pulmonary or pharyngolaryngeal malignancies has been widely studied, but only a few articles have focussed on lung cancers following other solid malignancies. Our purpose was to compare the characteristics and prognosis of patients with NSCLC according to the medical history of the extra-pulmonary and extra-pharyngolaryngeal solid malignancy. METHODS: Patients who underwent surgery for NSCLC from January 1980 to December 2009 in two French thoracic centres were reviewed. We compared patients with no history of cancer (Group 1) and patients with a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy (Group 2). RESULTS: There were 4992 patients: 4603 (92%) in Group 1 and 389 (8%) in Group 2. In comparison with Group 1, Group 2 showed an increasing incidence over the last 3 decades (2-8%), an older population (65.9 vs 61 years, P < 0.001), a higher proportion of women (34 vs 18%, P < 0.001), non-smokers (20 vs 10%, P < 0.001), adenocarcinomas (53 vs 40%, P < 0.001), T1 (16 vs 14%, P = 0.047) and second nodule in the same lobe (4 vs 2%, P < 0.001). The overall survival was not significantly different between the two groups (P = 0.09). In multivariate analysis, older age, male gender, pneumonectomy, higher T, higher N, incomplete resection and history of extra pulmonary-extra pharyngolaryngeal solid malignancy were significantly associated with a worse prognosis. CONCLUSIONS: Despite an earlier diagnosis, a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy is associated with a worse prognosis in patients with NSCLC undergoing surgical resection. Overall survival is particularly low after a history of bladder and upper gastrointestinal malignancies.
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[136]
TÍTULO / TITLE: - Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 19. doi: 10.3892/or.2013.2294.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2294
AUTORES / AUTHORS: - Pirozzi G; Tirino V; Camerlingo R; La Rocca A; Martucci N; Scognamiglio G; Franco R; Cantile M; Normanno N; Rocco G
INSTITUCIÓN / INSTITUTION: - Department of Experimental Oncology, National Cancer Institute, Pascale Foundation, I-80131 Naples, Italy.
RESUMEN / SUMMARY: - The epithelial-mesenchymal transition (EMT) is a program involved in embryonic development that is often activated during cancer invasion and metastasis. CD133 is the main marker identifying cancer stem cells (CSCs) in lung cancer. Circulating tumor cells (CTCs) are demonstrated to be useful as a biomarker for the diagnosis and treatment of cancer. The aim of this study was to correlate EMT, CSCs and CTCs with patient prognosis to verify whether they can contribute to better stratification of lung cancer patients at risk for recurrent and metastatic disease. Pulmonary venous blood was drawn after major pulmonary surgery in 45 patients with resectable non-small cell lung cancer (NSCLC) in order to identify CTCs. For the same patients, we also constructed prognostic lung tissue microarrays (TMA) for CD133 and c-kit and evaluated CSC and EMT markers using flow cytometry. Cytokeratin-positive cells were detectable in 11 (23.9%) cases. c-kit expression was heterogeneous in prognostic TMAs while CD133 expression was low or absent which was also confirmed by flow cytometry and RT-PCR. Flow cytometric analysis showed that the mean percentage of cells with CD133 expression was 1.6%. CD90 and CD326 markers were co-expressed with a mean percentage of 10.41%. When CD133 and CD90/CD326 expression was correlated with follow-up, CD133 showed a higher correlation with deceased patients when compared with CD90/CD326 co-expression (32.5 vs. 9.5%). CD133 expression demonstrated a strong significant association with patients exhibiting progressive disease when compared to CD90/CD326 expression (15 vs. 7.1%). CD133 may be significantly associated with invasion and metastatic spread of NSCLC. The co-expression of CD90, CD326 and CD133 has definite prognostic value in patients with NSCLC.
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[137]
TÍTULO / TITLE: - Detection of lung cancer in patients with pneumoconiosis by fluorodeoxyglucose-positron emission tomography/computed tomography: four cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Imaging. 2013 Jan 28. pii: S0899-7071(12)00335-X. doi: 10.1016/j.clinimag.2012.11.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.11.001
AUTORES / AUTHORS: - Yu H; Zhang H; Wang Y; Cui X; Han J
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, Qi lu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan 250012, China.
RESUMEN / SUMMARY: - We report 4 cases of lung cancer in patients with pneumoconiosis detected by F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), which could differentiate lung cancer and pneumoconiosis. FDG-PET/CT may be useful in cancer screening for patients with pneumoconiosis.
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[138]
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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[139]
TÍTULO / TITLE: - Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study.
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/mdt009
AUTORES / AUTHORS: - Le Treut J; Sault MC; Lena H; Souquet PJ; Vergnenegre A; Le Caer H; Berard H; Boffa S; Monnet I; Damotte D; Chouaid C
INSTITUCIÓN / INSTITUTION: - Department of Pneumology, Aix en Provence.
RESUMEN / SUMMARY: - BackgroundThe optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear. Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives.Patients and methodsProspective, multicentre, single-arm, phase II study with a centralised review of treatment-response and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days.ResultsEighteen centres included 42 patients (mean age, 59 +/- 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients.ConclusionsThe pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC).
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[140]
TÍTULO / TITLE: - A dramatic lung cancer course in a patient with a rare EGFR germline mutation exon 21 V843I: Is EGFR TKI resistance predictable?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Apr;80(1):81-4. doi: 10.1016/j.lungcan.2012.11.013. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.11.013
AUTORES / AUTHORS: - Demierre N; Zoete V; Michielin O; Stauffer E; Zimmermann DR; Betticher DC; Peters S
INSTITUCIÓN / INSTITUTION: - HFR Fribourg, Hopital Cantonal, Department of Internal Medicine, Division of Oncology, Fribourg, Switzerland.
RESUMEN / SUMMARY: - We report on the medical history of a Caucasian smoker woman diagnosed with a stage IV NSCLC adenocarcinoma, characterized by a rare epidermal growth factor receptor (EGFR) point mutation in exon 21 codon 843 (p.V843I/c.2527G>A/COSMIC ID 85894). This genetic alteration revealed to be germline, after its presence was demonstrated in chondroblasts from the bone biopsy. While it is the first description of germline V843I mutation without concomitant additional known EGFR activating mutation, we modeled the EGFR ATP catalytic domain in complex with ATP, gefitinib and erlotinib using computer-aided approaches to estimate possible changes in affinity upon the V843I mutation.
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[141]
TÍTULO / TITLE: - cAMP signalling decreases p300 protein levels by promoting its ubiquitin/proteasome dependent degradation via Epac and p38 MAPK in lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS Lett. 2013 Mar 20. pii: S0014-5793(13)00221-4. doi: 10.1016/j.febslet.2013.03.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.febslet.2013.03.010
AUTORES / AUTHORS: - Jeong MJ; Kim EJ; Cho EA; Ye SK; Kang GH; Jnhnn YS
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
RESUMEN / SUMMARY: - The transcriptional coactivator p300 functions as a histone acetyltransferase and a scaffold for transcription factors. We investigated the effect of cAMP signalling on p300 expression. The activation of cAMP signalling by the expression of constitutively active Galphas or by treatment with isoproterenol decreased the p300 protein expression in lung cancer cells. Isoproterenol promoted the ubiquitination and subsequent proteasomal degradation of p300 in an Epac-dependent manner. Epac promoted p300 degradation by inhibiting the activity of p38 MAPK. It is concluded that cAMP signalling decreases the level of the p300 protein by promoting its ubiquitin-proteasome dependent degradation, which is mediated by Epac and p38 MAPK, in lung cancer cells.
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[142]
TÍTULO / TITLE: - Spreaders and sponges define metastasis in lung cancer: A Markov chain mathematical model.
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-12-4488
AUTORES / AUTHORS: - Newton PK; Mason J; Bethel K; Bazhenova L; Nieva J; Norton L; Kuhn P
INSTITUCIÓN / INSTITUTION: - Aerospace and Mechanical Engineering, Viterbi School of Engineering, University of Southern California.
RESUMEN / SUMMARY: - The classic view of metastatic cancer progression is that it is a unidirectional process initiated at the primary tumor site, progressing to variably distant metastatic sites in a fairly predictable, though not perfectly understood, fashion. A Markov chain Monte Carlo mathematical approach can determine a pathway diagram that classifies metastatic tumors as ‘spreaders’ or ‘sponges’ and orders the timescales of progression from site to site. In light of recent experimental evidence highlighting the potential significance of self-seeding of primary tumors, we use a Markov chain Monte Carlo (MCMC) approach, based on large autopsy data sets, to quantify the stochastic, systemic, and often multi-directional aspects of cancer progression. We quantify three types of multi-directional mechanisms of progression: (i) self-seeding of the primary tumor; (ii) re-seeding of the primary tumor from a metastatic site (primary re-seeding); and (iii) re-seeding of metastatic tumors (metastasis re-seeding). The model shows that the combined characteristics of the primary and the first metastatic site to which it spreads largely determine the future pathways and timescales of systemic disease. For lung cancer, the main ‘spreaders’ of systemic disease are the adrenal gland and kidney, whereas the main ‘sponges’ are regional lymph nodes, liver, and bone. Lung is a significant self-seeder, although it is a ‘sponge’ site with respect to progression characteristics.
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[143]
TÍTULO / TITLE: - REGULATION OF LUNG CANCER METASTASIS BY Klf4-Numb-like SIGNALING.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4232
AUTORES / AUTHORS: - Vaira V; Faversani A; Martin NM; Garlick DS; Ferrero S; Nosotti M; Kissil JL; Bosari S; Altieri DC
INSTITUCIÓN / INSTITUTION: - Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico.
RESUMEN / SUMMARY: - Metastatic traits appear to be acquired by transformed cells with progenitor-like cancer-initiating properties, but there remains little mechanistic insight into this linkage. In this report, we show that the polarity protein Numbl, which is expressed normally in neuronal progenitors, becomes overexpressed and mislocalized in cancer cells from a variety of human tumors. Numbl overexpression relies on loss of the tumor suppressor microRNA miR-296), which actively represses translation of Numbl in normal cells. In turn, deregulated expression of Numbl mediates random tumor cell migration and invasion, blocking anoikis and promoting metastatic dissemination. In clinical specimens of non-small cell lung cancer, we found that Numbl overexpression correlated with a reduction in overall patient survival. Mechanistically, Numbl-mediated tumorigenesis involved suppression of a “stemness” transcriptional program driven by the stem cell programming transcription factor Klf4, thereby preserving a pool of progenitor-like cells in lung cancer. Our results reveal that Numbl-Klf4 signaling is critical to maintain multiple nodes of metastatic progression, including persistence of cancer-initiating cells, rationalizing its therapeutic exploitation to improve the treatment of advanced lung cancer.
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[144]
TÍTULO / TITLE: - Extracellular Signal-Regulated Kinase 5: A Potential Therapeutic Target for Malignant Mesotheliomas.
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-12-3202
AUTORES / AUTHORS: - Shukla A; Miller JM; Cason C; Sayan M; Macpherson MB; Beuschel SL; Hillegass J; Vacek PM; Pass HI; Mossman BT
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Pathology and Medical Biostatistics, University of Vermont College of Medicine, Burlington, Vermont; Lampire Biological Laboratories Inc., Pipersville, Pennsylvania; and Department of Cardiothoracic Surgery, New York University School of Medicine, New York, New York.
RESUMEN / SUMMARY: - PURPOSE: Malignant mesothelioma is a devastating disease with a need for new treatment strategies. In the present study, we showed the importance of extracellular signal-regulated kinase 5 (ERK5) in malignant mesothelioma tumor growth and treatment.EXPERIMENTAL DESIGN: ERK5 as a target for malignant mesothelioma therapy was verified using mesothelial and mesothelioma cell lines as well as by xenograft severe combined immunodeficient (SCID) mouse models.RESULTS: We first showed that crocidolite asbestos activated ERK5 in LP9 cells and mesothelioma cell lines exhibit constitutive activation of ERK5. Addition of doxorubicin resulted in further activation of ERK5 in malignant mesothelioma cells. ERK5 silencing increased doxorubicin-induced cell death and doxorubicin retention in malignant mesothelioma cells. In addition, shERK5 malignant mesothelioma lines exhibited both attenuated colony formation on soft agar and invasion of malignant mesothelioma cells in vitro that could be related to modulation of gene expression linked to cell proliferation, apoptosis, migration/invasion, and drug resistance as shown by microarray analysis. Most importantly, injection of shERK5 malignant mesothelioma cell lines into SCID mice showed significant reduction in tumor growth using both subcutaneous and intraperitoneal models. Assessment of selected human cytokine profiles in peritoneal lavage fluid from intraperitoneal shERK5 and control tumor-bearing mice showed that ERK5 was critical in regulation of various proinflammatory (RANTES/CCL5, MCP-1) and angiogenesis-related (interleukin-8, VEGF) cytokines. Finally, use of doxorubicin and cisplatin in combination with ERK5 inhibition showed further reduction in tumor weight and volume in the intraperitoneal model of tumor growth.CONCLUSION: ERK5 inhibition in combination with chemotherapeutic drugs is a beneficial strategy for combination therapy in patients with malignant mesothelioma. Clin Cancer Res; 19(8); 1-13. ©2013 AACR.
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[145]
TÍTULO / TITLE: - Results of platinum-based chemotherapy in unselected performance status (PS) 2 patients with advanced non-small cell lung cancer: a cohort study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):544. doi: 10.1007/s12032-013-0544-5. Epub 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0544-5
AUTORES / AUTHORS: - Jouveshomme S; Canoui-Poitrine F; Le Thuaut A; Bastuji-Garin S
INSTITUCIÓN / INSTITUTION: - Service de Pneumologie et d’Oncologie Thoracique, CHI Poissy-Saint-Germain, 78100 Saint-Germain en Laye, France. sjouveshomme@hpsj.fr
RESUMEN / SUMMARY: - Recent phase-III trials show that platinum-based chemotherapy (PBCT) for patients with advanced non-small cell lung cancer and poor performance status (PS) improves survival without increasing toxicity, compared to single-agent chemotherapy (CT). The aim of this study was to asses whether these results are transposable in a community population. About 260 consecutive patients with stage IIIB-IV NSCLC (25 % with PS 2) receiving a PBCT were prospectively included in the study and retrospectively analyzed. No difference was observed between PS 0-1 and 2 patients regarding tumor-control rate, symptom relief, and grade III-V toxicity. Median and 1-year survival of PS 2 patients was 6.2 months and 32 %, respectively. PS 1 and PS 2 patients continuing first-line CT beyond the first course shared the same survival. On the other hand, more PS 2 (31.8 vs. 9.3 % of PS 0-1 patients, p < 0.001) discontinued first-line CT after the first course with a poor clinical outcome. They were more likely to have lost weight and to have a high comorbidity score. PBCT in unselected PS 2 patients achieved survival rates similar to those observed in clinical trials, with no increase in toxicity. PS 2 patients continuing CT beyond the first course shared the same prognosis than PS 1 patients. However, almost one-third of PS 2 patients discontinued CT after the first course. Their prognosis was poor.
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[146]
TÍTULO / TITLE: - Efficacy of Rechallenge Chemotherapy in Patients With Sensitive Relapsed Small Cell Lung Cancer.
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.0b013e318286907b
AUTORES / AUTHORS: - Wakuda K; Kenmotsu H; Naito T; Akamatsu H; Ono A; Shukuya T; Nakamura Y; Tsuya A; Murakami H; Takahashi T; Endo M; Nakajima T; Yamamoto N
INSTITUCIÓN / INSTITUTION: - Divisions of *Thoracic Oncology daggerDiagnostic Radiology double daggerPathology, Shizuoka Cancer Center Hospital, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
RESUMEN / SUMMARY: - OBJECTIVES:: To evaluate the efficacy of rechallenge with current induction regimens for sensitive-relapse small cell lung cancer (SCLC) patients. METHODS:: We defined sensitive relapse as treatment-free interval (TFI>/=90 d). Sensitive-relapse SCLC patients who received second-line chemotherapy were separated into those treated with rechallenge chemotherapy (rechallenge group) and those treated with other regimens (other group). The endpoints were overall survival (OS), progression-free survival, and toxicity. RESULTS:: Sixty-five patients (19 rechallenge group and 46 other group) were assessable for efficacy and safety evaluation. No significant differences in age, sex, ECOG performance status at relapse, disease extent at diagnosis, or response to first-line treatment were found between the 2 groups, but TFI was significantly longer in the rechallenge group. Twenty-one patients of the other group received amrubicin. There was no significant difference in OS between the 2 groups [median survival time (MST): rechallenge group, 14.4 mo; other group, 13.1 mo; P=0.51]. In the patients treated with amrubicin, MST was 12.6 months. Comparing the rechallenge group with the patients treated with amrubicin, there was also no significant difference in OS (P=0.38). Both the rechallenge and other group included 11 patients with ex-sensitive relapse (TFI>/=180 d). There was no significant difference in OS between the 2 groups (MST 15.7 vs. 26.9 mo, P=0.46). CONCLUSIONS:: Rechallenge chemotherapy did not prove superior to other chemotherapies, suggesting that monotherapy, such as amrubicin, might be reasonable as second-line chemotherapy for sensitive-relapse SCLC patients.
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[147]
TÍTULO / TITLE: - Definition of a positive test result in computed tomography screening for lung cancer: a cohort study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Intern Med. 2013 Feb 19;158(4):246-52. doi: 10.7326/0003-4819-158-4-201302190-00004.
●● Enlace al texto completo (gratuito o de pago) 7326/0003-4819-158-4-201302190-00004
AUTORES / AUTHORS: - Henschke CI; Yip R; Yankelevitz DF; Smith JP
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA. Claudia.Henschke@mountsinai.org
RESUMEN / SUMMARY: - BACKGROUND: Low-dose computed tomography screening for lung cancer can reduce mortality among high-risk persons, but “false-positive” findings may result in unnecessary evaluations with attendant risks. The effect of alternative thresholds for defining a positive result on the rates of positive results and cancer diagnoses is unknown. OBJECTIVE: To assess the frequency of positive results and potential delays in diagnosis in the baseline round of screening by using more restrictive thresholds. DESIGN: Prospective cohort study. SETTING: Multi-institutional International Early Lung Cancer Action Program. PATIENTS: 21 136 participants with baseline computed tomography performed between 2006 and 2010. MEASUREMENTS: The frequency of solid and part-solid pulmonary nodules and the rate of lung cancer diagnosis by using current (5 mm) and more restrictive thresholds of nodule diameter. RESULTS: The frequency of positive results in the baseline round by using the current definition of positive result (any parenchymal, solid or part-solid, noncalcified nodule >/=5.0 mm) was 16% (3396/21 136). When alternative threshold values of 6.0, 7.0, 8.0 and 9.0 mm were used, the frequencies of positive results were 10.2% (95% CI, 9.8% to 10.6%), 7.1% (CI, 6.7% to 7.4%), 5.1% (CI, 4.8% to 5.4%), and 4.0% (CI, 3.7% to 4.2%), respectively. Use of these alternative definitions would have reduced the work-up by 36%, 56%, 68%, and 75%, respectively. Concomitantly, lung cancer diagnostics would have been delayed by at most 9 months for 0%, 5.0% (CI, 1.1% to 9.0%), 5.9% (CI, 1.7 to 10.1%), and 6.7% (CI, 2.2% to 11.2%) of the cases of cancer, respectively. LIMITATION: This was a retrospective analysis and thus whether delays in diagnosis would have altered outcomes cannot be determined. CONCLUSION: These findings suggest that using a threshold of 7 or 8 mm to define positive results in the baseline round of computed tomography screening for lung cancer should be prospectively evaluated to determine whether the benefits of decreasing further work-up outweigh the consequent delay in diagnosis in some patients.
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[148]
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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[149]
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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[150]
TÍTULO / TITLE: - Patient perceptions of barriers to the early diagnosis of lung cancer and advice for health service improvement.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Fam Pract. 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1093/fampra/cmt001
AUTORES / AUTHORS: - Walton L; McNeill R; Stevens W; Murray M; Lewis C; Aitken D; Garrett J
INSTITUCIÓN / INSTITUTION: - Health Systems, School of Population Health, University of Auckland, Auckland.
RESUMEN / SUMMARY: - Background and objective.Patient and systematic factors within primary and secondary care contribute to delay in timely diagnosis of lung cancer. This qualitative study aimed to explore New Zealand service users’ experiences of the pathway to lung cancer diagnosis, identify factors contributing to delay and provide advice for service improvement. METHODS: Two samples were recruited. Patients who presented to a hospital emergency department with suspicious symptoms (n = 19) were interviewed individually. Those with confirmed lung cancer (n = 20) took part in a focus group. Similar semi-structured interview schedules were used. Interviews and focus groups were audiorecorded and thematic analyses performed. Evident commonality led to an integrated interpretation. RESULTS: Patient delay was common but most had seen a GP before referral. No ED participant had seen a respiratory specialist prior ED admission, but after that, most had a seamless pathway. This contrasts with long waits for outpatient participants. Two central themes, ‘access to health services’ and ‘processes of care’, described factors influencing delay. Subthemes highlighted issues relating to symptom interpretation, health beliefs, provider continuity, relationships and perceived expertise that contributed to patient and GP delay. System complexity, information systems and resourcing issues were identified as barriers at the primary-secondary care interface and within secondary care. CONCLUSION: Reasons for diagnostic delay are complex and multifactorial. Solutions include community initiatives to educate and resource at-risk patients to seek help, supporting and resourcing primary care to increase timely referral and implementing strategies to reduce system complexity for GPs and patients, and the employment of care coordinators.
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[151]
TÍTULO / TITLE: - Stage I-II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt026
AUTORES / AUTHORS: - Verstegen NE; Oosterhuis JW; Palma DA; Rodrigues G; Lagerwaard FJ; van der Elst A; Mollema R; van Tets WF; Warner A; Joosten JJ; Amir MI; Haasbeek CJ; Smit EF; Slotman BJ; Senan S
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - BackgroundVideo-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic ablative radiotherapy (SABR) are both used for early-stage non-small-cell lung cancer. We carried out a propensity score-matched analysis to compare locoregional control (LRC).Patients and methodsVATS lobectomy data from six hospitals were retrospectively accessed; SABR data were obtained from a single institution database. Patients were matched using propensity scores based on cTNM stage, age, gender, Charlson comorbidity score, lung function and performance score. Eighty-six VATS and 527 SABR patients were matched blinded to outcome (1:1 ratio, caliper distance 0.025). Locoregional failure was defined as recurrence in/adjacent to the planning target volume/surgical margins, ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or had to be PET-positive and reviewed by a tumor board.ResultsThe matched cohort consisted of 64 SABR and 64 VATS patients with the median follow-up of 30 and 16 months, respectively. Post-SABR LRC rates were superior at 1 and 3 years (96.8% and 93.3% versus 86.9% and 82.6%, respectively, P = 0.04). Distant recurrences and overall survival (OS) were not significantly different.ConclusionThis retrospective analysis found a superior LRC after SABR compared with VATS lobectomy, but OS did not differ. Our findings support the need to compare both treatments in a randomized, controlled trial.
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[152]
TÍTULO / TITLE: - Camptothecin and cisplatin upregulate ABCG2 and MRP2 expression by activating the ATM/NF-kappaB pathway in lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1289-96. doi: 10.3892/ijo.2013.1805. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1805
AUTORES / AUTHORS: - Ke SZ; Ni XY; Zhang YH; Wang YN; Wu B; Gao FG
INSTITUCIÓN / INSTITUTION: - Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
RESUMEN / SUMMARY: - Multidrug resistance (MDR) formation is an important problem in lung cancer chemotherapy. Our study showed that both camptothecin and cisplatin could not only induce ATM and NF-kappaB activation but also upregulate expression of the MDR-related genes ABCG2, MRP2 in NCI-H446 cells. Moreover, camptothecin and cisplatin-induced ABCG2 and MRP2 upregulation could be impaired by ATM and NF-kappaB inhibitors, indicating a relationship between ATM, NF-kappaB activation and MDR formation in lung cancer chemo-therapy. Our study indicates that ATM may serve as a potential mole-cular target for MDR formation in lung cancer chemotherapy.
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[153]
TÍTULO / TITLE: - CYP2A6, CYP1A1, and CYP2D6 polymorphisms in lung cancer patients from Central South China.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):521. doi: 10.1007/s12032-013-0521-z. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0521-z
AUTORES / AUTHORS: - Huang FM; Chen HC; Khan MA; Yang FL; Wan XX; Xu AH; Ou-yang FD; Zhang DZ
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha 410013, Hunan, China.
RESUMEN / SUMMARY: - Lung cancer is a common cause of cancer-related death. The link between risk of lung cancer susceptibility and genetic polymorphisms in metabolic enzymes is well documented. In this study, the relationships between lung cancer susceptibility and polymorphisms in the phase I metabolic enzyme genes CYP1A1, CYP2D6, and CYP2A6 were investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 168 lung carcinoma patients from the Han ethnic group of Hunan Province in Central South China. Polymorphisms of the investigated genes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and two-step allelic-specific PCR assays. No significant differences were found between the frequencies in cases and controls for the genotypes wild-type (WW), heterozygous mutant, or homozygous mutant; for CYP1A1 or CYP2D6; or for the genotypes WW, heterozygous deletion, or null genotype for CYP2A6. The three-locus model (CYP2A6/CYP1A1/CYP2D6) had a maximum test sample accuracy that was significant (P < 0.001) with a cross-validation consistency of 10. These results indicated that the three-order interaction of CYP2A6, CYP1A1, and CYP2D6 polymorphisms might increase genetic susceptibility to lung cancer. We report the involvement of a three-order interaction between CYP1A1, CYP2A6, and CYP2D6 polymorphisms in lung cancer risk in people in Central South China, although no relationship between lung cancer risk and individual gene polymorphisms was found.
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[154]
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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[155]
TÍTULO / TITLE: - The lung cancer patient at the emergency department: A three-year retrospective study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 19. pii: S0169-5002(12)00651-4. doi: 10.1016/j.lungcan.2012.12.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.006
AUTORES / AUTHORS: - Gorham J; Ameye L; Berghmans T; Sculier JP; Meert AP
INSTITUCIÓN / INSTITUTION: - Service des Soins Intensifs et Urgences Oncologiques and Oncologie Thoracique, Belgium.
RESUMEN / SUMMARY: - INTRODUCTION: Currently, there are limited data on the lung cancer patient at the emergency department. Our objective is to review the medical charts of those patients to determine the frequency and main causes of emergency consultations and the predicting factors for hospital admissions and deaths. METHODS: We conducted a retrospective study including all patients with lung cancer consulting at the emergency department of a cancer hospital. RESULTS: From January 1, 2008 to December 31, 2010, 269 patients with lung cancer presented at the emergency, corresponding to 548 consultations (8.3% of all 6575 visits). During the same period, 626 patients for lung cancer were treated in our institution meaning that 43% of them are consulting at least once the emergency department during the course of their disease. The main reasons for consultation were respiratory symptoms (22.3%) and fever (19.9%). Emergency visit leads to hospital admission in 63% of the cases. In multivariate analysis, the main independent predictor factor of hospitalisation is arrival by ambulance (odd ratio 12), which is also the principal predictor of death during hospitalisation (odd ratio 9.5). The presence of signs at physical examination is also an important factor. CONCLUSION: Our study shows that emergency visit is a frequent event for lung cancer patients and has identified simple factors predicting hospitalisation and deaths.
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[156]
TÍTULO / TITLE: - Quantification of serum HBXAP DNA in lung cancer patients by quantitative fluorescent polymerase chain reaction.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biol Rep. 2013 Mar 2.
●● Enlace al texto completo (gratuito o de pago) 1007/s11033-013-2488-4
AUTORES / AUTHORS: - Hou YL; Chen H; Ge MJ; Li FZ; Xue CJ; Wu YF; Luo HX
INSTITUCIÓN / INSTITUTION: - Clinical Laboratories, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
RESUMEN / SUMMARY: - Hepatitis B virus x associated protein (HBXAP), as a subunit of chromatin remodeling and spacing factor, plays a critical role in cancer development through gene amplification. In this study, we aimed to quantify the levels of serum HBXAP DNA, to analyze and compare its diagnostic value with existing clinical parameters in lung cancer, and to potentially provide a novel tumor marker for lung cancer. Serum HBXAP DNA from 65 lung cancer patients and 20 healthy controls was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) analysis. The data were analyzed by statistical software SPSS 13.0. We found that serum HBXAP DNA levels in lung cancer patients were higher compared to healthy controls (u = 219.0, p = 0.001) and were closely associated with TNM stage and lymph node metastasis (p = 0.015 and p = 0.016, respectively). However, serum HBXAP DNA levels were not associated with patient age, gender, smoking status, histological type, or tumor size (p > 0.05). We identified a sensitivity of 61.9 % and a specificity of 93.7 % for the ability of HBXAP DNA levels to detect lung cancer at a cutoff value of 1,557.6 copies/mul. The sensitivity for existing lung-tumor markers, such as squamous cell carcinoma antigen, cytokeratin fragment 21-1, and neuron specific enolase, was increased from 35.7 %, 53.5 %, and 56.0 % to 75.0 %, 86.0 %, and 80.0 %, respectively, by inclusion of serum HBXAP DNA. Taken together, quantification of serum HBXAP DNA by FQ-PCR could potentially serve as a novel complementary tool for the clinical screening and detection of lung cancer.
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[157]
TÍTULO / TITLE: - Sequential Binary Gene-Ratio Tests Define a Novel Molecular Diagnostic Strategy for Malignant Pleural Mesothelioma.
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-12-2117
AUTORES / AUTHORS: - De Rienzo A; Richards WG; Yeap BY; Coleman MH; Sugarbaker PE; Chirieac LR; Wang YE; Quackenbush J; Jensen RV; Bueno R
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Surgery, Brigham and Women’s Hospital and Harvard Medical School.
RESUMEN / SUMMARY: - PURPOSE: To develop a standardized approach for molecular diagnostics, we used the gene-expression ratio bioinformatic technique to design a molecular signature to diagnose MPM from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histological subtype of MPM. In addition, we searched for pathways relevant in MPM in comparison to other related cancers to identify unique molecular features in MPM. EXPERIMENTAL DESIGN: We performed microarray analysis on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. We generated a sequential combination of binary gene-expression ratio tests able to discriminate MPM from other thoracic malignancies. We compared this method to other bioinformatic tools and validated this signature in an independent set of 170 samples. Functional enrichment analysis was performed to identify differentially expressed probes. RESULTS: A sequential combination of gene-expression ratio tests was the best molecular approach to distinguish MPM from all the other samples. Bioinformatic and molecular validations showed that the sequential gene ratio tests were able to identify the MPM samples with high sensitivity and specificity. In addition, the gene-ratio technique was able to differentiate the epithelioid from the sarcomatoid type of MPM. Novel genes and pathways specifically activated in MPM were identified. CONCLUSIONS: New clinically relevant molecular tests have been generated using a small number of genes to accurately distinguish MPMs from other thoracic samples supporting our hypothesis that the gene-expression ratio approach could be a useful tool in the differential diagnosis of cancers.
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[158]
TÍTULO / TITLE: - Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 11. pii: S0169-5002(13)00023-8. doi: 10.1016/j.lungcan.2013.01.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.013
AUTORES / AUTHORS: - Kaduthanam S; Gade S; Meister M; Brase JC; Johannes M; Dienemann H; Warth A; Schnabel PA; Herth FJ; Sultmann H; Muley T; Kuner R
INSTITUCIÓN / INSTITUTION: - Unit Cancer Genome Research, Division of Molecular Genetics, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Translational Research Unit, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
RESUMEN / SUMMARY: - The outcome of resectable non-small cell lung cancer (NSCLC) is critically determined by metastatic spread: About 30-50% of early-stage NSCLC patients encounter tumour recurrence within 5 years after surgery. A biomarker-driven stratification of early-stage lung cancer with a high risk of recurrence may improve therapy management and patient care. The aim of this study was to identify microRNAs (miRNAs) in serum of patients associated with early relapse in pulmonary adenocarcinoma. Serum samples were collected from 204 patients before surgery. miRNA screening was done using qRT-PCR based low-density arrays (664 miRNAs) comparing adenocarcinoma patients (n=40) with and without recurrence 24 months after surgery. Selected miRNAs associated with disease recurrence were validated in an independent patient cohort (n=114). miRNAs were also measured in advanced adenocarcinoma patients (n=29), and individuals with benign pulmonary diagnosis (n=21). Circulating miR-142-3p (p=0.005) and miR-29b (p=0.01) were identified in the screening and confirmed in the validation cohort to be increased in sera of early-stage adenocarcinoma patients suffering from recurrence within 24 months. Elevated miRNA levels were exclusively observed in the group of high-risk patient diagnosed for operable adenocarcinoma compared with benign diagnosis or advanced tumour disease. The differentiation between pulmonary adenocarcinoma patients with low and high risk for recurrence was improved by accounting for both miR-142-3p levels and tumour stage (p=0.007; AUC=0.78). In conclusion, circulating miR-142-3p was found to be associated with a high risk of recurrence in early-stage lung adenocarcinoma patients, and a putative serum marker for risk assessment.
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[159]
TÍTULO / TITLE: - High-dose, pulsatile erlotinib in two NSCLC patients with leptomeningeal metastases-One with a remarkable thoracic response as well.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Apr;80(1):102-5. doi: 10.1016/j.lungcan.2012.12.024. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2012.12.024
AUTORES / AUTHORS: - Kuiper JL; Smit EF
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary Diseases, VU University Medical Center, P.O. Box 7057 1007 MB Amsterdam, The Netherlands. Electronic address: jl.kuiper@vumc.nl.
RESUMEN / SUMMARY: - A considerable number of patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) develop leptomeningeal metastases. Leptomeningeal metastases are associated with deterioration of clinical symptoms and poor survival. Traditionally, treatment of metastases in the central nervous system consists of radiotherapy and less frequently, surgery. The role of systemic therapy is limited due to the blood-brain barrier inhibiting pharmacological doses to be reached in the central nervous system. Several case reports have described high-dose, pulsatile tyrosine kinase inhibitors as an effective treatment of leptomeningeal metastases, based on the hypothesis that higher concentrations in the cerebrospinal fluid can be reached by higher systemic concentrations. Here, we describe two patients with EGFR-mutated non-small cell lung cancer, with both clinical and radiological response to this high-dose, pulsatile regimen. Interestingly, one patient showed a remarkable response of intrathoracic response as well.
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[160]
TÍTULO / TITLE: - Bevacizumab and weekly paclitaxel for non-squamous non small cell lung cancer patients: A retrospective study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 13. pii: S0169-5002(13)00025-1. doi: 10.1016/j.lungcan.2013.01.015.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.015
AUTORES / AUTHORS: - Habib S; Delourme J; Dhalluin X; Petyt G; Tacelli N; Scherpereel A; Lafitte JJ; Cortot AB
INSTITUCIÓN / INSTITUTION: - Pulmonary and Thoracic Oncology Department, CHRU of Lille, France.
RESUMEN / SUMMARY: - BACKGROUND: Combination of bevacizumab and weekly paclitaxel showed synergitic effects, anti-tumor efficacy and a good toxicity profile for patients with breast cancer but has never been evaluated in non small cell lung cancer (NSCLC). We retrospectively reviewed safety and efficacy of this regimen in metastatic non-squamous NSCLC as fourth-line therapy or beyond. METHODS: Patients were identified from a prospective database. Treatment consisted in paclitaxel 80mg/m(2) on days 1, 8 and 15 and bevacizumab 15mg/kg on day 1, every 3 weeks until progression or unacceptable toxicity. RESULTS: Twenty patients were included in this study. Objective response rate at first evaluation was 40% (8/20), confirmed response rate was 15% (3/20) and disease control rate was 75% (15/20). The median progression-free survival and overall survival were 6.4 months (CI95% 4.1-9) and 9.6 months (CI95% 7-19.7). Grade 3-4 adverse events included neutropenia (4/20), onycholysis (2/20) and infection (2/20). One patient died from a bowel perforation and another one died from unknown cause. Prolonged responses were observed in a patient who had received bevacizumab as part of first-line chemotherapy and in another one who harbored an ALK rearrangement. CONCLUSIONS: In our experience, combination of bevacizumab and weekly paclitaxel exhibited acceptable toxicity and had encouraging anti-tumor efficacy as fourth-line treatment or beyond for non-squamous NSCLC patients, supporting further evaluation in larger prospective studies.
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[161]
TÍTULO / TITLE: - Pemetrexed-induced neutropenic enteritis and severe cutaneous hyperpigmentation in a patient with malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 19. pii: S0169-5002(13)00104-9. doi: 10.1016/j.lungcan.2013.02.019.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.019
AUTORES / AUTHORS: - Buchinger K; Stahel R; Niggemeier V; Gubler C; Franzen D
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
RESUMEN / SUMMARY: - Neutropenic enteritis (NE) or enterocolitis (NEC) is a rare, but potentially life-threatening side effect of neutropenia-inducing chemotherapy agents. Generally, its occurrence is attributed to leukemia-associated chemotherapies. Two cases of NE have been reported after the appliance of pemetrexed for treatment of non-small cell lung cancers. To our knowledge, NE has never been reported due to treatment with pemetrexed for malignant pleural mesothelioma (MPM). We present a case of MPM in a 77-year-old male suffering from severe NE one week after the seventeenth cycle of pemetrexed in the course of maintenance therapy for MPM, which could be treated successfully with antibiotic coverage and supportive measures. Concomitantly the patient showed a severe hyperpigmentation of his entire integument sparing the palms of both hands and the soles of his feet. After exclusion of alternative causes of skin hyperpigmentation, a pemetrexed-induced cutaneous hyperpigmentation was assumed according to two previous case reports. A combination of both pemetrexed-induced side effects in one patient has not been reported to date.
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[162]
TÍTULO / TITLE: - Silenced Expression of NFKBIA in Lung Adenocarcinoma Patients with a Never-smoking History.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Med Okayama. 2013 Feb;67(1):19-24.
AUTORES / AUTHORS: - Furukawa M; Soh J; Yamamoto H; Ichimura K; Shien K; Maki Y; Muraoka T; Tanaka N; Ueno T; Asano H; Tsukuda K; Toyooka S; Miyoshi S
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Okayama University Hospital, Okayama 700-8558, Japan.
RESUMEN / SUMMARY: - Nuclear factor of kappa-light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA), which is a tumor suppressor gene, was found to be silenced in lung adenocarcinomas. We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. NFKBIA expression was evaluated using immunohistochemistry. NFKBIA expression was negative in 16 of the 101 samples (15.8%). EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%), 1 (1.0%), and 2 (2.0%) of the 101 samples, respectively, in a completely mutually exclusive manner. Negative NFKBIA expression was observed significantly more frequently among the tumors with none of the three genetic alterations compared to those with such alterations (p0.009). In addition, negative NFKBIA expression was significantly more frequent among the EGFR-wild type samples compared to the EGFR-mutant samples (p0.013). In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion.
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[163]
TÍTULO / TITLE: - Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thorax. 2013 Feb 11. doi: 10.1136/thoraxjnl-2012-202297.
●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2012-202297
AUTORES / AUTHORS: - Walters S; Maringe C; Coleman MP; Peake MD; Butler J; Young N; Bergstrom S; Hanna L; Jakobsen E; Kolbeck K; Sundstrom S; Engholm G; Gavin A; Gjerstorff ML; Hatcher J; Johannesen TB; Linklater KM; McGahan CE; Steward J; Tracey E; Turner D; Richards MA; Rachet B
INSTITUCIÓN / INSTITUTION: - Cancer Research UK Cancer Survival Group, Department of Non Communicable Disease Epidemiology , London School of Hygiene and Tropical Medicine, , London, UK.
RESUMEN / SUMMARY: - BACKGROUND: The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004-2007. METHODS: Routinely collected population-based data were obtained on all adults (15-99 years) diagnosed with lung cancer in 2004-2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. RESULTS: Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. CONCLUSIONS: There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.
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[164]
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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[165]
TÍTULO / TITLE: - CT-guided thin needles percutaneous cryoablation (PCA) in patients with primary and secondary lung tumors: A preliminary experience.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Radiol. 2013 May;82(5):e246-53. doi: 10.1016/j.ejrad.2012.12.010. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2012.12.010
AUTORES / AUTHORS: - Pusceddu C; Sotgia B; Fele RM; Melis L
INSTITUCIÓN / INSTITUTION: - Division of Interventional Radiology, Department of Oncological Radiology, Businco Hospital, Regional Referral Center for Oncologic Diseases, Cagliari, Zip code 09100, Italy. Electronic address: clapusceddu@gmail.com.
RESUMEN / SUMMARY: - PURPOSE: To report the data of our initial experience with CT-guided thin cryoprobes for percutaneous cryoablation (PCA) in patients with primary and secondary pulmonary tumors. MATERIAL AND METHODS: CT-guided thin needles PCA was performed on 34 lung masses (11 NSCLC=32%; 23 secondary lung malignancies=68%) in 32 consecutive patients (24 men and 8 women; mean age 67+/-10 years) not suitable for surgical resection. Lung masses were treated using two types of cryoprobes: IceRod and IceSeed able to obtain different size of iceball. The number of probes used ranged from 1 to 5 depending on the size of the tumor. After insertion of the cryoprobes into the lesion, the PCA were performed with two 2 (91%) or 3 (9%) cycles each of 12min of freezing followed by a 4min active thawing phase and a 4min passive thawing phase for each one for all treatments. RESULTS: All cryoablation sessions were successfully completed. All primary and metastatic lung tumors were ablated. No procedure-related deaths occurred. Morbidity consisted of 21% (7 of 34) pneumothorax and 3% (1 of 34) cases asymptomatic small pulmonary hemorrhage, respectively, all of CTCAE grade 1 (Common Terminology Criteria for Adverse Events). Low density of entire lesion, central necrosis and solid mass appearance were identify in 21 (62%), 7 (21%) and 6 (17%) of cryoablated tumors, respectively. No lymphadenopathy developed in the region of treated lesions. Technical success (complete lack of enhancement) was achieved in 82%, 97% and 91% of treated lesions at 1-, 3- and 6-months CT follow-up scan, respectively (p<.000). Comparing the tumor longest diameter between the baseline and at 6 month CT images, technical success was revealed in 92% cases (p<.000). CONCLUSION: Our preliminary experience suggests that PCA is a feasible treatment option. Well-designed clinical trials with a larger patient population are necessary to further investigate the long-term results and prognostic factors.
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[166]
TÍTULO / TITLE: - Dose escalation, not “new biology,” can account for the efficacy of stereotactic body radiation therapy with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1159-60. doi: 10.1016/j.ijrobp.2012.11.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.11.003
AUTORES / AUTHORS: - Brown JM; Brenner DJ; Carlson DJ
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California. Electronic address: mbrown@stanford.edu.
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[167]
TÍTULO / TITLE: - Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Mar 21. pii: S0360-3016(13)00174-0. doi: 10.1016/j.ijrobp.2012.12.027.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.12.027
AUTORES / AUTHORS: - Weiss E; Fatyga M; Wu Y; Dogan N; Balik S; Sleeman W 4th; Hugo G
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia. Electronic address: eweiss@mcvh-vcu.edu.
RESUMEN / SUMMARY: - PURPOSE: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. METHODS AND MATERIALS: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). RESULTS: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. CONCLUSIONS: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.
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[168]
TÍTULO / TITLE: - FDG-PET Imaging in Patients With Pulmonary Carcinoid Tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279f0f5
AUTORES / AUTHORS: - Moore W; Freiberg E; Bishawi M; Halreiner MS; Matthews R; Baram D; Bilfinger TV
INSTITUCIÓN / INSTITUTION: - From the Department of Radiology, Stony Brook University Medical Center, Stony Brook, NY.
RESUMEN / SUMMARY: - PURPOSE: This study aimed to assess the imaging findings in patients with pathologically proven carcinoid tumors and determine if SUV can help to differentiate typical from atypical (more aggressive) pulmonary carcinoid tumors. PATIENTS AND METHODS: A retrospective review of patients with a biopsy-proven diagnosis of a pulmonary carcinoid tumor at our institution from 2002 to 2010 that had a preoperative PET scan was performed after institutional review board approval was obtained. PET results, including SUV uptake and location, were recorded as well as all data from pathology reports. Carcinoids were considered to be more aggressive if they showed pathological diagnosis consistent with atypical carcinoid, lymph node invasion, poor histological grade (poorly differentiated), or evidence of systemic metastases. Atypical carcinoid pathology consisted of focal necrosis or a higher mitotic index (2-10 per square millimeter) with features of nests, trabeculae, pleomorphic cells, or dense hyperchromasia. SUV uptake was then evaluated and compared between the typical and atypical carcinoid groups using nonparametric statistical methods. RESULTS: We identified 29 patients from 2002 to 2010 at our institution with a pathological diagnosis of pulmonary carcinoid. Twenty-three were histopathologically typical, and the other 6 showed atypia. Mean (SD) nodule size was 2.4 (1.3) cm in the typical group versus 5.0 (3.2) cm in the atypical group (P = 0.065). Mean (SD) SUV uptake in the typical carcinoid group was 2.7 (1.6) and in the atypical group the SUV was 8.1 (4.1) (P < 0.01). A cutoff SUV of 6 or greater is predictive of malignancy (odds ratio, 23.6; P < 0.01), as well as a nodule size of 3.5 cm or greater (odds ratio, 5.1; P = 0.024). CONCLUSIONS: Preoperative PET imaging result is frequently positive in carcinoid tumors, and the biological behavior correlates well with SUV; however, size is not as strong of a predictor of malignancy. Size of 3.5 cm or greater and SUV of 6 or greater have a predictive value of greater than 95% for malignant histology.
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[169]
TÍTULO / TITLE: - Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28090.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28090
AUTORES / AUTHORS: - Pros E; Lantuejoul S; Sanchez-Verde L; Castillo SD; Bonastre E; Suarez-Gauthier A; Conde E; Cigudosa JC; Lopez-Rios F; Torres-Lanzas J; Castellvi J; Cajal SR; Brambilla E; Sanchez-Cespedes M
INSTITUCIÓN / INSTITUTION: - Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, España.
RESUMEN / SUMMARY: - Growth factor receptors (GFRs) are amenable to therapeutic intervention in cancer and it is important to select patients appropriately. One of the mechanisms for activation of GFRs is gene amplification (GA) but discrepancies arising from the difficulties associated with data interpretation and the lack of agreed parameters confound the comparison of results from different laboratories. Here, we attempt to establish appropriate conditions for standardization of the determination of GA in a panel of GFRs. A NSCLC tissue microarray panel containing 302 samples was screened for alterations at ALK, FGFR1, FGFR2, FGFR3, ERBB2, IGF1R, KIT, MET and PDGFRA by FISH, immunostaining and/or real-time quantitative RT-PCR. Strong amplification was found for FGFR1, ERBB2, KIT/PDFGRA and MET, with frequencies ranging from 1 to 6%. Thresholds for overexpression and GA were established. Strong immunostaining was found in most tumors with ERBB2, MET and KIT amplification, although some tumors underwent strong immunostaining in the absence of GA. KIT and PDFGRA were always coamplified, but only one tumor showed PDGFRA overexpression, indicating that KIT is the main target. Amplification of FGFR1 predominated in squamous cell carcinomas, although the association with overexpression was inconclusive. Interestingly, alterations at ALK, MET, EGFR, ERBB2 and KRAS correlated with augmented levels of phospho-S6 protein, suggesting activation of the mTOR pathway, which may prove useful to pre-select tumors for testing. Overall, here, we provide with parameters for the determination of GA at ERBB2, MET, KIT and PDGFRA which could be implemented in the clinic to stratify lung cancer patients for specific treatments.
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[170]
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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[171]
TÍTULO / TITLE: - New insights into understanding the mechanisms, pathogenesis, and management of malignant mesotheliomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Pathol. 2013 Apr;182(4):1065-77. doi: 10.1016/j.ajpath.2012.12.028. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.12.028
AUTORES / AUTHORS: - Mossman BT; Shukla A; Heintz NH; Verschraegen CF; Thomas A; Hassan R
INSTITUCIÓN / INSTITUTION: - Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont. Electronic address: brooke.mossman@uvm.edu.
RESUMEN / SUMMARY: - Malignant mesothelioma (MM) is a relatively rare but devastating tumor that is increasing worldwide. Yet, because of difficulties in early diagnosis and resistance to conventional therapies, MM remains a challenge for pathologists and clinicians to treat. In recent years, much has been revealed regarding the mechanisms of interactions of pathogenic fibers with mesothelial cells, crucial signaling pathways, and genetic and epigenetic events that may occur during the pathogenesis of these unusual, pleiomorphic tumors. These observations support a scenario whereby mesothelial cells undergo a series of chronic injury, inflammation, and proliferation in the long latency period of MM development that may be perpetuated by durable fibers, the tumor microenvironment, and inflammatory stimuli. One culprit in sustained inflammation is the activated inflammasome, a component of macrophages or mesothelial cells that leads to production of chemotactic, growth-promoting, and angiogenic cytokines. This information has been vital to designing novel therapeutic approaches for patients with MM that focus on immunotherapy, targeting growth factor receptors and pathways, overcoming resistance to apoptosis, and modifying epigenetic changes.
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[172]
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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[173]
TÍTULO / TITLE: - Evaluation of 4-dimensional Computed Tomography to 4-dimensional Cone-Beam Computed Tomography Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Feb 22. pii: S0360-3016(13)00002-3. doi: 10.1016/j.ijrobp.2012.12.023.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.12.023
AUTORES / AUTHORS: - Balik S; Weiss E; Jan N; Roman N; Sleeman WC; Fatyga M; Christensen GE; Zhang C; Murphy MJ; Lu J; Keall P; Williamson JF; Hugo GD
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
RESUMEN / SUMMARY: - PURPOSE: To evaluate 2 deformable image registration (DIR) algorithms for the purpose of contour mapping to support image-guided adaptive radiation therapy with 4-dimensional cone-beam CT (4DCBCT). METHODS AND MATERIALS: One planning 4D fan-beam CT (4DFBCT) and 7 weekly 4DCBCT scans were acquired for 10 locally advanced non-small cell lung cancer patients. The gross tumor volume was delineated by a physician in all 4D images. End-of-inspiration phase planning 4DFBCT was registered to the corresponding phase in weekly 4DCBCT images for day-to-day registrations. For phase-to-phase registration, the end-of-inspiration phase from each 4D image was registered to the end-of-expiration phase. Two DIR algorithms-small deformation inverse consistent linear elastic (SICLE) and Insight Toolkit diffeomorphic demons (DEMONS)-were evaluated. Physician-delineated contours were compared with the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance, and false-positive and false-negative indices. The DIR results are compared with rigid registration of tumor. RESULTS: For day-to-day registrations, the mean DSC was 0.75 +/- 0.09 with SICLE, 0.70 +/- 0.12 with DEMONS, 0.66 +/- 0.12 with rigid-tumor registration, and 0.60 +/- 0.14 with rigid-bone registration. Results were comparable to intraobserver variability calculated from phase-to-phase registrations as well as measured interobserver variation for 1 patient. SICLE and DEMONS, when compared with rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the average symmetric distance to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79, respectively, compared with rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. CONCLUSIONS: Deformable image registration achieved comparable accuracy to reported interobserver delineation variability and higher accuracy than rigid-tumor registration. Deformable image registration performance varied with the algorithm and the patient.
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[174]
TÍTULO / TITLE: - Suboptimal health literacy in patients with lung cancer or head and neck cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Support Care Cancer. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1780-0
AUTORES / AUTHORS: - Koay K; Schofield P; Gough K; Buchbinder R; Rischin D; Ball D; Corry J; Osborne RH; Jefford M
INSTITUCIÓN / INSTITUTION: - Department of Cancer Experiences Research, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Victoria, 8006, Australia.
RESUMEN / SUMMARY: - BACKGROUND: Health literacy is the capacity to seek, understand and utilise health information to make informed health decisions. Suboptimal health literacy has been linked to poor health outcomes. This study assessed health literacy in patients treated for head and neck or lung cancer and associations between health literacy and demographic factors and distress levels. METHODS: Consecutive English-speaking patients were approached at Peter MacCallum Cancer Centre. Face-to-face interviews were conducted. Health literacy was assessed using the Shortened Test of Functional Health Literacy in Adults (S-TOFHLA) and Health Literacy Management Scale (HeLMS). Distress was assessed by the Distress Thermometer. RESULTS: Response rate was 73 % (n = 93). Using S-TOFHLA, prevalence of inadequate and marginal health literacy was 5.4 and 6.5 % respectively, and both groups were associated with older age (p = 0.043) and low education level (p = 0.009). Specific assessment of S-TOFHLA revealed that 70 % could not interpret prescription labels. HeLMS reported that 17 % had health literacy difficulties. Low scores on domains of HeLMS were associated with lower education level (p < 0.05) but younger age (p < 0.05). Distress was not associated with S-TOFHLA scores but related to low scores in two domains of HeLMS (p < 0.05). CONCLUSION: Using two different measures, a substantial proportion of patients have poor health literacy abilities and may experience difficulties in accessing health services.
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[175]
TÍTULO / TITLE: - Cytokine effects on cell survival and death of A549 lung carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cytokine. 2013 Mar;61(3):816-25. doi: 10.1016/j.cyto.2013.01.017. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cyto.2013.01.017
AUTORES / AUTHORS: - Kastamoulas M; Chondrogiannis G; Kanavaros P; Vartholomatos G; Bai M; Briasoulis E; Arvanitis D; Galani V
INSTITUCIÓN / INSTITUTION: - Department of Anatomy-Histology-Embryology, Faculty of Medicine, University of Ioannina, Greece.
RESUMEN / SUMMARY: - PURPOSE: IL-13, TNF-alpha and IL-1beta have various effects on lung cancer growth and death, but the signaling pathways mediating these effects have not been extensively analyzed. Therefore, the effects of IL-13, TNF-alpha and IL-1beta alone, and in combination with Fas, on cell viability and death as well as major signaling pathways involved in these effects were investigated in A549 lung carcinoma cells. RESULTS: Using MTT and flow cytometry, IL-13, TNF-alpha and IL-1beta pretreatment decreased Fas-induced cell death. These anti-cell death effects were attenuated by pretreatment with inhibitors of Nuclear factor-kappaB [NF-kappaB], Phoshatidylinositole-3 kinase [PI3-K], JNK, p38 and ERK1/2 pathways. Using Western blot, IL-13, TNF-alpha and IL-1beta treated cells showed time-dependent expression of p-ERK1/2, p-p38, p-JNK, p-Akt and p-IkappaBalpha proteins, decreased IkappaBalpha protein expression, no cleavage of Caspase-3 and PARP1 proteins and no notable alterations of Fas protein. IL-13 and TNF-alpha treated cells showed time-dependent increase of FLIP expression. CONCLUSION: IL-13, TNF-alpha and IL-1beta attenuate the pro-cell death effects of Fas on A549 cells, at least partially, by pathways involving the NF-kappaB, PI3-K and MAP kinases, but not by alterations of Fas protein expression. The IL-13 and TNF-alpha cell survival effects may also be due to increased expression of FLIP protein.
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[176]
TÍTULO / TITLE: - Pulmonary epithelioid haemangioendothelioma studies in vitro and in vivo: new diagnostic and treatment methods.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - In Vivo. 2013 Mar-Apr;27(2):221-5.
AUTORES / AUTHORS: - Palfoldi R; Radacs M; Csada E; Molnar Z; Pinter S; Tiszlavicz L; Molnar J; Valkusz Z; Somfay A; Galfi M
INSTITUCIÓN / INSTITUTION: - Department of Pulmonology, Faculty of Medicine, University of Szeged, Alkotmany street 36, H-6772, Deszk, Hungary. palfoldi@deszkikorhaz.hu
RESUMEN / SUMMARY: - BACKGROUND: Pulmonary epithelioid haemangioendothelioma is a rare endothelial tumour without standard treatment. For this reason, our aim is to present contemporary research outlining new therapeutic possibilities; thus in vitro and in vivo methods were combined. PATIENTS AND METHODS: Pulmonary epithelioid haemangioendothelioma was diagnosed in a 49-year-old female patient. A bronchial excision was obtained from a parenchymal lesion, and the excised sample was manipulated with in vitro-standardized experiments to support the diagnostic and therapeutic procedures. RESULTS: according to in vitro examination of tumour pulmonum and metastases from bone, carboplatin, docetaxel and pharmarubicin was the most effecient treatment modality. CONCLUSION: Currently, pulmonary epithelioid haemangioendothelioma does not have any standard treatment; the most efficient therapeutic regimen was gradually developed by combining in vitro and in vivo methods, which proved to be an efficient therapeutic modality hitherto.
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[177]
TÍTULO / TITLE: - Prognostic Value of the New International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Lung Adenocarcinoma Classification on Death and Recurrence in Completely Resected Stage I Lung Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e31828920c0
AUTORES / AUTHORS: - Hung JJ; Jeng WJ; Chou TY; Hsu WH; Wu KJ; Huang BS; Wu YC
INSTITUCIÓN / INSTITUTION: - *Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan daggerDepartment of Internal Medicine, Chang Gung Memorial Hospital and School of Medicine, Chang Gung University, Taipei, Taiwan double daggerInstitute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan section signDepartment of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ||Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
RESUMEN / SUMMARY: - OBJECTIVE:: This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage I lung adenocarcinoma. METHODS:: Histological classification of 283 patients undergoing surgical resection for stage I lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification after comprehensive histological subtyping with recording of the percentage of each histological component (lepidic, acinar, papillary, micropapillary, and solid) in 5% increments. Their impact on overall survival, recurrence, and postrecurrence survival was investigated. RESULTS:: The 5-year overall survival and recurrence-free rates were 81.6% and 76.9%, respectively. During follow-up, 57 (20.1%) patients developed recurrence. The 2-year postrecurrence survival rate was 72.3%. The solid predominant group is associated with significant more male sex, higher smoking exposure, larger tumor size, and more poorly differentiated histological grade. Lepidic predominant group had significantly better overall survival (P = 0.002). Micropapillary and solid predominant groups had significantly lower probability of freedom from recurrence (P = 0.004). Older age (P = 0.039), visceral pleural invasion to the surface (PL2) (P = 0.009), and high grade (micropapillary/solid predominant) of the new classification (P = 0.028) were predictors of recurrence in multivariate analysis. The solid predominant group tends to have significantly worse postrecurrence survival (P = 0.074). CONCLUSIONS:: The new adenocarcinoma classification has significant impact on death and recurrence in stage I lung adenocarcinoma. Patients with PL2 and micropapillary/solid predominant pattern have significant higher risk for recurrence. This information is important for patient stratification for aggressive adjuvant chemoradiation therapy.
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[178]
TÍTULO / TITLE: - Stromal plasma cells expressing immunoglobulin G4 subclass in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 1. pii: S0046-8177(13)00016-6. doi: 10.1016/j.humpath.2013.01.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2013.01.002
AUTORES / AUTHORS: - Fujimoto M; Yoshizawa A; Sumiyoshi S; Sonobe M; Kobayashi M; Koyanagi I; Aini W; Tsuruyama T; Date H; Haga H
INSTITUCIÓN / INSTITUTION: - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto 606-8507, Japan.
RESUMEN / SUMMARY: - Inflammatory cell infiltration in tumor stroma may represent the interaction between the tumor and the immune system. The significance of immunoglobulin (Ig) G4+ plasmacytic infiltration, however, is poorly understood. Here, we analyzed the number of stromal IgG4+ plasma cells and the IgG4/IgG ratio of plasma cells in 294 primary non-small cell lung cancers (NSCLCs) using tissue microarray (TMA) and conventional surgical specimens. In TMA, 35 (12%) cases of NSCLC revealed more than 20 IgG4+ plasma cells per high-power field. In surgical specimens, most (97%) of those IgG4+ plasma cell-enriched cases showed obliterative phlebitis or arteritis, one of the key morphologic features of IgG4-related disease, within or at the periphery of the tumor. Clinically, none of the patients showed symptoms associated with IgG4-related systemic diseases. In patients with stage I squamous cell carcinoma, IgG4-enriched stroma was significantly associated with a favorable prognosis (P = .04). In conclusion, considerable IgG4+ plasma cell infiltration can be seen in a minority of cases of NSCLC and might contribute to prognostic modulation of NSCLC.
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[179]
TÍTULO / TITLE: - A Phase I Study of Pomalidomide (CC-4047) in Combination with Cisplatin and Etoposide in Patients with Extensive-Stage Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):423-8. doi: 10.1097/JTO.0b013e318282707b.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318282707b
AUTORES / AUTHORS: - Ellis PM; Jungnelius U; Zhang J; Fandi A; Beck R; Shepherd FA
INSTITUCIÓN / INSTITUTION: - *Juravinski Cancer Centre, Hamilton, Ontario, Canada; daggerMcMaster University, Hamilton, Ontario, Canada; double daggerCelgene Corporation, Summit, New Jersey; section signPrincess Margaret Hospital, Toronto, Ontario, Canada; and paragraph sign University of Toronto, Toronto, Ontario, Canada.
RESUMEN / SUMMARY: - INTRODUCTION: : This phase I/IIA study evaluated the maximum-tolerated dose (MTD), safety, and clinical benefit of pomalidomide, an immunomodulatory drug (IMiD), combined with cisplatin+etoposide chemotherapy, in treatment-naive patients with extensive-stage (ES) small-cell lung cancer (SCLC). METHODS: : In this multicenter, open-label, dose-escalation study, patients received 21-day cycles of oral pomalidomide (1, 3, 5, and 4 mg/day) on days 1 to 14, plus cisplatin 25 mg/m and etoposide 100 mg/m administered intravenously on days 1 to 3; the MTD was determined during cycle 1 (standard 3+3 dose-escalation design), followed by a five-cycle extension phase. RESULTS: : Twenty-two patients with ES SCLC, with a median age of 64.5 years received one or more doses of the study medication. Dose-limiting toxicities included grade 4 cerebral ischemia and grade 5 sepsis (1-mg cohort), grade 4 transient ischemic attack (5-mg cohort), and grade 5 neutropenic infection (5-mg cohort). The MTD for pomalidomide was 4 mg/day. In the MTD phase, the most common pomalidomide-related adverse events (AEs) were fatigue (72.7%), nausea (45.5%), and neutropenia (40.9%); 31.8% of patients experienced pomalidomide-related serious AEs and 40.9% cisplatin/etoposide-related serious AEs. Overall response rate was 31.8% (7 of 22); these were partial responses. Stable disease and progressive disease occurred in four patients (18.2%) each. The median response duration was 12.4 weeks. Median overall survival was 49.6 weeks. CONCLUSIONS: : Pomalidomide at the MTD of 4 mg/day plus standard cisplatin+etoposide seems safe in treatment-naive patients with ES SCLC. However, addition of pomalidomide does not seem to improve the therapeutic index of chemotherapy alone.
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[180]
TÍTULO / TITLE: - Osteoporotic vertebral compression fractures: a rare complication of radiotherapy in a patient with lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Imaging. 2013 Mar;37(2):390-2. doi: 10.1016/j.clinimag.2012.05.016. Epub 2012 Jul 9.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.05.016
AUTORES / AUTHORS: - Noel-Savina E; Descourt R
INSTITUCIÓN / INSTITUTION: - Service d’Oncologie Thoracique, CHU Morvan, Brest, France. Electronic address: elise.ns@gmail.com.
RESUMEN / SUMMARY: - The development of bone fractures after radiotherapy is a rare event which mainly concerns the pelvis or the long bones. This complication is unusual in the vertebrae. We describe the case of a 66-year-old male patient with lung cancer who was treated with combined radio-chemotherapy and developed dorsal pain secondary to vertebral compression 4 months after the end of radiotherapy. Investigations led to a diagnosis of post-radiotherapy vertebral osteonecrosis. It is important to differentiate metastatic lesions from radiological complications. It is not possible to differentiate a metastasis from a recent osteoporotic compression fracture by imaging. A bone biopsy may therefore be necessary. Metastatic bone involvement is common in patients with lung cancer. When images are not typical of secondary progression, however, and there is no change in the general state of the patient, evidence of thoracic progression of the tumour or distal progression other than bone, vertebral osteoporotic complications should be considered. It is important that a wrong diagnosis is not made without histological proof of metastasis which has a poor prognosis.
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[181]
TÍTULO / TITLE: - Accelerated hyperfractionated radiotherapy within trimodality therapy concepts for stage IIIA/B non-small cell lung cancer: Markedly higher rate of pathologic complete remissions than with conventional fractionation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer. 2013 Mar 16. pii: S0959-8049(13)00162-7. doi: 10.1016/j.ejca.2013.02.030.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejca.2013.02.030
AUTORES / AUTHORS: - Pottgen C; Eberhardt W; Graupner B; Theegarten D; Gauler T; Freitag L; Abu Jawad J; Wohlschlaeger J; Welter S; Stamatis G; Stuschke M
INSTITUCIÓN / INSTITUTION: - Department of Radiotherapy, West German Tumour Centre, University of Duisburg-Essen, Essen, Germany. Electronic address: christoph.poettgen@uk-essen.de.
RESUMEN / SUMMARY: - BACKGROUND: Radiation dose escalation within definitive radiochemotherapy (RTx/CTx) was not successful for stage III non-small cell lung cancer (NSCLC) using conventional fractionation (CF). Accelerated-hyperfractionation (AHF) counteracts tumour cell repopulation. In this observational study, the effects of neoadjuvant RTx/CTx using AHF or CF were studied by histopathology and using the survival end-point. METHODS: Data from all consecutive lung cancer patients treated with neoadjuvant RTx/CTx and thoracotomy between 08/2000 and 06/2012 were analysed. Patients received induction chemotherapy (cisplatin-doublets) followed by concurrent RTx/CTx using AHF (45Gy/1.5Gy bid) or CF-RTx (46Gy/2Gy qd). For estimating the AHF versus CF treatment effects, multivariate analysis (MA), propensity score weighting (PS), and instrumental variable analysis (IV) were used. FINDINGS: 239 patients were treated, median age 58 (34-78)years, stage II/IIIA/B: 19/88/132, squamous cell/adenocarcinomas/other: 98/107/34; AHF/CF-RTx 112/127 patients. No significant differences between both groups, in tumour related factors (age, gender, Charlson comorbiditiy score, lactate dehydrogenase (LDH), haemoglobin, stage, histopathology and grading), existed. Crude rates of pathologic complete responses (pCR) in AHF and CF groups were 37% and 24% respectively. The dose fractionation effect on pCR was significant (p0.006, PS and IV analyses). There was a significant dependence of pCR on biologically effective dose. pCR also depended on treatment time (MA, p=0.04; PS, p=0.0004). Median treatment time was 22 d or 31 d using AHF or CF (p<0.0001), respectively. Adenocarcinomas had lower pCR rates in comparison to other histologies. Five-year survival of patients with pCR was 65%, independent of the fractionation. INTERPRETATION: This large monoinstitutional analysis demonstrates an increased effect of AHF on pCR of lung cancer which modifies overall survival.
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[182]
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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[183]
TÍTULO / TITLE: - Bone scintigraphy may help differentiate bone sclerotic lesions from osteoblastic metastases in tuberous sclerosis patients with concomitant pulmonary adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Imaging. 2013 Mar;37(2):382-5. doi: 10.1016/j.clinimag.2012.06.004. Epub 2012 Jul 15.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.06.004
AUTORES / AUTHORS: - Song L; Zhang Y; Zhang W
INSTITUCIÓN / INSTITUTION: - The Department of Nuclear Medicine, Peking University Third Hospital, Beijing, The People’s Republic of China.
RESUMEN / SUMMARY: - Tuberous sclerosis (TS) is a multisystem disorder characterized by widespread hamartomas in multiple organs, including the skeleton. We present a case of bone involvement in a patient with TS and concomitant pulmonary adenocarcinoma. Bone scintigraphy is useful in distinguishing the TS bone lesions from osteoblastic metastases.
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[184]
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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[185]
TÍTULO / TITLE: - Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):478-86. doi: 10.1097/JTO.0b013e31828354c8.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31828354c8
AUTORES / AUTHORS: - Labby ZE; Armato SG 3rd; Dignam JJ; Straus C; Kindler HL; Nowak AK
INSTITUCIÓN / INSTITUTION: - *Department of Radiology, The University of Chicago, Chicago, IL; daggerDepartment of Health Studies, The University of Chicago, Chicago, IL; double daggerDepartment of Medicine, The University of Chicago, Chicago, IL; section signDepartment of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; and ||School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
RESUMEN / SUMMARY: - INTRODUCTION: : The purpose of this study was to investigate the continuous changes in three distinct response assessment methods during treatment as a marker of response for patients with mesothelioma. Linear tumor thickness measurements, disease volume measurements, and lung volume measurements (a physiological correlate of disease volumes) were investigated in this study. METHODS: : Serial computed tomography scans were obtained during the course of clinically standard chemotherapy for 61 patients. For each of the 216 computed tomography scans, the aerated lung volumes were segmented using a fully automated method, and the pleural disease volume was segmented using a semiautomated method. Modified Response Evaluation Criteria in Solid Tumors linear-thickness measurements were acquired clinically. Diseased (ipsilateral) lung volumes were normalized by the respective contralateral lung volumes to account for the differences in inspiration between scans for each patient. Relative changes in each metric from baseline were tracked over the course of follow-up imaging. Survival modeling was performed using Cox proportional hazards models with time-varying covariates. RESULTS: : Median survival from pretreatment baseline imaging was 12.7 months. A negative correlation was observed between measurements of lung volume and disease volume, and a positive correlation was observed between linear-thickness measurements and disease volume. As continuous numerical parameters, all three response assessment methods were significant imaging biomarkers of patient prognosis in independent survival models. CONCLUSIONS: : Analysis of trajectories of linear-thickness measurements, disease volume measurements, and lung volume measurements during chemotherapy for patients with mesothelioma indicates that increasing linear thickness, increasing disease volume, and decreasing lung volume are all significantly and independently associated with poor patient prognosis.
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[186]
TÍTULO / TITLE: - Molecular Characterization of Acquired Resistance to the BRAF Inhibitor Dabrafenib in a Patient with BRAF-Mutant Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31828bb1b3
AUTORES / AUTHORS: - Rudin CM; Hong K; Streit M
INSTITUCIÓN / INSTITUTION: - *Johns Hopkins University, Baltimore, Maryland; and daggerGlaxoSmithKline-Oncology, Collegeville, Pennsylvania.
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[187]
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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[188]
TÍTULO / TITLE: - 4pi Noncoplanar Stereotactic Body Radiation Therapy for Centrally Located or Larger Lung Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Mar 20. pii: S0360-3016(13)00163-6. doi: 10.1016/j.ijrobp.2013.02.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2013.02.002
AUTORES / AUTHORS: - Dong P; Lee P; Ruan D; Long T; Romeijn E; Low DA; Kupelian P; Abraham J; Yang Y; Sheng K
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California.
RESUMEN / SUMMARY: - PURPOSE: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4pi planning system. METHODS AND MATERIALS: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4pi plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4pi without violating dose limits set by the clinical plans. The deliverability of 4pi plans was preliminarily tested. RESULTS: Using 4pi plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P</=.001), respectively, and R50 was reduced by more than 50%. Lung V20, V10, and V5 were reduced by 64%, 53%, and 32% (P</=.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4pi plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. CONCLUSIONS: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4pi plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4pi planning may increase efficacy and reduce toxicity.
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[189]
TÍTULO / TITLE: - Single nucleotide polymorphisms, haplotype association and tumour expression of the vascular endothelial growth factor (VEGF) gene with lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gene. 2013 Feb 28. pii: S0378-1119(13)00179-0. doi: 10.1016/j.gene.2013.01.064.
●● Enlace al texto completo (gratuito o de pago) 1016/j.gene.2013.01.064
AUTORES / AUTHORS: - Naykoo NA; Hameed I; Aasif M; Shaffi S; Yousuf Q; Bhat IA; Andrabi IA; Qasim I; Mir JI; Rasool R; Afroze D; Shah S; Shah ZA
INSTITUCIÓN / INSTITUTION: - Department of Immunology & Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India. Electronic address: drniyaznaik@gmail.com.
RESUMEN / SUMMARY: - VEGF contains several polymorphic sites known to influence its expression. We examined the possible association between +405(-634) C>G, +936 C>T, -2578 C>A and lung cancer in 199 Kashmiri patients and 401 healthy controls. VEGF +405 CG, +936 CT+TT and -2578 CA genotypes were significantly associated with lung cancer risk compared to VEGF +405 CC, +936 CC and -2578 AA+CC genotypes [OR=0.07 (0.04-0.13); P<0.0001, OR=0.36 (0.25-0.52); P<0.0001 and 0.08 (0.05-0.13); P<0.0001]. Haplotype analysis revealed that CGA and TGA haplotypes of the VEGF gene conveys the risk for lung cancer [OR=0.18 (0.10-0.33); P<0.0001 and 0.07 (0.03-0.13); P<0.0001]. VEGF expression revealed non-significant association with the genotypes of the three SNPs. In conclusion, the SNPs examined appear to influence lung cancer susceptibility while genotypes of the SNPs don’t appear to have a significant association with VEGF mRNA expression in lung tumours.
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[190]
TÍTULO / TITLE: - Long-Term Outcome of Proton Therapy and Carbon-Ion Therapy for Large (T2a-T2bN0M0) Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318288ab02
AUTORES / AUTHORS: - Iwata H; Demizu Y; Fujii O; Terashima K; Mima M; Niwa Y; Hashimoto N; Akagi T; Sasaki R; Hishikawa Y; Abe M; Shibamoto Y; Murakami M; Fuwa N
INSTITUCIÓN / INSTITUTION: - *Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; daggerDepartment of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Japan; double daggerDepartment of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan; section signDepartment of Radiation Physics, Hyogo Ion Beam Medical Center, Tatsuno, Japan; ||Divisionof Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Japan; and paragraph signCenter for Radiation Oncology, Dokkyo Medical University, Tochigi, Japan.
RESUMEN / SUMMARY: - INTRODUCTION:: Although many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non-small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification. METHODS:: From April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0. RESULTS:: The median follow-up period for living patients was 51 months (range, 24-103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients. CONCLUSION:: Particle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible.
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[191]
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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[192]
TÍTULO / TITLE: - Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer.
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/mds647
AUTORES / AUTHORS: - Zielinski C; Knapp S; Mascaux C; Hirsch F
INSTITUCIÓN / INSTITUTION: - Central European Cooperative Oncology Group (CECOG), Vienna.
RESUMEN / SUMMARY: - BackgroundTreatments of non-small-cell lung cancer (NSCLC)-particularly of the squamous subtype-are limited. In this article, we describe the immunomodulatory environment in NSCLC and the potential for therapeutic targeting of the immune system through cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) immune-checkpoint pathway blockade.Materials and methodsWe searched PubMed and presented abstracts for publications describing the clinical benefit of checkpoint blockade in NSCLC.ResultsAntibody-mediated checkpoint molecule blockade is being investigated in NSCLC, and of these approaches, the anti-CTLA-4 antibody ipilimumab has undergone the most extensive clinical study. By targeting the immune system rather than specific antigens, checkpoint blockade agents differ from vaccine therapy. In a phase II study in advanced NSCLC, phased ipilimumab with chemotherapy demonstrated the greatest efficacy in squamous NSCLC. A phase I study of nivolumab, an anti-PD-1 antibody, has suggested that this agent is also active against squamous and non-squamous NSCLC. Ongoing phase III studies are evaluating the therapeutic potential of these agents.ConclusionsAlthough treatment options for NSCLC are limited, a better understanding of the immune profile of this disease has facilitated the development of immunotherapeutics that target checkpoint blockade molecules, and clinical evaluation to date supports combining checkpoint blockade with chemotherapy for squamous NSCLC.
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[193]
TÍTULO / TITLE: - CHFR aberrant methylation involves a subset of human lung adenocarcinoma associated with poor clinical outcomes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Feb 14. pii: S0046-8177(12)00436-4. doi: 10.1016/j.humpath.2012.11.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.11.008
AUTORES / AUTHORS: - Koga T; Takeshita M; Ijichi K; Yano T; Maehara Y; Sueishi K
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Division of Pathophysiological and Experimental Pathology, Graduate School of Medical Sciences, Kyushu University 812-8582, Fukuoka, Japan; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: takaomi@pathol1.med.kyushu-u.ac.jp.
RESUMEN / SUMMARY: - Excluding epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion, the genetic alterations involved in lung adenocarcinogenesis, especially those linked to poor clinical outcomes, are still unknown. In this study, we analyzed abnormal checkpoint gene with forkhead-associated domain and ring finger (CHFR) methylation along with the above 3 mutations in 165 lung adenocarcinomas, evaluated the spectrum of each molecular abnormality, and correlated the results with clinical and pathologic variables. Reverse transcription-polymerase chain reaction assay, reverse transcription-polymerase chain reaction followed by direct DNA sequencing, and methylation-specific polymerase chain reaction were performed to detect these 3 mutations and CHFR hypermethylation. The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7%) or 16 (10%) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29%) or 13 (8%) cases, respectively. EGFR mutations occurred in patients who were negative for both CHFR hypermethylation and KRAS mutation. Among the 4 genetic or epigenetic abnormalities, only CHFR hypermethylation was significantly correlated with poor prognosis and lymphatic vessel invasion (P = .024). Histopathologically, the molecular abnormality that correlated with alveolar-destructive growth was the CHFR hypermethylation rather than the EGFR mutation (P = .03). Our results demonstrate that CHFR hypermethylation maybe one of the molecular abnormalities involved in a subset of lung adenocarcinomas with poor prognoses that might be induced by destructive growth and lymphatic vessel invasion of carcinoma cells. Thus, CHFR abnormality might be pursued as a novel therapeutic target against lung adenocarcinoma without an already-known mutation.
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[194]
- CASTELLANO -
TÍTULO / TITLE:Strategies de prise en charge des metastases cerebrales des malades atteints de cancers bronchiques primitifs<!--<RunningTitle>Metastases cerebrales et cancer bronchique primitif : strategies de prise en charge</RunningTitle>-->
TÍTULO / TITLE: - Management of brain metastases for lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bull Cancer. 2013 Mar 1;100(3):303-308.
●● Enlace al texto completo (gratuito o de pago) 1684/bdc.2013.1721
AUTORES / AUTHORS: - Barlesi F; Khobta N; Tallet A; Goncalves A; Azria D; Spano JP; Carpentier AF; Regis J; Metellus P
INSTITUCIÓN / INSTITUTION: - Aix-Marseille universite, Assistance publique-Hopitaux de Marseille, service d’oncologie multidisciplinaire et innovations therapeutiques, Hopital Nord, chemin des Bourrelly, 13915 Marseille Cedex 20, France, Groupe de recherche sur la prise en charge des metastases cerebrales (GRPCMac), France.
RESUMEN / SUMMARY: - Brain metastases from primary lung cancer represent 40% of all brain metastases. On the other hand, 10 to 80% of primary lung cancer patients will present with synchronous or metachronous brain metastases. Management of these patients is therefore a big challenge. The management will depend on the circumstances of diagnosis (symptomatic or not), the cancer history (synchronous or metachronous brain metastases), the histology and the number of lesions.
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[195]
TÍTULO / TITLE: - Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Mar;145(3):683-90; discussion 690-1. doi: 10.1016/j.jtcvs.2012.12.051.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2012.12.051
AUTORES / AUTHORS: - Hamaji M; Allen MS; Cassivi SD; Deschamps C; Nichols FC; Wigle DA; Shen KR
INSTITUCIÓN / INSTITUTION: - Division of General Thoracic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
RESUMEN / SUMMARY: - OBJECTIVE: To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). METHODS: Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with chi(2) test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. RESULTS: The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. CONCLUSIONS: Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.
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[196]
TÍTULO / TITLE: - Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinomas: Relationship with CT Characteristics and Histologic Subtypes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiology. 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13112553
AUTORES / AUTHORS: - Lee HJ; Kim YT; Kang CH; Zhao B; Tan Y; Schwartz LH; Persigehl T; Jeon YK; Chung DH
INSTITUCIÓN / INSTITUTION: - Departments of Radiology and Pathology, Seoul National University Hospital, 28 Yeongeon-dong, Chongno-gu, Seoul 110-744, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Cancer Research Institute, Xenotransplantation Research Center, Clinical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Clinical Radiology, University Hospital Munster, Munster, Germany.
RESUMEN / SUMMARY: - Purpose:To retrospectively identify quantitative computed tomographic (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected lung adenocarcinomas stratified by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) classification in an East Asian cohort of patients known to have a high prevalence of EGFR mutations.Materials and Methods:An institutional review board approved this study and waived informed consent. In 153 surgically resected lung adenocarcinomas, EGFR mutation was determined by direct DNA sequencing. Histologic subtype was classified according to IASLC/ATS/ERS classification of lung adenocarcinoma. At preoperative chest CT, the percentage of ground-glass opacity (GGO) volume and total tumor volume of each tumor were measured by using a semiautomated algorithm. Distribution of EGFR mutation according to histologic subtype, percentage of GGO volume, and total tumor volume was evaluated by using the Fisher exact test, the Student t test, trend analysis, and multiple logistic regression analysis.Results:Exon 21 missense mutation was more frequent in lepidic predominant adenocarcinomas than in other histologic subtypes (odds ratio, 3.44; 95% confidence interval: 1.53, 7.74; P = .003). GGO volume percentage in tumors with exon 21 missense mutation (61.7% +/- 31.9 [standard deviation]) was significantly higher than that in EGFR wild-type tumors (30.0% +/- 38.5) (P = .0001) and exon 19-mutated tumors (28.9% +/- 37.7) (P = .0006). A significant trend of prevalence of exon 21 missense mutation increasing along with increasing GGO volume (P = .0008) was found.Conclusion:GGO volume percentage in tumors with exon 21 missense mutation was significantly higher than that in tumors with other EGFR mutation status. This can be related to the fact that exon 21 missense mutation was significantly more frequent in lepidic predominant adenocarcinomas, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma, according to IASLE/ATS/ERS classification.© RSNA, 2013Supplemental material: radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13112553/-/DC1.
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[197]
TÍTULO / TITLE: - Simvastatin prevents proliferation and bone metastases of lung adenocarcinoma in vitro and in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasma. 2013;60(3):240-6. doi: 10.4149/neo_2013_032.
●● Enlace al texto completo (gratuito o de pago) 4149/neo_2013_032
AUTORES / AUTHORS: - Liu H; Wang Z; Li Y; Li W; Chen Y
RESUMEN / SUMMARY: - Objectives: To explore the mechanism about how HMG-CoA reductase (HMGR) inhibitor inhibit proliferation and bone metastases of lung adenocarcinoma in vitro and in vivo. Methods: The HMGR inhibitor simvastatin, human lung cancer cell line A549 and Balb/c nude mouse were used in this study. The mice were randomly divided into 2 groups: control group (0.9% NaCl solution, i.v.) and simvastatin group (5mg/kg simvastatin, i.v.). Ascratch assay using A549 cell monolayer was also tested. An invasion assay using collagen-coated membrane in trans-wells was applied to evaluate the effect of simvastatin on the metastatic potential of A549 cells in vitro. The expressions of CD44, PUMA, P53, MMP2 and MMP9 were determined by real-time PCR and western blotting; the phosphorylation status of MAPK/ERK signaling parthway was investigated by western blot. .Results: Compared with the control group, the migration of A549 cells in simvastatin-treated group was markedly inhibited (p </= 0.01). Untreated A549 cells showed marked invasion, while simvastatin significantly inhibited the invasion of tumor cells (p </= 0.001). Incubation of A549 cells with simvastatin significantly reduced the levels of CD44, MMP2 and MMP9 (p <0.01), while significantly increased p53 (p < 0.01). Simvastatin significantly inhibits tumor growth and bone metastasis in lung cancer xenograft mouse model, simvastatin can inhibit the kinase phosphorylation inMAPK/ERK signaling parthway. Conclusions: The HMGR inhibitor simvastatin prevents proliferation and osteolytic bone metastases of lung adenocarcinoma cells in vitro and vivo. Its mechanism may be associated with regulation of CD44, P53, MMP family and inactivation of MAPK/ERK signaling parthway. Keywords: simvastatin, bone metastases, lung carcinoma, p53, CD44, MAPK/ERK.
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[198]
TÍTULO / TITLE: - The role of surgical cytoreduction in the treatment of malignant pleural mesothelioma: Meeting summary of the International Mesothelioma Interest Group Congress, September 11-14, 2012, Boston, Mass.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Apr;145(4):909-10. doi: 10.1016/j.jtcvs.2013.01.039. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2013.01.039
AUTORES / AUTHORS: - Rusch V; Baldini EH; Bueno R; De Perrot M; Flores R; Hasegawa S; Klepetko W; Krug L; Lang-Lazdunski L; Pass H; Weder W; Sugarbaker DJ
INSTITUCIÓN / INSTITUTION: - Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.
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[199]
TÍTULO / TITLE: - Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1332-9. doi: 10.1016/j.ijrobp.2012.10.011. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijrobp.2012.10.011
AUTORES / AUTHORS: - Pang Q; Wei Q; Xu T; Yuan X; Lopez Guerra JL; Levy LB; Liu Z; Gomez DR; Zhuang Y; Wang LE; Mohan R; Komaki R; Liao Z
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center; Department of Radiation Oncology and Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
RESUMEN / SUMMARY: - PURPOSE: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade >/=2 or >/=3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. RESULTS: Grade >/=3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade >/=3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell’s C statistic. CONCLUSIONS: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.
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[200]
TÍTULO / TITLE: - Rapid Response of Brain Metastasis to Crizotinib in a Patient with ALK Rearrangement-Positive Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):e32-3. doi: 10.1097/JTO.0b013e3182843771.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182843771
AUTORES / AUTHORS: - Kaneda H; Okamoto I; Nakagawa K
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
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[201]
TÍTULO / TITLE: - Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Chest Med. 2013 Mar;34(1):99-111. doi: 10.1016/j.ccm.2012.12.005. Epub 2013 Jan 17.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ccm.2012.12.005
AUTORES / AUTHORS: - Haas AR; Sterman DH
INSTITUCIÓN / INSTITUTION: - Section of Interventional Pulmonology and Thoracic Oncology, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, 833 West Gates Building, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.
RESUMEN / SUMMARY: - There is evidence that improved treatments of malignant pleural mesothelioma are increasing the quality and quantity of life for patients with mesothelioma. Multimodality treatment programs that combine maximal surgical cytoreduction with novel forms of radiation therapy and more effective chemotherapy combinations may offer significant increases in survival for certain subgroups of patients with mesothelioma. Lung-sparing surgery may allow improvements in pulmonary function after surgery-based multimodality therapy, and potential longer overall survival than that seen with extrapleural pneumonectomy. Experimental treatments provide hope for all patients with mesothelioma, and in the future may be combined with standard therapy in multimodality protocols.
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[202]
TÍTULO / TITLE: - Esophagitis: a novel adverse event of crizotinib in a patient with ALK-positive non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):e23-4. doi: 10.1097/JTO.0b013e31827e2451.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827e2451
AUTORES / AUTHORS: - Srivastava N; VanderLaan PA; Kelly CP; Costa DB
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
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[203]
TÍTULO / TITLE: - Invited commentary: the etiology of lung cancer in men compared with women.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Epidemiol. 2013 Apr 1;177(7):613-6. doi: 10.1093/aje/kws444. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1093/aje/kws444
AUTORES / AUTHORS: - Alberg AJ; Wallace K; Silvestri GA; Brock MV
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer death among women in the United States and other Western nations. The predominant cause of lung cancer in women is active cigarette smoking. Secondhand exposure to tobacco smoke is another important cause. The hypothesis that women are more susceptible than men to smoking-induced lung cancer has not been supported by the preponderance of current data, as noted by De Matteis et al. (Am J Epidemiol. 2013;177(7):601-612) in the accompanying article. However, aspects of lung cancer in men and women continue to indicate potential male-female differences in the etiology of lung cancer, based on several observations: 1) among never smokers, women have higher lung cancer incidence rates than men; 2) there is evidence that estrogen may contribute to lung cancer risk and progression; and 3) there are different clinical characteristics of lung cancer in women compared with men, such as the higher percentage of adenocarcinomas in never smokers, the greater prevalence of epidermal growth factor receptor gene (EGFR) mutations in adenocarcinomas among never smokers, and better prognosis. Considered in total, observations such as these offer enticing clues that, even amid cigarette smoking and other commonalities in the etiology of lung cancer in men and women, distinct differences may remain to be delineated that could potentially be of scientific and clinical relevance.
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[204]
TÍTULO / TITLE: - Interstitial Lung Abnormalities in a CT Lung Cancer Screening Population: Prevalence and Progression Rate.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiology. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13120816
AUTORES / AUTHORS: - Jin GY; Lynch D; Chawla A; Garg K; Tammemagi MC; Sahin H; Misumi S; Kwon KS
INSTITUCIÓN / INSTITUTION: - Departments of Radiology and Preventive Medicine, Chonbuk National University Medical School and Hospital, Institute of Medical Science, Research Institute of Clinical Medicine, 634-18 Keumam-Dong, Jeonju, Jeonbuk 561-712, South Korea; Department of Radiology, National Jewish Health, Denver, Colorado; Department of Radiology, Sri Aurobindo Institute of Medical Sciences, Indore, India; Department of Radiology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; Department of Community Health Sciences, Brock University, St. Catharines, Ontario, Canada; Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.
RESUMEN / SUMMARY: - Purpose:To determine the prevalence of interstitial lung abnormalities (ILAs) at initial computed tomography (CT) examination and the rate of progression of ILAs on 2-year follow-up CT images in a National Lung Screening Trial population studied at a single site.Materials and Methods:The study was approved by the institutional review board and informed consent was obtained from all participants. Image review for this study was HIPAA compliant. We reviewed the CT images of 884 cigarette smokers who underwent low-dose CT at a single site in the National Lung Screening Trial. CT findings were categorized as having no evidence of ILA, equivocal for ILA, or ILA. We categorized the type of ILA as nonfibrotic (ground-glass opacity, consolidation, mosaic attenuation), or fibrotic (ground glass with reticular pattern, reticular pattern, honeycombing). We evaluated the temporal change of the CT findings (no change, improvement, or progression) of ILA at 2-year follow-up. A chi2 with Fisher exact test or unpaired t test was used to determine whether smoking parameters were associated with progression of ILA at 2-year follow-up CT.Results:The prevalence of ILA was 9.7% (86 of 884 participants; 95% confidence interval: 7.9%, 11.9%), with a further 11.5% (102 of 884 participants) who had findings equivocal for ILA. The pattern was fibrotic in 19 (2.1%), nonfibrotic in 52 (5.9%), and mixed fibrotic and nonfibrotic in 15 (1.7%) of the 86 participants with ILA. The percentage of current smokers (P = .001) and mean number of cigarette pack-years (P = .001) were significantly higher in those with ILA than those without. At 2-year follow-up of those with ILA (n = 79), findings of nonfibrotic ILA improved in 49% of cases and progressed in 11%. Fibrotic ILA improved in 0% and progressed in 37% of cases.Conclusion:ILA is common in cigarette smokers. Nonfibrotic ILA improved in about 50% of cases, and fibrotic ILA progressed in about 37%.© RSNA, 2013.
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[205]
TÍTULO / TITLE: - The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0697-z
AUTORES / AUTHORS: - Liu Y; Wang L; Lin XY; Wang J; Yu JH; Miao Y; Wang EH
INSTITUCIÓN / INSTITUTION: - Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China.
RESUMEN / SUMMARY: - The objective of the current study was to investigate the expression pattern and clinicopathological significance of differentiated embryo-chondrocyte-expressed gene 1 (DEC1) in patients with non-small-cell lung cancer (NSCLC). In 118 archived NSCLC tissues, the positive rate of DEC1 was reduced in human lung cancer samples (36/118, 30.5 %) compared with adjacent normal lung tissues (106/118, 89.8 %), as measured by immunohistochemical staining. Loss of DEC1 was correlated with poor differentiation (p = 0.005) and high p-TNM stage (p = 0.002). Consistently, downregulation of DEC1 by siRNA knockdown promoted the growth and colony formation in the A549 lung cancer cell line, and overexpression of DEC1 inhibited the growth and colony formation in the BE1 lung cancer cell line. In addition, a significant negative correlation was found between DEC1 and cyclin D1 (p = 0.014) in 118 cases of NSCLC. Knockdown of DEC1 resulted in the upregulation of cyclin D1, and overexpression of DEC1 led to the downregulation of cyclin D1. Together with the observation that DEC1 bound directly to the promoter region of cyclin D1 in A549 cells, these results indicate that loss of DEC1 may promote tumor progression in NSCLC through upregulation of cyclin D1, and DEC1 might serve as a novel therapeutic target of NSCLC.
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[206]
TÍTULO / TITLE: - Distinct Radiosensitivity of Lung Carcinoma Stem-Like Side Population and Main Population Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1388
AUTORES / AUTHORS: - Xia P; Gou WF; Wang JJ; Niu ZF; Chen S; Takano Y; Zheng HC
INSTITUCIÓN / INSTITUTION: - 1 Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, School of Basic Medical Science, China Medical University , Shenyang, P.R. China .
RESUMEN / SUMMARY: - Abstract Purpose: Lung cancer is a leading cause of cancer death worldwide. Efficacy of radiation therapy on lung cancer is hindered by many factors. Among these, both cancer stem-like side population (SP) and main population (MP) cells may contribute to tumorigenesis and resistance to radiation therapy. However, the detailed mechanism responsible for this effect remains unknown. Materials and Methods: The SP and MP cells were obtained from lewis lung carcinoma cells and analyzed the DNA dye (Hoechst 33342) method and flow cytometry. The levels of ABCG2 and CD133 markers were examined by reverse transcription polymerase chain reaction, Western blot, and immunofluorescence. The effects of ionizing radiation (IR) on the growth and apoptosis of SP and MP cells were determined by 3-(4, 5-dimethylthiazol-2-y)-2, 5-diphenylterazolium bromide (MTT), colony formation, and apoptosis assays. Mitochondrial membrane potential and intracellular reactive oxygen species production were measured by flow cytometry. Finally, the expression of Bax, Bcl-xL, Bcl-2, activated caspase-3 and caspase-9 proteins were examined by Western Blot. Results: IR decreased proliferation, increased apoptosis and mitochondria damage in MP, but not in SP cells. Protein levels of Bcl-2 and Bcl-xl were decreased, while Bax expression was increased in MP cells following IR exposure. In addition, increased activation of caspase-3 and caspase-9 were detected after IR exposure in MP cells, but not in SP cells. Conclusions: Our results show that IR decreases proliferation, increases apoptosis, and induces mitochondria damage in MP cells, but not in SP cells, through increased Bax and decreased Bcl-2 and Bcl-xl protein expression. This protein expression pattern induces activation of caspase-3 and caspase-9. This study suggests that IR exposure targets MP cells through a mitochondrial apoptosis pathway. However, more work is required to further confirm these results using in vivo xenograft models. More importantly, further studies are warranted to elucidate the radioresistant mechanisms of SP cells.
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[207]
TÍTULO / TITLE: - Use of Luminex xMAP bead-based suspension array for detecting microRNA in NSCLC tissues and its clinical application.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):792-9. doi: 10.1700/1217.13505.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13505
AUTORES / AUTHORS: - Wang Y; Shi J; Wu Y; Xu W; Wang Q; Zhang J; Jiang M; Gu G
INSTITUCIÓN / INSTITUTION: - Department of Clinical Laboratory, The First Affiliated Hospital of Suzhou University, Laboratory of Clinical Immunology in Jiangsu Province, Suzhou, China. guguohao@yahoo.com.cn
RESUMEN / SUMMARY: - BACKGROUND: We measured the expression of microRNA (miRNA) in non-small cell lung cancer (NSCLC) tissues using the Luminex xMAP bead-based suspension array. We discuss the feasibility of employing this method to detect miRNA in NSCLC and explore its value as a high-throughput miRNA array. METHODS: We performed the methodological analysis of xMAP with oligoribonucleic acid references. We detected the expression of miR-21, miR, miR-31, miR-222, miR-145 and miR 40 NSCLC cancer tissues and adjacent normal tissues by xMAP bead-based suspension array. We selected miR-191 and miR-103 as the house-keeping genes (internal control). We also analyzed the relationship between xMAP and RT-PCR. RESULTS: The methodological analysis parameters of xMAP are quite good. The expression of miR-21, miR, miR-31 and miR-222 was higher in NSCLC tissues than in adjacent tissues, while the expression of miR-145 and miR-126 was lower in NSCLC tissues than in adjacent tissues. The expression of miR-145 and miR-126 decreased with disease progression. The intraassay and interassay coefficients of variation were lower in xMAP than in RT-PCR. xMAP proved cheaper and more flexible in detecting multiple miRNAs of one sample. CONCLUSIONS: The Luminex xMAP bead-based suspension array for detecting miRNA has many advantages, such as allowing a smaller sample size (only 2 muL), no sample amplification, fast detection, high throughput, and flexible combination of multiple detection targets. The high throughput testing technology shows a great advantage in saving time and labor. We found that the Luminex xMAP bead-based suspension array is a good and feasible method for detecting miRNA expression with high-throughput technology.
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[208]
TÍTULO / TITLE: - Progesterone inhibits the migration and invasion of A549 lung cancer cells through membrane progesterone receptor alpha-mediated mechanisms.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 6. doi: 10.3892/or.2013.2336.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2336
AUTORES / AUTHORS: - Xie M; You S; Chen Q; Chen X; Hu C
INSTITUCIÓN / INSTITUTION: - Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer morbidity and mortality in the world. The incidence of lung cancer, particularly lung adenocarcinoma, is increasing in women compared to men. The role of sex hormones in the development of lung cancer has attracted substantial interest, but remains largely unknown. In this study, we demonstrated that membrane progesterone receptor alpha (mPRalpha) was expressed in a lung adenocarcinoma cell line, A549, and was located on the cell membrane. In additional experiments, we found that mPRalpha functioned as an essential mediator for progesterone (P4)-induced inhibitory effects on cell migration and invasion of A549 cells. Furthermore, PP1 (an Src pathway inhibitor), when co-incubated with P4, synchronously enhanced the inhibitory effects of P4 on cell migration and invasion. To explore the mechanisms of inhibition, we found that P4 and PP1 induced a cascade of molecular signaling events, such as dephosphorylation of focal adhesion kinase (FAK) and downregulation of matrix metalloproteinase 9 (MMP-9). Our study provides a mechanistic view on the effects of P4 through mPRalpha-->Src/FAK relevant pathways in human lung adenocarcinoma cells and may aid in the development of novel therapeutic tools for the treatment of lung cancer.
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[209]
TÍTULO / TITLE: - Irradiation-tolerant lung cancer cells acquire invasive ability dependent on dephosphorylation of the myosin regulatory light chain.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS Lett. 2013 Mar 18;587(6):732-6. doi: 10.1016/j.febslet.2013.01.055. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1016/j.febslet.2013.01.055
AUTORES / AUTHORS: - Ishihara S; Yasuda M; Nishioka T; Mizutani T; Kawabata K; Shirato H; Haga H
INSTITUCIÓN / INSTITUTION: - Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, Japan.
RESUMEN / SUMMARY: - Radiotherapy is one of the major treatment modalities for malignancies. However, cells surviving irradiation often display high levels of invasiveness. This study shows that irradiation-tolerant lung adenocarcinoma demonstrates high invasive capability depending on dephosphorylation of the myosin regulatory light chain (MRLC). In a collagen gel overlay condition, low-invasive subclones of lung adenocarcinoma (A549P-3) showed a round morphology and diphosphorylation of MRLC. In contrast, irradiation-tolerant A549P-3 cells (A549P-3IR) displayed high invasiveness and a lower level of MRLC diphosphorylation. In addition, inhibition of MRLC phosphatase activity decreased the invasive activity. These findings suggest that A549P-3IR cells acquire high invasiveness through MRLC dephosphorylation.
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[210]
TÍTULO / TITLE: - Exonic Mutations of TSC2/TSC1 Are Common but Not Seen in All Sporadic Pulmonary Lymphangioleiomyomatosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Respir Crit Care Med. 2013 Mar 15;187(6):663-5.
●● Enlace al texto completo (gratuito o de pago) 1164/ajrccm.187.6.663
AUTORES / AUTHORS: - Badri KR; Gao L; Hyjek E; Schuger N; Schuger L; Qin W; Chekaluk Y; Kwiatkowski DJ; Zhe X
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[211]
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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[212]
TÍTULO / TITLE: - HIF-1alpha up-regulates NDRG1 expression through binding to NDRG1 promoter, leading to proliferation of lung cancer A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biol Rep. 2013 May;40(5):3723-9. doi: 10.1007/s11033-012-2448-4. Epub 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1007/s11033-012-2448-4
AUTORES / AUTHORS: - Wang Q; Li LH; Gao GD; Wang G; Qu L; Li JG; Wang CM
INSTITUCIÓN / INSTITUTION: - Center for Electronic Microscope, Fourth Military Medical University, Xi’an, 710032, China.
RESUMEN / SUMMARY: - Hypoxia-inducible signaling pathway is involved in many pathological processes, such as adaptiveness regulation of plateau environment, myocardial ischemia and tumorigenesis. NDRG1 is a member of the N-myc downregulated gene (NDRG) family, and it has strong hypoxia stress reaction functions. Although the cellular responses to hypoxia are well known, little is known about the interaction between hypoxia-inducible transcription factor (HIF)-1alpha and NDRG1. In this study, we cloned HIF-1alpha CDS, NDRG1 promoter and its truncatures, constructed pCDNA3.0-Hif-1alpha and pGL3-basic-NDRG1. Reporter assay results showed that HIF-1alpha could bind to NDRG1 promoter to activate NDRG1 expression. Further results revealed that -1202 to -450 of NDRG1 promoter is the most important region for HIF-1alpha binding. Then, we constructed NDRG1 stable transfection cell line. Results from MTT, colony-forming assay and flow cytometry showed that NDRG1 overexpression results in more proliferation and less apoptosis of A549 lung cancer cells. Our study elucidates the mechanism of NGRG1 in hypoxia stress reactions and may provide new strategy for hypoxia injuries.
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[213]
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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[214]
TÍTULO / TITLE: - Differential effects of mesenchymal stem cells on a heterogeneous cell population within lung cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1600-3
AUTORES / AUTHORS: - Luo D; Yan X; Liu D; Zhou X; Liu G
INSTITUCIÓN / INSTITUTION: - Department of Respiratory, Southwest Hospital, Third Military Medical University of PLA, Gaotanyan Street 30, Shapingba District, Chongqing, 400038, China.
RESUMEN / SUMMARY: - Although mesenchymal stem cells (MSCs) promote lung cancer growth in vivo, in vitro studies indicate that they inhibit the proliferation of lung cancer cells. Because malignant tumors contain a heterogeneous cell population with variable capacity for self-renewal, the aim of this study was to determine whether the inconsistencies between in vitro and in vivo studies are a result of differential effects of MSCs on the heterogeneous cell population within lung cancer cell lines. Human MSCs were isolated from the bone marrow, and their cell surface antigen expression and multi-lineage differentiation capacity was examined at passage 10. CD133+ cells were isolated from A549 and H446 cell lines using immunomagnetic separation. The effects of MSCs on the growth and microsphere formation of heterogeneous cell populations within two lung cancer cell lines (A549 and H446) were compared. MSCs inhibited the in vitro proliferation of both cell lines, but significantly accelerated tumor formation and stimulated tumor growth in vivo (P < 0.05). In CD133+ cells isolated from both A549 and H446 cells, co-culture with MSCs for 1-3 days significantly increased their proliferation (P < 0.05). MSCs also significantly increased microsphere formation in both cell lines (P < 0.05). Selective stimulation of CD133+ cell growth may account for the discrepant effects of MSCs on lung cancer progression.
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[215]
TÍTULO / TITLE: - Cell uptake of paclitaxel solid lipid nanoparticles modified by cell-penetrating peptides in A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharmazie. 2013 Jan;68(1):47-53.
AUTORES / AUTHORS: - Zhang YL; Zhang ZH; Jiang TY; Ayman-Waddad; Jing-Li; Lv HX; Zhou JP
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China.
RESUMEN / SUMMARY: - The aim of this study was to investigate the cytotoxicity of paclitaxel solid lipid nanoparticles (SLN) modified with stearic acid octaarginine (SA-R8-PTX-SLN) as well as the cellular uptake of coumarin-6-loaded SLN modified with SA-R8 (SA-R8-C6-SLN) in human lung cancer cells, A549. SLN were prepared using a film dispersion method; and then their particle size, zeta potential, morphology, bound efficiency of SAR8, drug loading efficiency, and in vitro release were characterized. SA-R8-PTX-SLN and SA-R8-C6-SLN were incubated with A549 cells to measure their cytotoxicity and cellular uptake, respectively. The results indicated that the cytotoxicity of SA-R8-PTX-SLN was enhanced significantly with the increasing amount of SA-R8 and the cellular uptakes of SLN increased with the incubated concentrations and the incubated time of SLN. In contrast, SA-R8-SLN could significantly enhance the cellular uptake of SLN and the cytotoxicity of PTX in A549 cells. These in vitro results suggest that SA-R8-SLN could be proposed as alternative drug delivery system.
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[216]
TÍTULO / TITLE: - Single file streaming metastasis of Lewis lung carcinoma cells beginning within hours of orthotopic implantion visualized with GFP.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Biochem. 2013 Feb 26. doi: 10.1002/jcb.24516.
●● Enlace al texto completo (gratuito o de pago) 1002/jcb.24516
AUTORES / AUTHORS: - Rashidi B; Moossa AR; Hoffman RM
INSTITUCIÓN / INSTITUTION: - AntiCancer, Inc., 7917 Ostrow St., San Diego, CA 92111; Department of Surgery, University of California, 200 W. Arbor Dr., San Diego, CA 92103-8220.
RESUMEN / SUMMARY: - In this study, we visualized the origin of lung carcinoma metastasis after transducing tumor cells with green fluorescent protein (GFP) and transplanting them orthotopically in the middle lobe of the right lung of nude mice. Metastasis was visualized in live tissue at single cell resolution by GFP-expression as early as 18 hours post-tumor transplant. At this time, cells already had invaded inferiorly via a tubular lymphatic structure crossing the lower lobes of the lung to the ipsilateral diaphragmatic surface. By post-implantation day-2, the ipsilateral lower lobes of the lung were involved with metastatic cells. By post-implantation day-3, the ipsilateral lower lobes of the lung and the ipsilateral diaphragmatic surface were highly involved with streaming metastatic cells trafficking in single file. By day-4 post-implantation, cancer cells invaded across the diaphragm to the contralateral diaphragmatic surface. Metastatic cells then invaded superiorly through a lymphatic vessel to involve the contralateral mediastinal lymph nodes. In this model of lung cancer, the origin of metastasis was an inferior invasion from the implanted tumor via a lymphatic duct to the ipsilateral diaphragmatic surface. The cancer cells from this site invaded on the surface of the diaphragm to the contralateral diaphragmatic surface and proceeded superiorly through a lymphatic duct to contralateral lymph nodes. The use of GFP and the highly metastatic orthotopic lung cancer model allowed the visualization of the origin of metastasis at the single-cell level and demonstrated the critical role of lymphatic ducts and the diaphragmatic surface as the path to the contralateral side. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
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[217]
TÍTULO / TITLE: - Variations in Use of PET among Medicare Beneficiaries with Non-Small Cell Lung Cancer, 1998-2007.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiology. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1148/radiol.12120174
AUTORES / AUTHORS: - Dinan MA; Curtis LH; Carpenter WR; Biddle AK; Abernethy AP; Patz EF Jr; Schulman KA; Weinberger M
INSTITUCIÓN / INSTITUTION: - Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715; Duke Cancer Institute and Departments of Medicine and Radiology, Duke University School of Medicine, Durham, NC.
RESUMEN / SUMMARY: - Purpose:To explore demographic and regional factors associated with the use of positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) and to determine whether their associations with PET use has changed over time.Materials and Methods:The Office of Human Research Ethics at the University of North Carolina and the institutional review board of the Duke University Health System approved (with waiver of informed consent) this retrospective analysis of Surveillance Epidemiology and End Results Medicare data for Medicare beneficiaries given a diagnosis of NSCLC between 1998 and 2007. The primary outcome was change in the number of PET examinations 2 months before to 4 months after diagnosis, examined according to year and sociodemographic subgroup. PET use was compared between demographic and geographic subgroups and between early (1998-2000) and late (2005-2007) cohorts by using chi(2) tests. Factors associated with use of PET during the study period were further examined by using logit and linear probability multivariable regression analyses.Results:The final cohort included 46 544 patients with 46 935 cases of NSCLC. By 2005, more than half of patients underwent one or more PET examinations, regardless of demographic subgroup. In multivariable logistic regression analysis, patients who underwent PET were more likely to be married, nonblack, and younger than 80 years and to live in census tracts with higher education levels or in the Northeast (P < .001 for all). Living within 40 miles of a PET facility was initially associated with undergoing PET (P < .001), but this association disappeared by 2007. Imaging rates increased more rapidly in patients who were nonblack (P </= .01), patients who were younger than 81 years (P < .001), and patients who lived in the Northeast and South (P < .001).Conclusion:PET imaging among Medicare beneficiaries with NSCLC was initially concentrated among nonblack patients younger than 81 years. Despite widespread adoption among all subgroups, differences within demographic subgroups remained.© RSNA, 2013.
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[218]
TÍTULO / TITLE: - The endoplasmic reticulum stress marker CHOP predicts survival in malignant mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Apr 2;108(6):1340-7. doi: 10.1038/bjc.2013.66. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.66
AUTORES / AUTHORS: - Dalton LE; Clarke HJ; Knight J; Lawson MH; Wason J; Lomas DA; Howat WJ; Rintoul RC; Rassl DM; Marciniak SJ
INSTITUCIÓN / INSTITUTION: - 1] Division of Respiratory Medicine, Department of Medicine, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK [2] Cambridge Institute for Medical Research (CIMR), University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK.
RESUMEN / SUMMARY: - Background:Mesothelioma is an incurable cancer originating from the mesothelial cells that line the pleural, peritoneal and pericardial cavities. These cells synthesise large quantities of surface glycoproteins, rendering them dependent upon efficient endoplasmic reticulum (ER) function. When faced with elevated levels of secretory protein load, cells are said to experience ER stress, which has been implicated in the pathogenesis of many human diseases including cancer.Method:We set out to measure markers of ER stress in malignant mesothelioma and to determine whether ER stress signalling correlates with clinical parameters.Results:We observed that expression of the ER stress-responsive transcription factor C/EBP homologous protein (CHOP) correlated with patient survival and remained an independent prognostic variable in pairwise comparisons with all clinical variables tested. The most parsimonious multivariate model in our study comprised only performance status and CHOP staining. In contrast, expression of the ER stress-responsive phosphatase growth arrest and DNA damage 34 (GADD34) correlated with the degree of mesothelial differentiation, being lost progressively in biphasic and sarcomatoid mesotheliomas.Conclusion:Our findings suggest that staining for CHOP provides prognostic information that may be useful in the stratification of patients with mesothelioma. Staining for GADD34 may prove useful in classification of mesothelioma histopathology.
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[219]
TÍTULO / TITLE: - Lipocalin-2 is associated with radioresistance in oral cancer and lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1197-204. doi: 10.3892/ijo.2013.1815. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1815
AUTORES / AUTHORS: - Shiiba M; Saito K; Fushimi K; Ishigami T; Shinozuka K; Nakashima D; Kouzu Y; Koike H; Kasamatsu A; Sakamoto Y; Ogawara K; Uzawa K; Takiguchi Y; Tanzawa H
INSTITUCIÓN / INSTITUTION: - Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
RESUMEN / SUMMARY: - The aim of the present study was to identify a target molecule that could predict the efficacy of radiotherapy in oral squamous cell carcinoma (OSCC). We used DNA microarray analysis to identify differences in gene expression after X-ray irradiation. We compared the gene expression profiles between X-ray (8 Gy)-irradiated Ca9-22 cells (an OSCC-derived cell line) and unirradiated Ca9-22 cells. A total of 167 genes with a 2-fold higher level of expression induced by X-ray irradiation were identified. Lipocalin-2 (LCN2) had the greatest increase in expression after X-ray irradiation, and it was categorized in a network that has cancer-related functions with the Ingenuity Pathway Analysis tool. Upregulated expression of LCN2 mRNA was validated by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. When the LCN2 gene was knocked down in OSCC cells (Ca9-22 and HSC-2) and lung cancer cells (A549) by using small interfering RNA, the radiosensitivity of these cells was enhanced. Our findings suggest that the overexpression of LCN2 is likely associated with radioresistance in oral cancer and lung cancer cells, and that LCN2 expression levels could be used to predict radioresistance. Thus, regulating the expression or function of LCN2 could enhance the radiation response, resulting in a favorable outcome of radiotherapy.
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[220]
TÍTULO / TITLE: - Percutaneous computed tomography-guided lung biopsies: preliminary results using an augmented reality navigation system.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):775-82. doi: 10.1700/1217.13503.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13503
AUTORES / AUTHORS: - Grasso RF; Luppi G; Cazzato RL; Faiella E; D’Agostino F; Beomonte Zobel D; De Lena M
INSTITUCIÓN / INSTITUTION: - Universita Campus Bio-Medico, Via Alvaro Del Portillo 200, Rome, Italy.
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: “Augmented reality” is a technique to create a composite view by augmenting the real intervention field, visualized by the doctor, with additional information coming from a virtual volume generated using computed tomography (CT), magnetic resonance or ultrasound images previously acquired from the same patient. In the present study we verified the accuracy and validated the clinical use of an augmented reality navigation system produced to perform percutaneous CT-guided lung biopsies. METHODS: One hundred and eighty consecutive patients with solitary parenchymal lung lesions, enrolled using a nonrandom enrollment system, underwent percutaneous CT-guided aspiration and core biopsy using a traditional technique (group C, 90 patients) and navigation system assistance (group S, 90 patients). For each patient we recorded the largest lesion diameter, procedure time, overall number of CT scans, radiation dose, and complications. The entire experimental project was evaluated and approved by the local institutional review board (ethics committee). RESULTS: Each procedure was concluded successfully and a pathological diagnosis was reached in 96% of cases in group S and 90% of cases in group C. Procedure time, overall number of CT scans and incident x-ray radiation dose (CTDIvol) were significantly reduced in navigation system-assisted procedures (P <0.001; z = 5.64) compared with traditional CT-guided procedures. The percentage of procedural complications was 14% in group S and 17% in group C. CONCLUSION: The augmented reality navigation system used in this study was a highly safe, technically reliable and effective support tool in percutaneous CT-guided lung biopsy, allowing to shorten the procedure time and reduce the incident x-ray radiation dose to patients and the rate of insufficient specimens. Furthermore, it has the potential to increase the number of procedures executed in the allocated time without increasing the number of complications.
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[221]
TÍTULO / TITLE: - Hepatocyte growth factor promotes lung carcinogenesis in transgenic mice treated with diethylnitrosamine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):895-901.
AUTORES / AUTHORS: - Kojima A; Horiguchi N; Kakizaki S; Takayama H; Mori M
INSTITUCIÓN / INSTITUTION: - Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi Maebashi, Gunma 371-8511, Japan. kakizaki@showa.gunma-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: Hepatocyte growth factor (HGF) was initially discovered as a mitogen for hepatocytes, but it is also known to be related to carcinogenesis in many other organs. However, the role of HGF in lung carcinogenesis is not fully-understood. In this study, we investigated the role of HGF in lung carcinogenesis using HGF transgenic mice. MATERIALS AND METHODS: To elucidate the role of HGF in lung carcinogenesis, 5 mug/g body weight diethylnitrosamine (DEN) were administered intraperitoneally to HGF transgenic (TG) mice and wild-type (WT) mice at 15 days of age. The incidence and number of lung tumors, the expression of HGF and of its receptor (c-Met) were compared between HGF TG and WT mice. RESULTS: HGF overexpression accelerated DEN-induced lung carcinogenesis. Seventy-six percent of TG mice (versus 50% of WT mice) developed malignant lung tumors by 48 weeks. The incidence of lung tumors was significantly higher in the TG mice in comparison with WT mice (p<0.05). Furthermore, the mean diameter and number of tumors in each mouse were significantly higher in the TG mice compared to the WT mice (p<0.01). The northern blotting analyses revealed that there was overexpression of the HGF transgene in the lung tumors of TG mice in comparison with the surrounding non-tumorous lesions. The western blotting analyses of the tumor lesions revealed increased phosphorylation of c-Met. CONCLUSION: Our results suggest that HGF promotes lung carcinogenesis through the autocrine activation of the HGF/c-Met signaling pathway. The HGF/c-Met signaling pathway appears to have vital roles in lung carcinogenesis.
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[222]
TÍTULO / TITLE: - Well-differentiated papillary mesothelioma: a clinicopathological and immunohistochemical study of 18 cases with additional observation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Histopathology. 2013 Apr;62(5):805-13. doi: 10.1111/his.12089.
●● Enlace al texto completo (gratuito o de pago) 1111/his.12089
AUTORES / AUTHORS: - Chen X; Sheng W; Wang J
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - AIMS: To present our experience with 18 cases of well-differentiated papillary mesothelioma (WDPM), with an emphasis on its relationship to adenomatoid tumour and multicystic mesothelioma. METHODS AND RESULTS: Eighteen cases of WDPM were retrieved. Twenty cases of multicystic mesothelioma were selected for comparative study. The WDPM patients comprised 14 females and four males, with age ranging from 18 to 60 years (median 37 years). The tumour involved the abdominal or pelvic peritoneum (14 cases), the pleura (two cases), and the testicular tunica vaginalis (two cases). The majority of WDPMs were incidental findings during surgery for a wide variety of conditions. Histologically, 13 cases were consistent with classical WDPM. Two cases had a combined component of adenomatoid tumour, and three cases contained coexisting areas of multicystic mesothelioma. Among the multicystic mesothelioma cases, four had adenomatoid tumour-like foci present in the stroma. Immunohistochemically, all cases of WDPM and multicystic mesothelioma, as well as the coexisting combined components, were positive for mesothelial markers, with a low Ki67 index. This study also showed that WDPM was negative for epithelial membrane antigen and desmin. CONCLUSIONS: The simultaneous occurrence of WDPM, adenomatoid tumour and multicystic mesothelioma in some cases suggested histogenetic relationships among these three less aggressive mesotheliomas.
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[223]
TÍTULO / TITLE: - Evaluation of Adhesion Force and Binding Affinity of Phytohemagglutinin Erythroagglutinating to EGF Receptor on Human Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Med Chem. 2013 Jan 14.
AUTORES / AUTHORS: - Kuo WT; Dong GC; Yao CH; Huang JY; Lin FH
INSTITUCIÓN / INSTITUTION: - Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan. double@ntu.edu.tw.
RESUMEN / SUMMARY: - PHA-E has been reported to induce cell apoptosis by blocking EGFR on lung cancer cells. It was extracted from red kidney beans. Before clinical application, PHA-E has to be proved to have better affinity to EGFR than that of EGF due to the major in vivo competitor. The study would focus on how PHA-E tightly bind to EGFR and the results would compare with that of EGF. The adhesion force between EGFR and PHA-E, measured by AFM, was 207.14+/-74.42 pN that was higher than that of EGF of 183.65+/-86.93 pN. The binding affinity of EGFR to PHA-E and EGF was 2.4x10(-9)+/-1.4x10(-9) and 7.3x10(-8)+/-2.7x10(-8), respectively, that could be evaluated by equilibrium dissociation constant. The results showed that the binding affinity of PHA-E to EGFR was one order higher than EGF to EGFR. In the results of flow cytometer and confocal microscope, we found that binding efficiency of EGF to EGFR was decrease as the concentration of PHA-E increased. In the study of Western blot, the treatment of PHA-E to A-549 cells was resulted in dose-dependent decrease on EGFR phosphorylation. From the studies, we could conclude that PHA-E had better affinity to EGFR than that of the EGF. The interaction between PHA-E and EGFR could block EGF binding and then inhibit phosphorylation of EGFR on lung cancer cells. PHA-E could be developed into a new therapeutic molecule for lung cancer treatment and could be immobilized on the drug carrier as a targeting molecule to guide therapeutic particles to the tumor site.
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[224]
TÍTULO / TITLE: - Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Oncol. 2013 Feb 5. doi: 10.1002/jso.23321.
●● Enlace al texto completo (gratuito o de pago) 1002/jso.23321
AUTORES / AUTHORS: - Ried M; Potzger T; Braune N; Diez C; Neu R; Sziklavari Z; Schalke B; Hofmann HS
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, University Medical Center Regensburg, Regensburg, Germany. micha.ried@t-online.de.
RESUMEN / SUMMARY: - BACKGROUND: Assessing the pharmacokinetics of intrapleurally administered cisplatin during hyperthermic intrathoracic chemotherapy perfusion (HITHOC) following pleurectomy/decortication in patients with malignant pleural mesothelioma or advanced thymoma with pleural spread. METHODS: Pharmacokinetic analysis (ICP-MS) of intrapleural cisplatin with a dosage of 100 mg/m(2) (n = 5) or 150 mg/m(2) (n = 5) at 42 degrees C perfusate temperature. Simultaneous pleural perfusion fluid and serum samples were collected at the beginning and every 15 min. Serum samples were collected at the end of the operation, 6, 12, and 24 hr postoperative. RESULTS: Mean cisplatin levels in the perfusate slightly decreased during the HITHOC. The mean area under the curve ratios (AUC(perfusate) :AUC(serum) ) of cisplatin were nearly similar. The mean AUCs of cisplatin in the perfusate were approximately 58 and 55 times greater than detected in the serum. The mean peak of cisplatin in the serum was reached after 1 hr of HITHOC. The AUC of cisplatin in the serum did not significantly differ (P = 0.18) between both groups up to 24 hr after perfusion. CONCLUSIONS: HITHOC with cisplatin provides a pharmacological advantage of high local intrapleural cisplatin concentrations. Elevation of the cisplatin dosage to 150 mg/m(2) did not lead to a significant increase of the systemic cisplatin concentration. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.
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[225]
TÍTULO / TITLE: - Pleural Mesothelioma and Occupational Co-exposure to Asbestos, Mineral Wool and Silica.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Respir Crit Care Med. 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1164/rccm.201210-1911OC
AUTORES / AUTHORS: - Lacourt A; Gramond C; Audignon S; Ducamp S; Fevotte J; Gilg Soit Ilg A; Goldberg M; Imbernon E; Brochard P
INSTITUCIÓN / INSTITUTION: - Universite Bordeaux Segalen, Institut de Sante Publique d’Epidemiologie et de Developpement, Laboratoire Sante Travail Environnement, Centre INSERM U897, Equipe Associee en Sante Travail, Bordeaux, France.
RESUMEN / SUMMARY: - RATIONALE: Occupational co-exposure to asbestos and other fibers or particles could modify the carcinogenicity of asbestos with regard to pleural mesothelioma. OBJECTIVES: To estimate associations between pleural mesothelioma and occupational mineral wool and silica exposure and to study the impact of occupational co-exposure on the risk of pleural mesothelioma. METHODS: 1,199 male cases and 2,379 controls were included in a French pooled case-control study. Complete job histories were collected and occupational exposure to asbestos, mineral wool (MW), and silica were assessed by three French job exposure matrices. Unconditional logistic regression models adjusted for age, birth date, and occupational asbestos exposure were used to estimate odds ratios (OR) and 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: A significant association between mesothelioma and MW exposure was observed after adjustment for occupational asbestos exposure. OR for subjects exposed to less than 0.01 f/ml-y was 1.6 (95% CI: 1.2-2.1) and increased to 2.5 (95% CI: 1.8-3.4) for subjects exposed to more than 0.32 f/ml-y. All ORs for silica exposure were around the null. Co-exposure to either asbestos and MW or asbestos and silica seemed to increase the risk of pleural mesothelioma. ORs were 17.6 (95% CI: 11.8-26.2) and 9.8 (95% CI: 4.2-23.2) for subjects exposed to both asbestos and MW and for subjects exposed to both asbestos and silica, respectively, compared to 4.3 (95% CI: 1.9-9.8) for occupational asbestos exposure alone. CONCLUSION: Our results are in favour of an increased risk of pleural mesothelioma for subjects exposed to both asbestos and MW or asbestos and silica.
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[226]
TÍTULO / TITLE: - A phase II study of metronomic oral vinorelbine administered in the second line and beyond in non-small cell lung cancer (NSCLC): a phase II study of the Hellenic Oncology Research Group.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Chemother. 2013 Feb;25(1):49-55. doi: 10.1179/1973947812Y.0000000050.
●● Enlace al texto completo (gratuito o de pago) 1179/1973947812Y.0000000050
AUTORES / AUTHORS: - Kontopodis E; Hatzidaki D; Varthalitis I; Kentepozidis N; Giassas S; Pantazopoulos N; Vardakis N; Rovithi M; Georgoulias V; Agelaki S
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
RESUMEN / SUMMARY: - INTRODUCTION: Frequent administration of low doses of cytotoxic drugs (metronomic chemotherapy) has been suggested to suppress tumour growth possibly by inhibiting angiogenesis. We evaluated a metronomic regimen of oral vinorelbine in pre-treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: Forty-six pre-treated NSCLC patients received oral vinorelbine at a fixed dose of 50 mg three times a week. RESULTS: Treatment was administered as second-line in 12 (26.1%) patients and as third- or further-line in 34 (73.9%). Grade 3-4 neutropenia was observed in 23.9% and febrile neutropenia in 10.9%. Grade 3 fatigue was the most common severe non-hematologic toxicity (10.9%). Response rate was 10.9%; 19.6% achieved disease stabilization. Median tumour progression (TTP) was 2.2 months, median overall survival 9.4 months and the 1-year survival rate was 30.1%. CONCLUSION: The administration of metronomic oral vinorelbine is feasible and results in acceptable clinical efficacy associated with manageable toxicity in a population consisting mostly of heavily pre-treated NSCLC patients.
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[227]
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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[228]
TÍTULO / TITLE: - Generation of an effective anti-lung cancer vaccine by DTPP-mediated photodynamic therapy and mechanistic studies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lasers Med Sci. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s10103-013-1270-0
AUTORES / AUTHORS: - Zheng L; Li Y; Cui Y; Yin H; Liu T; Yu G; Lv F; Yang J
INSTITUCIÓN / INSTITUTION: - Laboratory of Laser Medicine, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, 300192, China.
RESUMEN / SUMMARY: - The objective of this study was to generate an effective vaccine against lung cancer using photosensitizing drug-mediated photodynamic therapy (PDT) and to study the mechanism. The efficiency of a photosensitizing drug (DTPP) was investigated by singlet oxygen yield determination, killing effect analysis, and cell apoptosis induction effect assessment. DTPP-based PDT tumor cell lysates and cell surface antigens obtained from acid-eluted adherent cells were then used as vaccines to prevent lung cancer using LA795 murine lung cells. The optimal protocol for PDT vaccine preparation was selected based on the tumor growth retardation effect of the vaccines, DTPP concentration, illumination dose, and numbers of DTPP-based PDT cells. To study the mechanism of the anti-tumor effect of vaccines, host anti-tumor immune responses were studied, including CD4+/CD8+ ratios and percentage of NK cells and serum cytokine levels. A comparison of cytokine (IFN-gamma and IL-1) secretion from splenocytes and tumor pathologic features from mice immunized with vaccines were compared with controls and showed that the optimal protocol for PDT vaccine preparation was LA795 cells exposed to 10 mug/ml DTPP photosensitizer for 24 h, illuminated with 7.2 J/cm2 at 20 mW/cm2 (630 nm) and 2 x 107 PDT cell lysates injected per mouse. DTPP-based PDT cell lysate vaccination had a significant inhibitory effect on tumor growth based on increased CD4+/CD8+ ratios, NK cell percentages, elevated serum IFN-gamma and IL-1 levels, and lymphocyte aggregation at the edge of tumors. Thus, DTPP-based PDT can induce LA795 cell apoptosis that can generate anti-tumor effects without use of an adjuvant.
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[229]
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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[230]
TÍTULO / TITLE: - Clinical significance of annexin II expression in human non-small cell lung cancer.
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/s13277-013-0715-1
AUTORES / AUTHORS: - Jia JW; Li KL; Wu JX; Guo SL
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, China.
RESUMEN / SUMMARY: - The aim of the present study is to explore the role of annexin II in the development and progression of human non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcription-polymerase chain reaction was conducted to detect annexin II mRNA expression. Annexin II protein expression was also determined by western blot. In addition, annexin II expression was analyzed by immunohistochemistry in 137 clinicopathologically characterized NSCLC cases. The correlation of annexin II expression with patients’ survival rate was assessed by Kaplan-Meier analysis and Cox regression. Our results showed that the expression levels of annexin II mRNA and protein in NSCLC tissues were significantly higher than those in non-cancerous tissues. Immunohistochemistry analysis showed that annexin II expression was significantly correlated with tumor diameter, pathological grade, pT status, pN status, and pleural invasion. The results of the Kaplan-Meier analysis indicated that a high expression level of annexin II resulted in a significantly poor prognosis of NSCLC patients. Multi-variate Cox regression analysis revealed that annexin II expression level was an independent prognostic parameter for the overall survival rate of NSCLC patients. In conclusion, these results suggested that annexin II up-regulation was associated with poor prognosis in NSCLC; therefore, it might act as a prognostic marker and a new potential target for NSCLC treatment.
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[231]
TÍTULO / TITLE: - Substantial risk affects the stage-dependent outcomes of cisplatin-based adjuvant chemotherapy for completely resected non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Today. 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0509-5
AUTORES / AUTHORS: - Yoshino I
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, 260-8670, Japan, iyoshino@faculty.chiba-u.jp.
RESUMEN / SUMMARY: - PURPOSE: Effective adjuvant chemotherapy (Adj.C) for completely resected non-small cell lung cancer (NSCLC) was recently established. However, there may be some unresolved adverse effects, as have been observed in early stage populations or long-term survivors after other types of Adj.C. The substantial risk in such patients was examined by a mathematical method. METHODS: Variables X and Y were defined by two outcomes of Adj.C: X = the ability to eliminate micro-metastasis and Y = the development of effects that threaten life. Then, the following formula was generated: Survival benefit = (death rate) X - (death rate) X Y - (survival rate) Y. We then solved for X and Y and verified our findings using reported data from clinical trials. RESULTS: By solving two simultaneous equations for the formula applied to the data for stage (1) IA and (2) IIIA in the LACE study (J Clin Oncol 26:5043-5051, 2008), X and Y were 2.6 and 1.9, respectively. When these values were applied in the formula for stage IB patients in the same study, the theoretical (-2.3 %) and reported values (2.5 %) were close. When these were applied for stage IB-IIIA patients in the IALT study (N Engl J Med 350:351-360, 2004), the theoretical (5.0 %) and reported values (4.1 %) were also similar. CONCLUSION: Assuming a substantial risk provides an explanation for the stage-dependent outcomes of Adj.C for completely resected NSCLC.
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[232]
TÍTULO / TITLE: - Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Mar 11. doi: 10.1038/onc.2013.42.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.42
AUTORES / AUTHORS: - Wang J; Tian X; Han R; Zhang X; Wang X; Shen H; Xue L; Liu Y; Yan X; Shen J; Mannoor K; Deepak J; Donahue JM; Stass SA; Xing L; Jiang F
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Hebei Medical University, Shijiazhuang, China.
RESUMEN / SUMMARY: - We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P=0.0001) and lymph node metastasis of NSCLC (P=0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 3’-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P=0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.Oncogene advance online publication, 11 March 2013; doi:10.1038/onc.2013.42.
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[233]
TÍTULO / TITLE: - Impact of renal function on treatment options and outcomes in advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 14. pii: S0169-5002(13)00070-6. doi: 10.1016/j.lungcan.2013.02.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.011
AUTORES / AUTHORS: - Kutluk Cenik B; Sun H; Gerber DE
INSTITUCIÓN / INSTITUTION: - Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, United States.
RESUMEN / SUMMARY: - INTRODUCTION: Certain chemotherapeutic agents commonly used for advanced non-small cell lung cancer (NSCLC) require minimum threshold renal function for administration. To determine how such requirements affect treatment options, we evaluated renal function patterns in this population. METHODS: We performed a single-center retrospective analysis of patients treated for stage IV NSCLC from 2000 to 2007. Associations between patient characteristics, calculated creatinine clearance (CrCl), and clinical outcomes were determined using univariate and multivariate analyses, Cox proportional hazard models, and mixed model analysis. RESULTS: 298 patients (3930 creatinine measurements) were included in the analysis. Patients had a median of 5 (interquartile range [IQR] 4-18) Cr measurements. Median baseline CrCl was 96mL/min (IQR 74-123mL/min); median nadir CrCl was 78mL/min (IQR 56-100mL/min). Renal function was associated with age (P<0.001), race (P=0.009), and gender (P=0.001). 23% of patients had a recorded CrCl<60mL/min (threshold for cisplatin), with median onset 83 days after diagnosis and median time to recover to >/=60mL/min of 27 (IQR 3-85) days; 11% of patients had a recorded CrCl<45mL/min (threshold for pemetrexed), with median onset 122 days after diagnosis and median recovery time of 36 (IQR 3-73) days. For both thresholds, approximately 35% of patients had no documented recovery. CONCLUSIONS: In this cohort of patients treated for stage IV NSCLC, renal function falls below commonly used thresholds for cisplatin and for pemetrexed in fewer than a quarter of patients. However, these declines may preclude administration of these drugs for prolonged periods.
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[234]
TÍTULO / TITLE: - Kinase activity of protein kinase calpha in serum as a diagnostic biomarker of human lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):485-8.
AUTORES / AUTHORS: - Kang JH; Mori T; Kitazaki H; Niidome T; Takayama K; Nakanishi Y; Katayama Y
INSTITUCIÓN / INSTITUTION: - Professor, Department of Applied Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Recently, we reported on the existence of activated protein kinase Calpha (PKCalpha) in blood and the possibility for its use in cancer diagnosis. MATERIALS AND METHODS: In the present study, serum samples collected from patients with different lung cancer types (small-cell cancer, adenocarcinoma, and anaplastic cancer) were phosphorylated with a PKCalpha-specific peptide substrate and the phosphorylation ratio was detected by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. RESULTS: When 13 patient serum samples were phosphorylated with peptide substrates, phosphorylated peaks were obtained in eight samples. However, no peak associated with the phosphorylated peptide was observed using serum samples obtained from 10 healthy persons. Moreover, broadly used cancer biomarkers (progastrin-releasing peptide, carcinoembryonic antigen, and cytokeratin-19 fragment) were identified in eight samples among the 13 samples studied. CONCLUSION: These results suggest that serum activated PKCalpha is a reliable biomarker, applicable to lung cancer diagnosis.
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[235]
TÍTULO / TITLE: - Multiple isoforms and differential allelic expression of CHRNA5 in lung tissue and lung adenocarcinoma.
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/bgt062
AUTORES / AUTHORS: - Falvella FS; Alberio T; Noci S; Santambrogio L; Nosotti M; Incarbone M; Pastorino U; Fasano M; Dragani TA
INSTITUCIÓN / INSTITUTION: - Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy.
RESUMEN / SUMMARY: - CHRNA5 gene expression variation may play a role in individual susceptibility to lung cancer. Analysis of CHRNA5 transcripts expressed in normal lung tissue detected the full-length transcript (isoform-1) and four splicing transcripts (isoform-2 to isoform-5), derived from the recognition of other splice sites in exon 5. Isoforms-2, -3 and -4 were found by protein modeling to form a completely folded, potentially functional extracellular domain and were observed at the protein level, whereas isoform-5 lacked a consistent part of the distorted beta sandwich and was not seen at the protein level. Only isoform-1 appeared to encode a complete, functional subunit able to fulfill the ion channel function. We previously reported that CHRNA5 expression is associated with genetic polymorphisms at this locus and that three haplotypes in its promoter region show functional regulation in vitro. Analysis of differential allelic expression (DAE) of three single nucleotide polymorphisms (rs503464, rs55853698 and rs55781567) tagging the expression haplotypes of the CHRNA5 promoter indicated statistically significant DAE at rs55853698 and rs55781567, in both normal lung and lung adenocarcinoma. Overall, our findings provide evidence for the presence of multiple CHRNA5 messenger RNA (mRNA) isoforms that may modulate the multimeric nicotine receptor and cis-regulatory variations in the CHRNA5 locus that act in vivo in the control of CHRNA5 mRNA expression, in normal lung tissue and in lung adenocarcinoma.
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[236]
TÍTULO / TITLE: - Long-term survival of advanced small cell carcinoma of the esophagus after resection: a case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):595-600.
AUTORES / AUTHORS: - Muguruma K; Ohira M; Tanaka H; Kubo N; Yamashita Y; Sawada T; Wakasa K; Hirakawa K
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. m1294441@msic.med.osaka-cu.ac.jp
RESUMEN / SUMMARY: - BACKGROUND: Small cell carcinoma of the esophagus is a rare and rapidly lethal disease. The mean survival for patients with advanced disease is 5.3 months, and only 10% live longer than one year. Case Report: We report a very unusual case in which a patient diagnosed with advanced disease is still alive 96 months after being treated by surgery-alone. This patient is a 61-year-old woman who was referred to our hospital with the chief complaints of dysphagia and vomiting. Endoscopy revealed a huge type-3 tumor on the abdominal esophagus invading the gastric cardia. Histopathology established the diagnosis of small cell carcinoma; computed tomography did not detect metastatic cells in the lymph nodes or other distant sites. We therefore performed radical resection, involving a lower esophagectomy, total gastrectomy, and splenectomy with regional lymph node dissection. The initial diagnosis of small cell carcinoma was confirmed, and classified as type-3 (13.8x7.5 cm), T3N1M0, stage III with invasion to the adventitia (T3) and lymph node metastases along the lesser curvature of the stomach (N1). Postoperative adjuvant chemotherapy using tegafur, gimestat, and otastat was discontinued due to poor tolerance, and the patient developed severe anorexia. The patient remains alive at the time of writing eight years and four months post-surgery, with no evidence of tumor. CONCLUSION: To our knowledge, this is the longest survival reported for a case of advanced small cell carcinoma of the esophagus treated by surgery-alone.
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[237]
TÍTULO / TITLE: - Lung cancer risks from plutonium: an updated analysis of data from the mayak worker cohort.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Res. 2013 Mar;179(3):332-42. doi: 10.1667/RR3054.1. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1667/RR3054.1
AUTORES / AUTHORS: - Gilbert ES; Sokolnikov ME; Preston DL; Schonfeld SJ; Schadilov AE; Vasilenko EK; Koshurnikova NA
INSTITUCIÓN / INSTITUTION: - a Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland;
RESUMEN / SUMMARY: - Workers at the Mayak nuclear facility in the Russian Federation offer a unique opportunity to evaluate health risks from exposure to inhaled plutonium. Risks of mortality from lung cancer, the most serious carcinogenic effect of plutonium, were evaluated in 14,621 Mayak workers who were hired in the period from 1948-1982, followed for at least 5 years, and either monitored for plutonium or never worked with plutonium. Over the follow-up period from 1953-2008, there were 486 deaths from lung cancer, 446 of them in men. In analyses that were adjusted for external radiation dose and smoking, the plutonium excess relative risk (ERR) per Gy declined with attained age and was higher for females than for males. The ERR per Gy for males at age 60 was 7.4 (95% CI: 5.0-11) while that for females was 24 (95% CI: 11-56). When analyses were restricted to plutonium doses <0.2 Gy, the ERR per Gy for males at age 60 was similar: 7.0 (95% CI: 2.5-13). Of the 486 lung cancer deaths, 105 (22%) were attributed to plutonium exposure and 29 (6%) to external exposure. Analyses of the 12,708 workers with information on smoking indicated that the relationship of plutonium exposure and smoking was likely sub-multiplicative (P = 0.011) and strongly indicated that it was super-additive (P < 0.001). Although extensive efforts have been made to improve plutonium dose estimates in this cohort, they are nevertheless subject to large uncertainties. Large bioassay measurement errors alone are likely to have resulted in serious underestimation of risks, whereas other sources of uncertainty may have biased results in ways that are difficult to predict.
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[238]
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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[239]
TÍTULO / TITLE: - Application of a spring-dashpot system to clinical lung tumor motion data.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Phys. 2013 Feb;40(2):021713. doi: 10.1118/1.4788643.
●● Enlace al texto completo (gratuito o de pago) 1118/1.4788643
AUTORES / AUTHORS: - Ackerley EJ; Cavan AE; Wilson PL; Berbeco RI; Meyer J
INSTITUCIÓN / INSTITUTION: - Department of Mathematics and Statistics, University of Canterbury, Christchurch, New Zealand.
RESUMEN / SUMMARY: - PURPOSE: The treatment efficacy of radiation therapy for lung tumors can be increased by compensating for breath-induced tumor motion. In this study, we quantitatively examine a mathematical model of pseudomechanical linkages between an external surrogate signal and lung tumor motion. METHODS: A spring-dashpot system based on the Voigt model was developed to model the correlation between abdominal respiratory motion and tumor motion during lung radiotherapy. The model was applied to clinical data obtained from 52 treatments (“beams”) from 10 patients, treated on the Mitsubishi Real-Time Radiation Therapy system, Sapporo, Japan. In Stage 1, model parameters were optimized for individual patients and beams to determine reference values and to investigate how well the model can describe the data. In Stage 2, for each patient the optimal parameters determined for a single beam were applied to data from other beams to investigate whether a beam-specific set of model parameters is sufficient to model tumor motion over a course of treatment. RESULTS: In Stage 1, the baseline root mean square (RMS) residual error for all individually optimized beam data was 0.90 +/- 0.40 mm (mean +/- 1 standard deviation). In Stage 2, patient-specific model parameters based on a single beam were found to model the tumor position closely, even for irregular beam data, with a mean increase with respect to Stage 1 values in RMS error of 0.37 mm. On average, the obtained model output for the tumor position was 95% of the time within an absolute bound of 2.0 and 2.6 mm in Stages 1 and 2, respectively. The model was capable of dealing with baseline, amplitude and frequency variations of the input data, as well as phase shifts between the input abdominal and output tumor signals. CONCLUSIONS: These results indicate that it may be feasible to collect patient-specific model parameters during or prior to the first treatment, and then retain these for the rest of the treatment period. The model has potential for clinical application during radiotherapy treatment of lung tumors.
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[240]
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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[241]
TÍTULO / TITLE: - MiRNA-125a-3p is a negative regulator of the RhoA-actomyosin pathway in A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Mar 21. doi: 10.3892/ijo.2013.1861.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1861
AUTORES / AUTHORS: - Huang B; Luo W; Sun L; Zhang Q; Jiang L; Chang J; Qiu X; Wang E
INSTITUCIÓN / INSTITUTION: - Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China.
RESUMEN / SUMMARY: - MicroRNAs (miRNAs) function as genetic modulators that regulate gene expression, and are, thus, involved in a wide range of biological roles, including tumor cell migration and invasion. MiR-125a-3p is a mature form of miR-125a, derived from the 3’-end of pre-miR-125a. Our group has previously reported that miR-125a-3p functions as a tumor suppressor gene that inhibits the migration and invasion of lung cancer cells. Here, we report the discovery of a new regulatory layer of the RhoA-actomyosin pathway through which miR-125a-3p controls tumor cell migration. Overexpression of miR-125a-3p by transfection of sensemiR125a-3p resulted in decreased RhoA protein levels, while the levels of RhoA mRNA remained constant. The concentrations of both RhoA-GTP protein and actin filaments decreased after miR-125a-3p overexpression in the A549 lung cancer cell line. Conversely, knockdown of miR-125a-3p by transfection of antisense-miR-125a-3p resulted in increased RhoA protein levels while the levels of RhoA mRNA remained unchanged. However, the concentration of both RhoA-GTP protein and actin filaments increased. To further demonstrate that RhoA is a potential target of miR125a-3p, luciferase reporter constructs containing the RhoA 3’UTR demonstrated reduced reporter activity after ectopic expression of miR-125a-3p. Moreover, luciferase reporter constructs containing the RhoA 3’UTR mutant did not show significantly changed reporter activity. Furthermore, A549 cells demonstrated reduced migratory capacity after treatment with the Rho inhibitor CT04. Our results indicate that the loss of miR-125a3p-controlled regulation of the RhoA-actomyosin pathway can lead to increased migration of tumor cells because of the upregulation of RhoA expression. In particular, an increased intracellular concentration of RhoA-GTP protein in A549 cells leads to the accumulation of actin filaments. These results provide new insights into the role of the miR-125a family in lung cancer.
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[242]
TÍTULO / TITLE: - Characteristics of Lung Cancers Harboring NRAS Mutations.
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-12-3173
AUTORES / AUTHORS: - Ohashi K; Sequis LV; Arcila ME; Lovly CM; Chen X; Rudin CM; Moran T; Camidge DR; Vnencak-Jones CL; Berry L; Pan Y; Sasaki H; Engelman JA; Garon EB; Dubinett SM; Franklin WA; Riely GJ; Sos ML; Kris MG; Dias-Santagata D; Ladanyi M; Bunn PA Jr; Pao W
INSTITUCIÓN / INSTITUTION: - Department of Hematology, Oncology, and Respiratory Medicine, Vanderbilt Univesity.
RESUMEN / SUMMARY: - PURPOSE: We sought to determine the frequency and clinical characteristics of patients with lung cancer harboring NRAS mutations. We used preclinical models to identify targeted therapies likely to be of benefit against NRAS mutant lung cancer cells. EXPERIMENTAL DESIGN: We reviewed clinical data from patients whose lung cancers were identified at 6 institutions or reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) to harbor NRAS mutations. 6 NRAS mutant cell lines were screened for sensitivity against inhibitors of multiple kinases (i.e. EGFR, ALK, MET, IGF-1R, BRAF, PI3K and MEK). RESULTS: Among 4562 patients with lung cancers tested, NRAS mutations were present in 30 (0.7%; 95% confidence interval, 0.45% to 0.94%); 28 of these had no other driver mutations. 83% had adenocarcinoma histology with no significant differences in gender. While 95% of patients were former or current smokers, smoking-related G:C>T:A transversions were significantly less frequent in NRAS mutated lung tumors compared to KRAS-mutant NSCLCs (NRAS: 13% (4/30), KRAS: 66% (1772/2733), p<0.00000001). 5 of 6 NRAS mutant cell lines were sensitive to the MEK inhibitors, selumetinib and trametinib, but not to other inhibitors tested. CONCLUSIONS: NRAS mutations define a distinct subset of lung cancers (~1%) with potential sensitivity to MEK inhibitors. While NRAS mutations are more common in current/former smokers, the types of mutations are not those classically associated with smoking.
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[243]
TÍTULO / TITLE: - 2a, a novel curcumin analog, sensitizes cisplatin-resistant A549 cells to cisplatin by inhibiting thioredoxin reductase concomitant oxidative stress damage.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Pharmacol. 2013 Mar 21. pii: S0014-2999(13)00204-5. doi: 10.1016/j.ejphar.2013.03.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejphar.2013.03.014
AUTORES / AUTHORS: - Zhou B; Huang J; Zuo Y; Li B; Guo Q; Cui B; Shao W; Du J; Bu X
INSTITUCIÓN / INSTITUTION: - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
RESUMEN / SUMMARY: - (1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(5-methylfuran-2-yl)hepta-1, 4,6-trien-3-one (2a), a novel curcumin analog, was previously synthesized in our laboratory as a potential thioredoxin reductase (TrxR) inhibitor with excellent growth inhibitory effects on several TrxR over-expressed cancer cells. In this study, our further studies show that 2a is able to inhibit the growth of cisplatin-resistant A549 (A549/CDDP) cells much more effectively in a dose-dependent manner than that of A549 cells in antiproliferative activity experiments. Moreover, 2a-pretreated A549/CDDP cells are sensitive to cisplatin treatment, which is accompanied by the inhibition of TrxR activity in A549/CDDP cells. As a consequence of targeting TrxR, 2a in turn remarkably up-regulates intracellular reactive oxygen species level, depletes glutathione (GSH), and reduces the GSH/GSSG ratio, suggesting that the intracellular redox balance is shifted to a more oxidative state. Consequently, concomitant with the cell growth inhibition of 2a, apoptosis is induced by 2a probably through increased oxidative stress in A549/CDDP cells. In conclusion, these observations demonstrated that TrxR inhibitors would be promising drugs to achieve a successful combinatory or single cancer chemotherapy.
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[244]
TÍTULO / TITLE: - Significant association of 5p15.33 (TERT-CLPTM1L genes) with lung cancer in Chinese Han population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Lung Res. 2013 Mar;39(2):91-8. doi: 10.3109/01902148.2012.762436. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3109/01902148.2012.762436
AUTORES / AUTHORS: - Zhao Z; Li C; Yang L; Zhang X; Zhao X; Song X; Li X; Wang J; Qian J; Yang Y; Jin L; Chen H; Lu D
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Genetic Engineering, School of Life Sciences and Fudan Taizhou Institute of Health Sciences, Fudan University, and Department of Cardiothoracic Surgery and Pneumology, Changhai Hospital of Shanghai, Shanghai, China.
RESUMEN / SUMMARY: - Lung cancer is a leading cause of cancer-related deaths throughout the world. Recent genome-wide association studies and consecutive validation supported that the 5p15.33 region containing telomerase reverse transcriptase gene (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) gene showed significant association with lung cancer in multiple populations. Here we studied a large Chinese Han cohort consisting of 1759 cases and 1804 controls. In the 1st stage (784 cases versus 782 controls) we genotyped 13 tag SNPs within 5p15.33 region to further investigate the association. After the 2nd stage validation (975 cases versus 1022 controls), the study clarified the association that rs2736100 of the TERT gene conferred the highest significant risk of lung cancer (P=4x10(-3) in the 1st stage association, P=4x10(-4) in the 2nd stage validation, and P=1x10(-5), odds ratio=1.24 in the combined population). The results provided the evidence of a cross-race susceptibility of the lung cancer locus.
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[245]
TÍTULO / TITLE: - Silence of ezrin modifies migration and actin cytoskeleton rearrangements and enhances chemosensitivity of lung cancer cells in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cell Biochem. 2013 May;377(1-2):207-18. doi: 10.1007/s11010-013-1586-x. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s11010-013-1586-x
AUTORES / AUTHORS: - Chen QY; Xu W; Jiao DM; Wu LJ; Song J; Yan J; Shi JG
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Disease, The 117th Hospital of PLA, 14 Lingyin Road, 310013, Hang Zhou, People’s Republic of China, cqyong117@163.com.
RESUMEN / SUMMARY: - Ezrin, primarily acts as a linker between the plasma membrane and the cytoskeleton, is involved in many cellular functions, including regulation of actin cytoskeleton, control of cell shape, adhesion, motility, and modulation of signaling pathways. Although ezrin is now recognized as a key component in tumor metastasis, its roles and the underlying mechanisms remain unclear. In the present study, we chose highly metastatic human lung carcinoma 95D cells, which highly express the ezrin proteins, as a model to examine the functional roles of ezrin in tumor suppression. An ezrin-silenced 95D cell line was established using lentivirus-mediated short hairpin RNA method. CCK-8 assay and soft agar assay analysis showed that downregulation of ezrin significantly suppressed the tumorigenicity and proliferation of 95D cells in vitro. cell migration and invasion studies showed that ezrin-specific deficiency in the cells caused the substantial reduction of the cell migration and invasion. In parallel, it also induced rearrangements of the actin cytoskeleton. Flow cytometry assay showed that changes in the ezrin protein level significantly affected the cell cycle distribution and eventual apoptosis. Furthermore, further studies showed that ezrin regulated the expression level of E-cadherin and CD44, which are key molecules involved in cell growth, migration, and invasion. Meanwhile, the suppression of ezrin expression also sensitized cells to antitumor drugs. Altogether, our results demonstrated that ezrin played an important role in the tumorigenicity and metastasis of lung cancer cells, which will benefit the development of therapeutic strategy for lung cancer.
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[246]
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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[247]
TÍTULO / TITLE: - Current adoptive immunotherapy in non-small cell lung cancer and potential influence of therapy outcome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Invest. 2013 Mar;31(3):197-205. doi: 10.3109/07357907.2013.775294.
●● Enlace al texto completo (gratuito o de pago) 3109/07357907.2013.775294
AUTORES / AUTHORS: - Zheng YW; Li RM; Zhang XW; Ren XB
INSTITUCIÓN / INSTITUTION: - Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital , Tianjin , China,1.
RESUMEN / SUMMARY: - Non-small cell lung cancer (NSCLC) is found worldwide with high incidence and poor prognoses. Nowadays, insights in the interaction between tumors and immune system have led to the development of immunotherapy as a fundamentally new concept for the treatment of NSCLC. Adoptive cell transfer represents an important advancement in cancer immunotherapy such as cytokine-induced killer and gammadelta T-cells. Recent clinical research studies provide evidence for the positive effects of adoptive immunotherapy, which is probably associated with levels of cytokines, cell doses, and immune microenvironment. This review summarizes the current condition of adoptive immunotherapy in NSCLC and the long-standing confusion in this field.
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[248]
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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[249]
TÍTULO / TITLE: - Therapeutic targeting malignant mesothelioma with a novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate via its selective uptake by the proton-coupled folate transporter.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):999-1011. doi: 10.1007/s00280-013-2094-0. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2094-0
AUTORES / AUTHORS: - Cherian C; Kugel Desmoulin S; Wang L; Polin L; White K; Kushner J; Stout M; Hou Z; Gangjee A; Matherly LH
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
RESUMEN / SUMMARY: - PURPOSE: We examined whether the novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate, compound 2, might be an effective treatment for malignant pleural mesothelioma (MPM), reflecting its selective membrane transport by the proton-coupled folate transport (PCFT) over the reduced folate carrier (RFC). METHODS: HeLa sublines expressing exclusively PCFT (R1-11-PCFT4) or RFC (R1-11-RFC6) and H2452 MPM cells were assayed for transport with [(3)H]compound 2. [(3)H]Polyglutamate metabolites of compound 2 were measured in R1-11-PCFT4 and H2452 cells. In vitro cell proliferation assays and colony formation assays were performed. Inhibition of glycinamide ribonucleotide formyltransferase (GARFTase) was assayed by nucleoside protection assays and in situ GARFTase assays with [(14)C]glycine. In vivo efficacy was established with early- and advanced-stage H2452 xenografts in severe-combined immunodeficient (SCID) mice administered intravenous compound 2. RESULTS: [(3)H]Compound 2 was selectively transported by PCFT and was metabolized to polyglutamates. Compound 2 selectively inhibited proliferation of R1-11-PCFT4 cells over R1-11-RFC6 cells. H2452 human MPM cells were sensitive to the antiproliferative effects of compound 2. By colony-forming assays with H2452 cells, compound 2 was cytotoxic. Compound 2 inhibited GARFTase in de novo purine biosynthesis. In vivo efficacy was confirmed toward early- and advanced-stage H2452 xenografts in SCID mice administered compound 2. CONCLUSIONS: Our results demonstrate potent antitumor efficacy of compound 2 toward H2452 MPM cells in vitro and in vivo, reflecting its efficient membrane transport by PCFT, synthesis of polyglutamates, and inhibition of GARFTase. Selectivity for non-RFC cellular uptake processes by tumor-targeted antifolates such as compound 2 presents an exciting new opportunity for treating solid tumors.
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[250]
TÍTULO / TITLE: - Association between a 15q25 gene variant, nicotine-related habits, lung cancer and COPD among 56 307 individuals from the HUNT study in Norway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Hum Genet. 2013 Feb 27. doi: 10.1038/ejhg.2013.26.
●● Enlace al texto completo (gratuito o de pago) 1038/ejhg.2013.26
AUTORES / AUTHORS: - Gabrielsen ME; Romundstad P; Langhammer A; Krokan HE; Skorpen F
INSTITUCIÓN / INSTITUTION: - Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
RESUMEN / SUMMARY: - Genetic studies have shown an association between single-nucleotide polymorphisms on chromosome 15q25 and smoking-related traits and diseases, such as quantity of smoking, lung cancer and chronic obstructive pulmonary disease (COPD). A discussion has centred on the variants and their effects being directly disease related or indirect via nicotine addiction. To address these discrepancies, we genotyped the single-nucleotide polymorphism rs16969968 in the CHRNA5/A3/B4 gene cluster at chromosome 15q25, in 56 307 individuals from a large homogenous population-based cohort, the North Trondelag Health Study (HUNT) in Norway. The variant was examined in relation to four different outcomes: lung cancer, loss of lung function equivalent to that of COPD, smoking behaviour and the use of smokeless tobacco (snus). Novel associations were found between rs16969968 and the motivational factor for starting to use snus, and the quantity of snus used. Our results also confirm and extend previous findings for associations between rs16969968 and lung cancer, loss of lung function equivalent to that of COPD, and smoking quantity. Our data suggest a role for rs16969968 in nicotine addiction, and the novel association with snus strengthens this observation.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.26.
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[251]
TÍTULO / TITLE: - Intakes of fruits, vegetables, and related vitamins and lung cancer risk: results from the Shanghai Men’s Health Study (2002-2009).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013;65(1):51-61. doi: 10.1080/01635581.2013.741757.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.741757
AUTORES / AUTHORS: - Takata Y; Xiang YB; Yang G; Li H; Gao J; Cai H; Gao YT; Zheng W; Shu XO
INSTITUCIÓN / INSTITUTION: - Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, USA.
RESUMEN / SUMMARY: - Most epidemiological studies evaluating the association of fruit and vegetable intakes on lung cancer risk were conducted in North American and European countries. We investigated the association of intakes of fruits, vegetables, dietary vitamins A and C, and folate with lung cancer risk among 61,491 adult Chinese men who were recruited into the Shanghai Men’s Health Study, a population-based, prospective cohort study. Baseline dietary intake was assessed through a validated food frequency questionnaire during in-home visits. Multivariate Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer risk associated with dietary intakes. During a median follow-up of 5.5 yr, 359 incident lung cancer cases accrued after the first year of follow-up and 68.8% of them were current smokers. Intakes of green leafy vegetables, beta-carotene-rich vegetables, watermelon, vitamin A, and carotenoids were inversely associated with lung cancer risk; the corresponding HR (95% CI) comparing the highest with the lowest quartiles were 0.72 (0.53-0.98), 0.69 (0.51-0.94), 0.65 (0.47-0.90), 0.63 (0.44-0.88), and 0.64 (0.46-0.88). Intake of all fruits and vegetables combined was marginally associated with lower risk. Our study suggests that the consumption of carotenoid-rich vegetables is inversely associated with lung cancer risk.
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[252]
TÍTULO / TITLE: - Breast metastasis from lung adenocarcinoma diagnosed with fine needle aspiration cytology: a case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Dec;36(4):1461-5.
AUTORES / AUTHORS: - Branica BV; Meniga IN; Puljic I; Marusic A; Chalfe N; Ivicevic A
INSTITUCIÓN / INSTITUTION: - University of Zagreb, School of Medicine, Zagreb University Hospital Centre, Department of Pathology and Cytology-Pulmonary Cytology, Division Jordanovac, Zagreb, Croatia. bozica.vrabec.branica@zg.t-com.hr
RESUMEN / SUMMARY: - Metastases to the breast from extramammary neoplasms are very rare. Correct diagnosis of breast malignancy is important for establishing appropriate management and for avoiding unnecessary radical surgery. Metastasized breast malignancies from non-small cell lung carcinoma are extremely rare. Here we report a 55-year old female patient with breast metastasis from lung adenocarcinoma which was diagnosed with fine needle aspiration cytology and confirmed by immunocytochemistry.
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[253]
TÍTULO / TITLE: - alpha-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Mar 16. pii: S0304-3835(13)00236-X. doi: 10.1016/j.canlet.2013.03.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.008
AUTORES / AUTHORS: - Michikoshi H; Nakamura T; Sakai K; Suzuki Y; Adachi E; Matsugo S; Matsumoto K
INSTITUCIÓN / INSTITUTION: - Division of Material Engineering, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
RESUMEN / SUMMARY: - alpha-Lipoic acid (alpha-LA), a naturally occurring anti-oxidant and co-factor for metabolic enzymes, suppresses the growth of different types of tumor cells. The mechanisms that are responsible for these results, however, remain to be elucidated. In the present study, we investigated the effects of alpha-LA on the proliferation and activation status of definitive receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and Met/hepatocyte growth factor (HGF) receptor, in gefitinib-sensitive human non-small cell lung cancer cells harboring EGFRs with an activating mutation. The enantiomers R-alpha-LA and S-alpha-LA suppressed cell proliferation and increased the level of reactive oxygen species in HCC-827 and PC-9 human non-small cell lung cancer cells in an indistinguishable dose-dependent fashion. A phospho-receptor tyrosine kinase array and cell cycle analysis indicated that alpha-LA decreased tyrosine phosphorylation levels of EGFR, ErbB2, and Met, and this was associated with an inhibition in the cell-cycle transition from the G1 phase to the S phase without inducing apoptosis. Gefitinib, an inhibitor for EGFR tyrosine kinase, inhibited EGFR tyrosine phosphorylation/activation and proliferation of the cells. Instead, the addition of HGF induced Met tyrosine phosphorylation, and this was associated with a resistance to gefitinib-induced growth inhibition, which meant a gain in proliferative ability. In the presence of gefitinib and HGF, the addition of alpha-LA suppressed Met tyrosine phosphorylation, and this was associated with an inhibition in cell growth. These results suggest that the suppression of tyrosine phosphorylation/activation of growth factor receptors that is critical for the proliferation of human non-small cell lung cancer cells is a mechanism by which alpha-LA exerts growth inhibition for cancer cells.
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[254]
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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[255]
TÍTULO / TITLE: - Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Oncol. 2013 Apr;52(3):506-13. doi: 10.3109/0284186X.2013.769063. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2013.769063
AUTORES / AUTHORS: - Colaco RJ; Huh S; Nichols RC; Morris CG; D’Agostino H; Flampouri S; Li Z; Pham DC; Bajwa AA; Hoppe BS
INSTITUCIÓN / INSTITUTION: - University of Florida Proton Therapy Institute , Jacksonville, Florida , USA.
RESUMEN / SUMMARY: - Abstract Background. Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods. Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results. The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.
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[256]
TÍTULO / TITLE: - Effect of insurance status on the surgical treatment of early-stage non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Apr;95(4):1221-6. doi: 10.1016/j.athoracsur.2012.10.079. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.10.079
AUTORES / AUTHORS: - Groth SS; Al-Refaie WB; Zhong W; Vickers SM; Maddaus MA; D’Cunha J; Habermann EB
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Division of Thoracic Surgery, Brigham and Women’s Hospital, Boston Massachusetts.
RESUMEN / SUMMARY: - BACKGROUND: Social disparities permeate non-small cell lung cancer (NSCLC) treatment, yet little is known about the effect of insurance status on the delivery of guideline surgical treatment for early-stage (I or II) NSCLC. METHODS: We used the California Cancer Registry (1996 through 2008) to identify patients 50 to 94 years old with early-stage NSCLC. We used logistic regression models to assess whether or not insurance status (private insurance, Medicare, Medicaid, no insurance, and unknown) had an effect on whether or not a lobectomy (or bilobectomy) is performed. RESULTS: A total of 10,854 patients met our inclusion criteria. Compared with patients with private insurance, we found that patients with Medicare (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI]: 0.79 to 0.95), Medicaid (aOR 0.45; 95% CI: 0.36 to 0.57), or no insurance (aOR 0.45; 95% CI: 0.29 to 0.70) were significantly less likely to undergo lobectomy, even after adjusting for patient factors (age, race, and gender) and tumor characteristics (histology and tumor size). Increasing age, African American race, squamous cell carcinoma, and increasing tumor size were significant independent negative predictors of whether or not a lobectomy was performed. CONCLUSIONS: Patients without private insurance were significantly less likely than patients with private insurance to undergo a lobectomy for early-stage NSCLC. The variables(s) contributing to this disparity have yet to be elucidated.
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[257]
TÍTULO / TITLE: - Promyelocytic leukemia zinc finger and histone H1.5 differentially stain low- and high-grade pulmonary neuroendocrine tumors: a pilot immunohistochemical study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Feb 14. pii: S0046-8177(12)00442-X. doi: 10.1016/j.humpath.2012.11.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.11.014
AUTORES / AUTHORS: - Hechtman JF; Beasley MB; Kinoshita Y; Ko HM; Hao K; Burstein DE
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Mount Sinai School of Medicine and Medical Center, New York, NY 10029. Electronic address: jaclyn.hechtman@mountsinai.org.
RESUMEN / SUMMARY: - Promyelocytic leukemia zinc finger is a zinc finger transcription factor that functions as a transcriptional repressor. Its expression has been shown to be down-regulated in hematopoietic, melanocytic, and mesothelial malignancies. Histone H1.5 is a variant of histone H1, a family of linker proteins that organizes chromosomes into higher order structures. Its function is of key importance in gene expression and has been linked to more aggressive forms of prostatic carcinoma. This study aimed to investigate the immunohistochemical detectability of promyelocytic leukemia zinc finger and histone H1.5 in pulmonary neuroendocrine tumors, comprising 11 carcinoid tumorlets, 24 typical carcinoids, 12 atypical carcinoids, 20 small cell carcinomas, 11 large cell neuroendocrine carcinomas, and 2 combined small cell carcinomas-large cell neuroendocrine carcinomas. Promyelocytic leukemia zinc finger immunohistochemistry revealed moderate or strong nuclear staining in all carcinoid tumorlets, 23 of 24 typical carcinoids, and 7 of 12 atypical carcinoids in contrast to 9 of 11 large cell neuroendocrine carcinomas, all small cell carcinoma, and both combined small cell carcinoma-large cell neuroendocrine carcinomas, which showed no nuclear immunoreactivity. Histone H1.5 immunohistochemistry revealed only focal or no immunoreactivity in all carcinoid tumorlets and 19 of 24 typical carcinoids, whereas 7 of 12 atypical carcinoids, 19 of 20 small cell carcinomas, 10 of 11 large cell neuroendocrine carcinomas, and both combined small cell carcinomas-large cell neuroendocrine carcinomas displayed positive (>/=10%) nuclear immunoreactivity-ranging from a minority of weak staining to a majority of strong staining cases. Our data suggest that the relative expression ratios of promyelocytic leukemia zinc finger and histone H1.5 may correlate with grade of pulmonary neuroendocrine tumors. Immunohistochemical stains for these markers, especially on small biopsies with crush artifact, may prove to be diagnostically useful.
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[258]
TÍTULO / TITLE: - A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):329-37. doi: 10.1097/JTO.0b013e31827ce554.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827ce554
AUTORES / AUTHORS: - Paz-Ares L; Balint B; de Boer RH; van Meerbeeck JP; Wierzbicki R; De Souza P; Galimi F; Haddad V; Sabin T; Hei YJ; Pan Y; Cottrell S; Hsu CP; RamLau R
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, IBIS & Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Servicio de Oncologia, Seville, España. lpazares@hotmail.com
RESUMEN / SUMMARY: - INTRODUCTION: This study evaluated the efficacy, safety, and pharmacokinetics of conatumumab combined with paclitaxel-carboplatin (PC) as first-line treatment for advanced non-small-cell lung cancer (NSCLC). METHODS: Patients (aged >18 years) with previously untreated advanced or recurrent NSCLC were randomized 1:1:1 (stratified by Eastern Cooperative Oncology Group performance status and disease stage) to receive up to six 3-week cycles of PC combined with conatumumab (arm 1, 3 mg/kg; arm 2, 15 mg/kg) or placebo (arm 3) every 3 weeks. The primary endpoint was progression-free survival (PFS). This study is registered with ClinicalTrials.gov (NCT00534027). RESULTS: Between August 8, 2007 and April 9, 2009, 172 patients were randomized (arm 1, n = 57; arm 2, n = 56; arm 3, n = 59). Median PFS was 5.4 months (95% confidence interval [CI] 4.1-6.3) in arm 1 (hazard ratio [HR] 0.84 [95% CI 0.57-1.24]; p = 0.41), 4.8 months (95% CI 3.2-6.5) in arm 2 (HR 0.93 [0.64-1.35]; p = 0.57), and 5.5 months (95% CI 4.3-5.7) in arm 3. There was an interaction between tumor histology and the effect of conatumumab on PFS (squamous HR 0.47 [0.23-0.94]; nonsquamous HR 1.08 [0.74-1.57]; interaction p = 0.039).The most common grade of three or more adverse events were neutropenia, anemia, and thrombocytopenia. There was no evidence of pharmacokinetic interactions between conatumumab and PC. Of 158 patients assessable for FCGR3A polymorphisms, conatumumab treatment was associated with a trend toward longer overall survival (HR 0.72 [0.43-1.23]) among V-allele carriers (V/V or F/V; n = 54) but not among F-allele homozygotes (n = 34; HR 1.37 [0.66-2.86]). CONCLUSION: Although well tolerated, the addition of conatumumab to PC did not improve outcomes in unselected patients with previously untreated advanced NSCLC.
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[259]
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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[260]
TÍTULO / TITLE: - PM induces Nrf2-mediated defense mechanisms against oxidative stress by activating PIK3/AKT signaling pathway in human lung alveolar epithelial A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biol Toxicol. 2013 Mar 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s10565-013-9242-5
AUTORES / AUTHORS: - Deng X; Rui W; Zhang F; Ding W
INSTITUCIÓN / INSTITUTION: - Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
RESUMEN / SUMMARY: - It has been well documented in in vitro studies that ambient airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 mum (PM2.5) is capable of inducing oxidative stress, which plays a key role in PM2.5-mediated cytotoxicity. Although nuclear factor erythroid-2-related factor 2 (Nrf2) has been shown to regulate the intracellular defense mechanisms against oxidative stress, a potential of the Nrf2-mediated cellular defense against oxidative stress induced by PM2.5 remains to be determined. This study was aimed to explore the potential signaling pathway of Nrf2-mediated defense mechanisms against PM2.5-induced oxidative stress in human type II alveolar epithelial A549 cells. We exposed A549 cells to PM2.5 particles collected from Beijing at a concentration of 16 mug/cm2. We observed that PM2.5 triggered an increase of intracellular reactive oxygen species (ROS) in a time-dependent manner during a period of 2 h exposure. We also found that Nrf2 overexpression suppressed and Nrf2 knockdown increased PM2.5-induced ROS generation. Using Western blot and confocal microscopy, we found that PM2.5 exposure triggered significant translocation of Nrf2 into nucleus, resulting in AKT phosphorylation and significant transcription of ARE-driven phases II enzyme genes, such as NAD(P)H:quinone oxidoreductase (NQO-1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) in A549 cells. Evaluation of signaling pathways showed that a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), but not an ERK ½ inhibitor (PD98059) or a p38 MAPK (SB203580), significantly down-regulated PM2.5-induced Nrf2 nuclear translocation and HO-1 mRNA expression, indicating PI3K/AKT is involved in the signaling pathway leads to the PM2.5-induced nuclear translocation of Nrf2 and subsequent Nrf2-mediated HO-1 transcription. Taken together, our results suggest that PM2.5-induced ROS may function as signaling molecules to activate Nrf2-mediated defenses, such as HO-1 expression, against oxidative stress induced by PM2.5 through the PI3K/AKT signaling pathway.
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[261]
TÍTULO / TITLE: - Systemic delivery of gemcitabine triphosphate via LCP nanoparticles for NSCLC and pancreatic cancer therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Apr;34(13):3447-58. doi: 10.1016/j.biomaterials.2013.01.063. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.063
AUTORES / AUTHORS: - Zhang Y; Kim WY; Huang L
INSTITUCIÓN / INSTITUTION: - Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
RESUMEN / SUMMARY: - Nucleoside analogs are a significant class of anti-cancer agent. As prodrugs, they terminate the DNA synthesis upon transforming to their active triphosphate metabolites. We have encapsulated a biologically activate nucleotide analog (i.e. gemcitabine triphosphate (GTP)), instead of the nucleoside (i.e. gemcitabine) derivative, into a novel Lipid/Calcium/Phosphate nanoparticle (LCP) platform. The therapeutic efficacy of LCP-formulated GTP was evaluated in a panel of human non-small-cell lung cancer (NSCLC) and human pancreatic cancer models after systemic administrations. GTP-loaded LCPs induced cell death and arrested the cell cycle in the S phase. In vivo efficacy studies showed that intravenously injected GTP-loaded LCPs triggered effective apoptosis of tumor cells, significant reduction of tumor cell proliferation and cell cycle progression, leading to dramatic inhibition of tumor growth, with little in vivo toxicity. Broadly speaking, the current study offers preclinical proof-of-principle that many active nucleotide or phosphorylated nucleoside analogs could be encapsulated in the LCP nanoplatform and delivered systemically for a wide variety of therapeutic applications.
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[262]
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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[263]
TÍTULO / TITLE: - Diagnostic performance of percutaneous lung biopsy using automated biopsy needles under CT-fluoroscopic guidance for ground-glass opacity lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Radiol. 2013 Feb;86(1022):20120447. doi: 10.1259/bjr.20120447.
●● Enlace al texto completo (gratuito o de pago) 1259/bjr.20120447
AUTORES / AUTHORS: - Yamagami T; Yoshimatsu R; Miura H; Yamada K; Takahata A; Matsumoto T; Hasebe T
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. yamagami@koto.kpu-m.ac.jp
RESUMEN / SUMMARY: - OBJECTIVE: The goal of our study was to evaluate the diagnostic performance of percutaneous lung biopsy under CT-fluoroscopic guidance for ground-glass opacity (GGO) lesions. METHODS: 85 percutaneous needle lung biopsies were performed in 73 patients. Specimens were obtained by core biopsy utilising an automated cutting needle and were evaluated histologically. Final diagnosis was confirmed by independent surgical pathology, independent culture results or clinical follow-up. RESULTS: Rates of adequate specimens obtained and of precise diagnosis by needle biopsy were 92.9% (79/85) and 90.6% (77/85) of evaluated lung lesions, respectively. Precise diagnosis was achieved in 87.1% (27/31) of lesions </=10 mm in diameter, 90.0% (36/40) of lesions >10 mm to </=20 mm and 100.0% (14/14) of lesions >20 mm. Precision in diagnosing GGO lesions according to the GGO component was 73.9% (17/23) for pure GGO lesions and 96.8% (60/62) for part-solid GGO lesions. Obtaining a precise diagnosis did not differ significantly according to the lesion size (p=0.3840), but differences were significant according to the GGO component (p=0.0047). Malignancy was accurately diagnosed in 35 of 36 malignant lesions for which surgery was later performed. The specific cell type determined from specimens obtained by needle biopsy was exactly the same as the final histological diagnosis obtained after surgery in 20 lesions. CONCLUSION: Tissue-core lung biopsy under CT-fluoroscopic guidance for a GGO lesion provides a high degree of diagnostic accuracy but is less reliable for determining the specific cell type. ADVANCES IN KNOWLEDGE: Percutaneous lung biopsy under CT-fluoroscopic guidance for GGO is useful in differentiating malignancy.
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[264]
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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[265]
TÍTULO / TITLE: - Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: correlation with vascular endothelial growth factor expression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Mar;145(3):702-7; discussion 707-8. doi: 10.1016/j.jtcvs.2012.12.023.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2012.12.023
AUTORES / AUTHORS: - Nwogu CE; Yendamuri S; Tan W; Kannisto E; Bogner P; Morrison C; Cheney R; Dexter E; Picone A; Hennon M; Hutson A; Reid M; Adjei A; Demmy TL
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. chumy.nwogu@roswellpark.org
RESUMEN / SUMMARY: - OBJECTIVES: Lymph node staging provides critical information in patients with non-small cell lung cancer (NSCLC). Lymphangiogenesis may be an important contributor to the pathophysiology of lymphatic metastases. We hypothesized that the presence of lymph node micrometastases positively correlates with vascular endothelial growth factors (VEGFs) A, C, and D as well as VEGF-receptor-3 (lymphangiogenic factors) expression in lymph nodes. METHODS: Forty patients with NSCLC underwent preoperative positron emission tomography-computed tomography and mediastinoscopy. Real-time polymerase chain reaction (RT-PCR) assays for messenger RNA expression of epithelial markers (ie, cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; and palate, lung, and nasal epithelium carcinoma-associated protein) were performed in selected fluorodeoxyglucose-avid lymph nodes. VEGF-A, VEGF-C, VEGF-D, and VEGF receptor-3 expression levels were measured in primary tumors and lymph nodes. Wilcoxon rank sum test was run for the association between the RT-PCR epithelial marker levels and VEGF expression levels in the lymph nodes. RESULTS: RT-PCR for cytokeratin 7; carcinoembryonic antigen-related cell adhesion molecule 5; or palate, lung, and nasal epithelium carcinoma-associated protein indicated lymph node micrometastatic disease in 19 of 35 patients (54%). There was a high correlation between detection of micrometastases and VEGF-A, VEGF-C, VEGF-D, or VEGF receptor-3 expression levels in lymph nodes. Median follow-up was 12.6 months. CONCLUSIONS: RT-PCR analysis of fluorodeoxyglucose-avid lymph nodes results in up-staging a patient’s cancer. Micrometastases correlate with the expression of VEGF in lymph nodes in patients with NSCLC. This may reflect the role of lymphangiogenesis in promoting metastases.
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[266]
TÍTULO / TITLE: - Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Pharmacother. 2013 Feb;47(2):189-97. doi: 10.1345/aph.1R002. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1345/aph.1R002
AUTORES / AUTHORS: - O’Bryant CL; Wenger SD; Kim M; Thompson LA
INSTITUCIÓN / INSTITUTION: - Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA. Cindy.OBryant@ucdenver.edu
RESUMEN / SUMMARY: - OBJECTIVE: To review the characteristics and clinical trial data of crizotinib in ALK-positive non-small cell lung cancer (NSCLC). DATA SOURCE: A literature search using PubMed/MEDLINE (up to December 2012) was performed using the terms crizotinib, ALK-positive, non-small cell lung cancer, and PF-02341066. STUDY SELECTION/DATA EXTRACTION: Phase 1, 2, and 3 trials evaluating the safety and efficacy of crizotinib in a cohort of patients with ALK rearrangements and advanced NSCLC were evaluated. All peer-reviewed articles with clinically relevant information were reviewed. DATA SYNTHESIS: ALK rearrangement results in an aberrant EML4-ALK fusion oncogene that constitutively activates ALK tyrosine kinase, resulting in inhibition of apoptosis and promotion of tumor cell proliferation. Approximately 3-5% of NSCLC exhibit this rearrangement. Crizotinib is an oral selective inhibitor of ALK and mesenchymal epithelial growth factor tyrosine kinases. Early phase trials with crizotinib showed improved response rates of 50-57% and extended duration of response of 6-10 months. Results of these studies led to accelerated Food and Drug Administration (FDA) approval of crizotinib. Further clinical trial results confirmed improvement in response rates, duration of response, as well as progression-free survival in ALK-positive patients with NSCLC receiving crizotinib. The drug undergoes hepatic metabolism by CYP3A4 and demonstrates autoinhibition of CY3A4, thus predisposing it to drug interactions. The most frequent toxicities with crizotinib include mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, and generally reversible, sometimes severe, elevations in aspartate aminotransferase and alanine aminotransferase. CONCLUSIONS: Crizotinib is a novel targeted anticancer agent that appears to be a favorable treatment option for patients with locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test.
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[267]
TÍTULO / TITLE: - TGF-beta1-induced epithelial-mesenchymal transition and acetylation of Smad2 and Smad3 are negatively regulated by EGCG in Human A549 lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 16. pii: S0304-3835(13)00130-4. doi: 10.1016/j.canlet.2013.02.018.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.018
AUTORES / AUTHORS: - Ko H; So Y; Jeon H; Jeong MH; Choi HK; Ryu SH; Lee SW; Yoon HG; Choi KC
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular Oncology, Cheil General Hospital & Women’s Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.
RESUMEN / SUMMARY: - Transforming growth factor-beta1, the key ligand of Smad-dependent signaling pathway, is critical for epithelial-mesenchymal transition during embryo-morphogenesis, fibrotic diseases, and tumor metastasis. In this study, we found that activation of p300/CBP, a histone acetyltransferase, by TGF-beta1 mediates Epithelial-mesenchymal transition (EMT) via acetylating Smad2 and Smad3 in TGF-beta1 signaling pathway. We demonstrated that treatment with EGCG inhibited p300/CBP activity in human lung cancer cells. Also, we observed that EGCG potently inhibited TGF-beta1-induced EMT and reversed the up-regulation of various genes during EMT. Our findings suggest that EGCG inhibits the induction of p300/CBP activity by TGF-beta1. Therefore, EGCG inhibits TGF-beta1-mediated EMT by suppressing the acetylation of Smad2 and Smad3 in human lung cancer cells.
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[268]
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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[269]
TÍTULO / TITLE: - Female sex and long-term survival post curative resection for non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cardiothorac Surg. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt139
AUTORES / AUTHORS: - Warwick R; Shackcloth M; Mediratta N; Page R; McShane J; Shaw M; Poullis M
INSTITUCIÓN / INSTITUTION: - Liverpool Heart and Chest Hospital, Liverpool, UK.
RESUMEN / SUMMARY: - OBJECTIVES: To determine whether patient sex has a significant effect on long-term outcomes post curative resection of non-small-cell lung cancer. METHODS: We retrospectively analysed a prospectively validated thoracic surgery database (n = 4212), from a single institution, from September 2001 to October 2012. Univariate, Cox multivariate and propensity analysis was performed. Long-term follow-up was carried out via the National Strategic Tracing Service that operates in the United Kingdom. RESULTS: One hundred per cent follow-up was achieved. Overall institutional in-hospital mortality was 2.0% for all thoracic resections. Median survival was 2.78 years (range 0-13 years). Two thousand two hundred and thirty-three males and 1979 females were included. Kaplan-Meier survival of all the patients demonstrated superior survival of females for all stages, P = 0.0003, and stage I, P = 0.0006. Female sex conferred no survival advantage in stage II, P = 0.7, and IIIa, P = 0.1. Sub-analysis by histological type demonstrated that females had superior survival with adenocarcinoma compared with males, P < 0.001, but no sex difference existed with squamous carcinomas, P = 0.2. Cox analyses demonstrated that female sex was an advantageous prognostic factor for the entire study group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.69-0.96] and Stage I only (HR 0.70, 95% CI 0.57-0.63). Sex was of no significance in Stage II and IIIa disease with regard to survival. Sub-analysis demonstrated that female sex was not a significant factor determining survival in patients with squamous carcinoma; however, it was significantly associated with increased survival in patients with adenocarcinoma (HR 0.63, 95% CI 0.51-0.78). A 1:1 propensity analysis confirmed the above findings. CONCLUSION: Propensity matching and Cox multivariate regression analysis confirmed the univariate finding that female sex is only associated with improved survival in patients with Stage I adenocarcinoma. Patient sex does not affect survival of patients with squamous carcinoma.
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[270]
TÍTULO / TITLE: - Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 May;34(16):4109-17. doi: 10.1016/j.biomaterials.2013.02.045. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.02.045
AUTORES / AUTHORS: - Xu Z; Gao Y; Hao Y; Li E; Wang Y; Zhang J; Wang W; Gao Z; Wang Q
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, The Second Hospital Affiliated to Dalian Medical University, Dalian 116027, China.
RESUMEN / SUMMARY: - Individualized treatment is a promising clinical strategy for lung cancer, and drug sensitivity testing is fundamental to this scheme. We aimed to develop an effective drug sensitivity test platform to support individualized treatment. We designed a microfluidic chip-based, three-dimensional (3D) co-culture drug sensitivity test platform. A mono-lung cancer cell line, a mixture of lung cancer and stromal cell lines, and cells from fresh lung cancer tissues were cultured in 3D under continuous media supplementation, mimicking the actual tumor microenvironment in vivo. The cells were treated with anti-cancer drugs according to a gradient concentration generator inside the chips to screen the appropriate chemotherapy schemes. We successfully cultured cell lines or primary cells with this device. We also smoothly assayed the sensitivities of different anti-cancer drugs in parallel and accurately screened appropriate-dose, single and combined-drug chemotherapy schemes for eight patients. Our microfluidic device is a simple, reliable, and high-throughput platform to test drug sensitivity. It would be possible for chemotherapists to screen the appropriate chemotherapy schemes to guide individualized treatment in lung cancer.
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[271]
TÍTULO / TITLE: - FUNCTIONAL GENETIC SCREENS IDENTIFY GENES ESSENTIAL FOR TUMOR CELL SURVIVAL IN HEAD-AND-NECK AND LUNG CANCER.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2539
AUTORES / AUTHORS: - Martens-de Kemp SR; Nagel R; Stigter-van Walsum M; van der Meulen IH; van Beusechem VW; Braakhuis BJ; Brakenhoff RH
INSTITUCIÓN / INSTITUTION: - Otolaryngology/Head-Neck Surgery, VU University Medical Center.
RESUMEN / SUMMARY: - PURPOSE: Despite continuous improvement of treatment regimes, the mortality rates for non-small cell lung cancer (NSCLC) and head-and-neck squamous cell carcinoma (HNSCC) remain disappointingly high and novel anticancer agents are urgently awaited. Experimental design: We combined the data from genome-wide siRNA screens on tumor cell lethality in a lung and a head-and-neck cancer cell line. RESULTS: We identified 71 target genes that appear essential for survival of both cancer types. We identified a cluster of 20 genes that play an important role during G2/M phase transition, underlining the importance of this cell cycle checkpoint for tumor cell survival. Five genes from this cluster (CKAP5, KPNB1, RAN, TPX2 and KIF11) were evaluated in more detail and shown to be essential for tumor cell survival in both tumor types, but most particularly in HNSCC. Phenotypes that were observed following siRNA-mediated knockdown of KIF11 (kinesin family member 11) were reproduced by inhibition of KIF11 using the small molecule inhibitor ispinesib (SB-715992). We showed that ispinesib induces a G2 arrest, causes aberrant chromosome segregation and induces cell death in HNSCC in vitro, while primary keratinocytes are less sensitive. Furthermore, growth of HNSCC cells engrafted in immune deficient mice was significantly inhibited after ispinesib treatment. CONCLUSION: This study identified a wide array of druggable genes for both lung and head-and-neck cancer. In particular, multiple genes involved in the G2/M checkpoint were shown to be essential for tumor cell survival, indicating their potential as anticancer targets.
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[272]
TÍTULO / TITLE: - Invasive Pulmonary Adenocarcinomas versus Preinvasive Lesions Appearing as Ground-Glass Nodules: Differentiation by Using CT Features.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiology. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1148/radiol.13120949
AUTORES / AUTHORS: - Lee SM; Park CM; Goo JM; Lee HJ; Wi JY; Kang CH
INSTITUCIÓN / INSTITUTION: - Departments of Radiology and Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, and Institute of Radiation Medicine, Seoul National University Medical Research Center, 101 Daehangno, Jongno-gu, Seoul 110-744, Korea.
RESUMEN / SUMMARY: - Purpose:To retrospectively investigate the differentiating computed tomographic (CT) features between invasive pulmonary adenocarcinoma (IPA) and preinvasive lesions appearing as ground-glass nodules (GGNs) in 253 patients.Materials and Methods:This study was approved by the institutional review board. From January 2005 to October 2011, 272 GGNs were pathologically confirmed (179 IPAs and 93 preinvasive lesions) in 253 patients and were included in this study. There were 64 pure GGNs and 208 part-solid GGNs. Preinvasive lesions consisted of 21 atypical adenomatous hyperplasias and 72 adenocarcinomas in situ. To identify the differentiating CT features between IPAs and preinvasive lesions and to evaluate their differentiating accuracy, logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed, respectively.Results:In pure GGNs, preinvasive lesions were significantly smaller and more frequently nonlobulated than IPAs (P < .05). Multivariate analysis revealed that lesion size was the single significant differentiator of preinvasive lesions from IPAs (P = .029). The optimal cut-off size for preinvasive lesions was less than 10 mm (sensitivity, 53.33%; specificity, 100%). In part-solid GGNs, there were significant differences in lesion size, solid portion size, solid proportion, margin, border, and pleural retraction between IPAs and preinvasive lesions (P < .05). Multivariate analysis revealed that smaller lesion size, smaller solid proportion, nonlobulated border, and nonspiculated margin were significant differentiators of preinvasive lesions (P < .05), with excellent differentiating accuracy (area under ROC curve, 0.905).Conclusion:In pure GGNs, a lesion size of less than 10 mm can be a very specific discriminator of preinvasive lesions from IPAs. In part-solid GGNs, preinvasive lesions can be accurately distinguished from IPAs by the smaller lesion size, smaller solid proportion, nonlobulated border, and nonspiculated margin.© RSNA, 2013.
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[273]
TÍTULO / TITLE: - Galectin-1 promotes lung cancer tumor metastasis by potentiating integrin alpha6beta4 and Notch1/Jagged2 signaling pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt040
AUTORES / AUTHORS: - Hsu YL; Wu CY; Hung JY; Lin YS; Huang MS; Kuo PL
INSTITUCIÓN / INSTITUTION: - Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
RESUMEN / SUMMARY: - Lung cancer is a major cancer, leading in both incidence and mortality in the world, and metastasis underlies the majority of lung cancer-related deaths. Galectin-1, a glycan-binding protein, has been shown to be overexpressed in lung cancer and involved in tumor-mediated immune suppression. However, the functional role of galectin-1 in lung cancer per se remains unknown. We demonstrate that ectopic expression of galectin-1 in a low-metastatic CL1-0 lung cancer cell line promotes its migration, invasion and epithelial-mesenchymal transition. Conversely, we also show that suppression of galectin-1 expression in highly invasive CL1-5 and A549 cells inhibits migration and invasion of lung cancer cell and causes a mesenchymal-epithelial transition. These effects may be transduced by increasing the expression of integrin alpha6beta4 and Notch1/Jagged2, which in turn co-operates in the phosphorylation of AKT. The effects of galectin-1 on cancer progression are reduced when integrin beta4 and Notch1 are absent. Further study has indicated that galectin-1 knockdown prevents the spread of highly metastatic Lewis lung carcinoma in vivo. Our study suggests that galectin-1 represents a crucial regulator of lung cancer metastasis. Thus, the detection and targeted treatment of galectin-1-expressing cancer serves as a new therapeutic target for lung cancer.
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[274]
TÍTULO / TITLE: - Tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone suppresses a newly identified anti-tumor IGFBP-3/IGFBP-3R system in lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 13. pii: S0169-5002(13)00075-5. doi: 10.1016/j.lungcan.2013.02.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.016
AUTORES / AUTHORS: - Harada A; Jogie-Brahim S; Oh Y
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
RESUMEN / SUMMARY: - IGFBP-3 is a tumor suppressor whose expression is frequently suppressed in lung cancer. NNK, the most potent tobacco carcinogen, enhanced cell proliferation of BEAS-2B normal lung epithelial cells and concomitantly suppressed IGFBP-3 expression through DNA methylation. Decreased IGFBP-3 expression and elevated levels of phospho-Akt, phospho-p65-NF-kappaB, and cyclin D1 were detected in tobacco carcinogen-induced tumorigenic derivatives of BEAS-2B. Overexpression of IGFBP-3 in NNKA, one of the derivatives, suppressed NF-kappaB activity and induced apoptosis, which was hindered by knocking-down of endogenous IGFBP-3R, an IGFBP-3 specific receptor. These results suggest that NNK inhibits IGFBP-3 expression to abrogate anti-tumor actions of the IGFBP-3/IGFBP-3R system in smoking-induced lung cancer.
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[275]
TÍTULO / TITLE: - Analyses of Radiation and Mesothelioma in the US Transuranium and Uranium Registries.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Public Health. 2013 Apr;103(4):710-716. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 2105/AJPH.2012.300928
AUTORES / AUTHORS: - Gibb H; Fulcher K; Nagarajan S; McCord S; Fallahian NA; Hoffman HJ; Haver C; Tolmachev S
INSTITUCIÓN / INSTITUTION: - Herman Gibb and Keri Fulcher are with Tetra Tech Sciences, Arlington, VA. Sumitha Nagarajan is with the American Registry of Pathology, Dover, DE. Stacey McCord and Sergei Tolmachev are with the US Transuranium and Uranium Registries, College of Pharmacy, Washington State University, Richland. Naz Afarin Fallahian is with the Department of Physics and Engineering Technology, Bloomsburg University of Pennsylvania, Bloomsburg. Heather J. Hoffman is with the Department of Epidemiology and Biostatistics, School of Public Health and Health Services, The George Washington University, Washington, DC. At the time of the writing, Cary Haver was with Tetra Tech Sciences.
RESUMEN / SUMMARY: - Objectives. We examined the relationship between radiation and excess deaths from mesothelioma among deceased nuclear workers who were part of the US Transuranium and Uranium Registries. Methods. We performed univariate analysis with SAS Version 9.1 software. We conducted proportionate mortality ratio (PMR) and proportionate cancer mortality ratio (PCMR) analyses using the National Institute for Occupational Safety and Health Life Table Analysis System with the referent group being all deaths in the United States. Results. We found a PMR of 62.40 (P < .05) and a PCMR of 46.92 (P < .05) for mesothelioma. PMRs for the 4 cumulative external radiation dose quartiles were 61.83, 57.43, 74.46, and 83.31. PCMRs were 36.16, 47.07, 51.35, and 67.73. The PMR and PCMR for trachea, bronchus, and lung cancer were not significantly elevated. Conclusions. The relationship between cumulative external radiation dose and the PMR and PCMR for mesothelioma suggests that external radiation at nuclear facilities is associated with an increased risk of mesothelioma. The lack of a significantly elevated PMR and PCMR for trachea, bronchus, and lung cancer suggests that asbestos did not confound this relationship.
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[276]
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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[277]
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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[278]
TÍTULO / TITLE: - Aldo-keto reductase 1C3 may be a new radioresistance marker in non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar 22. doi: 10.1038/cgt.2013.15.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.15
AUTORES / AUTHORS: - Xie L; Yu J; Guo W; Wei L; Liu Y; Wang X; Song X
INSTITUCIÓN / INSTITUTION: - Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, China.
RESUMEN / SUMMARY: - Human aldo-keto reductase 1C3, type 2 3alpha-hydroxysteroid dehydrogenase (HSD)/type 5 17beta-HSD (AKR1C3) is known to be involved in steroid, prostaglandin and lipid aldehyde metabolism. The role of AKR1C3 in the radiosensitivity to X-rays of human non-small-cell lung cancer (NSCLC) cells was explored. In this study, a specific small interfering RNA (siRNA) to target the AKR1C3 gene was used. A suite of readouts including cell survival were determined using a colony formation assay; apoptosis evaluated by Annexin V expression levels, irradiation-induced cytotoxicity established using a MTT cell viability assay and cell cycle distribution measured by flow cytometry were used in characterizing the role of the AKR1C3 gene. Although AKR1C3 was significantly overexpressed in both our radioresistant subclone cells and NSCLC tissues, a specific AKR1C3 siRNA significantly enhanced cell radiosensitivity and was concomitant with decreased expression of this gene. Furthermore, reduced interleukin-6 (IL-6)-mediated radioresistance was observed when siRNA was used to knock down AKR1C3 activity. This AKR1C3-mediated radioresistance was correlated with an arrest in the G2/M cell cycle and a decreased induction of apoptosis. AKR1C3 may present a potential therapeutic target in addressing radioresistance of NSCLC, and in particular in IL-6-mediated radioresistance.Cancer Gene Therapy advance online publication, 22 March 2013; doi:10.1038/cgt.2013.15.
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[279]
TÍTULO / TITLE: - Assessment of the robustness of volumetric-modulated arc therapy for lung radiotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Radiol. 2013 Mar;86(1023):20120498. doi: 10.1259/bjr.20120498. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1259/bjr.20120498
AUTORES / AUTHORS: - Edmunds K; Bedford J
INSTITUCIÓN / INSTITUTION: - The Royal Marsden NHS Foundation Trust, Sutton, UK. Katie.Edmunds@rmh.nhs.uk
RESUMEN / SUMMARY: - Volumetric-modulated arc therapy (VMAT) is increasingly popular as a treatment method in radiotherapy owing to the speed with which treatments can be delivered. However, there has been little investigation into the effect of increased modulation in lung plans with regard to interfraction organ motion. This is most likely to occur where the planning target volume (PTV) lies within areas of low density. This paper aims to investigate the effect of modulation on the dose distribution using simulated patient movement and to propose a method that is less susceptible to such movement. Simulated interfraction motion is achieved by moving the plan isocentre in steps of 0.5 cm and 1.0 cm in six directions for five clinical VMAT patients. The proposed planning method involves optimisation using a density override of 1 g cm(-3), within the PTV in lung, to reduce segment boosting in the periphery of the PTV. This investigation shows that modulation can result in an increase in the maximum dose of >25%, an increase in PTV near-maximum dose of 17% and a reduction in near-minimum dose by 46%. Unacceptable organ at risk (OAR) doses are also seen. The proposed method reduces modulation, resulting in a maximum dose increase of 10%. Although safeguards are in place to prevent the increased dose to OARs from patient movement, there is nothing to prevent the increased dose as a result of modulation in lung. A simple planning method is proposed to safeguard against this effect. Investigation suggests that, where modulation exists in a plan, this method reduces it and is clinically viable.
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[280]
TÍTULO / TITLE: - Association of carcinogenic polycyclic aromatic hydrocarbon emissions and smoking with lung cancer mortality rates on a global scale.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Environ Sci Technol. 2013 Apr 2;47(7):3410-6. doi: 10.1021/es305295d. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1021/es305295d
AUTORES / AUTHORS: - Motorykin O; Matzke MM; Waters KM; Massey Simonich SL
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, Oregon State University , Corvallis, Oregon 97331, United States.
RESUMEN / SUMMARY: - The objective of this research was to investigate the relationship between lung cancer mortality rates, carcinogenic polycyclic aromatic hydrocarbon (PAH) emissions, and smoking on a global scale, as well as for different socioeconomic country groups. The estimated lung cancer deaths per 100,000 people (ED100000) and age standardized lung cancer death rate per 100,000 people (ASDR100000) in 2004 were regressed on PAH emissions in benzo[a]pyrene equivalence (BaPeq), smoking prevalence, cigarette price, gross domestic product per capita, percentage of people with diabetes, and average body mass index using simple and multiple linear regression for 136 countries. Using stepwise multiple linear regression, a statistically significant positive linear relationship was found between loge(ED100000) and loge(BaPeq) emissions for high (p-value <0.01) and for the combination of upper-middle and high (p-value <0.05) socioeconomic country groups. A similar relationship was found between loge(ASDR100000) and loge(BaPeq) emissions for the combination of upper-middle and high (p-value <0.01) socioeconomic country groups. Conversely, for loge(ED100000) and loge(ASDR100000), smoking prevalence was the only significant independent variable in the low socioeconomic country group (p-value <0.001). These results suggest that reducing BaPeq emissions in the U.S., Canada, Australia, France, Germany, Brazil, South Africa, Poland, Mexico, and Malaysia could reduce ED100000, while reducing smoking prevalence in Democratic People’s Republic of Korea, Nepal, Mongolia, Cambodia, and Bangladesh could significantly reduce the ED100000 and ASDR100000.
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[281]
TÍTULO / TITLE: - Ubc9 promotes invasion and metastasis of lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1588-94. doi: 10.3892/or.2013.2268. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2268
AUTORES / AUTHORS: - Li H; Niu H; Peng Y; Wang J; He P
INSTITUCIÓN / INSTITUTION: - Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer-related mortality worldwide. The mortality is high mainly due to the lack of known effective screening procedures; there is a high tendency for early spread and systemic therapies do not cure metastatic disease. Thus, it is important to investigate the molecular mechanism(s) of lung cancer development and, specifically, to identify an effective method by which to inhibit the invasion and metastasis of lung cancer. Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays a key role in tumorigenesis. Whether Ubc9 is involved in the invasion and metastasis of lung cancer remains unknown. Herein, we report that Ubc9 exhibits an important role in lung cancer invasion and metastasis. We first investigated the biological effect of Ubc9 on lung cancer by cloning the Ubc9 gene into a eukaryotic expression plasmid and stably expressing it in the human small cell lung cancer cell line NCI-H446 in order to observe any biological changes. We further analyzed the effect of Ubc9 in an in vivo experiment, injecting NCI-H446 cells stably overexpressing Ubc9 into nude mice and analyzing their metastatic ability. Our results demonstrated that Ubc9 is expressed at higher levels in primary lung cancer tissue and metastatic nodules as compared to premalignant and/or normal tissue. Furthermore, we demonstrated that upregulation of Ubc9 expression promotes migration and invasion. Ubc9 likely plays an important role in cancer progression by promoting invasion and metastasis in lung cancer.
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[282]
TÍTULO / TITLE: - Epigallocatechin gallate promotes p53 accumulation and activity via the inhibition of MDM2-mediated p53 ubiquitination in human lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 12. doi: 10.3892/or.2013.2343.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2343
AUTORES / AUTHORS: - Jin L; Li C; Xu Y; Wang L; Liu J; Wang D; Hong C; Jiang Z; Ma Y; Chen Q; Yu F
INSTITUCIÓN / INSTITUTION: - Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
RESUMEN / SUMMARY: - Epigallocatechin gallate (EGCG), which is derived from green tea, is well known for its chemopreventive activity. Several studies have shown that p53 plays an important role in the activity of EGCG; however, the mechanism by which EGCG regulates p53 requires further investigation. In the present study, we showed that EGCG inhibits anchorage-independent growth of human lung cancer cells by upregulating p53 expression. EGCG treatment can substantially increase p53 stability, promote nuclear localization of p53 and decrease nuclear accumulation of MDM2. We also found that EGCG increases the phosphorylation of p53 at Ser15 and Ser20 and enhances its transcriptional activity. Although EGCG promotes MDM2 expression in a p53-dependent manner, the interaction between MDM2 and p53 was significantly inhibited following EGCG treatment, which resulted in the inhibition of MDM2-mediated p53 ubiquitination. Thus, our results suggest that the stabilization and activation of p53 may partly contribute to the anticancer activity of EGCG.
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[283]
TÍTULO / TITLE: - Correction to text and figure: high risk of malignant mesothelioma and pleural plaques in subjects born close to ophiolites.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chest. 2013 Mar 1;143(3):880. doi: 10.1378/chest.13-0227.
●● Enlace al texto completo (gratuito o de pago) 1378/chest.13-0227
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[284]
TÍTULO / TITLE: - Octa-arginine-modified pegylated liposomal doxorubicin: An effective treatment strategy for non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 16. pii: S0304-3835(13)00132-8. doi: 10.1016/j.canlet.2013.02.020.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.020
AUTORES / AUTHORS: - Biswas S; Deshpande PP; Perche F; Dodwadkar NS; Sane SD; Torchilin VP
INSTITUCIÓN / INSTITUTION: - Center for Pharmaceutical Biotechnology and Nanomedicine, 360 Huntington Avenue, 140 The Fenway, Northeastern University, Boston, MA 02115, United States.
RESUMEN / SUMMARY: - The present study aims to evaluate the efficacy of octa-arginine (R8)-modified pegylated liposomal doxorubicin (R8-PLD) for the treatment of non-small cell lung cancer, for which the primary treatment modality currently consists of surgery and radiotherapy. Cell-penetrating peptide R8 modification of Doxorubicin-(Dox)-loaded liposomes was performed by post-insertion of an R8-conjugated amphiphilic PEG-PE copolymer (R8-PEG-DOPE) into the liposomal lipid bilayer. In vitro analysis with the non-small cell lung cancer cell line, A549 confirmed the efficient cellular accumulation of Dox, delivered by R8-PLD compared to PLD. It led to the early initiation of apoptosis and a 9-fold higher level of the apoptotic regulator, caspase 3/7 (9.24+/-0.34) compared to PLD (1.07+/-0.19) at Dox concentration of 100mug/mL. The treatment of A549 monolayers with R8-PLD increased the level of cell death marker lactate dehydrogenase (LDH) secretion (1.2+/-0.1 for PLD and 2.3+/-0.1 for R8-PLD at Dox concentration of 100mug/mL) confirming higher cytotoxicity of R8-PLD than PLD, which was ineffective under the same treatment regimen (cell viability 90+/-6% in PLD vs. 45+/-2% in R8-PLD after 24h). R8-PLD had significantly higher penetration into the hypoxic A549 tumor spheroids compared to PLD. R8-PLD induced greater level of apoptosis to A549 tumor xenograft and dramatic inhibition of tumor volume and tumor weight reduction. The R8-PLD treated tumor lysate had a elevated caspase 3/7 expression than with R8-PLD treatment. This suggested system improved the delivery efficiency of Dox in selected model of cancer which supports the potential usefulness of R8-PLD in cancer treatment, lung cancer in particular.
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[285]
TÍTULO / TITLE: - Immunostaining with EGFR mutation-specific antibodies: a reliable screening method for lung adenocarcinomas harboring EGFR mutation in biopsy and resection samples.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 1. pii: S0046-8177(12)00450-9. doi: 10.1016/j.humpath.2012.12.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.12.002
AUTORES / AUTHORS: - Fan X; Liu B; Xu H; Yu B; Shi S; Zhang J; Wang X; Wang J; Lu Z; Ma H; Zhou X
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Clinical School of Medical College of Nanjing University, Nanjing Jinling Hospital, Nanjing, Jiangsu 210008, PR China.
RESUMEN / SUMMARY: - Mutation analysis of epidermal growth factor receptor (EGFR) is essential in determining the therapeutic strategy for lung adenocarcinoma. Immunohistochemical (IHC) staining with EGFR mutation-specific antibodies of del E746-A750 in exon 19 and L858R in exon 21 has been evaluated in resection specimens in a few studies but rarely in biopsy samples. A total of 169 cases (78 biopsies and 91 resected specimens) of lung adenocarcinoma with EGFR mutation status predefined by direct DNA sequencing were histologically examined, and IHC was performed using EGFR mutation-specific antibodies of del E746-A750 and L858R. The cases with positive results by IHC but negative results by direct DNA sequencing were examined by amplified refractory mutation system. Our results showed that the frequency of EGFR mutations for both E746-A750 deletion and L858R mutation was 38.5% (65/169) by DNA sequencing or amplified refractory mutation system and 34.3% (58/169) by IHC in lung adenocarcinomas. Based on molecular test results, the overall sensitivity, specificity, positive predictive value, and negative predictive value of IHC using these 2 antibodies in all (biopsy/resection) cases were 87.7% (80%/94.3%), 99.0% (97.9%/100%), 98.3% (96%/100%), and 92.8% (88.7%/96.6%), respectively. Lung adenocarcinomas with a predominant acinar, papillary, lepidic, or solid growth pattern more often harbor EGFR mutation of del E746-A750 or L858R. In conclusion, the immunostaining with EGFR del E746-A750 and L858R mutation antibodies is a reliable screening method with high specificity and sensitivity for identifying the EGFR mutation in both resected and biopsied lung adenocarcinomas.
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[286]
TÍTULO / TITLE: - Lung cancer circulating tumor cells isolated by the EpCAM-independent enrichment strategy correlate with Cytokeratin 19-derived CYFRA21-1 and pathological staging.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Chim Acta. 2013 Apr 18;419:57-61. doi: 10.1016/j.cca.2013.01.015. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cca.2013.01.015
AUTORES / AUTHORS: - Chen Q; Ge F; Cui W; Wang F; Yang Z; Guo Y; Li L; Bremner RM; Lin PP
INSTITUCIÓN / INSTITUTION: - Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
RESUMEN / SUMMARY: - BACKGROUND: Cytokeratin 19-derived CYFRA21-1 is an acceptable lung cancer biomarker. However, whether CYFRA21-1 correlates with lung cancer circulating tumor cells (CTCs) remains unclear. METHODS: CTCs in 42 lung cancer patients and 10 nonmalignant pulmonary disease patients were isolated by means of an EpCAM-independent enrichment strategy. Correlation of lung cancer CTCs with serum concentration of CYFRA21-1 and pathological staging was investigated. RESULTS: Among lung cancer patients in this study, 39% (7/18) of those with normal CYFRA21-1 (</=3.3ng/ml) and 62% (13/21) of high CYFRA21-1 (>3.3ng/ml) patients were found to have >/=3 CTCs/7.5ml blood. The CTCs-positive rate of stage I to IV lung cancer patients was 20% (2/10), 45% (5/11), 54% (6/11) and 70% (7/10), respectively. Comparing M0 vs M1 patients, the CTCs-positive rate was 43% (13/30) and 70% (7/10), respectively. All M1 patients (10/10) had one or more CTCs detected, whereas none of the nonmalignant pulmonary disease patients had detectable CTCs. CONCLUSION: Lung cancer CTCs isolated by the EpCAM-independent enrichment approach correlate with CYFRA21-1 and TNM staging. Correlation of CTCs and CYFRA21-1 in lung cancer patients is of potential clinical utility in terms of early diagnosis and predicting prognosis.
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[287]
TÍTULO / TITLE: - The relationship of metalloproteinase gene polymorphisms and lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Res. 2013 Feb 14. pii: S0022-4804(13)00069-3. doi: 10.1016/j.jss.2013.01.045.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jss.2013.01.045
AUTORES / AUTHORS: - Sanli M; Akar E; Pehlivan S; Bakir K; Tuncozgur B; Isik AF; Pehlivan M; Elbeyli L
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Gaziantep University, Gaziantep, Turkey. Electronic address: sanli@gantep.edu.tr.
RESUMEN / SUMMARY: - BACKGROUND: We analyzed the relationship between matrix metalloproteinase (MMP)-2, -7, and -13 gene expression and polymorphisms and disease susceptibility and prognosis in patients who had undergone surgery for non-small-cell lung cancers. MATERIALS AND METHODS: The study group consisted of 132 patients who had undergone radical surgery for non-small-cell lung cancers. The control group consisted of 80 healthy volunteers. We isolated deoxyribonuclease samples for use in analyzing gene polymorphisms from pathology blocks for the patient group and from blood samples for the control group. We identified MMP gene polymorphisms with polymerase chain reaction and restriction fragment length polymorphisms. Results were compared with those of the control group to evaluate disease susceptibility, correlation with other clinical parameters, and with survival and prognosis by using appropriate statistical methods. RESULTS: When we compared polymorphisms pertaining to MMP genes in healthy controls and lung tumor DNA, we observed a decrease in the MMP-2 (-735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes (P = 0.008, P = 0.047, and P = 0.047, respectively). For the MMP-7 (-181) polymorphism, the genotype did not differ significantly for disease susceptibility. Median overall survival time was 25.5 mo in the MMP-13 AA/AG genotypes and 9.3 mo in the GG genotype. CONCLUSIONS: Decreases in the MMP-2 (-735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes increase the risk for lung cancer. Furthermore, the presence of the MMP-13 (A77G) polymorphism GG genotype is an unfavorable prognostic factor.
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[288]
TÍTULO / TITLE: - ACR Appropriateness Criteria® Radiation Therapy for Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Clin Oncol. 2013 Apr;36(2):206-213.
●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e31827e5523
AUTORES / AUTHORS: - Kong FM; Lally BE; Chang JY; Chetty IJ; Decker RH; Ginsburg ME; Kestin LL; Langer CJ; Movsas B; Videtic GM; Willers H; Rosenzweig KE
INSTITUCIÓN / INSTITUTION: - *Ann Arbor Veteran Affairs Medical Center, University of Michigan, Ann Arbor, MI section signHenry Ford Health System, Detroit, MI #21st Century Oncology of Michigan, A Division of Michigan Healthcare Professionals, Farmington Hills, MI daggerDepartment of Radiation Oncology, University of Miami, Miami, FL double daggerMD Anderson Cancer Center, Houston, TX parallelYale University School of Medicine, New Haven, CT paragraph signSociety of Thoracic Surgeons, Columbia University, New York, NY section sign section signMount Sinai School of Medicine, New York, NY **Department of Medicine, University of Pennsylvania, Philadelphia, PA daggerdaggerCleveland Clinic Foundation, Cleveland, OH double daggerdouble daggerMassachusetts General Hospital, Boston, MA.
RESUMEN / SUMMARY: - The current standard of care for small cell lung cancer is combined-modality therapy, including the use of chemotherapy, surgery (in selected cases of limited stage of disease), and radiation therapy. This review will focus on the role, dose fractionation, technology and timing of thoracic radiation, and the role and dose regimen of prophylactic cranial irradiation for both limited and extensive stage of diseases. Consensus recommendation from experts is summarized in the tables for 2 typical case scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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[289]
TÍTULO / TITLE: - Phase II study of docetaxel in combination with everolimus for second- or third-line therapy of advanced non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):369-72. doi: 10.1097/JTO.0b013e318282709c.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318282709c
AUTORES / AUTHORS: - Ramalingam SS; Owonikoko TK; Behera M; Subramanian J; Saba NF; Kono SA; Gal AA; Sica G; Harvey RD; Chen Z; Klass CM; Shin DM; Fu H; Sun SY; Govindan R; Khuri FR
INSTITUCIÓN / INSTITUTION: - Department of Hematology and Medical Oncology, Emory University, Winship Cancer Institute, 1365 Clifton Road NE, Atlanta, GA 30322, USA. ssramal@emory.edu
RESUMEN / SUMMARY: - We conducted a phase II study of docetaxel in combination with everolimus, a mammalian target of rapamycin (mTOR) inhibitor, for salvage therapy of advanced non-small-cell lung cancer (NSCLC) based on promising preclinical and early-phase clinical data. Patients with advanced-stage NSCLC treated with one or two previous systemic therapy regimens were given docetaxel (60 mg/m) and everolimus (5 mg orally once daily on days 1-19) every 3 weeks. Archived tumor specimens were evaluated for markers of mTOR pathway activation (total and phosphorylated mTOR, Akt, S6, eIF4e, and 4EBP1). Twenty-eight patients were enrolled (median age: 62 years; male: 13; Caucasians: 19; adenocarcinoma: 20; performance status 0, 3; performance status 1, 23; 1 previous regimen, 16). A median of 3.5 cycles of therapy was administered. Two patients experienced partial response and 15 had stable disease (clinical benefit rate, 70%). The 6-month progression-free survival rate was 5%, and the median overall survival was 9.6 months. Low pAkt expression correlated with clinical benefit rate (p = 0.01) but not with progression-free survival or overall survival. The combination of everolimus and docetaxel was tolerated well, but the efficacy was relatively modest in an unselected population of patients with NSCLC.
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[290]
TÍTULO / TITLE: - Effects of nonstarch polysaccharides with different molecular weights on the development of lewis lung carcinoma in mice and efficiency of cytostatic therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bull Exp Biol Med. 2013 Jan;154(4):492-6.
AUTORES / AUTHORS: - Rybalkina OY; Razina TG; Lopatina KA; Amosova EN; Krylova SG; Efimova LA; Safonova EA; Zueva EP; Khotimchenko MY; Khotimchenko YS
INSTITUCIÓN / INSTITUTION: - Institute of Pharmacology, Siberian Division of the Russian Academy of Medical Sciences, Tomsk; A. V. Zhirmunsky Institute of Marine Biology, Far Eastern Division of the Russian Academy of Sciences; School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia. zep0929@mail.ru.
RESUMEN / SUMMARY: - The effects of nonstarch polysaccharides with different molecular weights on the development of Lewis’ lung carcinoma and efficiency of cyclophosphamide therapy in mice were studied. Treatment with these substances with low molecular weights (<30 kDa) caused no changes in the primary tumor growth, but inhibited its metastasizing, while nonstarch polysaccharides with high molecular weights (>400 kDa) inhibited the growth of Lewis’ lung carcinoma node. Antimetastatic effects of cyclophosphamide were stimulated by low and high molecular weight polysaccharides.
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[291]
TÍTULO / TITLE: - Successful Treatment of Preadolescents With Small Cell Carcinoma of the Ovary Hypercalcemic Type.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pediatr Hematol Oncol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318282cca8
AUTORES / AUTHORS: - Pressey JG; Kelly DR; Hawthorne HT
INSTITUCIÓN / INSTITUTION: - Departments of *Pediatrics, Division of Hematology-Oncology daggerPathology and Laboratory Medicine, Children’s Hospital of Alabama, University of Alabama at Birmingham, Birmingham, AL.
RESUMEN / SUMMARY: - BACKGROUND:: Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare tumor with a peak incidence in young adulthood that historically has carried a poor prognosis. OBSERVATIONS:: We present 2 advanced stage cases of SCCOHT in preadolescents successfully treated with a combination of cisplatin-based chemotherapy and surgical resection. The more recent patient also underwent consolidative high-dose chemotherapy with stem cell rescue and external beam radiotherapy. Her therapy was concluded with a maintenance course of bevacizumab. The patients are now disease-free 7 years and 30 months, respectively, after diagnosis. CONCLUSIONS:: With aggressive multimodal therapy SCCOHT is curable in children.
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[292]
TÍTULO / TITLE: - Non-Small Cell Lung Cancer Stage IV Long-Term Survival With Isolated Spleen Metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Apr;95(4):1432-4. doi: 10.1016/j.athoracsur.2012.08.086.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.08.086
AUTORES / AUTHORS: - Sardenberg RA; Pinto C; Bueno CA; Younes RN
INSTITUCIÓN / INSTITUTION: - Thoracic Surgery, Sao Jose Hospital, Sao Paulo, Brazil. Electronic address: rodafs@uol.com.br.
RESUMEN / SUMMARY: - Splenic metastasis is rare and generally associated with disseminated disease, often seen in breast cancer, colorectal and ovarian carcinoma, and melanoma. Isolated metastasis to the spleen is rare, with only 93 cases from all sources having been reported up to 2007. Moreover, isolated splenic metastasis from primary lung cancer is extremely rare, with only 11 cases reported to date. We report a case of isolated splenic metastasis in a woman 8 months after lobectomy for an adenocarcinoma in the right lung completely resected. After 8 years of follow-up, the patient is still alive with no evidence of metastatic recurrence.
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[293]
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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[294]
TÍTULO / TITLE: - Ecteinascidin 770, a tetrahydroisoquinoline alkaloid, sensitizes human lung cancer cells to anoikis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):505-12.
AUTORES / AUTHORS: - Powan P; Saito N; Suwanborirux K; Chanvorachote P
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulakongkorn University, Phatumwan, Bangkok, 10330 Thailand. pithi_chan@yahoo.com
RESUMEN / SUMMARY: - BACKGROUND: The strategies for achieving anti-metastasis have received increased research interest and clinical attention. The anoikis-sensitizing effect of ecteinascidin 770 (ET-770) was investigated in the present study in non-small cell lung cancer cells. MATERIALS AND METHODS: ET-770 isolated from Ecteinascidia thurstoni was tested for its anoikis-sensitizing effect on H23 and H460 human lung cancer cells by 2,3-b-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. The levels of proteins being involved in anoikis of cells were determined by western blot analysis. RESULTS: ET-770 was shown to enhance anoikis response of human lung cancer H23 cells in a dose-dependent manner. The underlying mechanism was investigated and it was found that ET-770 sensitized the cells by activating the p53 protein, which in turn down-regulated anti-apoptotic myeloid cell leukemia sequence-1 (MCL1) and up-regulated BCL2-associated X protein (BAX) proteins. However, B-cell lymphoma-2 (BCL2) proteins were not significantly affected by ET-770. Further, the anoikis sensitization of ET-770 was observed in H460 lung cancer cells. CONCLUSION: The present results reveal for the first time that ET-770 can sensitize anoikis through the p53 pathway and further development of this compound for therapeutic use is warranted.
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[295]
TÍTULO / TITLE: - A Phase II Study of Amrubicin as a Third-Line or Fourth-Line Chemotherapy for Patients With Non-Small Cell Lung Cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0901.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncologist. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1634/theoncologist.2012-0308
AUTORES / AUTHORS: - Harada T; Oizumi S; Ito K; Takamura K; Kikuchi E; Kuda T; Sugawara S; Suzuki A; Maemondo M; Fujita Y; Kinoshita I; Inoue A; Hommura F; Katsuura Y; Dosaka-Akita H; Isobe H; Nishimura M
INSTITUCIÓN / INSTITUTION: - Hokkaido Social Insurance Hospital, Sapporo, Japan;
RESUMEN / SUMMARY: - Amrubicin, a third-generation synthetic anthracycline agent, has favorable clinical activity and acceptable toxicity for the treatment of patients with non-small cell lung cancer (NSCLC) and small cell lung cancer. We conducted this study to evaluate the efficacy and safety of amrubicin for advanced NSCLC patients as a third- or fourth-line therapy. Eligible patients had recurrent or refractory advanced NSCLC after second- or third-line therapy. Patients received amrubicin, 35 mg/m2 i.v. on days 1-3 every 3 weeks. The primary endpoint was the disease control rate (DCR). Secondary endpoints were the overall survival (OS) time, progression-free survival (PFS) time, response rate, and toxicity profile. Of the 41 patients enrolled, 26 received amrubicin as a third-line and 15 received it as a fourth-line therapy. The median number of treatment cycles was two (range, 1-9). Objective responses were complete response (n = 0), partial response (n = 4), stable disease (n = 21), progressive disease (n = 15), and not evaluable (n = 1), resulting in a DCR of 61.0% (95% confidence interval, 46.0%-75.9%). The overall response rate was 9.8% (95% confidence interval, 0.6%-18.8%). The median PFS interval was 3.0 months, median OS time was 12.6 months, and 1-year survival rate was 53.7%. Grade 3 or 4 hematological toxicities were neutropenia (68%), anemia (12%), thrombocytopenia (12%), and febrile neutropenia (17%). Nonhematological toxicities were mild and reversible. No treatment-related deaths were observed. Amrubicin showed significant clinical activity with manageable toxicities as a third- or fourth-line therapy for patients with advanced NSCLC. This study provides relevant data for routine practice and future prospective trials evaluating third- or fourth-line treatment strategies for patients with advanced NSCLC.
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[296]
TÍTULO / TITLE: - Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Genet. 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1007/s00439-013-1270-y
AUTORES / AUTHORS: - Brenner DR; Brennan P; Boffetta P; Amos CI; Spitz MR; Chen C; Goodman G; Heinrich J; Bickeboller H; Rosenberger A; Risch A; Muley T; McLaughlin JR; Benhamou S; Bouchardy C; Lewinger JP; Witte JS; Chen G; Bull S; Hung RJ
INSTITUCIÓN / INSTITUTION: - International Agency for Research on Cancer, Lyon, France, brenner.darren@gmail.com.
RESUMEN / SUMMARY: - Recent evidence suggests that inflammation plays a pivotal role in the development of lung cancer. In this study, we used a two-stage approach to investigate associations between genetic variants in inflammation pathways and lung cancer risk based on genome-wide association study (GWAS) data. A total of 7,650 sequence variants from 720 genes relevant to inflammation pathways were identified using keyword and pathway searches from Gene Cards and Gene Ontology databases. In Stage 1, six GWAS datasets from the International Lung Cancer Consortium were pooled (4,441 cases and 5,094 controls of European ancestry), and a hierarchical modeling (HM) approach was used to incorporate prior information for each of the variants into the analysis. The prior matrix was constructed using (1) role of genes in the inflammation and immune pathways; (2) physical properties of the variants including the location of the variants, their conservation scores and amino acid coding; (3) LD with other functional variants and (4) measures of heterogeneity across the studies. HM affected the priority ranking of variants particularly among those having low prior weights, imprecise estimates and/or heterogeneity across studies. In Stage 2, we used an independent NCI lung cancer GWAS study (5,699 cases and 5,818 controls) for in silico replication. We identified one novel variant at the level corrected for multiple comparisons (rs2741354 in EPHX2 at 8q21.1 with p value = 7.4 x 10(-6)), and confirmed the associations between TERT (rs2736100) and the HLA region and lung cancer risk. HM allows for prior knowledge such as from bioinformatic sources to be incorporated into the analysis systematically, and it represents a complementary analytical approach to the conventional GWAS analysis.
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[297]
TÍTULO / TITLE: - Diffusion-weighted imaging (DWI) signal intensity and distribution represent the amount of cancer cells and their distribution in primary lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Imaging. 2013 Mar;37(2):265-72. doi: 10.1016/j.clinimag.2012.04.026. Epub 2012 Jun 8.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.04.026
AUTORES / AUTHORS: - Usuda K; Zhao XT; Sagawa M; Aikawa H; Ueno M; Tanaka M; Machida Y; Matoba M; Ueda Y; Sakuma T
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa, Japan. Electronic address: usuda@kanazawa-med.ac.jp.
RESUMEN / SUMMARY: - The aim of this study was to interpret diffusion-weighted imaging (DWI) signals in lung cancers. They were converted into several three-dimensional DWI signals patterns, which represent the degree of DWI signal intensity by height and the degree of distribution by area: flat, low elevation, irregular elevation, single-peak elevation, multiple-peak elevation, and nodular elevation. There were 39 adenocarcinomas and 21 squamous cell carcinomas. Three-dimensional DWI signals decreased significantly in order of cell differentiation. Tumor cellular densities were increased according to the increase in three-dimensional DWI signals. DWI signal intensity and distribution can represent the amount of cancer cells and their distribution in the carcinoma.
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[298]
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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[299]
TÍTULO / TITLE: - Role of selected genetic variants in lung cancer risk in african americans.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):391-7. doi: 10.1097/JTO.0b013e318283da29.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318283da29
AUTORES / AUTHORS: - Spitz MR; Amos CI; Land S; Wu X; Dong Q; Wenzlaff AS; Schwartz AG
INSTITUCIÓN / INSTITUTION: - *Dan L. Duncan Cancer Center, Houston, TX; daggerDepartment of Genetics, MD Anderson Cancer Center, Houston, TX; double daggerKarmanos Cancer Institute, Detroit, MI; and section signDepartment of Epidemiology, MD Anderson Cancer Center, Houston, TX.
RESUMEN / SUMMARY: - INTRODUCTION: : Black/white disparities in lung cancer incidence and mortality mandate an evaluation of underlying biological differences. We have previously shown higher risks of lung cancer associated with prior emphysema in African American compared with white patients with lung cancer. METHODS: : We therefore evaluated a panel of 1440 inflammatory gene variants in a two-phase analysis (discovery and replication), added top genome-wide association studies (GWAS) lung cancer hits from white populations, and 28 single-nucleotide polymorphisms (SNPs) from a published gene panel. The discovery set (477 self-designated African Americans cases, 366 controls matched on age, ethnicity, and gender) were from Houston, Texas. The external replication set (330 cases and 342 controls) was from the EXHALE study at Wayne State University. RESULTS: : In discovery, 154 inflammation SNPs were significant (p < 0.05) on univariate analysis, as was one of the gene panel SNPs (rs308738 in REV1, p = 0.0013), and three GWAS hits, rs16969968 p = 0.0014 and rs10519203 p = 0.0003 in the 15q locus and rs2736100, in the HTERT locus, p = 0.0002. One inflammation SNP, rs950286, was successfully replicated with a concordant odds ratio of 1.46 (1.14-1.87) in discovery, 1.37 (1.05-1.77) in replication, and a combined odds ratio of 1.40 (1.17-1.68). This SNP is intergenic between IRF4 and EXOC2 genes. We also constructed and validated epidemiologic and extended risk prediction models. The area under the curve (AUC) for the epidemiologic discovery model was 0.77 and 0.80 for the extended model. For the combined datasets, the AUC values were 0.75 and 0.76, respectively. CONCLUSIONS: : As has been reported for other cancer sites and populations, incorporating top genetic hits into risk prediction models, provides little improvement in model performance and no clinical relevance.
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[300]
TÍTULO / TITLE: - CNS metastases in non-small-cell lung cancer: Current role of EGFR-TKI therapy and future perspectives.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 27. pii: S0169-5002(13)00063-9. doi: 10.1016/j.lungcan.2013.02.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.004
AUTORES / AUTHORS: - Berger LA; Riesenberg H; Bokemeyer C; Atanackovic D
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine II; Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
RESUMEN / SUMMARY: - A considerable proportion of non-small-cell lung cancer (NSCLC) patients will develop central nervous system (CNS) metastases throughout the course of their disease and these manifestations cause significant morbidity and mortality. Accordingly, novel therapies with high efficacy and low toxicity are needed for NSCLC-related CNS metastases. In NSCLC patients with activating epidermal growth factor receptor gene (EGFR) mutations EGFR-specific tyrosine kinase inhibitors (TKI) represent effective and well tolerated modes of therapy, however, it has been unclear whether these drugs are also able to cross the blood-brain-barrier (BBB) and cause remission of CNS metastases. Recent studies suggest that this might indeed be the case and intracerebral response rates of 70-80% in molecularly selected patients are considerably higher compared to what would be expected for standard approaches like systemic chemotherapy and whole brain radiation therapy. Limitations in the application of EGFR-TKI may arise from genetic heterogeneity between the primary tumor and CNS metastases. Accordingly, the acquisition of repeated biopsies from all relevant metastatic sites, including the CNS, may be necessary to guide therapeutic decisions. However, even in EGFR-wildtype patients EGFR-TKI seem to represent a valuable second line therapy with response rates of about 10%. Application of EGFR-TKI in a “pulsative” pattern may help to overcome insufficient delivery of TKI to the cerebro-spinal fluid and may further increase response rates and time until progression. In the future, combination of EGFR-TKI with radiation or chemotherapy and/or incorporation of next-generation TKI should be evaluated regarding their potential for further optimizing therapy of NSCLC patients with CNS metastases.
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[301]
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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[302]
TÍTULO / TITLE: - Surgical resection of a metastatic skull tumor from lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):169e-71e. doi: 10.1700/1217.13515.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13515
AUTORES / AUTHORS: - Kuwata T; Iwata T; Iwanami T; Kawaguchi M
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Surgery, and 2Department of Pathology, Niigata Rousai Hospital, Niigata, Japan. t-kuwata@med.uoeh-u.ac.jp
RESUMEN / SUMMARY: - We present an interesting case of a metastatic skull tumor from a non-small cell lung cancer that was successfully resected. At present, 1 year after the surgery, the patient is alive with chemotherapy and has not shown any evidence of tumor recurrence.
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[303]
TÍTULO / TITLE: - Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancermediated malignant pleural effusion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 15. doi: 10.3892/or.2013.2349.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2349
AUTORES / AUTHORS: - Du N; Li X; Li F; Zhao H; Fan Z; Ma J; Fu Y; Kang H
INSTITUCIÓN / INSTITUTION: - Department of Oncology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
RESUMEN / SUMMARY: - Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to be efficient in suppressing the accumulation of pleural fluid. However, whether intrapleural delivery of bevacizumab can be used to treat MPE remains unknown. The aim of the present study was to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. A total of 72 NSCLC study subjects with MPE were randomly assigned to one of two groups. The first group received intrapleural bevacizumab (300 mg) with cisplatin (30 mg) therapy and the second group received intrapleural cisplatin (30 mg) therapy alone. Pleural fluid was collected from both groups prior to and following treatment. The levels of VEGF and carcinoembryonic antigen (CEA) in the pleural fluid were determined by ELISA. In 70 evaluable study subjects, the curative efficacy in the bevacizumab group was significantly higher than that found in the cisplatin group (83.33 vs. 50.00%, respectively; p<0.05). Therapy with combined bevacizumab plus cisplatin significantly reduced VEGF levels in the pleural fluid (p<0.01). In the bevacizumab group, the levels of VEGF in the pleural fluid were significantly lower compared to those of the cisplatin group after treatment, which showed greater efficacy (p<0.01). In addition, combination therapy showed greater efficacy in the patients with high levels of VEGF expression (p<0.01). There was no significant difference in grade III/IV adverse events between the two groups. All procedures were well tolerated by the patients. Combined intrapleural therapy with bevacizumab and cisplatin was effective and safe in managing NSCLC-mediated MPE. We propose that VEGF expression levels in MPE could serve as a prognostic marker for bevacizumab therapy.
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[304]
TÍTULO / TITLE: - A case report of dermatomyositis associated with small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):158e-61e. doi: 10.1700/1217.13512.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13512
AUTORES / AUTHORS: - Lee WY; Kastelik J; Campbell A; Avery G; McGivern D; Lind M
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Castle Hill Hospital, Castle Road, Cottingham,United Kingdom. wha-yong.lee@hey.nhs.uk
RESUMEN / SUMMARY: - Dermatomyositis associated with lung cancer is uncommon. Dermatomyositis associated with small cell lung cancer is very rare and carries a poor prognosis. We present a case of a patient with dermatomyositis associated with small cell carcinoma of the lung and review the literature.
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[305]
TÍTULO / TITLE: - Clinical application of immunocytochemical detection of ALK rearrangement on cytology slides for detection or screening of lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 20. pii: S0169-5002(13)00111-6. doi: 10.1016/j.lungcan.2013.03.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.03.006
AUTORES / AUTHORS: - Tanaka H; Tone K; Hayashi A; Morimoto T; Taima K; Tanaka Y; Nakagawa H; Takanashi S; Okumura K; Kurose A
INSTITUCIÓN / INSTITUTION: - Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8563 Japan; Course of Medical Sciences, Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8563 Japan. Electronic address: h-tanaka@cc.hirosaki-u.ac.jp.
RESUMEN / SUMMARY: - Immunohistochemical screening of Anaplastic lymphoma kinase (ALK) rearrangement has been regarded essential and routinely carried out to select treatment for lung adenocarcinoma. However, difficulty to approach a tumor by transbronchial lung biopsy (TBLB), it often fails to obtain tumor tissues whereas tumor cells are contained in cytology specimens simultaneously obtained when the bronchoscopy is done. Therefore we evaluated the expression of ALK protein by using immunohistochemistry (IHC) on TBLB specimens and immunocytochemistry (ICC) on brushing smear cytology slides in the same cases, and compared the concordance rate of IHC and ICC results. ICC was carried out on routine Papanicolau-stained slides after cytology diagnosis and decolorization. RESULTS: Eighteen patients with adenocarcinoma were extracted in the Hirosaki University Hospital and the Hirosaki National Hospital. IHC and ICC results showed a very high concordance rate: sensitivity of ICC in comparison with IHC was 85.7% (6/7), specificity was 100% (11/11), positive predictive value was 100% (6/6), and negative predictive value was 91.6% (11/12). Detection of ALK rearrangement using ICC on routine Papanicolau cytology slides is considered to be advantageous for lung cancer treatments.
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[306]
TÍTULO / TITLE: - Clinical applicability of staging small cell lung cancer according to the seventh edition of the TNM staging system.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Mar 21. pii: S0169-5002(13)00110-4. doi: 10.1016/j.lungcan.2013.03.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.03.005
AUTORES / AUTHORS: - Jhun BW; Lee KJ; Jeon K; Suh GY; Chung MP; Kim H; Kwon OJ; Sun JM; Ahn JS; Ahn MJ; Park K; Choi JY; Lee KS; Han J; Um SW
INSTITUCIÓN / INSTITUTION: - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - The two-stage system of limited and extensive disease has been widely employed for small cell lung cancer (SCLC). However, the International Association for the Study of Lung Cancer has proposed that the TNM classification should be incorporated into clinical practice. The purpose of this study was to evaluate the applicability of the Union for International Cancer Control (UICC) 7th TNM staging system to SCLC. We retrospectively reviewed the medical records of consecutive patients with newly diagnosed histologically proven SCLC between March 2005 and January 2010. Patients who had other concurrent malignancies or had combined-type SCLC were excluded. We assessed overall survival (OS) according to the T descriptor, N descriptor, M descriptor, and TNM stage grouping. In total, 320 SCLC patients were included. Median age was 65 years and 286 patients (89.4%) were male. Median OS was 12.7 months. There were no significant differences in OS according to the T descriptor (P=0.880). However, there were significant differences in OS according to the N (P<0.001) and M (P<0.001) descriptors and TNM stage grouping (P<0.001). Hazard ratios for OS, adjusted for known prognostic factors, differed significantly according to the N and M descriptor, and TNM stage grouping, but not according to the T descriptors. The UICC 7th TNM staging system may contribute to a more precise prognosis in SCLC patients. Further studies are required to evaluate the applicability of the TNM staging system to SCLC.
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[307]
TÍTULO / TITLE: - Pulmonary resection after chemoradiotherapy for advanced non-small cell lung cancer: the impact of presurgical radiation therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Today. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0520-x
AUTORES / AUTHORS: - Shiraishi T; Hiratsuka M; Yanagisawa J; Miyahara S; Yoshida Y; Makimoto Y; Hamatake D; Yamashita SI; Iwasaki A
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic, Breast, and Pediatric Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka City, Fukuoka, 814-0180, Japan, tshiraishi-ths@umin.ac.jp.
RESUMEN / SUMMARY: - PURPOSE: Chemoradiation therapy (CRT) is recommended as standard care for stage III non-small cell lung cancer (NSCLC), but some patients experience local recurrence after the treatment. Surgical resection after CRT involves high surgical risk, but is expected to increase the curability. This study was performed to investigate the impact of presurgical CRT on the postoperative outcome, focusing especially on the effect of radiation therapy. METHODS: Twenty-six patients with stage III (N2 or T3-4) NSCLC underwent pulmonary resection after CRT. A radiation dose up to 40-70 Gy was given with concurrent chemotherapy. The morbidity, mortality and survival after surgical resection were examined. RESULTS: Lung resection was performed as lobectomy (73 %) or pneumonectomy (19 %). Postoperative complications occurred in 12 patients (morbidity 46.1 %). The overall 5-year survival of the entire cohort was 69.7 %. The factors associated with favorable long-term survival included a pathological complete response (CR) and mediastinal node negative condition after CRT, and microscopic complete resection. CONCLUSION: Surgical resection for stage III patients after CRT may provide a survival benefit with acceptable morbidity. The surgical morbidity may be increased by prior radiation therapy, thus, surgeons should be familiar with the available countermeasures to reduce the surgical risk.
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[308]
TÍTULO / TITLE: - A fenestrated stent-graft for surgical resection of lung cancer invading the aortic arch.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Mar 25. pii: S0022-5223(13)00268-7. doi: 10.1016/j.jtcvs.2013.02.070.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2013.02.070
AUTORES / AUTHORS: - Nagata T; Nakamura Y; Yamamoto H; Sato M
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Graduate School of Medical and Dental Sciences Kagoshima University, Kagoshima, Japan.
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[309]
TÍTULO / TITLE: - Sensitization of lung cancer cells to cisplatin by beta-elemene is mediated through blockade of cell cycle progression: antitumor efficacies of beta-elemene and its synthetic analogs.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Mar;30(1):488. doi: 10.1007/s12032-013-0488-9. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0488-9
AUTORES / AUTHORS: - Li QQ; Wang G; Huang F; Li JM; Cuff CF; Reed E
INSTITUCIÓN / INSTITUTION: - West Virginia University School of Medicine, Morgantown, WV 26506, USA. liquenti@mail.nih.gov
RESUMEN / SUMMARY: - The development of effective agents for overcoming platinum chemoresistance in lung carcinoma continues to have high priority. We have demonstrated recently that beta-elemene, a novel antitumor compound, enhances cisplatin activity by triggering lung cancer cell death via apoptosis. Here, we investigated whether beta-elemene acts synergistically with cisplatin to inhibit non-small cell lung cancer (NSCLC) cell proliferation by blocking cell cycle progression. beta-Elemene substantially increased the suppressive effect of cisplatin on cell growth and proliferation in the NSCLC cell lines H460 and A549. Furthermore, beta-elemene augmented cisplatin in the cell cycle arrest of NSCLC cells at G(2)/M. This was associated with upregulated checkpoint kinase (CHK2) expression and reduced CDC2 activity (i.e., increased phosphorylation of CDC2 on Tyr-15 and decreased phosphorylation of CDC2 on Thr-161). Moreover, beta-elemene and cisplatin in combination clearly decreased the protein levels of cyclin B1 and CDC25C and increased the levels of p21(Cip1/Waf1), p27(Kip1), and GADD45 in these cells, compared with the effects of either agent alone at the same concentration. These results suggest that the beta-elemene-enhanced inhibitory effect of cisplatin on lung carcinoma cell proliferation is regulated by a CHK2-mediated CDC25C/CDC2/cyclin B1 signaling pathway and leads to the blockade of cell cycle progression at G(2)/M. A comparison of the cytotoxic efficacies of beta-elemene and three synthetic analogs (beta-elemenol, beta-elemenal, and beta-elemene fluoride) in the two lung cancer cell lines revealed that beta-elemenol and beta-elemene fluoride had the same antitumor efficacy as beta-elemene, whereas beta-elemenal was appreciably more potent than beta-elemene. Thus, although all three synthetic analogs of beta-elemene considerably suppressed NSCLC cell growth and proliferation, beta-elemenal may have greater potential as an anticancer alternative to beta-elemene in treating lung cancer and other tumors.
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[310]
TÍTULO / TITLE: - Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549 - Role of the 5-lipoxygenase.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Physiol Cell Physiol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1152/ajpcell.00412.2012
AUTORES / AUTHORS: - Holm JB; Grygorczyk R; Lambert IH
INSTITUCIÓN / INSTITUTION: - University of Copenhagen.
RESUMEN / SUMMARY: - Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT1) with the anti-asthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS, blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butylated hydroxytoluene, N-acetyl cysteine) and potentiated by H2O2. Ca2+ mobilization with ionomycin or ATP stimulates the swelling-induced taurine release whereas calmodulin inhibition (W7) inhibits the release. Chelation of the extracellular Ca2+ (EGTA) had no effect on swelling-induced taurine release but prevented ATP-induced stimulation. H2O2, ATP and ionomycin were unable to stimulate the taurine release in the presence of AA861 or Zafirlukast, placing 5-LO and CysLT1 as essential elements in the swelling-induced activation of VSOAC with ROS and Ca2+ as potent modulators. Inhibition of tyrosine kinases (genistein, cucurbitacin) reduces volume-sensitive taurine release, adding tyrosine kinases (Janus kinase) as regulators of VSOAC activity. Caspase 3 activity during hypoxia is unaffected by inhibition of 5-LO/CysLT1 but reduced when swelling-induced taurine loss via VSOAC is prevented by DIDS excess extracellular taurine, indicating a beneficial role of taurine under hypoxia.
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[311]
TÍTULO / TITLE: - Genomic landscape of non-small-cell lung cancer in smokers and never-smokers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thorax. 2013 Mar 2. doi: 10.1136/thoraxjnl-2013-203400.
●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2013-203400
AUTORES / AUTHORS: - Sritharan N
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[312]
TÍTULO / TITLE: - POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Int. 2013 Mar;63(3):158-68. doi: 10.1111/pin.12042.
●● Enlace al texto completo (gratuito o de pago) 1111/pin.12042
AUTORES / AUTHORS: - Ishii J; Sato H; Sakaeda M; Shishido-Hara Y; Hiramatsu C; Kamma H; Shimoyamada H; Fujiwara M; Endo T; Aoki I; Yazawa T
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama; Department of Pathology, Kyorin University School of Medicine, Mitaka.
RESUMEN / SUMMARY: - BRN2 is a developmental neural cell-specific POU domain transcription factor and is crucial for cell lineage determination. We investigated the importance of BRN2 in the expression of the lineage-specific transcription factors (achaete-scute homolog-like 1 (ASCL1) and NeuroD1 (ND1)) and neural/neuroendocrine marker molecules (neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYP) and chromogranin A (CHGA)) in small cell lung cancer (SCLC) using cultured lung cancer cells. All examined SCLC cell lines expressed BRN2, as well as ASCL1, ND1, NCAM1, SYP and CHGA. The expression levels of ASCL1, ND1, NCAM1, SYP and CHGA considerably decreased when BRN2 was knocked down in SCLC cells, and the addition of a BRN2 transgene into non-SCLC (NSCLC) cells induced the expression of ASCL1, ND1, NCAM1, SYP and CHGA. However, the BRN2 gene was not activated by the forced expression of ASCL1 or ND1 in NSCLC cells. The knockdown of BRN2 caused significant growth retardation with decrease of S to G2 phase population and mitotic cell rates and unaltered Ki-67-labeled or apoptotic cell rates in SCLC cells, indicating increase of G1 phase population. These findings suggest that BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of SCLC.
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[313]
TÍTULO / TITLE: - Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Apr;95(4):1181-8. doi: 10.1016/j.athoracsur.2013.01.012. Epub 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2013.01.012
AUTORES / AUTHORS: - Kobayashi M; Huang CL; Sonobe M; Kikuchi R; Ishikawa M; Imamura N; Kitamura J; Iwakiri S; Itoi K; Yasumizu R; Date H
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival. METHODS: One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index. RESULTS: The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p < 0.0001 and p = 0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p = 0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p = 0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p = 0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p = 0.0016), especially in patients with nonepithelioid tumors (p = 0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p = 0.0142). CONCLUSIONS: The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs.
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[314]
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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[315]
TÍTULO / TITLE: - Advantages of Proton Therapy in Non-Small Cell Lung Cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biother Radiopharm. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1089/cbr.2012.1343
AUTORES / AUTHORS: - Fan C; Li Y; Liu Q
INSTITUCIÓN / INSTITUTION: - 1 People’s Military Medical Press , Beijing, China .
RESUMEN / SUMMARY: - Abstract The advantage of proton therapy over conventional radiotherapy is enormous, with many clinical advantages. In this review, we summarized the important literature in the advantages of Proton Therapy in Non-small Cell Lung Cancers.
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[316]
TÍTULO / TITLE: - Annual number of lung cancer deaths potentially avertable by screening in the United States.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer. 2013 Apr 1;119(7):1381-5. doi: 10.1002/cncr.27813. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1002/cncr.27813
AUTORES / AUTHORS: - Ma J; Ward EM; Smith R; Jemal A
INSTITUCIÓN / INSTITUTION: - Surveillance Research Program, American Cancer Society, Atlanta, Georgia. jiemin.ma@cancer.org.
RESUMEN / SUMMARY: - BACKGROUND: The National Lung Screening Trial (NLST), which was conducted between 2002 and 2009, demonstrated that screening with low-dose computed tomography (LDCT) reduced lung cancer mortality by 20% among screening-eligible populations compared with chest x-ray. In this article, the authors provide an estimate of the annual number of lung cancer deaths that can be averted by screening, assuming the screening regimens adopted in the NLST are fully implemented in the United States. METHODS: The annual number of lung cancer deaths that can be averted by screening was estimated as a product of the screening effect, the US population size (obtained from the 2010 US Census data), the prevalence of screening eligibility (estimated using the 2010 National Health Interview Survey [NHIS] data), and the lung cancer mortality rates among screening-eligible populations (estimated using the NHIS data from 2000-2004 and the third National Health and Nutrition Examination Survey linked mortality files). Analyses were performed separately by sex, age, and smoking status, with Poisson regression analysis used for mortality rate estimation. Uncertainty of the estimates of the number of avertable lung cancer deaths was quantified by simulation. RESULTS: Approximately 8.6 million Americans (95% confidence interval [95% CI], 8.0 million-9.2 million), including 5.2 million men (95% CI, 4.8 million-5.7 million) and 3.4 million women (95% CI, 3.0 million -3.8 million), were eligible for lung cancer screening in 2010. If the screening regimen adopted in the NLST was fully implemented among these screening-eligible US populations, a total of 12,250 (95% CI, 10,170-15,671) lung cancer deaths (8990 deaths in men and 3260 deaths in women) would be averted each year. CONCLUSIONS: The data from the current study indicate that LDCT screening could potentially avert approximately 12,000 lung cancer deaths per year in the United States. Further studies are needed to estimate the number of avertable lung cancer deaths and the cost-effectiveness of LDCT screening under different scenarios of risk, various screening frequencies, and various screening uptake rates. (See editorial on pages 000-000, this issue.) Cancer 2013. © 2012 American Cancer Society.
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[317]
TÍTULO / TITLE: - Ablative Hypofractionated Radiotherapy Normalizes Tumor Vasculature in Lewis Lung Carcinoma Mice Model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Res. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1667/RR3116.1
AUTORES / AUTHORS: - Lan J; Wan XL; Deng L; Xue JX; Wang LS; Meng MB; Ling H; Zhang X; Mo XM; Lu Y
INSTITUCIÓN / INSTITUTION: - a Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University.
RESUMEN / SUMMARY: - Ablative hypofractionated radiotherapy (HFRT) significantly improves the overall survival of inoperable non-small cell lung cancer (NSCLC) patients compared with conventional radiation therapy. However, the radiobiological mechanisms of ablative HFRT remain largely unknown. The purpose of this study was to investigate the dynamic changes of tumor vessels and perfusion during and after ablative hypofractionated radiotherapy. Lewis lung carcinoma-bearing mice were treated with sham (control) and ablative hypofractionated radiotherapy of 12 Gy in 1 fraction (12 Gy/1F) and 36 Gy in 3 fractions (36 Gy/3F). Tumor microvessel density (MVD), morphology and function were examined at different times after irradiation. The results showed that, compared to the controls the MVD and hypoxia in ablative HFRT groups decreased, which were accompanied by an increase in the number of pericytes and their coverage of vessels. Functional tests revealed that tumor hypoxia and perfusion were improved, especially in the 36 Gy/3F group. Our results revealed that ablative hypofractionated radiotherapy not only repressed MVD and hypoxia, but also increased the vascular perfusion and the number of pericyte-covered vessels, suggesting that ablative HFRT normalized the tumor vasculature.
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[318]
TÍTULO / TITLE: - Association between Genetic Variants in Pre-MicroRNAs and Survival of Early-Stage NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318288dc0a
AUTORES / AUTHORS: - Hong MJ; Choi YY; Jang JA; Jung HJ; Lee SY; Lee WK; Yoo SS; Lee J; Cha SI; Kim CH; Lee E; Jeon HS; Son JW; Park JY
INSTITUCIÓN / INSTITUTION: - *Department of Biochemistry and Cell Biology, daggerDepartment of Internal Medicine, double daggerCenter of Biostatistics, section signDepartment of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; ||Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea; and paragraph signDepartment of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
RESUMEN / SUMMARY: - INTRODUCTION:: MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. Recent evidence indicates that altered miRNA expression plays an important role in the initiation and progression of lung cancer. Single nucleotide polymorphisms (SNPs) in pre-miRNAs could alter miRNAs processing, or expression, and hence, could influence the prognosis of lung cancer. To test this hypothesis, we evaluated the effects of four SNPs in pre-miRNAs (pre-miR-146a rs2910164, pre-miR-149 rs2292832, pre-miR-196a rs11614913, and pre-miR-499 rs3746444) on the survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS:: Three hundred sixty-three patients with surgically resected NSCLC were enrolled. The four SNPs were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS:: Of the four SNPs examined, the pre-miR-149 rs2292832T>C and pre-miR-196a rs11614913C>T were found to be significantly associated with OS and DFS. The rs2292832 TC or CC genotype exhibited a significantly better OS and DFS compared with the rs2292832 TT genotype (adjusted hazard ratio [aHR] for OS, 0.66; 95% confidence interval [CI], 0.47-0.92; p = 0.01 and aHR for DFS, 0.64; 95% CI, 0.48-0.87; p = 0.004). For the pre-miR-196a rs11614913C>T, patients with the CT or TT genotype had a significantly better OS and DFS than those with the CC genotype (aHR for OS, 0.70; 95% CI, 0.49-0.99; p = 0.05 and aHR for DFS, 0.66; 95% CI, 0.48-0.90; p = 0.01). When the two SNPs were combined, OS and DFS improved in a dose-dependent manner as the number of good genotypes increased (p = 0.002 and 0.0001, respectively). CONCLUSIONS:: These results suggest that miR-149 and miR-196a may be involved in the pathogenesis of NSCLC, and that rs2292832 and rs11614913 can be used as prognostic markers for patients with surgically resected early-stage NSCLC.
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[319]
TÍTULO / TITLE: - Phase II Study of Triplet Chemotherapy Using Tegafur-Uracil, Vinorelbine, Gemcitabine for Advanced Non-small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1163-7.
AUTORES / AUTHORS: - Minomo S; Asami K; Okishio K; Kawaguchi T; Fujita Y; Takata S; Tamura A; Saitou R; Atagi S
INSTITUCIÓN / INSTITUTION: - National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone, Sakai, Osaka 591-8555, Japan. s-atagi@kch.hosp.go.jp.
RESUMEN / SUMMARY: - Aim: To evaluate the efficacy and toxicity of triplet chemotherapy using tegafur-uracil (UFT), vinorelbine, and gemcitabine for patients with stage IIIB or IV non-small cell lung cancer. PATIENTS AND METHODS: A total of 32 patients were enrolled in this study. The patients were subjected to a treatment regimen consisting of intravenous vinorelbine and gemcitabine on days 6 and 13, and oral UFT on days 1-5 and 8-12. This treatment was repeated every three weeks. RESULTS: All patients had an initial performance status of 0 to 1. The objective response rate was 21.9%, median survival time was 13.9 months, and the one-year survival rate was 56.7%. Grade ¾ toxicities (% of patients) consisted of leukocytopenia (40.6%), neutropenia (56.3%), thrombocytopenia (3.1%), infection (9.4%), hypoxia (6.3%) and dyspnea (3.1%). CONCLUSION: Triplet chemotherapy using UFT, vinorelbine, and gemcitabine was well-tolerated, with an acceptable toxicity profile. However, the response rate and median survival did not encourage for additional investigation.
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[320]
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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[321]
TÍTULO / TITLE: - A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Epidemiol. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s10654-013-9793-z
AUTORES / AUTHORS: - Baltar VT; Xun WW; Johansson M; Ferrari P; Chuang SC; Relton C; Ueland PM; Midttun O; Slimani N; Jenab M; Clavel-Chapelon F; Boutron-Ruault MC; Fagherazzi G; Kaaks R; Rohrmann S; Boeing H; Weikert C; Bueno-de-Mesquita B; Boshuizen H; van Gils CH; Onland-Moret NC; Agudo A; Barricarte A; Navarro C; Rodriguez L; Castano JM; Larranaga N; Khaw KT; Wareham N; Allen NE; Crowe F; Gallo V; Norat T; Krogh V; Masala G; Panico S; Sacerdote C; Tumino R; Trichopoulou A; Lagiou P; Trichopoulos D; Rasmuson T; Hallmans G; Roswall N; Tjonneland A; Riboli E; Brennan P; Vineis P
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology, Faculty of Public Health, University of Sao Paulo, Av. Dr Arnaldo, 715, Sao Paulo, Sao Paulo, CEP 01246-904, Brazil, vbaltar@usp.br.
RESUMEN / SUMMARY: - The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.
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[322]
TÍTULO / TITLE: - Anti-metastatic effect of cantharidin in A549 human lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Pharm Res. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s12272-013-0044-3
AUTORES / AUTHORS: - Kim YM; Ku MJ; Son YJ; Yun JM; Kim SH; Lee SY
INSTITUCIÓN / INSTITUTION: - Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Kyeonggi-Do, 461-701, Korea.
RESUMEN / SUMMARY: - Cancer metastasis is represented by migration and invasion of cancer cells. Cancer cells invade into the blood or lymphatic vessels and this leads to the spread of cancer into the organs in distant sites. For cancer cells to migrate, extracellular matrix (ECM) must be degraded. Cantharidin, a compound derived from blister beetles, is known for its anti-cancer effect in several cancer cells. Here we report that cantharidin inhibits migration and invasion of A549 human lung cancer cell. We found that cantharidin inhibits activation of phosphatidylinositol 3-kinase/Akt signaling pathway. This leads to the selective attenuation of one of the gelatinases, matrix metalloproteinase 2, which can degrade components of ECM, and inhibits migration and invasion of A549 human lung cancer cell.
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[323]
TÍTULO / TITLE: - Evolution in surgical approach and techniques for lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thorax. 2013 Mar 5. doi: 10.1136/thoraxjnl-2012-203157.
●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2012-203157
AUTORES / AUTHORS: - Ng CS; Lau KK; Gonzalez-Rivas D; Rocco G
INSTITUCIÓN / INSTITUTION: - Department of Cardiothoracic Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, , Shatin, Hong Kong.
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[324]
TÍTULO / TITLE: - Dammarane-type saponins from heat-processed Gynostemma pentaphyllum show fortified activity against A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Pharm Res. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s12272-013-0086-6
AUTORES / AUTHORS: - Piao XL; Wu Q; Yang J; Park SY; Chen DJ; Liu HM
INSTITUCIÓN / INSTITUTION: - Institute of Chinese Minority Traditional Medicine, Minzu University of China, No. 27, Zhongguancun South Street, Haidian District, Beijing, 100081, China, xlpiao@163.com.
RESUMEN / SUMMARY: - An ethanol extract from heat-processed Gynostemma pentaphyllum showed more potent cytotoxic activity against human lung adenocarcinoma A549 cells than that of raw G. pentaphyllum. Four constituents were isolated from heat-processed G. pentaphyllum using resin HP-20, silica gel and reversed ODS column chromatography. They were identified by mass and NMR spectra as damulin A and damulin B, gypenoside L and gypenoside LI, respectively. To evaluate the efficacy of these four constituents, the MTT cytotoxicity assay was performed using A549 cells. Based on the structure of these four constituents, the results indicate that the hydroxyl group in C-2 and double bond in C20(21) and C20(22) positions are of importance in inhibition of A549 cell proliferation.
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[325]
TÍTULO / TITLE: - The Biophysical Property of A549 Cells Transferred by VEGF-D.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Scanning. 2013 Mar 22. doi: 10.1002/sca.21087.
●● Enlace al texto completo (gratuito o de pago) 1002/sca.21087
AUTORES / AUTHORS: - Wang Z; Wu XL; Wang X; Tian HX; Chen ZH; Li YQ
INSTITUCIÓN / INSTITUTION: - Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China.
RESUMEN / SUMMARY: - Vascular endothelial growth factor-D (VEGF-D) together with VEGF-C is considered to be associated with lymphangiogenesis and angiogenesis and involve in tumorization. This study aims to investigate the influence of exogenous VEGF-D gene on the biophysical property of cell surface of lung adenocarcinoma cell line. A panel of lung adenocarcinoma cell lines were examined the expression of VEGF-D and VEGF-C by real-time PCR. The VEGF-D recombinant plasmid containing enhanced green fluorescence protein (EGFP) was constructed and transfected to the cell line with no expression of VEGF-D and confirmed by real-time PCR and Western blot analysis. Topographic images of cells were obtained by using atomic force microscope (AFM) in contact mode. Unlike VEGF-C, VEGF-D was found to have a very low expression or undetectable expression in lung adenocarcinoma cell lines. The VEGF-D recombinant plasmid had been constructed successfully and was transferred into the human lung adenocarcinoma cell line A549 cells which had no endogenous expression of VEGF-D, and exogenous VEGF-D could be detected in mRNA and protein expression levels in the gene modified cells, while the VEGF-C gene expression had no change after VEGF-D transfection. After transfection, the irregular microspikes or nano clusters could observe on the surface of A549 cells, and VEGF-D transfected A549 cells became more rigid. The exogenous VEGF-D gene might cause the remarkable biophysical architectural changes in the A549 cells, which might as a novel biomarker for evaluation of its biological function. SCANNING 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
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[326]
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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[327]
TÍTULO / TITLE: - Rapid detection of exon 2-deleted AIMP2 mutation as a potential biomarker for lung cancer by molecular beacons.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biosens Bioelectron. 2013 Mar 6;46C:142-149. doi: 10.1016/j.bios.2013.02.037.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bios.2013.02.037
AUTORES / AUTHORS: - Jo SM; Kim Y; Jeong YS; Hee Oh Y; Park K; Kim HS
INSTITUCIÓN / INSTITUTION: - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
RESUMEN / SUMMARY: - Exon 2 deletion in aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) has been suggested to be associated with the progression of various cancers such as lung and ovarian cancers. However, few studies have been conducted regarding detection and relevance of exon 2-deleted AIMP2 (AIMP2-DX2) mutation to a specific cancer. Here, we demonstrate the rapid and simple detection of the AIMP2-DX2 mutation by molecular beacons and its relation to lung cancer. Real-time PCR with molecular beacons allowed a sensitive detection of the AIMP2-DX2 mutation as low as 0.3pg initial template. Dual-conjugated liposomes with folate and molecular beacon enabled fluorescence imaging of cancer cells harboring the AIMP2-DX2 mutation with high resolution. Association of the AIMP2-DX2 mutation with lung cancer was shown by analyzing tissue samples from lung cancer patients using real-time PCR. Approximately, 60% of lung cancer patients harbored the AIMP2-DX2 mutation, which implies a potential of the AIMP2-DX2 mutation as a prognostic biomarker for lung cancer. Molecular beacon-based approaches will find applications in the simple and rapid detection of mutations on nucleotides for diagnosing and monitoring the progression of relevant cancer.
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[328]
TÍTULO / TITLE: - Clinical Implication of MicroRNA for Lung Cancer.
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.2012.1401
AUTORES / AUTHORS: - Wang Y; Zhang X; Liu L; Li H; Yu J; Wang C; Ren X
INSTITUCIÓN / INSTITUTION: - 1 Department of Immunology, Tianjin Medical University Cancer Institute and Hospital , Tianjin, China .
RESUMEN / SUMMARY: - Abstract MicroRNAs (miRNAs) are a class of endogenous small noncoding regulatory RNAs, which are new regulators of gene expression. They interfere with multiple biological processes involved in tumorigenesis such as cell proliferation, cell cycle, apoptosis, angiogenesis, invasion, and metastasis. A large body of evidence shows that the aberrant expression of miRNAs in cancer patients provides numerous underlying merits as diagnostic, clinical pathological, prognostic markers, and as promising therapeutic targets of lung cancer, providing an insight into the clinical application for lung cancer. Here, we focus on specific miRNAs as biomarkers in lung cancer and briefly introduce the biological function and modification of miRNAs.
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[329]
TÍTULO / TITLE: - The effect of irregular breathing patterns on internal target volumes in four-dimensional CT and cone-beam CT images in the context of stereotactic lung radiotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Phys. 2013 Feb;40(2):021904. doi: 10.1118/1.4773310.
●● Enlace al texto completo (gratuito o de pago) 1118/1.4773310
AUTORES / AUTHORS: - Clements N; Kron T; Franich R; Dunn L; Roxby P; Aarons Y; Chesson B; Siva S; Duplan D; Ball D
INSTITUCIÓN / INSTITUTION: - Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne, Australia.
RESUMEN / SUMMARY: - PURPOSE: Stereotactic lung radiotherapy is complicated by tumor motion from patient respiration. Four-dimensional CT (4DCT) imaging is a motion compensation method used in treatment planning to generate a maximum intensity projection (MIP) internal target volume (ITV). Image guided radiotherapy during treatment may involve acquiring a volumetric cone-beam CT (CBCT) image and visually aligning the tumor to the planning 4DCT MIP ITV contour. Moving targets imaged with CBCT can appear blurred and currently there are no studies reporting on the effect that irregular breathing patterns have on CBCT volumes and their alignment to 4DCT MIP ITV contours. The objective of this work was therefore to image a phantom moving with irregular breathing patterns to determine whether any configurations resulted in errors in volume contouring or alignment. METHODS: A Perspex thorax phantom was used to simulate a patient. Three wooden “lung” inserts with embedded Perspex “lesions” were moved up to 4 cm with computer-generated motion patterns, and up to 1 cm with patient-specific breathing patterns. The phantom was imaged on 4DCT and CBCT with the same acquisition settings used for stereotactic lung patients in the clinic and the volumes on all phantom images were contoured. This project assessed the volumes for qualitative and quantitative changes including volume, length of the volume, and errors in alignment between CBCT volumes and 4DCT MIP ITV contours. RESULTS: When motion was introduced 4DCT and CBCT volumes were reduced by up to 20% and 30% and shortened by up to 7 and 11 mm, respectively, indicating that volume was being under-represented at the extremes of motion. Banding artifacts were present in 4DCT MIP images, while CBCT volumes were largely reduced in contrast. When variable amplitudes from patient traces were used and CBCT ITVs were compared to 4DCT MIP ITVs there was a distinct trend in reduced ITV with increasing amplitude that was not seen when compared to true ITVs. Breathing patterns with a rest period following expiration resulted in well-defined superior edges and were better aligned using an edge-to-edge alignment technique. In most cases, sinusoidal motion patterns resulted in the closest agreements to true values and the smallest misalignments. CONCLUSIONS: Strategies are needed to compensate for volume losses at the extremes of motion for both 4DCT MIP and CBCT images for larger and varied amplitudes, and for patterns with rest periods following expiration. Lesions moving greater than 2 cm would warrant larger treatment margins added to the 4DCT MIP ITV to account for the volume being under-represented at the extremes of motion. Lesions moving with a rest period following expiration would be better aligned using an edge-to-edge alignment technique. Sinusoidal patterns represented the ideal clinical scenario, reinforcing the importance of investigating clinically relevant motions and their effects on 4DCT MIP and CBCT volumes. Since most patients do not breathe sinusoidally this may lead to misinterpretation of previous studies using only sinusoidal motion.
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[330]
TÍTULO / TITLE: - p40 (DeltaNp63) and keratin 34betaE12 provide greater diagnostic accuracy than p63 in the evaluation of small cell lung carcinoma in small biopsy samples.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 22. pii: S0046-8177(13)00044-0. doi: 10.1016/j.humpath.2013.01.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2013.01.011
AUTORES / AUTHORS: - Butnor KJ; Burchette JL
INSTITUCIÓN / INSTITUTION: - The University of Vermont/Fletcher Allen Health Care, Burlington, VT 05401. Electronic address: kelly.butnor@vtmednet.org.
RESUMEN / SUMMARY: - The use of p63 has been advocated for separating small cell lung carcinoma from poorly differentiated non-small cell lung carcinoma, in particular, squamous cell lung carcinoma. However, p63 is not entirely specific in this distinction, as several studies have demonstrated p63 immunoreactivity in a proportion of small cell lung carcinomas. p40 (DeltaNp63) has recently been purported to be a highly specific marker for squamous cell lung carcinoma, but data regarding p40 (DeltaNp63) in small cell lung carcinoma, a key differential diagnostic consideration in biopsy samples of squamous cell lung carcinoma, are lacking. In this study, a total of 34 previously confirmed small cell lung carcinomas (27 bronchoscopic biopsy samples and 7 large specimens) were immunostained for p40 (DeltaNp63), p63, and keratin 34betaE12. All 34 small cell lung carcinomas were negative for p40 (DeltaNp63) and keratin 34betaE12. Although none of the large small cell lung carcinoma specimens exhibited p63 immunoreactivity, 12 (44.4%) of 27 biopsy samples of small cell lung carcinoma were positive for p63. The rate of p63 staining in small cell lung carcinoma biopsy samples differed significantly from that of p40 (DeltaNp63) and keratin 34betaE12 (P = .005). Ten cases of squamous cell lung carcinoma were also tested, all of which were positive for all 3 markers. These findings confirm that p63 immunoexpression is not uncommon in biopsy samples of small cell lung carcinoma. Positive p63 staining may be mistakenly interpreted as supportive of squamous differentiation and result in misclassification of small cell lung carcinoma as squamous cell lung carcinoma, a diagnostic error that has important therapeutic and prognostic consequences. To provide greater diagnostic accuracy, p40 (DeltaNp63) or keratin 34betaE12 should be used instead of p63 in the distinction of small cell lung carcinoma from non-small cell lung carcinoma in biopsy samples.
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[331]
TÍTULO / TITLE: - New modalities to treat laryngeal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:3-6.
AUTORES / AUTHORS: - Prgomet D
INSTITUCIÓN / INSTITUTION: - University of Zagreb, Zagreb University Hospital Center, University Department of Head and Neck Surgery, Zagreb, Croatia. drago.prgomet@zg.t-com.hr
RESUMEN / SUMMARY: - Early laryngeal cancer comprises T1 and T2 stages of the disease. Open functional operations achieve local control of the disease in 90-95% of T1 patients and in 70-90% of T2 patients. Primary RT achieves local control in 85-94% of T1 tumors and in 70-80% of patients with T2 tumors. Introduction of endoscopic laser surgery resulted in further popularization of preservation laryngeal surgery, whereby equally successful treatment results are achieved with minimal invasiveness. Quality of voice is also better after RT and laser resection. In the last century a golden standard of treatment of advanced laryngeal cancer (T3/T4 stage) was total laryngectomy (TL) with neck dissection followed by adjuvant RT. Overall 5 year survival was around 50%. Due to impact of TL on quality of life, “Larynx preservation strategy” (LPS) was developed in the early ‘90 for advanced stages of the disease. Novel approach is an introduction of targeted therapy, such as anti-EGFR monoclonal antibody, cetuximab. Concomitant cetuximab with RT achieves higher survival, and better locoregional disease control in comparison to administration of single RT modality. Therefore non-surgical methods of treatment of advanced laryngeal carcinoma are constantly changing and improving as new chemotherapeutics are being introduced into protocols. Uncritical enthusiasm with non-surgical methods of treatment resulted in higher incidence of treatment toxicities, higher rates of “salvage surgery” with more frequent adverse effects. That resulted in a consensus attempt around “LPS” project with reevaluation of clinical studies and uniform recommendations for future studies. When choosing appropriate therapy for oncological patient, quality of life (QOL) is a special category to be taken into account besides complications, pain, duration of treatment and overall benefit for the patient.
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[332]
TÍTULO / TITLE: - Three-year survival after surgery for primary malignant pericardial mesothelioma: report of a case.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Today. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0511-y
AUTORES / AUTHORS: - Fujita K; Hata M; Sezai A; Minami K
INSTITUCIÓN / INSTITUTION: - Department of Cardiovascular Surgery, Kitakanto Jyunkanki Hospital, 740 Shimohakoda, Hokkitsumachi, Shibukawa, Gunma, 377-0061, Japan, kishufujita@ccj.or.jp.
RESUMEN / SUMMARY: - A 59-year-old female underwent surgery for a primary malignant pericardial mesothelioma. She presented with progressive dyspnea, and several imaging studies demonstrated a 65 x 22 mm tumor in the aortopulmonary window, accompanied by massive pericardial effusion. The tumor was successfully excised with clean surgical margins under cardiopulmonary bypass, followed by patch reconstruction of the pulmonary artery, and was diagnosed as an epithelioid type of malignant pericardial mesothelioma. The patient tolerated the operation and subsequent adjuvant chemotherapy without any complications. She remained alive and asymptomatic for almost 3 years after surgery, despite the fact that the median survival of this disease is 6-10 months. This patient is the second longest postoperative survivor of this extremely rare, aggressive neoplasm.
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[333]
TÍTULO / TITLE: - New molecular targets in the treatment of NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Pharm Des. 2013 Feb 4.
AUTORES / AUTHORS: - Schettino C; Bareschino MA; Sacco PC; Maione P; Rossi A; Casaluce F; Sgambato A; Gridelli C
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, “S.G. Moscati” Hospital, Citta Ospedaliera, Contrada Amoretta, 83100 Avellino, Italy. cgridelli@libero.it.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of mortality world-wide. Non Small Cell Lung Cancer (NSCLC) is a particularly aggressive cancer, the optimum management of which is still being determined. In the next years modest survival improvement can be expected by chemotherapy. Advances in understanding of the molecular pathogenesis of lung cancer have led to the identification of several specific targets for therapeutic agents. Targeting the epidermal growth factor receptor (EGFR) has played a central role in advancing NSCLC research, treatment, and patient outcome over the last several years. In lung cancer,10-15% of NSCLC contain activating mutations in the EGFR kinase conferring hypersensitivity to the oral TKIs gefitinib and erlotinib, have been demonstrated to be important predictive factors when selecting patients to be treated with these two agents. More recently, another molecular abnormality, the translocation of the anaplastic lymphoma kinase (ALK) gene that drives NSCLC in a different group of patients has been found in 4 to 5% of NSCLC. The rearrangement results in an EML4 - AKL fusion gene, which increases ALK activity. Inhibitors of ALK kinase have been developed and investigated. Crizotinib, an orally ALK and met proto-oncogene (MET) inhibitor, was very well tolerated and produced dramatic antitumor activity in early-stage trials which facilitated a faster than normal move into late-stage trials for EML4-ALK - positive NSCLC patients treatment. In a phase III randomized showed progression free survival benefit as compared to chemotherapy in second-line setting. Several novel selective inhibitors of ALK kinase are currently in preclinical or early clinical testing. Since the discovery that Met pathway is one of the most frequently dysregulated pathways in human cancer. Met inhibitors, with varying kinase selectivity profiles ranging from highly selective to multi-targeted have been studied in the clinic and good progress has been achieved. A number of studies suggesting that the PI3K/Akt signaling pathway is central to NSCLC growth and survival. Given the importance of activated PI3K signaling in cancer, several PI3K inhibitors are currently one of the most recent drug targets in oncology, with several small molecules in early stages of clinical development. This review will focus on the role of EGFR, ALK, MET, and PI3K inhibitors in the treatment of NSCLC.
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[334]
TÍTULO / TITLE: - Outcomes and complications of endoscopic approaches for malignancies of the paranasal sinuses and anterior skull base.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Otol Rhinol Laryngol. 2013 Jan;122(1):54-9.
AUTORES / AUTHORS: - Suh JD; Ramakrishnan VR; Chi JJ; Palmer JN; Chiu AG
INSTITUCIÓN / INSTITUTION: - Department of Head and Neck Surgery, University of California-Los Angeles, Los Angeles, CA 90095, USA.
RESUMEN / SUMMARY: - OBJECTIVES: Malignant tumors of the paranasal sinuses are traditionally approached by a variety of external incisions. Recent advances in endoscopic endonasal surgery have allowed for some of these tumors to be treated endoscopically. The purpose of this study was to assess the outcomes and complications of the endoscopic approach in a series of patients with paranasal sinus malignancies. METHODS: A retrospective chart review was performed of patients with sinonasal or skull base malignancies treated with endoscopic or endoscopic-assisted resections at a tertiary care institution from 2002 to 2010. Patient data were collected on symptoms, tumor type, operative technique, and postoperative course. Baseline risk factors, overall and disease-free survival data, and surgical outcomes were compared between the two groups. RESULTS: Of the total 49 patients, 36 (73%) underwent an endoscopic approach and 13 (27%) underwent endoscopic-assisted approaches. Sarcomas (9 cases) were the most common tumor type, followed by squamous cell carcinoma (8), adenocarcinoma (8), and melanoma (7). The mean follow-up time for all patients was 3.58 years (range, 1.1 to 8.8 years). Surgical complications were more frequent with open approaches than with endoscopic approaches (23.1% versus 5.6%; p = 0.11). Medical complications were significantly more common with open approaches (38.5% versus 8.3%; p = 0.02). The disease-specific mortality rate was 8% (4 of 49). The local tumor recurrence rate was 16% (8 of 49). The 3-year disease-free survival rates were 86.8% in the endoscopic group and 67.7% in the open group (p = 0.047); however, the patients in the endoscopic group had lower T stages (p = 0.0068) and lower ASA scores (p = 0.03). CONCLUSIONS: Endoscopic approaches to the sinuses and skull base have become progressively more sophisticated with advances in skull base reconstruction, advances in surgical technique, and improvements in technology. This study demonstrates the relative safety and utility of the endoscopic approach for sinonasal and skull base malignancies. In carefully selected patients, endoscopic approaches demonstrate survival rates comparable to those of traditional surgery, and fewer perioperative complications. With appropriate planning and careful surgical decision-making, endoscopic surgery shows promise as a minimally invasive alternative in the treatment of sinonasal malignancies.
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[335]
TÍTULO / TITLE: - Video-assisted left main bronchial carcinoma resection and secondary carinal reconstruction.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Cardiovasc Surg. 2013 Mar 9. pii: S0022-5223(13)00191-8. doi: 10.1016/j.jtcvs.2013.02.038.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jtcvs.2013.02.038
AUTORES / AUTHORS: - Yin R; Qiu N; Zhu J; Xu L
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
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[336]
TÍTULO / TITLE: - Volume doubling time for lung cancer screening.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thorax. 2013 Mar 12. doi: 10.1136/thoraxjnl-2013-203448.
●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2013-203448
AUTORES / AUTHORS: - Colclough JM
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[337]
TÍTULO / TITLE: - Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Thorax. 2013 Mar 7. doi: 10.1136/thoraxjnl-2013-203396.
●● Enlace al texto completo (gratuito o de pago) 1136/thoraxjnl-2013-203396
AUTORES / AUTHORS: - Murray J
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[338]
TÍTULO / TITLE: - M14K and M38K malignant pleural mesothelioma cell lines preserve the same claudin-based phenotype in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - In Vivo. 2013 Mar-Apr;27(2):227-32.
AUTORES / AUTHORS: - Chaouche-Mazouni S; Copin MC; Lassalle P; Lebaili N; Cortot A; Scherpereel A
INSTITUCIÓN / INSTITUTION: - Department of Biology, Kouba High School, Algiers, Algeria.
RESUMEN / SUMMARY: - BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with few treatment options. Reliable tumour cell lines for mesothelioma research are rare. Claudins seem to be attractive targets for cancer therapy. Aim: To establish a claudin-based MPM phenotype and to verify whether it is preserved in vitro and in vivo. MATERIALS AND METHODS: Claudin-3 and -4 expression was examined by immunohistochemistry and immunoblotting in MPM (n=15) and lung adenocarcinoma (n=5) specimens. Claudin-3, -4 and -15 expression was also assessed in MPM versus adenocarcinoma cell lines and in MPM versus adenocarcinoma-derived tumour xenografts mouse models. RESULTS: A defined MPM phenotype was established: M14K and M38K cell lines highly express Claudin-15 and calretinin but not claudin-3 nor claudin-4. Similar results were obtained in xenograft mouse models. CONCLUSION: M14K and M38K cell lines, whether in vitro or in an animal model are representative models and appropriate in exploring new therapeutic strategies in MPM that may target claudins.
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[339]
TÍTULO / TITLE: - ALK gene translocations and amplifications in brain metastases of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 27. pii: S0169-5002(13)00055-X. doi: 10.1016/j.lungcan.2013.01.019.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.019
AUTORES / AUTHORS: - Preusser M; Berghoff AS; Ilhan-Mutlu A; Magerle M; Dinhof C; Widhalm G; Dieckmann K; Marosi C; Wohrer A; Hackl M; Zochbauer-Muller S; von Deimling A; Schoppmann SF; Zielinski CC; Streubel B; Birner P
INSTITUCIÓN / INSTITUTION: - Department of Medicine I, Medical University of Vienna, Austria; Comprehensive Cancer Center Vienna, Central Nervous System Tumours Unit (CCC-CNS), Austria. Electronic address: matthias.preusser@meduniwien.ac.at.
RESUMEN / SUMMARY: - BACKGROUND: Increased incidence of brain metastases (BM) in non-small cell lung cancer (NSCLC) with ALK translocations was postulated, however, ALK gene aberrations in NSCLC-BM have not been investigated so far. METHODS: We investigated ALK and EML4 gene aberrations (amplifications, translocations, inversions) by fluorescent in situ hybridization (FISH) (n=175) and ALK and EML4 protein expression by immunohistochemistry (n=221) in NSCLC BM and corresponding primary tumors. RESULTS: ALK translocations were found in 4/151 (2.6%; 3 of them involving EML4) of BM of adenocarcinomas (AC), 1/9 (11.1%) of adenosquamous carcinomas (ASC), 0/5 of squamous cell carcinomas (SCC) and 0/10 of large cell carcinomas (LCC). Rearrangement of ALK without involvement of EML4 was seen in 1 AC-BM and rearrangement of EML4 without involvement of ALK in 3 AC-BM, 1 ASC-BM and 1 LCC. ALK amplifications without gene rearrangements were found in BM of 16/151 (10.6%) AC, 2/5 (40%) SCC, 0/9 ASC and one LCC. ALK translocation status was constant between BM and primary tumors in 16 evaluable cases including two cases with ALK-EML4 translocations Among these 16 cases ALK amplification was seen in two BM and none of the primary tumors. All cases with translocations but not with amplifications of ALK showed protein expression. We found no association of ALK gene status with patient age, gender or overall survival time. CONCLUSIONS: ALK translocations and amplifications are found in approximately 3% and 11% of NSCLC-BM, respectively. While ALK translocations appear to be constant between primary tumors and BM, amplifications seem to be more prevalent in BM. ALK translocation, but not ALK amplification is associated with ALK protein overexpression. Further studies are needed to determine whether NSCLC-BM patients with ALK gene aberrations may benefit from specific inhibitor therapy.
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[340]
TÍTULO / TITLE: - Steroid sulphatase and oestrogen sulphotransferase in human non-small-cell lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 26. doi: 10.1038/bjc.2013.84.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.84
AUTORES / AUTHORS: - Iida S; Kakinuma H; Miki Y; Abe K; Sakurai M; Suzuki S; Niikawa H; Akahira J; Suzuki T; Sasano H
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
RESUMEN / SUMMARY: - Background:Steroid sulphatase (STS) is one of the steroid-metabolising enzymes involved in desulphating inactive steroid sulphates and oestrogen sulphotransferase (EST) sulphates active oestrogen. The roles of both STS and EST have not been examined in oestrogen-dependent non-small-cell lung cancer (NSCLC).Methods:We evaluated the immunoreactivity of STS and EST in NSCLC cases using immunohistochemistry. The function of STS and EST was further demonstrated using NSCLC cell lines.Results:The immunoreactivity of STS and EST was detected in 49.5% and 27.8% of NSCLC cases, respectively. The immunoreactivity of STS was significantly higher in female adenocarcinoma cases. The STS-positive NSCLCs were also significantly correlated in an inversed manner with tumour size and cell proliferation and tended to be associated with better clinical outcome. However, the immunoreactivity of EST was significantly correlated with intracellular oestradiol concentration. Results of in vitro analysis demonstrated that oestrone sulphate (E1-S) induced and pregnenolone sulphate (Preg-S) inhibited the proliferation in STS-expressing cell lines. The inhibition by Preg-S was reversed by a specific progesterone receptor blocker. Simultaneous addition of E1-S and Preg-S significantly suppressed the proliferation.Conclusion:In NSCLC patients, STS is considered a good prognostic factor. Results of our present study also indicated the benefits of potential progesterone therapy for NSCLC patients.British Journal of Cancer advance online publication, 26 March 2013; doi:10.1038/bjc.2013.84 www.bjcancer.com.
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[341]
TÍTULO / TITLE: - Nature’s necrosis factor when associated with erythrocytes may not only explain the surprises in lung cancer metastases but also suggest target therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Hypotheses. 2013 Mar 22. pii: S0306-9877(13)00083-2. doi: 10.1016/j.mehy.2013.02.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.mehy.2013.02.011
AUTORES / AUTHORS: - Onuigbo WI
INSTITUCIÓN / INSTITUTION: - Pathology Department, Medical Foundation and Clinic, P.O. Box 1792, Enugu 400001, Nigeria. Electronic address: wilson.onuigbo@gmail.com.
RESUMEN / SUMMARY: - Lung cancer is so strategically situated as regards the heart and aorta that it ought to scatter its metastasizing cells far and wide. However, at careful autopsy, instead of giant opportunities, only dwarf deposition may be detected. Indeed, up to seven patterns of its metastases demonstrate surprises. What explains these surprises? Consider the thoracic duct. When this 45cm long duct was obtained in its entirety, coiled in the Swiss-roll manner, processed in the usual way, and examined on a single microscope slide, necrosis of some transported lung cancer cells was found to be very intimately associated with the erythrocytes. Therefore, let this underlying natural mechanism be named as the “erythrocyte associated necrosis factor”, i.e., EANF. It is argued that this Factor operates differently from the suspected roles of both anoikis and stem cells. Accordingly, it is hypothesized that, if intravital video microscopy is used to obtain subsets of both necrotic and lively cancer cells from the thoracic duct of consenting lung cancer patients, the underlying EANF will definitely materialize. It is predicted that the manipulative replication of this Factor in leading centers will ensure progress. In sum, EANF would not only aid in our understanding of the outlined highly inefficient metastatic processes but also effect a breakthrough in the realms of target therapy.
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[342]
TÍTULO / TITLE: - Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mutagenesis. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1093/mutage/get008
AUTORES / AUTHORS: - Andujar P; Pairon JC; Renier A; Descatha A; Hysi I; Abd-Alsamad I; Billon-Galland MA; Blons H; Clin B; Danel C; Debrosse D; Galateau-Salle F; Housset B; Laurent-Puig P; Le Pimpec-Barthes F; Letourneux M; Monnet I; Regnard JF; Validire P; Zucman-Rossi J; Jaurand MC; Jean D
INSTITUCIÓN / INSTITUTION: - Centre Hospitalier Intercommunal de Creteil, Service de Pneumologie et de Pathologie Professionnelle, Creteil F-94000, France.
RESUMEN / SUMMARY: - Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.
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[343]
TÍTULO / TITLE: - Anticancer activity of fish oils against human lung cancer is associated with changes in formation of PGE(2) and PGE(3) and Alteration of Akt Phosphorylation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Carcinog. 2013 Jan 31. doi: 10.1002/mc.22008.
●● Enlace al texto completo (gratuito o de pago) 1002/mc.22008
AUTORES / AUTHORS: - Yang P; Cartwright C; Chan D; Ding J; Felix E; Pan Y; Pang J; Rhea P; Block K; Fischer SM; Newman RA
INSTITUCIÓN / INSTITUTION: - Department of General Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas.
RESUMEN / SUMMARY: - The beneficial effects of omega-3 fatty acids are believed to be due in part to selective alteration of arachidonate metabolism that involves cyclooxygenase (COX) enzymes. Here we investigated the effect of eicosapentaenoic acid (EPA) on the proliferation of human non-small cell lung cancer A549 (COX-2 over-expressing) and H1299 (COX-2 null) cells as well as their xenograft models. While EPA inhibited 50% of proliferation of A549 cells at 6.05 microM, almost 80 microM of EPA was needed to reach similar levels of inhibition of H1299 cells. The formation of prostaglandin (PG)E(3) in A549 cells was almost threefold higher than that of H1299 cells when these cells were treated with EPA (25 microM). Intriguingly, when COX-2 expression was reduced by siRNA or shRNA in A549 cells, the antiproliferative activity of EPA was reduced substantially compared to that of control siRNA or shRNA transfected A549 cells. In line with this, dietary menhaden oil significantly inhibited the growth of A549 tumors by reducing tumor weight by 58.8 +/- 7.4%. In contrast, a similar diet did not suppress the development of H1299 xenograft. Interestingly, the ratio of PGE(3) to PGE(2) in A549 was about 0.16 versus only 0.06 in H1299 xenograft tissues. Furthermore, PGE(2) up-regulated expression of pAkt, whereas PGE(3) downregulated expression of pAkt in A549 cells. Taken together, the results of our study suggest that the ability of EPA to generate PGE(3) through the COX-2 enzyme might be critical for EPA-mediated tumor growth inhibition which is at least partly due to down-regulation of Akt phosphorylation by PGE(3) . © 2013 Wiley Periodicals, Inc.
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[344]
TÍTULO / TITLE: - Clinical significance of serum adipokines levels in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):507. doi: 10.1007/s12032-013-0507-x. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0507-x
AUTORES / AUTHORS: - Kerenidi T; Lada M; Tsaroucha A; Georgoulias P; Mystridou P; Gourgoulianis KI
INSTITUCIÓN / INSTITUTION: - Respiratory Department, University Hospital of Larissa, University of Thessaly, 41110 Larissa, Greece. noraker@gmail.com
RESUMEN / SUMMARY: - Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients—mean age 62.9 +/- 9.2 years—with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information.
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[345]
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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[346]
TÍTULO / TITLE: - Combined inhibition of the EGFR and mTOR pathways in EGFR wild-type non-small cell lung cancer cell lines with different genetic backgrounds.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Mar 22. doi: 10.3892/or.2013.2357.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2357
AUTORES / AUTHORS: - Huang Y; Chen Y; Mei Q; Chen Y; Yu S; Xia S
INSTITUCIÓN / INSTITUTION: - Cancer Center of Tongji Hospital, Tongji Medical College, Huazhong University of science and technology, Wuhan, Hubei 430030, P.r. China.
RESUMEN / SUMMARY: - The epidermal growth factor receptor (EGFR) signaling pathway is widely activated in non-small cell lung cancer (NSCLC). However, only a subset of patients with NSCLC is sensitive to EGFR tyrosine kinase inhibitors (TKIs), particularly those with activating EGFR mutations. The mammalian target of rapamycin (mTOR) is another key intracellular kinase that plays an important role in the onset and progression of many types of human cancers and has been proven to be linked with primary resistance to EGFR inhibitors. We performed this study to investigate the combined inhibitory effect of the mTOR inhibitor RAD001 and the EGFR-TKI gefitinib in three EGFR wild-type NSCLC cell lines: A549 (PIK3CA wildtype), NCI-H460 (PIK3CA mutant) and NCI-H661 (PIK3CA wild-type). All cell lines demonstrate a poor response to gefitinib, but have a different genetic status for PIK3CA. We used MTT assays to measure cell proliferation. Flow cytometry was used to assess the effects on apoptosis and cell cycle arrest. Immunoblot analysis was used to evaluate the expression of downstream proteins. Treatment of RAD001 alone showed dose-dependent growth inhibition in all three cell lines. The combination of gefitinib and RAD001 resulted in synergistic growth inhibition in NCI-H460 cells, but only an additive inhibitory effect on A549 and NCI-H661 cells. Exposure to the combination of RAD001 and gefitinib led to a significant reduction in phosphorylated AKT levels in NCI-H460 cells; however, this was not noted in the other two cell lines. In conclusion, our data indicate that the dual inhibition of the EGFR/mTOR pathways may be a promising approach to treat EGFR wild-type NSCLC; however, this may be dependent on the PIK3CA mutation status.
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[347]
TÍTULO / TITLE: - Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomarkers. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 3109/1354750X.2013.777116
AUTORES / AUTHORS: - Lowe FJ; Luettich K; Gregg EO
INSTITUCIÓN / INSTITUTION: - British American Tobacco , Southampton , UK and.
RESUMEN / SUMMARY: - Abstract Manufacturers have developed prototype cigarettes yielding reduced levels of some tobacco smoke toxicants, when tested using laboratory machine smoking under standardised conditions. For the scientific assessment of modified risk tobacco products, tests that offer objective, reproducible data, which can be obtained in a much shorter time than the requirements of conventional epidemiology are needed. In this review, we consider whether biomarkers of biological effect related to oxidative stress can be used in this role. Based on published data, urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F2-isoprostanes, serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations show promise, while 4-hydroxynonenal requires further qualification.
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[348]
TÍTULO / TITLE: - ER homeostasis and motility of NSCLC cell lines can be therapeutically targeted with combined Hsp90 and HDAC inhibitors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pulm Pharmacol Ther. 2013 Feb 19. pii: S1094-5539(13)00061-8. doi: 10.1016/j.pupt.2013.02.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pupt.2013.02.004
AUTORES / AUTHORS: - Zismanov V; Drucker L; Gottfried M
INSTITUCIÓN / INSTITUTION: - Lung Cancer Research Laboratory, Meir Medical Center, Kfar Saba 44281, Israel; Sackler Faculty of Medicine, Tel Aviv University Ramat Aviv, Tel Aviv 69978, Israel. Electronic address: vic.zismanov@clalit.org.il.
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVE: Lung cancer remains the most common cause of cancer-related death in the world for which novel systemic treatments are urgently needed. Protein homeostasis that regulates protein levels and their fold is critical for cancer cell proliferation and survival. A complex network of cellular organelles and signaling cascades is involved in control of protein homeostasis including endoplasmic reticulum (ER). Thus, proteins in control of ER homeostasis are increasingly recognized as potential therapeutic targets. Molecular chaperone heat shock protein 90 (Hsp90) and histone deacetylase (HDAC) play an important role in ER homeostasis. Previous studies demonstrate that Hsp90 and HDAC inhibitors are individually functional against lung cancer. In this work we suggested that combined Hsp90 and HDAC inhibitors may elevate ER stress thereby enhancing the anti non small lung cancer (NSCLC) activity. METHODS AND RESULTS: Using an in vitro cell line model we demonstrated that 17-DMAG (HSP90 inhibitor) co-administration with PTACH (HDAC inhibitor) caused elevated ER stress (immunoblotting) (more than 110% upward arrow, p < 0.05) accompanied by apoptotic cell death (Annexin V) (7-21% upward arrow, p < 0.05). Moreover, 17-DMAG/PTACH treated cells lost the ability to migrate (scratch test) (57-85% downward arrow of scratch closure, p < 0.05). CONCLUSIONS: Our findings provide proof-of-concept that targeting ER homeostasis is therapeutically beneficial in lung cancer cell lines. Indeed, the elevated ER stress caused by 17-DMAG/PTACH combined treatment leads to increased cell death of NSCLC cell lines compared to the application of the drugs separately.
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[349]
TÍTULO / TITLE: - Detection of impaired homologous recombination repair in NSCLC cells and tissues.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):279-86. doi: 10.1097/JTO.0b013e31827ecf83.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827ecf83
AUTORES / AUTHORS: - Birkelbach M; Ferraiolo N; Gheorghiu L; Pfaffle HN; Daly B; Ebright MI; Spencer C; O’Hara C; Whetstine JR; Benes CH; Sequist LV; Zou L; Dahm-Daphi J; Kachnic LA; Willers H
INSTITUCIÓN / INSTITUTION: - Laboratory of Cellular & Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.
RESUMEN / SUMMARY: - INTRODUCTION: Homologous recombination repair (HRR) is a critical pathway for the repair of DNA damage caused by cisplatin or poly-ADP ribose polymerase (PARP) inhibitors. HRR may be impaired by multiple mechanisms in cancer, which complicates assessing the functional HRR status in cells. Here, we monitored the ability of non-small-cell lung cancer (NSCLC) cells to form subnuclear foci of DNA repair proteins as a surrogate of HRR proficiency. METHODS: We assessed clonogenic survival of 16 NSCLC cell lines in response to cisplatin, mitomycin C (MMC), and the PARP inhibitor olaparib. Thirteen tumor explants from patients with NSCLC were subjected to cisplatin ex vivo. Cells were assayed for foci of repair-associated proteins such as BRCA1, FANCD2, RAD51, and gamma-H2AX. RESULTS: Four cell lines (25%) showed an impaired RAD51 foci-forming ability in response to cisplatin. Impaired foci formation correlated with cellular sensitivity to cisplatin, MMC and olaparib. Foci responses complemented or superseded genomic information suggesting alterations in the ATM/ATR and FA/BRCA pathways. Because baseline foci in untreated cells did not predict drug sensitivity, we adapted an ex vivo biomarker assay to monitor damage-induced RAD51 foci in NSCLC explants from patients. Ex vivo cisplatin treatment of explants identified two tumors (15%) exhibiting compromised RAD51 foci induction. CONCLUSIONS: A fraction of NSCLC harbors HRR defects that may sensitize the affected tumors to DNA-damaging agents including PARP inhibitors. We propose that foci-based functional biomarker assays represent a powerful tool for prospective determination of treatment sensitivity, but will require ex vivo techniques for induction of DNA damage to unmask the underlying HRR defect.
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[350]
TÍTULO / TITLE: - NSCLC subtype prediction using cytologic fluid specimens from needle aspiration biopsies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Clin Pathol. 2013 Mar;139(3):309-16. doi: 10.1309/AJCPYOJYG56UNBSZ.
●● Enlace al texto completo (gratuito o de pago) 1309/AJCPYOJYG56UNBSZ
AUTORES / AUTHORS: - Cho A; Hur J; Hong YJ; Lee HJ; Kim YJ; Kim HY; Lee JW; Shim HS; Choi BW
INSTITUCIÓN / INSTITUTION: - Division of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea.
RESUMEN / SUMMARY: - This study evaluated the diagnostic usefulness of tumor marker concentrations in cytologic fluids (CF) for subtyping non-small cell lung cancer (NSCLC) and assessed the relationship between fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake with serum and CF tumor marker levels. This prospective study included 88 patients diagnosed with adenocarcinoma or squamous cell carcinoma (SCC). Cytokeratin-19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) concentrations in the CF samples were correlated with serum tumor marker concentrations, (18)F-FDG uptake, and NSCLC subtype. Fifty-eight patients were diagnosed with adenocarcinoma. Multivariate analysis revealed higher CF and serum SCCA levels; smoking status predicted SCC from adenocarcinoma. CF SCCA showed the highest accuracy (83%) in distinguishing between SCC and adenocarcinoma. CF samples obtained during routine needle aspiration biopsy procedure contain tumor marker levels sufficient to distinguish between SCC and adenocarcinoma; CF SCCA had the highest diagnostic accuracy.
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[351]
TÍTULO / TITLE: - Lung cancer mortality in European men: Trends and predictions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 20. pii: S0169-5002(13)00056-1. doi: 10.1016/j.lungcan.2013.01.020.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.020
AUTORES / AUTHORS: - Malvezzi M; Bosetti C; Rosso T; Bertuccio P; Chatenoud L; Levi F; Romano C; Negri E; La Vecchia C
INSTITUCIÓN / INSTITUTION: - Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy; Dipartimento di Scienze Cliniche e di Comunita, Universita degli Studi di Milano, Milan, Italy.
RESUMEN / SUMMARY: - Lung cancer mortality in men from the European Union (EU) peaked in the late 1980s at an age-standardised (world standard population) rate over 53/100,000 and declined subsequently to reach 44/100,000 in the early 2000s. To provide a comprehensive picture of recent trends in male lung cancer mortality in Europe, we analyzed available data from the World Health Organization up to 2009 and predicted future rates to 2015. Lung cancer mortality rates in EU men continued to fall over recent years, to reach a value of 41.1/100,000 in 2005-2009. The fall was similar at all-ages and in middle-aged men (less than 2% per year over most recent years), but was appreciably larger in young men (aged 20-44years, over 5% per year). A favourable trend is thus likely to be maintained in the foreseeable future, although the predicted overall EU rate in 2015 is still over 35/100,000, i.e., higher than the US rate in 2007 (33.7/100,000). Over most recent calendar years, overall male lung cancer rates were around 35-40/100,000 in western Europe, as compared to over 50/100,000 in central and eastern Europe. Within western Europe, lung cancer rates were lower in northern countries such as Sweden, but also Finland and the UK (below 30/100,000), where the tobacco-related epidemic started earlier and rates have long been declining, whereas mortality was high in Belgium (51.6), France (42.3), the Netherlands and España (around 43.0), where the epidemic started later but is persisting. Widespread measures for smoking control and cessation in middle-aged European men, i.e., in the generations where smoking prevalence used to be high, would lead to appreciable reductions in male lung cancer mortality in the near future. This is particularly urgent in central and eastern European countries.
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[352]
TÍTULO / TITLE: - Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Dairy Sci. 2013 Apr;96(4):2095-106. doi: 10.3168/jds.2012-6153. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 3168/jds.2012-6153
AUTORES / AUTHORS: - Tung YT; Chen HL; Yen CC; Lee PY; Tsai HC; Lin MF; Chen CM
INSTITUCIÓN / INSTITUTION: - Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
RESUMEN / SUMMARY: - Lung cancers are among the most common cancers in the world, and the search for effective and safe drugs for the chemoprevention and therapy of pulmonary cancer has become important. In this study, bovine lactoferrin (bLF) was used in both in vitro and in vivo approaches to investigate its activity against lung cancer. A human lung cancer cell line, A549, which expresses a high level of vascular endothelial growth factor (VEGF) under hypoxia, was used as an in vitro system for bLF treatment. A strain of transgenic mice carrying the human VEGF-A165 (hVEGF-A165) gene, which induces pulmonary tumors, was used as an in vivo lung cancer therapy model. We found that bLF significantly decreased proliferation of A549 cells by decreasing the expression of VEGF protein in a dose-dependent manner. Furthermore, oral administration of bLF at 300mg/kg of body weight 3 times a week for 1.5 mo to the transgenic mice overexpressing hVEGF-A165 significantly eliminated expression of hVEGF-A165 and suppressed the formation of tumors. Additionally, treatment with bLF significantly decreased the levels of proinflammatory cytokines, such as tumor necrosis factor-alpha, and antiinflammatory cytokines, such as IL-4 and IL-10. Levels of IL-6, which is both a proinflammatory and an antiinflammatory cytokine, were also reduced. Treatment with bLF decreased levels of tumor necrosis factor-alpha, IL-4, IL-6, and IL-10 cytokines, resulting in limited inflammation, which then restricted growth of the lung cancer. Our results revealed that bLF is an inhibitor of angiogenesis and blocks lung cell inflammation; as such, it has considerable potential for therapeutic use in the treatment of lung cancer.
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[353]
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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[354]
TÍTULO / TITLE: - Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mod Pathol. 2013 Mar 15. doi: 10.1038/modpathol.2013.34.
●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2013.34
AUTORES / AUTHORS: - Ordonez NG
INSTITUCIÓN / INSTITUTION: - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
RESUMEN / SUMMARY: - Both mesotheliomas and renal cell carcinomas can present a wide variety of cytomorphologic features and histologic patterns. Because of this, renal cell carcinomas metastatic to the pleura and lung can be confused with mesotheliomas. Recently, a variety of positive carcinoma markers, including kidney-associated markers, have become available. The aim of this study is to investigate the value of some of these markers, specifically PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4, for assisting in distinguishing pleural epithelioid mesotheliomas from metastatic renal cell carcinomas. To do so, a total of 40 pleural epithelioid mesotheliomas and 55 renal cell carcinomas (33 clear cell, 10 papillary, and 12 chromophobe) were investigated. In all, 91% of the renal cell carcinomas expressed claudin-4, 89% PAX8, 60% PAX2, 71% carbonic anhydrase IX, and 29% napsin A. All of the mesotheliomas were positive for carbonic anhydrase IX and were negative for all of the other markers. On the basis of these results, it is concluded that claudin-4 and PAX8 have a higher sensitivity and specificity for assisting in discriminating between pleural epithelioid mesotheliomas and renal cell carcinomas when compared with all of the other positive carcinoma markers that are, at present, recommended to be included in the immunohistochemical panels used in this differential diagnosis. Even though PAX2 and napsin A are highly specific, because of their low sensitivity, they have only a limited value. Carbonic anhydrase IX is not useful.Modern Pathology advance online publication, 15 March 2013; doi:10.1038/modpathol.2013.34.
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[355]
TÍTULO / TITLE: - Efficacy of bevacizumab-containing chemotherapy for non-squamous non-small cell lung cancer with bone metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2148-3
AUTORES / AUTHORS: - Tokito T; Shukuya T; Akamatsu H; Taira T; Ono A; Kenmotsu H; Naito T; Murakami H; Takahashi T; Endo M; Yamamoto N
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan, t.tokito@scchr.jp.
RESUMEN / SUMMARY: - PURPOSE: Skeletal-related events (SREs) negatively affect the quality of life of patients with cancer. Vascular endothelial growth factor receptor (VEGFR)-targeted therapy is effective against bone metastasis in animal models, but the clinical efficacy of anti-VEGFR inhibitors against bone metastases remains unclear. Therefore, we aimed to investigate the efficacy of chemotherapy with bevacizumab, an anti-VEGF antibody, against bone metastases. METHODS: We retrospectively reviewed consecutive patients with non-squamous non-small cell lung cancer who received first-line platinum-based chemotherapy with zoledronic acid at Shizuoka Cancer Center between 2007 and 2011. RESULTS: Of 25 patients, 13 received bevacizumab-based chemotherapy (BEV group) and 12 received chemotherapy without bevacizumab (non-BEV group). The overall response (54 vs. 8 %, p = 0.01) and disease control (100 vs. 50 %, p = 0.01) rates were higher in the BEV group than in the non-BEV group. The bone-specific response (23 vs. 0 %, p = 0.038) and disease control (100 vs. 67 %, p = 0.01) rates were also higher in the BEV group. The median time to progression (TTP) for bone metastases was higher in the BEV group (13.7 vs. 4.3 months, p = 0.06), whereas that for overall disease was similar between the groups (5.7 vs. 2.6 months, p = 0.17). The proportions of patients with SREs were 23 and 50 % in the BEV and non-BEV groups, respectively (p = 0.16). CONCLUSION: Bevacizumab might potentiate the antitumor activity of chemotherapy against systemic disease and bone metastases, prolonging bone-specific TTP and reducing the incidence of SRE.
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[356]
TÍTULO / TITLE: - Proliferation and maturation of intratumoral blood vessels in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 19. pii: S0046-8177(13)00024-5. doi: 10.1016/j.humpath.2013.01.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2013.01.004
AUTORES / AUTHORS: - Yazdani S; Miki Y; Tamaki K; Ono K; Iwabuchi E; Abe K; Suzuki T; Sato Y; Kondo T; Sasano H
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
RESUMEN / SUMMARY: - Non-small cell lung carcinoma is one of the most common leading causes of cancer mortality, and studying the features of intratumoral vessels, especially their generation and maturation, has become more important because of the recent application of antiangiogenic therapy. Vasohibin-1 has been recently considered one of the immunohistochemical markers for identifying neovascularization in archival materials. In addition, the functional maturation of blood vessels is considered to be related to pericyte formation around endothelial cells. Therefore, in this study, we evaluated the status of angiogenesis and maturation of intratumoral blood vessels in 93 patients with non-small cell lung carcinoma (50 with adenocarcinoma and 43 with squamous cell carcinoma) using immunohistochemistry of vasohibin-1, endoglin, CD31, and nestin. The vasohibin-1/CD31-positive ratio was significantly (P = .03) correlated with the Ki-67/CD31 ratio, confirming that the vasohibin-1/CD31-positive ratio represented the status of neovascularization in lung cancer. There were no statistically significant differences in vasohibin-1/CD31 ratios between adenocarcinoma and squamous cell carcinoma in both inner (P = .39) and outer areas (P = .36) of the tumor. The vasohibin-1/nestin-positive ratio, which represents the degrees of vascular maturation in proliferative vessels, was significantly lower in inner areas of adenocarcinoma (0.4 +/- 0.1) than those in squamous cell carcinoma (0.8 +/- 0.1) (P = .02). These results demonstrated that the degrees of maturation in newly formed blood vessels were less developed in inner areas of squamous cell carcinoma than adenocarcinoma, which may account partly for the complications of antivascular endothelial growth factor therapy more frequently detected in patients with squamous cell carcinoma.
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[357]
TÍTULO / TITLE: - MiR-449c targets c-Myc and inhibits NSCLC cell progression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - FEBS Lett. 2013 Mar 15. pii: S0014-5793(13)00204-4. doi: 10.1016/j.febslet.2013.03.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.febslet.2013.03.006
AUTORES / AUTHORS: - Miao LJ; Huang SF; Sun ZT; Gao ZY; Zhang RX; Liu Y; Wang J
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Open Laboratory of Clinical Medicine and Key Subject, Henan Institution of Higher Education, PR China. Electronic address: miaolily@126.com.
RESUMEN / SUMMARY: - MicroRNAs (miRNA) play an important role in tumorigenesis, proliferation, and differentiation. Altered miRNA expression in cancer indicates that miRNAs can function as tumor suppressors or oncogenes. MiR-449c downregulation in non-small cell lung cancer (NSCLC) compared with normal lung tissues was investigated in this study. NSCLC cell proliferation and invasion assays indicate that transfection of miR-449c expression plasmid inhibits the proliferation and invasion ability of NCI-H23 and NCI-H838 cells. In addition, miR-449c overexpression could suppress tumor growth in vivo. Morever, c-Myc was identified as a direct target gene of miR-449c. These findings clearly suggest that miR-449c downregulation and c-Myc amplification may be involved in the development of NSCLC.
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[358]
TÍTULO / TITLE: - Comparison of molecular testing methods for the detection of EGFR mutations in formalin-fixed paraffin-embedded tissue specimens of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Pathol. 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2012-201240
AUTORES / AUTHORS: - Lopez-Rios F; Angulo B; Gomez B; Mair D; Martinez R; Conde E; Shieh F; Tsai J; Vaks J; Current R; Lawrence HJ; de Castro DG
INSTITUCIÓN / INSTITUTION: - Laboratorio de Dianas Terapeuticas, Centro Integral Oncologico Clara Campal, Hospital Universitario Madrid Sanchinarro, Madrid, España.
RESUMEN / SUMMARY: - AIM: To conduct a methods correlation study of three different assays for the detection of mutations at EGFR gene in human formalin-fixed paraffin-embedded tumour (FFPET) specimens of non-small cell lung carcinomas (NSCLC). METHODS: We conducted a 2-site method comparison study of two european conformity (CE) in vitro diagnostic (IVD)-marked assays, the cobas EGFR Mutation Test and the Therascreen EGFR29 Mutation Kit, and 2x bidirectional Sanger sequencing. We blind-tested 124 NSCLC FFPET specimens with all three methods; the cobas test was performed at both sites. Positive (PPA) and negative percent agreements (NPA) were determined for the cobas test versus each of the other two methods. Specimens yielding discordant test results between methods were further tested using quantitative massively parallel pyrosequencing (MPP). RESULTS: PPA between cobas and Sanger was 98.8%; NPA was 79.3%. Overall there were seven discordant results. MPP confirmed an exon 19 deletion in two cases and L858R mutation in four cases. PPA between cobas and Therascreen was 98.9% and NPA was 100%. There was one discordant result. Reproducibility of the cobas test between the two sites was 99.2%. CONCLUSIONS: The invalid rates for the cobas test and Therascreen were lower than Sanger sequencing. The cobas and Therascreen assays showed a high degree of concordance, and both were more sensitive for the detection of exon 19 deletion and L858R mutations than Sanger. The cobas test was highly reproducible between the two testing sites, used the least amount of DNA input and was the only test with automated results reporting.
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[359]
TÍTULO / TITLE: - Influential factors, complications and survival rate of primary and salvage total laryngectomy for advanced laryngeal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:7-12.
AUTORES / AUTHORS: - Stankovic M; Milisavljevic D; Stojanov D; Zivic M; Zivaljevic S; Stankovic I; Petrovic S
INSTITUCIÓN / INSTITUTION: - University Clinical Center Nis, Clinic for Otorhinolaryngology, Nis, Serbia. milanorlstankovic@gmail.com
RESUMEN / SUMMARY: - This is a retrospective review of patients with advanced malignant neoplasms of the larynx treated with total laryngectomy. 387 total laryngectomies for advanced squamous cell carcinoma of larynx performed in the period between 1995 and 2007 were analyzed. Primary total laryngectomy (PRT) was performed in 316 patients, while initial radiotherapy radiotherapy (60-70 Gy) and concomitant chemotherapy (cisplatin-5 fluorouracil) with radiotherapy were applied in totally 71 patients who later received salvage total laryngectomy (STL). All the laryngectomies were performed by four surgeons, using the same routine surgical technique. Postoperative clinical examination was made every three months during five years. We documented the occurrence of: local and general complications, survival rate, residual and recurrent disease, lymph node metastasis, and other changes. Salvage total laryngectomy after previous radiotherapy (STL-pRT) and after chemoradiotherapy (STL-pCTRT) caused more frequent local complications than primary total laryngectomy (PTL). TNM stage and localization of primary laryngeal tumor had significant influence on five year survival rate. It amounted: 61.4% for PTL, 52.6% for STL-pCTRT, and 48.5% for STL-pRT. Incomplete response to initial treatment produced low survival rate. Salvage total laryngectomy caused more frequent local complications, especially after chemoradiotherapy when compared to primary laryngectomy. Survival rate was increased when chemotherapy is added to radiotherapy. Five year survival rate depended on TNM stage and localization of primary tumor.
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[360]
TÍTULO / TITLE: - Effects of simvastatin and rosuvastatin on RAS protein, matrix metalloproteinases and NF-kappaB in lung cancer and in normal pulmonary tissues.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Prolif. 2013 Apr;46(2):172-82. doi: 10.1111/cpr.12018.
●● Enlace al texto completo (gratuito o de pago) 1111/cpr.12018
AUTORES / AUTHORS: - Falcone D; Gallelli L; Di Virgilio A; Tucci L; Scaramuzzino M; Terracciano R; Pelaia G; Savino R
INSTITUCIÓN / INSTITUTION: - Department of Health Science, School of Medicine, University of Catanzaro, Catanzaro, Italy.
RESUMEN / SUMMARY: - OBJECTIVES: In this study, we have evaluated effects of 24-hour treatments with simvastatin or rosuvastatin on RAS protein, NF-kappaB and MMP expression in LC tissues obtained from 12 patients undergoing thoracic surgery. MATERIALS AND METHODS: Normal and lung tumour tissues obtained from each sample were exposed to simvastatin (2.5-30 mum) or rosuvastatin (1.25-30 mum) and western blot analysis was then performed. RESULTS: We documented increased expression of proteins, MMP-2, MMP-9 and NF-kappaB-p65 in LC tissues, with respect to normal tissues (P < 0.01). In the malignant tissues, simvastatin and rosuvastatin significantly (P < 0.01) and dose-dependently reduced RAS protein, MMP-2/9 and NF-kappaB-p65 expression. CONCLUSIONS: In conclusion, our results suggest that simvastatin and rosuvastatin could play a role in LC treatment by modulation of RAS protein, MMP-2/9 and NF-kappaB-p65.
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[361]
TÍTULO / TITLE: - Recurrent sinonasal melanoma—report of five surgical cases and short literature review.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:179-84.
AUTORES / AUTHORS: - Dzepina D; Kalogjera L; Baudoin T
INSTITUCIÓN / INSTITUTION: - University of Zagreb, Sestre milosrdnice University Hospital Center, Department of ENT - Head and Neck Surgery, Zagreb, Croatia. dzepina.davor@gmail.com
RESUMEN / SUMMARY: - The aim of this study is to present five surgical cases of recurrent sinonasal melanoma. We report the clinical course of this highly malignant disease and give a brief overview of the relevant literature. For the purpose of our presentation, inclusion criteria for all patients were initally negative surgical margins, surgery with curative intent without implementation of radiotherapy, and absence of distant metastatic spread at presentation (MO). They were diagnosed and treated at the same ENT/Head and Neck Surgery department and had clear surgical margins following first resection. The majority of five cases had local recurrences (average two) which were all amenable to at least one salvage operation. In conclusion, despite extensive disease at presentation, we recommend repeated attempts at local surgical salvage. However, this decision must be carefully considered, respecting postoperative quality of life, the estimated life expectancy as well as general socioeconomic issues in each particular case.
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[362]
TÍTULO / TITLE: - Relevance of an extensive follow-up after surgery for non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Respir J. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1183/09031936.00086712
AUTORES / AUTHORS: - Gourcerol D; Scherpereel A; Debeugny S; Porte H; Cortot AB; Lafitte JJ
INSTITUCIÓN / INSTITUTION: - Lille University Hospital (CHRU), France.
RESUMEN / SUMMARY: - There are no international guidelines for an appropriate and cost-effective follow-up for resected non-small cell lung cancer (NSCLC).We retrospectively reviewed the outcome of NSCLC patients after curative surgery. Follow-up included physical examination and chest X-Ray every 3 months, chest CT-scan, bronchoscopy, abdominal ultrasound, brain CT-scan and bone-scan every 6 months for 3 years then every year during 2 years. Prognostic factors and costs were analysed.Median overall survival (OS) following surgery for NSCLC in 162 patients was 38.5 months. Recurrence occurred in 85 patients (52.5%) including 41 symptomatic subjects (48%). Disease-free survival was similar between patients with asymptomatic recurrence vs symptomatic patients (11.4 vs. 12 months; p=0.41). Recurrence was detected by physical examination or chest X-ray in 47 patients (55.3%). Curative-intent therapy was provided in 18/44 (41%) patients with asymptomatic recurrence and in 4/41 (10%) symptomatic cases (p=0.001). Median OS from time of recurrence was higher in asymptomatic patients than in symptomatic patients (15.5 vs. 7.2 months; p=0.001). The cost per year of gained life was 32,700 USD (22,397euro).An extensive follow-up, with acceptable cost, may improve the outcome of patients with resected NSCLC through detection of asymptomatic recurrences; validation by prospective studies is required.
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[363]
TÍTULO / TITLE: - Lung parenchymal invasion in pulmonary carcinoid tumor: An important histologic feature suggesting the diagnosis of atypical carcinoid and poor prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 2. pii: S0169-5002(13)00012-3. doi: 10.1016/j.lungcan.2013.01.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.005
AUTORES / AUTHORS: - Ha SY; Lee JJ; Cho J; Hyeon J; Han J; Kim HK
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Republic of Korea.
RESUMEN / SUMMARY: - The majority of previous studies on pulmonary carcinoid tumor have usually focused on clinical behavior or outcome, seldom considering histopathologic features. We retrospectively collected 63 cases of resected pulmonary carcinoid tumors from 1995 to 2011 at Samsung Medical Center, Seoul, Korea. The clinical and pathological features were correlated and survival analyses were performed. Forty cases (63.5%) were classified as typical carcinoid (TC) and 23 cases (36.5%) were classified as atypical carcinoid (AC) according to WHO classification criteria. AC patients showed a higher frequency of current smoking status and a higher stage of the tumor by the American Joint Committee on Cancer than TC patients. The disease was associated with death and recurrence in five and seven patients, respectively, with almost all of the associations found in AC patients. The five-year survival rate of TC and AC were 100% and 83.5%, respectively, with AC showing poorer prognosis than TC in overall survival (OS) and disease free survival (DFS) (p=0.005 and p=0.002). Lung parenchymal invasion was observed more commonly in AC than in TC (39.1% vs 12.5%, p=0.01) and was a poor prognostic factor in OS and DFS. Rosette-like arrangements were found only in six cases of AC, while abundant basophilic cytoplasm mimicking paraganglioma and ossification were found only in TC. Through the comprehensive study of pulmonary carcinoid tumor in Korea, we suggest that lung parenchymal invasion could be a useful histologic feature to suspect the diagnosis of AC in daily practice as well as to predict the prognosis of carcinoid tumor.
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[364]
TÍTULO / TITLE: - Prognostic significance of vascular and lymphatic emboli in resected pulmonary adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Apr;95(4):1204-10. doi: 10.1016/j.athoracsur.2012.12.024. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.12.024
AUTORES / AUTHORS: - Strano S; Lupo A; Lococo F; Schussler O; Loi M; Younes M; Bobbio A; Damotte D; Regnard JF; Alifano M
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Hotel-Dieu Hospital, Paris Descartes University, Paris, France.
RESUMEN / SUMMARY: - BACKGROUND: The incidence of vascular and lymphatic emboli in a specimen of resected non-small cell lung cancer is variable according to different authors’ experience as well as prognostic significance in patients treated by surgery. We aimed at evaluating these factors in an unselected population of patients with primary pulmonary adenocarcinoma treated by major surgical resection. METHODS: Clinical and pathology records of all patients treated by lobectomy or pneumonectomy and nodal dissection for pulmonary adenocarcinoma between June 2001 and June 2006 were retrospectively reviewed. Impact on survival of age, sex, tobacco use, history of chronic obstructive pulmonary disease, extent of resection, pathologic stage, and presence of vascular and lymphatic emboli was studied by univariate analysis and multivariate analysis (for factors significantly associated with survival at univariate analysis). RESULTS: Five hundred three patients underwent lobectomy or pneumonectomy with nodal dissection for pathologically proven lung adenocarcinoma. There were 355 men and 148 women; mean age was 61.1 years, and 181 patients were 65 years old or older; 87% were current or former smokers; 90.3% had pulmonary lobectomy; and 9.7% had pneumonectomy. Pathologic stages were I, II, and III/IV in 45%, 17.9%, and 37.1%, respectively. Vascular emboli and lymphatic emboli were found in 183 of 503 patients (36.4%) and 149 of 503 (29.6%), respectively. Overall 5-year survival for the whole population was 50.7%. At univariate analysis, age more than 65 years (p = 0.0019), chronic obstructive pulmonary disease (p = 0.042), extent of resection (p = 0.047), pathologic stage (p < 0.0000001), T size (p = 0.0020), T and N variables (p = 0.0000016 and p < 0.0000001, respectively), presence of vascular emboli (p = 0.026), and presence of lymphatic emboli (p = 0.000021) were associated with worse prognosis. At multivariate analysis, age more than 65 years (p = 0.0047, relative risk 1.5), stage I versus II versus III versus IV (p = 0.00000032), and presence of lymphatic emboli (p = 0.05, relative risk 1.34) were identified as independent negative prognostic factors. CONCLUSIONS: In an unselected population of patients with pulmonary adenocarcinoma treated by lobectomy or pneumonectomy, the presence of lymphatic emboli is an independent negative prognostic factor.
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[365]
TÍTULO / TITLE: - Spiritual well-being in lung cancer survivors.
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/s00520-013-1757-z
AUTORES / AUTHORS: - Frost MH; Novotny PJ; Johnson ME; Clark MM; Sloan JA; Yang P
INSTITUCIÓN / INSTITUTION: - Mayo Clinic Rochester, 200 First Street SW, Charlton, 6, Rochester, MN, 55905, USA, frost.marlene@mayo.edu.
RESUMEN / SUMMARY: - PURPOSE: Spiritual well-being (SWB) among lung cancer survivors has not been well-delineated. Additionally, little is known about how SWB is affected over the trajectory of the disease process. The aims of this study were to examine the SWB of individuals with a diagnosis of lung cancer, to assess the stability of SWB over time, and to identify the factors associated with SWB. METHODS: A prospective cohort of patients with lung cancer first seen at the Mayo Clinic over a 10-year period of time was included in this study. Study entry was at the time of diagnosis or referral to the Mayo Clinic, and participation involved annual survey using the Functional Assessment in Chronic Illness Therapy-Spiritual Well-being, Medical Outcome Short Form 8, and Quality of Life (QOL) Linear Analog Scale Assessment. Associations were explored using Fisher’s exact test, chi-squared test, Kruskal-Wallis test, and Spearman correlations. Linear regression was used to explore multivariate relationships. RESULTS: There were 1,578 participants over a 10-year period of time. Group SWB scores were relatively high and stable over a 10-year period of time ([Formula: see text], standard deviation = 14.47-18.46, possible scale of 0-100). However, individual scores varied widely across almost the entire scale (2.1-100) and revealed a chaotic trajectory for SWB. Males, current smokers, and those with higher pack-years experienced lower SWB compared to females, nonsmokers, and those with lower pack-years (p < 0.0001, 0.0455, and 0.0004, respectively). SWB was strongly associated with overall QOL. CONCLUSIONS: SWB is an individualistic experience that can change dramatically over time for cancer survivors. Ongoing assessments are important.
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[366]
TÍTULO / TITLE: - Method for the validation of immunohistochemical staining using SCID mouse xenografts: expression of CD40 and CD154 in human non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1315-21. doi: 10.3892/or.2013.2275. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2275
AUTORES / AUTHORS: - Ishikawa K; Miyamoto M; Yoshioka T; Kadoya M; Li L; Mishra R; Ichinokawa K; Shoji Y; Matsumura Y; Hida Y; Kaga K; Kato T; Kaji M; Ohbuchi T; Itoh T; Dosaka-Akita H; Matsui Y; Hirano S
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, and Department of Thoracic Surgery, Sapporo-Minamisanjo Hospital, Sapporo, Hokkaido 060-8638, Japan. keidaiishikawa@hotmail.com
RESUMEN / SUMMARY: - This report proposes a concept for the standardization of immunohistochemical evaluation. Immunohistochemical staining has several problems associated with the sensitivity of the technical process and standardization of the assessment of potent staining. We provided data focusing on this concept through immunostaining for CD154 in non-small cell lung cancer (NSCLC). We used two types of anti-CD154 antibody as primary antibodies in immunohistochemical staining, as previously reported. Western blot analysis confirmed strong CD154 expression in the cultured cell line PC10, but not in LK2. We also assessed CD154 expression in SCID mouse xenografts of these cell lines. SCID xenograft data on western blot analysis were consistent with those of cultured cell lines. These xenografts could thus be used as positive or negative tissue controls for CD154 immunostaining. Primary antibodies should therefore be confirmed as recognizing target lesions, while control tissue specimens should be objectively confirmed as having target products using another experimental method. Our method would allow results to be unified at more than one laboratory and could act as an objective control assessment method in immunohistochemistry.
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[367]
TÍTULO / TITLE: - Building motion models of lung tumours from cone-beam CT for radiotherapy applications.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Phys Med Biol. 2013 Mar 21;58(6):1809-22. doi: 10.1088/0031-9155/58/6/1809. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1088/0031-9155/58/6/1809
AUTORES / AUTHORS: - Martin J; McClelland J; Yip C; Thomas C; Hartill C; Ahmad S; O’Brien R; Meir I; Landau D; Hawkes D
INSTITUCIÓN / INSTITUTION: - Centre for Medical Image Computing, University College London WC1E 6BT, UK.
RESUMEN / SUMMARY: - A method is presented to build a surrogate-driven motion model of a lung tumour from a cone-beam CT scan, which does not require markers. By monitoring an external surrogate in real time, it is envisaged that the motion model be used to drive gated or tracked treatments. The motion model would be built immediately before each fraction of treatment and can account for inter-fraction variation. The method could also provide a better assessment of tumour shape and motion prior to delivery of each fraction of stereotactic ablative radiotherapy. The two-step method involves enhancing the tumour region in the projections, and then fitting the surrogate-driven motion model. On simulated data, the mean absolute error was reduced to 1 mm. For patient data, errors were determined by comparing estimated and clinically identified tumour positions in the projections, scaled to mm at the isocentre. Averaged over all used scans, the mean absolute error was under 2.5 mm in superior-inferior and transverse directions.
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[368]
TÍTULO / TITLE: - 2D3D registration algorithm for lung brachytherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Phys. 2013 Feb;40(2):021913. doi: 10.1118/1.4788663.
●● Enlace al texto completo (gratuito o de pago) 1118/1.4788663
AUTORES / AUTHORS: - Zvonarev PS; Farrell TJ; Hunter R; Wierzbicki M; Hayward JE; Sur RK
INSTITUCIÓN / INSTITUTION: - McMaster University, Medical Physics and Applied Radiation Sciences, Hamilton, Ontario, Canada. zvonarp@mcmaster.ca
RESUMEN / SUMMARY: - PURPOSE: A 2D3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy. METHODS: The algorithm utilizes a rigid registration model based on a pixelvoxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated. RESULTS: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm. CONCLUSIONS: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.
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[369]
TÍTULO / TITLE: - Relationship of E-cadherin with cervical lymph node metastasis in laryngeal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:119-24.
AUTORES / AUTHORS: - Zvrko E; Mikic A; Jancic S
INSTITUCIÓN / INSTITUTION: - Clinical center of Montenegro, Clinic of Otorhinolaryngology and Maxillofacial Surgery, Podgorica, Montenegro. elvir@zvrko.me
RESUMEN / SUMMARY: - E-cadherin, a 120 kDa transmembrane protein, plays an important role in malignant progression and tumour differentiation. The loss or reduction in E-cadherin expression has been found in several tumours including laryngeal squamous cell carcinoma. The present study aimed to investigate the prognostic implications of changes in expression of the E-cadherin in laryngeal carcinoma. E-cadherin expression was determined by immunohistochemistry in paraffin- embedded tissue specimens from 80 patients. A staining score was given based on the percentage of cells stained (0-100%). E-cadherin expression varied greatly among tissue samples from 2 to 72 (median 25). Using the median expression of E-cadherin as a cut- off 41 (51.3%) tumours were classified in the “low E-cadherin” group and the rest, 39 (48.7%) tumours, consisted the “high E-cadherin” group. We found significant differences in the staining scores of E-cadherin between those tumours with and without nodal metastases (p = 0.025) and advanced clinical stage (TNM stage III and IV) (p = 0.014). The results of a stepwise logistic regression analysis showed that E-cadherin staining score and the location of primary tumour were independent predictors of nodal metastases. The immunohistochemical determination of E-cadherin expression may be useful instrument to characterise the metastatic potential of carcinomas. Larger studies are needed to confirm the role of E-cadherin expression in predicting the behavior of laryngeal squamous cell carcinomas.
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[370]
TÍTULO / TITLE: - Molecular Mechanism of Antiproliferation Potential of Acacia Honey on NCI-H460 Cell Line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013 Feb;65(2):296-304. doi: 10.1080/01635581.2013.756920.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2013.756920
AUTORES / AUTHORS: - Aliyu M; Odunola OA; Farooq AD; Rasheed H; Mesaik AM; Choudhary MI; Channa IS; Khan SA; Erukainure OL
INSTITUCIÓN / INSTITUTION: - a Department of Biochemistry , University of Ibadan , Ibadan , Oyo State , Nigeria.
RESUMEN / SUMMARY: - Lung cancer is one of the leading causes of death worldwide. We investigated the molecular mechanism of antiproliferation potential of Acacia honey on NCI-H460 cells by cell cycle, viability, cytokines, calcium ion and gene expression analysis. Acacia honey inhibited cells proliferation, arrested G0/G1 phase, stimulated cytokines, calcium ion release as well as suppressed p53 and Bcl-2 expression in a dose-dependent manner. We proposed that the molecular mechanism of the antiproliferation potential of Acacia honey on NCI-H460 cell line is due to cell cycle arrest, stimulation of cytokines and calcium ion as well as downregulation of Bcl-2 and p53 genes.
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[371]
TÍTULO / TITLE: - Alternating Chemotherapy with Amrubicin Plus Cisplatin and Weekly Administration of Irinotecan Plus Cisplatin for Extensive-stage Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):1117-23.
AUTORES / AUTHORS: - Noro R; Yoshimura A; Yamamoto K; Miyanaga A; Mizutani H; Minegishi Y; Seike M; Kubota K; Kosaihira S; Hino M; Ando M; Nomura K; Okano T; Kobayashi K; Uematsu K; Gemma A
INSTITUCIÓN / INSTITUTION: - Department of Clinical Oncology, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. ay1004@tokyo-med.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: A phase II study was conducted in order to determine the tumor efficacy and tolerance of alternating chemotherapy for extensive-stage small cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Twenty patients with previously-untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of amrubicin and cisplatin with weekly administration of irinotecan and cisplatin at 3- or 4-week intervals. RESULTS: The overall response rate was 85.0% (17/20). The median duration of overall survival and progression-free survival were 359 days and 227 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 20 (100%), 4 (20%) and 6 (30%) patients, respectively. With regard to non-hematological adverse events, grade 3 or 4 anorexia, diarrhea, febrile neutropenia and infection were observed in 5 (25%), 2 (10%), 2 (10%) and 2 (10%) patients, respectively. No treatment-related death occurred during either regimen. CONCLUSION: The novel alternating non-cross-resistant chemotherapy was probably active against ED-SCLC and had acceptable toxicities. Further evaluation of this treatment for ED-SCLC in randomized phase III trials is warranted.
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[372]
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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[373]
TÍTULO / TITLE: - Genomewide DNA Methylation Analysis Identifies Novel Methylated Genes in Non-Small-Cell Lung Carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182863ed2
AUTORES / AUTHORS: - Carvalho RH; Hou J; Haberle V; Aerts J; Grosveld F; Lenhard B; Philipsen S
INSTITUCIÓN / INSTITUTION: - *Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands; daggerCentre for Cancer Genomics, Erasmus MC, Rotterdam, The Netherlands; double daggerDutch Consortium for Systems Biology, Erasmus MC, Rotterdam, The Netherlands; section signUni BCCS, University of Bergen, Norway; ||Department of Lung Diseases, Erasmus MC, Rotterdam, The Netherlands; and paragraph signCenter for Biomedical Genetics, Erasmus MC, Rotterdam, The Netherlands.
RESUMEN / SUMMARY: - INTRODUCTION:: DNA methylation is part of the epigenetic regulatory mechanism present in all normal cells. It is tissue-specific and stably maintained throughout development, but often abnormally changed in cancer. Non-small-cell lung carcinoma (NSCLC) is the most deadly type of cancer, involving different tumor subtypes. This heterogeneity is a challenge for correct diagnosis and patient treatment. The stability and specificity make of DNA methylation a very suitable marker for epigenetic phenotyping of tumors. METHODS:: To identify candidate markers for use in NSCLC diagnosis, we used genomewide DNA methylation maps that we had previously generated by MethylCap and next-generation sequencing and listed the most significant differentially methylated regions (DMRs). The 25 DMRs with highest significance in their methylation scores were selected. The methylation status of these DMRs was investigated in 61 tumors and matching control lung tissues by methylation-specific polymerase chain reaction. RESULTS:: We found 12 novel DMRs that showed significant differences between tumor and control lung tissues. We also identified three novel DMRs for each of the two most common NSCLC subtypes, adenocarcinomas and squamous cell carcinomas. We propose a panel of five DMRs, composed of novel and known markers that exhibit high specificity and sensitivity to distinguish tumors from control lung tissues. CONCLUSION:: Novel markers will aid the development of a highly specific epigenetic panel for accurate identification and subtyping of NSCLC tumors.
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[374]
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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[375]
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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[376]
TÍTULO / TITLE: - Micropapillary components in a lung adenocarcinoma predict stump recurrence 8 years after resection: A case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 20. pii: S0169-5002(13)00021-4. doi: 10.1016/j.lungcan.2013.01.011.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.011
AUTORES / AUTHORS: - Watanabe M; Yokose T; Tetsukan W; Imai K; Tsuboi M; Ito H; Ishikawa Y; Yamada K; Nakayama H; Fujino S
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi Ward, Yokohama City, Kanagawa 241-8515, Japan. Electronic address: mwatanabe-tei@umin.ac.jp.
RESUMEN / SUMMARY: - We report a rare case of lung adenocarcinoma in which micropapillary components were considered to cause stump recurrence. A woman in her fifties was diagnosed with lung cancer in the right middle lobe with invasion to the upper lobe, which was treated by a right middle lobectomy together with upper lobe partial resection. The cancer was pathologically diagnosed as adenocarcinoma and had a free surgical margin. There was no recurrence during the following 5 years and 8 months, and thus periodical surveillance, including computed tomography, was stopped. However, 2 years and 7 months after this, she was discovered to have an abnormal shadow on chest radiography, and a thorough examination revealed a 3-cm-sized tumor involving the previous surgical margin. Therefore, she underwent right upper lobectomy. We pathologically re-evaluated the first tumor and found that it was an adenocarcinoma with a micropapillary component in the periphery, 6mm away from the surgical margin. In addition, a few tiny clusters of tumor cells were found to be floating within the alveolar spaces near the margin. The first and second tumors showed almost the same histological mixture of components of adenocarcinoma and the same EGFR mutation. From these results, we concluded the second tumor was a stump recurrence originating from the first tumor resection. This case illustrates the importance of careful pathological investigation when an autosuture instrument is used for a partial resection in a case of lung adenocarcinoma with micropapillary components. In such cases, it is particularly important to clarify if micropapillary components are floating near a stump.
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[377]
TÍTULO / TITLE: - Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: Implications for radiation target volume design.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 7. pii: S0169-5002(13)00020-2. doi: 10.1016/j.lungcan.2013.01.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.010
AUTORES / AUTHORS: - Olszyna-Serementa M; Socha J; Wierzchowski M; Kepka L
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, ul. Roentgena 5, 02-781 Warsaw, Poland.
RESUMEN / SUMMARY: - OBJECTIVE: Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (-) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. MATERIALS AND METHODS: Eighty R1-resected (37 ECE+ and 43 ECE-) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE- (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases. RESULTS: The actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE- and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00-9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE- and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE- group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65). CONCLUSION: PORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE- patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser importance. Omission of ENI in pN0-1 (extranodal-R1) patients resulted in an unacceptably high incidence of INF. We postulate the use of some form of ENI in this setting.
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[378]
TÍTULO / TITLE: - Association between microsomal epoxide hydrolase 1 T113C polymorphism and susceptibility to lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Apr;34(2):1045-52. doi: 10.1007/s13277-012-0644-4. Epub 2013 Feb 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-012-0644-4
AUTORES / AUTHORS: - Wang S; Zhu J; Zhang R; Wang S; Gu Z
INSTITUCIÓN / INSTITUTION: - Department of Emergency, the Fourth Affiliated Hospital of China Medical University, No. 102 Nan Qi Road, Heping District, Shenyang City, 110005, Liaoning Province, People’s Republic of China, doctorcmu@126.com.
RESUMEN / SUMMARY: - Previous case-control studies assessing the association between microsomal epoxide hydrolase 1 (EPHX1) T113C and susceptibility to lung cancer reported conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. PubMed and Embase databases were searched for all eligible studies. The strength of the association between EPHX1 T113C polymorphism and lung cancer risk was estimated by the pooled odds ratios (ORs) with its 95 % confidence interval. Twenty-four individual case-control studies involving a total of 4,970 lung cancer cases and 8,917 controls were finally included into the meta-analysis. When all 24 studies were included into the meta-analysis, the pooled results suggested that there was no association between EPHX1 T113C polymorphism and lung cancer risk under all four comparison models, and all P values for the pooled ORs were more than 0.05. In the subgroup analysis of Caucasians, the pooled results suggested that EPHX1 T113C polymorphism was associated with decreased risk of lung cancer under all four comparison models, and all P values for the pooled ORs were less than 0.05. However, in the subgroup analysis of Asians, the pooled results suggested that EPHX1 T113C polymorphism was associated with increased risk of lung cancer under three comparison models, and all P values for the pooled ORs were less than 0.05. There was no risk of publication bias. This current meta-analysis suggests that EPHX1 T113C polymorphism is associated with lung cancer risk, and there is an obvious race-specific effect in the association.
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[379]
TÍTULO / TITLE: - Cardiac dynamic magnetic resonance of a giant lung carcinoma invading the left atrium: do not let the imaging fool you.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cardiothorac Surg. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt039
AUTORES / AUTHORS: - Pozzoli A; Klinkenberg TJ; De Maat GE; Mariani MA
INSTITUCIÓN / INSTITUTION: - Department of Thoraxcentrum, University Medical Center Groningen, Groningen, Netherlands.
RESUMEN / SUMMARY: - This study aimed to report on a non-small-cell lung cancer (NSCLC) originating from the right lung lower lobe and circulatory extension into the left atrium. Atrial involvement is an uncommon feature of advanced NSCLC, occurring in up to 10% of patients with bronchogenic carcinoma. In this case, the neoplastic mass was enormous and diagnosed as a lung pleiomorph carcinoma, staged T4N2M0 and so far considered irresectable. Conventional static imaging (chest CT-positron emission tomography scan; cardiac MRI) failed to rule out any direct invasion into surrounding structures. Surgery is the gold standard treatment for the local control of NSCLC without distant metastasis. Finally, preoperative cardiac dynamic magnetic resonance imaging and transoesophageal echocardiography were crucial to assess resectability, showing the absence of tumour invasion inside the pulmonary circulation and in the left atrium, supporting the decision-making for a radical, curative, surgical resection.
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[380]
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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[381]
TÍTULO / TITLE: - The ALK translocation in advanced non-small-cell lung carcinomas: preapproval testing experience at a single cancer centre.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Histopathology. 2013 Mar;62(4):609-16. doi: 10.1111/his.12037. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1111/his.12037
AUTORES / AUTHORS: - Conde E; Angulo B; Izquierdo E; Munoz L; Suarez-Gauthier A; Plaza C; Dominguez N; Torres M; Madrigal L; Rubio-Viqueira B; Belda-Iniesta C; Hidalgo M; Lopez-Rios F
INSTITUCIÓN / INSTITUTION: - Laboratorio de Dianas Terapeuticas, Centro Integral Oncologico Clara Campal, Hospital Universitario Madrid Sanchinarro, Universidad San Pablo-CEU, Madrid, España.
RESUMEN / SUMMARY: - AIMS: To study the ALK translocation in patients with advanced non-small-cell lung carcinomas (NSCLCs) seen at a European cancer centre, and its association with EGFR mutations, KRAS mutations and MET amplification. METHODS AND RESULTS: The study included samples from 86 patients diagnosed with advanced NSCLC. ALK fluorescence in-situ hybridization (FISH) was performed using the ALK break-apart probe set (Vysis). ALK FISH-positive cases were defined as those with more than 15% break-apart signals or isolated red signals in 50 cells. EGFR and KRAS mutations were determined by direct sequencing. All ALK-positive cases were analysed retrospectively for MET amplification using a FISH assay, and for ALK mutations by sequencing. We found nine (10.5%) ALK-positive cases, all in adenocarcinomas and the majority in female patients (88.9%). Signet ring cells were observed in four (44.4%) of the nine patients. None of the ALK translocated cases showed MET amplifications or EGFR, KRAS and ALK mutations. CONCLUSIONS: The prevalence of ALK translocation in an unselected population of European patients with advanced NSCLCs was 10%. This alteration was mutually exclusive with EGFR and KRAS mutations, as well as with MET amplification. If multiplexing is considered at the preanalytical phase, lung biopsy specimens are sufficient for performing several predictive assays.
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[382]
TÍTULO / TITLE: - Identification of uncommon PIK3CA mutations in lung cancer by using pyrosequencing.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Mol Pathol. 2013 Mar;22(1):22-7. doi: 10.1097/PDM.0b013e31825f5f93.
●● Enlace al texto completo (gratuito o de pago) 1097/PDM.0b013e31825f5f93
AUTORES / AUTHORS: - Schildgen V; Lusebrink J; Appel JD; Wubben C; Engel-Riedel W; Ludwig C; Stoelben E; Schildgen O; Brockmann M
INSTITUCIÓN / INSTITUTION: - Institut fur Pathologie, Kliniken der Stadt Koln gGmbH, Koln, Germany.
RESUMEN / SUMMARY: - INTRODUCTION: Phospatidylinositol-3-kinases (PI3K) play an important role in various cell processes. Oncogenic mutations in the PIK3CA gene, which codes for the catalytic subunit, have been identified in various malignancies and activate the PI3K/AKT/mTOR pathway, which is a critical driver of tumorigenesis. METHODS: We tested 41 tumor samples with known KRAS, BRAF, and EGFR mutation status for the occurrence of mutations in the PIK3CA gene, using a pyrosequencing assay. RESULTS: Pyrosequencing revealed 2 mutations (4.9%) in the PIK3CA gene, one in exon 9 and the other in exon 20. Both mutations have not been identified yet in lung tumor tissue. DISCUSSION: The screening of our small patient cohort by pyrosequencing identified 2 mutations (4.9%) in PIK3CA, one in exon 9 (Q546H) and the other in exon 20 (M1043T). Both mutations have not been described in lung tumors yet and seem to be rather uncommon mutations. Future screening of large patient cohorts with pyrosequencing may contribute to the detection of more mutations in lung cancer because of the low limit of detections of this method and may contribute to a better understanding of the interaction of mutations and tumorigenesis.
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[383]
TÍTULO / TITLE: - Legal claims for malignant mesothelioma: Dealing with all cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 14. pii: S0169-5002(13)00022-6. doi: 10.1016/j.lungcan.2013.01.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.012
AUTORES / AUTHORS: - van der Bij S; Baas P; van de Vijver MJ; de Mol BA; Burgers JA
INSTITUCIÓN / INSTITUTION: - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Heidelberglaan 100, 3584 CX, The Netherlands. Electronic address: s.vanderbij@umcutrecht.nl.
RESUMEN / SUMMARY: - BACKGROUND: Apart of medical reasons, a definitive diagnosis of malignant mesothelioma may be required as a basis for a claim of financial compensation although a pathological source of conclusive evidence is missing. Clinical assessment of all available data is then the only option to come to a final conclusion. We evaluated the diagnostic work-up of a large cohort of Dutch patients who applied for financial compensation due to mesothelioma. We determined how often a pathological or clinical diagnosis can be made, and which factors are associated with making the final diagnosis malignant mesothelioma. METHODS: A flow diagram of the diagnostic work-up was constructed for patients that applied to the Dutch institute for asbestos victims between 2005 and 2008 (N=1498). Both pathological and clinical factors that may influence the diagnostic outcome were assessed. RESULTS: In 97 of the 1498 patients (6%) no pathologic diagnosis could be established because of an uncertain diagnosis (N=54), inadequate (N=22) or unavailable tumor samples (N=21). A final pathological diagnosis of malignant mesothelioma could most often be made when biopsy samples were available compared to those in whom only cytological material was available. In patients in who no conclusive diagnosis could be made, clinical assessment was performed. Eighty percent of patients (66/83) who were clinically assessed were considered to have mesothelioma. None of the clinical features analyzed were strongly associated with a confirmed diagnosis of malignant mesothelioma. DISCUSSION: Our study shows that only in a small number of the patients who applied no pathologic diagnosis could be obtained. Based on judgment of clinical experts in the majority of these cases a near to certain diagnosis could be made. Moreover, it is reasonable to obtain biopsy material from patients to increase the chance to obtain a confirmed diagnosis. Therefore, it is important to refer patients early for diagnostic procedures.
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[384]
TÍTULO / TITLE: - Small cell neuroendocrine tumor of the larynx—a small case series.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:201-4.
AUTORES / AUTHORS: - Mikic A; Zvrko E; Trivic A; Stefanovic D; Golubovic M
INSTITUCIÓN / INSTITUTION: - Clinical Center of Serbia, Institute of Otorhinolaryngology and Maxillofacial Surgery, Belgrade, Serbia. braca5@eunet.rs
RESUMEN / SUMMARY: - Neuroendocrine tumors are the most common nonsquamous types of laryngeal neoplasms. They are classified as typical carcinoids, atypical carcinoids, small-cell neuroendocrine carcinomas, and paragangliomas. The aim of the paper is to present four patients with small-cell neuroendocrine tumor arising in larynx. There were one woman and three men whose ages were 47-77 years; all of them had metastases when first seen. The clinical presentation and management of such type of tumor are discussed. Small-cell neuroendocrine carcinomas are very aggressive neoplasms. Patients could benefit from surgery, but radiotherapy and chemotherapy remain the treatment of choice. Examination of a large series is required to define the most useful diagnostic methods and the most successful treatment modalities.
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[385]
TÍTULO / TITLE: - Interventional embolization of giant thoracic tumors before surgical resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Radiol. 2013 Feb 1;54(1):61-6. doi: 10.1258/ar.2012.120339.
●● Enlace al texto completo (gratuito o de pago) 1258/ar.2012.120339
AUTORES / AUTHORS: - Liu FY; Wang MQ; Fan QS; Duan F; Wang ZJ; Song P
INSTITUCIÓN / INSTITUTION: - Department of Interventional Radiology, Chinese People’s Liberation Army General Hospital, Beijing, China.
RESUMEN / SUMMARY: - BACKGROUND: Preoperative embolization of tumors is a well-established procedure that has been successfully applied in various clinical situations. Preoperative embolization can reduce the vascularity of tumors resulting in a clearer operative field, less difficult dissection, decreased blood loss, and, in some cases, a decrease in tumor size. However, few studies have been conducted regarding the preoperative embolization of giant thoracic tumors. PURPOSE: To examine the effectiveness and safety of interventional embolization of giant thoracic tumors before surgical resection. MATERIAL AND METHODS: A total of 14 consecutive patients with giant thoracic tumors received angiography and the feeding arteries of the tumors were embolized using polyvinyl alcohol (PVA) particles and gelatin sponges 1 day before surgical resection. The patient records were retrospectively reviewed and data regarding diagnoses, embolization, and surgical resection were recorded. RESULTS: Angiography revealed the feeding arteries of the tumors to be characterized by multiple branches and thickened vessel trunks with abnormal distal branches superimposed of the tumor shadow. Embolization was successfully without complications in all patients, and all feeding vessels of each tumor were occluded. Embolization reduced the severity of bleeding during surgery and decreased the difficulty of resection of the tumor. No intraoperative or postoperative complications occurred. CONCLUSION: Interventional embolization is a safe and efficient method to facilitate the surgical resection of giant thoracic tumors.
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[386]
TÍTULO / TITLE: - Inhibiting proliferation of gefitinib-resistant, non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2132-y
AUTORES / AUTHORS: - Sudo M; Chin TM; Mori S; Doan NB; Said JW; Akashi M; Koeffler HP
INSTITUCIÓN / INSTITUTION: - Cancer Science Institute, National University of Singapore, Singapore, Singapore, makotosudo@live.jp.
RESUMEN / SUMMARY: - PURPOSE: Sensitivity to a tyrosine kinase inhibitor (TKI) is correlated with the presence of somatic mutations that affect the kinase domain of epidermal growth factor receptor (EGFR). Development of resistance to TKI is a major therapeutic problem in non-small cell lung cancer (NSCLC). Aim of this study is to identify agents that can overcome TKI resistance in NSCLC. METHODS: We used a carefully selected panel of 12 NSCLC cell lines to address this clinical problem. Initially, the cell lines were treated with a variety of 10 compounds. Cellular proliferation was measured via MTT assay. We then focused on the gefitinib-resistant, EGFR mutant cell lines [H1650: exon 19 and PTEN mutations; and H1975: exons 20 (T790M) and 21 (L858R)] to identify agents that could overcome TKI resistance. RESULTS: Both 17-DMAG (Hsp90 inhibitor) and belinostat (histone deacetylase inhibitor, HDACi) effectively decreased the growth of almost all NSCLC lines. Also, belinostat markedly decreased the expression of EGFR and phospho-Akt in the cells. Combination of 17-DMAG and belinostat synergistically inhibited in vitro proliferation of these cells. Furthermore, both agents and their combination almost completely prevented TKI-resistant tumor formation (EGFR T790M mutation) in a xenograft model. CONCLUSION: These results suggest that the combination of 17-DMAG and belinostat should be examined in a clinical trial for TKI-resistant NSCLC cell.
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[387]
TÍTULO / TITLE: - A three-drug induction chemotherapy with gemcitabine, carboplatin, and paclitaxel for stage III non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):533. doi: 10.1007/s12032-013-0533-8. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0533-8
AUTORES / AUTHORS: - Banna GL; Lipari H; Nicolosi M; Basile A; Fraggetta F; Vaglica M; Marletta F; Urso OE; Ippolito M; Terminella A; Saita S
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Cannizzaro Hospital, Via Messina 829, 95126 Catania, Italy. gbanna@yahoo.com
RESUMEN / SUMMARY: - The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18-75 years, ECOG PS 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m(2) on day 1, and i.v. gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3-G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2-72), median PFS was 10.5 months (95 % CI 9.9-11.4) and median OS was 21.1 months (95 % CI 19.7-22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2-19.7) and a median OS of 25.5 months (95 % CI 23.0-28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.
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[388]
TÍTULO / TITLE: - Noninvasive Characterization of the Histopathologic Features of Pulmonary Nodules of the Lung Adenocarcinoma Spectrum using Computer-Aided Nodule Assessment and Risk Yield (CANARY)-A Pilot Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):452-460.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182843721
AUTORES / AUTHORS: - Maldonado F; Boland JM; Raghunath S; Aubry MC; Bartholmai BJ; Deandrade M; Hartman TE; Karwoski RA; Rajagopalan S; Sykes AM; Yang P; Yi ES; Robb RA; Peikert T
INSTITUCIÓN / INSTITUTION: - *Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota; daggerDepartment of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota; double daggerDepartment of Physiology and Biomedical Engineering, Biomedical Imaging Resource, Mayo Clinic, Rochester, Minnesota; section signDepartment of Radiology, Mayo Clinic, Rochester, Minnesota; ||Department of Health Science Research, Division of Biostatistics, Mayo Clinic, Rochester, Minnesota; and **Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
RESUMEN / SUMMARY: - INTRODUCTION:: Pulmonary nodules of the adenocarcinoma spectrum are characterized by distinctive morphological and radiologic features and variable prognosis. Noninvasive high-resolution computed tomography-based risk stratification tools are needed to individualize their management. METHODS:: Radiologic measurements of histopathologic tissue invasion were developed in a training set of 54 pulmonary nodules of the adenocarcinoma spectrum and validated in 86 consecutively resected nodules. Nodules were isolated and characterized by computer-aided analysis, and data were analyzed by Spearman correlation, sensitivity, and specificity and the positive and negative predictive values. RESULTS:: Computer-aided nodule assessment and risk yield (CANARY) can noninvasively characterize pulmonary nodules of the adenocarcinoma spectrum. Unsupervised clustering analysis of high-resolution computed tomography data identified nine unique exemplars representing the basic radiologic building blocks of these lesions. The exemplar distribution within each nodule correlated well with the proportion of histologic tissue invasion, Spearman R = 0.87, p < 0.0001 and 0.89 and p < 0.0001 for the training and the validation set, respectively. Clustering of the exemplars in three-dimensional space corresponding to tissue invasion and lepidic growth was used to develop a CANARY decision algorithm that successfully categorized these pulmonary nodules as “aggressive” (invasive adenocarcinoma) or “indolent” (adenocarcinoma in situ and minimally invasive adenocarcinoma). Sensitivity, specificity, positive predictive value, and negative predictive value of this approach for the detection of aggressive lesions were 95.4, 96.8, 95.4, and 96.8%, respectively, in the training set and 98.7, 63.6, 94.9, and 87.5%, respectively, in the validation set. CONCLUSION:: CANARY represents a promising tool to noninvasively risk stratify pulmonary nodules of the adenocarcinoma spectrum.
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[389]
TÍTULO / TITLE: - Studies of styrene, styrene oxide and 4-hydroxystyrene toxicity in CYP2F2 knockout and CYP2F1 humanized mice support lack of human relevance for mouse lung tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Regul Toxicol Pharmacol. 2013 Feb 27;66(1):24-29. doi: 10.1016/j.yrtph.2013.02.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.yrtph.2013.02.008
AUTORES / AUTHORS: - Cruzan G; Bus J; Hotchkiss J; Sura R; Moore C; Yost G; Banton M; Sarang S
INSTITUCIÓN / INSTITUTION: - ToxWorks, Bridgeton, NJ, United States. Electronic address: toxworks@aol.com.
RESUMEN / SUMMARY: - Styrene (S) is lung tumorigenic in mice but not in rats. S and its alkene-oxidized metabolite styrene oxide (SO) were not lung toxic in CYP2F2(-/-) [knockout] mice, indicating S-induced mouse lung tumors are mediated through mouse-specific CYP2F2-generated ring-oxidized metabolite(s) in lung bronchioles. The human relevance of the CYP2F MOA was assessed by insertion of a human CYP2F1, 2A13, 2B6 transgene into CYP2F2(-/-) mice; CYP2F1 expression and activity were confirmed in the transgenic (TG) mice. No evidence of cytotoxicity or increased cell proliferation (BrdU labeling) was seen in TG mice treated with either S or SO (200mg/kg/day ip for 5days). In contrast to S and SO, 4HS (105mg/kg/day ip for 5days) increased BrdU labeling 5-10-fold in WT mice, <3-fold increase in KO mice and 2-4-fold in TG mice. The limited response of 4HS in KO and TG mice may result from intrinsic toxicity or from further metabolism; regardless of the MOA, these findings indicate that the CYP2F-mediated tumorigenic MOA in WT mice is not operative for S, SO, or for 4HS putatively derived from metabolism of S by CYP2F1 in humans, and thus S-induced mouse lung tumors are unlikely to be relevant to human risk.
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[390]
TÍTULO / TITLE: - Intrapleural hyperthermic perfusion chemotherapy in subjects with metastatic pleural malignancies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Respir Med. 2013 Feb 22. pii: S0954-6111(13)00036-X. doi: 10.1016/j.rmed.2013.01.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.rmed.2013.01.010
AUTORES / AUTHORS: - Isik AF; Sanli M; Yilmaz M; Meteroglu F; Dikensoy O; Sevinc A; Camci C; Tuncozgur B; Elbeyli L
INSTITUCIÓN / INSTITUTION: - Gaziantep University, Medical School, Thoracic Surgery Department, Universite Bulvari, Sehitkamil-Gaziantep, Turkey. Electronic address: abaybora@msn.com.
RESUMEN / SUMMARY: - OBJECTIVES: Malignant pleural effusion (MPE) means poor prognosis in the majority of cases. Intrapleural Hyperthermic perfusion chemotherapy (HIPEC) looks promising approach for these patients. We aimed to investigate whether cytoreductive surgery followed by HIPEC provides any survival benefit in cases with metastatic MPEs. METHODS: Between January 2009 and December 2011, 19 patients with metastatic MPEs were treated with HIPEC following surgical interventions such as pleurectomy/decortication and/or lung resection (Group 1). Comparison was done with historical control groups consisted of patients who received either talc pleurodesis or pleurectomy/decortication followed by systemic treatment for the management of metastatic MPEs between June 2007 and June 2008 (group 2 and 3). Statistical analyses including overall survival, disease free interval were done for the group comparisons. RESULTS: Median survival in group 1, 2 and 3 were 15.4, 6, 8 months, respectively. One year survival was 54.7% in group 1 where it was 0.6% and 0.8% in group 2 and 3, respectively. There was no operative mortality. Morbidity was occurred in 1 patient in group 1 (5.3%). CONCLUSIONS: HIPEC combined with cytoreductive surgery seems to be a promising treatment option for subjects with metastatic MPEs. Further studies are needed for the optimization of HIPEC method, drug of choice, and the best combination therapy for the multimodal treatment.
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[391]
TÍTULO / TITLE: - History of multiple previous malignancies should not be a contraindication to the surgical resection of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Mar;95(3):1000-5. doi: 10.1016/j.athoracsur.2012.11.072. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.11.072
AUTORES / AUTHORS: - Pages PB; Mordant P; Grand B; Badia A; Foucault C; Dujon A; Le Pimpec-Barthes F; Riquet M
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Georges Pompidou European Hospital, Paris Descartes University, Paris, France.
RESUMEN / SUMMARY: - BACKGROUND: Patients with a history of previous malignancy are often encountered in a discussion of surgical resection of non-small-cell lung cancer (NSCLC). The outcome of patients with 2 or more previous cancers remains unknown. METHODS: We performed a retrospective study including all patients undergoing resection for NSCLC from January 1980 to December 2009 at 2 French centers. We then compared the survival of patients without a history of another cancer (group 1), those with a history of a single malignancy (group 2), and those with a history of 2 or more previous malignancies (group 3). RESULTS: There were 5,846 patients: 4,603 (78%) in group 1, 1,147 (20%) in group 2, and 96 (2%) in group 3. The proportion of patients included in group 3 increased from 0.3% to 3% over 3 decades. Compared with groups 1 and 2, group 3 was associated with older age, a larger proportion of women, earlier tumor stage, less induction therapy, and fewer pneumonectomies. Despite this, postoperative complications and mortality were similar in groups 2 and 3, and higher than in group 1. Five-year survival rates were 44.6%, 35.1%, and 23.6% in groups 1, 2, and 3, respectively (p < 0.000001 for comparison between 3 groups; p = 0.18 for comparison between groups 2 and 3). In multivariate analysis, male sex, higher T stage, higher N stage, incomplete resection, and study group were significant predictors of adverse prognosis. CONCLUSIONS: Despite earlier diagnosis and acceptable long-term survival, patients operated on for NSCLC after 2 or 3 previous malignancies carried a worse prognosis than did those undergoing operation after 1 malignancy or if there was no previous diagnosis of cancer.
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[392]
TÍTULO / TITLE: - Platelet-derived growth factor-A and vascular endothelial growth factor-C contribute to the development of pulmonary tumor thrombotic microangiopathy in gastric cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Virchows Arch. 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s00428-013-1403-7
AUTORES / AUTHORS: - Abe H; Hino R; Fukayama M
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
RESUMEN / SUMMARY: - Pulmonary tumor thrombotic microangiopathy is a rare but lethal complication in cancer-bearing patients, particularly those with gastric cancer. It is characterized by cancer cell emboli with marked intimal proliferation. In the present study, we tried to elucidate the pathogenesis of pulmonary tumor thrombotic microangiopathy, notably angiogenic factors specific for cancer cells lodged in pulmonary arteries. An autopsy series of gastric cancer (51 cases) was reviewed for pulmonary tumor thrombotic microangiopathy and pulmonary tumor cell emboli without intimal proliferation. Pathological and immunohistochemical characteristics were compared between two groups. In eight cases in muscular pulmonary arteries, tumor thrombotic microangiopathy was noted, and in three cases pulmonary tumor emboli without intimal proliferation was noted. Histological features of pulmonary tumor thrombotic microangiopathy included small nests or single cancer cells accompanied by intimal proliferation, whereas in pulmonary tumor emboli large cell nests prevailed. By immunohistochemistry, in pulmonary tumor thrombotic microangiopathy, cancer cells expressed platelet-derived growth factor-A (7/8 cases) and vascular endothelial growth factor-C (8/8) more frequently than in pulmonary tumor emboli (0/3 and 1/3; P = 0.02 and P = 0.055, respectively). Expression of tissue factor, vascular endothelial growth factor-A and -D, osteopontin, fibroblast growth factor-2, and platelet-derived growth factor-B was similar in both groups. Platelet-derived growth factor-A and vascular endothelial growth factor-C might induce intimal proliferation in pulmonary arteries and contribute to the development of pulmonary tumor thrombotic microangiopathy.
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[393]
TÍTULO / TITLE: - Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse Interleukin 27 by means of cationic liposome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Immunol. 2013 Mar 21. pii: S0161-5890(13)00044-8. doi: 10.1016/j.molimm.2013.02.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molimm.2013.02.006
AUTORES / AUTHORS: - Zhang J; Tian H; Li C; Cheng L; Zhang S; Zhang X; Wang R; Xu F; Dai L; Shi G; Chen X; Li Y; Du T; Deng J; Liu Y; Yang Y; Wei Y; Deng H
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China.
RESUMEN / SUMMARY: - Interleukin-27 (IL-27), a novel IL-6/IL-12 family cytokine, plays an important role in the early regulation of Th1 responses. The cytokine IL-27 can exert a variety of immune-regulatory functions including cytotoxic T lymphocyte (CTL), CD4+, CD8+ T lymphocytes activation and interferon-gamma (IFN-gamma) production. In this study, we developed an effective and gene modified tumor cell vaccine. Lewis lung cancer cell LL/2 transfected with the DOTAP:cholesterol cationic liposome could express the mouse IL-27 (mIL-27) gene at a relative high level. The resultant transfectants were then irradiated with X-ray and used as a tumor cell vaccine. This tumor cell vaccine not only contained tumor associated antigen (TAA) of LL/2 cells but also secreted mIL-27 which could induce immune response in mice. The mice vaccinated with LL/2-mIL-27 performed strong tumor inhibiting effect accompanied with a high IFN-gamma production. Both CD4+ and CD8+ T lymphocytes were significantly elevated in these mice vaccinated with LL/2-mIL-27 cell vaccine. Moreover, after depletion of CD4+, CD8+ T lymphocytes by injection of antibodies against CD4 and CD8, the vaccinated mice inoculated with autologous LL/2 cells were not protected from tumor challenge. In contrast, vaccinated mice inoculated with autologous LL/2 cells were treated with antibody against natural killer (NK)cells or normal rat IgG still possessed strong antitumor activity. Our data suggested that DOTAP:cholesterol cationic liposome was quite useful in generating an autologous tumor cell vaccine and mIL-27 could be therapeutically used to potentiate the host antitumor immunity.
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[394]
TÍTULO / TITLE: - Cu(OTf) catalyzed three component reaction: Efficient synthesis of spiro[indoline-3,4’-pyrano[3,2-b]pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Feb 27. pii: S0960-894X(13)00271-0. doi: 10.1016/j.bmcl.2013.02.086.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.02.086
AUTORES / AUTHORS: - Parthasarathy K; Praveen C; Balachandran C; Senthil Kumar P; Ignacimuthu S; Perumal PT
INSTITUCIÓN / INSTITUTION: - Organic Chemistry Division, Central Leather Research Institute (CSIR), Adyar, Chennai 600 020, India; Analytical Research & Development, Orchid Chemicals & Pharmaceuticals Ltd, Research & Development Centre, Shozanganallur, Chennai 600 119, India.
RESUMEN / SUMMARY: - Cu(OTf)2 catalyzed efficient synthesis of spiropyrano[3,2-b]pyran-4(8H)-ones is accomplished via one-pot three component reaction between isatin, kojic acid and active methylenes. This synthetic protocol is operationally simple and affords product with good to excellent yields at a short reaction time. The synthesized compounds were evaluated for their tumor cell growth inhibitory activity against the human lung cancer cell line (A549) and found that 13 compounds exhibited moderate to good anticancer potency. Molecular docking studies were performed for all the synthesized compounds and the results showed that compound 4e showed greater affinity for anaplastic lymphoma kinase (ALK) receptor.
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[395]
TÍTULO / TITLE: - Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Mar 15;23(6):1839-45. doi: 10.1016/j.bmcl.2013.01.023. Epub 2013 Jan 22.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.01.023
AUTORES / AUTHORS: - Arun Y; Bhaskar G; Balachandran C; Ignacimuthu S; Perumal PT
INSTITUCIÓN / INSTITUTION: - Organic Chemistry Division, CSIR-Central Leather Research Institute, Chennai 600 020, India.
RESUMEN / SUMMARY: - Novel dispirooxindole-pyrrolidine derivatives have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3-(1H-indol-3-yl)-3-oxo-2-(2-oxoindolin-3-ylidene)propanenitrile, and also spiro compound of acenaphthenequinone obtained by the same optimized reaction condition. Synthesized compounds were evaluated for their antimicrobial activity and all the compounds shown significant activity. Anticancer activity was evaluated against A549 human lung adenocarcinoma cancer cell lines. Compounds 7b, 7g, 7i and 7r exhibit very good anticancer activity 62.96%, 62.03%, 67.67% and 60.22%, respectively, at the dose of 200mug/mL and compound 7i shows IC value in 50mug/mL.
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[396]
TÍTULO / TITLE: - Shedding of c-Met ectodomain correlates with c-Met expression in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomarkers. 2013 Mar;18(2):126-35. doi: 10.3109/1354750X.2012.751455.
●● Enlace al texto completo (gratuito o de pago) 3109/1354750X.2012.751455
AUTORES / AUTHORS: - Fu L; Guo W; Liu B; Sun L; Bi Z; Zhu L; Wang X; Liu B; Xie Q; Li K
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Huashan Hospital of Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - OBJECTIVE: The aim of this study is to reveal the correlation of shedding and expression of c-Met in non-small cell lung cancer (NSCLC) patient. MATERIALS AND METHODS: We measured soluble c-Met and c-Met level in a panel of pre-clinical models and 197 advanced Chinese NSCLC patients by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. RESULTS: Shedding of soluble c-Met associates with total c-Met amount in pre-clinical models, and soluble c-Met correlates with both c-Met expression level and tumor size in human, high soluble c-Met predicts poorer outcome.
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[397]
TÍTULO / TITLE: - Molecular determinations of EGFR and EML4-ALK on a single slide of NSCLC tissue.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Pathol. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2013-201502
AUTORES / AUTHORS: - Ulivi P; Puccetti M; Capelli L; Chiadini E; Bravaccini S; Calistri D; Zoli W; Amadori D; Candoli P
INSTITUCIÓN / INSTITUTION: - Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST-IRCCS), Meldola, FC, Italy.
RESUMEN / SUMMARY: - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) and anti-anaplastic lymphoma kinase (ALK) agents are highly effective for the treatment of non-small cell lung cancer (NSCLC) patients harbouring specific alterations, and molecular characterisation of the tumour is needed even when limited tumour material is available. METHODS: 20 patients with a known epidermal growth factor receptor (EGFR) gene status were enrolled: 10 had mutated and 10 had wild type tumours. FISH analysis was performed on one cytological or histological sample to determine EML4-ALK status, after which the same cells scraped off each slide were used to evaluate the EGFR status. RESULTS: In the 10 EGFR mutated patients, molecular analysis showed the same results as those obtained before the FISH test. One patient with an EGFR mutation also showed an EML4-ALK translocation, and both FISH-positive and FISH-negative cells maintained the EGFR mutation. CONCLUSIONS: EGFR mutation analysis can be performed on the same sample previously submitted to the EML4-ALK FISH procedure.
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[398]
TÍTULO / TITLE: - Improvement in the quality of molecular analysis of EGFR in non-small-cell lung cancer detected by three rounds of external quality assessment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Pathol. 2013 Apr;66(4):319-25. doi: 10.1136/jclinpath-2012-201227. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2012-201227
AUTORES / AUTHORS: - Deans ZC; Bilbe N; O’Sullivan B; Lazarou LP; de Castro DG; Parry S; Dodson A; Taniere P; Clark C; Butler R
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Medicine, UK NEQAS for Molecular Genetics, UK NEQAS Edinburgh, The Royal Infirmary of Edinburgh, , Edinburgh, UK.
RESUMEN / SUMMARY: - BACKGROUND: The clinical need to determine the presence of epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancers (NSCLC) in order to make informed decisions for patient treatment has seen the widespread introduction of EGFR molecular testing in many laboratories. To ensure high-quality molecular testing and allow laboratories to externally measure the standard of the service, an external quality assessment (EQA) scheme was provided to assess the whole testing process. METHODS: Formalin-fixed paraffin-embedded NSCLC tumour sections were distributed to laboratories for routine EGFR molecular testing, and the genotyping accuracy, interpretation of the result and clerical accuracy of the report were independently assessed. RESULTS: Three rounds of assessment have identified many genotyping errors and have highlighted the need for external assessment and education in many testing laboratories. The main issues raised were the importance of accurate genotyping, including the use of common mutation nomenclature, clear unambiguous interpretation of the result, the impact of tumour sample assessment regarding amount of tumour being analysed and the heterogeneity of the sample on the molecular test result. CONCLUSIONS: Improvements in all these areas were observed during the progression of the three EQA rounds, however, continuous unacceptably high genotyping error rates demonstrate the clear need for continual external assessment and education in this field.
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[399]
TÍTULO / TITLE: - Efficacy of two fluorescence in situ hybridization (FISH) probes for diagnosing malignant pleural effusions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 27. pii: S0169-5002(13)00060-3. doi: 10.1016/j.lungcan.2013.02.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.02.001
AUTORES / AUTHORS: - Rosolen DC; Kulikowski LD; Bottura G; Nascimento AM; Acencio M; Teixeira L; Vargas FS; Sales RK; Antonangelo L
INSTITUCIÓN / INSTITUTION: - Pulmonary Division, Heart Institute (InCor), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil; Clinical and Research Laboratory (LIM 03), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil.
RESUMEN / SUMMARY: - It is difficult to differentiate tumor cells in pleural fluid from reactive benign mesothelium. Fluorescence in situ hybridization (FISH) can increase diagnostic accuracy. Two hundred pleural fluid samples were analyzed by using FISH probes for chromosomes 11 and 17. Histological analysis was used to diagnose cancer. Clinical, radiological, and histological data were used to exclude malignancy. Eighty-two pleural effusion samples had positive cytology, 51 were benign, and 67 were atypical, but inconclusive. The 82 positive cases were confirmed to be malignant. Among the 51 negative cytology cases, videothoracoscopy-guided pleural biopsy revealed malignancy in three; aneuploid cells were detected by FISH in all cases. In 43 of the 67 cases with inconclusive cytology, malignancy was confirmed based on histology and fluorescence in situ hybridization. One case of parapneumonic effusion with no evidence of cancer during clinical follow-up had a suspicious cytology and positive fluorescence in situ hybridization result. The remaining 23 cases had no histological, radiological, clinical, or genetic evidence of malignancy. This study demonstrated that cytogenetic analysis of fresh pleural fluid samples using only two FISH probes is a valuable ancillary method for the identification of malignant pleural effusion, particularly in cases in which oncotic cytology is inconclusive.
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[400]
TÍTULO / TITLE: - Routine Intraoperative Frozen Section Analysis of Bronchial Margins Is of Limited Utility in Lung Cancer Resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Feb 13. pii: S0003-4975(12)02799-3. doi: 10.1016/j.athoracsur.2012.12.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.12.016
AUTORES / AUTHORS: - Owen RM; Force SD; Gal AA; Feingold PL; Pickens A; Miller DL; Fernandez FG
INSTITUCIÓN / INSTITUTION: - Section of General Thoracic Surgery, Emory University School of Medicine, Atlanta, Georgia.
RESUMEN / SUMMARY: - BACKGROUND: Residual disease at the bronchial margin after resection of non-small cell lung cancer (NSCLC) adversely affects survival. To ensure an R0 resection, thoracic surgeons commonly use intraoperative frozen section analysis of the bronchial margin. We hypothesize that frozen section of the bronchial margin is rarely positive and seldom changes intraoperative management. METHODS: Our institutional Society of Thoracic Surgery database was queried for all patients undergoing planned lobectomy for NSCLC from 2009 to 2011. Clinical variables, intraoperative data, and postoperative outcomes were reviewed. Specifically, intraoperative frozen section and final pathology results of all bronchial margins were examined. The frequency that frozen section results affected intraoperative decision making was evaluated. RESULTS: A total of 287 lobectomies for NSCLC were performed. Frozen section of the bronchial margin was performed in 270 patients (94.1%). There were 6 (2.2%) true-positive bronchial margins and 1 (0.4%) false-negative margin. In no cases did a positive frozen section lead to a change in operative management; reasons included unable to tolerate further resection (n = 5) and advanced-stage disease (n = 1). Positive margins were more frequent with open techniques (7%) than in video-assisted thoracoscopic operations (0.05%; p < 0.01). Tumors with positive margins were closer to the bronchial margin (1.0 vs 2.5 cm; p = 0.04). Frozen section was not used in 17 patients (5.9%), and none had positive margins on final pathology. CONCLUSIONS: Frozen section analysis of the bronchial margin rarely yields a positive result and infrequently changes intraoperative management in patients undergoing NSCLC resection. These data support selective use of intraoperative frozen section of bronchial margins during lobectomy for NSCLC.
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[401]
TÍTULO / TITLE: - MET and EGFR Mutations Identified in ALK-Rearranged Pulmonary Adenocarcinoma: Molecular Analysis of 25 ALK-Positive Cases.
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.0b013e318287c395
AUTORES / AUTHORS: - Boland JM; Jang JS; Li J; Lee AM; Wampfler JA; Erickson-Johnson MR; Soares I; Yang P; Jen J; Oliveira AM; Yi ES
INSTITUCIÓN / INSTITUTION: - *Departments of Laboratory Medicine and Pathology, daggerPulmonary and Critical Care Medicine, double daggerMolecular Pharmacology and Experimental Therapeutics, and section signEpidemiology, Mayo Clinic, Rochester, Minnesota; and ||Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China.
RESUMEN / SUMMARY: - INTRODUCTION:: Oncogenic ALK kinase activity associated with ALK gene rearrangement is the target of crizotinib, an ALK inhibitor recently approved by the Food and Drug Administration for the treatment of ALK-rearranged (ALK+) non-small cell lung cancers. ALK+ status is generally thought to be mutually exclusive of epidermal growth factor receptor (EGFR) and KRAS mutations. However, the mutation status of other genes is not widely known in ALK+ tumors. The aim of this study is to survey for mutations involving other genes in 25 ALK+ cases confirmed by fluorescent in situ hybridization. METHODS:: Using the DNA extracted from formalin-fixed paraffin-embedded tumor samples, a MassArray-based Lung Cancer Mutations Screening Panel was performed to test for 179 individual mutations in 10 genes, including EGFR, KRAS, BRAF, ERBB2, JAK2, AKT1, AKT2, KIT, MET and PIK3CA, which have been implicated in lung carcinogenesis and/or considered as potential therapeutic targets. RESULTS:: Five of 25 ALK+ cases showed additional genetic abnormalities, which were verified by gene sequencing. One patient had EGFR del L747-S752. The remaining four mutations were in the MET gene: MET N375S (n = 2) and MET R988C (n = 2). No MET amplification was found by fluorescent in situ hybridization in the four cases with MET mutation. No mutations were detected in the other genes tested. CONCLUSIONS:: In summary, additional mutations were found in 20% of ALK+ cases involving two of the 10 genes tested. Our study highlights that EGFR mutation can be present in ALK+ tumors, though uncommon. Clinical implication of MET mutation in our cases is uncertain and further study is needed.
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[402]
TÍTULO / TITLE: - Diagnosis of Regional Node Metastases in Lung Cancer with Computer-Aided 3D Measurement of the Volume and CT-Attenuation Values of Lymph Nodes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acad Radiol. 2013 Mar 5. pii: S1076-6332(13)00035-4. doi: 10.1016/j.acra.2013.01.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.acra.2013.01.013
AUTORES / AUTHORS: - Takahashi Y; Takashima S; Hakucho T; Miyake C; Morimoto D; Jiang BH; Numasaki H; Tomita Y; Nakanishi K; Higashiyama M
INSTITUCIÓN / INSTITUTION: - Osaka University Graduate School of Medicine, Division of Allied Health Sciences, Department of Diagnostic Radiological Imaging, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: yoshi_seat_128@yahoo.co.jp.
RESUMEN / SUMMARY: - RATIONALE AND OBJECTIVES: The aim of this study is to assess the usefulness of computer-aided three-dimensional (3D) measurement of volume and computed tomography (CT) attenuation values of nodes for diagnosing nodal metastases of lung cancer. MATERIALS AND METHODS: We measured three diameters, their ratios, volume, and CT values in 3D images of 191 nodes (64 malignant; 162 of <1 cm in short diameter) in 26 consecutive patients who underwent contrast-enhanced, thin-section, multidetector row CT before surgery. We separately studied statistically significant factors in a group of all nodes and in another group of nodes of <1 cm in short diameter with logistic modeling and evaluated their diagnostic accuracy. RESULTS: Significant factors were CT values (P < .001) and short diameter (P = .001) for the total node group, and CT values (P = .030) and 3D volume (P = .035) for the <1 cm node group. Optimal 83% accuracy was obtained with a criterion of short diameter of >7.4 mm and CT values of >103 Hounsfield unit (HU) for the total node group, whereas optimal 76% accuracy was obtained with a criterion of 3D volume of >1282 mm3 or CT values of >103 HU for the <1 cm node group. CONCLUSION: 3D measurement may be useful for diagnosing nodal metastases.
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[403]
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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[404]
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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[405]
TÍTULO / TITLE: - Cisplatin upregulates MSH2 expression by reducing miR-21 to inhibit A549 cell growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Pharmacother. 2013 Mar;67(2):97-102. doi: 10.1016/j.biopha.2012.11.008. Epub 2012 Dec 28.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biopha.2012.11.008
AUTORES / AUTHORS: - Zhang YX; Yue Z; Wang PY; Li YJ; Xin JX; Pang M; Zheng QY; Xie SY
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Tumour Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, 264003, China.
RESUMEN / SUMMARY: - miR-21 can act as an oncogene. MSH2 has been reported that it involved in the DNA mismatch repair (MMR) system and overexpression of MSH2 can induce cell apoptosis. We predicted that MSH2-3’-untranslated region (3’-UTR) was targeted by miR-21 using microRNA analysis softwares. To further explore the roles of miR-21 and MSH2 in A549 cells, we constructed pcDNA-GFP-msh-UTR vector (including MSH2-3’-UTR) to transfect A549 cells with miR-21, GFP positive cells were estimated under a fluorescence microscopy and by flow cytometry. We found miR-21 could obviously downregulate the expression of MSH2, which was further proved by western blotting. Moreover, we treated A549 cells with cisplatin and found that cisplatin could inhibit A549 cell growth in vitro and in vivo. We also found that cisplatin could downregulate miR-21 expression, while increase MSH2 expression in A549 cells. Our results demonstrated that cisplatin could upregulate the expression of MSH2 through downregulating miR-21 to inhibit A549 cell proliferation, which provides new gene targets for drug design or cancer therary.
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[406]
TÍTULO / TITLE: - KRAS Mutations as Prognostic and Predictive Markers in Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318283d958
AUTORES / AUTHORS: - Martin P; Leighl NB; Tsao MS; Shepherd FA
INSTITUCIÓN / INSTITUTION: - *Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario, Canada and daggerDepartment of Pathology, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario, Canada.
RESUMEN / SUMMARY: - A greater understanding of non-small-cell lung cancer at a molecular level has led to the identification of an increasing number of driver mutations. Extensive research of the KRAS gene as well as specific mutations has established its role in tumorigenesis. Nevertheless, the role of KRAS oncogene in non-small-cell lung cancer remains unclear. Recent studies indicated that mutant KRAS could be predictive of lack of response to chemotherapy, but large pooled analysis failed to confirm this result. The predictive value of KRAS mutation and EGFR-TKI treatment is more ambiguous with some recent evidence suggesting that it may be a negative predictive biomarker. This review provides an overview of RAS biology, assesses the utility of KRAS as a prognostic marker, and evaluates its role as a predictive marker for response to chemotherapy and EGFR-TKIs. In addition, we review some current studies that are targeting the KRAS pathway.
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[407]
TÍTULO / TITLE: - Optical Diagnosis for Lung Cancer Using Multiphoton Imaging.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Scanning. 2013 Feb 20. doi: 10.1002/sca.21076.
●● Enlace al texto completo (gratuito o de pago) 1002/sca.21076
AUTORES / AUTHORS: - Chen G; Wang L; Lu J; Zhu W; Zhang H; Chen J; Zhuo S; Yan J
INSTITUCIÓN / INSTITUTION: - Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, P.R. China.
RESUMEN / SUMMARY: - Currently, hematoxylin-eosin (H-E) stained histopathology is the golden standard for diagnosing lung cancer. This time-consuming procedure needs tissue biopsy, sample fixation, slicing, and labeling. Therefore, the availability of a noninvasive optical diagnosis that can obtain real-time analysis comparable to golden standard H-E stained histopathology will be of extraordinary benefit to the medical community. In this study, we investigated whether multiphoton imaging can make real-time optical diagnosis for normal and cancerous lung tissue, compared with H-E stained histopathology. In the normal lung tissue, we found that multiphoton imaging could display normal lung parenchyma composed of alveolar spaces separated by thin septa. In the cancerous lung tissue, multiphoton imaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. These cancer cells were characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio. All of these histopathological features of tissue architecture and cell morphology identified by multiphoton images were readily correlated with H-E staining images. All together, multiphoton imaging can make real-time optical diagnosis for lung cancer. This study provides the groundwork for further using multiphoton imaging to perform real-time noninvasive “optical biopsy” for lung cancer in the near future. SCANNING 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
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[408]
TÍTULO / TITLE: - Adiponectin affects lung epithelial A549 cell viability counteracting TNFa and IL-1ss toxicity through AdipoR1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Biochem Cell Biol. 2013 Mar 15. pii: S1357-2725(13)00071-X. doi: 10.1016/j.biocel.2013.03.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biocel.2013.03.003
AUTORES / AUTHORS: - Nigro E; Scudiero O; Sarnataro D; Mazzarella G; Sofia M; Bianco A; Daniele A
INSTITUCIÓN / INSTITUTION: - CEINGE - Biotecnologie Avanzate Scarl, Naples, Italy; IRCCS - Fondazione SDN, Naples, Italy.
RESUMEN / SUMMARY: - Adiponectin (Acrp30) exerts protective functions on metabolic and cellular processes as energy metabolism, cell proliferation and differentiation by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the biological role of Acrp30 in lung has not been completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been related to establishment and progression of chronic obstructive pulmonary disease (COPD) and lung cancer. Here, we investigated the effects of Acrp30 on A549, a human alveolar epithelial cell line, showing how, in a time and dose-dependent manner, it decreases cell viability and increases apoptosis through ERK1/2 and AKT. Furthermore, we examined the effects of Acrp30 on A549 cells exposed to TNFa and/or IL-1ss, two potent lung inflammatory cytokines. We showed that Acrp30, in dose- and time-dependent manner, reduces cytotoxic effects of TNFa and/or IL-1ss improving cell viability and decreasing apoptosis. In addition, Acrp30 inhibits NF-?B nuclear trans-activation and induces the expression of the anti-inflammatory IL-10 cytokine without modifying that of pro-inflammatory IL-6, IL-8, and MCP-1 molecules via ERK1/2 and AKT. Finally, specifically silencing AdipoR1 or AdipoR2, we observed that NF-?B inhibition is mainly mediated by AdipoR1. Taken together, our data provides novel evidence for a direct effect of Acrp30 on the proliferation and inflammation status of A549 cells strongly supporting the hypothesis for a protective role of Acrp30 in lung. Further studies are needed to fully elucidate the Acrp30 lung effects in vivo but our results confirm this adipokine as a promising therapeutic target in lung diseases.
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[409]
TÍTULO / TITLE: - Inferior turbinate osteoma as a cause of unilateral nose obstruction.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:189-91.
AUTORES / AUTHORS: - Grabovac S; Hadzibegovic AD; Markesic J
INSTITUCIÓN / INSTITUTION: - Bjelovar General Hospital, Department of Otorhinolaryngology, Bjelovar, Croatia.
RESUMEN / SUMMARY: - Osteomas are benign, slow growing bone tumors often seen in paranasal sinuses, mostly in the frontal sinus, whereas they are rare in the nasal cavity. Inferior turbinate osteoma is extremely rare and our case is the third reported in the literature to date. Symptoms vary depending on the location, size and spreading and nasal obstruction is the most common symptom. Treatment of osteomas is surgical and is reserved only for rapidly growing osteomas with symptoms of infection or compression. Although endoscopic surgery is preferred modality, external approach with lateral rhinotomy should be considered with larger osteomas especially those that involve the ethmoid labyrinth. In cases like ours, when large osteoma is localized on the inferior nasal turbinate, sublabial incision through the vestibulum is very suitable approach because it provides wide access and good visibility and leaves no visible scar.
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[410]
TÍTULO / TITLE: - A rare association of pulmonary carcinoid, lymphoma, and sjogren syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Surg. 2013 Mar;95(3):1086-7. doi: 10.1016/j.athoracsur.2012.06.051.
●● Enlace al texto completo (gratuito o de pago) 1016/j.athoracsur.2012.06.051
AUTORES / AUTHORS: - Taylor WS; Vaughan P; Trotter S; Rajesh PB
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Heartlands Hospital, Birmingham, United Kingdom. wstjtaylor@doctors.org.uk
RESUMEN / SUMMARY: - Pulmonary carcinoid and pulmonary lymphoma are both rare cancers and are seldom seen together. Cases have been reported of their coexistence in the gastrointestinal tract, but our literature searches only found a single case of their coexistence in the lung. We discuss our case as well as the literature to try to find a connection and explanation for this occurrence.
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[411]
TÍTULO / TITLE: - Factors Affecting Local Progression after Percutaneous Cryoablation of Lung Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Vasc Interv Radiol. 2013 Feb 28. pii: S1051-0443(13)00008-0. doi: 10.1016/j.jvir.2012.12.026.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jvir.2012.12.026
AUTORES / AUTHORS: - Yashiro H; Nakatsuka S; Inoue M; Kawamura M; Tsukada N; Asakura K; Yamauchi Y; Hashimoto K; Kuribayashi S
INSTITUCIÓN / INSTITUTION: - Departments of Diagnostic Radiology (H.Y., S.N., M.I., S.K.) and; Division of Radiology (H.Y.), Hiratsuka City Hospital, Kanagawa, Japan. Electronic address: yashiro@rad.med.keio.ac.jp.
RESUMEN / SUMMARY: - PURPOSE: To evaluate factors predicting local tumor progression after percutaneous cryoablation of lung tumors (PCLT). MATERIALS AND METHODS: Seventy-one consecutive patients with 210 tumors (11 primary and 199 metastatic pulmonary neoplasms; mean maximum diameter, 12.8 mm) were treated with 102 sessions of PCLT. Rates of local tumor progression and technique effectiveness were estimated by Kaplan-Meier method. Multiple variables were evaluated with the log-rank test, followed by uni- and multivariate multilevel analyses to identify independent risk factors, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. All statistical tests were two-sided. RESULTS: Median follow-up period was 454 days (range, 79-2,467 d). Local tumor progression occurred in 50 tumors (23.8%). One-, 2-, and 3-year local progression-free rates were 80.4%, 69.0%, and 67.7%, respectively, and technique effectiveness rates were 91.4%, 83.0%, and 83.0%, respectively. Existence of a thick vessel (diameter>/=3 mm) no more than 3 mm from the edge of the tumor was assessed as an independent factor (HR, 3.84; 95% CI, 1.59-9.30; P = .003) associated with local progression by multivariate analysis. CONCLUSIONS: Presence of a vessel at least 3 mm in diameter close to the tumor represents an independent risk factor for local progression after PCLT.
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[412]
TÍTULO / TITLE: - Significant frequency of allelic imbalance in 3p region covering RARbeta and MLH1 loci seems to be essential in molecular non-small cell lung cancer diagnosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Oncol. 2013 Jun;30(2):532. doi: 10.1007/s12032-013-0532-9. Epub 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s12032-013-0532-9
AUTORES / AUTHORS: - Antczak A; Migdalska-Sek M; Pastuszak-Lewandoska D; Czarnecka K; Nawrot E; Domanska D; Kordiak J; Gorski P; Brzezianska E
INSTITUCIÓN / INSTITUTION: - Department of General and Oncological Pulmonology, Medical University of Lodz, Kopcinskiego St.22, 90-153 Lodz, Poland.
RESUMEN / SUMMARY: - The aim of the study was to investigate the influence of allelic imbalance (AI) in several loci of tumor suppressor genes in 3p region on the non-small cell lung cancer (NSCLC) development. We evaluated the frequency of loss of heterozygosity and/or microsatellite imbalance (LOH/MSI) and assessed their association with patients’ characteristics (age, gender, tobacco addiction) and NSCLC classification according to TNM/AJCC staging. To analyze the potential role of AI involved in NSCLC pathogenesis, we allelotyped a group of 74 NSCLC patients using 7 microsatellite markers. The highest frequency of LOH/MSI, however, not statistically significant, was observed in RARbeta and MLH1 (p = 0.104 and p = 0.216, respectively) loci. The association between high LOH/MSI frequency in 3p region with male gender (p = 0.041) as well as with age (especially >60 years) for RARbeta and MLH1 genes (p = 0.0001 and p = 0.020, respectively) was documented. Statistically significant increased frequency of MLH1 allelic loss in squamous cell carcinoma (SCC) versus non-squamous cell carcinoma (non-SCC) was observed (p = 0.01). Significant increase in LOH/MSI frequency in 3p region (mainly in FHIT and MLH1 loci) in correlation with cigarette addiction in a lifetime (>/=40 years and >/=40 Pack Years) was also documented (p < 0.05). The highest LOH/MSI was revealed in RARbeta locus in IA tumors (p = 0.0001), while the similarly high allelic loss of MLH1 correlated with III A/B tumors (p = 0.0002), according to AJCC staging. The obtained results demonstrate that AI is influenced by tobacco smoking and seems to be vital in the molecular diagnosis of NSCLC, especially of SCC subtype.
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[413]
TÍTULO / TITLE: - Juvenile angiofibroma of the maxillary sinus.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:197-9.
AUTORES / AUTHORS: - Malvic G; Manestar D; Krstulja M; Corak D; Candrlic B; Kujundzic M; Velepic M; Starcevic R
INSTITUCIÓN / INSTITUTION: - University of Rijeka, Rijeka University Hospital Center, Clinic of Otorhinolaryngology, Head and Neck Surgery, Rijeka, Croatia. goran.malvic@gmail.com
RESUMEN / SUMMARY: - Juvenile angiofibromas are benign fibro-vascular tumours of the nasopharynx that develop in prepubertal and adolescent males. Typical symptoms are longstanding unilateral nasal obstruction occasionally followed by epistaxes and frequent severe intraoperative haemorrhage of the discovered mass. We report the case of a 14-year-old boy histologically diagnosed with a juvenile angiofibroma in spite of the atypical localisation of the polyploid mass of the left maxillary sinus.
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[414]
TÍTULO / TITLE: - The Effect of Provider Density on Lung Cancer Survival Among Blacks and Whites in the United States.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318287c24c
AUTORES / AUTHORS: - Backhus LM; Hayanga AJ; Au D; Zeliadt SB
INSTITUCIÓN / INSTITUTION: - *VA Puget Sound Healthcare System, Seattle, Washington; daggerDivision of Cardiothoracic Surgery, University of Washington, Seattle, Washington; double daggerDivision of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington; and section signVA Health Services Research and Development Service, Seattle, Washington.
RESUMEN / SUMMARY: - INTRODUCTION:: Lung cancer mortality rates may vary with access to specialty providers and local resources. We sought to examine the effect of access to care, using density of lung cancer care providers, on lung cancer mortality among blacks and whites in the United States. METHODS:: We examined U.S. county-level data for age-adjusted lung cancer mortality rates from 2003 to 2007. Our primary independent variable was per capita number of thoracic oncologic providers, adjusting for county-level smoking rates, socioeconomic status, and other geographic factors. Data were obtained from 2009 Area Resource File, National Center for Health Statistics, and the County Health Rankings Project. RESULTS:: Providers of lung cancer care were unevenly distributed among the U.S. counties. For example, 41.4% of the U.S. population reside in counties with less than four thoracic surgeons per 100,000 people, 23.4% in counties with 4 to 15 surgeons per 100,000 people, and 35.3% in counties with more than 15 surgeons per 100,000 people. Geographically, 4.3% of whites compared with 11.2% of blacks lived in high lung cancer mortality zones. Lung cancer mortality did not vary by density of thoracic surgeons or oncology services; however, higher primary care provider density was associated with lung cancer mortality reduction of 4.1 per 100,000 for whites. CONCLUSION:: Variation in provider density for thoracic oncology in the United States was not associated with a difference in lung cancer mortality. Lower mortality associated with higher primary care provider density suggests that equitable access to primary care may lead to reduced cancer disparities.
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[415]
TÍTULO / TITLE: - Lung Cancer Probably Related to Talc Exposure: A Case Report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ind Health. 2012 Dec 26.
AUTORES / AUTHORS: - Kim J; Oak C; Jang T; Jung M; Chun B; Park EK; Takahashi K
INSTITUCIÓN / INSTITUTION: - Department of Occupational and Environmental Medicine, College of Medicine, Kosin University.
RESUMEN / SUMMARY: - Industrial talc has been widely circulated in the world for a long time. The pure talc has little effects on humans, but inhalation of talc contaminated with asbestos can causes severe asbestos-related diseases such as lung cancer and malignant mesothelioma. Herein, we represent a case of lung cancer after occupational exposure to industrial talc in the rubber manufacturing industry.
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[416]
TÍTULO / TITLE: - Diesel motor exhaust and lung cancer mortality: reanalysis of a cohort study in potash miners.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Epidemiol. 2013 Feb;28(2):159-68. doi: 10.1007/s10654-013-9784-0. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s10654-013-9784-0
AUTORES / AUTHORS: - Mohner M; Kersten N; Gellissen J
INSTITUCIÓN / INSTITUTION: - Division Work and Health, Federal Institute for Occupational Safety and Health (BAuA), Noldnerstr. 40-42, 10317, Berlin, Germany, Moehner.Matthias@baua.bund.de.
RESUMEN / SUMMARY: - The aim of the reanalysis is to reassess lung cancer risk associated with occupational exposure to diesel motor exhaust in potash miners, while controlling for potential confounders such as smoking and previous occupational history. Our investigation is based on a cohort study of nearly 6,000 German potash miners, who were followed up from 1970 to 2001. The reanalysis also takes into account the employment periods before potash mining, in particular uranium mining. Different approaches (nested case-control study and Cox model) were used to adjust for confounding. The exposure estimates were recalculated, lagging the exposure by 5 years. Exposure groups were defined by tertiles of cumulative respirable elemental carbon (REC) exposure estimates and occupational categories, where exposure was estimated originally by representative measurements of total carbon for different occupations. The highest REC concentration was measured for production workers, about twice as much as for other occupations. The reanalysis revealed that while about 4 % of all study subjects had worked earlier in uranium mines, 10.3 % of later lung cancer cases did so. Although their absolute number was small, the corresponding relative risk estimator was significantly elevated. Our analysis did not show any notable association between cumulative REC exposure and lung cancer risk. Introducing cumulative REC exposure as a continuous variable into the conditional logistic regression model yielded an odds ratio of OR = 1.04 [0.70-1.53]95 % adjusted for smoking and previous employment. The study results give no evidence for an association between REC exposure and lung cancer risk. Only for very high cumulative dose, corresponding to at least 20 years of exposure in the production area, some weak hints for a possible risk increase could be detected. The study underlines the importance of assessing the entire occupational history in occupational studies, especially if the supposed dose-response-relationship is weak.
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[417]
TÍTULO / TITLE: - Percutaneously implanted markers in peripheral lung tumours: Report of complications.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Oncol. 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2013.764009
AUTORES / AUTHORS: - Persson GF; Josipovic M; Nygaard DE; Recke PV; Aznar M; Juhler-Nottrup T; Rosenschold PM; Korreman S; Specht L
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Copenhagen University Hospital , Rigshospitalet, Copenhagen , Denmark.
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[418]
TÍTULO / TITLE: - The diagnostic value of apolipoprotein E in malignant pleural effusion associated with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Chim Acta. 2013 Mar 21. pii: S0009-8981(13)00104-6. doi: 10.1016/j.cca.2013.03.013.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cca.2013.03.013
AUTORES / AUTHORS: - Wang Y; Chen Z; Chen J; Pan J; Zhang W; Pan Q; Ding H; Lin X; Wen X; Li Y; Meng QH
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
RESUMEN / SUMMARY: - BACKGROUND: Apolipoprotein E (apoE) levels have been shown to be elevated in pleural effusion of patients with non-small cell lung cancer (NSCLC). However, the diagnostic value of apoE in pleural effusion in NSCLC has not been well validated and established. METHODS: Samples of malignant pleural effusions (MPE) and benign effusions were collected and analyzed for apoE, tumor markers, and other biochemical changes. RESULTS: ApoE levels were significantly higher in MPE (n=160) than in benign pleural effusions (n=40). They were higher in adenocarcinoma-associated MPE than in squamous cell carcinoma- and large cell carcinoma-associated MPE. The receiver operating characteristic curve showed that the sensitivity and specificity of apoE for the diagnosis of MPE were 87.5% and 85.3%, respectively, at the cutoff 105ng/ml, and the area under the curve (AUC) was 0.748. For the diagnosis of adenocarcinoma-associated MPE, apoE achieved sensitivity and specificity of 70.8% and 83.30%, respectively, and the AUC was the highest of all the markers. CONCLUSIONS: ApoE levels are significantly increased in the pleural effusion of patients with NSCLC. Increased concentration of apoE in a pleural effusion is a potential marker for the diagnosis of MPE as well as for differential diagnosis of MPE in NSCLC.
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[419]
TÍTULO / TITLE: - Epidermal growth factor receptor inhibition in lung cancer: status 2012.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):373-84. doi: 10.1097/JTO.0b013e31827ed0ff.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827ed0ff
AUTORES / AUTHORS: - Hirsch FR; Janne PA; Eberhardt WE; Cappuzzo F; Thatcher N; Pirker R; Choy H; Kim ES; Paz-Ares L; Gandara DR; Wu YL; Ahn MJ; Mitsudomi T; Shepherd FA; Mok TS
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Division of Medical Oncology and Department of Pathology, University of Colorado Cancer Center, 12801 E. 17th Avenue, Aurora, CO 80045, USA. fred.hirsch@ucdenver.edu
RESUMEN / SUMMARY: - Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing.
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[420]
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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[421]
TÍTULO / TITLE: - Extrapulmonary small cell carcinoma mimicking malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Pathol. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1136/jclinpath-2012-201401
AUTORES / AUTHORS: - Noguchi K; Fujimoto N; Asano M; Fuchimoto Y; Ono K; Ozaki S; Hotta K; Kato K; Toda H; Taguchi K; Kishimoto T
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan.
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[422]
TÍTULO / TITLE: - The anticancer efficacy of paclitaxel liposomes modified with mitochondrial targeting conjugate in resistant lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 May;34(14):3626-38. doi: 10.1016/j.biomaterials.2013.01.078. Epub 2013 Feb 16.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.078
AUTORES / AUTHORS: - Zhou J; Zhao WY; Ma X; Ju RJ; Li XY; Li N; Sun MG; Shi JF; Zhang CX; Lu WL
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer-related death in humans and the multidrug resistance (MDR) is the major obstacle to successful chemotherapy of lung cancer. In this study, a d-alpha-tocopheryl polyethylene glycol 1000 succinate-triphenylphosphine conjugate (TPGS-TPP) was synthesized as the mitochondrial targeting molecule, and was incorporated onto the surface of paclitaxel liposomes to treat the drug-resistant lung cancer. Evaluations were performed on the human lung cancer A549 cells, the drug-resistant lung cancer A549/cDDP cells, and the drug-resistant lung cancer A549/cDDP cells xenografted nude mice. The yield of TPGS-TPP conjugate synthesized was about 50% and the particle size of targeting paclitaxel liposomes developed was approximately 80 nm. In comparison with taxol and regular paclitaxel liposomes, the targeting paclitaxel liposomes exhibited the strongest anticancer efficacy in vitro and in the drug-resistant A549/cDDP xenografted tumor model. The targeting paclitaxel liposomes could significantly enhance the cellular uptake, be selectively accumulated into the mitochondria, and cause the release of cytochrome C. This targeting delivery of drug initiated a cascade of caspase 9 and 3 reactions, activated the pro-apoptotic Bax and Bid proteins and suppressed the anti-apoptotic Bcl-2 protein, thereby enhancing the apoptosis by acting on the mitochondrial signaling pathways. In conclusion, the targeting paclitaxel liposomes have the potential to treat drug-resistant lung cancer.
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[423]
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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[424]
TÍTULO / TITLE: - WITHDRAWN: Expression analysis of Sca-1 and its significance in lung cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasma. 2013 Feb 4. doi: 10.4149/neo_2013_039.
●● Enlace al texto completo (gratuito o de pago) 4149/neo_2013_039
AUTORES / AUTHORS: - Zhou CH; Liao DG
RESUMEN / SUMMARY: - Ahead of Print article withdrawn by publisher. The purpose of the present study was to determine the expression of Sca-1, the stem cell marker, among various lung cancers and evaluate their utility. Immunohistochemistry was done in 151 surgically resected lung cancer specimens or biopsies, including 76 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 15 cases of small cell carcinoma, 6 cases of adenosquamous cell carcinoma and 4 cases of large cell carcinoma. The results showed that 88 (58.3%) cases were Sca-1 positive. Further analysis showed that in cases of adenocarcinoma, the rate of lymph node invasion and poor differentiation level of Sca-1(+) specimens were respectively higher than those of Sca-1(-) specimens. In cases with small cell carcinoma and squamous cell carcinoma, the rates of lymph node invasion of Sca-1(+) specimens were respectively higher than those of Sca-1(-) specimens. Survival analysis showed that for patients with adenocarcinoma and small cell carcinoma, the average survival time of Sca-1(+) patients was significantly shorter than that of Sca-1(-) patients. Further mutation analysis showed that EGFR mutation rates in Sca-1 (-) adenocarcinoma patients were significantly higher than those of Sca-1 (+) patients, while p53 and KRAS mutation rates in Sca-1 (-) adenocarcinoma and squamous cell carcinoma patients were respectively lower than those of Sca-1 (+) patients. Western blots analysis showed that expression of aSrc family tyrosine kinase, Fyn, was positively related with Sca-1 expression levels. These results suggested that Sca-1 expression in some human lung cancers was related with malignancy phenotype and survival time. Keywords: Sca-1 expression, stem cancer cell, lung cancer, malignancy phenotype.
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[425]
TÍTULO / TITLE: - SCUBE3 regulation of early lung cancer angiogenesis and metastatic progression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Exp Metastasis. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s10585-013-9575-8
AUTORES / AUTHORS: - Chou CH; Cheng YF; Siow TY; Kumar A; Peck K; Chang C
INSTITUCIÓN / INSTITUTION: - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
RESUMEN / SUMMARY: - Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is strongly expressed in extremely invasive lung carcinoma. We showed in our previous study that SCUBE3 triggers the transforming growth factor-beta pathway and subsequently promotes tumor angiogenesis and the epithelial-mesenchymal transition (EMT). However, the role of SCUBE3 in early tumor expansion hasn’t been fully demonstrated in vivo. The present study used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to temporally assess tumor angiogenesis in SCUBE3-knockdown and control non-small-cell lung carcinoma (NSCLC) cancer cells in the early tumor stage (weeks 1-3). We further evaluated the metastatic potential of the SCUBE3-knockdown and control tumor cells using a circulating tumor cell (CTC) assay. The differences in gene expression profile between these cell lines were determined using microarray analysis. The results show that SCUBE3 knockdown was associated with lower vascular permeability in the tumor and effectively inhibited the metastatic potential of NSCLC, as evidenced by the decreased CTCs in the mice bearing SCUBE3-knockdown tumors. Microarray analysis revealed that several genes involved in angiogenesis and EMT were down-regulated in SCUBE3-knockdown tumors, including matrix metalloproteinases (MMPs) 2, 9, and 14, (MMP-2, MMP-9, and MMP-14, respectively), fibronectin (FN-1), lysyl oxidase (LOX), hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1), early growth response protein 1 (EGR1), and interleukin 8 (IL-8). Together these data suggest that SCUBE3 is a potential target for pharmacological intervention. The findings of the present study also show that differences in vascular permeability precede the CTCs detection, indicating that DCE-MRI may be a sensitive biomarker for assessing tumor invasiveness.
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[426]
TÍTULO / TITLE: - FRET-based detection and genotyping of HPV-6 and HPV-11 causing recurrent respiratory papillomatosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Virol Methods. 2013 Mar 6;189(2):271-276. doi: 10.1016/j.jviromet.2013.01.025.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jviromet.2013.01.025
AUTORES / AUTHORS: - Combrinck CE; Seedat RY; Burt FJ
INSTITUCIÓN / INSTITUTION: - Department of Medical Microbiology and Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
RESUMEN / SUMMARY: - Recurrent respiratory papillomatosis (RRP) is a potentially life-threatening disease caused by human papillomavirus (HPV), usually HPV types 6 and 11. The conventional method used for detection and typing the RRP isolates in our laboratory is the polymerase chain reaction (PCR) and DNA sequencing method. A real-time PCR assay based on fluorescence resonance energy transfer (FRET) probe technology was developed for the detection and rapid genotyping of HPV-6 and-11 isolates from biopsy material. The primers and probes were designed using multiple alignments of HPV-6 and HPV-11 partial E6 and E7 sequences that included prototypic and non-prototypic variants. Real-time PCR followed by probe-specific melting-curve analysis allowed differentiation of HPV-6 and HPV-11. HPV-6 and HPV-11 amplicons were used to determine detection limits and inter- and intra-assay variability. The detection limit of the assay was 12.8 DNA copies for HPV-6 and 22.5 DNA copies for HPV-11. A total of 60 isolates were genotyped using the FRET real-time PCR assay and a 100% concordance was obtained when results were compared with genotyping based on conventional DNA sequencing. The real-time PCR assay based on FRET technology was able to detect and rapidly genotype HPV from tissue biopsy obtained from patients with RRP. The assay reduces the time required for genotyping from three working days to less than a day.
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[427]
TÍTULO / TITLE: - MicroRNA-365 regulates NKX2-1, a key mediator of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Mar 16. pii: S0304-3835(13)00234-6. doi: 10.1016/j.canlet.2013.03.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.006
AUTORES / AUTHORS: - Kang SM; Lee HJ; Cho JY
INSTITUCIÓN / INSTITUTION: - Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
RESUMEN / SUMMARY: - MicroRNAs constitute a class of small noncoding RNAs that play roles in tumorigenesis. We found that NKX2-1 protein levels were generally high in the lung cancer tissues whereas miRNA-365 expression levels were down-regulated. Ectopic miR-365 expression decreased NKX2-1 expression in lung cancer cell lines. Transfection of a miR-365 mimic led to reduced proliferation of lung cancer cells; conversely, a miR-365 inhibitor slightly increased cell proliferation. The NKX2-1 overexpression significantly increased the cell proliferation by overcoming the suppressive effect of miR-365. Our data suggest that miR-365 is an important regulator of NKX2-1 and can be a target for lung cancer therapies.
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[428]
TÍTULO / TITLE: - Small Cell Carcinoma of the Ovary of the Hypercalcemic Type Presenting in a 5-Year-Old Girl.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pediatr Hematol Oncol. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e31828308da
AUTORES / AUTHORS: - Kopp LM; Desoky S; Pugh J; Herzog CE
INSTITUCIÓN / INSTITUTION: - Departments of *Pediatrics daggerMedical Imaging double daggerPathology, University of Arizona, Tucson, AZ section signDivision of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX.
RESUMEN / SUMMARY: - Small cell carcinoma of the ovary, hypercalcemic type is a very rare, highly aggressive tumor associated with a poor prognosis. Diagnosis is typically challenging secondary to undifferentiated cells and the rarity of the tumor. We report our experience with a 5-year-old girl who presented with stage IV disease.
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[429]
TÍTULO / TITLE: - Mass invading the trachea: a rare presentation of tuberculosis simulating lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Infection. 2013 Apr;41(2):599-600. doi: 10.1007/s15010-013-0422-2. Epub 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s15010-013-0422-2
AUTORES / AUTHORS: - Hochhegger B; Zanetti G; Marchiori E
INSTITUCIÓN / INSTITUTION: - Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
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[430]
TÍTULO / TITLE: - Ablative or palliative stereotactic body radiotherapy with helical tomotherapy for primary or metastatic lung tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):655-60.
AUTORES / AUTHORS: - Marcenaro M; Vagge S; Belgioia L; Agnese D; Lamanna G; Mantero E; Gusinu M; Garelli S; Cavagnetto F; Agostinelli S; Corvo R
INSTITUCIÓN / INSTITUTION: - IRCCS San Martino-IST-National Cancer Research Institute and University, Lrago Rosanna Benzi 10, 16132 Genoa, Italy.
RESUMEN / SUMMARY: - AIM: To evaluate the feasibility and outcomes of stereotactic body radiotherapy (SBRT) by helical tomotherapy (HT) for patients with primary or secondary lung cancer. PATIENTS AND METHODS: Between March 2009 and January 2012, 56 patients were selected as candidates for the study and were divided into two subgroups. The ablative SBRT group included 27 patients with T1-T2 non-small cell lung cancer who received four to five large-dose fractions in two weeks and the palliative SBRT group included 29 patients with lung metastases treated with eight lower-dose fractions in four weeks. RESULTS: No differences in acute toxicities were found between different fractionation schemes with different overall treatment times. Actuarial local control at 24 months was better for the ablative group (69.6%) than for the palliative one (40.4%) (p=0.0019). CONCLUSION: HT-based SBRT was feasible and well-tolerated. Local control was satisfactory for patients treated with ablative SBRT but unsatisfactory for those treated with palliative SBRT. Outcomes also suggest the use of ablative SBRT fractionation for palliative intent.
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[431]
TÍTULO / TITLE: - Lung-sparing total pleurectomy: the surgical option of choice in malignant pleural mesothelioma?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cardiothorac Surg. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1093/ejcts/ezt022
AUTORES / AUTHORS: - Waller DA
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Glenfield Hospital, Leicester, UK.
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[432]
TÍTULO / TITLE: - Improved identification of peripheral lung tumors by using diffuse reflectance and fluorescence spectroscopy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung Cancer. 2013 Feb 9. pii: S0169-5002(13)00026-3. doi: 10.1016/j.lungcan.2013.01.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.lungcan.2013.01.016
AUTORES / AUTHORS: - Spliethoff JW; Evers DJ; Klomp HM; van Sandick JW; Wouters MW; Nachabe R; Lucassen GW; Hendriks BH; Wesseling J; Ruers TJ
INSTITUCIÓN / INSTITUTION: - Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands. Electronic address: j.spliethoff@nki.nl.
RESUMEN / SUMMARY: - INTRODUCTION: A significant number of transthoracic diagnostic biopsy procedures for lung lesions show indeterminate results. Such failures are potentially due to inadequate recognition of vital tumor tissue. The objective of this study was to evaluate whether optical spectroscopy at the tip of a biopsy needle device can improve the accuracy of transthoracic lung biopsies. METHODS: Ex vivo optical measurements were performed on lung tissue from 13 patients who underwent either lobectomy or segmental resection for primary non-small cell lung cancer or pulmonary metastases from various origins. From Diffuse Reflectance Spectroscopy (DRS) and Fluorescence Spectroscopy (FS) measurements, different parameters were derived such as tissue composition as well as physiological and metabolic characteristics. Subsequently, a classification and regression trees (CART) algorithm was used to classify the type of tissue based on the derived parameters. Histology analysis was used as gold standard to report sensitivity and specificity of the tissue classification based on the present optical method. RESULTS: Collective analysis of all DRS measurements showed an overall discrimination between lung parenchyma and tumor tissue with a sensitivity and specificity of 98 and 86%, respectively. When the data were analyzed per individual patient, eliminating inter-patient variation, 100% sensitivity and specificity was achieved. Furthermore, based on FS parameters, necrotic and non-necrotic tumor tissue could be distinguished with 91% sensitivity and specificity. CONCLUSION: This study demonstrates that DRS provides accurate diagnosis of malignant lung lesions, whereas FS enables identification of necrotic tissue. When both optical techniques are combined within a biopsy device, the diagnostic performance and the quality of transthoracic biopsies could significantly be enhanced.
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[433]
TÍTULO / TITLE: - The prognostic value of ratio-based lymph node staging in resected non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):429-35. doi: 10.1097/JTO.0b013e3182829c16.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182829c16
AUTORES / AUTHORS: - Qiu C; Dong W; Su B; Liu Q; Du J
INSTITUCIÓN / INSTITUTION: - *Institute of Oncology, Provincial Hospital Affiliated to Shandong University, Shandong University, #51 Weiliu Road, Jinan 250021, P. R. China; daggerDepartment of Medical Engineering, Provincial Hospital Affiliated to Shandong University, Shandong University, #324 Jingwu Road, Jinan 250021, P. R. China; and double daggerDepartment of thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, #324 Jingwu Road, Jinan 250021, P. R. China.
RESUMEN / SUMMARY: - INTRODUCTION: : Assessment of lymph node status is a critical issue in the surgical management of non-small-cell lung cancer (NSCLC). We sought to determine the prognostic value of metastatic lymph node ratio (LNR) in patients with radical surgery for NSCLC. METHODS: : We abstracted data from 480 consecutive patients undergoing radical surgery for NSCLC between 2006 and 2008 in our institution. Kaplan-Meier estimated the survival function using the number of metastatic lymph node (MLN) and LNR as categorized variables. The prognostic value of age, sex, smoking status, location of tumor, histology, pathology T stage, pathology N stage, surgical procedure, chemotherapy, MLN, and LNR were assessed using a multivariate Cox proportional hazards model for overall survival (OS) and disease-free survival (DFS). RESULTS: : The median numbers of examined lymph nodes and MLNs were 15 and 5, respectively. Optimal cutpoints of the LNR were calculated as 0, 0 to 0.35, and greater than 0.35. Patients with higher LNR were associated with worse OS and DFS in the whole series, whereas there was no significant difference in the OS and DFS of those patients classified as pathology N2. A multivariate analysis showed that the LNR staging, smoking status, and chemotherapy were revealed to be independent prognostic factors. CONCLUSIONS: : LNR is an independent predictor of survival in patients with NSCLC undergoing radical resection; the prognostic significance is more valuable in patients classified as pathology N1.
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[434]
TÍTULO / TITLE: - Perfusion Evaluation of Lung Cancer: Assessment Using Dual-input Perfusion Computed Tomography.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Imaging. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1097/RTI.0b013e318281dcee
AUTORES / AUTHORS: - Nakano S; Gibo J; Fukushima Y; Kaira K; Sunaga N; Taketomi-Takahashi A; Tsushima Y; Mori M
INSTITUCIÓN / INSTITUTION: - Departments of *Diagnostic Radiology and Nuclear Medicine double daggerRadiology, Gunma University Hospital, Maebashi section signDepartment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma daggerDepartment of Diagnostic Radiology, Ageo Central Hospital, Ageo, Saitama, Japan.
RESUMEN / SUMMARY: - PURPOSE:: The aim of this study was to investigate the feasibility of separately evaluating bronchial (BAP) and pulmonary arterial perfusion (PAP) of lung cancers using dual-input perfusion computed tomography. MATERIALS AND METHODS:: Twenty-nine lesions from 28 patients [19 men and 9 women; age, 65.8+/-11.3 y (mean+/-SD); range, 39 to 85 y] were included in this study (1 patient had 2 tumors). From computed tomography data, quantitative maps of PAP and BAP were created using the dual-input maximum-slope method. Total blood perfusion (TBP) was defined as the sum of PAP and BAP, and the percentage of PAP to TBP was defined as %PAP. Correlation of these values with tumor size, location, and pathologic type was statistically analyzed. RESULTS:: PAP ranged from 2.0 to 93.1 mL/min/100 mL (mean+/-SD, 26.8+/-26.4), BAP was 0 to 65.4 (25.1+/-19.12), TBP was 20.7 to 132.0 (52.0+/-29.0), and %PAP was 4% to 100% (48.8%+/-31.9%). PAP, TBP, and %PAP correlated negatively with tumor size (P<0.05). PAP and %PAP were higher in the peripheral zone than in the central zone (P<0.05). There was significant correlation between pathologic type and the respective perfusion parameters (P>0.05). CONCLUSIONS:: We were successful in separating the dual vascular supply to assess dual-input perfusion of lung cancer. We found perfusion of lung cancers to depend on tumor size and location. Acknowledging and assessing the dual vascular supply in lung perfusion may have clinical implications in the management of lung cancer treatment.
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[435]
TÍTULO / TITLE: - Pneumoconiosis and malignant mesothelioma in a family operated metal casting business that used industrial talc from New York State.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Ind Med. 2013 Feb 28. doi: 10.1002/ajim.22159.
●● Enlace al texto completo (gratuito o de pago) 1002/ajim.22159
AUTORES / AUTHORS: - Finkelstein MM
INSTITUCIÓN / INSTITUTION: - Department of Family and Community Medicine University of Toronto, Toronto, Ontario, Canada; Program in Occupational Health and Environmental Medicine McMaster University, Hamilton, Ontario, Canada. murray.finkelstein@utoronto.ca.
RESUMEN / SUMMARY: - BACKGROUND: The United States is second only to the People’s Republic of China in annual talc production. U.S. talc is used in the production of ceramics, paint, paper, plastics, roofing, rubber, cosmetics, flooring, caulking, and agricultural applications. A number of U.S. talc deposits consistently contain talc intergrown with amphiboles such as tremolite and/or anthophyllite. It has long been recognized that miners and millers of talc deposits are at risk for pneumoconiosis and it has recently been reported that it is prudent, on the balance of probabilities, to conclude that dusts from New York State talc ores are capable of causing mesothelioma in exposed workers. This is a report of the diagnosis of pneumoconiosis and mesothelioma in a husband and wife who operated a small metal casting business that used industrial talc from New York as a parting agent. METHODS: Case reports, including medical records and exposure histories, were provided by an attorney who had also commissioned laboratory investigation of the industrial talc product used in the factory. RESULTS: Mrs X was diagnosed with pneumoconiosis characterized by interstitial fibrosis and heavily calcified pleural plaques. Mr X had calcified pleural plaques and developed a fatal pleural mesothelioma. Samples of the industrial talc contained fibrous tremolite and anthophyllite. CONCLUSIONS: The author concludes that end users of industrial talc from New York State may be at risk of pneumoconiosis and malignant disease. End users of talcs from other regions of the United States, where talc formation arose from processes driven by regional metamorphism, might also be at risk. Am. J. Ind. Med. © 2013 Wiley Periodicals, Inc.
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[436]
TÍTULO / TITLE: - Patterns of DNA Mutations and ALK Rearrangement in Resected Node Negative Lung Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):408-414.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318283558e
AUTORES / AUTHORS: - Yip PY; Yu B; Cooper WA; Selinger CI; Ng CC; Kennedy CW; Kohonen-Corish MR; McCaughan BC; Trent RJ; Boyer MJ; Kench JG; Horvath LG; O’Toole SA
INSTITUCIÓN / INSTITUTION: - *Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; daggerKinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; double daggerSydney Medical School, University of Sydney, New South Wales, Australia; section signDepartment of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; ||Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; paragraph signSchool of Medicine, University of Western Sydney, New South Wales, Australia; #Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; and **St Vincent’s Clinical School, University of New South Wales, Australia.
RESUMEN / SUMMARY: - BACKGROUND:: Many studies have examined specific mutations in patients with resected lung adenocarcinoma across heterogeneous stages, comprising predominantly advanced/metastatic disease, but there is little data regarding the mutation profile of patients with early stage node negative disease. The aim of this study was to identify patterns of mutations in early stage node negative lung adenocarcinoma. METHODS:: A total of 204 patients who underwent resection for stage IB (sixth Ed American Joint Committee on Cancer) lung adenocarcinoma and received no neoadjuvant or adjuvant treatments were identified. Tumors were genotyped using the OncoCarta v1.0 kit (Sequenom, San Diego, CA) on the Sequenom MassARRAY platform. Fluorescence in situ hybridization for ALK rearrangement was also performed. RESULTS:: A total of 110 (54%) patients’ tumors harbored at least one mutation. KRAS, EGFR, PIK3CA, ALK, PDGFRA, AKT1, BRAF, FGFR1, and HRAS mutations were detected in tumors from 77 (37.7%), 29 (14.2%), 9 (4.4%), 2 (1%), 2 (1%), 1 (0.5%), 1 (0.5%), 1 (0.5%), and 1 (0.5%) patients respectively. Synchronous mutations (either comutations or double mutations) were identified in 18 (8.8%) patients. KRAS and PIK3CA mutations were associated with poorly differentiated tumors (p = 0.03; p = 0.02), whereas EGFR mutations were associated with well-differentiated tumors (p = 0.001). Five tumours contained EGFR mutations (one T790M and four exon 20 insertions), which are associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). CONCLUSIONS:: Diverse patterns of mutations are seen in resected node-negative lung adenocarcinoma including an unexpectedly low rate of ALK rearrangement, EGFR mutations associated with resistance to EGFR-TKIs and a high rate of synchronous mutations. These data may influence the design of future adjuvant targeted therapy trials.
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[437]
TÍTULO / TITLE: - Malignant pleural effusion resulting from metastasis of thyroid primaries: a cytomorphological analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Cytol. 2013;57(2):177-83. doi: 10.1159/000345696. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1159/000345696
AUTORES / AUTHORS: - Olson MT; Nuransoy A; Ali SZ
INSTITUCIÓN / INSTITUTION: - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
RESUMEN / SUMMARY: - BACKGROUND: Malignant serous cavity effusion caused by primary thyroid cancer is extremely rare in routine clinical practice. Therefore, it is often not included in the differential diagnostic workup of patients presenting with positive effusion cytology. METHODS: The clinical features were reviewed for 6 patients seen at our institution over the last 26 years for malignant effusion resulting from metastatic thyroid cancer. The cytomorphology from 4 of these cases was also reviewed. RESULTS: All of the patients found in this study presented with malignant pleural effusion - other serous cavity effusions resulting from metastatic thyroid carcinoma were not seen. These comprised 0.25% of all patients with a known history of thyroid carcinoma and 0.67% of all malignant pleural effusions. One patient had a history of bone metastases, but all the others had no pathological evidence of distant metastatic disease prior to the pleural effusion. CONCLUSIONS: Malignant pleural effusion rarely results from a thyroid carcinoma after some latency. The diagnosis requires immunohistochemical staining as well as the pertinent clinical context.
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[438]
TÍTULO / TITLE: - Perivascular epithelioid cell tumor located retroperitoneally with pulmonary lymphangioleiomyomatosis: report of a case.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Today. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0541-5
AUTORES / AUTHORS: - Pata G; Tironi A; Solaini L; Tiziano T; Ragni F
INSTITUCIÓN / INSTITUTION: - 2nd Division of General Surgery, Department of Medical and Surgical Sciences, Brescia Civic Hospital, P.le Spedali Civili 1, 25124, Brescia, Italy, giacomopata@alice.it.
RESUMEN / SUMMARY: - Perivascular epithelioid cell neoplasms, also known as “PEComas”, are unusual mesenchymal tumors, exhibiting perivascular epithelioid cell differentiation and characterized by a mixed myogenic and melanocytic phenotype. “PEComas not otherwise specified” (PEComas-NOS) are especially rare; consequently, there are no published large series, but only case reports. These tumors are rarely located retroperitoneally, with only about 15 such cases reported. We report a case of pulmonary diffuse lymphangioleiomyomatosis with large retroperitoneal PEComa-NOS in a 66-year-old woman. Treatment consisted only of tumor resection, without additional adjuvant therapy. We emphasize the importance of correct immunohistochemistry diagnosis, initiation of recommended treatment, and surveillance of this unique family of tumors.
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[439]
TÍTULO / TITLE: - CYP2A6 Genotype and Smoking Behavior in Current Smokers Screened for Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Subst Use Misuse. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 3109/10826084.2013.778280
AUTORES / AUTHORS: - Styn MA; Nukui T; Romkes M; Perkins KA; Land SR; Weissfeld JL
INSTITUCIÓN / INSTITUTION: - 1Department of Health and Community Systems, University of Pittsburgh School of Nursing, Pittsburgh , Pennsylvania USA.
RESUMEN / SUMMARY: - Functional CYP2A6 genetic variation partially determines nicotine metabolism. In 2005, we examined functional CYP2A6 variants associated with reduced metabolism (CYP2A6*2, CYP2A6*9, CYP2A6*4), smoking history, and change in smoking in 878 adult smokers undergoing lung cancer screening in an urban setting. At one year, 216 quit smoking for more than 30 days while 662 continued smoking. Compared to subjects who smoked 30 cigarettes per day at baseline, the odds of a reduced metabolism genotype was 52% higher in subjects smoking 20-29 cigarettes per day and 86% higher in subjects smoking less than 20 cigarettes per day (p-trend = 0.016). Reduced metabolism genotypes appeared unrelated to quitting. Though related to smoking dose, CYP2A6 may not influence cessation.
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[440]
TÍTULO / TITLE: - Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1308-14. doi: 10.3892/or.2013.2266. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2266
AUTORES / AUTHORS: - Suzuki M; Shiraishi K; Eguchi A; Ikeda K; Mori T; Yoshimoto K; Ohba Y; Yamada T; Ito T; Baba Y; Baba H
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556, Japan. smakoto@kumamoto-u.ac.jp
RESUMEN / SUMMARY: - Genome-wide DNA hypomethylation and gene hypermethylation play important roles in instability and carcino-genesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like growth factor binding protein 7 (IGFBP7) are known to be hypermethylated in various malignancies. The aim of the present study was to assess the precise methylation levels of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (NSCLC) using a pyrosequencing assay. Methylation of all regions was examined in 56 primary NSCLCs using a pyrosequencing assay. Changes in mRNA expression levels of SLIT2, MAL and IGFBP7 were measured before and after treatment with a demethylating agent. Methylation of these genes was also examined in 9 lung cancer cell lines using RT-PCR and a pyrosequencing assay. Frequencies of hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7, defined by predetermined cut off values, were 55, 64, 46 and 54% in NSCLCs, respectively and exhibited tumor-specific features. The hypermethylation of all genes was well correlated with changes in expression. The methylation level and frequency of MAL were significantly higher in smokers and in patients without EGFR mutations. Through accurate measurement of methylation levels using pyrosequencing, hypomethylation of LINE-1 and hypermethylation of SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various clinical features. Analysis of the methylation profiles of these genes may, therefore, provide novel opportunities for the therapy of NSCLCs.
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[441]
TÍTULO / TITLE: - Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Radiol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00330-013-2799-9
AUTORES / AUTHORS: - Heuvelmans MA; Oudkerk M; de Bock GH; de Koning HJ; Xie X; van Ooijen PM; Greuter MJ; de Jong PA; Groen HJ; Vliegenthart R
INSTITUCIÓN / INSTITUTION: - Center for Medical Imaging-North East Netherlands, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
RESUMEN / SUMMARY: - OBJECTIVE: To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals. METHODS: Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm3), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference. RESULTS: Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days. CONCLUSION: All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT </=232 days. Lowering the VDT cutoff may reduce false-positive referrals. KEY POINTS : * Lung nodules are common in CT lung cancer screening, most being benign * Short-term follow-up CT can identify fast-growing intermediate-size lung nodules * Most fast-growing nodules on short-term follow-up CT still prove to be benign * A new volume-doubling time (VDT) cut-off is proposed for lung screening * The optimised VDT cutoff may decrease false-positive case referrals for lung cancer.
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[442]
TÍTULO / TITLE: - Adenocarcinoma Contains More Immune Tolerance Regulatory T-cell Lymphocytes (Versus Squamous Carcinoma) in Non-small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lung. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s00408-013-9455-7
AUTORES / AUTHORS: - Black CC; Turk MJ; Dragnev K; Rigas JR
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA, Candice.C.Black@hitchcock.org.
RESUMEN / SUMMARY: - BACKGROUND: Regulatory T lymphocytes (Tregs) are known to have host-immune dampening effects in many tumors and to be associated with increased tumor recurrence. Pharmacologic therapies have been developed to target these cells and hence strengthen the host’s immune system. The FoxP3 gene is a marker of Tregs and can be visualized with immunohistochemistry (IHC). We investigated the presence and pattern of Tregs in non-small-cell lung tumors to determine possible therapeutic targets in lung cancer. METHODS: We selected archival samples of primary lung carcinoma and benign inflamed lung from 32 surgical resections. We created a tissue array containing duplicate cores from the N1 and N2 nodal stations from 16 of the cases along with paired benign lung and tumor. We used whole-slide analysis for the other 16 cases. We used FoxP3 IHC to visualize Tregs in all lymphoid tissue present and to assess the quantity and pattern within the tissues. RESULTS: All lymphoid tissue contains Tregs, but adenocarcinoma had significantly higher levels than both inflammatory lung controls and squamous carcinomas (p </= 0.008). Benign N1 lymph nodes (from patients with lung cancer) showed higher numbers of Tregs for adenocarcinoma versus squamous carcinoma. CONCLUSIONS: These findings reveal that Tregs are present in all lung tissues examined, but with significant enrichment in adenocarcinoma. This may lead to a more permissive microenvironment for adenocarcinoma and may explain aggressive patterns of tumor spread for this histology. Lung cancer patients with adenocarcinoma histology may benefit most from Treg-targeted therapy.
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[443]
TÍTULO / TITLE: - Effects of autocrine vascular endothelial growth factor (VEGF) in non-small cell lung cancer cell line A549.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biol Rep. 2013 Apr;40(4):3093-9. doi: 10.1007/s11033-012-2383-4. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1007/s11033-012-2383-4
AUTORES / AUTHORS: - Wang Y; Huang L; Yang Y; Xu L; Yang J; Wu Y
INSTITUCIÓN / INSTITUTION: - Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
RESUMEN / SUMMARY: - It is reported that the autocrine loop of the vascular endothelial growth factor (VEGF) is crucial for the survival and proliferation of non-small cell lung cancer (NSCLC) tumors. In this study we aimed to systematically investigate the role of autocrine vascular VEGF in NSCLC cell line A549 through inhibition of endogenous VEGF. A549 cells were transfected with florescence-labeled VEGF oligodeoxynucleotide with lipofectamine. For the experimental group, cells were transfected with VEGF anti-sense oligodeoxynucleotide (ASODN), sense oligodeoxynucleotide (SODN) and mutant oligodeoxynuleotide (MODN) respectively. For the control group cells were mock transfected with lipofectamine or culture medium. At indicated time point after transfection, the expression levels of VEGF mRNA and protein in A549 cells were analyzed by RT-PCR and ELISA respectively. Cell viability was measured by the MTT assay. Cell cycle distribution was detected by flow cytometry. As revealed by RT-PCR assay, the mRNA level of VEGF in cells transfected with ASDON was significantly lower than the other four groups (P < 0.05) at 24 and 48 h after transfection. ELISA assay yielded similar result with significantly decreased level of VEGF protein expression (P < 0.05). The survival fraction of A549 cells transfected with ASDON was significantly lower than the other four groups (P < 0.05) at 24 h after transfection. Also the percentage of G2 phase cells of ASODN group was significantly lower than other four groups. Our data indicate that VEGF expression is efficiently inhibited in A549 cells by ASODN transfection and this inhibition leads to inhibited cell growth and impaired cell cycle distribution.
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[444]
TÍTULO / TITLE: - Effect of rapamycin-induced tumor vessel thrombosis combined with docetaxel in non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Apr;24(4):406-14. doi: 10.1097/CAD.0b013e32835ec3b0.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32835ec3b0
AUTORES / AUTHORS: - Xu L; Qin Y; Huang J; Qin J; Gu J; Zhu H; Liu H; Cai Y; Wu X; Feng J
INSTITUCIÓN / INSTITUTION: - Departments of aRespiratory Medicine bHaematology cPathology dComprehensive Surgical Laboratory, Affiliated Hospital of Nantong University eDepartment of Pathological Staff Room, Nantong University, Nantong, Jiangsu, China.
RESUMEN / SUMMARY: - Lung cancer remains incurable in many cases despite current chemotherapies. We explored an approach combining a recently described antiangiogenic drug, rapamycin, with standard docetaxel cytotoxic therapy on the growth of non-small-cell lung cancer. Rapamycin alone inhibited tumor growth and upregulated apoptosis, with more pronounced effects when rapamycin and docetaxel were combined. Tumor vessel endothelium damage and thrombosis was evident with rapamycin treatment; this was concomitant with decreased microvessel density. In contrast, docetaxel was not antiangiogenic and did not reduce proliferation in tumors, despite its known cytotoxicity. Our data represent a new promising therapeutic regimen against non-small-cell lung cancer.
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[445]
TÍTULO / TITLE: - SIRT1 Regulates the Human Alveolar Epithelial A549 Cell Apoptosis Induced by Pseudomonas Aeruginosa Lipopolysaccharide.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Physiol Biochem. 2013;31(1):92-101. doi: 10.1159/000343352. Epub 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 1159/000343352
AUTORES / AUTHORS: - Liu X; Shao K; Sun T
INSTITUCIÓN / INSTITUTION: - Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
RESUMEN / SUMMARY: - Background: Sirtuin1 (SIRT1) is an NAD-dependent deacetylase that plays an inhibitory role in cell apoptosis, which is associated with p53 deacetylation. Lipopolysaccharide (LPS) is a key virulence factor produced by Pseudomonas aeruginosa and plays an important role in mediating the interactions between the bacterium and its host. However, the effect of SIRT1 in the regulation of LPS-induced human alveolar epithelial A549 cells apoptosis is unknown. Methods: Cell viability, apoptosis and reactive oxygen species (ROS) production were first examined in A549 cells that were treated with LPS. Relative cell signaling pathways were further explored by western blot analysis. Results: Exposure of A549 cells to LPS decreased cell viability in a concentration- and time- dependent manner. LPS stimulated cell apoptosis and ROS production while inhibiting the expression of SIRT1 in A549 cells. Activation of SIRT1 by exposure to resveratrol significantly reversed the effects of LPS on A549 cells. In contrast, inhibition of SIRT1 by nicotinamide had the opposite effects enhancing cell apoptosis and ROS production. Conclusion: SIRT1 plays an important role in regulating the human alveolar epithelial A549 cell apoptosis process induced by LPS.
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[446]
TÍTULO / TITLE: - FDG PET/CT Imaging of Extrapulmonary Small Cell Carcinoma of the Adrenal Gland.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318286bfcc
AUTORES / AUTHORS: - Dong A; Zuo C; Wang Y
INSTITUCIÓN / INSTITUTION: - From the Departments of *Nuclear Medicine, and daggerPathology, Changhai Hospital, Shanghai, China.
RESUMEN / SUMMARY: - Extrapulmonary small cell carcinoma (SCC) is an uncommon malignancy. A 57-year-old man was referred because of a 1-month history of left lumbago. MR images showed an ovoid tumor in the left adrenal gland. FDG PET/CT showed intense FDG uptake of the left adrenal tumor with thrombosis of the left renal vein. The patient underwent left adrenalectomy and nephrectomy. Histopathology revealed typical adrenal SCC with neoplastic thrombosis of the left renal vein. This case suggests that FDG PET/CT is useful for staging of extrapulmonary SCC.
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[447]
TÍTULO / TITLE: - MicroRNAs as lung cancer biomarkers and key players in lung carcinogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Biochem. 2013 Feb 8. pii: S0009-9120(13)00052-0. doi: 10.1016/j.clinbiochem.2013.01.024.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinbiochem.2013.01.024
AUTORES / AUTHORS: - Vannini I; Fanini F; Fabbri M
INSTITUCIÓN / INSTITUTION: - IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) S.r.l., Meldola, 47014 FC, Italy; Istituto Oncologico Romagnolo Coop. Soc. ONLUS, Forli, 47121 FC, Italy.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer deaths worldwide and few genetic markers enable to evaluate lung cancer risk. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during various cell processes such as apoptosis, differentiation and development. In these last years, many works confirm a role for miRNAs in the initiation and progression of lung cancer. miRNA profiling has the potential to classify tumors with high accuracy and predict outcome. Here, we describe the roles of miRNA in lung carcinogenesis and the possibility to use them as biological markers for diagnostic, prognostic and predictive purposes.
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[448]
TÍTULO / TITLE: - First-Line Management of EGFR-Mutated Advanced Lung Adenocarcinoma: Recent Developments.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Drugs. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s40265-013-0020-8
AUTORES / AUTHORS: - Liao BC; Lin CC; Yang JC
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
RESUMEN / SUMMARY: - Gefitinib and erlotinib are small-molecule reversible tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR). Objective responses have been observed frequently in patients with non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations, the most common being deletions in exon 19 and the exon 21 L858R mutation. EGFR mutations are prevalent in female patients, those who have never smoked, those of Asian ethnicity and those who have adenocarcinoma histology. Given the efficacy of EGFR TKIs in advanced NSCLC in the salvage setting, and their favourable toxicity profile compared with conventional chemotherapy, there is considerable interest in evaluating their efficacy in the first-line treatment of advanced NSCLC. To date, there have been several phase II and phase III studies that have examined the efficacy of first-line single-agent EGFR TKIs in unselected, clinically selected or molecularly selected populations. Here we review and compare the differences in these phase III trials. Most phase III trials chose progression-free survival (PFS) rather than overall survival (OS) as their primary endpoint. PFS was prolonged but OS was not. The recent development of novel irreversible EGFR TKIs, such as afatinib and dacomitinib, is also reviewed.
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[449]
TÍTULO / TITLE: - Non-functional parathyroid gland carcinoma, a rare malignant tumor of the head and neck.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:23-5.
AUTORES / AUTHORS: - Kotromanovic Z; Birtic D; Vceva A; Medic D; Zubcic Z; Mihalj H; Kotromanovic Z; Eric S; Dmitrovic B; Stefanic M
INSTITUCIÓN / INSTITUTION: - “J. J. Strossmayer” University, Osijek University Hospital Centre, Department of Otorhinolaryngology Head and Neck Surgery, Osijek, Croatia.
RESUMEN / SUMMARY: - Carcinoma of the parathyroid gland is a very rare tumor of the head and neck. The largest number of carcinomas are discovered by chance. (intraoperatively, during surgery removal of the parathyroid gland are adenomas). Around 1% of the primary parathyreoidism is caused by the cancer of parathyroid glands. Only 10% of these rare tumors make up dysfunctional cancer of parathyroid glands. There have been 24 cases reported of this disease in the literature. The focus of our study is to present a case of this disease and to review the published literature to date.
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[450]
TÍTULO / TITLE: - Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Cancer Prev. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1097/CEJ.0b013e32835f3be9
AUTORES / AUTHORS: - Tang D; Shen Y; Wang M; Yang R; Wang Z; Sui A; Jiao W; Wang Y
INSTITUCIÓN / INSTITUTION: - aDepartment of Thoracic Surgery bCentral Laboratory, The Affiliated Hospital, Medical College, Qingdao University, Qingdao, China.
RESUMEN / SUMMARY: - Recent diagnostic procedure advances have considerably improved early lung cancer detection. However, the invasive, unpleasant, and inconvenient nature of current diagnostic procedures limits their application. There is a great need for novel noninvasive biomarkers for early lung cancer diagnosis. In the present study, we aimed to determine whether microRNA (miRNA) blood signatures are suitable for early detection of lung cancer. Using quantitative reverse transcriptase PCR analysis, we first selected and identified three aberrant plasma expression miRNAs (miR-21, miR-145, and miR-155) in a training set of 62 patients and 60 healthy smokers to define a panel that had high diagnostic efficiency for lung cancer. Then, we validated the detective ability of this miRNA panel in a testing set of 34 malignant tumor patients, 30 patients with benign pulmonary nodules and 32 healthy smokers. In the training set, miR-21 and miR-155 showed higher plasma expression levels, whereas miR-145 showed a lower expression level in patients with malignant cancer, compared with healthy controls (P</=0.001). The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.847, which helped distinguish lung cancer from healthy smokers with 69.4% sensitivity and 78.3% specificity. A logistic regression model with the best prediction was constructed on the basis of miR-21, miR-145, and miR-155. Validation of the miRNA panel in the testing set confirmed their diagnostic value, which yields a significant improvement over any single one. Plasma miR-21, miR-145, and miR-155 have strong potential as novel noninvasive biomarkers for early detection of lung cancer.
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[451]
TÍTULO / TITLE: - Ineffectiveness of Crizotinib on Brain Metastases in Two Cases of Lung Adenocarcinoma with EML4-ALK Rearrangement.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):e30-1. doi: 10.1097/JTO.0b013e318288dc2d.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318288dc2d
AUTORES / AUTHORS: - Maillet D; Martel-Lafay I; Arpin D; Perol M
INSTITUCIÓN / INSTITUTION: - *Centre Leon Berard, Lyon Cedex, France; and daggerCentre Hospitalier de Macon, Boulevard Louis Escande, Macon, France.
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[452]
TÍTULO / TITLE: - A Retrospective Study of the Novel Combination of Paclitaxel and S1 for Pretreated Advanced Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chemotherapy. 2013 Jan 31;58(6):454-460.
●● Enlace al texto completo (gratuito o de pago) 1159/000345624
AUTORES / AUTHORS: - Aono N; Ito Y; Nishino K; Uchida J; Kumagai T; Akazawa Y; Okuyama T; Yoshinami T; Imamura F
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
RESUMEN / SUMMARY: - Background: Recently, multiple-line chemotherapy has become popular for non-small cell lung cancer (NSCLC). The survival time of patients is influenced by patient characteristics and subsequent treatments. Methods: The usefulness of paclitaxel plus S1 (PTX+S1) was evaluated in 46 pretreated NSCLC patients. Time from the start of individual regimens till the start of the next one (TNR) was calculated for regimens administered to the study population including PTX+S1 and analyzed by the shared frailty Cox model. Results: The response rate and the median progression-free survival time of PTX+S1 were 32.6% and 253 days, respectively. Substantial difference in TNR was observed in epidermal growth factor receptor mutation status and in line and type of regimens, but not in stage, age, sex, performance status and histology, by univariate analysis. Multivariate analysis revealed that PTX+S1 was only one factor to prolong TNR. Conclusion: Because of long progression-free survival and long TNR, further evaluation of PTX+S1 is necessary.
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[453]
TÍTULO / TITLE: - Bronchoscopic findings for bevacizumab-related pulmonary hemorrhage in advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Invest New Drugs. 2013 Mar 24.
●● Enlace al texto completo (gratuito o de pago) 1007/s10637-013-9951-x
AUTORES / AUTHORS: - Okamoto K; Okamoto I; Miyazaki M; Tanaka K; Kaneda H; Nakagawa K
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
RESUMEN / SUMMARY: - We report contemporaneous bronchoscopic findings for a case of bevacizumab-related pulmonary hemorrhage in a patient with advanced non-small cell lung cancer (NSCLC). Flexible bronchoscopy at diagnosis revealed abnormal capillary dilation that was suggestive of endobronchial involvement at the primary tumor location. The patient developed massive hemoptysis despite of marked tumor shrinkage achieved by bevacizumab-containing chemotherapy. Emergency flexible bronchoscopy for hemoptysis suggested that the location of the primary tumor was the source of bleeding. Subsequent follow-up flexible bronchoscopy revealed an ulcerative mucosal-like lesion associated with a white necrotic substance as well as attenuation of the dilation of submucosal vessels compared with that apparent at diagnosis. Our case report highlights the potential mechanistic insights into bevacizumab-related bleeding and importance of performing bronchoscopy at diagnosis in NSCLC patients, given that abnormal bronchoscopic findings may be a risk factor for bleeding.
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[454]
TÍTULO / TITLE: - Response to crizotinib rechallenge after initial progression and intervening chemotherapy in ALK lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):e21. doi: 10.1097/JTO.0b013e31827a892c.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827a892c
AUTORES / AUTHORS: - Browning ET; Weickhardt AJ; Camidge DR
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Division of Medical Oncology, University of Colorado Denver, Aurora, CO 80045, USA. Eiko.browning@ucdenver.edu
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[455]
TÍTULO / TITLE: - Larynx preservation: advantages and limitations.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:231-3.
AUTORES / AUTHORS: - Rakusic Z; Bisof V
INSTITUCIÓN / INSTITUTION: - University of Zagreb, Zagreb University Hospital Center, Department of Oncology, Zagreb, Croatia. zoran.rakusic1@zg.t-com.hr
RESUMEN / SUMMARY: - For a long time standard treatment approach for resectable squamous cell carcinoma of larynx was surgery with or without subsequent radiotherapy. Surgery, particulary total laryngectomy, has been associated with serious impairment of quallity of life. Between nonsurgical approaches, concurrent cisplatin based chemoradiotherapy has become a very promising treatment modality for larynx preservation. However, concurrent chemotherapy has been associated with serious toxicity. The most recent treatment approach in larynx preservation is related to taxan based induction chemotherapy.
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[456]
TÍTULO / TITLE: - Justice and lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Philos. 2013 Apr;38(2):219-34. doi: 10.1093/jmp/jht001. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1093/jmp/jht001
AUTORES / AUTHORS: - Wilson A
INSTITUCIÓN / INSTITUTION: - *Department of Philosophy, University of Miami, Coral Gables, FL 33124, USA. aaron.philosophy@gmail.com.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer deaths, yet research funding is by far the lowest for lung cancer than for any other cancer compared with respective death rates. Although this discrepancy should appear alarming, one could argue that lung cancer deserves less attention because it is more attributable to poor life choices than other common cancers. Accordingly, the general question that I ask in this article is whether victims of more avoidable diseases, such as lung cancer, deserve to have their needs taken into less consideration than those of less avoidable diseases, on the grounds of either retributive or distributive justice. Such unequal treatment may be the “penalty” one incurs for negligent or reckless behavior. However, I hope to show that such unequal treatment cannot be supported by any coherent accounts of retributive or distributive justice.
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[457]
TÍTULO / TITLE: - A 75-year-old man with progressive bronchioalveolar carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Semin Oncol. 2013 Feb;40(1):e1-8. doi: 10.1053/j.seminoncol.2012.11.004.
●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.004
AUTORES / AUTHORS: - Baikadi M; Lovly C; Horn L; Reckamp KL; Noonan K; Laskin J; Morris GJ
INSTITUCIÓN / INSTITUTION: - Northeast Radiation Oncology Center Scranton, PA, USA.
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[458]
TÍTULO / TITLE: - Epidemiology of laryngeal cancer in Osijek-Baranja County (eastern Croatia).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Coll Antropol. 2012 Nov;36 Suppl 2:107-10.
AUTORES / AUTHORS: - Rosso M; Kraljik N; Mihaljevic I; Siric L; Sos D; Vranjes Z
INSTITUCIÓN / INSTITUTION: - J. J. Strossmayer University, Osijek University Hospital Centre, Department of Otorhinolaryngology and Head and Neck Surgery, Osijek, Croatia. rossom@net.hr
RESUMEN / SUMMARY: - The aim of this retrospective study was to provide the incidence and mortality rate for all patients with laryngeal carcinoma diagnosed in Osijek-Baranja County, during the period of 1999-2008. In this period, there were 329 registered patients, from which 301 (91.5%) males, and 28 (8.5%) females. Age-standardized rate (ASR World) laryngeal cancer incidence was 6.4/100,000 (13.4/100,000 for males and 0.9/100,000 for females). In the same period, 238 people, including 224 (94.1%) men and 14 (5.9%) women died of laryngeal carcinoma. Age-standardized rate (ASR World) laryngeal cancer mortality was 4.4/100,000 (9.8/100,000 for males and 0.5/100 000 for females). There is a significant decline in mortality in males and increased mortality in females. Laryngeal carcinoma is a significant public health problem in the Osijek-Baranja county. Although the study period shows a tendency to decrease in the number of new cases and deaths, in the times ahead it is important to focus the emphasis on prevention and early detection with the goal of reducing incidence and mortality.
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[459]
TÍTULO / TITLE: - Increased mean lung density: Another independent predictor of lung cancer?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Radiol. 2013 Feb 20. pii: S0720-048X(13)00054-5. doi: 10.1016/j.ejrad.2013.01.020.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejrad.2013.01.020
AUTORES / AUTHORS: - Sverzellati N; Randi G; Spagnolo P; Marchiano A; Silva M; Kuhnigk JM; La Vecchia C; Zompatori M; Pastorino U
INSTITUCIÓN / INSTITUTION: - Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma, Italy. Electronic address: nicola.sverzellati@unipr.it.
RESUMEN / SUMMARY: - OBJECTIVES: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. METHODS: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n=119) and controls (n=989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. RESULTS: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1s (FEV(1)) independently of MLD (OR 5.37, 95% CI: 2.63-10.97 for FEV(1)<60% vs. FEV(1)>/=90%), and with increasing MLD independently of FEV(1) (OR 3.00, 95% CI: 1.60-5.63 for MLD>-823 vs. MLD<-857 Hounsfield units). CONCLUSION: Emphysema per se was not associated with lung cancer whereas decreased FEV(1) was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.
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[460]
TÍTULO / TITLE: - Multiple Primary Hepatic Malignant Mesotheliomas Mimicking Cystadenocarcinomas on Enhanced CT and FDG PET/CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31828da61d
AUTORES / AUTHORS: - Dong A; Dong H; Zuo C
INSTITUCIÓN / INSTITUTION: - From the *Department of Nuclear Medicine, Changhai Hospital, and daggerDepartment of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
RESUMEN / SUMMARY: - A 50-year-old woman presented with upper abdominal pain for 2 months. Abdominal enhanced CT showed multiple hypodense cystic tumors in the liver with heterogeneous enhanced septations. FDG PET/CT showed hypermetabolic peripheral regions and internal septations of the tumors with SUVmax of 6.3. Multiple hepatic cystadenocarcinomas were suspected. The patient underwent resection of the tumors. Epithelial mesothelioma was confirmed by pathology. This case indicates primary hepatic mesothelioma should be added to the differential diagnosis of FDG-avid malignant hepatic tumors.
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[461]
TÍTULO / TITLE: - Balancing radiation pneumonitis versus locoregional tumor control in non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):e35-6. doi: 10.1097/JTO.0b013e318286ce6c.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e318286ce6c
AUTORES / AUTHORS: - Troost EG; Hoffmann AL; Bussink J
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Radiation Oncology, Radboud University Nijmegen, Medical Centre, Nijmegen, The Netherlands.
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[462]
TÍTULO / TITLE: - Role of 18F-FDG PET/CT in the Staging of Pediatric Peritoneal Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318266cc21
AUTORES / AUTHORS: - Abikhzer G; Gourevich K; Arkovitz M; Postovsky S; Keidar Z
INSTITUCIÓN / INSTITUTION: - From the Departments of *Nuclear Medicine, daggerPediatric Surgery, and double daggerPediatric Oncology, Rambam Health Care Campus, Haifa, Israel.
RESUMEN / SUMMARY: - A 7-year-old girl with a 1-month history of diffuse abdominal pain underwent an ultrasound which showed a pelvic mass with multiple peritoneal implants and ascites. An US-guided core biopsy of one of the implants as well as a transrectal biopsy of the pelvic tumor showed pathological findings consistent with epithelioid mesothelioma. We describe the findings on F-FDG PET/CT in pediatric peritoneal mesothelioma.
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[463]
TÍTULO / TITLE: - Rare pleural tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Chest Med. 2013 Mar;34(1):113-36. doi: 10.1016/j.ccm.2012.12.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ccm.2012.12.001
AUTORES / AUTHORS: - Erb CT; Johnson KM; Kim AW
INSTITUCIÓN / INSTITUTION: - Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, 300 Cedar Street, TAC S-441, New Haven, CT 06520, USA.
RESUMEN / SUMMARY: - Primary pleural tumors other than mesothelioma account for fewer than 1% of all lung cancers, and consequently they pose diagnostic and management challenges. Their treatment must be targeted toward the specific tumor type and is often quite different from the treatment for mesothelioma or metastases. Despite the best efforts at diagnosing and treating these tumors, the prognosis associated with some of the benign and many of the malignant variants of these tumors remains poor. In this review, we describe the radiologic and pathologic features of the less common primary pleural tumors and propose a diagnostic approach to their evaluation.
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[464]
TÍTULO / TITLE: - Unclassified pleomorphic and spindle cell pulmonary neoplasm with brain metastases after prasugrel.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cardiology. 2013;124(2):85-90. doi: 10.1159/000346382. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1159/000346382
AUTORES / AUTHORS: - Serebruany VL; Dinicolantonio JJ; Can MM; Goto S
INSTITUCIÓN / INSTITUTION: - Heart Drug Research Laboratories, Johns Hopkins University, Towson, Md., USA.
RESUMEN / SUMMARY: - Background: There was an excess of new solid neoplasms (112 vs. 69), and cancer deaths (24 vs. 15) after prasugrel in the TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition). These cancers usually occur after 4 months following prasugrel, and women are especially at risk. The hypothesis has been offered that prasugrel, but not aspirin or clopidogrel, causes indirect modulation of tumor growth, and/or enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates via the inability to keep cancer locally within the platelet thrombi due to excessive chronic platelet inhibition. Case Report: A 70-year old female diabetic patient underwent drug-eluting stent implantation. The patient received a loading dose of prasugrel (60 mg), followed by prasugrel 10 mg/daily as well as aspirin (81 mg/daily). After 4 months on dual antiplatelet therapy she expectorated blood when coughing. A lung X-ray and CT scan revealed numerous lung nodules later diagnosed as unclassified pleomorphic and spindle cell malignant solid neoplasm. The patient died following multiple brain metastasis. Conclusion: Female gender, duration of prasugrel exposure, rare unclassified neoplasm pathology type and a tumor of a highly metastatic and aggressive nature in the index patient should be regarded with caution. The effects of novel antiplatelet agents on the onset of cancer should be tested in future mega-trials.
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[465]
TÍTULO / TITLE: - PET/CT Demonstration and Monitoring of Thoracic and Abdominal Wall Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182867d38
AUTORES / AUTHORS: - Nguyen BD
INSTITUCIÓN / INSTITUTION: - From the Department of Radiology, Mayo Clinic, Scottsdale, Arizona.
RESUMEN / SUMMARY: - Mesothelioma is a malignancy arising from the embryonic coelomic mesodermal lining forming the pleura, peritoneum, pericardium, and tunica vaginalis. It is mostly induced by exposure to asbestos. The author presents a 77-year-old woman with an atypical manifestation of epithelioid mesothelioma, which does not follow the expected clinical characteristics of this disease mentioned above. In this case, PET/CT provides useful information concerning the extension of the lesions to thoracic and abdominal walls not fully evaluated by the initial conventional cross-sectional imaging. PET/CT also allows an accurate therapeutic monitoring of the disease.
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[466]
TÍTULO / TITLE: - Surgery in Mesothelioma - Where Do We Go after MARS?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31828353d7
AUTORES / AUTHORS: - Hiddinga BI; van Meerbeeck JP
INSTITUCIÓN / INSTITUTION: - *Department of Thoracic Oncology, Antwerp University Hospital, Antwerp, Belgium; and daggerDepartment of Thoracic Oncology, Ghent University Hospital, Ghent, Belgium.
RESUMEN / SUMMARY: - The role of surgery in the management of malignant pleural mesothelioma remains controversial. Surgical resection consists of different procedures for diagnostic or therapeutic reasons. The latter includes either an extrapleural pleuropneumonectomy (EPP) or lung-sparing operations like debulking of the parietal and visceral pleura by pleurectomy/decortication (P/D) or extended pleurectomy/decortication, in which further debulking of the diaphragm or pericardium is included. Because of the modest outcome of surgery as single-modality therapy, combinations of chemotherapy, surgery, and radiation therapy were initiated as a new treatment strategy to improve prognosis. The observations that patients treated with P/D had an equal to better outcome than those treated with EPP, and that EPP with perioperative chemotherapy was better than EPP alone, raises the issue whether performing a P/D with perioperative chemotherapy would result in a further improvement of outcome with a lower operative mortality than with EPP and perioperative chemotherapy. This is the rationale for the next European Organisation for Research and Treatment of Cancer trial exploring the feasibility of P/D with perioperative chemotherapy.
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[467]
TÍTULO / TITLE: - Pulmonary Neuroendocrine Tumor Incidentally Detected by 18F-CH PET/CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Apr;38(4):e196-9. doi: 10.1097/RLU.0b013e318266cbf1.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318266cbf1
AUTORES / AUTHORS: - Treglia G; Lococo F; Petrone G; Inzani F; Perotti G; Porziella V; Granone P; Rindi G; Giordano A; Rufini V
INSTITUCIÓN / INSTITUTION: - From the *Institute of Nuclear Medicine and daggerDepartment of Thoracic Surgery; and double daggerInstitute of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
RESUMEN / SUMMARY: - We report the case of a pulmonary neuroendocrine tumor (NET) incidentally detected by F-CH PET/CT performed during restaging in a 68-year-old patient affected by prostate cancer. To clarify the nature of the pulmonary lesion, the patient underwent a CT-guided biopsy which revealed the presence of a pulmonary NET. A subsequent Ga-DOTANOC PET/CT demonstrated the somatostatin receptor expression in the pulmonary lesion. The patient underwent a right lung lobectomy; at pathology, a well-differentiated NET was confirmed. Our case highlights that pulmonary NETs should be considered in the differential diagnosis of pulmonary lesions showing uptake of radiolabeled choline.
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[468]
TÍTULO / TITLE: - Heterogeneous 18F-FDG Uptake in Recurrent Respiratory Papillomatosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182868af9
AUTORES / AUTHORS: - Yu JP; Barajas RF Jr; Olorunsola D; Sugrue LP; Hernandez-Pampaloni M
INSTITUCIÓN / INSTITUTION: - From the Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.
RESUMEN / SUMMARY: - Recurrent respiratory papillomatosis (RRP) describes an infection of the upper aerodigestive tract by the human papilloma virus most commonly affecting the larynx with rare lung involvement in 1%-2% of affected patients. We describe an unusual case of a 28-year-old male patient with a longstanding history of RRP where a whole-body PET/CT obtained for disease staging revealed multiple cavitary pulmonary nodules in addition to the more typical tracheobronchial papillomas. In the case described herein, we report heterogeneous uptake of F-FDG among these RRP lesions, suggesting significant unexpected variability in the underlying metabolic behavior of these lesions.
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[469]
TÍTULO / TITLE: - Np63 (p40) Distribution Inside Lung Cancer: A Driver Biomarker Approach to Tumor Characterization.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Surg Pathol. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1177/1066896913476750
AUTORES / AUTHORS: - Pelosi G; Rossi G; Cavazza A; Righi L; Maisonneuve P; Barbareschi M; Graziano P; Pastorino U; Garassino M; de Braud F; Papotti M
RESUMEN / SUMMARY: - DeltaNp63 (henceforth simply p40) is a squamous/basal-type biomarker corresponding to nontransactivating (non-TA) isoforms of p63 gene. Its prospective relevance as driver biomarker in lung cancer has not yet been thoroughly investigated. In all, 72 adenocarcinomas (ADs), 27 squamous cell carcinomas (SQCs), 13 pleomorphic carcinomas (PLCs), 10 small-cell lung carcinomas (SCLCs), 5 large-cell neuroendocrine carcinomas (LCNECs), 5 adenosquamous carcinomas (ADSQCs), 3 large-cell carcinomas with basaloid features (B-LCC), 2 carcinoids, 2 carcinosarcomas (CS), 2 salivary-gland type tumors (SGTTs) of the lung, and 5 pleural malignant epithelioid mesotheliomas (MEMs) were prospectively diagnosed by morphology and verified by immunohistochemistry for p40, p63, and thyroid transcription factor 1 (TTF1). Histological scores (HS) were devised by multiplying the percentage of immunoreactive cells (0 to 100%) by immunostaining intensity (low = 1 vs strong = 2, according to internal controls). There was a nonrandom distribution of p40 across the diverse tumor groups and cell differentiation lineages, with p40-HS > 100 closely paralleling squamous or myoepithelial carcinomas (SQC, B-LCC, SQC-containing PLC, ADSQC with predominant SQC, SGTT), and p40-HS </= 10 pinpointing AD, AD-containing PLC, or CS and neuroendocrine (NE) tumors. At variance, p63-HS was significantly higher than p40 in AD (P < .0001) and NE tumors (P = .0156), with positive predictive value being 83% and 95% and overall accuracy being 95% and 99%, respectively. Also, TTF1 was shared by gland-differentiated and NE tumors. MEM cases were always negative for all biomarkers. The HS-guided assessment of p40 allowed an effective orientation among thoracic malignancies at the level of individual tumor patients thereby contributing to prospectively realize a driver, holistic approach to cancer characterization.
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[470]
TÍTULO / TITLE: - Incidence of non-small-cell lung cancer among California Hispanics according to neighborhood socioeconomic status.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):287-94. doi: 10.1097/JTO.0b013e31827bd7f5.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827bd7f5
AUTORES / AUTHORS: - Wong ML; Clarke CA; Yang J; Hwang J; Hiatt RA; Wang S
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University of California-San Francisco, CA, USA.
RESUMEN / SUMMARY: - INTRODUCTION: Lung cancer incidence is associated with markers of lower socioeconomic status (SES) in whites, blacks, and Asians but with markers of higher SES in Hispanics. The magnitude and etiology of this positive gradient in Hispanics remain undefined. We examined non-small-cell lung cancer (NSCLC) incidence and ever-smoking rates among California Hispanics according to measures of SES. METHODS: We computed neighborhood (n)SES-specific incidence rates by sex and race or ethnicity for 74,179 NSCLC cases in the California Cancer Registry, 1998-2002. Associations between nSES and NSCLC incidence were examined, using incidence rate ratios and linear trend tests, and stratified by age, stage, and histology. Ever-smoking rates among Hispanics were obtained from California Health Interview Survey 2001 data, and odds ratios for ever-smoking were calculated for measures of SES and acculturation. RESULTS: Compared with the lowest nSES quintile, the NSCLC incidence in the highest quintile was 1.86 and 1.18 times higher for Hispanic women and men, respectively. The positive nSES gradients remained significant for all ages, stages, and nonsquamous histologies in women, and only for older age, local or regional stages, and adenocarcinoma histology in men. Ever-smoking rates were associated with English-speaking households and U.S.-born status for Hispanic women and low education and U.S.-born status for Hispanic men. CONCLUSIONS: For California Hispanics, higher nSES was strongly associated with increased NSCLC incidence in women, but weakly associated in men, and ever-smoking rates were strongly correlated with increased acculturation. This finding may portend an increasing burden of NSCLC in Hispanic women, given future trends in acculturation and SES.
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[471]
TÍTULO / TITLE: - Targeting c-MET in the battle against advanced nonsmall-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Opin Oncol. 2013 Mar;25(2):130-6. doi: 10.1097/CCO.0b013e32835daf37.
●● Enlace al texto completo (gratuito o de pago) 1097/CCO.0b013e32835daf37
AUTORES / AUTHORS: - Landi L; Minuti G; D’Incecco A; Cappuzzo F
INSTITUCIÓN / INSTITUTION: - Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
RESUMEN / SUMMARY: - PURPOSE OF REVIEW: The mesenchymal-epidermal transition (c-MET) receptor tyrosine kinase has a central role in the cancer cell’s survival. MET and its ligand, hepatocyte growth factor (HGF), have recently been identified as promising targets in solid tumors, including nonsmall-cell lung cancer (NSCLC). RECENT FINDINGS: Aberrant MET activation can be the result of different mechanisms such as MET and HGF overexpression, MET gene amplification or mutation. Retrospective studies in NSCLC showed that MET gene copy number is a negative prognostic factor, although few data are available on the role of MET mutations. In preclinical models, cell lines with MET gene amplification are extremely sensitive to MET inhibition. Although the inner presence of gene amplification is a rare event (1-7% cases), MET amplification has emerged as one of the critical events for acquired resistance in epidermal growth factor receptor (EGFR) mutated lung adenocarcinomas refractory to EGFR-tyrosine kinase inhibitors (TKIs). In NSCLC with acquired resistance to EGFR-TKIs, MET amplification occurs in up to 20% cases and preclinical and clinical data indicated MET and EGFR co-inhibition as a potential effective strategy to overcome resistance. SUMMARY: MET has recently emerged as a promising target, and ongoing trials will clarify the role of anti-MET strategies in NSCLC.
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[472]
TÍTULO / TITLE: - Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar;8(3):322-8. doi: 10.1097/JTO.0b013e31827db604.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31827db604
AUTORES / AUTHORS: - Sholl LM; Weremowicz S; Gray SW; Wong KK; Chirieac LR; Lindeman NI; Hornick JL
INSTITUCIÓN / INSTITUTION: - Department of Pathology Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA. lmsholl@partners.org
RESUMEN / SUMMARY: - INTRODUCTION: ALK gene rearrangements occur in approximately 5% of lung adenocarcinomas (ACAs), leading to anaplastic lymphoma kinase (ALK) overexpression and predicting response to targeted therapy. Fluorescence in situ hybridization (FISH) is the standard procedure for detection of ALK rearrangements in lung ACA but requires specialized equipment and expertise. Immunohistochemistry (IHC) for ALK protein overexpression is a promising screening modality, with reports of newer antibodies showing excellent sensitivity and specificity for ALK-rearranged lung ACA. METHODS: In this study, we analyzed ALK IHC (5A4 clone) in 186 cases from our clinical service and compared it with ALK FISH and EGFR and KRAS mutation status. RESULTS: Twelve cases had concordant ALK protein overexpression and ALK rearrangement by FISH. Three ALK-rearranged cases lacked ALK protein expression. Of these discrepant cases, one had a coexisting EGFR mutation and a subtle atypical ALK rearrangement manifested as a break in the 5’ centromeric portion of the FISH probe. One case had a concurrent BRAF mutation. Follow-up testing on a metastasis revealed absence of the ALK rearrangement, with persistent BRAF mutation. In one ALK-rearranged protein negative case, very limited tissue remained for ALK IHC, raising the possibility of false negativity because of protein expression heterogeneity. Importantly, ALK protein expression was detected in one case initially thought not to have an ALK rearrangement. In this case, FISH was falsely negative because of interference by benign reactive nuclei. After correcting for these cases, ALK IHC was 93% sensitive and 100% specific as compared with FISH. CONCLUSIONS: ALK IHC improves the detection of ALK rearrangements when used together with FISH, and its use in lung ACA genetic testing algorithms should be considered.
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[473]
TÍTULO / TITLE: - Pathobiological Implications of MUC4 in Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Apr;8(4):398-407.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e3182829e06
AUTORES / AUTHORS: - Majhi PD; Lakshmanan I; Ponnusamy MP; Jain M; Das S; Kaur S; Shimizu ST; West WW; Johansson SL; Smith LM; Yu F; Rolle CE; Sharma P; Carey GB; Batra SK; Ganti AK
INSTITUCIÓN / INSTITUTION: - *Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE; daggerDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE; double daggerEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE; section signCenter for Collaboration on Research, Design and Analysis, College of Public Health, University of Nebraska Medical Center, Omaha, NE; ||Department of Biostatistics College of Public Health, University of Nebraska Medical Center, Omaha, NE; paragraph signSection of Hematology-Oncology Department of Medicine, University of Chicago, Chicago, IL; #Department of Pathology and Creighton Medical Laboratories, Creighton University Medical Center, Omaha, NE; **Department of Internal Medicine, VA Nebraska-Western Iowa Health Care System, Omaha, NE; daggerdaggerDivision of Oncology-Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE.
RESUMEN / SUMMARY: - INTRODUCTION:: Altered expression of MUC4 plays an oncogenic role in various cancers, including pancreatic, ovarian, and breast. This study evaluates the expression and role of MUC4 in non-small-cell lung cancer (NSCLC). METHODS:: We used a paired system of MUC4-expressing (H292) and MUC4-nonexpressing (A549) NSCLC cell lines to analyze MUC4-dependent changes in growth rate, migration, and invasion using these sublines. We also evaluated the alterations of several tumor suppressor, proliferation, and metastasis markers with altered MUC4 expression. Furthermore, the association of MUC4 expression (by immunohistochemistry) in lung cancer samples with patient survival was evaluated. RESULTS:: MUC4-expressing lung cancer cells demonstrated a less proliferative and metastatic phenotype. Up-regulation of p53 in MUC4-expressing lung cancer cells led to the accumulation of cells at the G2/M phase of cell cycle progression. MUC4 expression attenuated Akt activation and decreased the expression of Cyclins D1 and E, but increased the expression of p21 and p27. MUC4 expression abrogated cancer cell migration and invasion by altering N- & E-cadherin expression and FAK phosphorylation. A decrease in MUC4 expression was observed with increasing tumor stage (mean composite score: stage I, 2.4; stage II, 1.8; stage III, 1.4; and metastatic, 1.2; p = 0.0093). Maximal MUC4 expression was associated with a better overall survival (p = 0.042). CONCLUSION:: MUC4 plays a tumor-suppressor role in NSCLC by altering p53 expression in NSCLC. Decrease in MUC4 expression in advanced tumor stages also seems to confirm the novel protective function of MUC4 in NSCLC.
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[474]
TÍTULO / TITLE: - Visceral Pleural Invasion Classification in Non-Small-Cell Lung Cancer in the 7th Edition of the Tumor, Node, Metastasis Classification for Lung Cancer: Validation Analysis Based on a Large-Scale Nationwide Database.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Oncol. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1097/JTO.0b013e31828632b8
AUTORES / AUTHORS: - Kawase A; Yoshida J; Miyaoka E; Asamura H; Fujii Y; Nakanishi Y; Eguchi K; Mori M; Sawabata N; Okumura M; Yokoi K
INSTITUCIÓN / INSTITUTION: - *Division of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; daggerDepartment of Mathematics, Science University of Tokyo, Tokyo, Japan; double daggerDivision of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan; section signDepartment of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Science and Medical School, Nagoya, Japan; ||Department of Clinical Medicine, Research Institute for Diseases of the Chest, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; paragraph signDepartment of Medical Oncology, Teikyo University School of Medicine, Tokyo, Japan; #Department of Pulmonary Medicine, Sapporo-Kosei General Hospital, Hokkaido, Japan; **Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; and daggerdaggerDivision of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
RESUMEN / SUMMARY: - OBJECTIVE:: In the 7th tumor, node, metastasis (TNM) classification, visceral pleural invasion (VPI) is defined as invasion beyond the elastic layer, including invasion to the visceral pleural surface, and T1 tumors with VPI are upgraded to T2a. To validate this, we analyzed the survival of non-small-cell lung cancer patients from a nationwide database and evaluated the prognostic impact of VPI. METHODS:: The clinicopathological characteristics and prognosis of 4995 patients who were included in the registry study of the Japanese Joint Committee of Lung Cancer Registry were retrospectively analyzed with a special interest in the prognostic impact of VPI. These patients underwent surgery in 2004 and were pathologically staged as T1a-3N0. VPI was defined as including PL1 and PL2 according to the 7th TNM Classification, but the Japanese Joint Committee of Lung Cancer Registry did not collect data regarding staining or how extensively VPI was evaluated in each participating institution. RESULTS:: The survival differences were statistically significant between PL0 and PL1, PL1 and PL2, as well as PL2 and T3. There were no significant survival differences between T1a with VPI and T1b without VPI, or between T1a with VPI and T2a without VPI. There were no significant survival differences between T1b with VPI and T2a without VPI, or between T1b with VPI and T2b without VPI. There were no significant survival differences between T2a with VPI and T2b without VPI, or between T2b with VPI and T2b without VPI. T3 showed significantly worse prognosis than T2a with VPI and T2b with VPI. CONCLUSIONS:: In addition to the current TNM classification recommendations, in which T1 tumors with VPI are upgraded to T2a, T2a tumors with VPI should be classified as T2b.
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[475]
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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[476]
TÍTULO / TITLE: - PROFILing non-small-cell lung cancer patients for treatment with crizotinib according to anaplastic lymphoma kinase abnormalities: translating science into medicine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Pharmacother. 2013 Apr;14(5):597-608. doi: 10.1517/14656566.2013.778828. Epub 2013 Mar 9.
●● Enlace al texto completo (gratuito o de pago) 1517/14656566.2013.778828
AUTORES / AUTHORS: - Pilotto S; Peretti U; Novello S; Rossi G; Milella M; Giaj Levra M; Ciuffreda L; Massari F; Brunelli M; Tortora G; Bria E
INSTITUCIÓN / INSTITUTION: - University of Verona, Azienda Ospedaliera Universitaria Integrata (A.O.U.I.), ‘G.B. Rossi’ Academic Hospital, Medical Oncology , P.zza L.A. Scuro 10, 37124, Verona , Italy +390458128502, +390458128140 ; emiliobria@yahoo.it.
RESUMEN / SUMMARY: - Introduction: In the recent years, the growing attention to the molecular background of non-small-cell lung cancer (NSCLC) led to the identification of different molecular subtypes according to genetic abnormalities driving the disease development and progression. Whereas the addicted pathways were successfully inhibited (such as the mutant epidermal growth factor receptor), clinicians have witnessed a dramatic survival improvement. In this regard, the molecular portrait of adenocarcinoma was recently enriched by the identification of a specific patients’ subgroup characterized by abnormalities in the anaplastic lymphoma kinase (ALK), with unclear prognostic features but impressive response to specific inhibitors. Areas covered: In this article, updated data derived from the development and the use of crizotinib (the most advanced in development among tyrosine kinase ALK inhibitors) in comparison with standard second-line chemotherapy for patients affected by ALK-altered NSCLC are reviewed. Expert opinion: Taking into account the available data, pretreated NSCLC patients carrying the ALK-translocation require a selected targeted therapy which significantly improves activity, efficacy and symptoms control versus chemotherapy. In this context, the identification of this disease entity and the availability of such impressive therapeutic targeting represent a further step toward the understanding of the molecular complexity behind the adenocarcinoma of the lung.
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[477]
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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[478]
TÍTULO / TITLE: - Comment on “Effects of treatment regimens on survival in patients with malignant pleural mesothelioma”. Letter to the Editor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Rev Med Pharmacol Sci. 2013 Feb;17(3):424-5.
AUTORES / AUTHORS: - Fiorica F; Fisichella R
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, University Hospital “S. Anna” Ferrara, Italy. francesco.fiorica@unife.it.
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[479]
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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[480]
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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[481]
TÍTULO / TITLE: - Human immunodeficiency virus status has no effect on survival in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - CA Cancer J Clin. 2013 Mar 5. doi: 10.3322/caac.21179.
●● Enlace al texto completo (gratuito o de pago) 3322/caac.21179
AUTORES / AUTHORS: - Barton MK
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[482]
TÍTULO / TITLE: - Outcomes of Chemoradiation for Patients with Locally Advanced Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Intern Med J. 2013 Mar 19. doi: 10.1111/imj.12138.
●● Enlace al texto completo (gratuito o de pago) 1111/imj.12138
AUTORES / AUTHORS: - Spina R; Chu SY; Chatfield M; Chen J; Tin MM; Boyer M
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
RESUMEN / SUMMARY: - BACKGROUND: Historically, long-term survival rates in locally advanced non-small-cell lung cancer (NSCLC) have been disappointingly low, and treatment toxicities have been significant. AIMS: To assess survival outcomes, treatment toxicities, patterns of disease recurrence and prognostic variables for patients with locally advanced NSCLC treated with concurrent chemoradiation. METHODS: Patients who completed treatment with chemotherapy and simultaneous chest irradiation for locally advanced NSCLC at the Royal Prince Alfred Hospital (Sydney, Australia) in the period January 1994 to July 2009 were identified. We retrospectively reviewed the patients’ medical records to obtain patient demographic data, clinical data, information on tumour characteristics and treatment administered, and outcome data such as survival, treatment toxicities and tumour recurrence patterns. RESULTS: Our patient cohort consisted largely of urban-dwelling male smokers with good baseline performance status. As of December 2012, 93/105 patients had died. Median overall and progression-free survival was 20 months and 11 months, respectively. The 5-year survival rate was 17%. Eight patients had survived longer than 8 years, and 13 patients enjoyed progression-free survival longer than 3 years. Locoregional tumour recurrence occurred most frequently, followed by brain and bone metastases. Adverse effects from chemoradiation included varying degrees of gastrointestinal, pulmonary and haematological toxicity. Three deaths occurred from radiation-induced pneumonitis. Weight loss at presentation was statistically significantly associated with worse overall survival in univariate analyses (P=0.01). CONCLUSIONS: Our survival results are consistent with the recent international literature, and indicate that a proportion of patients with locally advanced NSCLC can enjoy prolonged survival following treatment with concurrent chemoradiation.
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[483]
TÍTULO / TITLE: - Association of pre-operative brain pathology with post-operative delirium in a cohort of non-small cell lung cancer patients undergoing surgical resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Psychooncology. 2013 Mar 4. doi: 10.1002/pon.3262.
●● Enlace al texto completo (gratuito o de pago) 1002/pon.3262
AUTORES / AUTHORS: - Root JC; Pryor KO; Downey R; Alici Y; Davis ML; Holodny A; Korc-Grodzicki B; Ahles T
INSTITUCIÓN / INSTITUTION: - Memorial Sloan-Kettering Cancer Center, Department of Psychiatry and Behavioral Sciences, New York, NY, USA; Weill Cornell Medical College, Department of Anesthesiology, New York, NY, USA.
RESUMEN / SUMMARY: - OBJECTIVE: Post-operative delirium is associated with pre-operative cognitive difficulties and diminished functional independence, both of which suggest that brain pathology may be present in affected individuals prior to surgery. Currently, there are few studies that have examined imaging correlates of post-operative delirium. To our knowledge, none have examined the association of delirium with existing structural pathology in pre-operative cancer patients. Here, we present a novel, retrospective strategy to assess pre-operative structural brain pathology and its association with post-operative delirium. Standard of care structural magnetic resonance imaging (MRIs) from a cohort of surgical candidates prior to surgery were analyzed for white matter hyperintensities and cerebral atrophy. METHODS: We identified 23 non-small cell lung cancer patients with no evidence of metastases in the brain pre-operatively, through retrospective chart review, who met criteria for post-operative delirium within 4 days of surgery. 24 age- and gender-matched control subjects were identified for comparison to the delirium sample. T1 and fluid-attenuated inversion recovery sequences were collected from standard of care pre-operative MRI screening and assessed for white matter pathology and atrophy. RESULTS: We found significant differences in white matter pathology between groups with the delirium group exhibiting significantly greater white matter pathology than the non-delirium group. Measure of cerebral atrophy demonstrated no significant difference between the delirium and non-delirium group. CONCLUSIONS: In this preliminary study utilizing standard of care pre-operative brain MRIs for assessment of structural risk factors to delirium, we found white matter pathology to be a significant risk factor in post-operative delirium. Limitations and implications for further investigation are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
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[484]
TÍTULO / TITLE: - Efficacy and safety of human fibrinogen-thrombin patch (TachoSil®) in the treatment of postoperative air leakage in patients submitted to redo surgery for lung malignancies: a randomized trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Interact Cardiovasc Thorac Surg. 2013 Feb 17.
●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivs571
AUTORES / AUTHORS: - Filosso PL; Ruffini E; Sandri A; Lausi PO; Giobbe R; Oliaro A
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, University of Torino, San Giovanni Battista Hospital, Turin, Italy.
RESUMEN / SUMMARY: - OBJECTIVESPrevious studies of the human fibrinogen-thrombin patch TachoSil® for air leak management in thoracic surgery have excluded patients undergoing redo surgery, a group at high risk of persistent air leaks. This is the first study to assess TachoSil® in patients undergoing redo surgery.METHODSPatients who had undergone pulmonary resection for primary lung cancer or lung metastasis and were scheduled for completion lobectomy plus lymphadenectomy due to tumour recurrence were eligible. After complete lobectomy, patients with intraoperative Macchiarini grade 3 air leaks (or >30% of the tidal volume at plethysmographic assessment) were randomized to receive either TachoSil® or further lung parenchymal stapling/suturing procedures according to standard surgical practice.RESULTSA total of 24 patients were randomized to TachoSil® (n = 13) or standard treatment (n = 11). Mean duration of surgery was significantly shorter in the TachoSil® group than in the standard group (3.6 vs 4.0 h; P = 0.023). The mean duration of air leaks was also significantly reduced in the TachoSil® group (4.7 vs 10.0 days; P < 0.001), and the removal of both the first and the second chest tubes occurred earlier (mean 3.8 vs 5.5 days; P = 0.005; and 6.1 vs 10.8 days; P < 0.001, respectively). TachoSil® was also effective in reducing persistent (>/=9 days) air leaks (1 vs 7 patients; P = 0.008). There were no significant differences between groups in other postoperative complications. Mean length of hospital stay was significantly shorter in TachoSil®-treated patients (6.9 vs 9.5 days; P < 0.001).CONCLUSIONSTachoSil® was superior to standard stapling and suturing aerostatic techniques in reducing postoperative air leaks in patients undergoing redo thoracic surgery.
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[485]
TÍTULO / TITLE: - A Pilot Study To Investigate Adherence to Long-Acting Opioids among Patients with Advanced Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Palliat Med. 2013 Apr;16(4):391-6. doi: 10.1089/jpm.2012.0400. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1089/jpm.2012.0400
AUTORES / AUTHORS: - Yoong J; Traeger LN; Gallagher ER; Pirl WF; Greer JA; Temel JS
INSTITUCIÓN / INSTITUTION: - 1 Caritas Christi Hospice, St. Vincent’s Hospital (Melbourne) , Victoria, Australia .
RESUMEN / SUMMARY: - Abstract Background: Uncontrolled pain remains prevalent in patients with advanced cancer and has been associated with worse quality of life and greater health care utilization. Poor adherence to analgesics may represent a modifiable barrier to pain management. Objective: This pilot study aimed to establish feasibility/utility of evaluating self-reported adherence to long-acting (LA) opioids in patients with advanced lung cancer, and to explore rates and correlates of adherence. Methods: Consecutive patients attending an ambulatory thoracic oncology clinic with a diagnosis of advanced lung cancer and a current LA opioid regimen were approached to complete a brief questionnaire during their clinic visit. Participants reported LA opioid adherence during the past 4 weeks (0%-100%) and knowledge of their LA opioid regimen, and completed the Patient Health Questionnaire-2 (PHQ-2) depression screen. Demographic and clinical information were confirmed via electronic health record review. Results: Fifty-four eligible patients were approached to reach our target sample (n=50; enrollment=92.6%). Self-reported adherence to LA opioids was 85.4% (standard deviation [SD]=21.0). Twenty-eight percent reported a frequency of medication use that did not match the prescribed daily frequency. Lower adherence was associated with inaccurate frequency (p=0.004), positive depression screen (p=0.005), and older age (p=0.04). Conclusions: Our results demonstrate the feasibility of integrating self-report assessments of LA opioid adherence into a thoracic oncology clinic. Patients reported high adherence, but more than one-quarter did not accurately report the prescribed frequency of daily doses. Understanding of LA opioid regimens may be a critical indicator of adherence in patients with advanced cancer.
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[486]
TÍTULO / TITLE: - The place of pemetrexed in the management of non-small-cell lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Rev Anticancer Ther. 2013 Mar;13(3):257-66. doi: 10.1586/era.12.171.
●● Enlace al texto completo (gratuito o de pago) 1586/era.12.171
AUTORES / AUTHORS: - Tomasini P; Greillier L; Khobta N; Barlesi F
INSTITUCIÓN / INSTITUTION: - Aix-Marseille Universite - Assistance Publique Hopitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations Department, Chemin des Bourrely, 13915 Marseille Cedex 20, France.
RESUMEN / SUMMARY: - Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. Chemotherapy is included in the management of the majority of NSCLC patients either in addition to a local treatment (surgery/radiotherapy) or alone. In this setting, pemetrexed has become one of the most important partners of current chemotherapy regimens for nonsquamous NSCLC patients. Indeed, pemetrexed demonstrated a comparable efficacy to other previously available drugs in NSCLC, with however a better safety profile and an easier schedule of administration. In addition, pemetrexed demonstrated a greater efficacy in nonsquamous NSCLC that lead to an exploration of the underlying potential biological background. It is now suggested that the tumor thymidylate synthase level may act as a predictor of pemetrexed efficacy, therefore potentially providing clinicians in the future with a predictor of efficacy, which it is usually lacking with standard chemotherapies.
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[487]
TÍTULO / TITLE: - Therapeutic cancer vaccines in the treatment of non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Rev Vaccines. 2013 Mar;12(3):263-70. doi: 10.1586/erv.13.14.
●● Enlace al texto completo (gratuito o de pago) 1586/erv.13.14
AUTORES / AUTHORS: - Limacher JM; Spring-Giusti C; Bellon N; Ancian P; Rooke R; Bonnefoy JY
INSTITUCIÓN / INSTITUTION: - Transgene SA, Boulevard Gonthier d’Andernach, Parc d’Innovation - CS80166, 67405 Illkirch Graffenstaden Cedex, France.
RESUMEN / SUMMARY: - Therapeutic vaccines are different from the well-known prophylactic vaccines in that they are designed to treat patients already suffering from a disease instead of preventing the disease in healthy individuals. Several therapeutic vaccines are today in late-stage clinical development for non-small-cell lung cancer. These vaccines use different approaches including peptides, cell lines and viral vectors, and explore different settings within the pathology. Some are given in monotherapy while others are combined with the classic therapies used with non-small-cell lung cancer. This review gives a summary of the therapeutic vaccines currently in late-stage clinical development for non-small-cell lung cancer.
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[488]
TÍTULO / TITLE: - Suppression of autophagy by CDCP1 signaling is essential for anchorage-independent survival of lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Sci. 2013 Mar 20. doi: 10.1111/cas.12154.
●● Enlace al texto completo (gratuito o de pago) 1111/cas.12154
AUTORES / AUTHORS: - Uekita T; Fujii S; Miyazawa Y; Hashiguchi A; Abe H; Sakamoto M; Sakai R
INSTITUCIÓN / INSTITUTION: - Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, Tokyo.
RESUMEN / SUMMARY: - CUB domain-containing protein 1 (CDCP1) has been implicated in promoting metastasis of cancer cells through several mechanisms, including the inhibition of anoikis, cell death triggered by a loss of extracellular matrix interactions. However, the mechanism inhibiting cell death regulated by CDCP1 remains elusive. Inhibition of CDCP1 expression using small interfering RNA (siRNA) induced the cell death of suspended cancer cells without cleaving caspase-3, a marker of apoptosis; cell death was not inhibited by a general caspase inhibitor, suggesting that the loss of CDCP1 induces caspase-independent cell death. In contrast, knockdown of CDCP1 as well as protein kinase Cdelta (PKCdelta), a downstream effector of CDCP1, in a suspension culture of lung cancer cells resulted in marked induction of membranous microtubule-associated protein 1 light chain 3 (LC3)-II protein, a hallmark of autophagy and caused the formation of an autophagosome structure visualized using green fluorescent protein (GFP)-tagged LC3-II. Expression and phosphorylation of exogenous CDCP1 by Fyn kinase reduced the formation of autophagosomes and inhibited phosphorylation of CDCP1 by PP2, a Src kinase inhibitor or inhibited PKCdelta by rottlerin, stimulating autophagosome formation. Moreover, death of suspended lung cancer cells induced by CDCP1 siRNA or by PKCdelta siRNA was reduced by the autophagy inhibitor 3-methyladenine. These results indicate that CDCP1-PKCdelta signaling plays a critical role in inhibiting autophagy, which is responsible for anoikis resistance of lung cancer cells.
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[489]
TÍTULO / TITLE: - Clinicopathological and prognostic significance of HIF-1alpha and HIF-2alpha expression in small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Res Pract. 2013 Mar;209(3):184-9. doi: 10.1016/j.prp.2012.10.017. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1016/j.prp.2012.10.017
AUTORES / AUTHORS: - Luan Y; Gao C; Miao Y; Li Y; Wang Z; Qiu X
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Tianjin Medical University, Tianjin, China. Electronic address: yajingluan123@126.com.
RESUMEN / SUMMARY: - Previous work from our laboratory has demonstrated that urokinase plasminogen activator receptor (uPAR) may be a potential stem-like cell marker in SCLC. Hypoxia inducible factor (HIF) has been shown to transcriptionally regulate uPAR expression. Therefore, the aim of this study was to evaluate the relationship between HIF-1alpha/HIF-2alpha and uPAR expression, and to investigate the role of HIF-1alpha/HIF-2alpha in the clinical pathology and prognosis of patients with SCLC. Immunohistochemical analysis showed that HIF-1alpha/HIF-2alpha staining was mainly present in the nuclei of cancer cells. HIF-1alpha-positive cells were diffusely distributed in the nests of the tumor, while HIF-2alpha-positive cells were frequently distributed around necrotic regions. HIF-1alpha and HIF-2alpha were expressed in 22/45 (48.9%) and in 11/45 (24.4%) of SCLC patients, respectively; HIF-1alpha did not correlate with any of the clinicopathological parameters as evaluated in our study. In contrast, a significant association of HIF-2alpha with uPAR expression, tumor growth and distant metastasis (p=0.001, 0.010 and 0.008, respectively) was noted; Kaplan-Meier survival analysis demonstrated that HIF-1alpha and HIF-2alpha expressions were related to shortened overall survival (p=0.027 and 0.001, respectively). However, in multivariate analysis, only HIF-2alpha expression and distant metastasis were the independent prognostic indicators of SCLC (p=0.004 and 0.018, respectively). Our results suggest that HIF-2alpha may represent a more aggressive phenotype in SCLC. HIF-2alpha, in addition to HIF-1alpha, needs to be considered when developing drugs that target HIF pathway.
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[490]
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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[491]
TÍTULO / TITLE: - EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Feb;12(2):220-9. doi: 10.1158/1535-7163.MCT-12-0620. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0620
AUTORES / AUTHORS: - Arcila ME; Nafa K; Chaft JE; Rekhtman N; Lau C; Reva BA; Zakowski MF; Kris MG; Ladanyi M
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. arcilam@mskcc.org
RESUMEN / SUMMARY: - In contrast to other primary epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas, insertions in exon 20 of EGFR have been generally associated with resistance to EGFR-tyrosine kinase inhibitors. Their molecular spectrum, clinicopathologic characteristics, and prevalence are not well established. Tumors harboring EGFR exon 20 insertions were identified through an algorithmic screen of 1,500 lung adenocarcinomas. Cases were first tested for common mutations in EGFR (exons 19 and 21) and KRAS (exon 2) and, if negative, further analyzed for EGFR exon 20 insertions. All samples underwent extended genotyping for other driver mutations in EGFR, KRAS, BRAF, ERBB2/HER2, NRAS, PIK3CA, MEK1, and AKT by mass spectrometry; a subset was evaluated for ALK rearrangements. We identified 33 EGFR exon 20 insertion cases [2.2%, 95% confidence interval (CI), 1.6-3.1], all mutually exclusive with mutations in the other genes tested (except PIK3CA). They were more common among never-smokers (P < 0.0001). There was no association with age, sex, race, or stage. Morphologically, tumors were similar to those with common EGFR mutations but with frequent solid histology. Insertions were highly variable in position and size, ranging from 3 to 12 bp, resulting in 13 different insertions, which, by molecular modeling, are predicted to have potentially different effects on erlotinib binding. EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases, representing the third most common type of EGFR mutation after exon 19 deletions and L858R. Insertions are structurally heterogeneous with potential implications for response to EGFR inhibitors.
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[492]
TÍTULO / TITLE: - Sex as an independent prognostic factor in a population-based non-small cell lung cancer cohort.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Can Respir J. 2013 Jan;20(1):30-4.
AUTORES / AUTHORS: - Pitz MW; Musto G; Navaratnam S
RESUMEN / SUMMARY: - BACKGROUND: Males with non-small cell lung cancer (NSCLC) tend to experience worse outcomes, as do those with nonadenocarcinoma histology; however, the independent effects of these factors remain unclear. OBJECTIVE: To evaluate the independent effect of sex and histology on mortality in a population of patients with NSCLC. METHODS: All patients with NSCLC in Manitoba from 1985 to 2004 were identified from the Manitoba Cancer Registry. Treatment data were extracted from the Manitoba Health administrative databases and linked to the registry. Cox regression analysis was used to determine the independent effect of sex on survival. RESULTS: A total of 10,908 patients (6665 male, 4243 female) with NSCLC were identified. Females had a median overall survival of 9.4 months versus 6.8 months for males (P<0.001). The adjusted HR for death for males compared with females was 1.13 (95% CI 1.04 to 1.23; P=0.004). Sex modified the effect of surgical treatment on survival (HR 1.26 [95% CI 1.13 to 1.40]; P<0.001). Adenocarcinoma histology modified the effect of sex on survival (HR 1.36 [95% CI 1.24 to 1.50]; P<0.001) when treatment was accounted for. CONCLUSION: Females experienced a significantly better survival rate than males independent of treatment, age, year of diagnosis and histology. This was greatest in surgically treated patients and in those with adenocarcinoma.
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[493]
TÍTULO / TITLE: - Oroxylin A sensitizes non-small cell lung cancer cells to anoikis via glucose-deprivation-like mechanisms: c-Src and hexokinase II.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 Mar 15. pii: S0304-4165(13)00087-1. doi: 10.1016/j.bbagen.2013.03.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbagen.2013.03.009
AUTORES / AUTHORS: - Wei L; Dai Q; Zhou Y; Zou M; Li Z; Lu N; Guo Q
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
RESUMEN / SUMMARY: - BACKGROUND: Cellular metabolism, particularly glycolysis, is altered during the metastatic process and is highly associated with tumor progression and apoptosis resistance. Oroxylin A, a natural plant flavonoid, exhibits chemopreventive and therapeutic anti-inflammatory and anticancer potential. However, the anticancer effects of oroxylin A on non-small cell lung carcinoma (NSCLC) remain poorly understood. METHODS: In vitro studies were performed using 2D and 3D conditions. The effects on anoikis-sensitization and glycolysis-inhibition of oroxylin A in human non-small cell lung cancer A549 cells were examined. In vivo murine lung metastasis experiments were utilized to assess the anti-metastatic capacity of oroxylin A. RESULTS: ROS-mediated activation of c-Src following detachment caused anoikis resistance in A549 cells. Oroxylin A sensitized A549 cells to anoikis by inactivating the c-Src/AKT/HK II pathway in addition to inducing the dissociation of HK II from mitochondria. Prior to sensitizing A549 cells to anoikis, oroxylin A decreased the ATP level and inhibited glycolysis. Furthermore, oroxylin A inhibited lung metastasis of A549 cells in vivo in nude mice. CONCLUSIONS: Oroxylin A sensitized anoikis, which underlies distinct glucose-deprivation-like mechanisms that involved c-Src and HK II. GENERAL SIGNIFICANCE: The findings in this study indicated that oroxylin A could potentially be utilized in the development of improved metastatic cancer treatments.
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[494]
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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[495]
TÍTULO / TITLE: - Prognostic Impact of Pleural Invasion in 1488 Patients with Surgically Resected Non-small Cell Lung Carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt039
AUTORES / AUTHORS: - Oyama M; Miyagi Maeshima A; Tochigi N; Tsuta K; Kawachi R; Sakurai H; Watanabe S; Asamura H; Tsuda H
INSTITUCIÓN / INSTITUTION: - 1Department of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo.
RESUMEN / SUMMARY: - OBJECTIVE: This study aimed to verify the prognostic impact of pleural invasion according to the revised TNM classification, seventh edition. METHODS: The study consisted of 1488 patients with surgically resected non-small cell carcinoma. The degree (pl0-3) and location of pleural invasion were examined using hematoxylin and eosin- and elastica van Gieson-stained slides, and outcome was compared with stratification by several clinicopathological factors. RESULTS: The 5-year overall survival rates of 1008, 260, 85 and 135 patients with pl0, pl1, pl2 and pl3 tumours were 80, 60, 55 and 52%, respectively. Overall survival differed significantly between patients with pl0 tumours and those with pl1 tumours (P < 0.0001). The difference was significant for patients with 1<</= 2 cm (P = 0.004), 2<</= 3 cm (P = 0.003) and 3<</= 5 cm (P = 0.02) tumours. The overall survival of pl0 patients was also significantly better in patients with adenocarcinoma (P < 0.0001) than squamous cell carcinoma (P = 0.043). The overall survival of pl0 patients was significantly better in patients without lymph node metastasis (P < 0.0001) than in those with lymph node metastasis. The 5-year overall survival rates of patients with interlobar, lateral, mediastinal and diaphragmatic pl3 tumours were 65, 51, 51 and 40%, respectively. Overall survival did not differ significantly among these four groups. CONCLUSIONS: Outcome differs between patients with pl0 tumours and those with pl1-3 tumours, particularly among patients with 1<</= 2 cm, 2 <</= 3 cm and 3<</= 5 cm tumours, adenocarcinoma histology and no lymph node metastasis. The location of pl3 pleural invasion did not affect outcome significantly.
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[496]
TÍTULO / TITLE: - Poly(beta-amino ester) Nanoparticle Delivery of TP53 Has Activity against Small Cell Lung Cancer In Vitro and In Vivo.
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-12-0956
AUTORES / AUTHORS: - Kamat CD; Shmueli RB; Connis N; Rudin CM; Green JJ; Hann CL
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: 1Sidney Kimmel Comprehensive Cancer Center, and 2Department of Biomedical Engineering, the Translational Tissue Engineering Center, and the Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
RESUMEN / SUMMARY: - Small cell lung cancer (SCLC) is an aggressive disease with one of the highest case-fatality rates among cancer. The recommended therapy for SCLCs has not changed significantly over the past 30 years; new therapeutic approaches are a critical need. TP53 is mutated in the majority of SCLC cases and its loss is required in transgenic mouse models of the disease. We synthesized an array of biodegradable poly(beta-amino ester) (PBAE) polymers that self-assemble with DNA and assayed for transfection efficiency in the p53-mutant H446 SCLC cell line using high-throughput methodologies. Two of the top candidates were selected for further characterization and TP53 delivery in vitro and in vivo. Nanoparticle delivery of TP53 resulted in expression of exogenous p53, induction of p21, induction of apoptosis, and accumulation of cells in sub-G1 consistent with functional p53 activity. Intratumoral injection of subcutaneous H446 xenografts with polymers carrying TP53 caused marked tumor growth inhibition. This is the first demonstration of TP53 gene therapy in SCLC using nonviral polymeric nanoparticles. This technology may have general applicability as a novel anticancer strategy based on restoration of tumor suppressor gene function. Mol Cancer Ther; 12(4); 1-11. ©2013 AACR.
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[497]
TÍTULO / TITLE: - Epirubicin loaded to pre-polymerized poly(butyl cyanoacrylate) nanoparticles: Preparation and in vitro evaluation in human lung adenocarcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Colloids Surf B Biointerfaces. 2013 Feb 11;107C:115-123. doi: 10.1016/j.colsurfb.2013.02.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.colsurfb.2013.02.002
AUTORES / AUTHORS: - Yordanov G; Evangelatov A; Skrobanska R
INSTITUCIÓN / INSTITUTION: - Sofia University St. Kliment Ohridski, Faculty of Chemistry and Pharmacy, 1 “James Bourchier” Blvd., 1164 Sofia, Bulgaria. Electronic address: g.g.yordanov@gmail.com.
RESUMEN / SUMMARY: - This article describes the preparation of epirubicin-loaded nanoparticles, prepared by loading of the drug in pre-polymerized poly(butyl cyanoacrylate) nanoparticles, their physicochemical characterization and in vitro evaluation on human lung adenocarcinoma (A549) cells. Nanoparticles were also coated in aqueous dispersions with two different non-ionic surfactants (Pluronic F68 and Polysorbate 80). All particles were spherical in shape, with monomodal size distributions. The zeta-potentials at pH 7.4 increased with augmentation of the particle drug content. The increased drug content was found to correlate with the initial concentration of the drug, used for the particle preparation. In vitro studies on A549 cells showed that the drug-loaded nanoparticles, as well as the combinations of free drug and empty nanoparticles, exhibited higher cytotoxicity than the free drug alone. The presence of surfactants also resulted in increased cytotoxicity. Fluorescent imaging of epirubicin internalization by the adenocarcinoma cells revealed that the free drug was predominantly localized in the cell nucleus, while a cytoplasmic localization was observed for the nanoparticle-bound drug formulations, suggesting the probability of nanoparticle endocytosis. Thus the hereby presented results could be useful for development of nanoparticle-based anthracycline formulations for treatment of lung adenocarcinoma.
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[498]
TÍTULO / TITLE: - Novel chiral ferrocenylpyrazolo[1,5-a][1,4]diazepin-4-one derivatives - Synthesis, characterization and inhibition against lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Med Chem. 2013 Feb 24;63C:256-268. doi: 10.1016/j.ejmech.2013.02.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejmech.2013.02.016
AUTORES / AUTHORS: - Shen SL; Shao JH; Luo JZ; Liu JT; Miao JY; Zhao BX
INSTITUCIÓN / INSTITUTION: - Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Shanda Nanlu 27, Jinan, Shandong 250100, PR China.
RESUMEN / SUMMARY: - A series of novel 2-ferrocenyl-7-hydroxy-5-phenethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diaz epin-4-one derivatives with optical activity (2) was synthesized in the microwave-assisted condition and characterized by means of IR, 1H NMR and mass spectroscopy, and furthermore confirmed by X-ray analysis of a representative compound ®-2a. Preliminary biological evaluation showed that some compounds could suppress the growth of A549, H322 and H1299 lung cancer cells. Among the tested compounds, 2b-d were more effective and might perform their action through cell cycle arrest for A549 cell. Whereas these compounds inhibited growth of H1299 and H322 cells by inducing apoptosis. The anti-tumor activities of these compounds were related to the nature of substituents in benzene moiety. In addition, the results indicated also that compounds 2b-d possessed notable cytotoxicity and selectivity for A549 vs H1299 and H322 lung cancer cells.
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[499]
TÍTULO / TITLE: - Lipid-coated gold nanoparticles promote lamellar body formation in A549 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 Feb 4. pii: S1388-1981(13)00037-1. doi: 10.1016/j.bbalip.2013.01.018.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbalip.2013.01.018
AUTORES / AUTHORS: - Wang M; Petersen NO
INSTITUCIÓN / INSTITUTION: - Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada; National Institute for Nanotechnology, Edmonton, Alberta, Canada.
RESUMEN / SUMMARY: - Gold nanoparticles (GNPs) have been applied as diagnostic and therapeutic agents because they can be targeted, localized, and be heated to cause cell death. However, their use has been limited by their relatively low biocompatibility. In this work, we coated the GNPs’ surface by a biocompatible phospholipid bilayer composed of 1-stearoyl-2-oleoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (SOPG). We tested their interaction with A549 cells to investigate their uptake and intracellular fate as well as the response of the cells to the presence of the GNPs. We used flow cytometry and confocal microscopy to show that the SOPG coated GNPs were readily taken up by the A549 cells. Transmission electron microscopy (TEM) images and fluorescence images further showed that the number of granular structures in the cells was increased following exposure to the lipid coated GNPs. Co-localization experiments demonstrated that SOPG coated GNPs localize in acidic compartments in a time dependent manner and that the number of these increase as the cells are exposed to the GNPs suggesting that they induce formation of lamellar bodies (LBs) which in A549 cells in turn can serve as a means of exporting the GNPs.
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[500]
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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[501]
TÍTULO / TITLE: - The proangiogenic phenotype of natural killer cells in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasia. 2013 Feb;15(2):133-42.
AUTORES / AUTHORS: - Bruno A; Focaccetti C; Pagani A; Imperatori AS; Spagnoletti M; Rotolo N; Cantelmo AR; Franzi F; Capella C; Ferlazzo G; Mortara L; Albini A; Noonan DM
INSTITUCIÓN / INSTITUTION: - Scientific and Technology Park, IRCCS MultiMedica, Milan, Italy.
RESUMEN / SUMMARY: - The tumor microenvironment can polarize innate immune cells to a proangiogenic phenotype. Decidual natural killer (dNK) cells show an angiogenic phenotype, yet the role for NK innate lymphoid cells in tumor angiogenesis remains to be defined. We investigated NK cells from patients with surgically resected non-small cell lung cancer (NSCLC) and controls using flow cytometric and functional analyses. The CD56(+)CD16(-) NK subset in NSCLC patients, which represents the predominant NK subset in tumors and a minor subset in adjacent lung and peripheral blood, was associated with vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and interleukin-8 (IL-8)/CXCL8 production. Peripheral blood CD56(+)CD16(-) NK cells from patients with the squamous cell carcinoma (SCC) subtype showed higher VEGF and PlGF production compared to those from patients with adenocarcinoma (AdC) and controls. Higher IL-8 production was found for both SCC and AdC compared to controls. Supernatants derived from NSCLC CD56(+)CD16(-) NK cells induced endothelial cell chemotaxis and formation of capillary-like structures in vitro, particularly evident in SCC patients and absent from controls. Finally, exposure to transforming growth factor-beta(1) (TGFbeta(1)), a cytokine associated with dNK polarization, upregulated VEGF and PlGF in peripheral blood CD56(+)CD16(-) NK cells from healthy subjects. Our data suggest that NK cells in NSCLC act as proangiogenic cells, particularly evident for SCC and in part mediated by TGFbeta(1).
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[502]
TÍTULO / TITLE: - Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer. 2013 Mar 2;12:16. doi: 10.1186/1476-4598-12-16.
●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-12-16
AUTORES / AUTHORS: - Zinn RL; Gardner EE; Dobromilskaya I; Murphy S; Marchionni L; Hann CL; Rudin CM
INSTITUCIÓN / INSTITUTION: - Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine, Cancer Research Building 2, Room 544 1550 Orleans Street, Baltimore, MD, USA. rudin@jhmi.edu.
RESUMEN / SUMMARY: - BACKGROUND: New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies. METHODS: We explored the combination of ABT-737 and chloroquine, an inhibitor of autophagy, in preclinical models of SCLC. These included cell culture analyses of viability and of autophagic and apoptotic pathway induction, as well as in vivo analyses of efficacy in multiple xenograft models. RESULTS: Combination treatment of SCLC lines with ABT-737 and chloroquine decreased viability and increased caspase-3 activation over treatment with either single agent. ABT-737 induced several hallmarks of autophagy. However, knockdown of beclin-1, a key regulator of entry into autophagy, diminished the efficacy of ABT-737, suggesting either that the effects of chloroquine were nonspecific or that induction but not completion of autophagy is necessary for the combined effect of ABT-737 and chloroquine. ABT-737 and chloroquine in SCLC cell lines downregulated Mcl-1 and upregulated NOXA, both of which may promote apoptosis. Treatment of tumor-bearing mice demonstrated that chloroquine could enhance ABT-737-mediated tumor growth inhibition against NCI-H209 xenografts, but did not alter ABT-737 response in three primary patient-derived xenograft models. CONCLUSION: These data suggest that although ABT-737 can induce autophagy in SCLC, autophagic inhibition by choroquine does not markedly alter in vivo response to ABT-737 in relevant preclinical models, arguing against this as a treatment strategy for SCLC.
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[503]
TÍTULO / TITLE: - DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Microvasc Res. 2013 Mar 1. pii: S0026-2862(13)00026-5. doi: 10.1016/j.mvr.2013.02.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.mvr.2013.02.006
AUTORES / AUTHORS: - Zhang JL; Wang Z; Hu W; Chen SS; Lou XE; Zhou HJ
INSTITUCIÓN / INSTITUTION: - Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of China; The Second Affiliated Hospital (Binjiang Branch), School of Medicine, Zhejiang University, Hangzhou Binjiang Hospital, Hangzhou 310052, People’s Republic of China.
RESUMEN / SUMMARY: - Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit anti-angiogenic and anti-tumor effects apart from its antimalarial activity. In this study, we demonstrate that the combined treatment of cisplatin (CDDP) and DHA exerts a strong, synergistic anti-proliferative effect in human lung carcinoma cells, including A549 and A549/DDP cells, with an average combination index below 0.7. Moreover, the in vivo anti-tumor efficacy of CDDP treatment was increased by DHA. The enhanced anti-cancer activities were also accompanied by reduced tumor microvessel density, increased CDDP concentration within A549 and A549/DDP xenograft BALB/c athymic mice models and suppressed expression of the vascularization-related proteins HIF-1alpha and VEGF both in vivo and in vitro. Furthermore, the level of apoptosis in the tumor cells increased with the combined treatment of DHA and CDDP. Taken together, our results indicate that a combination of DHA and CDDP treatments synergistically affects tumor angiogenesis, and these results provide a clear rationale for the investigation of these drugs in future clinical trials.
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[504]
TÍTULO / TITLE: - Axitinib for the treatment of advanced non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Investig Drugs. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1517/13543784.2013.775243
AUTORES / AUTHORS: - King JW; Lee SM
INSTITUCIÓN / INSTITUTION: - University College Hospital London NHS Foundation Trust, Oncology Department , 235 Euston Road, London NW1 2BU , UK +44 0207 380 9091 ; +44 0207 380 9055 ; judyking@doctors.org.uk.
RESUMEN / SUMMARY: - Introduction: Lung cancer is the most frequently diagnosed cancer in men and comprises 23% of total cancer deaths worldwide. The majority of patients present with advanced disease, for whom the 5-year survival is < 5%. Since angiogenesis plays a central role in tumourigenesis, inhibiting this pathway may improve outcomes in non-small-cell lung cancer (NSCLC). Axitinib is one of the latest and most potent anti-angiogenic tyrosine kinase inhibitors (TKI) currently being evaluated to treat NSCLC. Areas covered: In this review, the rationale for targeting angiogenesis in lung cancer, other angiogenic agents in NSCLC, axitinib’s mechanism of action, pharmacology and metabolism, and the preclinical and clinical data to date in NSCLC will be discussed. Expert opinion: Several TKI which target angiogenesis pathways have resulted in improved response rates and progression-free survival in NSCLC, but no improvement in overall survival in clinical trials. Axitinib is a more potent inhibitor of vascular endothelial growth factor receptors than other TKI, but this has yet to translate into a clinical benefit. Phase II trials are ongoing, but the published data to date has yet to support a role for axitinib in the treatment algorithm for NSCLC.
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[505]
TÍTULO / TITLE: - Multimodality Treatment of Pleural Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Oncol Clin N Am. 2013 Apr;22(2):345-55. doi: 10.1016/j.soc.2012.12.004. Epub 2012 Dec 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.soc.2012.12.004
AUTORES / AUTHORS: - Shersher DD; Liptay MJ
INSTITUCIÓN / INSTITUTION: - Thoracic Oncology Program, Rush University Medical Center, Rush Professional Office Building, 1725 West Harrison Street, Suite 774, Chicago, IL 60612, USA; Department of General Surgery, Rush University Medical Center, Rush Professional Office Building, 1725 West Harrison Street, Suite 774, Chicago, IL 60612, USA.
RESUMEN / SUMMARY: - Although the treatment of malignant pleural mesothelioma has been refined during the past two decades, overall survival from this rather uncommon disease is still extremely poor. Here we review the current multimodal diagnostic and treatment options for patients with mesothelioma and discuss promising new experimental concepts in this disease.
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[506]
TÍTULO / TITLE: - Stereotactic Body Radiation Therapy for Stage I Non-small-cell Lung Cancer: A Historical Overview of Clinical Studies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Apr;43(4):345-50. doi: 10.1093/jjco/hyt014. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt014
AUTORES / AUTHORS: - Onishi H; Araki T
INSTITUCIÓN / INSTITUTION: - *Department of Radiology, School of Medicine, Yamanashi University, 1110 Shimokato, Chuo City, Yamanashi 409-3898, Japan. honishi@yamanashi.ac.jp.
RESUMEN / SUMMARY: - Because of difficulties with stabilization, breathing motion and dosimetry, stereotactic body radiotherapy for lung cancer has only been practiced for the past 15 years. However, a large amount of case data has rapidly been accumulated in recent years. Stereotactic body radiotherapy for Stage I non-small-cell lung cancer has been actively investigated in inoperable patients since around 1995, and a number of clinical trials have been undertaken. Early studies from 2001 presented a 3-year local control rate of 94% and a 3-year overall survival rate of 66% for patients receiving 50-60 Gy in 10 fractions. Another study in 2005, using 48 Gy in four fractions, presented a 3-year local control rate of 98% and 3-year overall survival rates of 83% for Stage IA patients and 72% for Stage IB patients. A multi-institutional study showed favorable local control and survival rates in a group receiving a biologically effective dose of 100 Gy. A dose-escalation study in the USA suggested a maximum tolerated dose of 60 Gy in three fractions. A Phase II clinical trial (RTOG0236) followed, with a reported 3-year local control rate of 98% and a 3-year overall survival rate of 56% for patients who received 60 Gy in three fractions. A Japanese Phase II clinical trial (JCOG0403) investigated a dose of 48 Gy in four fractions among 165 Stage IA patients, showing a 3-year survival rate of 76% and a 3-year locally progression-free survival rate of 69% for the operable group. An overview of past clinical trials in stereotactic body radiotherapy for Stage I non-small-cell lung cancer and current issues is presented and discussed.
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[507]
TÍTULO / TITLE: - Anti-Yo Antibody-mediated Paraneoplastic Cerebellar Degeneration in a Female Patient with Pleural Malignant Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt031
AUTORES / AUTHORS: - Tanriverdi O; Meydan N; Barutca S; Ozsan N; Gurel D; Veral A
INSTITUCIÓN / INSTITUTION: - 1Department of Medical Oncology, Mugla Sitki Kocman University Education and Research Hospital, Mugla.
RESUMEN / SUMMARY: - Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive diziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.
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[508]
TÍTULO / TITLE: - Nicotinamide N-methyltransferase in Non-small Cell Lung Cancer: Promising Results for Targeted Anti-cancer Therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biochem Biophys. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s12013-013-9574-z
AUTORES / AUTHORS: - Sartini D; Morganti S; Guidi E; Rubini C; Zizzi A; Giuliante R; Pozzi V; Emanuelli M
INSTITUCIÓN / INSTITUTION: - Sezione di Biochimica, Dipartimento di Scienze Cliniche Specialistiche e Odontostomatologiche, Universita Politecnica delle Marche, Via Ranieri 65, 60131, Ancona, Italy, davide_sartini@libero.it.
RESUMEN / SUMMARY: - Lung cancer, predominantly non-small cell lung cancer (NSCLC), is currently the most common cause of malignancy-related death in the world. Despite advances in both detection and treatment, its incidence rate is still increasing. Therefore, effective strategies for early detection as well as molecular therapeutic targets are urgently needed. We focused on the enzyme nicotinamide N-methyltransferase (NNMT). NNMT expression levels were investigated in tumor, tumor-adjacent, and surrounding tissue samples of 25 patients with NSCLC by Real-Time PCR, Western blot analysis, and catalytic activity assay. NNMT enzyme activity in NSCLC was then correlated with clinicopathological characteristics. Results obtained showed NNMT upregulation (mRNA and protein) in tumor compared with both tumor-adjacent and surrounding tissue. Moreover, NSCLC displayed significantly higher activity levels than those determined in both tumor-adjacent and surrounding tissue. Interestingly, both tumor-adjacent and surrounding tissue samples of unfavorable cases (N+) seem to display higher activity levels than those of favorable NSCLCs (N0). The present work shows a marked increase of NNMT enzyme activity in NSCLC and suggests that normal-looking tissue of unfavorable cases seems to change toward cancer. Further studies may establish whether NNMT could represent a target for an effective anti-cancer therapy.
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[509]
TÍTULO / TITLE: - Unilateral tongue atrophy and pulmonary malignancy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neth J Med. 2013 Jan;71(1):32-5.
AUTORES / AUTHORS: - Schulkes KJ; Bossink AW
INSTITUCIÓN / INSTITUTION: - Department of Pulmonology, Diakonessenhuis, Utrecht, the Netherlands. kschulkes@gmail.com
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[510]
TÍTULO / TITLE: - Clinicopathological Features of Patients with Malignant Mesothelioma in a Multicenter, Case-Control Study: No Role for ABO-Rh Blood Groups.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):249-53.
AUTORES / AUTHORS: - Utkan G; Urun Y; Cangir AK; Kilic D; Ozdemir NY; Oztuna DG; Bulut E; Arslan UY; Kocer M; Kavukcu S; Icli F
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey E-mail : yukselurun@gmail.com.
RESUMEN / SUMMARY: - Background: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studies have observed an association between ABO blood groups and risk of certain malignancies, including pancreatic and gastric cancer; however, no information on any association with MM risk is available. The aim of this study was to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rh factor. Materials and Methods: In 252 patients with MM, the ABO blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluated in the patient group. Results: The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO blood group distribution of the 252 patients with MM was comparable with the general population. The median overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients. The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001]. Conclusions: The results of this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine in combination with cisplatin. We did not observe a statistically significant association between ABO blood group and risk of MM.
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[511]
TÍTULO / TITLE: - Long-term survival of a small cell lung cancer patient with proper endobronchial management.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pneumologia. 2012 Oct-Dec;61(4):245-8.
AUTORES / AUTHORS: - Kiani A; Khosravi A; Moghaddam AS; Jabbari H; Fakhri M
INSTITUCIÓN / INSTITUTION: - Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
RESUMEN / SUMMARY: - Small cell lung cancer (SCLC) is considered as a disease with poor prognosis and early metastasis with a very short survival. Endobronchial involvement is fairly common finding in SCLC and can cause respiratory symptoms. In this report we present a 47-year-old man diagnosed with small cell lung cancer. In the disease course, primary involvement of right bronchus spread to left bronchus and carina. Scheduled sessions of bronchoscopic interventions with electrocautery and argon plasma coagulation were used to maintain his large airways open. The intrabronchial interventions were accompanied by six courses of cisplatin-based chemotherapy as a standard treatment. Although patient’s definite diagnosis was extensive SCLC, he remained in a good condition for 5 years. In last year of his follow up, headache and dizziness were added to his occasional respiratory symptoms. Brain MRI identified metastatic lesion in his brain. Hence, brain radiotherapy was suggested, but he refused further aggressive treatment. Seven months later, he died of brain metastatic lesion. Considering long survival of this patient with adequate and proper scheduled endobronchial interventions along with standard courses of chemotherapy, we conclude that this combined treatment strategy in patients with endobronchial involvement might increase survival.
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[512]
TÍTULO / TITLE: - MicroRNA-33a functions as a bone metastasis suppressor in lung cancer by targeting parathyroid hormone related protein.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 Mar 1. pii: S0304-4165(13)00073-1. doi: 10.1016/j.bbagen.2013.02.022.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbagen.2013.02.022
AUTORES / AUTHORS: - Kuo PL; Liao SH; Hung JY; Huang MS; Hsu YL
INSTITUCIÓN / INSTITUTION: - Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
RESUMEN / SUMMARY: - BACKGROUND: Bone is a common site of metastasis for lung cancer, and is associated with significant morbidity and a dismal prognosis. MicroRNAs (miRNAs) are increasingly implicated in regulating the progression of malignancies. METHODS: The efficacy of miR-33a or anti-miR-33a plasmid was assessed by Real-time PCR. Luciferase assays were using One-Glo Luciferase Assay System. Measurement of secreted factors was determined by ELISA kit. RESULTS: We have found that miR-33a, which is downregulated in lung cancer cells, directly targets PTHrP (parathyroid hormone-related protein), a potent stimulator of osteoclastic bone resorption, leading to decreased osteolytic bone metastasis. We also found that miR-33a levels are inversely correlated with PTHrP expression between human normal bronchial cell line and lung cancer cell lines. The reintroduction of miR-33a reduces the stimulatory effect of A549 on the production of osteoclastogenesis activator RANKL (receptor activator of nuclear factor kappa-B ligand) and M-CSF (macrophage colony-stimulating factor) on osteoblasts, while the expression of PTHrP is decreased in A549 cells. miR-33a overexpression also reduces the inhibitory activity of A549 on the production of OPG (osteoprotegerin), an osteoclastogenesis inhibitor. In addition, miR-33a-mediated PTHrP downregulation results in decreased IL-8 secretion in A549, which contributes to decreased lung cancer-mediated osteoclast differentiation and bone resorption. CONCLUSIONS: These findings have led us to conclude that miR-33a may be a potent tumor suppressor, which inhibits direct and indirect osteoclastogenesis through repression of PTHrP. GENERAL SIGNIFICANCE: miR-33a may even predict a poor prognosis for lung cancer patients.
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[513]
TÍTULO / TITLE: - Significant Expression of Thyroid Transcription Factor-1 in Pulmonary Squamous Cell Carcinoma Detected by SPT24 Monoclonal Antibody and CSA-II System.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Appl Immunohistochem Mol Morphol. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1097/PAI.0b013e31828acad2
AUTORES / AUTHORS: - Kashima K; Hashimoto H; Nishida H; Arakane M; Yada N; Daa T; Yokoyama S
INSTITUCIÓN / INSTITUTION: - *Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Yufu, Oita daggerDepartment of Bioscience, Division of Oral Pathology, Kyushu Dental College, Kitakyushu, Japan.
RESUMEN / SUMMARY: - In contrast to the usefulness of thyroid transcription factor-1 (TTF-1) in distinguishing primary adenocarcinoma of the lung from metastatic lesions, TTF-1 expression in pulmonary squamous cell carcinoma is reported to be at low level and not a suitable immunohistochemical marker. We hypothesized that the highly sensitive detection system, CSA-II, can visualize even faint expression of TTF-1 in pulmonary squamous cell carcinoma. In this study, 2 commercially available clones of TTF-1 monoclonal antibody, 8G7G3/1 and SPT24, were used for staining 38 cases of pulmonary squamous cell carcinoma, in combination with the CSA-II and the conventional detection system, EnVision. The combined use of the 8G7G3/1 clone with EnVision and CSA-II showed a positive reaction in only 1 and 4 cases, respectively. The use of SPT24 clone showed positive staining in 5 cases with EnVision and in 20 of 38 cases (52.6%) with the CSA-II. Interestingly, positive staining by the SPT24-CSA-II technique of samples from tissue blocks preserved for <2 years was 73.6% compared with only 31.5% in those preserved for >2 years. In addition, a 6-month preservation of the cut sections resulted in stain fading and decreased positivity (50%), compared with freshly cut sections. We conclude that the use of the SPT24 monoclonal antibody with the CSA-II system can detect even weak expression of TTF-1 in pulmonary squamous cell carcinoma. This staining technique can potentially allow the discrimination of primary squamous cell carcinoma of the lung from metastatic lesions, especially in freshly prepared paraffin sections.
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[514]
TÍTULO / TITLE: - ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.
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-12-0868
AUTORES / AUTHORS: - Sun Y; Nowak KA; Zaorsky NG; Winchester CL; Dalal K; Giacalone NJ; Liu N; Werner-Wasik M; Wasik MA; Dicker AP; Lu B
INSTITUCIÓN / INSTITUTION: - 1Rad Onc, Thomas Jefferson University.
RESUMEN / SUMMARY: - Crizotinib (PF02341066) is a tyrosine kinase inhibitor of ALK that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion, found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials PF02341066 has shown a significant therapeutic benefit as a single agent, the effectiveness of combining it with other therapeutic modalities including ionizing radiation remains unknown. To further elucidate the role of PF02341066 in tumor inhibition, we examined its effects alone and in combination with radiation on downstream signaling, apoptosis, and radiosensitivity in two NSCLC cell lines in vitro: H3122, which harbors the EML4-ALK fusion; and H460, which does not. We also examined the in vivo effects of PF02341066 in H3122 mouse xenografts. In the H3122 cell line, PF02341066 inhibited phosphorylation of ALK and its downstream effectors: AKT, ERK, and STAT3. H3122 cells treated with a combination of PF02341066 and radiation showed an increase in cellular apoptosis and were sensitized to radiation therapy (dose enhancement ratio, 1.43; p < 0.0001). Moreover, in a H3122 xenograft model, the combined treatment resulted in greater tumor growth inhibition than either treatment alone (p < 0.05). None of these effects was observed in the EML4-ALK-negative H460 cells. Our findings indicate that PF02341066 acts as a radiation sensitizer in cells harboring the EML4-ALK fusion, providing a rationale for a clinical trial combining ALK inhibitor with radiation in the NSCLC expressing ALK.
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[515]
TÍTULO / TITLE: - Reports of ‘growth’ in survivors of non-small cell lung cancer and healthy controls: what is the value-added by the cancer experience?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Psychooncology. 2013 Mar 15. doi: 10.1002/pon.3281.
●● Enlace al texto completo (gratuito o de pago) 1002/pon.3281
AUTORES / AUTHORS: - Andrykowski MA; Steffens RF; Bush HM; Tucker TC
INSTITUCIÓN / INSTITUTION: - University of Kentucky, Department of Behavioral Science, Lexington, KY, USA.
RESUMEN / SUMMARY: - BACKGROUND: Reports of ‘growth’ following cancer diagnosis and treatment are common and are considered evidence for the transformative potential of the cancer experience. However, reports of growth are also common in the general population. This study sought to identify the unique, ‘value-added’ with regard to the nature and magnitude of growth represented by the cancer experience. METHODS: Lung cancer (LC) survivors (n = 190; mean 15 months post-diagnosis) completed the Posttraumatic Growth Inventory (PTGI), reporting changes occurring ‘as a result of having cancer’. Community-based, healthy controls (HC) (n = 152) completed the PTGI, reporting changes occurring ‘in the past year’. RESULTS: Reports of growth were common in both the LC and HC groups. However, the LC group reported greater total PTGI scores (effect size (ES) = 0.39 SD) and greater growth for 3 of 5 subscales (ESs 0.34-0.48 SD). The LC group was more likely to report any degree of change for 11 of 21 PTGI items (mean odds ratio (OR) across 21 items = 1.92) and were more likely to report ‘moderate’ to ‘very great’ change for eight of 21 items (mean OR = 1.75). The LC group was more likely to report growth in the areas of social relationships and appreciation for life. CONCLUSIONS: In sum, the growth evidenced by LC survivors after diagnosis quantitatively and qualitatively differs from growth reported by the general population over a similar period. Estimates of the value-added by the cancer experience suggest a magnitude representing at least the lower range of clinical significance. Copyright © 2013 John Wiley & Sons, Ltd.
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[516]
TÍTULO / TITLE: - Ultrasound finding predictive of malignant pleural effusion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Can Respir J. 2013 Jan;20(1):10.
AUTORES / AUTHORS: - Grondin-Beaudoin B; Dumoulin E
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[517]
TÍTULO / TITLE: - Acute Radiation Esophagitis Caused by High-dose Involved Field Radiotherapy with Concurrent Cisplatin and Vinorelbine for Stage III Non-small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Technol Cancer Res Treat. 2013 Jan 25.
●● Enlace al texto completo (gratuito o de pago) 7785/tcrt.2012.500319
AUTORES / AUTHORS: - Kuroda Y; Sekine I; Sumi M; Sekii S; Takahashi K; Inaba K; Horinouchi H; Nokihara H; Yamamoto N; Kubota K; Murakami N; Morota M; Mayahara H; Ito Y; Tamura T; Nemoto K; Itami J
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan. yuuki.kuroda.96@gmail.com.
RESUMEN / SUMMARY: - Purpose of this study is to obtain dose-volume histogram (DVH) predictors and threshold values for radiation esophagitis caused by high-dose involved field radiotherapy (IFRT) with concurrent chemotherapy in patients with stage III non-small cell lung cancer (NSCLC). Thirty-two patients treated by 66 Gy/33 Fr, 72 Gy/36 Fr, and 78 Gy/39 Fr thoracic radiotherapy without elective nodal irradiation plus concurrent cisplatin and vinorelvine were reviewed. Acute radiation esophagitis was evaluated according to common terminology criteria for adverse events version 4.0, and correlations between grade 2 or worse radiation esophagitis and DVH parameters were investigated. Grade 0-1, 2, 3, and 4-5 of radiation esophagitis were seen in 11 (34.4%), 20 (62.5%), 1 (3.1%), and 0 (0%) of the patients, respectively. Multivariate analysis revealed that whole esophagus V35 is a predictor of radiation esophagitis (OR = 0.74 [95%CI; 0.60-0.91], p = 0.006). There is a significant difference (38.4% vs. 89.4%, p = 0.027) in the cumulative rates of acute esophagitis according to V35 values of more than 20% versus less. As compared with other factors concerning patient and tumor and treatment factors, V35 </= 20% of the esophagus was an independent predictor (HR 5 0.29 [95%CI; 0.09-0.85], p 5 0.025). In conclusion, whole esophagus V35 < 20% is proposed in high-dose IFRT with concurrent chemotherapy for stage III NSCLC patients.
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[518]
TÍTULO / TITLE: - Is galectin-3 antibody a useful marker in the diagnosis of malignant pleural mesothelioma?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Immunoassay Immunochem. 2013 Apr;34(2):111-25. doi: 10.1080/15321819.2012.690356.
●● Enlace al texto completo (gratuito o de pago) 1080/15321819.2012.690356
AUTORES / AUTHORS: - Mlika M; Ayadi-Kaddour A; Ksantini M; Bouraoui S; Mzabi S; El Mezni F
INSTITUCIÓN / INSTITUTION: - a Department of Pathology , Abderrahman Mami Hospital , Ariana , Tunis , Tunisia.
RESUMEN / SUMMARY: - Malignant pleural mesothelioma (MPM) is a challenging diagnosis characterized by the absence of real specific diagnostic markers. Positivity with the galectin-3 antibody was assessed by a cytoplasmic expression in 17 MPM. Fourteen cases expressed the galectin-3 antibody. The three negative cases consisted of epithelioid, biphasic, and sarcomatoid MPM. The 14 positive cases consisted of epithelioid MPM in 12 cases, sarcomatoid MPM in one case, and biphasic MPM in one case. In spite of our inability to prove the real diagnostic value of the galectin-3 antibody, our findings make us wonder about the implication of this antibody in the carcinogenesis of MPM.
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[519]
TÍTULO / TITLE: - Both gefitinib and erlotinib induced drug-related interstitial lung disease in a patient with pulmonary adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Chin Med Assoc. 2013 Mar;76(3):173-5. doi: 10.1016/j.jcma.2013.01.012. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jcma.2013.01.012
AUTORES / AUTHORS: - Wang KF; Chang CY; Chang SC; Liu YC; Yuan MK; Yang YH
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, ROC.
RESUMEN / SUMMARY: - Treatment for non-small-cell lung cancer with gefitinib and erlotinib is efficacious. However, while many studies have reported on gefitinib-related interstitial lung disease (ILD), less published data are available regarding erlotinib-induced ILD. Here, we report a case of pulmonary adenocarcinoma who developed ILD due to gefitinib initially and erlotinib thereafter. The two episodes of ILD were treated successfully with the discontinuation of the tyrosine kinase inhibitors and high-dose intravenous corticosteroids.
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[520]
TÍTULO / TITLE: - Demographics and cell types of bronchial carcinoma of a tertiary care hospital in bangladesh.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mymensingh Med J. 2013 Jan;22(1):15-9.
AUTORES / AUTHORS: - Barman TK; Shahidullah M; Debnath CR; Hasan I; Alam NA; Paul GK; Pandit H
INSTITUCIÓN / INSTITUTION: - Dr Tushar Kanti Barman, Assistant Professor, Department of Medicine, Mymensingh Medical College (MMC), Mymensingh, Bangladesh.
RESUMEN / SUMMARY: - Geographical and socio-economic factors such as climate, culture, ethnic origin, diet and life style such as smoking have been noted to influence the occurrence of bronchial carcinoma. We conducted this study to document the frequency of various histological types of bronchial carcinoma and correlated it with their demographic characteristics. This descriptive study was carried out among admitted patient with the suspicion of Bronchial carcinoma from January 2010 to January 2011 in medicine units of Mymensingh Medical College Hospital, Mymensingh. Among those only 30 consecutive histopathologically &/or cytological confirmed cases of Bronchial carcinoma were included in the study. No age, gender, environmental or occupational limits were applied for the selection of patients. Patients already diagnosed by some other hospital presenting to our unit with complications were not included in the study. Age rang were 26-70 years. Majority of patients i.e. 63.33% (n=19) were found to be in their fourth and sixth decade of life. Males were 86.66% (n=26) as compared to females 13.44% (n=4) and male to female ratio were 6.5:1. The majority of the patients were belonged to urban areas 63.34% (n=19), while 36.66% (n=11) came from the Rural population. In this study smokers were 86.66% (n=26) and nonsmokers were 13.33% (n=4). In Occupational distribution farmers were 33.33% (n=10), service holders were 20% (n=6), businessman were 16.66% (n=5), all the female were house wife 13.33% (n=4). Specimens for histopathological study were collected by trans-thoracic needle aspiration under CT or ultrasono-guided. The results of cell types in histopathologically proven 30 Bronchial carcinoma patients were; 10(33.36%) adenocarcinoma, 7(23.33%) squamous cell carcinoma, 6(20%) small cell carcinoma, 4(13.33%) large cell carcinoma and 3(10%) non-small cell carcinoma.
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[521]
TÍTULO / TITLE: - Time-to-tumor dose threshold analysis for intratracheal particle instillation-induced lung tumors in a large carcinogenicity study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Occup Environ Health. 2012 Oct-Dec;18(4):278-91. doi: 10.1179/2049396712Y.0000000007.
●● Enlace al texto completo (gratuito o de pago) 1179/2049396712Y.0000000007
AUTORES / AUTHORS: - Roller M
INSTITUCIÓN / INSTITUTION: - Advisory Office for Risk Assessment, Dortmund, Germany. markus.roller@bmr-online.de
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVES: A comprehensive time-to-tumor analysis of the 16 dose groups which received intratracheal instillations of “respirable granular bio-durable particles without known significant specific toxicity” (GBP) in a large carcinogenicity study with rats should be conducted. METHODS: The primary lung tumors were mathematically treated as observed in an incidental context (non-fatal occult tumors), based on biological observations and on the fact that lifetime was not considerably reduced even in groups with high tumor frequency. Maximum likelihood estimates of the parameters of time-to-tumor multistage Weibull models were calculated. RESULTS: Retained dust volume is a highly significantly better dose measure than instilled dust mass, where particle size is taken into account; there is no empirical support for a dose threshold from this study. CONCLUSIONS: Carcinogenicity studies with intratracheal instillation can lead to results that are relevant for the assessment of relative carcinogenic potencies of particles. A dose threshold for GBP is not supported.
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[522]
TÍTULO / TITLE: - Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Pharmacol Sin. 2013 Apr;34(4):531-40. doi: 10.1038/aps.2012.196. Epub 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1038/aps.2012.196
AUTORES / AUTHORS: - Lei W; Liu HB; Wang SB; Zhou XM; Zheng SD; Guo KN; Ma BY; Xia YL; Tan WS; Liu XY; Wang YG
INSTITUCIÓN / INSTITUTION: - Xinyuan Institute of Medicine and Biotechnology, College of Biological Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.
RESUMEN / SUMMARY: - Aim:The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions.Methods:The recombinant virus Ad.sp-E1A(Delta24)-TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad.sp-E1A(Delta24) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad.sp-E1A(Delta24)-TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses.Results:Infection of A549 lung cancer cells with Ad.sp-E1A(Delta24)-TSLC1 induced high level expression of TSLC1. Furthermore, the Ad.sp-E1A(Delta24)-TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad.sp-E1A(Delta24)-TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad.sp-E1A(Delta24)-TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad.sp-E1A(Delta24)-TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues.Conclusion:The oncolytic adenovirus Ad.sp-E1A(Delta24)-TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer.
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[523]
TÍTULO / TITLE: - Assessment of FDG retention differences between the FDG-avid benign pulmonary lesion and primary lung cancer using dual-time-point FDG-PET imaging.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Nucl Med. 2013 Feb 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s12149-013-0698-4
AUTORES / AUTHORS: - Kaneko K; Sadashima S; Irie K; Hayashi A; Masunari S; Yoshida T; Omagari J
INSTITUCIÓN / INSTITUTION: - PET Imaging Center, Koga Hospital 21, 3-3-8 Miyanojin, Kurume, 839-0801, Japan, kkaneko-kyu@umin.ac.jp.
RESUMEN / SUMMARY: - PURPOSE: The aim of this study was to clarify FDG retention differences between FDG-avid benign pulmonary lesions (BPLs) and primary lung cancers (PLCs), and between tuberculous and non-tuberculous BPLs using dual-time-point FDG-PET imaging. METHODS: Thirty-four BPLs and 47 PLCs with a maximal standardized uptake value (SUVmax) >2.5 and a maximal axial diameter >10 mm were enrolled. We compared the retention index (RI) among different types of lesions, and evaluated the relationship between RI and SUV(max) at 1 h (SUV(1)). Glucose transporter-1 (Glut-1) and hexokinase (HK)-2 expression was assessed in eight non-tuberculous BPLs. RESULTS: BPLs and PLCs showed similar high RIs (mean +/- SD 33.6 +/- 22.6 and 32.5 +/- 23.7, respectively; p = 0.95). In BPLs, both tuberculous and non-tuberculous lesions showed high RIs (39.1 +/- 25.8 and 30.3 +/- 20.3, respectively; p = 0.43). However, BPLs and PLCs exhibited a different relationship between RI and SUV(1). BPLs tended to show lower RIs with higher SUV(1)s, and a mild negative correlation, whereas PLCs showed persistent high RIs and no significant correlation. Glut-1 and HK-2 expression was found in 75 and 12.5 % of non-tuberculous BPLs, respectively. CONCLUSIONS: FDG-avid BPLs could show high RIs regardless of their being tuberculous and non-tuberculous lesions, and no significant difference with PLC RIs was found. FDG-avid BPLs and PLCs showed different relationships between RI and SUV(1), and it seemed to be related with different mechanisms of high FDG retention. However, the mechanisms of high FDG retention in FDG-avid BPLs remain unclear, and this matter requires further investigation.
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[524]
TÍTULO / TITLE: - Dual EGFR inhibition in combination with anti-VEGF treatment: A phase I clinical trial in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncotarget. 2013 Jan;4(1):118-27.
AUTORES / AUTHORS: - Falchook GS; Naing A; Hong DS; Zinner R; Fu S; Piha-Paul SA; Tsimberidou AM; Morgan-Linnell SK; Jiang Y; Bastida C; Wheler JJ; Kurzrock R
INSTITUCIÓN / INSTITUTION: - Department of Investigational Cancer Therapeutics (Phase I Program), U.T. MD Anderson Cancer Center, Houston, TX.
RESUMEN / SUMMARY: - BACKGROUND: Preclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models. METHODS: We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response. RESULTS: Thirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade >/=2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD) >/=6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD>/=6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD>/=6 months or uPR. Correlation between grade of rash and rate of SD>/=6 months/PR was observed (p less than 0.01). CONCLUSION: The combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC.
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[525]
TÍTULO / TITLE: - Multimodality Approach to Management of Stage III Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Oncol Clin N Am. 2013 Apr;22(2):319-28. doi: 10.1016/j.soc.2012.12.014.
●● Enlace al texto completo (gratuito o de pago) 1016/j.soc.2012.12.014
AUTORES / AUTHORS: - Scarpaci A; Mitra P; Jarrar D; Masters GA
INSTITUCIÓN / INSTITUTION: - Medical Oncology, Albert Einstein Medical Center Philadelphia, 5501 Old York Road, Philadelphia, PA 19141, USA. Electronic address: apscarpaci@gmail.com.
RESUMEN / SUMMARY: - Stage III non-small cell lung cancer represents a heterogeneous group of patients who are best managed with a multidisciplinary approach, including evaluation for surgical, radiation, and chemotherapeutic options.
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[526]
TÍTULO / TITLE: - FDG-PET SUV-max values do not correlate with EGFR mutation status in lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Respirology. 2013 Mar 15. doi: 10.1111/resp.12083.
●● Enlace al texto completo (gratuito o de pago) 1111/resp.12083
AUTORES / AUTHORS: - Putora PM; Fruh M; Muller J
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Kantonsspital St. Gallen, Switzerland.
RESUMEN / SUMMARY: - Previous reports suggest a correlation between FDG PET SUVmax and EGFR mutation status in lung cancer. We analyzed FDG PET SUVmax in 14 patients with EGFR mutations and a control group of 14 subjects with wild-type EGFR adenocarcinomas. The mean SUV value was 10.7 for EGFR mutated adenocarcinomas and 9.9 for wild-type tumours. There was no correlation between SUV values and EGFR mutation status. Omitting EGFR testing in lung cancers with low SUVmax is not appropriate.
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[527]
TÍTULO / TITLE: - Molecular features in arsenic-induced lung tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer. 2013 Mar 19;12(1):20.
●● Enlace al texto completo (gratuito o de pago) 1186/1476-4598-12-20
AUTORES / AUTHORS: - Hubaux R; Becker-Santos DD; Enfield KS; Rowbotham D; Lam S; Lam WL; Martinez VD
RESUMEN / SUMMARY: - Arsenic is a well-known human carcinogen, which potentially affects ~160 million people worldwide via exposure to unsafe levels in drinking water. Lungs are one of the main target organs for arsenic-related carcinogenesis. These tumors exhibit particular features, such as squamous cell-type specificity and high incidence among never smokers. Arsenic-induced malignant transformation is mainly related to the biotransformation process intended for the metabolic clearing of the carcinogen, which results in specific genetic and epigenetic alterations that ultimately affect key pathways in lung carcinogenesis. Based on this, lung tumors induced by arsenic exposure could be considered an additional subtype of lung cancer, especially in the case of never-smokers, where arsenic is a known etiological agent. In this article, we review the current knowledge on the various mechanisms of arsenic carcinogenicity and the specific roles of this metalloid in signaling pathways leading to lung cancer.
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[528]
TÍTULO / TITLE: - A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy.
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-12-0785
AUTORES / AUTHORS: - Gurpinar E; Grizzle WE; Shacka JJ; Mader BJ; Li N; Piazza NA; Russo S; Keeton AB; Piazza GA
INSTITUCIÓN / INSTITUTION: - 1Pharmacology and Toxicology, University of Alabama at Birmingham.
RESUMEN / SUMMARY: - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer therapy. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 microM compared with 44-52 microM for SS. SSA also suppressed DNA synthesis and caused a G0/G1 cell cycle arrest. SSA-induced cell death was associated with characteristics of autophagy, but significant caspase activation or PARP cleavage were not observed after treatment at its IC50 value. siRNA knockdown of Atg7 attenuated SSA-induced autophagy and cell death, while pan-caspase inhibitor ZVAD was not able to rescue viability. SSA treatment also inhibited Akt/mTOR signaling and the expression of downstream proteins that are regulated by this pathway. Overexpression of a constitutively active form of Akt was able to reduce autophagy markers and confer resistance to SSA-induced cell death. Our findings provide evidence that SSA inhibits lung tumor cell growth by a mechanism involving autophagy induction through the suppression of Akt/mTOR signaling. This unique mechanism of action along with its increased potency and lack of cyclooxygenase inhibition support the development of SSA or related analogs for the prevention and/or treatment of lung cancer.
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[529]
TÍTULO / TITLE: - Assessing specific causation of mesothelioma following exposure to chrysotile asbestos-containing brake dust.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Occup Environ Health. 2012 Oct-Dec;18(4):329-36. doi: 10.1179/2049396712Y.0000000002.
●● Enlace al texto completo (gratuito o de pago) 1179/2049396712Y.0000000002
AUTORES / AUTHORS: - Freeman MD; Kohles SS
INSTITUCIÓN / INSTITUTION: - Department of Public Health & Preventive Medicine, Oregon Health & Science University, OR, USA.
RESUMEN / SUMMARY: - BACKGROUND: The question of whether chrysotile asbestos-containing brake dust can plausibly serve as a cause of mesothelioma in an exposed individual has become a matter of heated debate in the medical literature despite multiple international, federal, and state governmental agencies acknowledging a causal association. OBJECTIVES: We describe and provide an analysis of various industry and academic perspectives contributing to the debate. METHODS: A framework is presented for evaluating the general and specific causal relationship between brake dust exposure and mesothelioma utilizing the principles of forensic epidemiology, and by applying the Bradford-Hill criteria. RESULTS AND CONCLUSIONS: We conclude that there is a “net” of evidence favoring a causal relationship between brake dust-associated chrysotile exposure and mesothelioma. The industry-sponsored position that there is insufficient evidence to support a contiguous “chain” of causation is specious from both a methodologic and evidentiary perspective. Finally, we suggest a semiquantitative approach for the evaluation of individual causation in putative cases of mesothelioma with a history of significant brake dust exposure.
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[530]
TÍTULO / TITLE: - Role of 2-[18F]fluoro-2-deoxyglucose positron emission tomography in preoperative management of solid-type small-sized lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Nucl Med. 2013 Mar 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s12149-013-0715-7
AUTORES / AUTHORS: - Saisho S; Yasuda K; Maeda A; Yukawa T; Okita R; Hirami Y; Shimizu K; Nakata M
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Kawasaki Medical School Hospital, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan, s.saisho@med.kawasaki-m.ac.jp.
RESUMEN / SUMMARY: - OBJECTIVE: 2-[18F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is routinely used for the diagnosis of primary lung cancer. However, the role of FDG-PET in the diagnosis and staging of small-sized lung cancer has not been sufficiently evaluated. The purpose of this study was to determine the utility of FDG-PET for preoperative staging of solid-type small-sized lung cancer manifesting as solid-component predominant nodules. METHODS: One-hundred and eighteen patients with solid-type small-sized (</=2 cm) lung cancer diagnosed as clinical stage IA based on thin-slice computed tomography (TS-CT) were included in this study. Before surgery, FDG-PET was performed in 78 patients (CT/PET group), and TS-CT alone was performed in 40 patients (CT group). Clinical and pathological stage and prognosis were retrospectively reviewed according to whether FDG-PET had been performed. RESULTS: No significant differences in clinical factors were observed when comparing the CT/PET group and the CT group. Of the 78 patients in the CT/PET group, 12 (15.4 %) were diagnosed with clinical stage IIA or IIIA disease based on FDG-PET findings, but no advanced cases with contraindications for curative surgery were seen. In the CT/PET group, the pathological stage was IA in 66 patients, IB in eight patients, IIA in one patient, and IIIA in three patients; 16 patients had incorrectly staged disease. The accurate staging rate was 79.5 % for the CT-PET group and 70.0 % for the CT group (P = 0.262). Among patients diagnosed with clinical stage IA disease, the 3-year overall survival rate was 85.5 % for the 66 patients in the CT/PET group and 76.8 % for the 40 patients in the CT group (P = 0.554). No significant difference was observed in accuracy of preoperative staging and prognosis between the two groups. CONCLUSIONS: FDG-PET produced no clear benefit for the preoperative management of patients with solid-type clinical T1aN0M0 lung cancer, in terms of postoperative survival and the concordance rate of clinical and pathological stage.
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[531]
TÍTULO / TITLE: - Non-small cell lung cancer evaluated with quantitative contrast-enhanced CT and PET-CT: net enhancement and standardized uptake values are related to tumour size and histology.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Sci Monit. 2013 Feb 7;19:95-101. doi: 1.
AUTORES / AUTHORS: - Brunese L; Greco B; Setola FR; Lassandro F; Guarracino MR; De Rimini M; Piccolo S; De Rosa N; Muto R; Bianco A; Muto P; Grassi R; Rotondo A
INSTITUCIÓN / INSTITUTION: - Department of Medicine and Health Sciences, Universita del Molise, Contrada Tappino, Campobasso, Italy. lucabrunese@libero.it
RESUMEN / SUMMARY: - BACKGROUND: Personalized cancer therapy remains a challenge. In this context, we attempted to identify correlations between tumour angiogenesis, tumour metabolism and tumour cell type. To this aim, we used single=phase multidetector computed tomography (MDCT) and hybrid positron emission tomography-computed tomography (PET/CT) to determine whether net enhancement and standardized uptake value (SUVmax) were correlated with tumour size and cytology in patients affected by non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Our study included 38 patients (30 men, 8 women, mean age 70) with a NSCLC measuring between 3 cm and 7 cm, using a 16-slice multidetector CT (Brilliance Philips) and with PET-CT (Biograph 16 Siemens Medical Solutions). The following lesion parameters were evaluated: maximum diameter, medium density before contrast injection (CTpre), medium density after contrast injection (CTpost average), density in the most enhanced part of the lesion after contrast (CTpost max), net enhancement, SUVmax, age, and cytology. Correlation coefficient and p-value were computed for each pair of variables. In addition, correlations were computed for each pair of variables, and for all combinations of tumour types. We focused on subsets of data with more than 10 observations, and with correlation r>0.500 and p<0.05. RESULTS: A weak correlation (r=0.32; p=0.048) was found between SUVmax and tumour size; the correlation was stronger for masses larger than 31 mm (r=0.4515; p=0.0268). No other correlations were found among the variables examined. CONCLUSIONS: Our data may have prognostic significance, and could lead to more appropriate surgical treatment and better treatment outcome.
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[532]
TÍTULO / TITLE: - ALK Status Testing in Non-Small Cell Lung Carcinoma: Correlation Between Ultrasensitive IHC and FISH.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Mol Diagn. 2013 Mar 13. pii: S1525-1578(13)00040-8. doi: 10.1016/j.jmoldx.2013.01.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jmoldx.2013.01.004
AUTORES / AUTHORS: - Minca EC; Portier BP; Wang Z; Lanigan C; Farver CF; Feng Y; Ma PC; Arrossi VA; Pennell NA; Tubbs RR
INSTITUCIÓN / INSTITUTION: - Departments of Molecular and Anatomic Pathology, Pathology and Laboratory Medicine Institute, Cleveland, Ohio.
RESUMEN / SUMMARY: - ALK gene rearrangements in advanced non-small cell lung carcinomas (NSCLC) are an indication for targeted therapy with crizotinib. Fluorescence in situ hybridization (FISH) using a recently approved companion in vitro diagnostic class FISH system commonly assesses ALK status. More accessible IHC is challenged by low expression of ALK-fusion transcripts in NSCLC. We compared ultrasensitive automated IHC with FISH for detecting ALK status on 318 FFPE and 40 matched ThinPrep specimens from 296 patients with advanced NSCLC. IHC was concordant with FFPE-FISH on 229 of 231 dual-informative samples (31 positive and 198 negative) and with ThinPrep-FISH on 34 of 34 samples (5 positive and 29 negative). Two cases with negative IHC and borderline-positive FFPE-FISH (15% and 18%, respectively) were reclassified as concordant based on negative matched ThinPrep-FISH and clinical data consistent with ALK-negative status. Overall, after including ThinPrep-FISH and amending the false-positive FFPE-FISH results, IHC demonstrated 100% sensitivity and specificity (95% CI, 0.86 to 1.00 and 0.97 to 1.00, respectively) for ALK detection on 249 dual-informative NSCLC samples. IHC was informative on significantly more samples than FFPE-FISH, revealing additional ALK-positive cases. The high concordance with FISH warrants IHC’s routine use as the initial component of an algorithmic approach to clinical ALK testing in NSCLC, followed by reflex FISH confirmation of IHC-positive cases.
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[533]
TÍTULO / TITLE: - Potential of (18)F-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Nucl Med Mol Imaging. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2348-4
AUTORES / AUTHORS: - Choi NC; Chun TT; Niemierko A; Ancukiewicz M; Fidias PM; Kradin RL; Mathisen DJ; Lynch TJ; Fischman AJ
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA, nchoi@partners.org.
RESUMEN / SUMMARY: - PURPOSE: We investigated the metabolic response of lung cancer to radiotherapy or chemoradiotherapy by (18)F-FDG PET and its utility in guiding timely supplementary therapy. METHODS: Glucose metabolic rate (MRglc) was measured in primary lung cancers during the 3 weeks before, and 10-12 days (S2), 3 months (S3), 6 months (S4), and 12 months (S5) after radiotherapy or chemoradiotherapy. The association between the lowest residual MRglc representing the maximum metabolic response (MRglc-MMR) and tumor control probability (TCP) at 12 months was modeled using logistic regression. RESULTS: We accrued 106 patients, of whom 61 completed the serial (18)F-FDG PET scans. The median values of MRglc at S2, S3 and S4 determined using a simplified kinetic method (SKM) were, respectively, 0.05, 0.06 and 0.07 mumol/min/g for tumors with local control and 0.12, 0.16 and 0.19 mumol/min/g for tumors with local failure, and the maximum standard uptake values (SUVmax) were 1.16, 1.33 and 1.45 for tumors with local control and 2.74, 2.74 and 4.07 for tumors with local failure (p < 0.0001). MRglc-MMR was realized at S2 (MRglc-S2) and the values corresponding to TCP 95 %, 90 % and 50 % were 0.036, 0.050 and 0.134 mumol/min/g using the SKM and 0.70, 0.91 and 1.95 using SUVmax, respectively. Probability cut-off values were generated for a given level of MRglc-S2 based on its predicted TCP, sensitivity and specificity, and MRglc </=0.071 mumol/min/g and SUVmax </=1.45 were determined as the optimum cut-off values for predicted TCP 80 %, sensitivity 100 % and specificity 63 %. CONCLUSION: The cut-off values (MRglc </=0.071 mumol/min/g using the SKM and SUVmax </=1.45) need to be tested for their utility in identifying patients with a high risk of residual cancer after standard dose radiotherapy or chemoradiotherapy and in guiding a timely supplementary dose of radiation or other means of salvage therapy.
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[534]
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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[535]
TÍTULO / TITLE: - ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer.
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-12-0618
AUTORES / AUTHORS: - Zinn RL; Gardner EE; Marchionni L; Murphy SC; Dobromilskaya I; Hann CL; Rudin CM
INSTITUCIÓN / INSTITUTION: - 1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine.
RESUMEN / SUMMARY: - New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). IGF-1R inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC, and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways including PI3K-Akt and MAPK. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R and the closely related insulin receptor (IR). Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 < 1 muM. Cell line expression of IGF-1R, IR, IGF-1, IGF-2, IGFBP3, and IGFBP6 did not correlate with sensitivity to OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (p=0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared to mock treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach.
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[536]
TÍTULO / TITLE: - Erlotinib plus parenteral nutrition: an opportunity to get through the hardest days of advanced non-small cell lung cancer with cancer anorexia-cachexia syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Hosp Palliat Care. 2013 Mar;30(2):210-3. doi: 10.1177/1049909113476930. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1177/1049909113476930
AUTORES / AUTHORS: - Zang YS; Fang Z; Li B
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University/ Center for diagnosis and treatment of Lung Cancer of the Chinese Peoples’s Liberation Army, Shanghai, China.
RESUMEN / SUMMARY: - This case study details the poor performance status of a patient with non-small cell lung cancer and cancer anorexia-cachexia syndrome got through the hardest days of high tumor burden and malnutrition, by using a combined therapy of lung cancer-targeted therapy drug and parenteral nutrition. The related literatures were reviewed.
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[537]
TÍTULO / TITLE: - Severe pulmonary vein stenosis due to invasion of metastatic lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anadolu Kardiyol Derg. 2013 Feb 21. doi: 10.5152/akd.2013.094.
●● Enlace al texto completo (gratuito o de pago) 5152/akd.2013.094
AUTORES / AUTHORS: - Can MM
INSTITUCIÓN / INSTITUTION: - Clinic of Cardiology, Malatya State Hospital, Malatya-Turkey. mehmetmustafacan@yahoo.com.
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[538]
TÍTULO / TITLE: - The HSP90 inhibitor NVP-AUY922 potently inhibits non-small cell lung cancer growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0998
AUTORES / AUTHORS: - Garon EB; Finn RS; Hamidi H; Dering J; Pitts S; Kamranpour N; Desai AJ; Hosmer W; Ide S; Avsar E; Rugaard Jensen M; Quadt C; Liu M; Dubinett SM; Slamon DJ
INSTITUCIÓN / INSTITUTION: - 1Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA.
RESUMEN / SUMMARY: - Heat shock protein 90 (HSP90) is involved in protein folding and functions as a chaperone for numerous client proteins, many of which are important in non-small cell lung cancer (NSCLC) pathogenesis. We sought to define preclinical effects of the HSP90 inhibitor NVP-AUY922 and identify predictors of response. We assessed in vitro effects of NVP-AUY922 on proliferation and protein expression in NSCLC cell lines. We evaluated gene expression changes induced by NVP-AUY922 exposure. Xenograft models were evaluated for tumor control and biological effects. NVP-AUY922 potently inhibited in vitro growth in all 41 NSCLC cell lines evaluated with IC50 < 100 nM. IC100 (complete inhibition of proliferation) < 40 nM was seen in 36 of 41 lines. Consistent gene expression changes after NVP-AUY922 exposure involved a wide range of cellular functions, including consistently decreased dihydrofolate reductase (DHFR) after exposure. NVP-AUY922 slowed growth of A549 (KRAS mutant) xenografts, and achieved tumor stability and decreased epidermal growth factor receptor (EGFR) protein expression in H1975 xenografts, a model harboring a sensitizing and a resistance mutation for EGFR tyrosine kinase inhibitors in the EGFR gene. This data will help inform the evaluation of correlative data from a recently completed phase II NSCLC trial and a planned phase IB trial of NVP-AUY922 in combination with pemetrexed in NSCLC.
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[539]
TÍTULO / TITLE: - Regression of Lung Cancer by Hypoxia Sensitizing Ruthenium Polypyridyl Complexes.
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-12-1130
AUTORES / AUTHORS: - Yadav A; Janaratne T; Krishnan A; Singhal SS; Yadav S; Dayoub AS; Hawkins DL; Awasthi S; Macdonnell FM
INSTITUCIÓN / INSTITUTION: - 1Department of Chemistry and Biochemistry, University of Texas at Arlington.
RESUMEN / SUMMARY: - The ruthenium (II) polypyridyl complexes (RPCs) Delta-[(phen)(2)Ru(tatpp)]Cl(2) (Delta-[3]Cl(2)) and DeltaDelta-[(phen)(2)Ru(tatpp)Ru(phen)(2)]Cl(4) (DeltaDelta-[4]Cl(4)) are a new generation of metal-based anti-tumor agents. These RPCs bind DNA via intercalation of the tatpp ligand which itself is redox-active and easily reduced at biologically relevant potentials. We have previously shown that RPC 4(4+) cleaves DNA when reduced by glutathione to a radical species, and that this DNA cleavage is potentiated under hypoxic conditions in vitro. Here we show that 3(2+) also exhibits free-radical mediated DNA cleavage in vitro, and that 3(2+) and 4(4+) both exhibit selective cytotoxicity towards cultured malignant cell lines, and marked inhibition of tumor growth in vivo. The murine acute toxicity of RPCs 3(2+) and 4(4+) (maximum tolerable doses (MTD’s) ~ 65 mumol/kg) is comparable with that for cisplatin (LD(50) ~57 mumol/kg) but unlike cisplatin, RPC’s are generally cleared from the body unchanged via renal excretion without appreciable metabolism or nephrotoxic side effects. RPCs 3(2+) and 4(4+) are demonstrated to suppress growth of human non-small cell lung carcinoma (~83%), show potentiated cytotoxicity in vitro under hypoxic conditions, and induce apoptosis through both intrinsic and extrinsic pathways. The novel hypoxia-enhanced DNA cleavage activity and biological activity suggest a promising new anti-cancer pharmacophore based on metal complexes with aromatic ligands that are easily reduced at biologically accessible potentials.
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[540]
TÍTULO / TITLE: - Applications of array-CGH for lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Methods Mol Biol. 2013;973:297-324. doi: 10.1007/978-1-62703-281-0_19.
●● Enlace al texto completo (gratuito o de pago) 1007/978-1-62703-281-0_19
AUTORES / AUTHORS: - Craddock KJ; Lam WL; Tsao MS
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Toronto General Hospital University Health Network, Toronto, ON, Canada. ken.craddock@utoronto.ca
RESUMEN / SUMMARY: - This chapter summarizes the current knowledge on gene copy number changes found in lung tumors, and their application in the diagnosis, prognostication, and prediction of response to chemotherapy. Examples of the identification of specific “driver” oncogenes within amplified DNA segments are described. A model of how array-CGH could be integrated clinically into the routine workup of lung cancers in clinical laboratory is proposed.
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[541]
TÍTULO / TITLE: - Multidisciplinary Management of Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Oncol Clin N Am. 2013 Apr;22(2):329-43. doi: 10.1016/j.soc.2012.12.002. Epub 2013 Jan 9.
●● Enlace al texto completo (gratuito o de pago) 1016/j.soc.2012.12.002
AUTORES / AUTHORS: - Goldberg SB; Willers H; Heist RS
INSTITUCIÓN / INSTITUTION: - Department of Hematology/Oncology, Yale Cancer Center, 333 Cedar Street, FMP-130, PO Box 208032, New Haven, CT 06520, USA.
RESUMEN / SUMMARY: - The standard treatment of limited-stage small cell lung cancer (SCLC) is concurrent cisplatin and etoposide with thoracic radiation therapy, whereas treatment of extensive-stage disease is typically chemotherapy alone with a platinum compound plus etoposide. Surgical resection of early disease is generally reserved for patients with small, node-negative disease. Prophylactic cranial irradiation reduces the development of brain metastases and prolongs survival in patients with both limited-stage and extensive-stage disease who have responded to chemotherapy. Further understanding of the molecular underpinnings of SCLC is necessary to develop better treatment options and improve outcomes for patients.
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[542]
TÍTULO / TITLE: - Emerging mitotic inhibitors for non-small cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Emerg Drugs. 2013 Mar;18(1):97-107. doi: 10.1517/14728214.2013.777426.
●● Enlace al texto completo (gratuito o de pago) 1517/14728214.2013.777426
AUTORES / AUTHORS: - Casaluce F; Sgambato A; Maione P; Ciardiello F; Gridelli C
INSTITUCIÓN / INSTITUTION: - Second University of Naples, Department of Clinical and Experimental Medicine , Naples , Italy.
RESUMEN / SUMMARY: - Introduction: Mitosis is the key event of the cell cycle, and microtubules play an important part in an array of cellular functions besides mitosis, including maintenance of cell shape, cell locomotion, and the movement of intracellular organelles. Various anti-microtubule agents interfere with normal progression of mitosis, such as taxanes and vinca alkaloids. These compounds are widely used in the treatment of advanced non-small cell lung cancer (NSCLC), but their use has been limited by toxicity profile (hematologic and not), acquired resistance, and hypersensitivity reactions. Areas covered: Recently innovative drug carrier such as nanoparticle showed to reduce toxicity and improve drugs’ efficacy. Nanoparticle albumin-bound (nab)-paclitaxel has been recently approved for the use in breast and NSCLC with very promising results in pancreatic adenocarcinoma. Furthermore, the identification of novel mitotic drug targets other than microtubules has gained recently much attention, such as aurora kinases, Polo-like kinase1 (PLK1), kinesin spindle protein (KSP), and centromeric protein E (CENPE). Expert opinion: Despite recent advances in treatment, NSCLC continues to be the leading cause of cancer death worldwide. Novel agents that target the spindle microtubule elements of mitosis, as well as those that target the non-microtubule effectors of mitosis, are under investigation.
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[543]
TÍTULO / TITLE: - Long term survival of patients with unsuspected n2 disease in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Thorac Cardiovasc Surg. 2013 Feb;46(1):49-55. doi: 10.5090/kjtcs.2013.46.1.49. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 5090/kjtcs.2013.46.1.49
AUTORES / AUTHORS: - Lee DH; Kim JB; Keum DY; Hwang I; Park CK
INSTITUCIÓN / INSTITUTION: - Department of Thoracic and Cardiovascular Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Korea.
RESUMEN / SUMMARY: - BACKGROUND: The aim of this study was to determine the survival rate of patients with non-small cell lung cancer (NSCLC) who were preoperatively diagnosed with a negative N2 lymph node, but postoperatively confirmed as a positive N2 node based on a pathological evaluation. MATERIALS AND METHODS: The hospital records of 248 patients from 1994 to 2009 with resected primary NSCLC who were preoperatively diagnosed with negative N2 lymph node, were retrospectively reviewed. Of these, after surgery, there were 148 (59.7%) patients with pathological N0, 54 (21.8%) with pathological N1 and 46 (18.5%) with pathological N2. RESULTS: The median follow-up period was 24 months (range, 1 to 132 months). The 5-year disease free survival rates were 60% in pN0, 44% in pN1, and 29% in pN2. The 5-year overall survival rates were 63.1% in pN0, 51.9% in pN1, and 33.5% in pN2. There were no statistically significant differences between pN1 and pN2 (p=0.326 and p=0.106, respectively). Thirty-three (71.7%) of the 46 pN2 patients had single-zone metastasis, and 13 patients (28.3%) had multiple-zone metastases over the two nodal zone metastasis. There were no statistical differences in the 5-year disease free survival rate and the 5-year overall survival rates between the two groups. CONCLUSION: The 5-year disease free survival and the overall survival rate of the patients with unsuspected N2 disease were statistically similar with that of the patients with pathological N1 disease. There was no statistically significant difference between the patients with a single-zone metastasis and a multiple zone metastasis.
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[544]
TÍTULO / TITLE: - Surgical outcomes in patients with small cell lung cancer: comparative analysis of computed tomograpy-detected patients with others.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg Oncol. 2013 Mar 8;11:61. doi: 10.1186/1477-7819-11-61.
●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-61
AUTORES / AUTHORS: - Koizumi T; Fukushima T; Hamanaka K; Shiina T; Yoshida K; Kondo R; Yamamoto R; Nishizawa N
INSTITUCIÓN / INSTITUTION: - Comprehensive Cancer Therapy, Division of Clinical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi Matsumoto Nagano, Matsumoto city 390-8621, Japan. tomonobu@shinshu-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: It is shown that low-dose computed tomography (CT) screening is useful for a reduction in lung-cancer-specific mortality in heavy smokers. However, the information about effectiveness according to the histological types of lung cancer has not been adequately investigated especially small cell lung cancer (SCLC). The present study was performed to see the clinical benefit of CT screening in patients with SCLC following thoracotomy. METHODS: We retrospectively reviewed the outcome in patients with early stage SCLC who initially underwent thoracotomy. The clinical stages and actuarial survival were estimated according to the three means of detection of SCLC: chest CT, radiographic screen, and symptomatically prompted cases. RESULTS: Sixty-nine patients (men/women, 63/6; mean age, 70 years) with SCLC underwent thoracotomy between 1991 and 2010 including chest CT (n = 13), radiographic screening (n = 39), and symptomatically prompted cases (n = 17). Pathological staging information included stage IA (n = 25), IB (n = 8), IIA (n = 13), IIB (n = 5), IIIA (n = 11), and IIIB (n = 7). Median survival time was 30.0 (95% confidence interval (CI): 22.0 to 57.0) months, with overall survival at 5 years of 34.3% (95% CI, 23.47 to 47.3). Nine patients (69%) with stage I were detected by CT which was significantly higher than those in other detection arms. However, there were no significant differences in the survival between CT and other detection arms. CONCLUSIONS: CT examination may be useful for detection in early stage SCLC potentially suitable for surgery, but the contribution to better clinical outcome in patients with SCLC remains unclear.
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[545]
TÍTULO / TITLE: - Skin rash by gefitinib is a sign of favorable outcomes for patients of advanced lung adenocarcinoma in Japanese patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Springerplus. 2013 Dec;2(1):22. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1186/2193-1801-2-22
AUTORES / AUTHORS: - Sugiura Y; Nemoto E; Kawai O; Ohkubo Y; Fusegawa H; Kaseda S
INSTITUCIÓN / INSTITUTION: - Pulmonary and Thoracic Surgery, National Hospital Organization, Kanagawa National Hospital, 666-1 Ochiai, Hadano, Kanagawa, 257-8585 Japan.
RESUMEN / SUMMARY: - Skin rash is one of the notorious adverse events of gefitinib as well as other epidermal growth factor receptor tyrosine kinase inhibitors. The differences of response rate and frequency of adverse events between ethnic groups are well known. Some reports demonstrated the correlation between development of rash and efficacy in Caucasian patients treated with erlotinib, gefitinib or cetuximab. We analyzed clinical course of Japanese patients of lung adenocarcinoma in order to assess the relation between adverse events and efficacy of gefitinib. Between January 2008 and June 2012, 24 Japanese patients administered gefitinib 250 mg daily. The adverse events were evaluated in accordance with Common Terminology Criteria For Adverse Events v4.0 (CTCAE). Objective response to gefitinib was evaluated with using computed tomography every 1-2 months. The relationship between each adverse event and objective response was examined by chi-square test. The Log-rank Test was used to assess the relationship between the presence of skin rash and overall survival. Twenty four patients with a median age of 67 years (range 55-89) entered were 16 female and 8 male patients; the pathological diagnosis of all patients was adenocarcinoma. Skin rash in CTCAE occurred in 10. The objective response and overall survival among the patients with skin rash was significantly superior to the patients without skin rash. Skin rash by gefitinib correlates with improved clinical outcomes among advanced lung adenocarcinoma patients.
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[546]
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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[547]
TÍTULO / TITLE: - Moving towards molecular-guided treatments: erlotinib and clinical outcomes in non-small-cell lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Future Oncol. 2013 Mar;9(3):327-45. doi: 10.2217/fon.13.6.
●● Enlace al texto completo (gratuito o de pago) 2217/fon.13.6
AUTORES / AUTHORS: - Santarpia M; De Pas TM; Altavilla G; Spaggiari L; Rosell R
INSTITUCIÓN / INSTITUTION: - Medical Oncology Unit of Respiratory Tract & Sarcomas, New Drugs Development Division, European Institute of Oncology, Milan, Italy.
RESUMEN / SUMMARY: - Erlotinib is an orally administered small-molecule inhibitor of EGF receptor (EGFR) tyrosine kinase that is approved for the treatment of non-small-cell lung cancer (NSCLC) and pancreatic cancer. Erlotinib was first approved for the treatment of unselected NSCLC patients with advanced disease after failure of at least one prior chemotherapy regimen, and it was subsequently demonstrated to also confer a significant clinical benefit as maintenance therapy after first-line platinum-based chemotherapy. In all clinical studies, erlotinib treatment was associated with a good safety profile. Activating mutations in the EGFR gene have emerged as the strongest predictive marker of response to tyrosine kinase inhibitors, erlotinib and gefitinib, independently of other clinical and molecular features. Results from recently published, randomized Phase III trials showed that first-line erlotinib significantly prolongs progression-free survival in patients with advanced EGFR mutation-positive NSCLC with favorable tolerability, compared with standard chemotherapy. EGFR mutation testing is a crucial factor in the decision-making process regarding the most appropriate initial treatment option for patients. Specific molecular alterations in crucial genes have been discovered and associated with resistance to erlotinib, limiting its efficacy. New targeted agents and combined-treatment strategies are now under evaluation in clinical trials of NSCLC patients following progression to tyrosine kinase inhibitors.
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[548]
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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[549]
TÍTULO / TITLE: - A Trial-Based Cost-Effectiveness Analysis of Erlotinib Alone versus Platinum-Based Doublet Chemotherapy as First-Line Therapy for Eastern Asian Nonsquamous Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e55917. doi: 10.1371/journal.pone.0055917. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055917
AUTORES / AUTHORS: - Wang S; Peng L; Li J; Zeng X; Ouyang L; Tan C; Lu Q
INSTITUCIÓN / INSTITUTION: - Department of Pharmacy, the Second Xiangya Hospital of Central South University, Changsha Hunan, China ; School of Pharmaceutical Sciences, Central South University, Changsha Hunan, China.
RESUMEN / SUMMARY: - INTRODUCTION: Lung cancer, the most prevalent malignant cancer in the world, remains a serious threat to public health. Recently, a large number of studies have shown that an epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR TKI), Erlotinib, has significantly better efficacy and is better tolerated in advanced non-small cell lung cancer (NSCLC) patients with a positive EGFR gene mutation. However, access to this drug is severely limited in China due to its high acquisition cost. Therefore, we decided to conduct a study to compare cost-effectiveness between erlotinib monotherapy and carboplatin-gemcitabine (CG) combination therapy in patients with advanced EGFR mutation-positive NSCLC. METHODS: A Markov model was developed from the perspective of the Chinese health care system to evaluate the cost-effectiveness of the two treatment strategies; this model was based on data from the OPTIMAL trial, which was undertaken at 22 centres in China. The 10-year quality-adjusted life years (QALYs), direct costs, and incremental cost-effectiveness ratio (ICER) were estimated. To allow for uncertainties within the parameters and to estimate the model robustness, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. RESULTS: The median progression-free survival (PFS) obtained from Markov model was 13.2 months (13.1 months was reported in the trial) in the erlotinib group while and 4.64 months (4.6 months was reported in the trial) in the CG group. The QALYs were 1.4 years in the erlotinib group and 1.96 years in the CG group, indicating difference of 0.56 years. The ICER was most sensitive to the health utility of DP ranged from $58,584.57 to $336,404.2. At a threshold of $96,884, erlotinib had a 50%probability of being cost-effective. CONCLUSIONS: Erlotinib monotherapy is more cost-effective compared with platinum-based doublets chemotherapy as a first-line therapy for advanced EGFR mutation- positive NSCLC patients from within the Chinese health care system.
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[550]
TÍTULO / TITLE: - Chronic obstructive pulmonary disease and vascular disease delay timeliness of early stage lung cancer resectional surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - COPD. 2013 Apr;10(2):133-7. doi: 10.3109/15412555.2012.728260. Epub 2013 Mar 28.
●● Enlace al texto completo (gratuito o de pago) 3109/15412555.2012.728260
AUTORES / AUTHORS: - Seda G; Stafford CC; Parrish JS; Praske SP; Daheshia M
INSTITUCIÓN / INSTITUTION: - 1Department of Pulmonary Medicine, Naval Medical Center San Diego , San Diego, California , USA.
RESUMEN / SUMMARY: - Abstract Introduction: Lung cancer remains the leading cause of cancer death in the United States and worldwide. Timeliness to diagnosis and referral for resectional surgey is key to successful management for early stage disease. Methods: We investigated the contribution of medical co-morbidities in the timeliness to resectional surgery for non-small cell lung cancer (NSCLC). A retrospective record review of NSCLC surgery cases at Naval Medical Center San Diego (NMCSD) from 2004 to 2009 from the tumor registry was conducted. Results: More than 75% of NSCLC patients exhibited at least one co-morbidity. Of the 84 patients, 26% of patients had diabetes, patients with different vascular co-morbidities accounted for 39%, whereas 33% of subjects had COPD. Patients with sleep apnea or liver disease each accounted for 6%. Vascular disease co-morbidity and COPD in NSCLC patients significantly delayed time from initial cardiothoracic surgery evaluation to thoracotomy (p = 0.01-0.02 and p < 0.05 respectively). Conclusion: Although significances of different co-morbities in the development NSCLC cannot be extrapolated, theses data show that COPD and vascular diseases are significant risk factors that delay surgical treatment of early stage lung cancer.
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[551]
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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[552]
TÍTULO / TITLE: - Spinal Infarction Related to the Adjuvant Chemotherapy for Surgically Resected Non-small Cell Lung Cancer: Report of a Case.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt032
AUTORES / AUTHORS: - Matsutani N; Kawamura M
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
RESUMEN / SUMMARY: - We report the development of spinal infarction during adjuvant chemotherapy with tegafur, gimeracil and oteracil (TS-1) after surgery for lung adenocarcinoma. A 69-year-old female had a left upper lobectomy for pulmonary adenocarcinoma, T2aN0M0. Six weeks after the surgery, tegafur, gimeracil and oteracil were administered orally as adjuvant chemotherapy for 1 year. After 10 months of adjuvant chemotherapy, the patient suddenly showed signs of numbness and weakness in both lower limbs. The patient did not have a previous medical history, and was receiving only tegafur, gimeracil and oteracil with the stomach medication. Neurological findings showed muscle weakness, numbness and a loss of tendon reflex in both lower limbs, as well as bladder and rectal disturbance. Blood tests, brain magnetic resonance imaging and chest computed tomography showed no signs of abnormalities or metastasis. Magnetic resonance imaging of the spine showed a hyperintense lesion between the Th12 and L1 spinal levels by T2-weighted image. A spinal fluid test indicated no abnormalities, and cytological diagnosis was class II. Anti-aquaporin 4, anti-ganglioside and anti-neuronal autoantibodies were all negative. These results indicated that the patient had a spinal infarction, rather than myelitis or paraneoplastic neurological syndrome. The patient was treated with heparin and steroid pulse treatment followed by rehabilitation, and recovered sufficiently to be able to walk using a cane after 2 months. The development of spinal infarction during anti-cancer chemotherapy has not been previously reported. In this case, an association of spinal infarction with the use of adjuvant chemotherapy was strongly indicated due to the lack of abnormalities in coagulability, atherosclerotic lesions and aortic disease.
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[553]
TÍTULO / TITLE: - Flare response versus disease progression in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Radiol Case Rep. 2012 Nov;6(11):34-42. doi: 10.3941/jrcr.v6i11.1109. Epub 2012 Nov 1.
●● Enlace al texto completo (gratuito o de pago) 3941/jrcr.v6i11.1109
AUTORES / AUTHORS: - Al-Nabhani K; Syed R; Haroon A; Almukhailed O; Bomanji J
INSTITUCIÓN / INSTITUTION: - Institute of Nuclear Medicine, University College London Hospitals, London, UK. alnabhani5@hotmail.com
RESUMEN / SUMMARY: - We present a case report of a patient with metastatic non-small cell lung cancer (NSCLC) who had a series of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans for assessment of response to treatment. A restaging 18F-FDG PET/CT scan after six cycles showed increased FDG activity in the bone lesions with reduced activity in the lung and liver lesions. The increased bone activity was considered to be due to flare phenomenon rather than metastasis. A short interval follow up scan after 1 month was advised to confirm this interpretation but this repeat scan showed disease relapse. Although the flare phenomenon does exist, caution should be exercised in attributing increased tracer uptake in the lesions in patients with adenocarcinoma of lung and especially those who have received erlotinib during the course of their treatment. Distinguishing the ‘flare phenomenon’ and ‘disease progression’ is at times difficult but is important since misdiagnosis may result in an unnecessary delay in patient management.
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[554]
TÍTULO / TITLE: - CD133 expression: a potential prognostic marker for non-small cell lung cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Clin Oncol. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s10147-013-0541-x
AUTORES / AUTHORS: - Mizugaki H; Sakakibara-Konishi J; Kikuchi J; Moriya J; Hatanaka KC; Kikuchi E; Kinoshita I; Oizumi S; Dosaka-Akita H; Matsuno Y; Nishimura M
INSTITUCIÓN / INSTITUTION: - First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
RESUMEN / SUMMARY: - BACKGROUND: CD133 is a membrane glycoprotein containing five transmembrane loops. Previous reports suggest that a CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal characteristics has biological features of a cancer stem cell. In addition, the presence of CD133-positive cells was associated with a significantly poorer prognosis for some solid tumors, compared to those with CD133-negative cells. However, the clinicopathological significance of CD133 in non-small cell lung cancer (NSCLC) remains controversial. METHODS: We conducted immunohistochemical assessment of 161 NSCLCs surgically resected at Hokkaido University Hospital between 1982 and 1994 to evaluate correlations between CD133 expression and various clinicopathological features. RESULTS: CD133 expression was significantly correlated with pathological stages (pStages) II, III, and IV for the various NSCLC types analyzed and was an independent factor for unfavorable prognosis in this population (hazard ratio = 3.157, P = 0.015). CONCLUSION: CD133 expression was correlated with pStage and was predictive of unfavorable prognosis in patients with pStages II, III, and IV NSCLC. These results suggest the possibility of using CD133 as a novel prognostic marker in these patients.
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[555]
TÍTULO / TITLE: - Solitary lung metastasis after radical prostatectomy in presence of undetectable PSA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arch Ital Urol Androl. 2012 Dec;84(4):208-10.
AUTORES / AUTHORS: - Pepe P; Fraggetta F; Tornabene F; Nicolosi M; Aragona F
INSTITUCIÓN / INSTITUTION: - Urology Unit, Cannizzaro Hospital, Catania, Italy. piepepe@hotmail.com
RESUMEN / SUMMARY: - Clinical recurrence in the absence of biochemical PSA failure is uncommon and accounts for less than 1%; we report a rare case of solitary lung metastasis in a patient with undetectable PSA level (<0.1 ng/mL) after radical prostatectomy (RP) for prostate cancer (PCa). An asymptomatic 75-year-old man nine years after RP showed a solitary lung mass (about 2 cm) at chest radiography; the 18-FDG-PET/CT confirmed the presence of an isolated mass suspicious for primitive pulmonary cancer. The initial histological specimen after RP showed a mixed acinar and ductal PCa (Gleason score 7, pT3aNO stage, negative surgical margins). A segmental pulmonary resection was performed and definitive specimen demonstrated a single ductal PCa metastasis; after six months from surgery the patient was free from recurrence. In conclusion, in patients with atypical PCa variants imaging studies may be considered in the follow up even in presence of undetectable PSA because they could benefit from early salvage therapy.
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[556]
TÍTULO / TITLE: - Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Mar 21;11:71. doi: 10.1186/1479-5876-11-71.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-71
AUTORES / AUTHORS: - Zhong G; Cheng X; Long H; He L; Qi W; Xiang T; Zhao Z; Zhu B
INSTITUCIÓN / INSTITUTION: - Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People’s Republic of China. oncology_bozhu@yahoo.com.cn.
RESUMEN / SUMMARY: - BACKGROUND: CD8+ T cells are key members of adaptive immunity against tumorigenesis. As subset of CD8+ T cells, effector T cells (Te) and memory T cells ™ have different biological activities. The former can kill tumor cells but come into apoptosis in a certain period and the latter is static with the ability of self-renewal. Previous studies showed that microRNAs (miRNA) played critical roles in regulating adaptive immunity. This study aimed to identify the different expression of miRNAs between Te and Tm cells in tumor-bearing mice and to sort out the target miRNAs which can be regulated to improve anti-tumor activities of CD8+ T cells. METHODS: miRNA expression profiling was performed on CD8+ Te and Tm cells from mice with Lewis lung carcinoma. Differentially expressed miRNA (miRNA-15b) was chosen and analyzed by qRT-PCR. Then, flow cytometry, ELISA, and CFSE kit were used to evaluate the biological effects of miRNA-15b on apoptosis, cytokine secretion, phenotype, and proliferation of CD8+ T cell. The possible downstream target genes of this miRNA were also analyzed. RESULTS: Analysis of miRNA microarray and qRT-PCR showed that the level of miRNA-15b was higher in CD8+ Tm cells than in Te cells. Higher expression of miRNA-15b was observed in CD8+ T cells from tumor-bearing mice than those from healthy ones. Transfection of CD8+ T cells with miRNA-15b mimics could prevent T cells from apoptosis by inhibiting the translation of DEDD (Death Effector Domain-containing DNA binding protein). Moreover, ectopic miRNA-15b could inhibit the activation of CD8+ T cells (via repressing the production of IL-2 and IFN-gamma and expression of CD69) and promote expression of CD44 through unknown pathways. CONCLUSION: Up-regulation of miRNA-15b in tumor environment might negatively regulate anti-tumor immunity through inhibiting function of CD8+ T cells. miRNA-15b might be a potential therapeutic target for immunotherapy.
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[557]
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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[558]
TÍTULO / TITLE: - Imaging Characteristics of Stage I Non-Small Cell Lung Cancer on CT and FDG-PET: Relationship with Epidermal Growth Factor Receptor Protein Expression Status and Survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Radiol. 2013 Mar;14(2):375-83. doi: 10.3348/kjr.2013.14.2.375. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 3348/kjr.2013.14.2.375
AUTORES / AUTHORS: - Lee Y; Lee HJ; Kim YT; Kang CH; Goo JM; Park CM; Paeng JC; Chung DH; Jeon YK
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Seoul National University Hospital, Seoul 110-744, Korea. ; Department of Radiology, SMG-SNU Boramae Medical Center, Seoul 156-707, Korea.
RESUMEN / SUMMARY: - OBJECTIVE: To identify CT and FDG-PET features associated with epidermal growth factor receptor (EGFR) protein overexpression, and to evaluate whether imaging features and EGFR-overexpression can help predict clinical outcome. MATERIALS AND METHODS: In 214 patients (M : F = 129 : 85; mean age, 63.2) who underwent curative resection of stage I non-small cell lung cancer, EGFR protein expression status was determined through immunohistochemical analysis. Imaging characteristics on CT and FDG-PET was assessed in relation to EGFR-overexpression. Imaging features and EGFR-overexpression were also evaluated for clinical outcome by using the Cox proportional hazards model. RESULTS: EGFR-overexpression was found in 51 patients (23.8%). It was significantly more frequent in tumors with an SUVmax > 5.0 (p < 0.0001), diameter > 2.43 cm (p < 0.0001), and with ground glass opacity </= 50% (p = 0.0073). SUVmax > 5.0 (OR, 3.113; 95% CI, 1.375-7.049; p = 0.006) and diameter > 2.43 cm (OR, 2.799; 95% CI, 1.285-6.095; p = 0.010) were independent predictors of EGFR overexpression. Multivariate analysis showed that SUVmax > 4.0 (hazard ratio, 10.660; 95% CI, 1.370-82.966; p = 0.024), and the presence of cavitation within a tumor (hazard ratio, 3.122; 95% CI, 1.143-8.532; p = 0.026) were factors associated with poor prognosis. CONCLUSION: EGFR-overexpression is associated with high SUVmax, large tumor diameter, and small GGO proportion. CT and FDG-PET findings, which are closely related to EGFR overexpression, can be valuable in the prediction of clinical outcome.
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[559]
TÍTULO / TITLE: - Study of survival in patients with malignant lung lesions treated with radiofrequency.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1011-7
AUTORES / AUTHORS: - Galbis Caravajal JM; Jornet Fayos J; Cuenca Torres M; Molla Olmos E; Estors Guerrero M; Sanchez Garcia F; Martinez Hernandez NJ; Esturi Navarro R; Pastor Del Campo A; Vano Molina M
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, La Ribera University Hospital, Alcira, Valencia, España, jgalbis@hospital-ribera.com.
RESUMEN / SUMMARY: - OBJECTIVE: To report on the survival of a series of patients with primary and metastatic lung tumours treated with radiofrequency (RF). Four years ago we published our preliminary experience with the use of this technique. MATERIALS AND METHODS: For a period of 8 years we have treated 59 patients (by means of a total of 70 procedures) with primary or metastatic pulmonary neoplastic lesions, which fulfilled inclusion criteria to perform the technique. They were in all cases non-surgical lesions that had been either previously treated or not. The technique was performed in the radiology suite, under conscious analgo-sedation. We treated primary pulmonary lesions, neoplastic recurrences, or metastases with curative or palliative intention (pain management). RESULTS: Current global survival rate is 19 patients (32 %) with a mean of 26.61 +/- 3.17 months (range: 20.38 +/- 32.83) and a median of 16.00 +/- 3.57 (range: 8.99-23.00). If we establish the difference between primary and metastatic tumours, mean survival is 27.62 +/- 4.12 months in primary tumours (median: 16.00) vs. 24.65 +/- 4.47 months in metastatic tumours (median: 16.00). When we studied the survival in those cases with a curative intent, mean survival in primary tumours was 30.97 +/- 4.57 months (median: 21.00) vs. 25.14 +/- 4.68 (median: 16.00) months in metastatic tumours. CONCLUSIONS: RF ablation of lung lesions is a minimally invasive procedure that is useful in primary tumours (especially in stage I) and metastatic ones. RF has proven its usefulness in the multidisciplinary treatment of this pathology due to the low incidence of serious complications and survival obtained, considering that patients are elderly with significant comorbidity.
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[560]
TÍTULO / TITLE: - XRCC3 Gene Polymorphism Is Associated with Survival in Japanese Lung Cancer Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2012 Dec 5;13(12):16658-67. doi: 10.3390/ijms131216658.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms131216658
AUTORES / AUTHORS: - Osawa K; Nakarai C; Uchino K; Yoshimura M; Tsubota N; Takahashi J; Kido Y
INSTITUCIÓN / INSTITUTION: - Faculty of Health Sciences, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan. osawakysr@gmail.com.
RESUMEN / SUMMARY: - We focused on OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met and examined the relationship between the different genotypes and survival of Japanese lung cancer patients. A total of 99 Japanese lung cancer patients were recruited into our study. Clinical data were collected, and genotypes of the target genes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Survival analysis to verify the impact of these gene polymorphisms on the clinical outcome of lung cancer showed that lung squamous cell carcinoma patients with the Thr/Met genotype at XRCC3 had a significantly shorter survival time than those with the Thr/Thr genotype (13 months versus 48 months; log-rank test, p < 0.0001). Cox regression analysis showed that the carriers of XRCC3 genotypes were at a significantly higher risk [adjusted hazard ratio (HR) = 9.35, 95% confidence interval (CI) = 2.52-34.68, p = 0.001; adjusted HR = 9.05, 95% CI = 1.89-44.39, p = 0.006]. Our results suggest that XRCC3 Thr241Met may act as a favorable prognostic indicator for lung squamous cell carcinoma patients.
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[561]
TÍTULO / TITLE: - Southwestern Oncology Group Phase II Trial (S0526) of Pemetrexed in Bronchioloalveolar Carcinoma Subtypes of Advanced Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Feb 14. pii: S1525-7304(12)00271-9. doi: 10.1016/j.cllc.2012.12.004.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.12.004
AUTORES / AUTHORS: - Lau DH; Moon J; Davies AM; Sanborn RE; Hirsch FR; Franklin WA; Ruzich JC; Redman MW; Gandara DR
INSTITUCIÓN / INSTITUTION: - University of California, Davis, Sacramento, CA. Electronic address: derick.lau@ucdmc.ucdavis.edu.
RESUMEN / SUMMARY: - BACKGROUND: Pemetrexed, a multitargeted antifolate drug, is an active agent in non-small-cell lung cancer (NSCLC), especially adenocarcinomas. Based on preclinical data supporting the relevance of alpha-folate receptors in adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype, this trial was designed to assess pemetrexed in patients with this pathologic subtype of lung adenocarcinoma. PATIENTS AND METHODS: Patients with histologically confirmed stage IIIB (with malignant pleural effusion) or stage IV adenocarcinoma with BAC features or pure BAC were eligible. Treatment consisted of pemetrexed, 500 mg/m(2), administered intravenously every 21 days. RESULTS: Of 27 patients enrolled, 24 were eligible and assessable for adverse events: Toxicity was primarily hematologic, consisting of leukopenia/neutropenia, thrombocytopenia, and anemia. The median follow-up among patients still alive (n = 8) was 35 months (range, 26-47 months). Among 17 patients with measurable disease, the response rate was 23% (all partial responses; 95% confidence interval [CI], 10%-56%). The median progression-free survival (PFS) and overall survival (OS) were 6 and 25 months, respectively. CONCLUSION: Pemetrexed is active and well tolerated and, in patients with adenocarcinoma BAC subtypes, likely related to its underlying mechanism of action as a multitargeted antifolate drug.
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[562]
TÍTULO / TITLE: - Lung cancer screening with computer aided detection chest radiography: design and results of a randomized, controlled trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59650. doi: 10.1371/journal.pone.0059650. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059650
AUTORES / AUTHORS: - Mazzone PJ; Obuchowski N; Phillips M; Risius B; Bazerbashi B; Meziane M
INSTITUCIÓN / INSTITUTION: - Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
RESUMEN / SUMMARY: - INTRODUCTION: The sensitivity of CT based lung cancer screening for the detection of early lung cancer is balanced by the high number of benign lung nodules identified, the unknown consequences of radiation from the test, and the potential costs of a CT based screening program. CAD chest radiography may improve the sensitivity of standard chest radiography while minimizing the risks of CT based screening. METHODS: Study subjects were age 40-75 years with 10+ pack-years of smoking and/or an additional risk for developing lung cancer. Subjects were randomized to receive a PA view chest radiograph or placebo control (went through the process of being imaged but were not imaged). Images were reviewed first without then with the assistance of CAD. Actionable nodules were reported and additional evaluation was tracked. The primary outcome was the rate of developing symptomatic advanced stage lung cancer. RESULTS: 1,424 subjects were enrolled. 710 received a CAD chest radiograph, 29 of whom were found to have an actionable lung nodule on prevalence screening. Of the 15 subjects who had a chest CT performed for additional evaluation, a lung nodule was confirmed in 4, 2 of which represented lung cancer. Both of the cancers were seen by the radiologist unaided and were identified by the CAD chest radiograph. The cumulative incidence of symptomatic advanced lung cancer was 0.42 cases per 100 person-years in the control arm; there were no events in the screening arm. CONCLUSIONS: Further evaluation is necessary to determine if CAD chest radiography has a role as a lung cancer screening tool. ClinicalTrials.gov identifier NCT01663155.
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[563]
TÍTULO / TITLE: - Co-introduced functional CCR2 potentiates in vivo anti-lung cancer functionality mediated by T cells double gene-modified to express WT1-specific T-cell receptor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56820. doi: 10.1371/journal.pone.0056820. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056820
AUTORES / AUTHORS: - Asai H; Fujiwara H; An J; Ochi T; Miyazaki Y; Nagai K; Okamoto S; Mineno J; Kuzushima K; Shiku H; Inoue H; Yasukawa M
INSTITUCIÓN / INSTITUTION: - Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Ehime, Japan.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR) or chimeric antigen receptor (CAR) has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor. METHODOLOGY/PRINCIPAL FINDINGS: Human lung cancer cells variously express a tumor antigen, Wilms’ Tumor gene product 1 (WT1), and an inflammatory chemokine, CCL2. However, CCR2, the relevant receptor for CCL2, is rarely expressed on activated T-lymphocytes. A HLA-A2402(+) human lung cancer cell line, LK79, which expresses high amounts of both CCL2 and WT1 mRNA, was employed as a target. Normal CD8(+) T cells were retrovirally gene-modified to express both CCR2 and HLA-A*2402-restricted and WT1(235-243) nonapeptide-specific TCR as an effector. Anti-tumor functionality mediated by these effector cells against LK79 cells was assessed both in vitro and in vivo. Finally the impact of CCL2 on WT1 epitope-responsive TCR signaling mediated by the effector cells was studied. Introduced CCR2 was functionally validated using gene-modified Jurkat cells and human CD3(+) T cells both in vitro and in vivo. Double gene-modified CD3(+) T cells successfully demonstrated both CCL2-tropic tumor trafficking and cytocidal reactivity against LK79 cells in vitro and in vivo. CCL2 augmented the WT1 epitope-responsive TCR signaling shown by relevant luciferase production in double gene-modified Jurkat/MA cells to express luciferase and WT1-specific TCR, and CCL2 also dose-dependently augmented WT1 epitope-responsive IFN-gamma production and CD107a expression mediated by these double gene-modified CD3(+) T cells. CONCLUSION/SIGNIFICANCE: Introduction of the CCL2/CCR2 axis successfully potentiated in vivo anti-lung cancer reactivity mediated by CD8(+) T cells double gene-modified to express WT1-specific TCR and CCR2 not only via CCL2-tropic tumor trafficking, but also CCL2-enhanced WT1-responsiveness.
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[564]
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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[565]
TÍTULO / TITLE: - A Feasibility Study of Induction Pemetrexed Plus Cisplatin Followed by Pleurectomy/Decortication Aimed at Macroscopic Complete Resection for Malignant Pleural Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt035
AUTORES / AUTHORS: - Shimokawa M; Hasegawa S; Fukuoka K; Okada M; Yokoi K; Tanaka F; Yamanaka T; Daimon T; Nakano T
INSTITUCIÓN / INSTITUTION: - 1Clinical Research Institute, National Kyushu Cancer Center, Fukuoka.
RESUMEN / SUMMARY: - A prospective multi-institutional study has been initiated in Japan to evaluate the feasibility of induction chemotherapy using pemetrexed plus cisplatin, followed by pleurectomy/decortication aimed at macroscopic complete resection in patients with resectable malignant pleural mesothelioma. The study was initiated on September 2012, for which 24 patients will be recruited over a period of 2 years. The primary endpoint is the macroscopic complete resection rate, regardless of the surgical technique employed (i.e. pleurectomy/decortication or extrapleural pneumonectomy). The secondary endpoints are the pleurectomy/decortication rate, macroscopic complete resection rate by pleurectomy/decortication, pulmonary function at 3 months after surgery, adverse events, treatment-related mortality, response rate to chemotherapy and 3-year overall survival rate.
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[566]
TÍTULO / TITLE: - Relationship between Lung Adenocarcinoma Histological Subtype and Patient Prognosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Jan 31.
AUTORES / AUTHORS: - Urer HN; Kocaturk CI; Gunluoglu MZ; Arda N; Bedirhan MA; Fener N; Dincer SI
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Yedikule Teaching Hospital for ChestDiseases and Thoracic Surgery, Zeytinburnu, Istanbul, Turkey.
RESUMEN / SUMMARY: - Purpose: Lung adenocarcinoma (AC) demonstrates various histological subtypes within the tumour tissue. A panel established jointly by the IASLC, ATS and ERS classifi ed invasive lung ACs based on the predominant histological subtype. We examined the distribution of tumours in lung AC patients according to histological subtype and analysed the effects of this classification on survival. Methods: The records of patients who had pulmonary resection for lung cancer between January 2000 and December 2009 were reviewed and 226 lung AC patients who fulfi lled the inclusion criteria were identified. Histological subtypes of the ACs and their ratios in the tumour tissue were determined. Tumours were classified according to the predominant histological subtype and subsequently graded. The relationship between the predominant histological subtype, grade and survival were analysed. Results: Tumours were predominantly acinar in 99 cases (43.8%), solid in 89 (39.3%), lepidic in 20 (8.8%), and papillary in 11 (4.8%), whereas 7 tumours (3%) were variants of AC. Stage significantly affected survival (p = 0.001); however, the predominant histological subtype had no significant effect. The 5-year survival rate for patients with histologically grade II tumours was 48.6%, whereas that in patients with grade III tumours was 56%. (p = 0.69). Conclusion: Invasive lung ACs may be defined by their predominant histological subtype. However, it is not yet possible to conclude that this classification is related to survival.
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[567]
TÍTULO / TITLE: - Treatment outcome for patients with primary NSCLC and synchronous solitary metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1008-2
AUTORES / AUTHORS: - Xu Q; Wang Y; Liu H; Meng S; Zhou S; Xu J; Schmid-Bindert G; Zhou C
INSTITUCIÓN / INSTITUTION: - Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China.
RESUMEN / SUMMARY: - INTRODUCTION: Non-small cell lung cancer (NSCLC) patients with synchronous solitary metastasis were generally considered as stage IV and believed to be incurable. Recently, growing evidence has indicated that surgical treatment may provide these patients with a survival benefit. The aim of this study was to retrospectively analyze the effectiveness of different treatments for primary tumors and solitary metastases. MATERIALS AND METHODS: Patients older than 18 years with histologically confirmed stage IV NSCLC and a confirmed synchronous solitary metastasis that diagnosed within 2 months of primary NSCLC. Patients with uncontrolled massive pleural effusion were excluded. Between February 2002 and October 2010, 213 patients were considered eligible and enrolled in this cohort. RESULTS: The median survival time (MST) for the 213 patients was 12.6 months. Forty-five patients received primary pulmonary tumor surgery in the entire cohort. The MSTs of patients who received primary tumor resection and those who did not were 31.8 and 11.4 months (p < 0.01). The MST of the patients with solitary brain metastasis was 12.3 months. Forty-one patients who received brain surgical treatment or SRS had a MST of 15.4 months and others who only received WBRT had a MST of 11.5 months (p = 0.002). Gender, the stage of the primary tumor, PS and whether the primary tumor was removed all affected prognosis independently. CONCLUSIONS: Aggressive local and metastasis treatments could lead to better clinical outcomes and thus provide an option for clinicians in the future management of patients with NSCLC and synchronous solitary metastasis.
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[568]
TÍTULO / TITLE: - Paraneoplastic myasthenia gravis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Ark Med Soc. 2013 Feb;109(9):180-2.
AUTORES / AUTHORS: - Vora A; Chacko JG
INSTITUCIÓN / INSTITUTION: - Jones Eye Institute, Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
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[569]
TÍTULO / TITLE: - Antitumor effects of L-BLP25 Antigen-Specific tumor immunotherapy in a novel human MUC1 transgenic lung cancer mouse model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Mar 13;11(1):64.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-64
AUTORES / AUTHORS: - Wurz GT; Gutierrez AM; Greenberg BE; Vang DP; Griffey SM; Kao CJ; Wolf M; Degregorio MW
RESUMEN / SUMMARY: - BACKGROUND: L-BLP25 antigen-specific cancer immunotherapeutic agent is currently in phase III clinical trials for non-small cell lung cancer. Using a novel human MUC1 transgenic (hMUC1.Tg) lung cancer mouse model, we evaluated effects of L-BLP25 combined with low-dose cyclophosphamide (CPA) pretreatment on Th1/Th2 cytokine production and antitumor activity. METHODS: A chemically-induced lung tumor model was developed in hMUC1.Tg C57BL/6 mice by administering 10 weekly 0.75-mg/g doses of the chemical carcinogen urethane by intraperitoneal injection. Serum cytokines associated with Th1/Th2 polarization and inflammation were measured by multiplex cytokine assay during tumorigenesis. Antitumor activity of L-BLP25 (10 mug) with CPA (100 mg/kg) pretreatment was evaluated following either one or two eight-week cycles of treatment by preparing lung whole mounts and counting tumor foci, and assessing IFN-gamma production by ELISpot assay. RESULTS: During the carcinogenesis phase, no detectable Th1- or Th2-associated cytokine responses were observed, but levels of pro-inflammatory cytokines were increased with distinctive kinetics. A single cycle of L-BLP25 consisting of eight weekly doses was ineffective, whereas adding a second cycle given during tumor progression showed a significant reduction in the incidence of tumor foci. Administering two cycles of L-BLP25 induced Th1 cytokines IL-12, IL-2 and IFNgamma at 24 h after the last dose, while Th2 and inflammatory cytokines were elevated to a lesser extent. CONCLUSIONS: Urethane-induced lung tumors in hMUC1.Tg mice can be used as a model to assess the efficacy of the MUC1 antigen-specific cancer immunotherapeutic agent L-BLP25. The results indicate that the antitumor response to L-BLP25 requires at least two cycles and pre-treatment with CPA. In addition, monitoring pro-inflammatory serum cytokines may be useful as a biomarker of L-BLP25 response. Taken together, the preclinical lung tumor model can be utilized for determining effective combinations of L-BLP25 with chemotherapy and/or other immunotherapies.
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[570]
TÍTULO / TITLE: - Impact of Smoking History on Postoperative Pulmonary Complications: A Review of Recent Lung Cancer Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Mar 22.
AUTORES / AUTHORS: - Seok Y; Hong N; Lee E
INSTITUCIÓN / INSTITUTION: - Kyungpook National University Medical Center, Department of Thoracic and Cardiovascular Surgery.
RESUMEN / SUMMARY: - Purpose: Smoking is a well-known risk factor for postoperative pulmonary complications. As a consequence of pre and postoperative procedures continuing to be developed, postoperative complications continue to decrease. In this study, smoking as a risk factor for postoperative pulmonary complications is studied.Methods: From January 2005 to June 2009, postoperative pulmonary complications and smoking factors were analyzed from among 232 lung cancer patients with a smoking history. Smoking factors included cessation duration and pack-years. Also, relationships between pulmonary complications and patient factors, including gender, age, histological features, surgery methods, pulmonary function test, and body mass index were analyzed.Results: Univariate and multivariate analysis revealed that smoking factors were not significant risk factors for the development of postoperative pulmonary complications.Conclusion: Recently, the effect of smoking on the development of postoperative pulmonary complications has been reduced due to the increase in quality of pre and postoperative management and surgery procedures. Accordingly, there seems to be no need to delay operative procedures to secure a significant duration of smoking cessation duration in lung cancer patients.
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[571]
TÍTULO / TITLE: - Adult biphasic pulmonary blastoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Conn Med. 2013 Jan;77(1):19-22.
AUTORES / AUTHORS: - Jethava A; Dasanu CA
INSTITUCIÓN / INSTITUTION: - Department of Hospital Medicine, Saint Francis Hospital and Medical Center, Hartford, USA.
RESUMEN / SUMMARY: - Pulmonary blastoma is a rare malignant tumor, histologically resembling the fetal lung. Since its first description in 1945, only about 200 cases have been reported worldwide. This tumor predominantly affects children, but has also been reported in adults with a peak incidence in the fourth decade of life. Pulmonary blastoma has a variable clinical course that cannot be determined by its histological appearance. We report a 51-year-old patient with a large biphasic pulmonary blastoma who was treated with surgical excision. The patient remains disease-free eleven months postoperatively. As relapse rates are high in patients with large biphasic (type 2) tumors, the patient is being monitored closely. Although a rare occurrence after the age of 20, pulmonary blastoma should remain in the differential diagnosis of a lung mass in an adult.
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[572]
TÍTULO / TITLE: - Challenges and opportunities in patient-specific, motion-managed and PET/CT-guided radiation therapy of lung cancer: review and perspective.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Med. 2012 Aug 31;1(1):18. doi: 10.1186/2001-1326-1-18.
●● Enlace al texto completo (gratuito o de pago) 1186/2001-1326-1-18
AUTORES / AUTHORS: - Bowen SR; Nyflot MJ; Gensheimer M; Hendrickson KR; Kinahan PE; Sandison GA; Patel SA
INSTITUCIÓN / INSTITUTION: - University of Washington Medical Center, Department of Radiation Oncology, 1959 NE Pacific St, Box 356043, Seattle, WA 98195, USA. srbowen@uw.edu.
RESUMEN / SUMMARY: - The increasing interest in combined positron emission tomography (PET) and computed tomography (CT) to guide lung cancer radiation therapy planning has been well documented. Motion management strategies during treatment simulation PET/CT imaging and treatment delivery have been proposed to improve the precision and accuracy of radiotherapy. In light of these research advances, why has translation of motion-managed PET/CT to clinical radiotherapy been slow and infrequent? Solutions to this problem are as complex as they are numerous, driven by large inter-patient variability in tumor motion trajectories across a highly heterogeneous population. Such variation dictates a comprehensive and patient-specific incorporation of motion management strategies into PET/CT-guided radiotherapy rather than a one-size-fits-all tactic. This review summarizes challenges and opportunities for clinical translation of advances in PET/CT-guided radiotherapy, as well as in respiratory motion-managed radiotherapy of lung cancer. These two concepts are then integrated into proposed patient-specific workflows that span classification schemes, PET/CT image formation, treatment planning, and adaptive image-guided radiotherapy delivery techniques.
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[573]
TÍTULO / TITLE: - Depression, survival, and epidermal growth factor receptor genotypes in patients with metastatic non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Palliat Support Care. 2013 Feb 11:1-7.
●● Enlace al texto completo (gratuito o de pago) 1017/S1478951512001071
AUTORES / AUTHORS: - Pirl WF; Traeger L; Greer JA; Jackson V; Lennes IT; Gallagher E; Sequist L; Temel JS
INSTITUCIÓN / INSTITUTION: - Center for Psychiatric Oncology and Behavioral Sciences, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
RESUMEN / SUMMARY: - Objective: Although depression appears to be associated with worse survival from cancer, the underlying mechanisms of this association are unknown. Tumor epidermal growth factor receptor (EGFR) genotype is a known predictor of survival in metastatic non-small cell lung cancer (NSCLC) and appears to be associated with depression. We hypothesized that tumor EGFR genotype may account for a relationship between depression and survival in this population. We investigated this possible relationship in a cohort of patients with metastatic NSCLC, in which we had previously demonstrated an association between depression and worse survival. Method: A cohort of 151 patients with newly diagnosed metastatic NSCLC were enrolled and followed in a randomized controlled trial of early palliative care. At enrollment, 150 had depression assessed with the Patient Health Questionnaire-9 (PHQ-9), and categorical scoring for major depressive syndrome (MDS) was used for analyses. Patients with tumor tissue available underwent EGFR genotyping. Associations with survival were tested using Cox proportional hazards models, adjusting for potential confounders. Results: Twenty-one patients (14.0%) met criteria for MDS. Forty-four patients (29.3%) had EGFR genotyping, and 17 (38.6%) of these harbored EGFR mutations. Patients with EGFR mutations had significantly lower PHQ-9 scores (p = 0.03), and none met criteria for depression. EGFR mutations were significantly associated with superior survival (p = 0.02). When both depression and EGFR genotype were simultaneously entered into the model, only EGFR mutations remained significantly associated with survival (p = 0.02), and the effect of depression was attenuated. Significance of results: Depression is associated with worse survival in metastatic NSCLC, and this relationship may be at least partially explained by tumor EGFR genotype. Further study into whether depression could be associated with specific biologic properties of cancer that vary by genotype is warranted.
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[574]
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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[575]
TÍTULO / TITLE: - Depression and undertreatment of depression: potential risks and outcomes in black patients with lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Psychosoc Oncol. 2013 Mar;31(2):123-35. doi: 10.1080/07347332.2012.761320.
●● Enlace al texto completo (gratuito o de pago) 1080/07347332.2012.761320
AUTORES / AUTHORS: - Traeger L; Cannon S; Pirl WF; Park ER
INSTITUCIÓN / INSTITUTION: - a Center for Psychiatric Oncology and Behavioral Sciences , Massachusetts General Hospital , Boston , MA , USA.
RESUMEN / SUMMARY: - In the United States, Black men are at higher risk than White men for lung cancer mortality whereas rates are comparable between Black and White women. This article draws from empirical work in lung cancer, mental health, and health disparities to highlight that race and depression may overlap in predicting lower treatment access and utilization and poorer quality of life among patients. Racial barriers to depression identification and treatment in the general population may compound these risks. Prospective data are needed to examine whether depression plays a role in racial disparities in lung cancer outcomes.
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[576]
TÍTULO / TITLE: - Detection and clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e54170. doi: 10.1371/journal.pone.0054170. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054170
AUTORES / AUTHORS: - Bai H; Wang Z; Wang Y; Zhuo M; Zhou Q; Duan J; Yang L; Wu M; An T; Zhao J; Wang J
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
RESUMEN / SUMMARY: - PURPOSE: This study evaluated occurrence and potential clinical significance of intratumoral EGFR mutational heterogeneity in Chinese patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Eighty-five stage IIIa-IV NSCLC patients who had undergone palliative surgical resection were included in this study. Of these, 45 patients carried EGFR mutations (group-M) and 40 patients were wild-type (group-W). Each tumor sample was microdissected to yield 28-34 tumor foci and Intratumoral EGFR mutation were determined using Denaturing High Performance Liquid Chromatography (DHPLC) and Amplification Refractory Mutation System (ARMS). EGFR copy numbers were measured using fluorescence in situ hybridization (FISH). RESULTS: Microdissection yielded 1,431 tumor foci from EGFR mutant patients (group-M) and 1,238 foci from wild-type patients (group-W). The EGFR mutant frequencies in group-M were 80.6% (1,154/1,431) and 87.1% (1,247/1,431) using DHPLC and ARMS, respectively. A combination of EGFR-mutated and wild-type cells was detected in 32.9% (28/85) of samples by DHPLC and 28.2% (24/85) by ARMS, supporting the occurrence of intratumoral heterogeneity. Thirty-one patients (36.5%) were identified as EGFR FISH-positive. Patients harboring intratumoral mutational heterogeneity possessed lower EGFR copy numbers than those tumors contained mutant cells alone (16.7% vs. 71.0%, P<0.05). Among 26 patients who had received EGFR-TKIs, the mean EGFR mutation content was higher in patients showing partial response (86.1%) or stable disease (48.7%) compared with patients experiencing progressive disease (6.0%) (P = 0.001). There also showed relationship between progression-free survival (PFS) and different content of EGFR mutation groups (pure wild type EGFR, EGFR mutation with heterogeneity and pure mutated EGFR) (P = 0.001). CONCLUSION: Approximately 30% of patients presented intratumoral EGFR mutational heterogeneity, accompanying with relatively low EGFR copy number. EGFR mutant content was correlated with the response and prognosis of EGFR-TKIs.
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[577]
TÍTULO / TITLE: - Bronchial Anthracofibrosis and Macroscopic Tissue Pigmentation on EBUS-TBNA Predict a Low Probability of Metastatic Lymphadenopathy in Korean Lung Cancer Patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Korean Med Sci. 2013 Mar;28(3):383-7. doi: 10.3346/jkms.2013.28.3.383. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 3346/jkms.2013.28.3.383
AUTORES / AUTHORS: - Kim MA; Lee JC; Choi CM
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - The identification of mediastinal lymph nodes (LNs) in lung cancer is an important step of treatment decision and prognosis prediction. The endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used to assess the mediastinal LNs and tissue confirmation in lung cancer. As use of bronchoscopy or EBUS-TBNA has been increased, bronchial anthracofibrosis (BAF) has been detected frequently. Moreover, BAF is often accompanied by mediastinal lymphadenopathy and showed false-positive positron emission tomography uptake, which mimics metastatic lymphadenopathy in lung cancer patients. However, clinical implication of BAF during bronchoscopy is not well understood in lung cancer. We retrospectively reviewed 536 lung cancer patients who performed EBUS-TBNA and observed BAF in 55 patients. A total of 790 LNs were analyzed and macroscopic tissue pigmentation was observed in 228 patients. The adjusted odds ratio for predicting malignant LN was 0.46 for BAF, and 0.22 for macroscopic tissue pigmentation. The specificity of BAF and macroscopic tissue pigmentation for predicting a malignant LN was 75.7% and 42.2%, respectively, which was higher than the specificity of using LN size or standard uptake value on PET. In conclusion, BAF and macroscopic tissue pigmentation during EBUS-TBNA are less commonly found in malignant LNs than reactive LNs in Korean lung cancer patients.
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[578]
TÍTULO / TITLE: - Bronchial Stump Coverage with Fibrin Glue-Coated Collagen Fleece in Lung Cancer Patients Who Underwent Pneumonectomy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Feb 28.
AUTORES / AUTHORS: - Seok Y; Cho S; Lee E
INSTITUCIÓN / INSTITUTION: - Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Medical Center, Daegu, Korea.
RESUMEN / SUMMARY: - Purpose: Bronchopleural fistula (BPF) is a serious complication following pneumonectomy in lung cancer patients. The aim of this retrospective study is to investigate the efficacy of bronchial stump reinforcement with a collagen fleece coated with fibrin glue(TachoComb®).Methods: The bronchial stumps of 43 lung cancer patients who underwent pneumonectomy between January 1998 and January 2003 were covered with pericardial fat pad.From February 2003 to the March 2011, we used TachoComb to cover the bronchial stumps of all lung cancer patients undergoing pneumonectomy (20 cases). Several preoperative, intraoperative, and postoperative variables were recorded retrospectively.Results:Univariate analysis of comorbidities and risk factors did not show any significant differences between the two groups except for neoadjuvant chemotherapy. Postpneumonectomy BPF occurred in three of the 43 (7%) patients who had pericardial fat pad coverage and in none of the patients treated by TachoComb.Conclusion:Reinforcement of the bronchial stump with TachoComb is a simple procedure, comparable to coverage with viable tissue, and should be considered in the prevention of postpneumonectomy BPF.
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[579]
TÍTULO / TITLE: - Temozolomide and/or Erlotinib in the Treatment of Lung Cancer Patients With Progressive Central Nervous System Metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Neurol Res. 2012 Feb 1;2(1):1-9.
●● Enlace al texto completo (gratuito o de pago) 4021/jnr85w
AUTORES / AUTHORS: - Lukas RV; Nicholas MK; Villaflor V; Hoffman PC; Salgia R
INSTITUCIÓN / INSTITUTION: - Department of Neurology, University of Chicago, USA.
RESUMEN / SUMMARY: - Patients with lung cancer who develop brain metastases have a poor prognosis. Those patients with progressive brain metastases tend to have a dismal prognosis. Currently, there is no standard of care for the treatment of these patients. In this manuscript, we present a retrospective evaluation of 10 patients treated at our institution with a combination of temozolomide and/or erlotinib after disease progression in the central nervous system following radiation therapy. Median overall survival was 28 weeks. Median time to progression in the central nervous system was 14 weeks. Median time to progression systemically was 7.5 weeks. Some patients demonstrated prolonged stability of disease. A palliative regimen of temozolomide and/or erlotinib could be considered in progressive central nervous system metastases from lung cancer.
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[580]
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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[581]
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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[582]
TÍTULO / TITLE: - Skin rash as a surrogate marker of clinical response of targeted therapy using gefitinib in advanced or metastatic non-small-cell lung cancer—a retrospective study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Indian Med Assoc. 2012 Jul;110(7):474-6, 493.
AUTORES / AUTHORS: - Acharyya S; Sau S; Dasgupta P; Chakraborty A; Gangopadhyay S
INSTITUCIÓN / INSTITUTION: - Bankura Sammilani Medical College, Bankura 722102.
RESUMEN / SUMMARY: - This retrospective review of a single institution case series study was conducted to correlate the objective response and skin rash of gefitinib in patients with advanced or metastatic non-small-cell lung cancer(NSCLC). One hundred and forty-nine patients with advanced or metastatic NSCLC were treated with gefitinib (250 mg/day) as second line systemic therapy. Baseline patient characteristics were: More than 75% patients were above 50 years of age, males 64%; adenocarcinoma 52%. Sixty-one patients were excluded from the analysis due to varying reasons; only 88 remaining in the analysis. Partial response was observed in 15 patients (17%), and 34 patients (38.6%) had stable disease. The rest 39 patients (44.3%) had progressive disease on gefitinib therapy. There was a significantly longer median time to progression (TTP) of 7 months in females as compared to 5 months in males (p = 0.001). A highly significant association (p = 0.001) was observed between the grade of skin toxicity and the median time to disease progression, with the median TTP being 4 months in patients experiencing no skin toxicity as compared to 7 months with those grade 2 skin toxicity and 12 months with grade 3 skin toxicity. Gender (p = 0.003), and presence of skin toxicity (p = 0.0001) were having significant difference in median overall survival. On multivariate testing of the same using Cox regression analysis only presence of skin toxicity (p = 0.012) and gender (p = 0.003) was found to significant factors. Thus it can be concluded that occurrence of skin rash and female gender were associated with improved survival with gefitinib for recurrent NSCLC patients.
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[583]
TÍTULO / TITLE: - Association of epidermal growth factor receptor and K-Ras mutations with smoking history in non-small cell lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Feb;5(2):495-498. Epub 2012 Nov 23.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.829
AUTORES / AUTHORS: - Baykara O; Tansarikaya M; Demirkaya A; Kaynak K; Tanju S; Toker A; Buyru N
INSTITUCIÓN / INSTITUTION: - Departments of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Kocamustafapasa, Istanbul 34098;
RESUMEN / SUMMARY: - Lung cancer, a major health problem affecting the epithelial lining of the lower respiratory tract, is considered to be one of the deadliest types of cancer in males and females and it is well-known that smoking is the chief cause of lung cancer. In addition to smoking and environmental factors, genetic susceptibility may also contribute to the development of lung cancer. Previous studies have shown that certain non-small cell lung cancer (NSCLC) patients harbor gain-of-function mutations in the epidermal growth factor receptor gene (EGFR). Phosphorylated EGFR triggers the activation of intracellular signal transduction pathways, including the RAS-MAPK, PI3K-Akt and STAT pathways. However, K-Ras gene point mutations in codons 12, 13 or 61 cause the inactivation of GTPase activity which results in overstimulation of cellular growth and gives rise to neoplastic development. Our aim was to investigate the presence and association of EGFR and K-Ras mutations in 50 primary NSCLC patients with a smoking history by using real-time PCR and sequencing. EGFR mutations were detected in four patients (8%). Two of these mutations were L858R mutations and the remaining two were deletion mutations spanning between codons 746 and 750. The L858R mutation was significantly associated with smoking status (P=0.003). K-Ras codon 12 and 61 mutations were also observed in four patients. However, no association was observed between K-Ras mutations and the tumor staging, gender, histology and smoking status of the patients.
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[584]
TÍTULO / TITLE: - High prevalence of gene abnormalities in young patients with lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Dis. 2013 Feb;5(1):27-30. doi: 10.3978/j.issn.2072-1439.2012.12.02.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.12.02
AUTORES / AUTHORS: - Nagashima O; Ohashi R; Yoshioka Y; Inagaki A; Tajima M; Koinuma Y; Iwakami S; Iwase A; Sasaki S; Tominaga S; Takahashi K
INSTITUCIÓN / INSTITUTION: - Division of Respiratory Medicine, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu-shi, Chiba 279-0021, Japan;
RESUMEN / SUMMARY: - BACKGROUND: Recently, driver oncogenes in adenocarcinoma of the lung were identified, and several molecular target agents were introduced in the clinical setting. However, there are few reports on the frequency of gene abnormalities in young patients with lung cancer. MATERIALS AND METHODS: Twelve patients with lung adenocarcinoma aged 40 or younger at Juntendo University Urayasu Hospital or Juntendo University Hospital from July 2004 to March 2010 were analyzed for driver oncogene status including EGFR activating mutation, EML4-ALK fusion gene, and K-ras mutation. RESULTS: Four patients showed EGFR gene mutation. Five out of 7 EGFR mutation-negative patients showed positive results for EML4-ALK gene fusion. One case whose EGFR mutation was indeterminate. CONCLUSIONS: Driver oncogene including EGFR mutation and EML4-ALK fusion gene was identified in 9 of 12 cases (75%). Examination of gene abnormalities is essential in young patients with non-small cell lung cancer to provide the best treatment.
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[585]
TÍTULO / TITLE: - Clinicopathologic indices can improve patient selection in malignant mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncology (Williston Park). 2012 Dec;26(12):1175-6.
AUTORES / AUTHORS: - Sugarbaker DJ
INSTITUCIÓN / INSTITUTION: - Brigham and Women’s Hospital, Boston, Massachusetts, USA.
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[586]
TÍTULO / TITLE: - Efficacy and Safety of Oral Topotecan and Bevacizumab Combination as Second-Line Treatment for Relapsed Small-Cell Lung Cancer: An Open-Label Multicenter Single-Arm Phase II Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Feb 4. pii: S1525-7304(12)00268-9. doi: 10.1016/j.cllc.2012.12.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.12.003
AUTORES / AUTHORS: - Spigel DR; Waterhouse DM; Lane S; Legenne P; Bhatt K
INSTITUCIÓN / INSTITUTION: - Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN. Electronic address: dspigel@tnonc.com.
RESUMEN / SUMMARY: - BACKGROUND: Topotecan is currently the only US Federal Drug Administration (FDA)-approved drug for second-line treatment of relapsed small-cell lung cancer (SCLC). We investigated the efficacy and safety of a novel topotecan-bevacizumab combination in treating relapsed SCLC. PATIENTS AND METHODS: Each 21-day treatment cycle consisted of bevacizumab (15 mg/kg) administration on day 1 and oral topotecan (2.3 mg/m(2)/d) administration on days 1 to 5. Treatment was continued for 8 cycles or until disease progression/toxicity. The primary objective was evaluation of 3-month progression-free survival (PFS). Overall response rate (ORR), duration of response, time to response (TTR), and overall survival (OS) were secondary objectives. RESULTS: The study enrolled 50 patients between July 2008 and May 2010. The 3-month PFS was 65% (95% confidence interval [CI], 49.3%-76.9%), which was promising compared with the historical control of 50% (P = .017) but did not meet the predefined criteria for clinically meaningful improvement. Median PFS was 6.24 months for the sensitive subgroup (progression time from end of previous chemotherapy > 90 days; n = 27) and 2.91 months for the resistant subgroup (progression time </= 90 days; n = 23). No patient achieved complete response (CR), and the ORR was 16%. Twenty (40%) patients had stable disease (SD) and 13 (26%) had progressive disease (PD). Median OS, TTR, and duration of response were 7.4, 1.3, and 4.7 months, respectively. The worst reported adverse events (AEs) were grade ½ in 11 (22%) patients and grade 3/4/5 in 39 (78%) patients. CONCLUSION: Improvement in the 3-month PFS after treatment with topotecan-bevacizumab was promising compared with the historical control and justifies additional studies with this regimen.
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[587]
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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[588]
TÍTULO / TITLE: - Bronchopulmonary carcinoid presenting as dexamethasone suppressible Cushing’s syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - W V Med J. 2013 Jan-Feb;109(1):26-8.
AUTORES / AUTHORS: - Sofka S; Jackson T
INSTITUCIÓN / INSTITUTION: - West Virginia University, USA.
RESUMEN / SUMMARY: - INTRODUCTION: Cushing’s Syndrome is an endocrine condition with complex diagnostic pathways. Cortisol suppression from high dose dexamethasone usually points to the pituitary as the cause. We present the case of a patient with dexamethasone suppressible Cushing’s Syndrome from a bronchopulmonary carcinoid tumor. The tumor was only able to be localized with bronchoscopy. Our objective is to inform other physicians of dexamethasone suppressible carcinoid tumors which may require bronchoscopy to localize. CASE REPORT: A 52-year-old female presented with signs and symptoms of Cushing’s Syndrome. Cortisol and ACTH levels were significantly elevated. High dose dexamethasone suppressed cortisol production. However, no pituitary source was found. Standard imaging did not localize an ectopic source. The patient continued to have significant morbidity from the hypercortisolism. In order to avoid adrenalectomy, a bronchoscopy was empirically performed which revealed a bronchopulmonary carcinoid tumor. DISCUSSION: Bronchopulmonary carcinoid tumor should be in the differential diagnosis of dexamethasone suppressible Cushing’s Syndrome if a pituitary source is not localized. Also, we suggest that bronchoscopy be added to the diagnostic algorithm when conventional imaging studies fail to reveal the ectopic source. This may result in cure of the carcinoid malignancy as well as the Cushing’s Syndrome.
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[589]
TÍTULO / TITLE: - Development of a nursing model for life adjustment in patients with lung cancer in Japan.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nurs Health Sci. 2013 Feb 14. doi: 10.1111/nhs.12033.
●● Enlace al texto completo (gratuito o de pago) 1111/nhs.12033
AUTORES / AUTHORS: - Horii N; Maekawa A
INSTITUCIÓN / INSTITUTION: - Department of Nursing, College of Life and Health Sciences, Chubu University, Kasugai-city, Aichi-Ken, Japan.
RESUMEN / SUMMARY: - The aim of this study was to obtain basic data about the support for life adjustment in lung cancer patients in Japan. We identified factors that affect life adjustment in people with lung cancer, developed a model for life adjustment support of lung cancer patients, and investigated its validity. A survey was conducted using self-completed questionnaires, and responses were received by 203 individuals. Analysis of the responses revealed that life adjustment was regulated by six factors associated with positive self-evaluation: stress dissipation, fighting spirit, helplessness/hopelessness, full discussion with doctor about treatment, clarity of thought, and support network size. A model search with covariance structure analysis was conducted. The resulting model was revealed to have a goodness-of-fit index of 0.963, an adjusted goodness-of-fit index of 0.930, a comparative fit index of 0.974, and a root mean square error of approximation of 0.040. The findings suggest that improvements in quality of life can be expected by combining a positive self-evaluation in lung cancer patients and interventions to raise self-adjustment ability with the use of this Model, although it requires further testing.
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[590]
TÍTULO / TITLE: - Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Feb 6;14(2):3440-55. doi: 10.3390/ijms14023440.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14023440
AUTORES / AUTHORS: - Pastor MD; Nogal A; Molina-Pinelo S; Melendez R; Romero-Romero B; Mediano MD; Lopez-Campos JL; Garcia-Carbonero R; Sanchez-Gastaldo A; Carnero A; Paz-Ares L
INSTITUCIÓN / INSTITUTION: - Biomedicine Institute of Seville, Seville 41013, España. luis.pazares.sspa@juntadeandalucia.es.
RESUMEN / SUMMARY: - Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.
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[591]
TÍTULO / TITLE: - Measurement of mid-arm muscle circumference and prognosis in stage IV non-small cell lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):1063-1067. Epub 2013 Jan 11.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1128
AUTORES / AUTHORS: - Tartari RF; Ulbrich-Kulczynski JM; Filho AF
INSTITUCIÓN / INSTITUTION: - Department of Nutrition, Santa Casa de Misericordia Hospital;
RESUMEN / SUMMARY: - Overall survival (OS) varies widely in patients with stage IV non-small cell lung cancer (NSCLC). Strong prognostic factors are still needed to improve decision-making regarding standard treatment options, to stratify patients for inclusion in innovative therapeutic trials and to identify patients who would be best treated with palliative care rather than with systemic chemotherapy. Mid-arm muscle circumference (MAMC) is a bedside anthropometric measurement that estimates somatic protein reserve, an early indicator of nutritional depletion. This measurement is simple, non-invasive, objective and inexpensive to perform. We evaluated MAMC as a potential prognostic factor in patients with stage IV NSCLC. A total of 56 non-selected consecutive patients with stage IV NSCLC were evaluated. The MAMC measurement results for these patients were expressed as a percentage of the expected reference values, adjusted for gender and age. Patients were categorized as normal (MAMC >/=90%) or depleted (MAMC <90%). The mean age of patients was 63 years (range 47-80), and the mean MAMC was 89 (range 66-122), with 55% of patients classified as depleted. The median OS was 6.2 months (95% CI, 5.1-7.3). In the subgroup with normal MAMC, the median OS was 10.2 months (95% CI, 9.2-11.1). In patients classified as depleted, the median OS was 5.0 months (95% CI, 4.2-5.8). The difference in OS between these two subgroups was highly significant (p<0.001 by the log-rank test; HR=0.21; 95% CI, 0.09-0.5 for patients with normal MAMC). In a multivariate analysis with Karnofsky status, age and gender as covariates, the difference in OS between the MAMC groups remained statistically significant (p<0.001, according to the Cox proportional hazards model). MAMC is a strong independent prognostic factor in stage IV NSCLC patients. Patients with MAMC <90% of the expected value had poor OS.
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[592]
TÍTULO / TITLE: - Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiol Oncol. 2012 Dec;46(4):354-9. doi: 10.2478/v10019-012-0031-1. Epub 2012 Nov 9.
●● Enlace al texto completo (gratuito o de pago) 2478/v10019-012-0031-1
AUTORES / AUTHORS: - Rozman A; Silar M; Kosnik M
INSTITUCIÓN / INSTITUTION: - Department for Endoscopy ; Department for Pulmonology, University Clinic Golnik, Slovenia.
RESUMEN / SUMMARY: - BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.
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[593]
TÍTULO / TITLE: - Pulmonary cryptococcoma mimicking pulmonary malignancy in an immunocompetent adult: a case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ethiop Med J. 2012 Jul;50(3):275-8.
AUTORES / AUTHORS: - Kebede T; Reda N
INSTITUCIÓN / INSTITUTION: - Department of Radiology, School of Medicine, College of Health Sciences, Addis Ababa University (AAU).
RESUMEN / SUMMARY: - Pulmonary cryptococcal infection is commonly seen in HIV patients and in patients who have compromised cell mediated immunity. Its occurrence in immunocompetent individuals is uncommon. Here we present a young adult who presented with cough and hemoptysis and is negative for HIV testing and has no clinical and laboratory evidences of conditions compromising his cell mediated immunity. Radiologically manifested as a solitary huge parenchymal mass lesion mimicking lung malignancy. He was finally diagnosed as having pulmonary cryptococcoma after open biopsy. This is an uncommon manifestation of cryptococcoma in immunologically competent patient.
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[594]
TÍTULO / TITLE: - Toxicity of initial chemotherapy in older patients with lung cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Geriatr Oncol. 2013 Jan 1;4(1):64-70. Epub 2012 Oct 10.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jgo.2012.09.003
AUTORES / AUTHORS: - Zauderer MG; Sima CS; Korc-Grodzicki B; Kris MG; Krug LM
INSTITUCIÓN / INSTITUTION: - Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Department of Medicine, Weill Cornell Medical College, 300 East 66th Street, New York, NY 10065 USA.
RESUMEN / SUMMARY: - Despite the growing number of elderly patients with lung cancers, we lack adequate information about how best to treat them. A phase III trial demonstrated a survival benefit of doublet chemotherapy in elderly patients with lung cancers compared to single agents at the cost of increased toxicity. We undertook this study to identify and describe chemotherapy-associated toxicity patterns among elderly patients treated for lung cancers. We reviewed records of patients age 70 or older with metastatic lung cancers who received initial chemotherapy at the Memorial Sloan-Kettering Cancer Center during 2008 and 2009. We identified 70 patients: 28 (40%) completed at least 4 cycles of chemotherapy without dose reduction but 31 (44%) required hospitalization for toxicity. Baseline albumin <3.5 g/dL and anemia were associated with grade 3-5 chemotherapy-associated toxicity. Also, an increase in platelets from cycle 1 to cycle 2 was associated with chemotherapy-associated toxicity. No other statistically significant associations between chemotherapy-associated toxicity and putative biologic and functional risk factors, including age and performance status, were identified. Patients deemed eligible for chemotherapy by their physicians were just as likely to have severe chemotherapy-associated toxicity requiring hospitalization as to finish an initial course of therapy without any serious problems. An increase in platelet count from cycle 1 to cycle 2 was associated with increased toxicity. Additional research, such as exploration of inflammatory cytokines (PDGF, IL6, and IGF-1) to identify the mechanisms of chemotherapy tolerance and prospective evaluation and validation of existing metrics, is needed so that all patients can be appropriately risk stratified.
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[595]
TÍTULO / TITLE: - Immunohistochemical evaluation of p53 expression in lung cancer of patients with paraneoplastic rheumatic syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Oncol. 2013 Mar;35(1):41-4.
AUTORES / AUTHORS: - Lysenko SA
INSTITUCIÓN / INSTITUTION: - Pirogov National Medical University, Ministry of Health of Ukraine, Vinnitsa 21018, Ukraine.
RESUMEN / SUMMARY: - Aim: To study p53 expression in the tumor tissue of lung cancer (LC) patients with paraneoplastic rheumatic syndrome (PNRS). Materials and Methods: There have been used either biopsy or surgically resected tumor samples of 140 LC patients (83 patients without PNRS, 57 patients with PNRS). For evaluation of p53 expression in LC samples, immunohistochemical analysis was performed. Results: It has been shown that p53 expression in tumor samples from LC patients with PNRS was significantly higher compared to that in LC patients without PNRS. It has been shown that p53 expression is more frequently registered in patients with lung adenocarcinoma with PNRS than in patients with lung adenocarcinoma without this syndrome. Conclusion: The presence of PNRS in LC patients with p53 expression is associated with higher aggressiveness of tumor.
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[596]
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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[597]
TÍTULO / TITLE: - Rapidly evolving asymptomatic eosinophilia in a patient with lung adenocarcinoma causes cognitive disturbance and respiratory insufficiency: Case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):495-498. Epub 2012 Nov 9.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1020
AUTORES / AUTHORS: - Lo CH; Jen YM; Tsai WC; Chung PY; Kao WY
INSTITUCIÓN / INSTITUTION: - Departments of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, R.O.C.
RESUMEN / SUMMARY: - Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic. In this report, we presented the case of an 82-year-old patient with poorly differentiated lung adenocarcinoma and asymptomatic eosinophilia. The patient’s condition worsened rapidly over a week, with episodes of cognitive disturbance, shortness of breath and acute kidney dysfunction. These symptoms were associated with a 4-fold increase in circulating eosinophil counts. The poor condition hindered further anticancer treatment. Treatment of the eosinophilia with corticosteroids and hydroxyurea significantly reduced circulating eosinophil counts to below the initial levels. Results of this case report suggested that lung cancer patients should be monitored closely for rapidly worsening symptoms of cognitive disturbance and respiratory insufficiency as signs of life-threatening asymptomatic eosinophilia, in order to initiate corticosteroid treatment.
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[598]
TÍTULO / TITLE: - Resistance to DNA-damaging treatment in non-small cell lung cancer tumor-initiating cells involves reduced DNA-PK/ATM activation and diminished cell cycle arrest.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Jan 31;4:e478. doi: 10.1038/cddis.2012.211.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2012.211
AUTORES / AUTHORS: - Lundholm L; Haag P; Zong D; Juntti T; Mork B; Lewensohn R; Viktorsson K
INSTITUCIÓN / INSTITUTION: - Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
RESUMEN / SUMMARY: - Increasing evidence suggests that tumor-initiating cells (TICs), also called cancer stem cells, are partly responsible for resistance to DNA-damaging treatment. Here we addressed if such a phenotype may contribute to radio- and cisplatin resistance in non-small cell lung cancer (NSCLC). We showed that four out of eight NSCLC cell lines (H125, A549, H1299 and H23) possess sphere-forming capacity when cultured in stem cell media and three of these display elevated levels of CD133. Indeed, sphere-forming NSCLC cells, hereafter called TICs, showed a reduced apoptotic response and increased survival after irradiation (IR), as compared with the corresponding bulk cell population. Decreased cytotoxicity and apoptotic signaling manifested by diminished poly (ADP-ribose) polymerase (PARP) cleavage and caspase 3 activity was also evident in TICs after cisplatin treatment. Neither radiation nor cisplatin resistance was due to quiescence as H125 TICs proliferated at a rate comparable to bulk cells. However, TICs displayed less pronounced G2 cell cycle arrest and S/G2-phase block after IR and cisplatin, respectively. Additionally, we confirmed a cisplatin-refractory phenotype of H125 TICs in vivo in a mouse xenograft model. We further examined TICs for altered expression or activation of DNA damage repair proteins as a way to explain their increased radio- and/or chemotherapy resistance. Indeed, we found that TICs exhibited increased basal gammaH2AX (H2A histone family, member X) expression and diminished DNA damage-induced phosphorylation of DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia-mutated (ATM), Kruppel-associated protein 1 (KAP1) and monoubiquitination of Fanconi anemia, complementation group D2 (FANCD2). As a proof of principle, ATM inhibition in bulk cells increased their cisplatin resistance, as demonstrated by reduced PARP cleavage. In conclusion, we show that reduced apoptotic response, altered DNA repair signaling and cell cycle perturbations in NSCLC TICs are possible factors contributing to their therapy resistance, which may be exploited for DNA damage-sensitizing purposes.
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[599]
TÍTULO / TITLE: - Spinal Tuberculosis (Pott’s disease) Mimicking Paravertebral Malignant Tumor in a Child Presenting with Spinal Cord Compression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Lab Physicians. 2012 Jul;4(2):98-100. doi: 10.4103/0974-2727.105590.
●● Enlace al texto completo (gratuito o de pago) 4103/0974-2727.105590
AUTORES / AUTHORS: - Emir S; Erdem AY; Demir HA; Kacar A; Tunc B
INSTITUCIÓN / INSTITUTION: - Department of Pediatric Hematology Oncology, SB Ankara Children’s Hematology Oncology Training and Research Hospital, Ankara, Turkey.
RESUMEN / SUMMARY: - Paravertebral tumors may interfere with the radiological and clinical features of spinal tuberculosis. We report a case of a 3-year-old boy with spinal tuberculosis who was initially misdiagnosed as having a paraspinal tumor. The diagnosis of tuberculosis was made on the basis of intraoperative findings and confirmed by histopathology. This case highlights the importance of awareness of the different radiographic features of spinal tuberculosis, which can mimic a spinal malignancy. In order to avoid delayed diagnosis, pediatricians and radiologists must be aware of spinal tuberculosis, which may interfere with other clinical conditions.
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[600]
TÍTULO / TITLE: - Postoperative complications in elderly patients after lung cancer surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Interact Cardiovasc Thorac Surg. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivt034
AUTORES / AUTHORS: - Shiono S; Abiko M; Sato T
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.
RESUMEN / SUMMARY: - OBJECTIVESThe purpose of this study was to identify the risk factors for postoperative complications in elderly patients undergoing lung cancer surgery. These complications remain higher in elderly patients than in young patients, and decreasing their incidence is an important goal. We investigated surgical factors in particular, including surgical time, blood loss and thoracotomy length.METHODSBetween January 2000 and September 2009, 567 patients underwent lung cancer surgery at our institution. We retrospectively reviewed the records of 119 patients who underwent lobectomy, aged 75 years or older, for possible postoperative complication risk factors.RESULTSThe patients’ median age was 77 years (range, 75-88 years); there were 79 men and 40 women. There were no perioperative or postoperative deaths. Postoperative complications developed in 41 (34.5%) patients, including 17 (14.3%) with arrhythmia, 10 (8.4%) with prolonged air leak, 10 (8.4%) with delirium, 8 (6.7%) with pneumonia, 4 (3.4%) with hypoxia, 2 (1.7%) with cerebrovascular disease and 1 (0.8%) with postoperative haemorrhage. Univariate analysis showed that the risk factors for postoperative complications consisted of longer surgery time (P = 0.002), blood loss (P = 0.021) and undergoing surgery prior to May 2004 (P = 0.002). Multivariate analysis revealed that surgery time (P = 0.041) and surgery prior to May 2004 (P = 0.008) were independent risk factors for postoperative complications.CONCLUSIONSThis study demonstrates that the quality of surgery is an important factor in determining the risk of postoperative complications. Severe adhesions and lung inflammation are conditions that make lung cancer surgery difficult; a skillful and meticulous surgical technique is required in elderly patients.
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[601]
TÍTULO / TITLE: - EGFR Mutation Testing in Patients with Advanced Non-Small Cell Lung Cancer: A Comprehensive Evaluation of Real-World Practice in an East Asian Tertiary Hospital.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56011. doi: 10.1371/journal.pone.0056011. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056011
AUTORES / AUTHORS: - Choi YL; Sun JM; Cho J; Rampal S; Han J; Parasuraman B; Guallar E; Lee G; Lee J; Shim YM
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - INTRODUCTION: Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. METHODS: Our retrospective cohort included 1,503 NSCLC patients aged >/=18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. RESULTS: This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. CONCLUSIONS: In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.
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[602]
TÍTULO / TITLE: - Comparative analysis of carboplatin and paclitaxel combination chemotherapy schedules in previously untreated patients with advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):761-767. Epub 2013 Jan 15.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1134
AUTORES / AUTHORS: - Shimizu T; Yokoi T; Tamaki T; Kibata K; Inagaki N; Nomura S
INSTITUCIÓN / INSTITUTION: - First Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
RESUMEN / SUMMARY: - The combination of carboplatin and paclitaxel is one of the most commonly used regimens for the treatment of non-small cell lung cancer (NSCLC). We aimed to compare the standard tri-weekly and weekly schedules of this treatment, while considering treatment-related hematological toxicities. We retrospectively analyzed the weekly [paclitaxel, 70 mg/m(2)/week on days 1, 8 and 15, and carboplatin, area under the curve (AUC)=6, every 4 weeks] and standard tri-weekly (paclitaxel, 200 mg/m(2), and carboplatin, AUC=6, on day 1 every 3 weeks] schedules in patients with previously untreated advanced NSCLC. A total of 167 patients were enrolled in this study. The median age of the patients was 65 years (range, 31-79 years). The weekly and standard arms included 73 and 94 patients, respectively. The incidence of grade 3 or 4 neutropenia and neuropathy was significantly decreased in the weekly arm compared with the standard arm (37.0 vs. 70.2%). The median survival and progression-free survival times were 11.8 and 4.2 months, respectively, in the weekly arm and 11.6 and 3.1 months, respectively, in the standard arm. The results of the multivariate analysis indicated that the weekly schedule [hazard ratio (HR)=0.634, P=0.0262] and grade 3 or 4 neutropenia (HR=0.372, P=0.0007) were independent favorable prognostic factors for overall survival time. In conclusion, the weekly schedule of carboplatin and paclitaxel was less toxic than and potentially superior to the standard tri-weekly schedule. However, further optimization of the dose and schedule is warranted.
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[603]
TÍTULO / TITLE: - Laryngeal cancer: smoking is not the only risk factor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - B-ENT. 2012;8(4):273-8.
AUTORES / AUTHORS: - Vassileiou A; Vlastarakos PV; Kandiloros D; Delicha E; Ferekidis E; Tzagaroulakis A; Nikolopoulos TP
INSTITUCIÓN / INSTITUTION: - 1st ENT Department, University of Athens, Hippokrateion General Hospital, Athens, Greece.
RESUMEN / SUMMARY: - AIM: To investigate the role of smoking, alcohol, coffee consumption, demographic factors, toxic agents, and occupation in laryngeal carcinogenesis. MATERIALS/METHODS: A case-control study included 70 patients with histologically confirmed laryngeal cancer and 70 controls with non-neoplastic conditions unrelated to diet/smoking/alcohol. Relative risk, odds ratio (OR), and 95% confidence intervals were estimated using multiple logistic regression. RESULTS: Current smokers had 19.46 OR of laryngeal cancer compared to non-smokers (p = 0.006). The respective OR for alcohol consumption was 3.94 (p = 0.006). While the risk increased in heavy drinkers, there was no difference in duration of alcohol consumption. There was a strong and consistent relation between laryngeal cancer and the consumption of Greek/Turkish coffee cups/day (p = 0.002, OR = 1.77). Diesel exhaust fumes also seemed to increase the risk of laryngeal cancer, although the association was found to be no longer significant after analysis with logistic regression. CONCLUSION: The present study confirmed the relation of smoking and alcohol with laryngeal cancer. However, other factors such as coffee and diesel exhaust fumes may play an important role in laryngeal carcinogenesis.
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[604]
TÍTULO / TITLE: - FoxM1 Is Associated with Poor Prognosis of Non-Small Cell Lung Cancer Patients through Promoting Tumor Metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59412. doi: 10.1371/journal.pone.0059412. Epub 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059412
AUTORES / AUTHORS: - Xu N; Jia D; Chen W; Wang H; Liu F; Ge H; Zhu X; Song Y; Zhang X; Zhang D; Ge D; Bai C
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - BACKGROUND: FoxM1 has been reported to be important in initiation and progression of various tumors. However, whether FoxM1 has any indication for prognosis in non-small cell lung cancer patients remains unclear. METHODOLOGYPRINCIPAL FINDINGS: In this study, FoxM1 expression in tumor cells was examined first by immunohistochemistry in 175 NSCLC specimens, the result of which showed that FoxM1 overexpression was significantly associated with positive smoking status (P = 0.001), poorer tissue differentiation (P = 0.0052), higher TNM stage (P<0.0001), lymph node metastasis (P<0.0001), advanced tumor stage (P<0.0001), and poorer prognosis (P<0.0001). Multivariable analysis showed that FoxM1 expression increased the hazard of death (hazard ratio, 1.899; 95% CI, 1.016-3.551). Furthermore, by various in vitro and in vivo experiments, we showed that targeted knockdown of FoxM1 expression could inhibit the migratory and invasive abilities of NSCLC cells, whereas enforced expression of FoxM1 could increased the invasion and migration of NSCLC cells. Finally, we found that one of the cellular mechanisms by which FoxM1 promotes tumor metastasis is through inducing epithelial-mesenchymal transition (EMT) program. CONCLUSIONS: These results suggested that FoxM1 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting tumor metastasis.
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[605]
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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[606]
- CASTELLANO -
TÍTULO / TITLE:Relacao entre a magnitude de sintomas e a qualidade de vida: analise de agrupamentos de pacientes com cancer de pulmao no Brasil.
TÍTULO / TITLE: - Relationship between the magnitude of symptoms and the quality of life: a cluster analysis of lung cancer patients in Brazil.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Bras Pneumol. 2013 Feb;39(1):23-31.
AUTORES / AUTHORS: - Franceschini J; Jardim JR; Fernandes AL; Jamnik S; Santoro IL
INSTITUCIÓN / INSTITUTION: - Universidade Federal de Sao Paulo, Sao Paulo, SP, Brasil.
RESUMEN / SUMMARY: - OBJECTIVE: Lung cancer patients often experience profound physical and psychosocial changes as a result of disease progression or treatment side effects. Fatigue, pain, dyspnea, depression, and sleep disturbances appear to be the most common symptoms in such patients. The objective of the present study was to examine the prevalence of symptoms in lung cancer patients in order to identify subgroups (clusters) of patients, grouped according to the magnitude of the symptoms, as well as to compare the quality of life among the identified subgroups. METHODS: A cross-sectional study involving agglomerative hierarchical clustering. A total of 50 lung cancer patients were evaluated in terms of their demographic characteristics and their scores on three quality of life questionnaires, namely the 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), the Functional Assessment of Cancer Therapy-Lung, and the Medical Outcomes Study 36-item Short-form Survey. The cluster analysis took into account the magnitude of the most prevalent symptoms as assessed by the EORTC QLQ-C30 symptom scale scores; those symptoms were fatigue, pain, dyspnea, and insomnia. RESULTS: Three clusters (subgroups)_of patients were identified on the basis of the magnitude of the four most prevalent symptoms. The three subgroups of patients were as follows: patients with mild symptoms (n = 30; 60%); patients with moderate symptoms (n = 14; 28%); and patients with severe symptoms (n = 6; 12%). The subgroup of patients with severe symptoms had the worst quality of life, as assessed by the total scores and by the integrated domains of all three instruments. CONCLUSIONS: This study highlights the importance of symptom cluster assessment as an important tool to assess the quality of life of patients with chronic diseases, such as lung cancer.
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[607]
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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[608]
TÍTULO / TITLE: - New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56284. doi: 10.1371/journal.pone.0056284. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056284
AUTORES / AUTHORS: - Lee YR; Yu DS; Liang YC; Huang KF; Chou SJ; Chen TC; Lee CC; Chen CL; Chiou SH; Huang HS
INSTITUCIÓN / INSTITUTION: - Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.
RESUMEN / SUMMARY: - Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI’s 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active NSC747854 showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy.
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[609]
TÍTULO / TITLE: - In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):409-12.
AUTORES / AUTHORS: - Yin HT; Zhang DG; Wu XL; Huang XE; Chen G
INSTITUCIÓN / INSTITUTION: - Department of Radiotherapy, the Central Hospital of Xuzhou, Affiliated Hospital of Southeast University, Nanjing, China E-mail : huangxinen06@yahoo.com.cn, gangchennjmu@yahoo.cn.
RESUMEN / SUMMARY: - Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.
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[610]
TÍTULO / TITLE: - Assessing the nutritional status of elderly Chinese lung cancer patients using the Mini-Nutritional Assessment (MNA(®)) tool.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Interv Aging. 2013;8:287-91. doi: 10.2147/CIA.S41941. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 2147/CIA.S41941
AUTORES / AUTHORS: - Zhang L; Su Y; Wang C; Sha Y; Zhu H; Xie S; Kwauk S; Zhang J; Lin Y; Wang C
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin.
RESUMEN / SUMMARY: - PURPOSE: This study assessed the nutritional status of elderly Chinese lung cancer inpatients using a revised version of the Mini-Nutritional Assessment (MNA(®)) tool. PATIENTS AND METHODS: The revised version of the MNA tool was used to assess the nutritional status of 180 elderly Chinese lung cancer inpatients prior to their scheduled surgery between June 2010 and July 2011. Patients’ demographic data, anthropometric parameters, and biochemical markers were collected and analyzed. RESULTS: Among the 180 inpatients who underwent the MNA, 9% were malnourished (MNA score < 19), 33% were at risk of malnutrition (MNA score 19-23), and 58% were well nourished (MNA score >/= 24). There was significant correlation between the MNA scores of patients who were malnourished, at risk of malnutrition, and well nourished (P < 0.001), as well as between total MNA score and most MNA questions. The three patient groups with different nutritional statuses differed significantly in their responses to anthropometrics and global, diet, and subjective assessments. CONCLUSION: Incidence rates of malnutrition prior to surgery are high among elderly Chinese lung cancer inpatients. The revised MNA is a valid and reliable tool that can be used to assess and prevent malnutrition among these inpatients.
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[611]
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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[612]
TÍTULO / TITLE: - A potential therapeutic strategy for malignant mesothelioma with gene medicine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:572609. doi: 10.1155/2013/572609. Epub 2013 Jan 16.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/572609
AUTORES / AUTHORS: - Tada Y; Shimada H; Hiroshima K; Tagawa M
INSTITUCIÓN / INSTITUTION: - Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
RESUMEN / SUMMARY: - Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.
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[613]
TÍTULO / TITLE: - Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):435-439. Epub 2012 Nov 27.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1048
AUTORES / AUTHORS: - Kaburagi T; Satoh H; Hayashihara K; Endo T; Hizawa N; Kurishima K; Nishimura Y; Hashimoto T; Nakamura H; Kishi K; Inagaki M; Nawa T; Ichimura H; Ishikawa H; Kagohashi K; Fukuoka T; Shinohara Y; Kamiyama K; Sato Y; Sakai M; Matsumura T; Uchiumi K; Furukawa K
INSTITUCIÓN / INSTITUTION: - Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital and Regional Cancer Center, Kasama 309-1793;
RESUMEN / SUMMARY: - To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41-57 days) and 5.3 months (134-181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.
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[614]
TÍTULO / TITLE: - Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin J Cancer Res. 2013 Feb;25(1):90-4. doi: 10.3978/j.issn.1000-9604.2012.12.07.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2012.12.07
AUTORES / AUTHORS: - Gu A; Shi C; Xiong L; Chu T; Pei J; Han B
INSTITUCIÓN / INSTITUTION: - Department of pulmonary medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
RESUMEN / SUMMARY: - OBJECTIVE: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. RESULTS: A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. CONCLUSIONS: The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.
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[615]
TÍTULO / TITLE: - Intrafractional setup errors in patients undergoing non-invasive fixation using an immobilization system during hypofractionated stereotactic radiotherapy for lung tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Radiat Res. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1093/jrr/rrt001
AUTORES / AUTHORS: - Watanabe M; Onishi H; Kuriyama K; Komiyama T; Marino K; Araya M; Saito R; Aoki S; Maehata Y; Tominaga R; Oguri J; Sano N; Araki T
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, University of Yamanashi, 1110, Chuo-city, Yamanashi 409-3898, Japan.
RESUMEN / SUMMARY: - Intrafractional setup errors during hypofractionated stereotactic radiotherapy (SRT) were investigated on the patient under voluntary breath-holding conditions with non-invasive immobilization on the CT-linac treatment table. A total of 30 patients with primary and metastatic lung tumors were treated with the hypofractionated SRT with a total dose of 48-60 Gy with four treatment fractions. The patient was placed supine and stabilized on the table with non-invasive patient fixation. Intrafractional setup errors in Right/Left (R.L.), Posterior/Anterior (P.A.), and Inferior/Superior (I.S.) dimensions were analyzed with pre- and post-irradiation CT images. The means and one standard deviation of the intrafractional errors were 0.9 +/- 0.7mm (R.L.), 0.9 +/- 0.7mm (P.A.) and 0.5 +/- 1.0 mm (I.S.). Setup errors in each session of the treatment demonstrated no statistically significant difference in the mean value between any two sessions. The frequency within 3mm displacement was 98% in R.L., 98% in P.A. and 97% in I.S. directions. SRT under the non-invasive patient fixation immobilization system with a comparatively loose vacuum pillow demonstrated satisfactory reproducibility of minimal setup errors with voluntary breath-holding conditions that required a small internal margin.
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[616]
TÍTULO / TITLE: - Utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer and atelectasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Multidiscip Respir Med. 2013 Mar 18;8(1):21. doi: 10.1186/2049-6958-8-21.
●● Enlace al texto completo (gratuito o de pago) 1186/2049-6958-8-21
AUTORES / AUTHORS: - Yin LJ; Yu XB; Ren YG; Gu GH; Ding TG; Lu Z
INSTITUCIÓN / INSTITUTION: - Department of Radiotherapy, Dalian Central Hospital, Dalian 116033, China. kevin.liu@thepbpc.org.
RESUMEN / SUMMARY: - BACKGROUND: To investigate the utilization of PET-CT in target volume delineation for three-dimensional conformal radiotherapy in patients with non-small cell lung cancer (NSCLC) and atelectasis. METHODS: Thirty NSCLC patients who underwent radical radiotherapy from August 2010 to March 2012 were included in this study. All patients were pathologically confirmed to have atelectasis by imaging examination. PET-CT scanning was performed in these patients. According to the PET-CT scan results, the gross tumor volume (GTV) and organs at risk (OARs, including the lungs, heart, esophagus and spinal cord) were delineated separately both on CT and PET-CT images. The clinical target volume (CTV) was defined as the GTV plus a margin of 6-8 mm, and the planning target volume (PTV) as the GTV plus a margin of 10-15mm. An experienced physician was responsible for designing treatment plans PlanCT and PlanPET-CT on CT image sets. 95% of the PTV was encompassed by the 90% isodose curve, and the two treatment plans kept the same beam direction, beam number, gantry angle, and position of the multi-leaf collimator as much as possible. The GTV was compared using a target delineation system, and doses distributions to OARs were compared on the basis of dose-volume histogram (DVH) parameters. RESULTS: The GTVCT and GTVPET-CT had varying degrees of change in all 30 patients, and the changes in the GTVCT and GTVPET-CT exceeded 25% in 12 (40%) patients. The GTVPET-CT decreased in varying degrees compared to the GTVCT in 22 patients. Their median GTVPET-CT and median GTVPET-CT were 111.4 cm3 (range, 37.8 cm3-188.7 cm3) and 155.1 cm3 (range, 76.2 cm3-301.0 cm3), respectively, and the former was 43.7 cm3 (28.2%) less than the latter. The GTVPET-CT increased in varying degrees compared to the GTVCT in 8 patients. Their median GTVPET-CT and median GTVPET-CT were 144.7 cm3 (range, 125.4 cm3-178.7 cm3) and 125.8 cm3 (range, 105.6 cm3-153.5 cm3), respectively, and the former was 18.9 cm3 (15.0%) greater than the latter. Compared to PlanCT parameters, PlanPET-CT parameters showed varying degrees of changes. The changes in lung V20, V30, esophageal V50 and V55 were statistically significant (Ps< 0.05 for all), while the differences in mean lung dose, lung V5, V10, V15, heart V30, mean esophageal dose, esophagus Dmax, and spinal cord Dmax were not significant (Ps> 0.05 for all). CONCLUSIONS: PET-CT allows a better distinction between the collapsed lung tissue and tumor tissue, improving the accuracy of radiotherapy target delineation, and reducing radiation damage to the surrounding OARs in NSCLC patients with atelectasis.
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[617]
TÍTULO / TITLE: - Incidental pathologically proven pulmonary hamartoma in a patient with carcinoma tongue.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - British Medical J (BMJ). Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista bmj.com/search.dtl
●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Mar 25;2013. pii: bcr2013008942. doi: 10.1136/bcr-2013-008942.
●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2013-008942
AUTORES / AUTHORS: - Jindal A; Madan K; Nijhawan R; Singh N
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
RESUMEN / SUMMARY: - Pulmonary hamartomas are usually clinically silent and found incidentally on chest radiographs. They can lead to diagnostic confusion especially in patients who have been previously treated for primary cancers at other sites. This can lead to consideration of metastatic malignancy as the primary diagnostic possibility. In this case, evaluation of a solitary pulmonary nodule (SPN) in a patient with carcinoma of tongue led to the diagnosis of pulmonary chondroid hamartoma. This highlights the fact that a pulmonary nodule in a patient with progressive cancer at another site does not always indicate pulmonary metastasis.
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[618]
TÍTULO / TITLE: - Hypoxia affects in vitro growth of newly established cell lines from patients with malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res. 2013 Feb;34(1):13-21.
AUTORES / AUTHORS: - Goudarzi H; Hida Y; Takano H; Teramae H; Iizasa H; Hamada J
INSTITUCIÓN / INSTITUTION: - Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Sapporo 060-0815, Japan.
RESUMEN / SUMMARY: - Human malignant pleural mesothelioma (MPM) is highly aggressive, and its prognosis is very poor. For an early diagnosis of MPM and developing new therapeutic strategies against the malignancy, it is necessary to better understand biological characteristics of MPM. In this study, we established two cell lines from pleural effusions derived from patients with MPM. Both cell lines expressed tumor markers of mesothelioma such as mesothelin, podoplanin, WT1, calretinin and keratin 5/6 whereas they did not express either CEA or TTF-1 which are often used as markers of lung adenocarcinoma. The cell lines harboured wild-type TP53, produced hyaluronic acid, and were not infected with SV40. When these two cell lines were cultured under hypoxia (1% O(2)), they showed particular responses to the hypoxic condition, distinct from those to normoxic condition (21% O(2)). Namely, the ability to form a colony originating from a single cell (plating efficiency and cloning efficiency) was stimulated under hypoxia in both cell lines. On the other hand, when the assays of cell growth were started at a relatively high cell density, the growth of both cell lines, regardless of anchorage-dependent or -independent, decreased under hypoxia. The differences of their growth between under hypoxia and under normoxia, and those depending on the cell density, may provide useful hints for developing a new strategy for diagnosis or therapy of MPM.
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[619]
TÍTULO / TITLE: - Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e53475. doi: 10.1371/journal.pone.0053475. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053475
AUTORES / AUTHORS: - Swartz MD; Peterson CB; Lupo PJ; Wu X; Forman MR; Spitz MR; Hernandez LM; Vannucci M; Shete S
INSTITUCIÓN / INSTITUTION: - Division of Biostatistics, University of Texas School of Public Health, Houston, Texas, United States of America. Michael.D.Swartz@uth.tmc.edu
RESUMEN / SUMMARY: - PURPOSE: Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions. METHODS: We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status. RESULTS: Rs6893114 in MTRR (odds ratio [OR] = 2.10; 95% credible interval [CI]: 1.20-3.48) and alcohol (drinkers vs. non-drinkers, OR = 0.48; 95% CI: 0.26-0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR = 1.70; 95% CI: 1.10-2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR = 0.42; 95% CI: 0.19-0.88) and betaine*rs16948305 (OR = 0.54; 95% CI: 0.30-0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR = 0.25; 95% CI: 0.11-0.58; rs10512948; OR = 0.61; 95% CI: 0.41-0.90; rs2924471; OR = 3.31; 95% CI: 1.66-6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43-0.95) and three SNP*nutrient interactions (choline*rs10475407; OR = 1.62; 95% CI: 1.11-2.42; choline*rs11134290; OR = 0.51; 95% CI: 0.27-0.92; and riboflavin*rs8767412; OR = 0.40; 95% CI: 0.15-0.95) were associated with lung cancer risk in never smokers. CONCLUSIONS: This study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk.
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[620]
TÍTULO / TITLE: - A false positive fluorodeoxyglucose lymphadenopathy in a patient with pulmonary carcinoid tumor and previous breast reconstruction after bilateral mastectomy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gen Thorac Cardiovasc Surg. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s11748-013-0223-7
AUTORES / AUTHORS: - Bille A; Girelli L; Leo F; Pastorino U
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, IRCCS Foundation National Institute of Cancer, Via Venezian, 120100, Milan, Italy, andrea_bille@hotmail.it.
RESUMEN / SUMMARY: - We present a case of a 60-year-old woman with a positive fluorodeoxyglucose integrated positron emission tomography and computed tomography (PET/TC) mammary chain lymphadenopathy and carcinoid tumor of the left lower lobe who had a previous bilateral mastectomy and breast reconstruction for breast cancer. She underwent a right muscle sparing mini-thoracotomy and mammary chain lymphadenectomy; the final histopathology showed granulomatous reaction to silicone.
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[621]
TÍTULO / TITLE: - Metastasis Dynamics for Non-Small-Cell Lung Cancer: Effect of Patient and Tumor-Related Factors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Mar 15. pii: S1525-7304(13)00028-4. doi: 10.1016/j.cllc.2013.01.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2013.01.002
AUTORES / AUTHORS: - Kelsey CR; Fornili M; Ambrogi F; Higgins K; Boyd JA; Biganzoli E; Demicheli R
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Duke Cancer Institute, Durham, NC.
RESUMEN / SUMMARY: - BACKGROUND: We studied event dynamics (probability of an event occurring over a specific time interval) in patients undergoing surgery for early-stage non-small-cell lung cancer (NSCLC) according to patient and tumor characteristics. METHODS: By using a database of 1506 patients who underwent initial surgery for NSCLC, event dynamics, based on a time-specific hazard rate, were evaluated. The event of interest was the development of distant metastases, with or without a local recurrence. The effect of sex, tumor size, nodal involvement, histology, lymphovascular space invasion, pleural invasion, age, and race were studied. RESULTS: The hazard rate for developing distant metastases was not constant over time but was characterized by specific peaks, the first being approximately 9 months after surgery and the second at 18 to 20 months for men and 24 to 26 months for women. For women, the hazard rate peaked considerably in the first year. For men, the hazard rate peaks were smaller but lasted for a longer duration. Pathologic factors associated with a higher risk of recurrence (eg, size, lymph node involvement, pleural invasion) all increased the sex-specific hazard rates. CONCLUSIONS: The probability of developing distant metastases after surgery for NSCLC peaks at specific and consistent time intervals after surgery, with specific differences between men and women. A factor-specific modulation of peak heights that ranged from no impact (eg, race) to relevant effects for primary tumor size, nodal involvement, and pleural invasion, possibly related to sex, was also observed. The bimodal distant metastases dynamics may be an intrinsic feature of metastatic progression in NSCLC.
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[622]
TÍTULO / TITLE: - Response to Cabozantinib in Patients with RET Fusion-Positive Lung Adenocarcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-13-0035
AUTORES / AUTHORS: - Drilon A; Wang L; Hasanovic A; Suehara Y; Lipson D; Stephens PJ; Ross J; Miller VA; Ginsberg MS; Zakowski MF; Kris MG; Ladanyi M; Rizvi NA
INSTITUCIÓN / INSTITUTION: - 1Dept. of Medicine, Memorial Sloan-Kettering Cancer Center.
RESUMEN / SUMMARY: - The discovery of RET fusions in lung cancers has uncovered a new therapeutic target for patients whose tumors harbor these changes. In an unselected population of non-small cell lung cancers (NSCLCs), RET fusions are present in 1-2% of cases. This incidence rises substantially, however, in never-smokers with lung adenocarcinomas that lack other known driver oncogenes. While pre-clinical data provide experimental support for the use of RET inhibitors in the treatment of RET fusion-positive tumors, clinical data on response are lacking. We report preliminary data for the first three patients treated with the RET inhibitor cabozantinib on a prospective phase 2 trial for patients with RET fusion-positive NSCLCs (NCT01639508). Confirmed partial responses were observed in two patients, including one harboring a novel TRIM33-RET fusion. A third patient with a KIF5B-RET fusion has had prolonged stable disease approaching 8 months (31 weeks). All three patients remain progression-free on treatment.
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[623]
TÍTULO / TITLE: - Pneumocystis jiroveci pneumonia and colonization in patients with advanced lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):601-604. Epub 2012 Nov 29.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1052
AUTORES / AUTHORS: - Togashi Y; Masago K; Ito Y; Sakamori Y; Okuda C; Fukuhara A; Nagai H; Kim YH; Mishima M
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
RESUMEN / SUMMARY: - Pneumocystis jiroveci pneumonia (PCP) has long been recognized as a cause of mortality in immuno-compromised populations, including those with advanced lung cancer. Although Pneumocystis colonization has only recently been described due to the development of more sensitive molecular techniques, including polymerase chain reaction (PCR), it is unknown whether Pneumocystis colonization leads to the development of PCP. In the present study, we aimed to determine the prevalence of Pneumocystis colonization in advanced lung cancer patients. Furthermore, the association between PCP and Pneumocystis colonization was also investigated. Advanced lung cancer patients with no indication of PCP were evaluated to determine the prevalence of Pneumocystis colonization. We analyzed their oral wash (OW) samples and retrospectively evaluated advanced lung cancer patients with PCP by analyzing their sections of formalin-fixed, paraffin-embedded lung tissues obtained following a diagnosis of lung cancer. Pneumocystis colonization was determined by a PCR test for Pneumocystis jiroveci (P. jiroveci). No P. jiroveci was detected by PCR in the OW samples of 47 advanced lung cancer patients with no indication of PCP, or in the lung tissues of four advanced lung cancer patients with PCP. These results indicate that PCP is not associated with Pneumocystis colonization in advanced lung cancer patients, although this study is limited since this was a cross-sectional and retrospective study.
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[624]
TÍTULO / TITLE: - Sunlight may increase the FDG uptake value in primary tumors of patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):773-776. Epub 2013 Jan 7.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1112
AUTORES / AUTHORS: - Mutlu H; Buyukcelik A; Kaya E; Kibar M; Seyrek E; Yavuz S; Calikusu Z
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Acibadem Kayseri Hospital, Kayseri 38000;
RESUMEN / SUMMARY: - Currently, positron emission tomography with computerized tomography (PET-CT) is the most sensitive technique for detecting extracranial metastases in non-small cell lung cancer (NSCLC). It has been reported that there is a correlation between the maximal standardized uptake value (SUV(max)) of primary tumors and prognosis in patients with NSCLC. The effect of sunlight exposure on PET-CT SUV(max) value is not known. Therefore, we aimed to evaluate the effect of sunlight exposure on PET-CT SUV(max) value in patients with NSCLC. A total of 290 patients with NSCLC from two different regions of Turkey (Kayseri, n=168 and Adana, n=122) that have different climate and sunlight exposure intensity, were included in the study. Age, gender, histology of cancer, cancer stage, smoking status, comorbidity and SUV(max) of the primary tumor area at the time of staging were evaluated as prognostic factors. In the multivariate analysis, we detected that the region was the only independent factor affecting SUV(max) (P=0.019). We identified that warmer climate and more sunlight exposure significantly increases the SUV(max) value of the primary tumor area in patients with NSCLC. Further studies are warranted to clarify the issue.
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[625]
TÍTULO / TITLE: - Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onco Targets Ther. 2013;6:125-34. doi: 10.2147/OTT.S42245. Epub 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S42245
AUTORES / AUTHORS: - Boutsikou E; Kontakiotis T; Zarogoulidis P; Darwiche K; Eleptheriadou E; Porpodis K; Galaktidou G; Sakkas L; Hohenforst-Schmidt W; Tsakiridis K; Karaiskos T; Zarogoulidis K
INSTITUCIÓN / INSTITUTION: - Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece.
RESUMEN / SUMMARY: - BACKGROUND: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC). We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC. METHODS: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5) and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group), 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival. RESULTS: Over 4 years of follow-up, there was no statistically significant difference in survival and time to progression between the four treatment groups. After two cycles of chemotherapy, responders and nonresponders were divided according to their response in order to examine the role of initial response as an independent factor in survival and response when a biological agent is combined with chemotherapy. Nonresponders, who received additional therapy with bevacizumab or combination therapy, had a survival benefit [657 days (95% confidence interval 349-970) and 681 days (95% confidence interval 315-912), respectively], which was statistically significant compared with continuation of cytotoxic chemotherapy (P < 0.001). The combination therapy had a safety profile comparable with that of bevacizumab and erlotinib taken individually. CONCLUSION: Administration of bevacizumab and erlotinib in combination with first-line chemotherapy, followed by bevacizumab and erlotinib monotherapy as maintenance, showed promising results in patients with NSCLC, with reduced toxicity as compared with chemotherapy alone, but did not translate into longer overall survival.
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[626]
TÍTULO / TITLE: - Continuous morphine infusion for end-stage lung cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):972-974. Epub 2012 Dec 28.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1101
AUTORES / AUTHORS: - Kim YH; Okuda C; Sakamori Y; Masago K; Togashi Y; Mishima M
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
RESUMEN / SUMMARY: - End-stage cancer patients frequently receive continuous morphine infusion (CMI) to alleviate the various symptoms associated with cancer progression or adverse events; however, there have been a limited number of studies concerning such patients. We conducted a retrospective analysis of 79 end-stage lung cancer patients who received CMI at the Kyoto University Hospital, Kyoto, Japan between 2008 and 2010. Thirty-one patients (39%) received CMI intravenously and 48 (61%) received it subcutaneously. The patients were divided into four groups based on the indications for CMI: group A (uncontrolled pain; n=9), group B (dyspnea; n=44), group C (both dyspnea and pain; n=13) and group D (an inability to take oral medicine; n=13). The median maximum dose of morphine in groups A-D was 60.0, 25.0, 50.0 and 15.0 mg/day, respectively. The median survival time from the start of CMI was 4 days (range 0-136). In our limited experience, pain, dyspnea and the inability to take oral medicine were identified as indications for CMI in end-stage lung cancer patients, with dyspnea being the major indication for CMI. Patients in group B (dyspnea) required a lower dose of morphine for alleviation compared with those in groups A (uncontrolled pain) and C (both dyspnea and pain). The survival time from the initiation of CMI was markedly shorter in patients with dyspnea (groups B and C) than in patients without dyspnea (group A). Further studies are required to facilitate the effective and appropriate use of CMI in end-stage lung cancer patients. Dyspnea was the major indication for CMI in end-stage lung cancer patients, and the survival time was extensively limited in such patients.
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[627]
TÍTULO / TITLE: - Primary tumor PET/CT [(1)(8)F]FDG uptake is an independent predictive factor for regional lymph node metastasis in patients with non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Imaging. 2013 Feb 7;12:566-72. doi: 10.1102/1470-7330.2012.0040.
●● Enlace al texto completo (gratuito o de pago) 1102/1470-7330.2012.0040
AUTORES / AUTHORS: - Li M; Wu N; Zheng R; Liang Y; Liu Y; Zhang W; Li N; Zhao P
INSTITUCIÓN / INSTITUTION: - Department of Diagnostic Radiology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, Peoples Republic of China.
RESUMEN / SUMMARY: - AIM: To investigate the correlation between [(1)(8)F]fluorodeoxyglucose (FDG) uptake in a primary tumor and pathologic N stages, and to further analyze the possible risk factors contributing to the regional lymph node metastasis. PATIENTS AND METHODS: Eighty patients with non-small cell lung cancer (NSCLC) who underwent positron emission tomography/computed tomography were enrolled in the study. The FDG uptake in the primary tumor was compared for the different N staging groups and further correlation was performed. The degree of FDG uptake in the primary tumor and other possible variables related to the incidence of lymph node metastasis were examined by univariate and logistic multivariate analysis. FDG uptake was quantitated using the maximum standardized uptake value (SUVmax). RESULTS: Statistically significant differences were found in the SUVmax of the primary tumors among different N staging groups (F = 4.124, P = 0.023), and the correlation between them was also statistically significant (r = 0.438, P = 0.000). Univariate analysis showed that blood tumor markers, primary tumor size, histologic grade, and SUVmax of the primary tumor were significantly associated with lymph node involvement. Logistic multivariate analysis showed that blood tumor makers and SUVmax of primary tumor might be considered as significant predictive factors for lymph node metastasis in patients with NSCLC. CONCLUSION: Our results show that there is a significant relationship between the SUVmax of the primary tumor and the pathologic N stage of NSCLC. FDG uptake by the primary tumor may be an independent predictor of regional lymph node metastasis in patients with NSCLC.
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[628]
TÍTULO / TITLE: - Lung tumor microenvironment induces specific gene expression signature in intratumoral NK cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Immunol. 2013;4:19. doi: 10.3389/fimmu.2013.00019. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 3389/fimmu.2013.00019
AUTORES / AUTHORS: - Gillard-Bocquet M; Caer C; Cagnard N; Crozet L; Perez M; Fridman WH; Sautes-Fridman C; Cremer I
INSTITUCIÓN / INSTITUTION: - Centre de Recherche des Cordeliers, INSERM, U872 Paris, France ; Universite Pierre et Marie Curie Paris, France ; Universite Paris Descartes Paris, France.
RESUMEN / SUMMARY: - Natural killer (NK) cells are able to recognize and kill tumor cells, however whether they contribute to tumor immunosurveillance is still debated. Our previous studies demonstrated the presence of NK cells in human lung tumors. Their comparison with NK cells from non-tumoral lung tissues and with blood NK cells from the same individuals revealed a decreased expression of some NK receptors and impaired ex vivo cytotoxic functions occurring specifically in NK cells isolated from the tumor microenvironment. The aim of the present study was to characterize the transcriptional profile of such intratumoral NK cells, by comparative microarray analysis of sorted NK cells isolated from non-tumoral (Non-Tum-NK) and tumoral (Tum-NK) lung tissues of 12 Non-Small Cell Lung Cancer patients. Our results reveal a specific gene expression signature of Tum-NK cells particularly in activation processes and cytotoxicity, confirming that tumor environment induces modifications in NK cells biology. Indeed, intratumoral NK cells display higher expression levels of NKp44, NKG2A, Granzymes A and K, and Fas mRNA. A particular pattern of receptors involved in chemotaxis was also observed, with an overexpression of CXCR5 and CXCR6, and a lower expression of CX3CR1 and S1PR1 genes in Tum-NK as compared to Non-Tum-NK cells. The precise identification of the molecular pathways modulated in the tumor environment will help to decipher the role of NK cells in tumor immunosurveillance and will open future investigations to manipulate their antitumoral functions.
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[629]
TÍTULO / TITLE: - An Integrated Expression Profiling Reveals Target Genes of TGF-beta and TNF-alpha Possibly Mediated by MicroRNAs in Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56587. doi: 10.1371/journal.pone.0056587. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056587
AUTORES / AUTHORS: - Saito A; Suzuki HI; Horie M; Ohshima M; Morishita Y; Abiko Y; Nagase T
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan ; Division for Health Service Promotion, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
RESUMEN / SUMMARY: - EMT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-beta elicited EMT in Smad-dependent manner and TNF-alpha accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion. TNF-alpha stimulated the phosphorylation of Smad2 linker region, and this effect was attenuated by inhibiting MEK or JNK pathway. Comprehensive expression analysis unraveled genes differentially regulated by TGF-beta and TNF-alpha, such as cytokines, chemokines, growth factors and ECM (extracellular matrices), suggesting the drastic change in autocrine/paracrine signals as well as cell-to-ECM interactions. Integrated analysis of microRNA signature enabled us to identify a subset of genes, potentially regulated by microRNAs. Among them, we confirmed TGF-beta-mediated induction of miR-23a in lung epithelial cell lines, target genes of which were further identified by gene expression profiling. Combined with in silico approaches, we determined HMGN2 as a downstream target of miR-23a. These findings provide a line of evidence that the effects of TGF-beta and TNF-alpha were partially mediated by microRNAs, and shed light on the complexity of molecular events elicited by TGF-beta and TNF-alpha.
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[630]
TÍTULO / TITLE: - Polymorphisms of CHRNA5-CHRNA3-CHRNB4 Gene Cluster and NSCLC Risk in Chinese Population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Transl Oncol. 2012 Dec;5(6):448-52. Epub 2012 Dec 1.
AUTORES / AUTHORS: - Li Z; Bao S; Xu X; Bao Y; Zhang Y
INSTITUCIÓN / INSTITUTION: - Zhejiang Chinese Medicine University, Hangzhou, China.
RESUMEN / SUMMARY: - AIM: To explore the potential association between single-nucleotide polymorphisms (SNPs) and haplotypes of the CHRNA5-CHRNA3-CHRNB4 gene cluster and the non-small cell lung cancer (NSCLC) susceptibility in never-smoking Chinese. METHODS: A case-control study was conducted with 200 NSCLC patients and 200 healthy controls, matched on age and sex. Five SNPs distributed in CHRNA5-CHRNA3-CHRNB4 gene cluster were selected for genotyping. The association between genotype and lung cancer risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. RESULTS: For CHRNA3 rs578776 status, data were available in 199 NSCLC patients and 199 controls. The G/G homozygote in CHRNB4 rs7178270 had a reduced risk of developing NSCLC (OR = 0.553; 95% CI = 0.309-0.989; P = .0437), especially squamous cell carcinoma (SQC) (OR = 0.344; 95% CI = 0.161-0.732; P = .0043), compared with those who carry at least one C allele (C/C and C/G). The polymorphisms of rs578776, rs938682, rs17486278, and rs11637635 were not significantly different between controls and cases or between controls and histologic subgroups, adenocarcinoma and SQC, respectively. CONCLUSIONS: In our study, we found that the SNP of CHRNB4 rs7178270 is significantly associated with reduced risk of NSCLC, especially with reduced risk of SQC in never-smoking Chinese population.
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[631]
TÍTULO / TITLE: - A study of 131iodine-labeling of histamine-indomethacin: its in vivo therapeutic effect and anti-tumor mechanisms in Lewis-bearing lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 26;8(1):74.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-74
AUTORES / AUTHORS: - Lu G; Zhang G; Zhang C; Chen C; Liu R
RESUMEN / SUMMARY: - BACKGROUND: In our research,we study the effect of 131iodine-labeled histamine-indomethacin (131I-His-IN). We focus on its in vivo therapeutic effect and anti-tumor mechanisms in Lewis-bearing lung cancer. METHODS: I-His-IN was administered by garage to the mice. At different timepoints, we made autoradiography (ARG) slices to observe the distribution of 131I-His-IN in the cellular, and the sliced samples underwent hematoxylin and eosin (HE) staining for observation of tumor necrosis. Before treatment, the groups of mice underwent 18F-FDG (18F- fluorodeoxyglucose) positron emission tomography-computed tomography (PET-CT) scans ,and they were then given physiologic saline, 131I, IN, His-IN, and 131I-His-IN, respectively, three times daily for seven days. Seven days later, all the mice underwent 18F-FDG PET-CT scans again. We calculated the maximum standard uptake value (SUVmax) of the region of interest (ROI) and tumor inhibition rate at the same time. RESULTS: In ARG groups, black silver particle was concentrated in the nucleus and cytoplasm. 131I-His-IN mainly concentrated in tumor tissues. At 8 hours after 131I-His-IN, the radioactivity uptake in tumor tissue was higher than in other organs (F=3.46,P<0.05). For the 18F-FDG PET-CT imaging, the tumor tissus’es SUVmax of t he ROI was lower compared to other groups after the treatment with 131I-His-IN. The tumor inhibitory rate (54.8%) in 131I-His-IN group was higher than in other groups,too, In the 131I-His-IN group the vascular endothelial growth factor (VEGF) decreased gradually compared to other groups. The tumor tissue necrotized obviously in 131I-His-IN group. CONCLUSIONS: Through these animal experiments, we found 131I-His-IN could inhibit the Lewis lung cancer cells. 131I-His-IN focused at the cell nucleus and cytoplasm. It could reduce VEGF and increase tumor inhibitory rate. At the same time, 18F-FDG PET-CT scan could be used for a curative effect and monitoring of disease prognosis.
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[632]
TÍTULO / TITLE: - Therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer in vivo and in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Clin Exp Pathol. 2013;6(3):421-30. Epub 2013 Feb 15.
AUTORES / AUTHORS: - Yu F; Lv M; Cai H; Li D; Yuan X; Lv Z
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, Tenth People’s Hospital of Tongji University Shanghai, China.
RESUMEN / SUMMARY: - OBJECTIVE: To investigate the in vivo and in vitro therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer (NSCLC). METHODS: MTT was done to measure the cell proliferation; flow cytometry to detect cell apoptosis; Transwell invasion assay to determine the invasiveness of NSCLC. In addition, HE staining, TUNEL staining and immunohistochemistry for CD34 were employed to investigate the influence of 188Re-MAG3-depreotide on the growth of NSCLC. RESULTS: 1) Within 2-6 days, the inhibitory effect of 188Re-MAG3-depreotide on the proliferation of A549 cells and SPC-A1 cells increased over time. 2) At 48 h after treatment with 188Re-MAG3-depreotide, the apoptosis rate of A549 cells and SPC-A1 cells was 23.1% and 22.6%, respectively. 3) After 188Re-MAG3-depreotide treatment, the number of invasive A549 cells and SPC-A1 cells was reduced by about 3 times when compared with control group. 4) The cancer in the control group presented with unlimited growth. The cancer growth continued after treatment with 188Re or MAG3-depreotide alone, while the cancer growth was markedly inhibited after 188Re-MAG3-depreotide treatment when compared with control group. CONCLUSION: 188Re-MAG3-depreotide can inhibit the proliferation and invasion of A549 cells and SPC-A1 cells. Treatment with 7.4MBq 188Re-MAG3-depreotide via tail vein can significantly suppress the in vivo cancer growth and induce the apoptosis of cancer cells. These findings demonstrate that 188Re-MAG3-depreotide can induce the apoptosis of NSCLC cells and directly kill the NSCLC cells, which provide evidence for the radiotherapy of NSCLC.
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[633]
TÍTULO / TITLE: - Analysis of the expression of the Notch3 receptor protein in adult lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):499-504. Epub 2012 Nov 19.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1033
AUTORES / AUTHORS: - Zhou M; Jin WY; Fan ZW; Han RC
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Jinshan Branch of the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 201500;
RESUMEN / SUMMARY: - Abnormalities in the Notch signaling system are considered to play a role in the tumorigenesis of bronchiogenic carcinoma. The present study aimed to investigate the expression of Notch3 in adult lung cancer patients and its role in the pathogenesis of primary bronchiogenic carcinoma. The expression of the Notch3 protein in lung squamous cell carcinoma, adenocarcinoma, small cell carcinoma and corresponding non-tumor tissues was detected by immunohistochemistry. To investigate the expression of Notch3 in adenocarcinoma tissues, Notch3 mRNA and protein expression were measured with reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. It was demonstrated that Notch3 had a stronger positive degree of expression in lung squamous cell carcinoma and adenocarcinoma compared with the corresponding non-tumor tissue (P<0.01). The expression of Notch3 in small cell carcinoma tissue was lower compared with that of the corresponding non-tumor tissue (P<0.01). The expression of Notch3 in the lung adenocarcinoma group was the highest of the three lung carcinoma groups (P<0.01). RT-PCR revealed that the expression of Notch3 mRNA in the lung adenocarcinoma group was higher than that of the normal lung group, but there was no statistically significant difference (P=0.05). The expression of Notch1 protein in the lung adenocarcinoma group was significantly higher compared with the normal lung group (P<0.01), as shown by western blot analysis. Notch3 may be involved in the pathogenesis of bronchogenic carcinoma, in particular in the promotion of the lung cancer oncogene, and a difference in its expression may exist in the various pathological types.
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[634]
TÍTULO / TITLE: - Stereotactic radiosurgery for single brain metastases from non-small cell lung cancer: progression of extracranial disease correlates with distant intracranial failure.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 19;8(1):64.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-64
AUTORES / AUTHORS: - Kress MA; Oermann E; Ewend MG; Hoffman RB; Chaudhry H; Collins B
RESUMEN / SUMMARY: - BACKGROUND: Limited data exist regarding management of patients with a single brain lesion with extracranial disease due to non-small cell lung cancer (NSCLC). METHODS: Eighty-eight consecutive patients with a single brain lesion from NSCLC in the presence of extracranial disease were treated with stereotactic radiosurgery (SRS) alone. Local control (LC), distant intracranial failure (DIF), overall survival (OS), and toxicity were assessed. The logrank test was used to identify prognostic variables. RESULTS: Median OS was 10.6 months. One-year DIF was 61%; LC 89%. Treatments were delivered in 1--5 fractions to median BED10 = 60Gy. Five patients developed radionecrosis. Factors associated with shortened OS included poor performance status (PS) (p = 0.0002) and higher Recursive Partitioning Analysis class (p = 0.017). For patients with PS 0, median survival was 22 months. DIF was associated with systemic disease status (progressive vs. stable) (p = 0.0001), as was BED (p = 0.021) on univariate analysis, but only systemic disease (p = 0.0008) on multivariate analysis. CONCLUSIONS: This study identifies a patient population that may have durable DIF after treatment with SRS alone. These data support the need for prospective studies to optimize patient selection for up-front SRS and to characterize the impact of DIF on patients’ quality of life.
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[635]
TÍTULO / TITLE: - Clinico-pathological Profile of Lung Cancer at AIIMS: A Changing Paradigm in India.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):489-94.
AUTORES / AUTHORS: - Malik PS; Sharma MC; Mohanti BK; Shukla NK; Deo S; Mohan A; Kumar G; Raina V
INSTITUCIÓN / INSTITUTION: - Departments of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India E-mail : vinodraina@hotmail.com.
RESUMEN / SUMMARY: - Background: Lung cancer is one of the commonest and most lethal cancers throughout the world. The epidemiological and pathological profile varies among different ethnicities and geographical regions. At present adenocarcinoma is the commonest histological subtype of non-small cell lung cancer (NSCLC) in most of the Western and Asian countries. However, in India squamous cell carcinoma has been reported as the commonest histological type in most of the series. The aim of the study was to analyze the current clinico-pathological profile and survival of lung cancer at our centre. Materials and Methods: We analyzed 434 pathologically confirmed lung cancer cases registered at our centre over a period of three years. They were evaluated for their clinical and pathological profiles, treatment received and outcome. The available histology slides were reviewed by an independent reviewer. Results: Median age was 55 years with a male:female ratio of 4.6:1. Some 68% of patients were smokers. There were 85.3% NSCLC and 14.7% SCLC cases. Among NSCLCs, adenocarcinoma was the commonest histological subtype after the pathology review. Among NSCLC, 56.8% cases were of stage IV while among SCLC 71.8% cases had extensive stage disease. Some 29% of patients could not receive any anticancer treatment. The median overall and progression free survivals of the patients who received treatment were 12.8 and 7.8 months for NSCLC and 9.1 and 6.8 months for SCLC. Conclusions: This analysis suggests that adenocarcinoma may now be the commonest histological subtype also in India, provided a careful pathological review is done. Most of the patients present at advanced stage and outcome remains poor.
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[636]
TÍTULO / TITLE: - Rib fracture after stereotactic radiotherapy for primary lung cancer: prevalence, degree of clinical symptoms, and risk factors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 7;13:68. doi: 10.1186/1471-2407-13-68.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-68
AUTORES / AUTHORS: - Nambu A; Onishi H; Aoki S; Tominaga L; Kuriyama K; Araya M; Saito R; Maehata Y; Komiyama T; Marino K; Koshiishi T; Sawada E; Araki T
INSTITUCIÓN / INSTITUTION: - Department of Radiology, University of Yamanashi, Chuo City, Yamanashi Prefecture, Japan. nambu-a@gray.plala.or.jp
RESUMEN / SUMMARY: - BACKGROUND: As stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate alpha/beta ratios for discriminating between fracture and non-fracture groups were also investigated. METHODS: Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of alpha/beta ratios (1-10 Gy). Receiver operating characteristics analysis was used to define the most appropriate alpha/beta ratio. RESULTS: Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an alpha/beta ratio of 8 Gy. CONCLUSIONS: Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an alpha/beta ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients.
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[637]
TÍTULO / TITLE: - DART-bid (Dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily)-a novel approach for non-resected NSCLC: final results of a prospective study, correlating radiation dose to tumor volume.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 5;8:49. doi: 10.1186/1748-717X-8-49.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-49
AUTORES / AUTHORS: - Wurstbauer K; Deutschmann H; Dagn K; Kopp P; Zehentmayr F; Lamprecht B; Porsch P; Wegleitner B; Studnicka M; Sedlmayer F
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology and radART-Institute for research and development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria. k.wurstbauer@salk.at.
RESUMEN / SUMMARY: - BACKGROUND: Sequential chemo-radiotherapies with intensive radiation components deliver promising results in non-resected non-small cell lung cancer (NSCLC). In general, radiation doses are determined by dose constraints for normal tissues, not by features relevant for tumor control. DART-bid targets directly the doses required for tumor control, correlating doses to tumor volume in a differentiated mode. MATERIALS/METHODS: Radiation doses to primary tumors were aligned along increasing tumor size within 4 groups (<2.5 cm/2.5-4.5 cm/4.5-6.0 cm/>6.0 cm; mean number of three perpendicular diameters). ICRU-doses of 73.8 Gy/79.2 Gy/84.6 Gy/90.0 Gy, respectively, were applied. Macroscopically involved nodes were treated with a median dose of 59.4 Gy, nodal sites about 6 cm cranial to involved nodes electively with 45 Gy. Fractional doses were 1.8 Gy twice daily (bid).2 cycles chemotherapy were given before radiotherapy.Between 2004 and 2009, 160 not selected patients with 164 histologically/cytologically proven NSCLC were enrolled; Stage I: 38 patients; II: 6 pts.; IIIA: 69 pts.; IIIB: 47 pts. Weight loss >5%/3 months: 38 patients (24%).Primary endpoints are local and regional tumor control rates at 2 years (as >90% of locoregional failures occur within 2 years). Secondary endpoints are survival and toxicity. With a minimum follow-up time of 2 years for patients alive, the final results are presented. RESULTS: 32 local and 10 regional recurrences occurred. The local and regional tumor control rates at 2 years are 77% and 93%, respectively.The median overall survival (OS) time is 28.0 months, the 2- and 5-year OS rates are 57% and 19%, respectively. For stage III patients, median OS amounts to 24.3 months, 2- /5-year OS rates to 51% and 18%, respectively.2 treatment-related deaths (progressive pulmonary fibrosis) occurred in patients with pre-existing pulmonary fibrosis. Further acute and late toxicity was mild. CONCLUSIONS: This novel approach yields a high level of locoregional tumor control and survival times. In general it is well tolerated. In all outcome parameters it seems to compare favourably with simultaneous chemo-radiotherapies, at present considered ‘state of the art’; and is additionally amenable for an unselected patient population.
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[638]
TÍTULO / TITLE: - The use of proton-beam therapy in the treatment of non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Rev Med Devices. 2013 Mar;10(2):239-45. doi: 10.1586/erd.12.81.
●● Enlace al texto completo (gratuito o de pago) 1586/erd.12.81
AUTORES / AUTHORS: - Oshiro Y; Sakurai H
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, Tsukuba University, Ibaraki, Japan.
RESUMEN / SUMMARY: - Lung cancer is the most common cause of cancer death worldwide. Surgical resection has played a major role in the treatment of non-small-cell lung cancer (NSCLC); however, the disease is often detected in a progressive and inoperable form. Surgical resection may also be impossible for early-stage NSCLC due to medical conditions, such as pulmonary or cardiovascular disease and old age. Radiotherapy plays an important role for these patients. Proton-beam therapy is a particle radiotherapy with an excellent dose localization that permits treatment of lung cancer by administering a high dose to the tumor while minimizing damage to the surrounding normal tissues. Thus, proton beams are increasingly being used for lung cancer. In this context, the authors review the current knowledge on proton-beam therapy for the treatment of NSCLC.
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[639]
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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[640]
TÍTULO / TITLE: - Protein Phosphorylation Profiling Using an In Situ Proximity Ligation Assay: Phosphorylation of AURKA-Elicited EGFR-Thr654 and EGFR-Ser1046 in Lung Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e55657. doi: 10.1371/journal.pone.0055657. Epub 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055657
AUTORES / AUTHORS: - Chen TC; Liu YW; Huang YH; Yeh YC; Chou TY; Wu YC; Wu CC; Chen YR; Cheng HC; Lu PJ; Lai JM; Huang CY
INSTITUCIÓN / INSTITUTION: - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
RESUMEN / SUMMARY: - The epidermal growth factor receptor (EGFR), which is up-regulated in lung cancer, involves the activation of mitogenic signals and triggers multiple signaling cascades. To dissect these EGFR cascades, we used 14 different phospho-EGFR antibodies to quantify protein phosphorylation using an in situ proximity ligation assay (in situ PLA). Phosphorylation at EGFR-Thr654 and -Ser1046 was EGF-dependent in the wild-type (WT) receptor but EGF-independent in a cell line carrying the EGFR-L858R mutation. Using a ProtoAarray containing approximately 5000 recombinant proteins on the protein chip, we found that AURKA interacted with the EGFR-L861Q mutant. Moreover, overexpression of EGFR could form a complex with AURKA, and the inhibitors of AURKA and EGFR decreased EGFR-Thr654 and -Ser1046 phosphorylation. Immunohistochemical staining of stage I lung adenocarcinoma tissues demonstrated a positive correlation between AURKA expression and phosphorylation of EGFR at Thr654 and Ser1046 in EGFR-mutant specimens, but not in EGFR-WT specimens. The interplay between EGFR and AURKA provides an explanation for the difference in EGF dependency between EGFR-WT and EGFR-mutant cells and may provide a new therapeutic strategy for lung cancer patients carrying EGFR mutations.
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[641]
TÍTULO / TITLE: - Early detection of lung cancer risk using data mining.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):595-8.
AUTORES / AUTHORS: - Ahmed K; Emran AA; Jesmin T; Mukti RF; Rahman MZ; Ahmed F
INSTITUCIÓN / INSTITUTION: - Department of Information and Communication Technology, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh E-mail : emrangeb@gmail.com, emranbge@mbstu.ac.bd.
RESUMEN / SUMMARY: - Background: Lung cancer is the leading cause of cancer death worldwide Therefore, identification of genetic as well as environmental factors is very important in developing novel methods of lung cancer prevention. However, this is a multi-layered problem. Therefore a lung cancer risk prediction system is here proposed which is easy, cost effective and time saving. Materials and Methods: Initially 400 cancer and non-cancer patients’ data were collected from different diagnostic centres, pre-processed and clustered using a K-means clustering algorithm for identifying relevant and non-relevant data. Next significant frequent patterns are discovered using AprioriTid and a decision tree algorithm. Results: Finally using the significant pattern prediction tools for a lung cancer prediction system were developed. This lung cancer risk prediction system should prove helpful in detection of a person’s predisposition for lung cancer. Conclusions: Most of people of Bangladesh do not even know they have lung cancer and the majority of cases are diagnosed at late stages when cure is impossible. Therefore early prediction of lung cancer should play a pivotal role in the diagnosis process and for an effective preventive strategy.
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[642]
TÍTULO / TITLE: - Overexpression of high mobility group protein B1 correlates with the proliferation and metastasis of lung adenocarcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 6. doi: 10.3892/mmr.2013.1362.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1362
AUTORES / AUTHORS: - Sun KK; Ji C; Li X; Zhang L; Deng J; Zhong N; Wu XY
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Surgery, Thoracic Surgery Division, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, P.R. China.
RESUMEN / SUMMARY: - High mobility group protein B1 (HMGB1) plays an important role in a number of clinical conditions, such as autoimmunity, cardiovascular disease and cancer. Evidence suggests that HMGB1 is critical in the development and progression of numerous types of tumor. However, the underlying molecular mechanisms for the HMGB1-mediated progression and metastasis of lung cancer have not yet been elucidated. In this study, we investigated the role of HMGB1 in lung adenocarcinoma and the mechanisms by which it contributes to carcinogenesis and metastasis. We demonstrated that there was an increase in the expression of HMGB1 in primary cancer tissues compared to the matched adjacent non-cancerous tissues. The expression levels of TOB1 in the normal human bronchial epithelial (HBE) cell line and 10 lung cancer cell lines were determined by reverse transcription-PCR (RT-PCR). The results revealed that HMGB1 expression increased in 8 cell lines compared with the HBE cell line. The A549 and NCI-H1975 cells were transfected with HMGB1 recombinant plasmid. We discovered that the overexpression of HMGB1 promoted cell growth and metastasis in the 2 cell lines. Further investigation revealed that exogenously expressed HMGB1 enhanced the activation of p38 and Erk1/2, in addition to the expression of nuclear factor (NF)-kappaB. We propose that HMGB1 functions as a tumor promoter and that it regulates the proliferation and invasion of lung cancer cells by modulating the activation of the Erk1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways.
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[643]
TÍTULO / TITLE: - Upregulation of c-FLIP-short in response to TRAIL promotes survival of NSCLC cells, which could be suppressed by inhibition of Ca(2+)/calmodulin signaling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 7;4:e522. doi: 10.1038/cddis.2013.51.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.51
AUTORES / AUTHORS: - Kaminskyy VO; Surova OV; Piskunova T; Zborovskaya IB; Tchevkina EM; Andera L; Zhivotovsky B
INSTITUCIÓN / INSTITUTION: - Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden.
RESUMEN / SUMMARY: - TNF-related apoptosis-inducing ligand (TRAIL) is a promising cytokine for killing tumor cells. However, a number of studies have demonstrated that different cancer cells resist TRAIL treatment and, moreover, TRAIL can promote invasion and metastasis in resistant cells. Here we report that TRAIL rapidly activates caspase-8 in a panel of non-small-cell lung carcinomas (NSCLCs). Adenocarcinomas derived from the lung in addition to high caspase-8 expression are characterized by increased expression of DR4 compared with adjacent non-neoplastic tissues. Blocking DR4 or lowering caspase-8 expression significantly reduced apoptosis in NSCLC cell lines, indicating the importance of DR4 and signifying that higher levels of caspase-8 in lung adenocarcinomas make them more susceptible to TRAIL treatment. Despite rapid and robust initial responsiveness to TRAIL, surviving cells quickly acquired resistance to the additional TRAIL treatment. The expression of cellular-FLIP-short (c-FLIP) was significantly increased in surviving cells. Such upregulation of c-FLIP was rapidly reduced and TRAIL sensitivity was restored by treatment with cycloheximide. Silencing of c-FLIP, but not c-FLIP-long (c-FLIP), resulted in a remarkable increase in apoptosis and significant reduction of clonogenic survival. Furthermore, chelation of intracellular Ca or inhibition of calmodulin caused a rapid proteasomal degradation of c-FLIP, a significant increase of the two-step processing of procaspase-8, and reduced clonogenicity in response to TRAIL. Thus, our results revealed that the upregulation of DR4 and caspase-8 expression in NSCLC cells make them more susceptible to TRAIL. However, these cells could survive TRAIL treatment via upregulation of c-FLIP, and it is suggested that blocking c-FLIP expression by inhibition of Ca/calmodulin signaling significantly overcomes the acquired resistance of NSCLC cells to TRAIL.
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[644]
TÍTULO / TITLE: - The relationship between XRCC1 and XRCC3 gene polymorphisms and lung cancer risk in northeastern Chinese.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56213. doi: 10.1371/journal.pone.0056213. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056213
AUTORES / AUTHORS: - Guo S; Li X; Gao M; Li Y; Song B; Niu W
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Medical Genomics, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
RESUMEN / SUMMARY: - BACKGROUND: The prevalence of lung cancer in China will be the world’s highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genes with lung cancer risk in northeastern Chinese. METHODOLOGY/PRINCIPAL FINDINGS: This study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions) method. Data were analyzed by R language and multifactor dimensionality reduction (MDR) software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002) and Arg399Gln (P = 0.017), and in allele distributions of Thr241Met (P = 0.005). Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR): 2.47; 95% confidence interval (95% CI): 1.48-4.13; P<0.001). For Thr241Met, significance persisted under allelic (OR = 1.63; 95% CI: 1.14-2.33; P = 0.005), additive (OR = 1.64; 95% CI: 1.16-2.32; P = 0.005) and dominant (OR = 1.67; 95% CI: 1.17-2.38; P = 0.004) models. However, common allele combinations were comparable in frequency between patients and controls. In interaction analysis, the overall best MDR model included Arg399Gln and Thr241Met polymorphisms, with a maximal testing accuracy of 63.18% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0175). CONCLUSIONS: Our study significantly demonstrated an independent and synergistic contribution of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms to lung cancer susceptibility in northeastern Chinese.
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[645]
TÍTULO / TITLE: - Immunohistochemical detection of mutations in the epidermal growth factor receptor gene in lung adenocarcinomas using mutation-specific antibodies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Feb 18;8(1):27.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-27
AUTORES / AUTHORS: - Xiong Y; Bai Y; Leong N; Laughlin TS; Rothberg PG; Xu H; Nong L; Zhao J; Dong Y; Li T
RESUMEN / SUMMARY: - ABSTRACT: BACKGROUND: The recent development of antibodies specific for the major hotspot mutations in the epidermal growth factor receptor (EGFR), L858R and E746_A750del, may provide an opportunity to use immunohistochemistry (IHC) as a screening test for EGFR gene mutations. This study was designed to optimize the IHC protocol and the criteria for interpretation of the results using DNA sequencing as the gold-standard. METHODS: Tumor sections from fifty lung adenocarcinoma specimens from Chinese patients were immunostained using L858R and E746_A750del-specific antibodies using three different antigen retrieval solutions, and the results were evaluated using three different sets of criteria. The same specimens were used for DNA purification and analysis of EGFR gene mutations. RESULTS: In this study the optimal buffer for antigen retrieval was EDTA (pH 8.0), and the optimal scoring method was to call positive results when there was moderate to strong staining of membrane and/or cytoplasm in >10% of the tumor cells. Using the optimized protocol, L858R-specific IHC showed a sensitivity of 81% and a specificity of 97%, and E746_A750del-specific IHC showed a sensitivity of 59% and a specificity of 100%, both compared with direct DNA analysis. Additionally, the mutant proteins as assessed by IHC showed a more homogeneous than heterogeneous pattern of expression. CONCLUSIONS: Our data demonstrate that mutation-specific IHC, using optimized procedures, is a reliable prescreening test for detecting EGFR mutations in lung adenocarcinoma. Virtual Slides The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/2059012601872392.
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[646]
TÍTULO / TITLE: - Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 1;13:44. doi: 10.1186/1471-2407-13-44.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-44
AUTORES / AUTHORS: - Wu M; Tu T; Huang Y; Cao Y
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Animal Models and Human Disease Mechanism, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
RESUMEN / SUMMARY: - BACKGROUND: To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. METHODS: Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. RESULTS: Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro. CONCLUSIONS: The two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer.
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[647]
TÍTULO / TITLE: - TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncotarget. 2013 Jan;4(1):163-73.
AUTORES / AUTHORS: - Bourboulia D; Han H; Jensen-Taubman S; Gavil N; Isaac B; Wei B; Neckers L; Stetler-Stevenson WG
INSTITUCIÓN / INSTITUTION: - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Advanced Technology Center, 8717 Grovemont Circle, Bethesda, MD, USA.
RESUMEN / SUMMARY: - Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) plays an essential role in regulating matrix remodeling, cell growth, differentiation, angiogenesis and apoptosis in vitro and in vivo. We have recently shown that TIMP-2-mediated inhibition of tumor growth is independent of matrix metalloproteinase-mediated mechanisms, and is a consequence of modulating both the tumor cells and the tumor microenvironment. In the current study we aim to identify the molecular pathways associated with these effects. We analyzed the transcriptional profile of the human lung cancer cell line A549 upon overexpression of TIMP-2 and Ala+TIMP-2 (mutant that does not inhibit MMP activity), and we found changes in gene expression predominantly related to decreased tumor development and metastasis. Increased E-cadherin expression in response to both TIMP-2 and Ala+TIMP-2 expression was confirmed by real time quantitative RT-PCR and immunoblotting. A549 cells treated with epidermal growth factor (EGF) displayed loss of cobblestone morphology and cell-cell contact, while cells overexpressing TIMP-2 or Ala+TIMP-2 were resistant to EGF-induced morphological changes. Moreover, exogenous treatment with recombinant Ala+TIMP-2 blocked EGF induced down-regulation of E-cadherin. In vivo, immunohistochemistry of A549 xenografts expressing either TIMP-2 or Ala+TIMP-2 demonstrated increased E-cadherin protein levels. More importantly, transcriptional profile analysis of tumor tissue revealed critical pathways associated with effects on tumor-host interaction and inhibition of tumor growth. In conclusion, we show that TIMP-2 promotes an anti-tumoral transcriptional profile in vitro and in vivo, including upregulation of E-cadherin, in A549 lung cancer cells.
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[648]
TÍTULO / TITLE: - Efficacy of Recombinant Adenoviral Human p53 Gene in Treatment of Malignant Pleural or Peritoneal Effusions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Zhongguo Fei Ai Za Zhi. 2013 Mar 20;16(3):153-6. doi: 10.3779/j.issn.1009-3419.2013.03.07.
●● Enlace al texto completo (gratuito o de pago) 3779/j.issn.1009-3419.2013.03.07
AUTORES / AUTHORS: - Zhang X; Hu Y; Wang J; Zhang S; Tao H; Jing S; Wu B
INSTITUCIÓN / INSTITUTION: - Department of Oncology, the General Hospital of Chinese PLA, Beijing 100853, China;National Key Lab of Molecular Oncology, Cancer Institute & Hospital, CAMS, Beijing 100021, China.
RESUMEN / SUMMARY: - BACKGROUND: Once the malignant pleural or peritoneal effusion is developed it is difficult to control. This report presents a new method for controlling the malignant effusions. METHODS: Forty-eight patients, 29 males and 19 females with an average age of 61.2 years old, who were satisfied with the study inclusion criteria, were recruited in this study. Twenty-seven and 21 patients had a malignant pleural and peritoneal effusion, respectively. After draining most of fluids, these patients received intra-cavity infusion of rAd-p53 once per week for 4 weeks, at dose of 2x10(1)(2) viral particles (VP) diluted into 200 mL of saline solution for pleural effusions, and 4x10(1)(2) VP diluted into 500 mL of saline solution for peritoneal effusions. RESULTS: Participants were followed up for a median time of 13.6 month. A total of 11 cases, 7 with pleural effusions and 4 with peritoneal effusions achieved a complete response (CR), and 20 cases (12 pleural effusions and 8 peritoneal effusions) had a partial response (PR). The overall response rate is 64.6%. Patients’ quality of life, assessed by using Karnofsky performance scale (KPS) scores, was improved by an average of 26.4. The one-year of overall survival rate was 54.2% with a median survival time of 12.5 months. There were no serious side effects observed except for self-limited fever found in 79.8% of the cases. CONCLUSIONS: Intra-cavity infusion of rAd-p53 is an effective and safe treatment for the patients with malignant pleural or peritoneal effusions, especially for those patients who can’t tolerate the standard treatments.
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[649]
TÍTULO / TITLE: - Positron emission tomography/computed tomography in cases with tuberculosis mimicking lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Braz J Infect Dis. 2013 Mar 6. pii: S1413-8670(13)00050-0. doi: 10.1016/j.bjid.2012.05.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bjid.2012.05.005
AUTORES / AUTHORS: - Boyaci H; Basyigit I; Baris SA
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary Disease, School of Medicine, Kocaeli University, Umuttepe, Turkey. Electronic address: haboyaci@yahoo.com.
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[650]
TÍTULO / TITLE: - Explorations of lung cancer stigma for female long-term survivors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nurs Inq. 2013 Feb 16. doi: 10.1111/nin.12024.
●● Enlace al texto completo (gratuito o de pago) 1111/nin.12024
AUTORES / AUTHORS: - Brown C; Cataldo J
INSTITUCIÓN / INSTITUTION: - Center for Tobacco Control Research and Education, University of California, San Francisco, CA, USA.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer death in women, accompanied by greater psychological distress than other cancers. There is minimal but increasing awareness of the impact of lung cancer stigma (LCS) on patient outcomes. LCS is associated with increased symptom burden and decreased quality of life. The purpose of this study was to explore the experience of female long-term lung cancer survivors in the context of LCS and examine how participants discursively adhere to or reject stigmatizing beliefs. Findings situated within Cataldo and colleagues’ theoretical model include: (1) addiction and tobacco marketing as possible precursors for LCS, (2) the possible role of expert providers as LCS enhancers, (3) response of overlapping complicated identity shifts, (4) simultaneous rejection and assumption of LCS, and (5) information control via advocacy activities as a LCS mitigation response. These findings expand the current understanding of LCS, and call for future conceptual exploration and theoretical revision, particularly with respect to the possibility of interaction between relevant/related stigma(s) and LCS. As the number of women living with lung cancer increases, with longer survival times, the effect of LCS and other experiences of discrimination on patient outcomes could be substantial.
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[651]
TÍTULO / TITLE: - Association between survivin gene promoter -31G/C and -644C/T polymorphisms and non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genet Mol Res. 2013 Feb 28;12(AOP).
●● Enlace al texto completo (gratuito o de pago) 4238/2013.February.28.9
AUTORES / AUTHORS: - Aynaci E; Coskunpinar E; Eren A; Kum O; Oltulu YM; Akkaya N; Turna A; Yaylim I; Yildiz P
INSTITUCIÓN / INSTITUTION: - Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey.
RESUMEN / SUMMARY: - Lung cancer is the most common cancer worldwide. Survivin is one of the first reported inhibitors of apoptosis proteins, which is an important family of proteins that regulate apoptosis. The survivin gene is located on human chromosome 17q25, which is composed of 142 amino acids. A common polymorphism of the survivin gene promoter -31G/C has been shown to influence cancer risk. This genetic variant has been associated with overexpression of survivin at both protein and mRNA levels in cancer cells. We examined promoter (-31G\C) genotype frequency in a patient group (N = 146), 77.4% GG, 18.5% GC, 4.1% CC, and in a control group (N = 98), 57.1% GG, 34.7% GC, 8.2% CC. These distributions were significantly different. Promoter (-644C\T) genotype frequency in the patient group was 40.4% TT, 48.6% TC, 11% CC, and in the control group it was 551% TT, 40.8% TC, 4.1% CC; these distributions were also significantly different. Individuals carrying the survivin 31 GC genotype and those carrying the survivin 644 CC genotype had a significantly decreased risk of having non-small-cell lung cancer.
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[652]
TÍTULO / TITLE: - Investigation of Radiation-induced Transcriptome Profile of Radioresistant Non-small Cell Lung Cancer A549 Cells Using RNA-seq.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59319. doi: 10.1371/journal.pone.0059319. Epub 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059319
AUTORES / AUTHORS: - Yang HJ; Kim N; Seong KM; Youn H; Youn B
INSTITUCIÓN / INSTITUTION: - Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.
RESUMEN / SUMMARY: - Radioresistance is a main impediment to effective radiotherapy for non-small cell lung cancer (NSCLC). Despite several experimental and clinical studies of resistance to radiation, the precise mechanism of radioresistance in NSCLC cells and tissues still remains unclear. This result could be explained by limitation of previous researches such as a partial understanding of the cellular radioresistance mechanism at a single molecule level. In this study, we aimed to investigate extensive radiation responses in radioresistant NSCLC cells and to identify radioresistance-associating factors. For the first time, using RNA-seq, a massive sequencing-based approach, we examined whole-transcriptome alteration in radioresistant NSCLC A549 cells under irradiation, and verified significant radiation-altered genes and their chromosome distribution patterns. Also, bioinformatic approaches (GO analysis and IPA) were performed to characterize the radiation responses in radioresistant A549 cells. We found that epithelial-mesenchymal transition (EMT), migration and inflammatory processes could be meaningfully related to regulation of radiation responses in radioresistant A549 cells. Based on the results of bioinformatic analysis for the radiation-induced transcriptome alteration, we selected seven significant radiation-altered genes (SESN2, FN1, TRAF4, CDKN1A, COX-2, DDB2 and FDXR) and then compared radiation effects in two types of NSCLC cells with different radiosensitivity (radioresistant A549 cells and radiosensitive NCI-H460 cells). Interestingly, under irradiation, COX-2 showed the most significant difference in mRNA and protein expression between A549 and NCI-H460 cells. IR-induced increase of COX-2 expression was appeared only in radioresistant A549 cells. Collectively, we suggest that COX-2 (also known as prostaglandin-endoperoxide synthase 2 (PTGS2)) could have possibility as a putative biomarker for radioresistance in NSCLC cells.
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[653]
TÍTULO / TITLE: - Single-agent chemotherapy compared with combination chemotherapy as second-line treatment in extensive-stage small cell lung cancer: a retrospective analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1013-5
AUTORES / AUTHORS: - Song Z; Shao L; Lin B; Zhang Y
INSTITUCIÓN / INSTITUTION: - Department of Chemotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, 310022, People’s Republic of China.
RESUMEN / SUMMARY: - OBJECTIVE: This retrospective analysis evaluates the clinical outcomes of extensive-stage small cell lung cancer (SCLC) patients who received second-line chemotherapy after platinum-based first-line chemotherapy, especially focusing on efficacy and toxicity between single-agent and combination chemotherapy. METHODS: We retrospectively reviewed 193 patients who received second-line chemotherapy for extensive-stage SCLC. Patients relapsing or progressing beyond 90 days were defined as sensitive recurrence patients, and below 90 days as refractory recurrence patients. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. RESULTS: 138 patients received combination chemotherapy and 55 received single-agent treatment. The objective response rate (ORR) was 25.4 % in the combination group and 9.1 % in the single-agent group (p = 0.012). The disease control rate (DCR) was 65.2 and 34.5 %, respectively, (p < 0.001). The progression-free survival (PFS) was 3.80 months in the combination group and 2.13 months in the single-agent group (p = 0.001). In the sensitive recurrence group, the median PFS was 3.80 months in combination group and 3.23 months in single-agent group (p = 0.092). In the refractory recurrence group, the median PFS was 2.83 and 1.30 months, respectively (p = 0.001). The grade III/IV toxicity in single-agent group is much lower than the combination group (56.4 vs. 74.6 %, p = 0.013). CONCLUSION: Our retrospective data suggest a potential role of prolonging the PFS for combination treatment in extensive-stage SCLC second-line treatment, especially for the refractory recurrence patients, but with more toxicity as compared to single-agent.
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[654]
- CASTELLANO -
TÍTULO / TITLE:Baixas doses incrementais de amrubicina para o tratamento de metastase na medula ossea, proveniente de cancer de pulmao de pequenas celulas.
TÍTULO / TITLE: - Incremental low doses of amrubicin for the treatment of bone marrow metastasis in small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Bras Pneumol. 2013 Feb;39(1):108-110.
AUTORES / AUTHORS: - Asai N; Ohkuni Y; Matsuda M; Narita M; Kaneko N
INSTITUCIÓN / INSTITUTION: - Kameda Medical Center, Kamogawa, Japao.
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[655]
TÍTULO / TITLE: - Pulmonary Mucinous Cystadenocarcinoma: Report a Case and Review of CT Findings.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Radiol. 2013 Mar;14(2):384-8. doi: 10.3348/kjr.2013.14.2.384. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 3348/kjr.2013.14.2.384
AUTORES / AUTHORS: - Choi YA; Lee HY; Han J; Choi JY; Kim J; Kwon OJ; Lee KS
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
RESUMEN / SUMMARY: - A pulmonary mucinous cystadenocarcinoma is an extremely rare tumor that is considered to be a cystic variant of mucin-producing lung adenocarcinoma. We present a case of pulmonary mucinous cystadenocarcinoma in a 54-year-old woman. Chest CT scans showed a 4.3-cm-sized, lobulated, well-defined, and homogeneous mass in the right middle lobe with peripheral stippled calcifications that demonstrated low-attenuation with no enhancement after contrast administration; (18)F-fluorodeoxyglucose (FDG) PET/CT demonstrated mild heterogeneous FDG uptake. The mass was diagnosed as adenocarcinoma with mucin production by transbronchial lung biopsy. Right middle lobectomy was performed, and the pathologic examination disclosed a pulmonary mucinous cystadenocarcinoma.
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[656]
TÍTULO / TITLE: - Thromboprophylaxis in ambulatory lung cancer treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin J Oncol Nurs. 2013 Feb;17(1):74-9. doi: 10.1188/13.CJON.74-79.
●● Enlace al texto completo (gratuito o de pago) 1188/13.CJON.74-79
AUTORES / AUTHORS: - Cavaliere L
INSTITUCIÓN / INSTITUTION: - Jefferson School of Nursing, Thomas Jefferson University, Philadelphia, PA, USA. loretta.cavaliere@jefferson.edu
RESUMEN / SUMMARY: - Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, are common problems experienced by patients with lung cancer that can impact treatment plans, prognoses, and survival. Patients with lung cancer are at greatest risk for development of VTE in the ambulatory care treatment setting. Literature does exist on VTE management for medical and surgical oncology inpatients, as well as clinical guidelines for inpatient prophylaxis; however, published evidence is lacking on outpatient risk and thromboprophylaxis in medical oncology outpatients, particularly patients with lung cancer. Because patients with lung cancer treated in the ambulatory setting have established risks for VTE, they may benefit from thromboprophylaxis. Clinical guidelines for outpatient thromboprophylaxis direct the clinical practice for thromboprophylaxis in lung cancer treatment. The purpose of the current article is to explore the VTE risks associated with ambulatory lung cancer treatment and to review the recommended guidelines for thromboprophylaxis to guide clinical decision making for patients with lung cancer.
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[657]
TÍTULO / TITLE: - A unique case of well differentiated papillary mesothelioma involving an inguinal hernia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Indian J Pathol Microbiol. 2012 Oct;55(4):546-8. doi: 10.4103/0377-4929.107810.
●● Enlace al texto completo (gratuito o de pago) 4103/0377-4929.107810
AUTORES / AUTHORS: - Anirudhan TN; Chakravarthy R; Jothishankar P
INSTITUCIÓN / INSTITUTION: - Department of Histopathology, Apollo Specialty Hospitals, Teynampet, Chennai, India.
RESUMEN / SUMMARY: - Well Differentiated Papillary Mesothelioma (WDPM) is an uncommon tumor occurring predominantly in the peritoneum of young women with no history of asbestos exposure. In this report, we present a case of 48 year old male patient presenting with indirect inguinal hernia and incidental finding of a WDPM in the hernial sac during surgery. The unusual site of presentation and the relative rarity of this neoplasm in males evoke much clinico-pathological interest.
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[658]
TÍTULO / TITLE: - Overexpression of aldolase A and cytokeratin 19 in ovine pulmonary adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pol J Vet Sci. 2012;15(4):703-9.
AUTORES / AUTHORS: - Kycko A; Reichert M
INSTITUCIÓN / INSTITUTION: - Department of Pathology, National Veterinary Research Institute, Al. Partyzantow 57, 24-100 Pulawy, Poland. anna.kycko@piwet.pulawy.pl
RESUMEN / SUMMARY: - Ovine pulmonary adenocarcinoma (OPA) is a transmissible lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). In the present study the protein profiles of five neoplastic and three non-neoplastic sheep lung tissues were examined for the identification of proteins overexpressed in ovine pulmonary adenocarcinoma. Lung sections of the experimental group of sheep were collected during necropsies for proteomic and immunohistochemical examination. Two dimensional electrophoresis (2DE) was performed using gel strips with immobilized pH gradient 3-10. As a result of 2DE gel analysis 14 spots characterized by over 2-fold higher expression in tumour proteomes were selected for mass spectrometry. In eleven spots more than one polypeptide was identified indicating overlapping of proteins in gels. In two spots demonstrating over 3-fold higher expression in OPA proteomes, single proteins: cytokerarin 19 (CK19) and aldolase A were identified. Immunohistochemical studies revealed that CK19 and aldolase A were expressed in the cytoplasm of epithelial cells of bronchioles in non-neoplastic lung sections, as well as epithelial cells of bronchioles and neoplastic cells in lung sections of OPA affected sheep. The results indicate that the overexpression of the two proteins reflects the presence of neoplastic cells in the lungs of OPA affected sheep.
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[659]
TÍTULO / TITLE: - Ionizing Radiation Potentiates Dihydroartemisinin-Induced Apoptosis of A549 Cells via a Caspase-8-Dependent Pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59827. doi: 10.1371/journal.pone.0059827. Epub 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059827
AUTORES / AUTHORS: - Chen T; Chen M; Chen J
INSTITUCIÓN / INSTITUTION: - MOE Key Laboratory of Laser Life Science and SATCM Third Grade Laboratory of Chinese Medicine and Photonics Technology, College of Biophotonics, South China Normal University, Guangzhou, China.
RESUMEN / SUMMARY: - This report is designed to explore the molecular mechanism by which dihydroartemisinin (DHA) and ionizing radiation (IR) induce apoptosis in human lung adenocarcinoma A549 cells. DHA treatment induced a concentration- and time-dependent reactive oxygen species (ROS)-mediated cell death with typical apoptotic characteristics such as breakdown of mitochondrial membrane potential (Deltapsim), caspases activation, DNA fragmentation and phosphatidylserine (PS) externalization. Inhibition of caspase-8 or -9 significantly blocked DHA-induced decrease of cell viability and activation of caspase-3, suggesting the dominant roles of caspase-8 and -9 in DHA-induced apoptosis. Silencing of proapoptotic protein Bax but not Bak significantly inhibited DHA-induced apoptosis in which Bax but not Bak was activated. In contrast to DHA treatment, low-dose (2 or 4 Gy) IR induced a long-playing generation of ROS. Interestingly, IR treatment for 24 h induced G2/M cell cycle arrest that disappeared at 36 h after treatment. More importantly, IR synergistically potentiated DHA-induced generation of ROS, activation of caspase-8 and -3, irreparable G2/M arrest and apoptosis, but did not enhance DHA-induced loss of Deltapsim and activation of caspase-9. Taken together, our results strongly demonstrate the remarkable synergistic efficacy of combination treatment with DHA and low-dose IR for A549 cells in which IR potentiates DHA-induced apoptosis largely by enhancing the caspase-8-mediated extrinsic pathway.
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[660]
TÍTULO / TITLE: - Vector-mediated selective expression of lethal factor, a toxic element of Bacillus anthracis, damages A549 cells via inhibition of MAPK and AKT pathways.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Med Sci. 2013;10(3):292-8. doi: 10.7150/ijms.5570. Epub 2013 Jan 27.
●● Enlace al texto completo (gratuito o de pago) 7150/ijms.5570
AUTORES / AUTHORS: - Zhuo W; Tao G; Zhang L; Chen Z
INSTITUCIÓN / INSTITUTION: - Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China. zhuowenlei@yahoo.com.cn
RESUMEN / SUMMARY: - Lethal factor (LF), a major toxic element of Bacillus anthracis combined with its protective antigen (PA), enters the cells through the cytomembrane receptors and causes damage to the host cells, thereby leading to septicemia, toxemia, and meningitis with high mortality. LF has been identified as a potential biotech-weapon, which can impede cancer growth in vascular endothelial cells because of its cytotoxicity. However, the feasibility of LF application and further investigations has been limited because LF is nonspecific. To solve this problem, we constructed a vector that contained the LF sequence, which was regulated by a tumor-specific human telomerase reverse transcriptase promoter (hTERTp). Results showed that LF was selectively expressed in lung cancer A549 cells but not in normal cells, thereby resulting in A549 cell apoptosis. The results also revealed that the inhibition of mitogen-activated protein kinase and AKT pathways was partially involved in the process. Thus, hTERTp-regulated LF increase could be a promising approach in lung cancer-targeted therapy.
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[661]
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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[662]
TÍTULO / TITLE: - Curettage and diathermy: a treatment for feline nasal planum actinic dysplasia and superficial squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Small Anim Pract. 2013 Feb;54(2):92-8. doi: 10.1111/jsap.12025.
●● Enlace al texto completo (gratuito o de pago) 1111/jsap.12025
AUTORES / AUTHORS: - Jarrett RH; Norman EJ; Gibson IR; Jarrett P
INSTITUCIÓN / INSTITUTION: - Pukekohe Veterinary Centre, 11 Edinburgh St, Pukekohe, 2120, New Zealand.
RESUMEN / SUMMARY: - OBJECTIVE: To evaluate curettage and diathermy as a treatment for actinic dysplasia and superficial squamous cell carcinoma of the feline nasal planum. METHODS: Thirty-four cats clinically assessed to have actinic dysplasia and superficial squamous cell carcinoma involving less than 50% of the nasal planum were treated with a three-cycle curettage and diathermy procedure. Degree of dysplasia, response to treatment, adverse effects, owner perceptions, time to recurrence and proportion disease free at 1 year were evaluated. RESULTS: Lesions ranged from actinic keratoses to invasive squamous cell carcinoma. A complete response to treatment was obtained in all cats. The median follow-up time was 18 . 2 (IQR: 12 . 0-22 . 8) months. Two cats had a clinical recurrence of lesions at 161 and 192 days after treatment. The probability of remaining disease free after 12 months was 0 . 94 (95% CI: 0 . 85-1 . 0). Median time to recurrence was not reached. The procedure was well tolerated with a good cosmetic outcome and no significant post-operative complications. CLINICAL SIGNIFICANCE: This study suggests that curettage and diathermy is an effective treatment for feline actinic dysplasia and for superficial squamous cell carcinoma involving less than 50% of the nasal planum. Curettage and diathermy is an easily mastered technique, requiring minimal equipment.
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[663]
TÍTULO / TITLE: - Synchronous appearance and improvement with anticancer chemotherapy of paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome complicated with small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Rinsho Shinkeigaku. 2013;53(2):104-8.
AUTORES / AUTHORS: - Koriyama H; Kyoraku I; Yamashita S; Shiomi K; Matsumoto N; Nakazato M
INSTITUCIÓN / INSTITUTION: - Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki.
RESUMEN / SUMMARY: - A 62-year-old man who had suffered from instability of gait and double vision for two months was admitted to our hospital because of weakness of the extremities and ataxia of the extremities and trunk. Chest X-rays and CT scans showed enlargement of the left hilar lymph nodes and a nodular shadow in the left lung. Transbronchial biopsy revealed small cell lung cancer. We diagnosed the patient with two conditions: paraneoplastic cerebellar degeneration (PCD), based on cerebellar ataxia, the presence of Hu antineuronal antibodies, and the absence of cerebellar atrophy and malignancy; and Lambert-Eaton myasthenic syndrome (LEMS), based on weakness of the extremities, the presence of P/Q-type voltage-gated calcium channel antibodies, and waxing in the evoked electromyogram. Anticancer chemoradiation therapy that was started within three months of symptom onset resulted in reductions in size of the hilar lymph nodes and the nodule. Concurrently, cerebellar ataxia, weakness of the extremities, and double vision all disappeared. Anticancer chemotherapy is effective against LEMS while usually less effective against PCD. Early commencement of anticancer chemotherapy is recommended for the treatment of PCD with LEMS.
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[664]
TÍTULO / TITLE: - Factors associated with referral to medical oncology and subsequent use of adjuvant chemotherapy for non-small-cell lung cancer: a population-based study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Oncol. 2013 Feb;20(1):30-7. doi: 10.3747/co.20.1178.
●● Enlace al texto completo (gratuito o de pago) 3747/co.20.1178
AUTORES / AUTHORS: - Kankesan J; Shepherd FA; Peng Y; Darling G; Li G; Kong W; Mackillop WJ; Booth CM
INSTITUCIÓN / INSTITUTION: - Division of Cancer Care and Epidemiology, Queen’s University Cancer Research Institute, Kingston, ON.
RESUMEN / SUMMARY: - BACKGROUND: Adjuvant chemotherapy (act) for non-small-cell lung cancer (nsclc) is associated with improved survival in the general population, but may be underutilized. We explored the factors associated with referral to medical oncology and subsequent use of act among all patients with resected nsclc in Ontario, Canada. METHODS: The Ontario Cancer Registry was used to identify all incident cases of nsclc diagnosed in Ontario during 2004-2006. We linked electronic records of treatment and of physician billing to identify surgery, act, and medical oncology consultation. A multivariate logistic regression model was used to evaluate factors associated with referral to medical oncology and subsequent use of act. RESULTS: Among 3354 cases of nsclc resected in Ontario during 2004-2006, 1830 (55%) were seen postoperatively by medical oncology, and 1032 (31%) were treated with act. Patients more than 70 years of age were less likely than younger patients to have a consultation [odds ratio (or): 0.4; p < 0.001]. A higher proportion of cases with stage ii or iii nsclc than with stage i disease were referred (ors: 2.7, 2.0 respectively; p < 0.005). We observed substantial geographic variation in the proportion of surgical cases referred (range: 32%-88%) that was not explained by differences in case mix. Among cases referred to medical oncology, older patients (age 60-69 years, or: 0.4; age 70+ years, or: 0.1; p < 0.001) with greater comorbidity (Charlson comorbidity index: 3+; or: 0.5; p < 0.05) and a longer postoperative stay (median length of stay: 7+ days; or: 0.7; p = 0.001) were less likely to receive act. Use of act was greater in patients with stage ii or iii than with stage i disease (ors: 3.0, 2.7 respectively; p < 0.001); use also varied with geographic location (range: 46%-63%). CONCLUSIONS: The initial decision to refer to medical oncology is associated with age and stage of disease, and those factors have an even greater effect on the decision to offer act. Comorbidity and postoperative length of stay were not associated with initial referral, but were associated with use of act in patients seen by medical oncology.
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[665]
TÍTULO / TITLE: - Role of FGF receptors as an emerging therapeutic target in lung squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Future Oncol. 2013 Mar;9(3):377-86. doi: 10.2217/fon.12.190.
●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.190
AUTORES / AUTHORS: - Lim SM; Kim HR; Shim HS; Soo RA; Cho BC
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Gu, Seoul 120-752, Korea.
RESUMEN / SUMMARY: - Recent advances in molecular medicine and high-throughput sequencing technologies have achieved major cancer strategies and therapeutics over the past decades. For example, identification of oncogenic EGF receptor mutations that are present in up to 20% of lung adenocarcinoma patients confer exquisite sensitivity to EGF receptor inhibitors. However, currently known ‘druggable’ targets are enriched in the subgroup of adenocarcinomas and individuals who have never smoked. We present an overview of FGFs and FGF receptor (FGFR) signaling in cancer, and the role of FGFR1 as a novel druggable target in lung squamous cell carcinoma. FGFR1 amplification in lung squamous cell carcinoma is required for the survival of FGFR1-amplified cell lines. Currently, clinical reagents that target the FGFs and FGFRs are being developed accordingly. This review focuses on the emerging role of FGFR1 as a therapeutic target in lung squamous cell carcinoma and reviews current agents that are in clinical development for the treatment of FGFR-dependent cancer.
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[666]
TÍTULO / TITLE: - Huge Solitary Fibrous Tumor of the Pleura with Hypoglycemia and Hypokalemia: A Case Report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Jan 31.
AUTORES / AUTHORS: - Li Z; Wang J; Zhu Q; Li H; Chen Y; Chen L
INSTITUCIÓN / INSTITUTION: - Department of Cardiothoracic Surgery, the First Affiliated Hospi tal of Nanjing Medical University, Nanjing, China.
RESUMEN / SUMMARY: - The occurrence of hypoglycemia with an intrathoracic tumor is referred to as Doege- Potter syndrome (DPS). However, the association between hypokalemia and DPS is rare. We report a case of a solitary fibrous tumor of the pleura with refractory hypoglycemia and hypokalemia. A 57-year-old male was admitted to our hospital for unconsciousness. His serum glucose and potassium levels were low. Radiological findings revealed a large tumor occupying the left hemithorax. Despite being treated with glucose and potassium replacement therapy, the patient still suffered from repetitive fasting hypoglycemic and hypokalemia episodes. After the tumor was completely resected, his serum levels of glucose and potassium returned to normal level.
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[667]
TÍTULO / TITLE: - A case report on bronchoalveolar carcinoma presenting as non-resolving consolidation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med J Islam Repub Iran. 2012 Aug;26(3):140-2.
AUTORES / AUTHORS: - Shoib S; Malik JA; Arif T; Bashir H
INSTITUCIÓN / INSTITUTION: - MBBS, MD Student, Department of Psychiatry, Govt Medical College Srinagar, Kashmir, India.
RESUMEN / SUMMARY: - Bronchoalveolar carcinoma presenting as non-resolving consolidation is an uncommon presentation. The typical presentation of bronchoalveolar carcinoma is asymptomatic (solitary nodule) and remains without symptoms even as disease disseminates. We report a case of bronchoalveolar carcinoma presenting as non-resolving consolidation in a young male with productive cough, exertional breathlessness and physical examination revealing the features of right lower consolidation on x-ray chest, with subsequent CT of the chest and bronchoscopic examination revealed bronchoalveolar carcinoma. Patient had a good score and was managed conservatively.
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[668]
TÍTULO / TITLE: - Partial Anomalous Pulmonary Venous Connection Associated with Lung Cancer in the Same Lobe: Report of a Case.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Jan 31.
AUTORES / AUTHORS: - Asakura K; Izumi Y; Kohno M; Watanabe M; Arai T; Nomori H
INSTITUCIÓN / INSTITUTION: - Division of General Thoracic Surgery, Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
RESUMEN / SUMMARY: - A 64-year-old man with primary lung cancer (cT1aN0M0) was diagnosed as having partial anomalous pulmonary venous connection (PAPVC) in the same lobe by preoperative chest computed tomography (CT). The anomalous vein originated from left upper lobe pulmonary vein and flowed into the left brachiocephalic vein. Although the patient was asymptomatic, cardiac catheterization revealed that pulmonary-systemic blood flow ratio (Qp/Qs ratio) was 2.0, and his pulmonary arterial pressure was marginally elevated (60/18 mmHg). We performed left upper lobectomy as the definitive treatment for both lung cancer and PAPVC. His pulmonary arterial pressure decreased after lobectomy (33/16 mmHg). He is living well without relapse of lung cancer 56 months after surgery. Although PAPVC is detectable on computed tomography, out of 7 previous reports of PAPVC associated with lung cancer, only 2 cases were diagnosed preoperatively. The presence of PAPVC should be kept in mind before major lung resections.
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[669]
TÍTULO / TITLE: - Genetic variation of the natural killer gene complex has a role in lung cancer susceptibility.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Dis. 2013 Feb;5(1):3-5. doi: 10.3978/j.issn.2072-1439.2012.11.12.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.11.12
AUTORES / AUTHORS: - Logan RW; Sarkar DK
INSTITUCIÓN / INSTITUTION: - Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA;
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[670]
TÍTULO / TITLE: - Three Dimensional Computed Tomography Lung Modeling is Useful in Simulation and Navigation of Lung Cancer Surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Jan 31.
AUTORES / AUTHORS: - Ikeda N; Yoshimura A; Hagiwara M; Akata S; Saji H
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan.
RESUMEN / SUMMARY: - The number of minimally invasive operations, such as video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy, has enormously increased in recent years. These operations require extreme knowledge of the anatomy of pulmonary vessels and bronchi in each patient, and surgeons must carefully dissect the branches of pulmonary vessels during operation. Thus, foreknowledge of the anatomy of each patient would greatly contribute to the safety and accuracy of the operation. The development of multi-detector computed tomography (MDCT) has promoted three dimensional (3D) images of lung structures. It is possible to see the vascular and bronchial structures from the view of the operator; therefore, it is employed for preoperative simulation as well as navigation during operation. Due to advances in software, even small vessels can be accurately imaged, which is useful in performing segmentectomy. Surgical simulation and navigation systems based on high quality 3D lung modeling, including vascular and bronchial structures, can be used routinely to enhance the safety operation, education of junior staff, as well as providing a greater sense of security to the operators.
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[671]
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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[672]
TÍTULO / TITLE: - Thoracoscopic surgery for non-small-cell lung cancer: elderly vs. octogenarians.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Cardiovasc Thorac Ann. 2013 Feb;21(1):56-60. doi: 10.1177/0218492312455528.
●● Enlace al texto completo (gratuito o de pago) 1177/0218492312455528
AUTORES / AUTHORS: - Srisomboon C; Koizumi K; Haraguchi S; Mikami I; Iijima Y; Shimizu K
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Surgery, Department of Surgery, Nippon Medical School, Tokyo, Japan. chaisits1968@yahoo.com
RESUMEN / SUMMARY: - BACKGROUND: Octogenarians are rarely referred for surgical treatment of lung cancer owing to the morbidity and mortality of pulmonary resection, their frailty, and limited lifespan. We reviewed the results of thoracoscopic surgery, performed completely under the monitor, for treatment of primary non-small-cell lung cancer in octogenarians, and compared them with those in elderly patients. PATIENTS AND METHODS: Between September 25, 2002 and August 25, 2011, a retrospective database of 24 octogenarians and 70 elderly patients (age range, 75-79 years) who underwent thoracoscopic surgery for treatment of primary non-small-cell lung cancer were reviewed. Demographic, histopathologic, preoperative, perioperative, postoperative, outcome variables, and survival were assessed. RESULTS: In the octogenarian group, 29% had postoperative respiratory complications, 4% had postoperative cardiac complications, operative mortality was 4%, the recurrence rate was 8%, and the postsurgical 5-year survival rate was 74%. In the elderly group, 25% had postoperative respiratory complications, 6% had postoperative cardiac complications, operative mortality was 3%, the recurrence rate was 6%, and the postsurgical 5-year survival rate was 80%. CONCLUSIONS: Thoracoscopic surgery for treatment of primary non-small-cell lung cancer can be performed with similar postoperative complication rates, operative mortality, and survival in octogenarians when compared to elderly patients.
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[673]
TÍTULO / TITLE: - Surgery for Elderly Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Feb 28.
AUTORES / AUTHORS: - Liu HC; Huang WC; Wu CL; Huang JT; Chen CH; Chen YJ
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
RESUMEN / SUMMARY: - Objective: There are still controversies about the surgical benefits for elderly lung cancer.The aims of this study were to assess impacts of aging for non-small cell lung cancer(NSCLC) following pulmonary resection.Methods: A retrospective study was undertaken for patients operated at a curative intent from January 1998 to October 2008. Patients were divided into two groups: Group 1 consisted of patients aged at least 75 years old, and group 2 were patients less than 75 years old. Perioperative characteristics and details, hospital courses, surgery-related morbidities, surgical mortality, and survival were compared between groups.Results: Of 442 eligible patients, 73 patients (16.5%) were in group 1 (mean age 78.3years) and 369 (83.5%) patients were in group 2 (mean age 62.5 years). The following data were compared with statistical significance: hospital stay (17.8 vs. 8.9 days), mortality rate (8.2 vs. 2.2%), morbidity rate (26.0 vs. 13.3%), and length in intensive care unit (5.7vs. 3.2 days). The main causes for morbidities in group 1 showed cardiopulmonary-related. Tumor stage without considering age had statistically significant influence on survival. Survivals of two groups were comparative. (p= 0.10) Intriguingly, the disease-related survival (28.3 months; p= 0.008) and progression-free survival (25.0 months; p<0.001) in group 1 were significantly better than group 2 (20.2 and 12.2 months).Conclusions: Although operation for NSCLC in the elderly patients causes more complications, especially in the cardiopulmonary system, their outcome showed better than their younger counterparts. Pulmonary resection for elderly patients may get longer disease control. Elderly patients with physical fit for surgery should not be considered as a contraindication to pulmonary resection based on age alone.
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[674]
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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[675]
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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[676]
TÍTULO / TITLE: - Circulating tumor cells as a diagnostic test for malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Med Diagn. 2012 May;6(3):171-3. doi: 10.1517/17530059.2012.676042.
●● Enlace al texto completo (gratuito o de pago) 1517/17530059.2012.676042
AUTORES / AUTHORS: - Pinton G; Manente AG; Moro L; Mutti L
INSTITUCIÓN / INSTITUTION: - University of Piemonte Orientale “A. Avogadro”, Department of Pharmaceutical Sciences , Novara , Italy.
RESUMEN / SUMMARY: - The detection of circulating tumor cells (CTCs) may have important prognostic and therapeutic implications; therefore, we expect a broader range of tumor types in which CTC detection and count will routinely be conducted in the coming years. This article evaluates the application of CTC as a potentially useful diagnostic and prognostic test in malignant pleural mesothelioma (MMe). MMe is a rare but increasingly prevalent, highly aggressive asbestos exposure-related tumor. MMe develops after long time latency, is rarely diagnosed at early stages, is poorly sensitive to conventional treatments and presents a very short survival upon diagnosis. Pursuing research of CTC in MMe can represent a very important task for all the clinical and preclinical scientists working on blood biomarkers of this tumor. Possibly in combination with other diagnostic tools, such as a thoracoscopy and advanced imaging, CTC can represent a promising tool for MMe prognosis and follow-up. Further studies to confirm value of CTC test in MMe are warranted.
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[677]
TÍTULO / TITLE: - Molecular markers as therapeutic targets in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin J Cancer. 2013 Feb;32(2):59-62. doi: 10.5732/cjc.013.10011.
●● Enlace al texto completo (gratuito o de pago) 5732/cjc.013.10011
AUTORES / AUTHORS: - Tseng HH; He B
INSTITUCIÓN / INSTITUTION: - Thoracic Oncology Program. Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. biao.he@ucsfmedctr.org.
RESUMEN / SUMMARY: - Lung cancer is responsible for 29% of cancer deaths in the United States and has very low 5-year survival rates of approximately 11% in men and 15% in women. Although the early diagnosis of lung cancer may increase the survival rate with adequate treatment, advanced lung cancers are often metastasized and receive limited benefit from therapeutic regimens. As conventional treatments for lung cancer reach their limitations, researchers have attempted to discover novel drug therapies aimed at specific targets contributing to the progression of tumorigenesis. Recent advances in systems biology have enabled the molecular biology of lung carcinogenesis to be elucidated. Our understanding of the physiologic processes of tumor development provide a means to design more effective and specific drugs with less toxicity, thereby accelerating the delivery of new drug therapies to the patient’s bedside.
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[678]
TÍTULO / TITLE: - LKB1 Mutation Sensitizes NSCLC Cells to Phenformin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar;3(3):OF14. doi: 10.1158/2159-8290.CD-RW2013-023. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2013-023
RESUMEN / SUMMARY: - Phenformin, a metformin analogue, selectively induces apoptosis in LKB1-mutant NSCLC models.
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[679]
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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[680]
TÍTULO / TITLE: - A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Imaging Radiat Oncol. 2013 Feb;57(1):105-12. doi: 10.1111/j.1754-9485.2012.02470.x. Epub 2013 Jan 17.
●● Enlace al texto completo (gratuito o de pago) 1111/j.1754-9485.2012.02470.x
AUTORES / AUTHORS: - Bettington CS; Tripcony L; Bryant G; Hickey B; Pratt G; Fay M
INSTITUCIÓN / INSTITUTION: - Radiation Oncology Services, Mater Centre, South Brisbane, Queensland, Australia. Catherine_Bettington@health.qld.gov.au
RESUMEN / SUMMARY: - PURPOSE: To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). METHODS AND MATERIALS: At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane & Women’s Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40 Gy in 15 fractions (‘the 40 Gy/15# group’) or 45 Gy in 30 fractions (‘the 45 Gy/30# group’). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. RESULTS: Of 118 eligible patients, there were 38 patients in the 40 Gy/15# group and 41 patients in the 45 Gy/30# group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2-37 months) in the 40 Gy/15# group and 26 months (95% CI 1-48 months) in the 45 Gy/30# group. The 5-year overall survival rates were 20% and 25%, respectively (P = 0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P = 0.01) and whether salvage chemotherapy was given at the time of relapse (P = 0.057). CONCLUSIONS: Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival.
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[681]
TÍTULO / TITLE: - Successful treatment of an intrathoracic bronchogenic cyst in a Holstein-Friesian calf.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Vet Scand. 2013 Feb 19;55:14. doi: 10.1186/1751-0147-55-14.
●● Enlace al texto completo (gratuito o de pago) 1186/1751-0147-55-14
AUTORES / AUTHORS: - Berchtold B; Meylan M; Gendron K; Morath U; Rytz U; Lejeune B
INSTITUCIÓN / INSTITUTION: - Clinic for Ruminants, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Berne, Berne, Switzerland. beatrice.lejeune@bluewin.ch.
RESUMEN / SUMMARY: - A 5-(1/2)-month-old female Holstein-Friesian calf was presented with a history of recurring ruminal tympany and poor development. The absence of lung sounds on the right hemithorax suggested a right-sided intrathoracic pathology. Radiography and computed tomography revealed a large thin-walled cavernous lesion with a gas-fluid interface which almost completely filled the right thoracic cavity. Fluid aspirated from the lesion was clear, yellowish and odorless. These findings led to the diagnosis of a bronchogenic cyst. Thoracotomy was performed under general anesthesia. The cyst strongly adhered to the adjacent lung tissue. After removal of the free wall, the adjacent lung tissue was sealed using surgical stapling instruments, and the non-removable part of the wall was curetted and rinsed. The intensive postoperative management included antibiotic therapy, oxygen supplementation and regional lidocaine infusion. Anti-inflammatory drugs were administered for further pain control. The calf recovered well and was released from the clinic on postoperative day 11. Intra- or extrathoracic bronchogenic cysts result from abnormal budding during the embryonic development of the tracheobronchial system. Successful treatment of this calf despite the size of the lesion and the invasive character of the surgical intervention indicates that resection of bronchogenic cysts in cattle may be an option for valuable animals.
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[682]
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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[683]
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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[684]
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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[685]
TÍTULO / TITLE: - Therapy response evaluation with FDG-PET/CT in small cell lung cancer: a prognostic and comparison study of the PERCIST and EORTC criteria.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Imaging. 2013 Mar 5;13:73-80. doi: 10.1102/1470-7330.2013.0008.
●● Enlace al texto completo (gratuito o de pago) 1102/1470-7330.2013.0008
AUTORES / AUTHORS: - Ziai D; Wagner T; El Badaoui A; Hitzel A; Woillard JB; Melloni B; Monteil J
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, Dupuytren Hospital, Limoges, France; Department of Radiology, Hospital, Brive, France.
RESUMEN / SUMMARY: - Introduction: Small cell lung cancer (SCLC) is an aggressive form of lung cancer with poor prognosis. Adequate staging and therapeutic evaluation is necessary for therapy planning. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been shown to be useful for staging and therapy response evaluation. The European Organization for Research and Treatment of Cancer (EORTC) and Positron Emission Tomography Response Criteria In Solid Tumors (PERCIST) criteria were compared in the evaluation of response assessment and prognostic factors were defined in a cohort of SCLC patients. Methods: Twenty-nine consecutive patients with SCLC were included in this study. Sixteen patients had extensive disease and 13 had limited disease. All patients had chemotherapy, 21 had thoracic radiotherapy. FDG-PET/CT scans were performed before and after therapy to evaluate treatment response. Metabolic responses were assessed using the EORTC criteria and PERCIST criteria. Univariate and multivariate analysis were performed using a Cox model to investigate the association between progression-free and overall survival time with a number of covariates. Results: There was perfect concordance between the EORTC and PERCIST criteria. Eight patients had a complete metabolic response (CMR), 9 had a partial metabolic response (PMR), 5 had stable metabolic disease (SMD) and 7 had progressive metabolic disease (PMD). Overall survival time in patients with CMR was significantly longer compared with patients who did not have CMR. The initial or delayed CMR and post-therapeutic standardized uptake value corrected for lean body mass were significantly associated with overall survival. Conclusion: CMR on post-therapeutic FDG-PET/CT in patients with SCLC is an important prognostic factor and may help decision making for therapeutic management.
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[686]
TÍTULO / TITLE: - Lung cancer risk from occupational and environmental radon and role of smoking in two Czech nested case-control studies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Environ Res Public Health. 2013 Mar 7;10(3):963-79. doi: 10.3390/ijerph10030963.
●● Enlace al texto completo (gratuito o de pago) 3390/ijerph10030963
AUTORES / AUTHORS: - Tomasek L
INSTITUCIÓN / INSTITUTION: - National Radiation Prtotection Institute, Bartoskova 28, Prague, Czech Republic. ladislav.tomasek@suro.cz
RESUMEN / SUMMARY: - The aim of the present study was to evaluate the risk of lung cancer from combined exposure to radon and smoking. Methodologically, it is based on case-control studies nested within two Czech cohort studies of nearly 11,000 miners followed-up for mortality in 1952-2010 and nearly 12,000 inhabitants exposed to high levels of radon in homes, with mortality follow-up in 1960-2010. In addition to recorded radon exposure, these studies use information on smoking collected from the subjects or their relatives. A total of 1,029 and 370 cases with smoking information have been observed in the occupational and environmental (residential) studies, respectively. Three or four control subjects have been individually matched to cases according to sex, year of birth, and age. The combined effect from radon and smoking is analyzed in terms of geometric mixture models of which the additive and multiplicative models are special cases. The resulting models are relatively close to the additive interaction (mixing parameter 0.2 and 0.3 in the occupational and residential studies, respectively). The impact of the resulting model in the residential radon study is illustrated by estimates of lifetime risk in hypothetical populations of smokers and non-smokers. In comparison to the multiplicative risk model, the lifetime risk from the best geometric mixture model is considerably higher, particularly in the non-smoking population.
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[687]
TÍTULO / TITLE: - Clinical and pathological features are still the best determinants of prognosis in mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncology (Williston Park). 2012 Dec;26(12):1176, 1178, 1180.
AUTORES / AUTHORS: - Miller AC; Hassan R
INSTITUCIÓN / INSTITUTION: - Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
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[688]
TÍTULO / TITLE: - Understanding of Tobacco and Lung Cancer Among Medical Students in Kathmandu University School of Medical Sciences (KUSMS).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Kathmandu Univ Med J (KUMJ). 2012 Jul;10(39):60-5.
AUTORES / AUTHORS: - Khatiwada P; Kayastha SR; Pant P; Khanal KR; Giri A; Khatiwoda P; Mali A
INSTITUCIÓN / INSTITUTION: - Richa Bajimaya Memorial Foundation, Kathmandu, Nepa.
RESUMEN / SUMMARY: - Background Often, lung cancer is diagnosed at terminal stages. Poor awareness about the symptoms or risk factors of lung cancer among medics may be one of the factors for delayed diagnosis. Objective We explored the knowledge of medical students and their behavior with the patients of lung cancer. Method Qualitative and quantitative approaches were used for data collection from 153 medical student of Kathmandu University School of Medical Sciences from December 2011 to May 2012. Results Among the results, eighty-nine students had over 80% knowledge of the 14 cancer warning signs, among them 83% knew the nine risk factors for lung cancer. Twenty-three students told lung cancer can be hereditary. Sixty five percent of all participants believed that lung cancer can be detected at early stage; of them 81% told that it can be treated. About 24% of the total students were current or exsmokers and about half of them believed that lung cancer does not occur in light smokers. Only 10% have heard of Framework Convention on Tobacco Control in Nepal. Conclusion Study finds that all medical students who know about any cancers may not necessarily have knowledge about lung cancers. Their perception about the cause of lung cancer may be influenced by their smoking behavior and there was little knowledge of public health measures for smoking control. Awareness about national policies needs to be increased.
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[689]
TÍTULO / TITLE: - Changes in lung function after surgery for mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Cardiovasc Thorac Ann. 2013 Feb;21(1):48-55. doi: 10.1177/0218492312454017.
●● Enlace al texto completo (gratuito o de pago) 1177/0218492312454017
AUTORES / AUTHORS: - Ploenes T; Osei-Agyemang T; Krohn A; Waller CF; Duncker-Rohr V; Elze M; Passlick B
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, University Medical Center Freiburg, Freiburg, Germany. Till.Ploenes@uniklinik-freiburg.de
RESUMEN / SUMMARY: - BACKGROUND: The effect of pleurectomy/decortication or extrapleural pleuropneumonectomy on pulmonary function has not yet been evaluated. The aim of this study was to determine the parameters of pulmonary function before and after pleurectomy/decortication or extrapleural pleuropneumonectomy. METHODS: We conducted a review of 48 patients with unilateral malignant pleural mesothelioma who underwent pleurectomy/decortication or extrapleural pleuropneumonectomy. Data including medical history, histology, survival, and pre- and postoperative pulmonary function were extracted from the medical database of the University Medical Center Freiburg, or sought by telephone interview with the general practitioner or patients. RESULTS: 25 patients underwent extrapleural pleuropneumonectomy and 23 had pleurectomy/decortication. Pulmonary function was not significantly reduced in the pleurectomy/decortication group postoperatively. In the extrapleural pleuropneumonectomy group, the median preoperative total lung capacity of 4.8 L (77.7%) differed significantly from the postoperative total lung capacity of 3.5 L (55.3%; p <0.0006). The median vital capacity was significantly reduced from 2.8 L (77.7%) preoperatively to 1.8 L (47.6%) postoperatively (p <0.0002). Other parameters were also highly significantly reduced after extrapleural pleuropneumonectomy. CONCLUSIONS: Pleurectomy/decortication preserved good pulmonary function, whereas extrapleural pleuropneumonectomy significantly reduced pulmonary function, which may lead to dyspnea and influence the quality of life of these patients.
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[690]
TÍTULO / TITLE: - Lung Cancer Knowledge among Secondary School Male Teachers in Kudat, Sabah, Malaysia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):103-9.
AUTORES / AUTHORS: - Al-Naggar RA; Kadir SY
INSTITUCIÓN / INSTITUTION: - Community Medicine Department, International Medical School, Management and Science University, Malaysia E-mail: radhwan888@yahoo.com.
RESUMEN / SUMMARY: - Background: The objective of this study is to determine knowledge about lung cancer among secondary school male teachers in Kudat, Sabah, Malaysia. Materials and Methods: A cross-sectional study was conducted among three secondary schools located in Kudat district, Sabah, Malaysia during the period from June until September 2012. The protocol of this study was approved by ethics committee of Management and Science University, Malaysia. The aims were explained and a consent form was signed by each participant. Respondents were chosen randomly from each school with the help of the headmasters. Self-administrated questionnaires, covering socio-demographic characteristics and general knowledge of lung cancer, were distributed. Once all 150 respondents completed the questionnaire, they passed it to their head master for collecting and recording. All the data were analyzed using Statistical Package for the Social Sciences (SPSS) version 13. ANOVA and t-test were applied for univariate analysis; and multiple linear regression for multivariate analysis. Results: A total of 150 male secondary school teachers participated in this study. Their mean age was 35.6-/+6.5 (SD); maximum 50 and minimum 23 years old. More than half of the participants were Malay and married (52%, 79%; respectively). Regarding the knowledge about lung cancer, 57.3% of the participants mentioned that only males are affected by lung cancer. Some 70.7% mentioned that lung cancer can be transmitted from one person to another. More than half (56.7%) reported that lung cancer is not the leading cause of death in Malaysian males. As for risk factors, the majority reported that family history of lung cancer is not involved. However, 91.3% were aware that cigarettes are the main risk factor of lung cancer and more than half (52%) believed that second-hand smoking is one of the risk factor of lung cancer. More than half (51.3%) were not aware that asbestos, ionizing radiation and other cancer causing substances are risk factors for lung cancer. Quitting smoking, avoiding second-hand smoking and avoiding unnecessary x-ray image of the chest (53.3%, 96.0%, 87.3%; respectively) are the main preventive measures mentioned by the participants. For the factors that influence the participants knowledge, univariate and multivariate analysis showed that only race was significant. Conclusions: Overall, the knowledge of school male teachers about lung cancer was low. However, few items were scored high: cigarettes are the main risk factor; avoiding second-hand smoking; and avoiding x-rays. Interventions to increase lung cancer awareness are needed to improve early detection behavior. Increase the price of pack of cigarettes to RM 20 and banning smoking in public places such as restaurants are highly recommended as primary preventive measures.
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[691]
TÍTULO / TITLE: - Asperolide A, a Marine-Derived Tetranorditerpenoid, Induces G2/M Arrest in Human NCI-H460 Lung Carcinoma Cells, Is Mediated by p53-p21 Stabilization and Modulated by Ras/Raf/MEK/ERK Signaling Pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mar Drugs. 2013 Jan 29;11(2):316-31. doi: 10.3390/md11020316.
●● Enlace al texto completo (gratuito o de pago) 3390/md11020316
AUTORES / AUTHORS: - Lv C; Sun W; Sun H; Wei S; Chen R; Wang B; Huang C
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, College of Basic Medical Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Rhchen1964@sohu.com.
RESUMEN / SUMMARY: - Here we first demonstrate that asperolide A, a very recently reported marine-derived tetranorditerpenoid, leads to the inhibition of NCI-H460 lung carcinoma cell proliferation by G2/M arrest with the activation of the Ras/Raf/MEK/ERK signaling and p53-dependent p21 pathway. Treatment with 35 muM asperolide A (2 x IC(50)) resulted in a significant increase in the proportion of G2/M phase cells, about a 2.9-fold increase during 48 h. Immunoblot assays demonstrated time-dependent inhibition of G2/M regulatory proteins. Moreover, asperolide A significantly activated MAP kinases (ERK1/2, JNK and p38 MAP kinase) by phosphorylation, and only the inhibition of ERK activation by PD98059 reversed downregulation of G2/M regulatory proteins CDC2, and suppressed upregulation of p21 and p-p53 levels. Transfection of cells with dominant-negative Ras (RasN17) mutant genes up-regulated asperolide A-induced the decrease of cyclin B1 and CDC2, suppressed Raf, ERK activity and p53-p21 expression, and at last, abolished G2/M arrest. This study indicates that asperolide A-induced G2/M arrest in human NCI-H460 lung carcinoma cells relys on the participation of the Ras/Raf/MEK/ERK signaling pathway in p53-p21 stabilization. An in vivo study with asperolide A illustrated a marked inhibition of tumor growth, and little toxcity compared to Cisplatin therapy. Overall, these findings provide potential effectiveness and a theoretical basis for the therapeutic use of asperolide A in the treatment of malignancies.
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[692]
TÍTULO / TITLE: - Caveolin-1 Regulates Endothelial Adhesion of Lung Cancer Cells via Reactive Oxygen Species-Dependent Mechanism.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57466. doi: 10.1371/journal.pone.0057466. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057466
AUTORES / AUTHORS: - Chanvorachote P; Chunhacha P
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand.
RESUMEN / SUMMARY: - The knowledge regarding the role of caveolin-1 (Cav-1) protein on endothelium adhesion of cancer cells is unclear. The present study revealed that Cav-1 plays a negative regulatory role on cancer-endothelium interaction. Endogenous Cav-1 was shown to down-regulate during cell detachment and the level of such a protein was conversely associated with tumor-endothelial adhesion. Furthermore, the ectopic overexpression of Cav-1 attenuated the ability of the cancer cells to adhere to endothelium while shRNA-mediated Cav-1 knock-down exhibited the opposite effect. We found that cell detachment increased cellular hydrogen peroxide and hydroxyl radical generation and such reactive oxygen species (ROS) were responsible for the increasing interaction between cancer cells and endothelial cells through vascular endothelial cell adhesion molecule-1 (VCAM-1). Importantly, Cav-1 was shown to suppress hydrogen peroxide and hydroxyl radical formation by sustaining the level of activated Akt which was critical for the role of Cav-1 in attenuating the cell adhesion. Together, the present study revealed the novel role of Cav-1 and underlying mechanism on tumor adhesion which explain and highlight an important role of Cav-1 on lung cancer cell metastasis.
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[693]
TÍTULO / TITLE: - Activation of the FGF2-FGFR1 Autocrine Pathway: A Novel Mechanism of Acquired Resistance to Gefitinib in NSCLC Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Res. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0652
AUTORES / AUTHORS: - Terai H; Soejima KN; Yasuda H; Nakayama S; Hamamoto J; Arai D; Ishioka K; Ohgino K; Ikemura S; Sato T; Yoda S; Satomi R; Naoki K; Betsuyaku T
INSTITUCIÓN / INSTITUTION: - Keio University, School of Medicine.
RESUMEN / SUMMARY: - Almost all patients with non-small cell lung cancer (NSCLC) who harbor an epidermal growth factor receptor (EGFR) mutation initially respond well to EGFR-tyrosine kinase inhibitors (TKIs) eventually experience relapse. Acquiring resistance to EGFR-TKIs is strongly associated with the mortality of these patients and a thorough elucidation of the mechanism of acquiring resistance to EGFR-TKIs is of great importance. In this study, we have established a gefitinib-resistant cell line model by long-term exposure to gefitinib. We used originally gefitinib-sensitive lung cancer cell lines, namely PC9 and HCC827. We found that the expressions of both FGFR1 and FGF2 were increased in PC9 gefitinib-resistant (PC9 GR) cells compared to those in PC9 naive (PC9 na) cells. We found that proliferation of the PC9 GR cells was dependent on FGF2-FGFR1 pathway. Inhibition of either FGF2 or FGFR1 by siRNA or FGFR inhibitor (PD173074) restored the gefitinib sensitivity in PC9 GR cells. We propose FGF2-FGFR1 activation through autocrine loop is a novel mechanism of acquiring resistance to EGFR-TKIs and that this loop be targeted to overcome acquired resistance to EGFR-TKIs in a subset of NSCLC patients.
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[694]
TÍTULO / TITLE: - CCAAT/Enhancer-Binding Protein-alpha Suppresses Lung Tumor Development in Mice through the p38alpha MAP Kinase Pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57013. doi: 10.1371/journal.pone.0057013. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057013
AUTORES / AUTHORS: - Sato A; Yamada N; Ogawa Y; Ikegami M
INSTITUCIÓN / INSTITUTION: - Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
RESUMEN / SUMMARY: - The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) is a basic leucine zipper transcription factor and is expressed in alveolar type II cells, alveolar macrophages and Clara cells in the lung. Although decrease or absence of C/EBPalpha expression in human non-small cell lung cancer suggests a possible role of C/EBPalpha as a lung tumor suppressor, there is no direct proof for this hypothesis. In this study, we investigated, for the first time, the role of C/EBPalpha in lung tumors in vivo using transgenic mice with lung epithelial specific conditional deletion of Cebpa (Cebpalpha(Delta/Delta) mice) and a urethane-induced lung tumor model. C/EBPalpha expression in the lung was dispensable, and its deletion was not oncogenic under unstressed conditions. However, at 28 wk after urethane injection, the number and size of tumors and the tumor burden were significantly higher in Cebpalpha(Delta/Delta) mice than in littermate control mice. Urethane-injected Cebpalpha(Delta/Delta) mice showed highly proliferative adenomas and adenocarcinomas in the lung, and survival time after urethane-injection was significantly shorter than that in control mice. In control mice, C/EBPalpha was strongly induced in the tumor tissues at 28 weeks after urethane-injection, but became weakened or absent as tumors progressed after long-term observation for over 1 year. Using intraperitoneal injection of p38 inhibitor (SB203580), we demonstrated that the induction of C/EBPalpha is strongly regulated by the p38 MAP kinase in murine alveolar epithelial cells. A high correlation was demonstrated between the expression of C/EBPalpha and p38alpha MAP kinase in tumor cells, suggesting that C/EBPalpha silencing in tumor cells is caused by down-regulation of p38alpha MAP kinase. In conclusion, the role of C/EBPalpha as a lung tumor suppressor was demonstrated for the first time in the present study, and the extinguished C/EBPalpha expression through p38alpha inactivation leads tumor promotion and progression.
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[695]
TÍTULO / TITLE: - Cardiac tamponade as the first symptom of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pneumonol Alergol Pol. 2013;81(2):149-53.
AUTORES / AUTHORS: - Gromadzinski L; Przelaskowski P; Januszko-Giergielewicz B; Gorny J; Stankiewicz A; Kazarnowicz A; Pruszczyk P
RESUMEN / SUMMARY: - Pericardial effusion is a relatively common clinical problem. It is, however, rarely the first symptom of cancer. Cardiac tamponade testifies to an advanced stage of cancer and is a negative prognostic factor. This paper presents a patient in whom cardiac tamponade was the first symptom of lung cancer. A 63-year-old male, habitual smoker, was admitted to hospital due to progressive symptoms of exertional dyspnoea lasting for a few days and chest pain. Echocardiographic examination revealed a large amount of fluid in the pericardium with echocardiographic signs of a life-threatening cardiac tamponade. The patient underwent pericardial puncture and additional imaging examinations. Lung adenocarcinoma was recognized as the underlying disease. Due to the recurrence of the life-threatening cardiac tamponade, video-assisted thoracoscopic pericardial fenestration was performed and systemic chemotherapy was introduced with good results.
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[696]
TÍTULO / TITLE: - Individualized risk prediction model for lung cancer in Korean men.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e54823. doi: 10.1371/journal.pone.0054823. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054823
AUTORES / AUTHORS: - Park S; Nam BH; Yang HR; Lee JA; Lim H; Han JT; Park IS; Shin HR; Lee JS
INSTITUCIÓN / INSTITUTION: - Biometric Research Branch, National Cancer Center, Goyang, Republic of Korea.
RESUMEN / SUMMARY: - PURPOSE: Lung cancer is the leading cause of cancer deaths in Korea. The objective of the present study was to develop an individualized risk prediction model for lung cancer in Korean men using population-based cohort data. METHODS: From a population-based cohort study of 1,324,804 Korean men free of cancer at baseline, the individualized absolute risk of developing lung cancer was estimated using the Cox proportional hazards model. We checked the validity of the model using C statistics and the Hosmer-Lemeshow chi-square test on an external validation dataset. RESULTS: The risk prediction model for lung cancer in Korean men included smoking exposure, age at smoking initiation, body mass index, physical activity, and fasting glucose levels. The model showed excellent performance (C statistic = 0.871, 95% CI = 0.867-0.876). Smoking was significantly associated with the risk of lung cancer in Korean men, with a four-fold increased risk in current smokers consuming more than one pack a day relative to non-smokers. Age at smoking initiation was also a significant predictor for developing lung cancer; a younger age at initiation was associated with a higher risk of developing lung cancer. CONCLUSION: This is the first study to provide an individualized risk prediction model for lung cancer in an Asian population with very good model performance. In addition to current smoking status, earlier exposure to smoking was a very important factor for developing lung cancer. Since most of the risk factors are modifiable, this model can be used to identify those who are at a higher risk and who can subsequently modify their lifestyle choices to lower their risk of lung cancer.
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[697]
TÍTULO / TITLE: - Oral treatment with etoposide in small cell lung cancer - dilemmas and solutions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiol Oncol. 2013 Mar;47(1):1-13. doi: 10.2478/raon-2013-0008. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 2478/raon-2013-0008
AUTORES / AUTHORS: - Rezonja R; Knez L; Cufer T; Mrhar A
INSTITUCIÓN / INSTITUTION: - Krka, d.d., Novo mesto, Slovenia.
RESUMEN / SUMMARY: - BACKGROUND: Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be at risk for excess toxicity. CONCLUSIONS: The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.
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[698]
TÍTULO / TITLE: - EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Med Sci. 2013;10(3):320-30. doi: 10.7150/ijms.4609. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 7150/ijms.4609
AUTORES / AUTHORS: - Antonicelli A; Cafarotti S; Indini A; Galli A; Russo A; Cesario A; Lococo FM; Russo P; Mainini AF; Bonifati LG; Nosotti M; Santambrogio L; Margaritora S; Granone PM; Dutly AE
INSTITUCIÓN / INSTITUTION: - Thoracic Surgery and Lung Transplantation Unit, Foundation IRCCS (Scientific Institute for Research Hospitalization and Health Care) “Ca’ Granda” General Hospital, University of Milan, Milan, Italy.
RESUMEN / SUMMARY: - The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.
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[699]
TÍTULO / TITLE: - Chemotherapy management of malignant pleural mesothelioma: a phase II study comparing two popular chemotherapy regimens.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1015-3
AUTORES / AUTHORS: - Habib EE; Fahmy ES
INSTITUCIÓN / INSTITUTION: - Department of Clinical Oncology, Cairo University Faculty of Medicine, Cairo, Egypt, cairo.oncology@gmail.com.
RESUMEN / SUMMARY: - PURPOSE: The aim of this prospective, phase II clinical study is to evaluate the activity of gemcitabine and cisplatin in comparison to pemetrexed and carboplatin in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: The patients were recruited from May 2008 to May 2011. One group included 21 cases who received cisplatin and gemcitabine. The other group included 19 cases who received pemetrexed and carboplatin. RESULTS: Response is superior in the pemetrexed group (p = 0.041). The median follow-up was 18 months (range 6-30 months). Cumulative survival at 1.5 years was 57.8 % for the pemetrexed carboplatin group. For the gemcitabine cisplatin group, the cumulative survival proportion at 1.5 years was 41 % (p = 0.0599). CONCLUSIONS: Pemetrexed plus carboplatin are a step forward in the treatment of mesothelioma, the prognosis for these patients remains poor. Cheaper combinations as gemcitabine and cisplatin may be considered sufficient to treat cases with advanced mesothelioma.
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[700]
TÍTULO / TITLE: - Transcriptome sequencing of tumor subpopulations reveals a spectrum of therapeutic options for squamous cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58714. doi: 10.1371/journal.pone.0058714. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058714
AUTORES / AUTHORS: - Barrett CL; Schwab RB; Jung H; Crain B; Goff DJ; Jamieson CH; Thistlethwaite PA; Harismendy O; Carson DA; Frazer KA
INSTITUCIÓN / INSTITUTION: - Moores UCSD Cancer Center, University of California San Diego, La Jolla, California, United States of America ; Department of Pediatrics and Rady Children’s Hospital, University of California San Diego, La Jolla, California, United States of America.
RESUMEN / SUMMARY: - BACKGROUND: The only therapeutic options that exist for squamous cell lung carcinoma (SCC) are standard radiation and cytotoxic chemotherapy. Cancer stem cells (CSCs) are hypothesized to account for therapeutic resistance, suggesting that CSCs must be specifically targeted. Here, we analyze the transcriptome of CSC and non-CSC subpopulations by RNA-seq to identify new potential therapeutic strategies for SCC. METHODS: We sorted a SCC into CD133- and CD133+ subpopulations and then examined both by copy number analysis (CNA) and whole genome and transcriptome sequencing. We analyzed The Cancer Genome Atlas (TCGA) transcriptome data of 221 SCCs to determine the generality of our observations. RESULTS: Both subpopulations highly expressed numerous mRNA isoforms whose protein products are active drug targets for other cancers; 31 (25%) correspond to 18 genes under active investigation as mAb targets and an additional 4 (3%) are of therapeutic interest. Moreover, we found evidence that both subpopulations were proliferatively driven by very high levels of c-Myc and the TRAIL long isoform (TRAILL) and that normal apoptotic responses to high expression of these genes was prevented through high levels of Mcl-1L and Bcl-xL and c-FlipL-isoforms for which drugs are now in clinical development. SCC RNA-seq data (n = 221) from TCGA supported our findings. Our analysis is inconsistent with the CSC concept that most cells in a cancer have lost their proliferative potential. Furthermore, our study suggests how to target both the CSC and non-CSC subpopulations with one treatment strategy. CONCLUSIONS: Our study is relevant to SCC in particular for it presents numerous potential options to standard therapy that target the entire tumor. In so doing, it demonstrates how transcriptome sequencing provides insights into the molecular underpinnings of cancer propagating cells that, importantly, can be leveraged to identify new potential therapeutic options for cancers beyond what is possible with DNA sequencing.
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[701]
TÍTULO / TITLE: - Primary small cell carcinoma of the stomach: a case report with an immunohistochemical and molecular genetic analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Clin Exp Pathol. 2013;6(3):524-30. Epub 2013 Feb 15.
AUTORES / AUTHORS: - Terada T
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Shizuoka City Shimizu Hospital Shizuoka, Japan. piyo0111jp@yahoo.co.jp
RESUMEN / SUMMARY: - Small cell carcinoma (SCC) of the stomach is extremely rare; about 110 cases have been reported in the world literature. Immunohistochemical studies of various antigens and genetic studies of KIT and platelet-derived growth factor-alpha (PDGFRA) have not been performed in gastric SCC. An 84-year-old man consulted our hospital because of epigastralgia and weakness. Blood test showed anemia and increased CA19-9 (233 U/ml). Endoscopic examination revealed a large Borrmann type III tumor measuring 6x8 cm in the stomach. Biopsies from the tumor revealed typical small cell carcinoma with very scant cytoplasm, hyperchromatic nuclei, absent nucleoli, molded nuclei, and increased nucleo-cytoplasmic ratio. Immunohistochemically, the tumor cells were positive for pancytokeratin (PCK) WSS, PCK MNF-116, PCK AE1/3, PCK CAM5.2, cytokeratin (CK) 34BE12, CK 5/6, CK7, CK8, CK18, vimentin, EMA, KIT (CD117), CD56, synaptophysin, chromogranin, NSE, CA19-9, CEA, p53 protein, and Ki67 antigen (Ki-67 labeling = 60%). The tumor cells were negative for CK14, CK19, CK20, PDGFRA, CD45, CD45RO, CD3, CD20, CD30, and CD79a. A retrospective genetic analysis using PCR-direct sequencing method in paraffin sections identified no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. Various imaging modalities including CT and MRI showed multiple small metastases in the liver, bilateral lungs, and perigastric lymph nodes. The patient was thus inoperative. The patient is now treated by cisplatin-based chemotherapy four months after the first manifestation.
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[702]
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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[703]
TÍTULO / TITLE: - Successful management of an intra-operative pulmonary tumor embolism during resection of a retroperitoneal leiomyosarcoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Mar;126(5):980-1.
AUTORES / AUTHORS: - Zhu SM; Guo SH; Li LJ; Luo LH; Yao YX
INSTITUCIÓN / INSTITUTION: - Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
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[704]
TÍTULO / TITLE: - Combined anticancer activity of osthole and cisplatin in NCI-H460 lung cancer cells in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Mar;5(3):707-710. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2013.889
AUTORES / AUTHORS: - Xu XM; Zhang Y; Qu D; Liu HB; Gu X; Jiao GY; Zhao L
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
RESUMEN / SUMMARY: - Drug combination therapies are common practice in the treatment of cancer. Cisplatin is the most active chemotherapeutic agent for lung cancer treatment. Osthole is a natural compound extracted from a number of medicinal plants. To determine whether osthole enhances the anticancer effect of cisplatin in human lung cancer, we treated NCI-H460 cells with osthole alone or in combination with cisplatin and evaluated cell growth and apoptosis using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and fluorescence microscopy. The results showed that, in comparison with single agent treatment, the combination of osthole and cisplatin resulted in greater efficacy in growth inhibition and apoptosis induction. Western blot analysis revealed that the combination effect of osthole and cisplatin was due to regulation of the Bcl-2 family proteins. Findings of this investigation suggested that osthole combined with cisplatin is a potential clinical chemotherapeutic approach in human lung cancer.
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[705]
TÍTULO / TITLE: - Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):387-92.
AUTORES / AUTHORS: - Zhan M; Qu Q; Wang G; Liu YZ; Tan SL; Lou XY; Yu J; Zhou HH
INSTITUCIÓN / INSTITUTION: - Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China E-mail : hhzhou01@gmail.com.
RESUMEN / SUMMARY: - Objective: The aim of the present study was to explore mechanisms by which let-7c suppresses NSCLC cell proliferation. Methods: The expression level of let-7c was quantified by qRT-PCR. A549 and H1299 cells were transfected with let-7c mimics to restore the expression of let-7c. The effects of let-7c were then assessed by cell proliferation, colony formation and cell cycle assay. Mouse experiments were used to confirm the effect of let-7c on tumorigenicity in vivo. Luciferase reporter assays and Western blotting were performed to identify target genes for let-7c. Results: HOXA1 was identified as a novel target of let-7c. MTS, colony formation and flow cytometry assays demonstrated that forced expression of let-7c inhibited NSCLC cell proliferation by inducing G1 arrest in vitro, consistent with inhibitory effects induced by knockdown of HOXA1. Mouse experiments demonstrated that let-7c expression suppressed tumorigenesis. Furthermore, we found that let-7c could regulate the expression of HOXA1 downstream effectors CCND1, CDC25A and CDK2. Conclusions: Collectively, these results demonstrate let-7c inhibits NSCLC cell proliferation and tumorigenesis by partial direct targeting of the HOXA1 pathway, which suggests that restoration of let-7c expression may thus offer a potential therapeutic intervention strategy for NSCLC.
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[706]
TÍTULO / TITLE: - Silencing SATB1 with siRNA inhibits the proliferation and invasion of small cell lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 5;13(1):8. doi: 10.1186/1475-2867-13-8.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-8
AUTORES / AUTHORS: - Huang B; Zhou H; Wang X; Liu Z
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, the First Affiliated Hospital of Liaoning Medical University, No, 2 People street, 121000, Jinzhou, Liaoning, People’s Republic of China. huangbo60@yahoo.cn.
RESUMEN / SUMMARY: - BACKGROUND: Small cell lung cancer (SCLC) is a special kind of lung cancers, lymph or blood metastasis of SCLC usually occurs in early stage. Studies in breast and colon cancer showed over expression of SATB1 could promote tumor cell growth and inhibit apoptosis. Therefore, we studied the expression of SATB1 in SCLC. METHODS: The level of SATB1 was analyzed in SCLC tissues, metastatic lymphoid nodes and adjacent normal lung tissues by immunohistochemistry. Meanwhile, small interfering SATB1-targeting RNA was constructed and transfected into human SCLC cell line NCI-H446 to evaluate the effects of SATB1-siRNA on cell proliferation, invasion and apoptosis. RESULT: SATB1 protein was overexpressed in SCLC tissues and metastasis lymphoid nodes compared with adjacent normal lung tissues. Compared with control group, SATB1-siRNA inhibits the proliferation and invasion of SCLC cells and induces SCLC cells apoptosis statistically (P<0.05) in vitro. CONCLUSION: Our results suggest that SATB1 plays an important role in the metastasis of human SCLC cell.
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[707]
TÍTULO / TITLE: - Treatment of lung cancer using nanoparticle drug delivery systems.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Drug Discov Technol. 2013 Jun 1;10(2):170-6.
AUTORES / AUTHORS: - Chandolu V; Dass CR
INSTITUCIÓN / INSTITUTION: - School of Biomedical and Health Sciences, Bldg 6, Victoria University, St Albans 3021, Australia. crispin.dass@vu.edu.au.
RESUMEN / SUMMARY: - Context: One of the leading causes of cancer-associated deaths in most men and women in the Western world is lung cancer. There are various types of treatments depending on the type and the stage of the cancer. A recent type of therapy is targeted gene therapy which aims to target genes that cause lung cancer. However, this therapy has some drawbacks including lack of proper vectors for delivery. These drawbacks can potentially be overcome by using various types of nanoparticles. Objective: To review current literature on the treatment of lung cancer with nanoparticles. Methods: Researchers have attempted to treat lung cancer with a variety of types of nanoparticle matrices including lipid, polylactide-co-glycolide, albumin, poly (omega-pentadecalactone-co-butylene-co-succinate), cerium oxide, gold, ultra-small superparamagnetic iron oxide nanoparticles, super paramagnetic iron oxide, lipid-polycation-DNA, N-[1-(2,3- dioleoyloxyl)propyl]-NNN-trimethylammoniummethylsulfate, silica-overcoated magnetic cores, and polyethyleneglycol phosphatidylethanolamine. There are various ways in which nanoparticles enhance drug delivery, and these include encapsulation against immune response, tissue penetration, target selectivity and specificity, delivery monitoring, promoting apoptosis, and blocking pathways for cancer initiation and progression. Conclusion: In the past decade, a lot has been said about targeting of NPs for lung and other cancers, but little has been actually successfully delivered to date. Nevertheless, nanoparticles can act as good vectors for delivering drug to the target neoplastic lesions within the lung, increase cellular uptake, increase tissue penetration and help in tracking the drug. In the future, combination therapies may play a key role in the treatment of lung cancer using the existing therapies.
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[708]
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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[709]
TÍTULO / TITLE: - Endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer: the first experience in Hong Kong.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hong Kong Med J. 2013 Feb;19(1):20-6.
AUTORES / AUTHORS: - Wong MK; Ho JC; Loong F; Lam DC; Wong WM; Tam TC; Han L; Ip MS
INSTITUCIÓN / INSTITUTION: - Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
RESUMEN / SUMMARY: - OBJECTIVE: To investigate the diagnostic performance and safety of endobronchial ultrasound-guided transbronchial needle aspiration in patients presenting with radiological features of lung cancer. DESIGN: Prospective case series. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive patients with mediastinal or hilar abnormalities suspected of or confirmed as having lung cancer underwent endobronchial ultrasound-guided transbronchial needle aspiration and presented between August 2006 and December 2010. MAIN OUTCOME MEASURES: Diagnostic performance (including sensitivity, specificity, negative predictive value and accuracy), procedural complications, and tissue adequacy for molecular profiling. RESULTS: A total of 269 procedures were performed in 259 patients, with malignancy confirmed in 210 (81%) of them. In the whole cohort with confirmed or suspected lung cancer, the overall sensitivity, specificity, negative predictive value, and accuracy of endobronchial ultrasound-guided transbronchial needle aspiration were 87%, 100%, 74%, and 91%, respectively. Among 42 patients with tumour samples sent for mutation tests (epidermal growth factor receptor and/or anaplastic lymphoma kinase), 40 (95%) were found to be adequate. No complication or mortality ensued from these procedures. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspiration is highly effective in determining the diagnosis and lymph node staging in patients with lung cancer. In combination with its excellent safety profile, it should be considered a frontline diagnostic test for patients presenting with mediastinal abnormalities suspicious of lung cancer.
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[710]
TÍTULO / TITLE: - Therapeutic Efficacy of C-Kit-Targeted Radioimmunotherapy Using 90Y-Labeled Anti-C-Kit Antibodies in a Mouse Model of Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59248. doi: 10.1371/journal.pone.0059248. Epub 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059248
AUTORES / AUTHORS: - Yoshida C; Tsuji AB; Sudo H; Sugyo A; Kikuchi T; Koizumi M; Arano Y; Saga T
INSTITUCIÓN / INSTITUTION: - Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan ; Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
RESUMEN / SUMMARY: - : Small cell lung cancer (SCLC) is an aggressive tumor and prognosis remains poor. Therefore, the development of more effective therapy is needed. We previously reported that high levels of an anti-c-kit antibody (12A8) accumulated in SCLC xenografts. In the present study, we evaluated the efficacy of two antibodies (12A8 and 67A2) for radioimmunotherapy (RIT) of an SCLC mouse model by labeling with the (90)Y isotope. METHODS: (111)In- or (125)I-labeled antibodies were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays in c-kit-expressing SY cells and in vivo by biodistribution in SY-bearing mice. Therapeutic efficacy of (90)Y-labeled antibodies was evaluated in SY-bearing mice upto day 28 and histological analysis was conducted at day 7. RESULTS: [(111)In]12A8 and [(111)In]67A2 specifically bound to SY cells with high affinity (8.0 and 1.9 nM, respectively). 67A2 was internalized similar to 12A8. High levels of [(111)In]12A8 and [(111)In]67A2 accumulated in tumors, but not in major organs. [(111)In]67A2 uptake by the tumor was 1.7 times higher than for [(111)In]12A8. [(90)Y]12A8, but not [(90)Y]67A2, suppressed tumor growth in a dose-dependent manner. Tumors treated with 3.7 MBq of [(90)Y]12A8, and 1.85 and 3.7 MBq of [(90)Y]67A2 (absorbed doses were 21.0, 18.0 and 35.9 Gy, respectively) almost completely disappeared approximately 2 weeks after injection, and regrowth was not observed except for in one mouse treated with 1.85 MBq [(90)Y]67A2. The area of necrosis and fibrosis increased depending on the RIT effect. Apoptotic cell numbers increased with increased doses of [(90)Y]12A8, whereas no dose-dependent increase was observed following [(90)Y]67A2 treatment. Body weight was temporarily reduced but all mice tolerated the RIT experiments well. CONCLUSION: Treatment with [(90)Y]12A8 and [(90)Y]67A2 achieved a complete therapeutic response when SY tumors received an absorbed dose greater than 18 Gy and thus are promising RIT agents for metastatic SCLC cells at distant sites.
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[711]
TÍTULO / TITLE: - A Resectable Pancreatic Metastasis from Pulmonary Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Jan 31.
AUTORES / AUTHORS: - Igai H; Kamiyoshihara M; Nagashima T; Ohtaki Y; Shimizu K
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Maebashi Red Cross Hospital, Gunma, Japan.
RESUMEN / SUMMARY: - A 67-year-old man, diagnosed as primary pulmonary adenocarcinoma by intraoperative fine-needle aspiration biopsy cytology, underwent right lower lobectomy with radical lymphadenectomy. The pathological stage was Stage IIA (pT1bN1M0, N-reason: 12Lpositive). After surgery, nodular shadows without intrathoracic lymph node or distant metastasis were demonstrated metachronously three times by follow-up CT. Wedge resection was performed for each of the tumors, and the pathological diagnosis in each case was primary pulmonary adenocarcinoma, Stage IA (T1b), IA (T1a) and IA (T1a), respectively.Five years after the initial pulmonary resection, a follow-up abdominal CT revealed a20-mm nodular shadow. We suspected that this pancreatic tumor might be a primary rather than metastatic one, therefore, pancreatoduodenectomy was performed. Pathological examination revealed adenocarcinoma that was positive for thyroid transcription factor (TTF)-1, allowing a final diagnosis of metastatic pulmonary adenocarcinoma.This case is very rare, because most cases of pancreatic metastasis from lung cancer have already widespread disease at the time of diagnosis.This case illustrates that pancreatic metastasis from pulmonary adenocarcinoma should be borne in mind, even if the pancreatic tumor is a solitary lesion without additional organ metastasis.
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[712]
TÍTULO / TITLE: - Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Mar 12. doi: 10.1002/cncy.21288.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21288
AUTORES / AUTHORS: - Cai G; Wong R; Chhieng D; Levy GH; Gettinger SN; Herbst RS; Puchalski JT; Homer RJ; Hui P
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
RESUMEN / SUMMARY: - BACKGROUND: The identification of molecular alterations has an important therapeutic implication in patients with lung adenocarcinomas. In the current study, the authors evaluated their experience with the identification of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement using cytological specimens of primary and metastatic lung adenocarcinoma. METHODS: A total of 54 cases of lung adenocarcinomas (11 primary and 43 metastatic tumors) in which molecular tests were performed were retrieved. Molecular tests were performed on the cell block material of 19 effusions and 35 fine-needle aspirates. EGFR mutation was evaluated by polymerase chain reaction sequencing analysis of exons 18, 19, 20, and 21. KRAS mutation was tested using polymerase chain reaction-single-strand conformational polymorphism analysis of codons 12 and 13. ALK gene rearrangement was evaluated by fluorescence in situ hybridization using an ALK break apart probe. RESULTS: Molecular tests were successful in 49 of 54 cases (91%). Evaluation of EGFR mutation, KRAS mutation, and ALK gene rearrangement were performed in 49 cases, 14 cases, and 22 cases, respectively. EGFR mutations were found in 14 of 49 cases (29%), including 5 primary and 9 metastatic tumors. Three metastatic/recurrent adenocarcinomas demonstrated an additional EGFR T790M mutation that was not identified in the original specimens. KRAS mutation was detected in 3 of 14 cases (21%) including 1 primary and 2 metastatic tumors. ALK gene rearrangement was evident in 3 of 22 cases (14%), all of which were metastatic tumors. CONCLUSIONS: The results of the current study have demonstrated the feasibility of using cytological specimens for EGFR mutation, KRAS mutation, and ALK gene rearrangement analysis. Repeating molecular testing in metastatic/recurrent lung adenocarcinomas may uncover newly acquired molecular alterations. Cancer (Cancer Cytopathol) 2013; © 2013 American Cancer Society.
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[713]
TÍTULO / TITLE: - Risk of second cancer from scattered radiation of intensity-modulated radiotherapies with lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 4;8(1):47. doi: 10.1186/1748-717X-8-47.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-47
AUTORES / AUTHORS: - Kim DW; Chung WK; Shin D; Hong S; Park SH; Park SY; Chung K; Lim YK; Shin D; Lee SB; Lee HH; Yoon M
INSTITUCIÓN / INSTITUTION: - Department of Radiological Science, College of Health Science, Korea University, Jeongneung 3-dong, Seongbuk-gu, Seoul, Korea. radioyoon@gmail.com.
RESUMEN / SUMMARY: - PURPOSE: To compare the risk of secondary cancer from scattered and leakage doses following intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and tomotherapy (TOMO) in patients with lung cancer. METHODS: IMRT, VMAT and TOMO were planned for five lung cancer patients. Organ equivalent doses (OEDs) are estimated from the measured corresponding secondary doses during irradiation at various points 20 to 80 cm from the iso-center by using radio-photoluminescence glass dosimeter (RPLGD). RESULTS: The secondary dose per Gy from IMRT, VMAT and TOMO for lung cancer, measured 20 to 80 cm from the iso-center, are 0.02~2.03, 0.03~1.35 and 0.04~0.46 cGy, respectively. The mean values of relative OED of secondary dose of VMAT and TOMO, which is normalized by IMRT, ranged between 88.63% and 41.59% revealing 88.63% and 41.59% for thyroid, 82.33% and 41.85% for pancreas, 77.97% and 49.41% for bowel, 73.42% and 72.55% for rectum, 74.16% and 81.51% for prostate. The secondary dose and OED from TOMO became similar to those from IMRT and VMAT as the distance from the field edge increased. CONCLUSIONS: OED based estimation suggests that the secondary cancer risk from TOMO is less than or comparable to the risks from conventional IMRT and VMAT.
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[714]
TÍTULO / TITLE: - Evaluation of safety and efficacy of tivantinib in the treatment of inoperable or recurrent non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Manag Res. 2013;5:15-20. doi: 10.2147/CMAR.S29995. Epub 2013 Jan 17.
●● Enlace al texto completo (gratuito o de pago) 2147/CMAR.S29995
AUTORES / AUTHORS: - Broggini M; Garassino MC; Damia G
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy.
RESUMEN / SUMMARY: - Tivantinib is a selective, oral, non-ATP-competitive, small molecule inhibitor of the c-Met receptor, tyrosine kinase, which is implicated at different levels of tumor cell migration, invasion, proliferation, and metastasis. Tivantinib has shown antitumor activity in various human tumor cell lines and in xenograft models of human cancers, including non-small-cell lung cancer. Few therapeutic options are available at present for advanced non-small-cell lung cancer, so there is a pressing need for new therapeutic strategies to improve response and survival. Amplification of Met has been reported in more than 20% of lung tumors that have acquired resistance to epidermal growth factor receptor inhibitors, implying that treatment of these tumors with a c-Met inhibitor should overcome resistance. Tivantinib has shown interesting and promising results in advanced non-small-cell lung cancer and appears to be well tolerated, either alone or in combination with other drugs. An interesting additional feature is the ability of the drug to delay development of new metastasis, in agreement with the proposed role of Met in this particular setting.
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[715]
TÍTULO / TITLE: - Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Feb 28. doi: 10.1002/cncy.21269.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21269
AUTORES / AUTHORS: - Matsumoto S; Nabeshima K; Kamei T; Hiroshima K; Kawahara K; Hata S; Marukawa K; Matsuno Y; Taguchi K; Tsujimura T
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Fukuoka University Hospital and School of Medicine, Fukuoka, Japan.
RESUMEN / SUMMARY: - BACKGROUND: In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH). METHODS: For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion-positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics. RESULTS: Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cell-in-cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion-negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs. CONCLUSIONS: These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
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[716]
TÍTULO / TITLE: - Malignant pleural mesothelioma forming a huge mediastinal mass and causing atrial fibrillation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Indian J Pathol Microbiol. 2012 Oct;55(4):513-5. doi: 10.4103/0377-4929.107794.
●● Enlace al texto completo (gratuito o de pago) 4103/0377-4929.107794
AUTORES / AUTHORS: - Kuwabara H; Tsuji H; Inada Y; Shibayama Y
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Osaka Medical College, Osaka, Japan.
RESUMEN / SUMMARY: - A patient with malignant pleural mesothelioma was admitted with atrial fibrillation. Chest computed tomography showed a huge mediastinal tumor adjacent to the heart. Autopsy revealed a 12 x 9.5 -cm mediastinal mass involving the right lung, which distorted and stretched the myocardial sleeve surrounding the right inferior pulmonary vein. This case demonstrates that advanced malignant pleural mesothelioma can cause atrial fibrillation, possibly by stimulating myocardium around a pulmonary vein.
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[717]
TÍTULO / TITLE: - Bronchial carcinoid presenting as multiple lung abscesses.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Coll Physicians Surg Pak. 2013 Mar;23(3):229-30. doi: 03.2013/JCPSP.229230.
AUTORES / AUTHORS: - Waheed Z; Irfan M; Fatimi S; Shahid R
INSTITUCIÓN / INSTITUTION: - Department of Medicine, The Aga Khan University Hospital, Karachi.
RESUMEN / SUMMARY: - Bronchial carcinoid tumours is a rare group of pulmonary malignant neoplasm that is derived from neuroendocrine system. Bronchial carcinoid usually present with hilar masses, atelactasis, bronchiectasis, or post-obstructive pneumonia. This case describes a very unusual presentation of bronchial carcinoid tumour with multiple lung abscesses involving the whole lung. This report is of an adult lady who presented with multiple lung abscesses involving her whole of the right lung. She was found to have an endo-bronchial lesion in her right main bronchus which eventually turned out to be carcinoid tumour. She responded to resection and antibiotic therapy.
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[718]
TÍTULO / TITLE: - Th17/Treg imbalance in malignant pleural effusion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Huazhong Univ Sci Technolog Med Sci. 2013 Feb;33(1):27-32. doi: 10.1007/s11596-013-1066-2. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s11596-013-1066-2
AUTORES / AUTHORS: - Yang WB; Ye ZJ; Xiang F; Zhang JC; Zhou Q
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Diseases, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China, wbingyang@yahoo.cn.
RESUMEN / SUMMARY: - Both T helper IL-17-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in malignant pleural effusion (MPE). However, the possible imbalance between Th17 cells and Tregs, as well as the association of Th17/Treg and Th1/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as Th1/Th2 balance in MPE. The number of Th17, Tregs, Th1, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Th17, Tregs, Th1, and Th2 cells was explored. It was found that the number of Th17, Tregs, Th1, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Th17 cells was correlated negatively with Tregs in MPE, but not in blood. Th17 cells and Th17/Treg ratio were positively, and Tregs were negatively, correlated with Th1 cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Th17 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Th17/Treg imbalance exists in MPE.
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[719]
TÍTULO / TITLE: - Lack of any Association between Blood Groups and Lung Cancer, Independent of Histology.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):453-6.
AUTORES / AUTHORS: - Oguz A; Unal D; Tasdemir A; Karahan S; Aykas F; Mutlu H; Cihan YB; Kanbay M
INSTITUCIÓN / INSTITUTION: - Medical Oncology Clinic, Kayseri Education and Research Hospital, Turkey E-mail : oguzarzu@yahoo.com.
RESUMEN / SUMMARY: - Introduction: Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. Materials and Methods: The files of 307 pathologically confirmed lung cancer patients were were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. Results: There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. Conclusions: In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.
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[720]
TÍTULO / TITLE: - Gefitinib Monotherapy in Advanced non-small-cell Lung Cancer: A Retrospective Analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JNMA J Nepal Med Assoc. 2012 Apr-Jun;52(186):66-71.
AUTORES / AUTHORS: - Shrestha S; Joshi P
INSTITUCIÓN / INSTITUTION: - Om cancer Care Center, Om hospital and Research Center, Chabahil, Kathmandu, Nepal.
RESUMEN / SUMMARY: - Introduction: There is no published data in Nepal regarding the use of gefitinib in patients with non-small cell lung cancer (NSCLC). Therefore, a retrospective analysis was conducted to evaluate the response and toxicity profile of Gefitinib alone in patients with advanced NSCLC and unknown epidermal growth factor receptor (EGFR) status. Methods: A single institutional retrospective study was conducted for the period from January 2004 to December 2006 involving patients with locally advanced or metastatic NSCLC who received gefitinib as monotherapy Primary objective was to evaluate the objective tumor response rate. Results: A total of 36 patients with advanced NSCLC who received gefitinib 250 mg orally once daily as 1st, 2nd, 3rd, and 4th line treatment in 7, 14, 9, and 6 patients respectively were included in the analysis. Comparable number of patients pertaining to sex, smoking status, and tumor histology were included. The overall response rate at 3 months was 60% including 47% in males and 68% in females. After one month 38% and 6.6% patients with adenocarcinoma and squamous histology respectively responded to gefitinib therapy. The median progression-free survival was 5.7 months. Toxicities were generally mild with diarrhea, rash and pruritus being the most commonly observed side effects. Conclusion: In this single-center experience, gefitinib demonstrated clinically significant response in overall population and provided good palliation in pretreated patients. Keywords: Advanced stage NSCLCs, EGFR-TKIs, Gefitinib, monotherapy, Nepal.
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[721]
TÍTULO / TITLE: - The role of Human papilloma virus (HPV) genotyping in recurrent respiratory papillomatosis in Rasoul Akram Hospital.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med J Islam Repub Iran. 2012 May;26(2):90-3.
AUTORES / AUTHORS: - Izadi F; Hamkar R; Ghanbari H; Abdolmotallebi F; Jahandideh H
INSTITUCIÓN / INSTITUTION: - MD, Associated professor of Otolaryngolgy-Head and Neck Surgery, Department of Otolaryngology, ENT.HNS research center, Tehran University of Medical Sciences, Tehran, Iran. izadimd@yahoo.com.
RESUMEN / SUMMARY: - BACKGROUND: The most common laryngeal mass in children is recurrent respiratory papillomatosis (RRP). Studies have attempted to correlate viral typing and its aggressiveness. METHOD: 29 patients with histologically confirmed RRP enrolled in adjuvant therapies. Patients underwent several surgical interventions. RESULTS: HPV genotyping demonstrated 45% HPV-6 and 55% HPV-11. The mean age at the first surgical intervention was 52.39 months (SD=102.28) (range from 4 months to 426 months). The mean number of surgical intervention was 10.39 (SD=7.76) (range from 2 to 30). The mean time of surgical intervals was 4.63 months (SD=4.02) (range from 2 to 24 months). In fourteen patients (48%) tracheotomy was done. All patients who had tracheotomy received alpha-interferon. One of our cases was a male who had pulmonary extension with HPV-6. CONCLUSION: A review of patients with RRP was regarding to HPV genotyping and need for adjuvant therapy and tracheostomy. Mean number of surgical procedure was 10/40 and nearly fourteen patients (48%) need to tracheotomy. The clinical differences between HPV6 and HPV11 disease may not be accurately predictable. Patients with less age and with HPV-11 seemed to have more severe problems, but these differences were not statistically significant which needs much more investigations for reasonable starting point of evaluation for these differences.
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[722]
TÍTULO / TITLE: - Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57020. doi: 10.1371/journal.pone.0057020. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057020
AUTORES / AUTHORS: - Wang P; Gao Q; Suo Z; Munthe E; Solberg S; Ma L; Wang M; Westerdaal NA; Kvalheim G; Gaudernack G
INSTITUCIÓN / INSTITUTION: - Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway ; Department of Cellular Therapy, Oslo University Hospital, Radiumhospitalet, Oslo, Norway ; Cancer Stem Cell Innovation Centre, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway ; Department of Hematology, Henan Tumor Hospital, Zhengzhou, People’s Republic of China.
RESUMEN / SUMMARY: - Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44(high)) and a main population which was either weakly positive or negative for CD44 (CD44(low/-)). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(high)CD90(+) sub-population. Moreover, these CD44(high)CD90(+) cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(high)CD90(+) population a good candidate for the lung CSCs. Both CD44(high)CD90(+) and CD44(high)CD90(-) cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/-) cells were lacking this potential. These results indicate that CD44(high)CD90(+) sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high) sub-population.
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[723]
TÍTULO / TITLE: - Chemosensitizing activities of cyclotides from Clitoria ternatea in paclitaxel-resistant lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):641-644. Epub 2012 Nov 22.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1042
AUTORES / AUTHORS: - Sen Z; Zhan XK; Jing J; Yi Z; Wanqi Z
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050;
RESUMEN / SUMMARY: - Cyclotides comprise a family of circular mini-peptides that have been isolated from various plants and have a wide range of bioactivities. Previous studies have demonstrated that cyclotides have antitumor effects and cause cell death by membrane permeabilization. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of cyclotides from Clitoria ternatea in paclitaxel-resistant lung cancer cells. In this study, a total of seven cyclotides were selected for colorimetric cell viability assay (MTT assay) to evaluate their anticancer and chemosensitizing activities in the lung cancer cell line A549 and its sub-line A549/paclitaxel. Results suggested that certain cyclotides had significant anticancer and chemosensitizing abilities; such cyclotides were capable of causing multi-fold decreases in the half maximal inhibitory concentration (IC(50)) value of cliotides in the presence of paclitaxel. More importantly, their bioactivities were found to be correlated with their net charge status. In conclusion, cyclotides from C. ternatea have potential in chemosensitization application.
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[724]
TÍTULO / TITLE: - Synergistic effect of afatinib with su11274 in non-small cell lung cancer cells resistant to gefitinib or erlotinib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59708. doi: 10.1371/journal.pone.0059708. Epub 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059708
AUTORES / AUTHORS: - Chen G; Noor A; Kronenberger P; Teugels E; Umelo IA; De Greve J
INSTITUCIÓN / INSTITUTION: - Department of Pathology, First Affiliated Hospital, Guangxi Medical University, Nanning Guangxi, People’s Republic of China ; Laboratory of Medical and Molecular Oncology, Department of Medical Oncology, Oncology Center, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
RESUMEN / SUMMARY: - Epidermal growth factor receptor (EGFR) and c-MET receptors are expressed on many non-small cell lung cancer (NSCLC) cells. Current single agent therapeutic targeting of a mutant EGFR has a high efficacy in the clinic, but is not curative. Here, we investigated the combination of targeting EGFR and c-MET pathways in NSCLC cells resistant to receptor tyrosine kinase inhibitors (TKIs), using RNA interference and inhibition by TKIs. Different NSCLC cell lines with various genomic characteristics (H358, H1650 and H1975) were transfected with EGFR-specific-siRNA, T790M-specific-siRNA, c-MET siRNA or the combination. Subsequently EGFR TKIs (gefitinib, erlotinib or afatinib) or monoclonal antibody cetuximab were combined respectively with the c-MET-specific TKI su11274 in NSCLC cell lines. The cell proliferation, viability, caspase-3/7 activity and apoptotic morphology were monitored by spectrophotometry, fluorimetry and fluorescence microscopy. The combined effect of EGFR TKIs, or cetuximab and su11274, was evaluated using a combination index. The results showed that the cell lines that were relatively resistant to EGFR TKIs, especially the H1975 cell line containing the resistance T790M mutation, were found to be more sensitive to EGFR-specific-siRNA. The combination of EGFR siRNA plus c-MET siRNA enhanced cell growth inhibition, apoptosis induction and inhibition of downstream signaling in EGFR TKI resistant H358, H1650 and H1975 cells, despite the absence of activity of the c-MET siRNA alone. EGFR TKIs or cetuximab plus su11274 were also consistently superior to either agent alone. The strongest biological effect was observed when afatinib, an irreversible pan-HER blocker was combined with su11274, which achieved a synergistic effect in the T790M mutant H1975 cells. In a conclusion, our findings offer preclinical proof of principle for combined inhibition as a promising treatment strategy for NSCLC, especially for patients in whom current EGFR-targeted treatments fail due to the presence of the T790M-EGFR-mutation or high c-MET expression.
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[725]
TÍTULO / TITLE: - Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 14;13(1):16.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-16
AUTORES / AUTHORS: - Nguyen HT; Zhuang Y; Sun L; Kantrow SP; Kolls JK; You Z; Zhuo Y; Shan B
RESUMEN / SUMMARY: - ABSTRACT: A fribotic tumor microenvironment promotes progression of cancer. In this study, we utilize a reconstituted basement membrane mimics Matrigel based three-dimensional organotypic culture (rBM 3-D) to investigate the mechanisms that mediate the tumor promoting effects of the fibrogenic mediators TGF-beta1 and type I collagen (Col-1) on lung adenocarcinoma cells. Similar to normal alveolar epithelial cells, the well-differentiated lung adenocarcinoma cells in rBM 3-D culture undergo acinar morphogeneis that features polarized epithelial cell spheres with a single central lumen. Either TGF-beta1 or Col-1 modestly distorts acinar morphogenesis. On the other hand, TGF-beta1 and Col-1 synergistically induce a transition from acinar morphology into stellate morphology that is characteristic of invasive and metastatic cancer cells. Inhibition of the Src kinase activity abrogates induction of stellate morphology, activation of Akt and mTOR, and the expression of tumor promoting genes by TGF-beta1 and Col-1. To a similar extent, pharmacological inhibition of mTOR abrogates the cellular responses to TGF-beta1 and Col-1. In summary, we demonstrate that TGF-beta1 and Col-1 promote stellate morphogenesis of lung cancer cells. Our findings further suggest that the Src-Akt-mTOR axis mediates stellate morphogenesis. These findings also indicate that rBM 3-D culture can serve as an ideal platform for swift and cost-effective screening of therapeutic candidates at the interface of the tumor and its microenvironment.
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[726]
TÍTULO / TITLE: - Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):1043-1047. Epub 2013 Jan 7.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1108
AUTORES / AUTHORS: - Chunhacha P; Sriuranpong V; Chanvorachote P
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences; Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand ; Cell-based Drug and Health Products Development Research Unit; Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand.
RESUMEN / SUMMARY: - Epithelial-mesenchymal transition (EMT) is implicated in cancer pathological processes, particularly cancer invasion and metastasis. The present study demonstrated that EMT was critical for the metastasic potential of lung cancer cells isolated from a patient. P1 primary lung cancer cells were found to exhibit increased anoikis resistance compared with established A549, H23 and H460 lung cancer cells. Results of migration and invasion assays revealed that the invasion capability of P1 and A549 cells was higher than that of H23 and H460 cells. However, the migration of P1 cells was similar to that of H23 and H460 cells while A549 demonstrated a superior migrating ability. Western blot analysis indicated that while E-cadherin levels in all lung cancer cells were identified as comparable, P1 cells expressed the highest levels of N-cadherin. In the present study, detachment of cells was demonstrated for the first time to stimulate further transition of E-cadherin to N-cadherin. In addition, this obervation was more pronounced in P1 cells. These observations highlight the importance of EMT in cancer metastasis. In order to study the effect of ethnicity on cancer cell behavior, in the future a large number of Thai patient-derived cell lines must be analyzed.
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[727]
TÍTULO / TITLE: - Low-dose etoposide-treatment induces endoreplication and cell death accompanied by cytoskeletal alterations in A549 cells: Does the response involve senescence? The possible role of vimentin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 5;13(1):9. doi: 10.1186/1475-2867-13-9.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-9
AUTORES / AUTHORS: - Litwiniec A; Gackowska L; Helmin-Basa A; Zuryn A; Grzanka A
INSTITUCIÓN / INSTITUTION: - Laboratory of Biotechnology, Department of Genetics and Breeding of Root Crops, Plant Breeding and Acclimatization Institute - National Research Institute Radzikow, 05-870 Blonie, Research Division in Bydgoszcz, Powstancow Wielkopolskich 10, 85-090, Bydgoszcz, Poland. annalitwiniec@wp.pl.
RESUMEN / SUMMARY: - BACKGROUND: Senescence in the population of cells is often described as a program of restricted proliferative capacity, which is manifested by broad morphological and biochemical changes including a metabolic shift towards an autophagic-like response and a genotoxic-stress related induction of polyploidy. Concomitantly, the cell cycle progression of a senescent cell is believed to be irreversibly arrested. Recent reports suggest that this phenomenon may have an influence on the therapeutic outcome of anticancer treatment. The aim of this study was to verify the possible involvement of this program in the response to the treatment of the A549 cell population with low doses of etoposide, as well as to describe accompanying cytoskeletal alterations. METHODS: After treatment with etoposide, selected biochemical and morphological parameters were examined, including: the activity of senescence-associated ss-galactosidase, SAHF formation, cell cycle progression, the induction of p21Cip1/Waf1/Sdi1 and cyclin D1, DNA strand breaks, the disruption of cell membrane asymmetry/integrity and ultrastructural alterations. Vimentin and G-actin cytoskeleton was evaluated both cytometrically and microscopically. RESULTS AND CONCLUSIONS: Etoposide induced a senescence-like phenotype in the population of A549 cells. Morphological alterations were nevertheless not directly coupled with other senescence markers including a stable cell cycle arrest, SAHF formation or p21Cip1/Waf1/Sdi1 induction. Instead, a polyploid, TUNEL-positive fraction of cells visibly grew in number. Also upregulation of cyclin D1 was observed. Here we present preliminary evidence, based on microscopic analyses, that suggest a possible role of vimentin in nuclear alterations accompanying polyploidization-depolyploidization events following genotoxic insults.
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[728]
TÍTULO / TITLE: - Comparative analysis of the transduction efficiency of five adeno associated virus serotypes and VSV-G pseudotype lentiviral vector in lung cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Virol J. 2013 Mar 14;10:86. doi: 10.1186/1743-422X-10-86.
●● Enlace al texto completo (gratuito o de pago) 1186/1743-422X-10-86
AUTORES / AUTHORS: - Chen C; Akerstrom V; Baus J; Lan MS; Breslin MB
INSTITUCIÓN / INSTITUTION: - Research Institute For Children, Children’s Hospital New Orleans, New Orleans, LA, 70118, USA. mbreslin@chnola-research.org.
RESUMEN / SUMMARY: - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the US. Recombinant vectors based on adeno-associated virus (AAV) and lentivirus are promising delivery tools for gene therapy due to low toxicity and long term expression. The efficiency of the gene delivery system is one of the most important factors directly related to the success of gene therapy. METHODS: We infected SCLC cell lines, SHP-77, DMS 53, NCI-H82, NCI-H69, NCI-H727, NCI-H1155, and NSCLC cell lines, NCI-H23, NCI-H661, and NCI-H460 with VSV-G pseudo-typed lentivirus or 5 AAV serotypes, AAV2/1, AAV2/2, AAV2/4, AAV2/5, and AAV2/8 expressing the CMV promoter mCherry or green fluorescent protein transgene (EGFP). The transduction efficiency was analyzed by fluorescent microscopy and flow cytometry. RESULTS: Of all the serotypes of AAV examined, AAV2/1 was the optimal serotype in most of the lung cancer cell lines except for NCI-H69 and NCI-H82. The highest transduction rate achieved with AAV2/1 was between 30-50% at MOI 100. Compared to all AAV serotypes, lentivirus had the highest transduction efficiency of over 50% at MOI 1. Even in NCI-H69 cells resistant to all AAV serotypes, lentivirus had a 10-40% transduction rate. To date, AAV2 is the most widely-used serotype to deliver a transgene. Our results showed the transduction efficiency of AAVs tested was AAV2/1 > AA2/5 = AAV2/2> > AAV2/4 and AAV2/8. CONCLUSIONS: This study demonstrated that VSV-G pseudotyped lentivirus and AAV2/1 can mediate expression of a transgene for lung cancer gene therapy. Overall, our results showed that lentivirus is the best candidate to deliver a transgene into lung cancer cells for treatment.
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[729]
TÍTULO / TITLE: - betaArrestin-1 and Mcl-1 modulate self-renewal growth of cancer stem-like side-population cells in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55982. doi: 10.1371/journal.pone.0055982. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055982
AUTORES / AUTHORS: - Singh S; Bora-Singhal N; Kroeger J; Laklai H; Chellappan SP
INSTITUCIÓN / INSTITUTION: - Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
RESUMEN / SUMMARY: - Side population (SP) cells have been reported to have properties of cancer stem-like cells (CSCs) in non-small cell lung carcinoma (NSCLC), yet their molecular features have not been fully elucidated. Here we show that, NSCLC-SP cells were enriched in G(0)/G-(1) phase of cell cycle, had higher aldehyde dehydrogenase activity as well as higher clonogenic and self-renewing ability compared to main population (MP) cells. Interestingly, SP cells were also able to trans-differentiate into angiogenic tubules in vitro and were highly tumorigenic as compared to MP cells. SP-derived tumors demonstrated the intratumoral heterogeneity comprising of both SP and MP cells, suggesting the self-renewal and differentiation ability of SP cells are manifested in vivo as well. betaArrestin-1 (betaArr1) is involved in the progression of various cancers including NSCLCs and we find that depletion of betaArr1 significantly blocked the SP phenotype; whereas depletion of betaArr2 had relatively minor effects. Ectopic expression of betaArr1 resulted in increased SP frequency and ABCG2 expression while abrogation of betaArr1 expression suppressed the self-renewal growth and expansion of A549 cells. Anti-apoptotic protein Mcl-1 is known to be one of the key regulators of self-renewal of tissue stem cells and is thought to contribute to survival of NSCLC cells. Our experiments show that higher levels of Mcl-1 were expressed in SP cells compared to MP cells at both transcriptional and translational levels. In addition, Obatoclax, a pharmacological inhibitor of Mcl-1, could effectively prevent the self-renewal of both EGFR-inhibitor sensitive and resistant NSCLC cells. In conclusion, our findings suggest that betaArr1 and Mcl-1 are involved in the self-renewal and expansion of NSCLC-CSCs and are potential targets for anti-cancer therapy.
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[730]
TÍTULO / TITLE: - Phosphotyrosine Profiling of NSCLC Cells in Response to EGF and HGF Reveals Network Specific Mediators of Invasion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Proteome Res. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1021/pr301192t
AUTORES / AUTHORS: - Johnson H; Lescarbeau RS; Gutierrez JA; White FM
INSTITUCIÓN / INSTITUTION: - Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts, United States.
RESUMEN / SUMMARY: - Growth factor signaling is deregulated in cancer and often leads to invasion, yet receptor tyrosine kinase signaling pathways driving invasion under different growth factor conditions are not well understood. To identify specific signaling molecules regulating invasion of A549 non-small cell lung carcinoma (NSCLC) cells downstream of the epidermal growth factor receptor (EGFR) and Met, quantitative site-specific mass spectrometric analysis of tyrosine phosphorylation was performed following epidermal growth factor (EGF) or hepatocyte growth factor (HGF) stimulation, at three different growth factor concentrations and at two time points. Through this analysis, the temporal and concentration dependent phosphorylation profiles were obtained for 131 and 139 sites downstream of EGF and HGF stimulation, respectively. To characterize the effect of these signaling network alterations, we quantified 3D cell migration/invasion through Matrigel. Partial least-squares regression (PLSR) analysis was performed to identify the tyrosine phosphorylation sites most strongly correlated with EGF and/or HGF mediated invasion. Potential common and specific signaling events required for driving invasion downstream of EGFR and Met were identified using either a combined or two independent PLSR models, based on the quantitative EGF or HGF data. Our data highlight the integration and compartmentalization of signaling required for invasion in cancer.
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[731]
TÍTULO / TITLE: - A gene expression profile test to resolve head & neck squamous versus lung squamous cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Mar 11;8:44. doi: 10.1186/1746-1596-8-44.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-44
AUTORES / AUTHORS: - Lal A; Panos R; Marjanovic M; Walker M; Fuentes E; Kubicek GJ; Henner WD; Buturovic LJ; Halks-Miller M
INSTITUCIÓN / INSTITUTION: - Pathwork Diagnostics, 595 Penobscot Dr, Redwood City, CA 94063, USA. anita.lal08@gmail.com.
RESUMEN / SUMMARY: - BACKGROUND: The differential diagnosis between metastatic head & neck squamous cell carcinomas (HNSCC) and lung squamous cell carcinomas (lung SCC) is often unresolved because the histologic appearance of these two tumor types is similar. We have developed and validated a gene expression profile test (GEP-HN-LS) that distinguishes HNSCC and lung SCC in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2160-gene classification model. METHODS: The test was validated in a blinded study using a pre-specified algorithm and microarray data files for 76 metastatic or poorly-differentiated primary tumors with a known HNSCC or lung SCC diagnosis. RESULTS: The study met the primary Bayesian statistical endpoint for acceptance. Measures of test performance include overall agreement with the known diagnosis of 82.9% (95% CI, 72.5% to 90.6%), an area under the ROC curve (AUC) of 0.91 and a diagnostics odds ratio (DOR) of 23.6. HNSCC (N = 38) gave an agreement with the known diagnosis of 81.6% and lung SCC (N = 38) gave an agreement of 84.2%. Reproducibility in test results between three laboratories had a concordance of 91.7%. CONCLUSION: GEP-HN-LS can aid in resolving the important differential diagnosis between HNSCC and lung SCC tumors. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/1753227817890930.
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[732]
TÍTULO / TITLE: - Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55752. doi: 10.1371/journal.pone.0055752. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055752
AUTORES / AUTHORS: - Demidyuk IV; Shubin AV; Gasanov EV; Kurinov AM; Demkin VV; Vinogradova TV; Zinovyeva MV; Sass AV; Zborovskaya IB; Kostrov SV
INSTITUCIÓN / INSTITUTION: - Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia. duk@img.ras.ru
RESUMEN / SUMMARY: - Proprotein convertases (PCs) is a protein family which includes nine highly specific subtilisin-like serine endopeptidases in mammals. The system of PCs is involved in carcinogenesis and levels of PC mRNAs alter in cancer, which suggests expression status of PCs as a possible marker for cancer typing and prognosis. The goal of this work was to assess the information value of expression profiling of PC genes. Quantitative polymerase chain reaction was used for the first time to analyze mRNA levels of all PC genes as well as matrix metalloproteinase genes MMP2 and MMP14, which are substrates of PCs, in 30 matched pairs of samples of human lung cancer tumor and adjacent tissues without pathology. Significant changes in the expression of PCs have been revealed in tumor tissues: increased FURIN mRNA level (p<0.00005) and decreased mRNA levels of PCSK2 (p<0.007), PCSK5 (p<0.0002), PCSK7 (p<0.002), PCSK9 (p<0.00008), and MBTPS1 (p<0.00004) as well as a tendency to increase in the level of PCSK1 mRNA. Four distinct groups of samples have been identified by cluster analysis of the expression patterns of PC genes in tumor vs. normal tissue. Three of these groups covering 80% of samples feature a strong elevation in the expression of a single gene in cancer: FURIN, PCSK1, or PCSK6. Thus, the changes in the expression of PC genes have a limited number of scenarios, which may reflect different pathways of tumor development and cryptic features of tumors. This finding allows to consider the mRNAs of PC genes as potentially important tumor markers.
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[733]
TÍTULO / TITLE: - Surgical treatment of non-small-cell lung cancer in octogenarians.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Interact Cardiovasc Thorac Surg. 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1093/icvts/ivt020
AUTORES / AUTHORS: - Guerra M; Neves P; Miranda J
INSTITUCIÓN / INSTITUTION: - Department of Cardiothoracic Surgery, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nove de Gaia, Portugal.
RESUMEN / SUMMARY: - Reluctance to recommend lung cancer surgery for octogenarians is partly based on the expectation that the rate of complications and mortality is higher in this group of patients, and on the impression that the life expectancy of an octogenarian with lung cancer is limited by death from natural causes. Moreover, the belief that radiation therapy and observation yield similar results to surgery in early-stage disease have influenced low resection rates in this population. Nevertheless, advances in surgical techniques, anaesthesia and postoperative care have made surgical lung resection a safer procedure than it was in the past. Judging from the more recent findings, surgery should not be withheld because of postoperative mortality, but suboptimal or palliative treatment may be necessary in patients with poor physical or mental function. To enable informed decision-making, both patients and clinicians need information on the risks of surgical treatment. In this review, available information from the literature was collected in an effort to understand the real benefit of surgical treatment in octogenarians with non-small-cell lung cancer, and to determine what should be done or avoided during the selection course.
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[734]
TÍTULO / TITLE: - Recurrent spontaneous pneumothorax in a 42 years old woman with pulmonary lymphangioleiomyomatosis: insights and pitfalls of the surgical treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Med Res. 2013 Feb;5(1):70-4. doi: 10.4021/jocmr1170w. Epub 2013 Jan 11.
●● Enlace al texto completo (gratuito o de pago) 4021/jocmr1170w
AUTORES / AUTHORS: - Spiliopoulos K; Tsantsaridou A; Papamichali R; Kimpouri K; Salemis NS; Koukoulis GK; Tsilimingas NB
INSTITUCIÓN / INSTITUTION: - Department of Thoracic and Cardiovascular Surgery, University of Thessaly, Larissa, Greece.
RESUMEN / SUMMARY: - Lymphangioleiomyomatosis (LAM) is a rare disease that occurs predominantly in females between the ages of 30 and 50 years and is clinically characterized by progressive dyspnoea on exertion, recurrent pneumothoraces, abdominal and thoracic lymphadenopathy, as well tumors-like angiomyolipomas and lymphangiomyomas. We present the case of a 42-year-old woman, who developed recurrent pneumothoraces and was subsequently diagnosed with LAM. Although pneumothorax is a common complication of the disease, its optimal approach to treatment and prevention remains unclear. Chemical or surgical pleurodesis are often performed in order to prevent recurrence, but may predispose to perioperative complications in the event of future lung transplantation.
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[735]
TÍTULO / TITLE: - CXCR4/CXCL12 axis in non small cell lung cancer (NSCLC) pathologic roles and therapeutic potential.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Theranostics. 2013;3(1):26-33. doi: 10.7150/thno.4922. Epub 2013 Jan 13.
●● Enlace al texto completo (gratuito o de pago) 7150/thno.4922
AUTORES / AUTHORS: - Wald O; Shapira OM; Izhar U
INSTITUCIÓN / INSTITUTION: - Department of Cardiothoracic Surgery, Hadassah University Hospital, Jerusalem, Israel. ori.wald@mail.huji.ac.il
RESUMEN / SUMMARY: - Lung cancer is the second most common malignancy and the leading cause of cancer-related death in the western world. Moreover, despite advances in surgery, chemotherapy and radiotherapy, the death rate from lung cancer remains high and the reported overall five-year survival rate is only 15%. Thus, novel treatments for this devastating disease are urgently needed. Chemokines, a family of 48 chemotactic cytokines interacts with their 7 transmembrane G-protein-coupled receptors, to guide immune cell trafficking in the body under both physiologic and pathologic conditions. Tumor cells, which express a relatively restricted repertoire of chemokine and chemokine receptors, utilize and manipulate the chemokine system in a manner that benefits both local tumor growth and distant dissemination. Among the 19 chemokine receptors, CXCR4 is the receptor most widely expressed by malignant tumors and whose role in tumor biology is most thoroughly studied. The chemokine CXCL12, which is the sole ligand of CXCR4, is highly expressed in primary lung cancer as well as in the bone marrow, liver, adrenal glands and brain, which are all sites for lung cancer metastasis. This review focuses on the pathologic role of the CXCR4/CXCL12 axis in NSCLC and on the potential therapeutic implication of targeting this axis for the treatment of NSCLC.
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[736]
TÍTULO / TITLE: - Focus on the potential role of ficlatuzumab in the treatment of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biologics. 2013;7:61-8. doi: 10.2147/BTT.S28908. Epub 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 2147/BTT.S28908
AUTORES / AUTHORS: - D’Arcangelo M; Cappuzzo F
INSTITUCIÓN / INSTITUTION: - Cancer Center, University of Colorado, Aurora (CO), USA ; Department of Oncology, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
RESUMEN / SUMMARY: - Lung cancer treatment has rapidly changed in the last few years thanks to novel insights into cancer biology. Several biomarkers and signaling pathways have been recognized as conceivable targets for treatment, and among them is the mesenchymal-epithelial transition/hepatocyte growth factor (c-MET/HGF) axis. Alterations in the c-MET gene and aberrations of MET and HGF expression impact on lung cancer prognosis and are involved in resistance to epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations. Several anti-MET and anti-HGF strategies are currently under investigation, including monoclonal antibodies. Ficlatuzumab is a monoclonal antibody directed against HGF that is currently under investigation in NSCLC. The aim of the present review is to critically review available data on HGF and ficlatuzumab in NSCLC.
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[737]
TÍTULO / TITLE: - Evaluation and comparison of New 4DCT based strategies for proton treatment planning for lung tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 25;8(1):73.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-73
AUTORES / AUTHORS: - Wang N; Patyal B; Ghebremedhin A; Bush D
RESUMEN / SUMMARY: - Purpose: To evaluate different strategies for proton lung treatment planning based on four-dimensional CT (4DCT) scans.Methods and Materials: Twelve cases, involving only gross tumor volumes (GTV), were evaluated. Single image sets of (1) maximum intensity projection (MIP3) of end inhale (EI), middle exhale (ME) and end exhale (EE) images; (2) average intensity projection (AVG) of all phase images; and (3) EE images from 4DCT scans were selected as primary images for proton treatment planning. Internal target volumes (ITVs) outlined by a clinician were imported into MIP3, AVG, and EE images as planning targets. Initially, treatment uncertainties were not included in planning. Each plan was imported into phase images of 4DCT scans. Relative volumes of GTVs covered by 95% of prescribed dose and mean ipsilateral lung dose of a phase image obtained by averaging the dose in inspiration and expiration phases were used to evaluate the quality of a plan for a particular case. For comparing different planning strategies, the mean of the averaged relative volumes of GTVs covered by 95% of prescribed dose and its standard deviation for each planning strategy for all cases were used. Then, treatment uncertainties were included in planning. Each plan was recalculated in phase images of 4DCT scans. Same strategies were used for plan evaluation except dose-volume histograms of the planning target volumes (PTVs) instead of GTVs were used and the mean and standard deviation of the relative volumes of PTVs covered by 95% of prescribed dose and the ipsilateral lung dose were used to compare different planning strategies. RESULTS: MIP3 plans without treatment uncertainties yielded 96.7% of the mean relative GTV covered by 95% of prescribed dose (standard deviations of 5.7% for all cases). With treatment uncertainties, MIP3 plans yielded 99.5% of mean relative PTV covered by 95% of prescribed dose (standard deviations of 0.7%). Inclusion of treatment uncertainties improved PTV dose coverage but also increased the ipsilateral mean lung dose in general, and reduced the variations of the PTV dose coverage among different cases. Plans based on conventional axial CT scan (CVCT) gave the poorest PTV dose coverage (about 96% of mean relative PTV covered by 95% isodose) compared to MIP3 and EE plans, which resulted in 100% of PTV covered by 95% isodose for tumors with relatively large motion. AVG plans demonstrated PTV dose coverage of 89.8% and 94.4% for cases with small tumors. MIP3 plans demonstrated superior tumor coverage and were least sensitive to tumor size and tumor location. CONCLUSION: MIP3 plans based on 4DCT scans were the best planning strategy for proton lung treatment planning.
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[738]
TÍTULO / TITLE: - Preclinical Demonstration of Synergistic Active Nutrients/Drug (AND) Combination as a Potential Treatment for Malignant Pleural Mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58051. doi: 10.1371/journal.pone.0058051. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058051
AUTORES / AUTHORS: - Volta V; Ranzato E; Martinotti S; Gallo S; Russo MV; Mutti L; Biffo S; Burlando B
INSTITUCIÓN / INSTITUTION: - Molecular Histology and Cell Growth Laboratory, San Raffaele Science Institute, Milano, Italy.
RESUMEN / SUMMARY: - Malignant pleural mesothelioma (MPM) is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug). In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.
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[739]
TÍTULO / TITLE: - Combination of single walled carbon nanotubes/graphene oxide with paclitaxel: a reactive oxygen species mediated synergism for treatment of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nanoscale. 2013 Mar 14;5(7):2818-29. doi: 10.1039/c3nr33190c.
●● Enlace al texto completo (gratuito o de pago) 1039/c3nr33190c
AUTORES / AUTHORS: - Arya N; Arora A; Vasu KS; Sood AK; Katti DS
INSTITUCIÓN / INSTITUTION: - Department of Biological Sciences and Bioengineering, Indian Institute of Technology - Kanpur, Kanpur-208016, Uttar Pradesh, India. dsk@iitk.ac.in.
RESUMEN / SUMMARY: - Heterogeneity in tumors has led to the development of combination therapies that enable enhanced cell death. Previously explored combination therapies mostly involved the use of bioactive molecules. In this work, we explored a non-conventional strategy of using carbon nanostructures (CNs) [single walled carbon nanotube (SWNT) and graphene oxide (GO)] for potentiating the efficacy of a bioactive molecule [paclitaxel (Tx)] for the treatment of lung cancer. The results demonstrated enhanced cell death following combination treatment of SWNT/GO and Tx indicating a synergistic effect. In addition, synergism was abrogated in the presence of an anti-oxidant, N-acetyl cysteine (NAC), and was therefore shown to be reactive oxygen species (ROS) dependent. It was further demonstrated using bromodeoxyuridine (BrdU) incorporation assay that treatment with CNs was associated with enhanced mitogen associated protein kinase (MAPK) activation that was ROS mediated. Hence, these results for the first time demonstrated the potential of SWNT/GO as co-therapeutic agents with Tx for the treatment of lung cancer.
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[740]
TÍTULO / TITLE: - Update on antiangiogenic treatment of advanced non-small cell lung cancer (NSCLC).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Mar;8(1):15-26. doi: 10.1007/s11523-013-0261-1. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0261-1
AUTORES / AUTHORS: - Schmid-Bindert G
INSTITUCIÓN / INSTITUTION: - Interdisciplinary Thoracic Oncology, Department of Surgery, University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany, gerald.schmid-bindert@medma.uni-heidelberg.de.
RESUMEN / SUMMARY: - Bevacizumab is a monoclonal antibody that specifically inhibits vascular endothelial growth factor, and is the first antiangiogenic agent to be approved for first-line treatment of advanced non-small cell lung cancer (NSCLC). Evidence from two large phase III trials demonstrates that bevacizumab combined with chemotherapy improves outcomes for patients with non-squamous NSCLC. In patients with adenocarcinoma without epidermal growth factor receptor (EGFR) mutation, a median overall survival of 18.0 months is achieved. Several post-registration phase IV studies have confirmed bevacizumab’s efficacy and tolerability profile and have clarified the eligibility criteria. Clinical research is still ongoing to define the role of bevacizumab in different settings, such as single-agent bevacizumab for continuation maintenance therapy in advanced disease, treatment beyond disease progression, adjuvant therapy in early-stage NSCLC, or bevacizumab in combination with other targeted agents. A number of antiangiogenic tyrosine kinase inhibitors (TKI) have also been investigated in phase II and III trials. None of these drugs has proven significant clinical benefit in unselected patient populations. This article reviews the extensive information from randomized trials and large observational studies for bevacizumab in advanced NSCLC, and shortly describes the current clinical development of antiangiogenic monoclonal antibodies, TKIs and related compounds.
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[741]
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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[742]
TÍTULO / TITLE: - Gli as a novel therapeutic target in malignant pleural mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57346. doi: 10.1371/journal.pone.0057346. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057346
AUTORES / AUTHORS: - Li H; Lui N; Cheng T; Tseng HH; Yue D; Giroux-Leprieur E; Do HT; Sheng Q; Jin JQ; Luh TW; Jablons DM; He B
INSTITUCIÓN / INSTITUTION: - Thoracic Oncology Program, Department of Surgery, University of California San Francisco, San Francisco, California, United States of America.
RESUMEN / SUMMARY: - Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh) signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I). A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo) inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.
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[743]
TÍTULO / TITLE: - Killing Effect of Ad5/F35-APE1 siRNA Recombinant Adenovirus in Combination with Hematoporphrphyrin Derivative-Mediated Photodynamic Therapy on Human Nonsmall Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:957913. doi: 10.1155/2013/957913. Epub 2012 Dec 27.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/957913
AUTORES / AUTHORS: - Xia L; Guan W; Wang D; Zhang YS; Zeng LL; Li ZP; Wang G; Yang ZZ
INSTITUCIÓN / INSTITUTION: - Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
RESUMEN / SUMMARY: - The main goal of this work is to investigate the killing effects and molecular mechanism of photodynamic therapy (PDT) mediated by the Ad5/F35-APE1 siRNA recombinant adenovirus in combination with a hematoporphrphyrin derivative (HpD) in the A549 human lung adenocarcinoma cell line in vitro to provide a theoretical reference for treating lung cancer by HpD-PDT. By using the technologies of MTT, flow cytometry, ELISA, and western blot, we observed that the proliferation inhibition and apoptosis of the A549 cells were significantly higher than the control group (P < 0.05) after HpD-PDT was performed. The inhibitory efficiency is dependent on the HpD concentration and laser intensity dose. The inhibitory effect on the proliferation of A549 cells of Ad5/F35-APE1 siRNA is more significant after combining with PDT, as indicated by a significant elevation of the intracellular ROS level and the expression of inflammatory factors (P < 0.05). The HpD-PDT-induced expression of the APE1 protein reached the peak after 24 h in A549 cells. The inhibition of APE1 expression in A549 cells was most significant after 48 hours of infection by Ad5/F35-APE1 siRNA recombinant adenovirus (10 MOI). In conclusion, the Ad5/F35-APE1 siRNA recombinant adenovirus could efficiently inhibit the HpD-PDT-induced APE1 expression hence could significantly enhance the killing effect of HpD-PDT in lung cancer cells.
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[744]
TÍTULO / TITLE: - Comparative study of epidermal growth factor receptor mutation analysis on cytology smears and surgical pathology specimens from primary and metastatic lung carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Jan 30. doi: 10.1002/cncy.21273.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21273
AUTORES / AUTHORS: - Khode R; Larsen DA; Culbreath BC; Parrish S; Walker KL; Sayage-Rabie L; Beissner RS; Rao A
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Scott & White Memorial Hospital and Texas A&M University Health Science Center, Temple, Texas.
RESUMEN / SUMMARY: - BACKGROUND: The detection of epidermal growth factor receptor (EGFR) mutations on small biopsy or fine-needle aspiration samples is required to guide therapy in nonsmall cell lung cancer (NSCLC). In this study, the authors compared results from EGFR mutation testing on both cytologic smears and surgical specimens and also compared the performance of platforms using 2 different technologies (pyrosequencing and real-time polymerase chain reaction) for both specimen types. METHODS: Specimens from 114 patients were divided into 2 subsets. The first subset had 60 paired cytology smears and surgical specimens, including 37 paired specimens from the same site and 23 paired specimens from different sites. The second subset consisted of nonpaired cytology smears and formalin-fixed, paraffin-embedded (FFPE) tissues (including 8 cell blocks), which were compared on the pyrosequencing and real-time polymerase chain reaction platforms. Laser-capture microscopy was used to enrich tumor in the FFPE specimens before DNA extraction. RESULTS: All cytology smears that were used in the study were adequate for analysis on both platforms. Comparison between smears and concurrent FFPE tissues from the same anatomic site had a concordance rate of 97%. The concordance rate between the pyrosequencing platform and the real-time polymerase chain reaction platform was 84% and 85% for FFPE tissues and cytology smears, respectively. CONCLUSIONS: The current results indicated that direct extraction and analysis of EGFR mutations from cytology smears can be performed successfully on both a pyrosequencing platform and a real-time polymerase chain reaction platform with results comparable to those achieved in matched surgical specimens. In fine-needle aspiration/endobronchial ultrasound samples with limited tissue, cytology smears can be important for molecular analysis. Cancer (Cancer Cytopathol) 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. © 2012 American Cancer Society.
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[745]
TÍTULO / TITLE: - Associations between dietary intake of choline and betaine and lung cancer risk.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e54561. doi: 10.1371/journal.pone.0054561. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054561
AUTORES / AUTHORS: - Ying J; Rahbar MH; Hallman DM; Hernandez LM; Spitz MR; Forman MR; Gorlova OY
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. jying@mdanderson.org
RESUMEN / SUMMARY: - Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55-0.88) and 0.51(0.39-0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former (p(trend) = 0.002) and current (p(trend)<0.0001) smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking.
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[746]
TÍTULO / TITLE: - Primary lung cancer complicated by malignant lymphoma in two cases of epstein-barr virus infection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Oncol. 2012 May;5(2):367-72. doi: 10.1159/000341158. Epub 2012 Jul 10.
●● Enlace al texto completo (gratuito o de pago) 1159/000341158
AUTORES / AUTHORS: - Ohno Z; Tamaki H; Ohsuga T; Iwata H; Yasuda N; Mori Y
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine and, Chuno Kosei Hospital, Seki, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Double cancer is defined as the co-existence of two pathologically distinct cancers. Double cancer consisting of a lung adenocarcinoma and a malignant lymphoma has seldom been reported in time synchronous cases or prior to cases of primary lung cancer, except in those after treatment for malignant lymphoma. CASE PRESENTATION: Case 1 was a 71-year-old woman who was treated at our hospital for chronic hepatitis C, nontuberculous mycobacteria infection, and bronchiectasis. She was diagnosed with a stage IV lung adenocarcinoma (cT1bN2M1b) with a synchronous complicating diffuse large B-cell-type lymphoma. Case 2 was a 62-year-old man who had undergone resection of a stage IB lung adenocarcinoma (pT2aN0M0). Thirty months after the surgery, a diffuse large B-cell-type lymphoma was discovered. In both cases, high antiviral capsid antigen IgG antibody titers were observed. CONCLUSION: Epstein-Barr virus may be associated with the incidence of multiple cancers given the pathological evidence from our two double cancer cases.
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[747]
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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[748]
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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[749]
TÍTULO / TITLE: - Surgery for NSCLC in the era of personalized medicine.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Clin Oncol. 2013 Apr;10(4):235-44. doi: 10.1038/nrclinonc.2013.22. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2013.22
AUTORES / AUTHORS: - Mitsudomi T; Suda K; Yatabe Y
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.
RESUMEN / SUMMARY: - The discovery in 2004 of activating mutations in the EGFR gene opened the era of personalized medicine in thoracic oncology. Treatment with drugs that target EGFR typically results in dramatic tumour response compared with conventional chemotherapy in patients with non-small-cell lung cancer. Subsequently, newer driver oncogenes such as ALK, ROS1 and RET have been discovered. Nevertheless, surgery has become safer and less invasive in the past 10-15 years. In the era of personalized medicine, thoracic surgeons have to think about their evolving roles. In this article, we discuss four topics relevant to this issue. Firstly, the value of surgical specimens as opposed to biopsy specimens for further understanding tumour biology is discussed. Secondly, extended indication of surgery in the era of targeted therapy is considered. Thirdly, in clinical trials that examine neoadjuvant therapy in patients selected by appropriate biomarkers, the important role of surgeons is highlighted. Finally, the possibility of personalizing the surgical procedure itself according to lung cancer subtypes defined by biomarkers is reviewed.
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[750]
TÍTULO / TITLE: - Prognostic significance of the combined score of endothelial expression of nucleolin and CD31 in surgically resected non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54674. doi: 10.1371/journal.pone.0054674. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054674
AUTORES / AUTHORS: - Zhao H; Huang Y; Xue C; Chen Y; Hou X; Guo Y; Zhao L; Hu Zh; Huang Y; Luo Y; Zhang L
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
RESUMEN / SUMMARY: - Nucleolin is implicated to play a role in angiogenesis, a vital process in tumor growth and metastasis. However, the presence and clinical relevance of nucleolin in human non small cell lung cancer (NSCLC) remains largely unknown. In this study, we explored the expression and prognostic implication of nucleolin in surgically resected NSCLC patients. A cohort of 146 NSCLC patients who underwent surgical resection was selected for tissue microarray. In this tissue microarray, nucleolin expression was measured by immunofluorescence. Staining for CD31, a marker of endothelial cells, was performed to mark blood vessels. A Cox proportional hazards model was used to assess the prognostic significance of nucleolin. Nucleolin expression was observed in 34.2% of all patients, and 64.1% in high CD31 expression patients. The disease-free survival (DFS) was significantly shorter in patients with high nucleolin (CD31(hi)NCL(hi)) compared to patients with low tumor blood vessels (CD31(lo)NCL(lo)) (5 ys of DFS 24% vs 64%, p = 0.002). Such a difference was demonstrated in the following stratified analyses: stage I (p<0.001), squamous cell carcinoma and adenosquamous cell carcinoma (p = 0.028), small tumor (<5 cm, p = 0.008), and surgery alone (p = 0.015). Multivariate analysis further revealed that nucleolin expression independently predicted for worse survival (p = 0.003). This study demonstrates that nucleolin is associated with the clinical outcomes in postoperative NSCLC patients. Thus, the expression levels of nucleolin may provide a new prognostic marker to identify patients at higher risk for treatment failure, especially in some subgroups.
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[751]
TÍTULO / TITLE: - Improved classification of lung cancer tumors based on structural and physicochemical properties of proteins using data mining models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58772. doi: 10.1371/journal.pone.0058772. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058772
AUTORES / AUTHORS: - Ramani RG; Jacob SG
INSTITUCIÓN / INSTITUTION: - Department of Information Science and Technology, College of Engineering, Guindy, Anna University, Chennai, Tamilnadu, India.
RESUMEN / SUMMARY: - Detecting divergence between oncogenic tumors plays a pivotal role in cancer diagnosis and therapy. This research work was focused on designing a computational strategy to predict the class of lung cancer tumors from the structural and physicochemical properties (1497 attributes) of protein sequences obtained from genes defined by microarray analysis. The proposed methodology involved the use of hybrid feature selection techniques (gain ratio and correlation based subset evaluators with Incremental Feature Selection) followed by Bayesian Network prediction to discriminate lung cancer tumors as Small Cell Lung Cancer (SCLC), Non-Small Cell Lung Cancer (NSCLC) and the COMMON classes. Moreover, this methodology eliminated the need for extensive data cleansing strategies on the protein properties and revealed the optimal and minimal set of features that contributed to lung cancer tumor classification with an improved accuracy compared to previous work. We also attempted to predict via supervised clustering the possible clusters in the lung tumor data. Our results revealed that supervised clustering algorithms exhibited poor performance in differentiating the lung tumor classes. Hybrid feature selection identified the distribution of solvent accessibility, polarizability and hydrophobicity as the highest ranked features with Incremental feature selection and Bayesian Network prediction generating the optimal Jack-knife cross validation accuracy of 87.6%. Precise categorization of oncogenic genes causing SCLC and NSCLC based on the structural and physicochemical properties of their protein sequences is expected to unravel the functionality of proteins that are essential in maintaining the genomic integrity of a cell and also act as an informative source for drug design, targeting essential protein properties and their composition that are found to exist in lung cancer tumors.
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[752]
TÍTULO / TITLE: - Detection and characterization of classical and “uncommon” exon 19 Epidermal Growth Factor Receptor mutations in lung cancer by pyrosequencing.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 13;13:114. doi: 10.1186/1471-2407-13-114.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-114
AUTORES / AUTHORS: - Righi L; Cuccurullo A; Vatrano S; Cappia S; Giachino D; Giuli PD; Ardine M; Novello S; Volante M; Scagliotti GV; Papotti M
INSTITUCIÓN / INSTITUTION: - Divisions of Pathology, University of Torino, Regione Gonzole 10, Torino, Orbassano, 10043, Italy. luisella.righi@unito.it.
RESUMEN / SUMMARY: - BACKGROUND: The management of advanced stage non-small cell lung cancer is increasingly based on diagnostic and predictive analyses performed mostly on limited amounts of tumor tissue. The evaluation of Epidermal Growth Factor Receptor (EGFR) mutations have emerged as the strongest predictor of response to EGFR-tyrosine kinase inhibitors mainly in patients with adenocarcinoma. Several EGFR mutation detection techniques are available, having both sensitivity and specificity issues, being the Sanger sequencing technique the reference standard, with the limitation of a relatively high amount of mutated cells needed for the analysis. METHODS: A novel nucleotide dispensation order for pyrosequencing was established allowing the identification and characterization of EGFR mutation not definable with commercially and clinically approved kits, and validated in a consecutive series of 321 lung cancer patients (246 biopsies or cytology samples and 75 surgical specimens). RESULTS: 61/321 (19%) mutated cases were detected, 17 (27.9%) in exon 21 and 44 (72.1%) in exon 19, these latter corresponding to 32/44 (72.7%) classical and 12/44 (27.3%) uncommon mutations. Furthermore, a novel, never reported, point mutation, was found, which determined a premature stop codon in the aminoacidic sequence that resulted in a truncated protein in the tyrosine kinase domain, thus impairing the inhibitory effect of specific therapy. CONCLUSIONS: The novel dispensation order allows to detect and characterize both classical and uncommon EGFR mutations. Although several phase III studies in genotypically defined groups of patients are already available, further prospective studies assessing the role of uncommon EGFR mutations are warranted.
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[753]
TÍTULO / TITLE: - Case images: squamous cell lung cancer metastasis in the left atrium: an interesting case with cardiac images.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Turk Kardiyol Dern Ars. 2012 Oct;40(7):654. doi: 10.5543/tkda.2012.28458.
AUTORES / AUTHORS: - Sengul C; Sunbul A; Ozveren O; Degertekin M
INSTITUCIÓN / INSTITUTION: - Department of Cardiology, Universal Group Camlica Hospital, Istanbul, Turkey.
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[754]
TÍTULO / TITLE: - Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55714. doi: 10.1371/journal.pone.0055714. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055714
AUTORES / AUTHORS: - Wang XM; Li J; Yan MX; Liu L; Jia DS; Geng Q; Lin HC; He XH; Li JJ; Yao M
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
RESUMEN / SUMMARY: - OBJECTIVE: To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes. METHODS: To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting dilution monoclone assay. We then analyzed those genes’ biological activities by knocking down their expression in SPC-A-1sci cells using siRNA and lenti-viral shRNA vectors, followed by determinations of the invasion and migration capabilities of the resulting cell lines in vitro as well as their potential for inducing occurrence and metastasis of lung cancer in vivo. To examine the clinical relevance of these findings, we analyzed the expression levels of the identified genes in human lung cancer tissues (n = 135) and matched adjacent normal tissues by immunohistochemical (IHC) staining. RESULTS: Three monoclonal cell strains characterized with high, medium or low metastatic abilities were successfully selected. Gene array and bioinformatics analyses implied that osteopontin, LAMB3 and ITGB1 were key genes involved in lung cancer. Knockdown of these genes suppressed human lung cancer cell invasion and metastasis in vitro and in vivo. Clinical sample analyses indicated that osteopontin, LAMB3 and ITGB1 protein expression levels were higher in lung cancer patients, compared to non-cancerous adjacent tissues, and correlated with lymphatic metastasis. CONCLUSIONS: We confirmed that osteopontin, LAMB3 and ITGB1 played important roles in the occurrence and metastasis of lung cancer, thus provided important clues to understanding the molecular mechanism of metastasis and contributing to the therapeutic treatment of lung cancer.
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[755]
TÍTULO / TITLE: - The use of stained cytologic direct smears for ALK gene rearrangement analysis of lung adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Mar 27. doi: 10.1002/cncy.21286.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21286
AUTORES / AUTHORS: - Betz BL; Dixon CA; Weigelin HC; Knoepp SM; Roh MH
INSTITUCIÓN / INSTITUTION: - Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.
RESUMEN / SUMMARY: - BACKGROUND: Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are present in approximately 5% of lung adenocarcinomas. Crizotinib is approved for the treatment of lung adenocarcinomas harboring ALK rearrangements. Patients with advanced stage lung cancer are not candidates for surgical resection of their primary tumors. For these patients, cytologic specimens often represent the only diagnostic tissue available. Cell blocks (CBs) are routinely used for molecular studies; however, insufficient CB cellularity can impede the performance of these assays. METHODS: Thirty-two cytology cases of lung adenocarcinomas were analyzed by fluorescence in situ hybridization (FISH) for ALK rearrangements. Diff-Quik-stained smears were examined to identify tumor cell-enriched areas that were marked using a diamond-tipped scribe. Paired ALK rearrangement FISH was performed using smears and CBs in each case. RESULTS: An ALK rearrangement was detected on direct smears and CB sections in 5 (16%) and 4 (13%), respectively, of the 32 cases studied. Concordant FISH results for smears and CBs were observed in 31 (97%) of 32 cases. In the 1 discordant case, an ALK rearrangement was detected on the direct smear but not in the CB. Reverse transcriptase-polymerase chain reaction analysis of this CB revealed the presence of an EML4-ALK rearrangement, thereby confirming a false-negative FISH result in the CB. CONCLUSIONS: Stained cytologic direct smears can be effectively used for ALK rearrangement analysis by FISH. This approach represents a useful safeguard when insufficient CB cellularity is encountered and could prevent delays in treatment in this era of precision medicine. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
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[756]
TÍTULO / TITLE: - Cyclin D1 polymorphism in non-small cell lung cancer in a Portuguese population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biomark. 2012 Jan 1;12(2):65-72. doi: 10.3233/CBM-130294.
●● Enlace al texto completo (gratuito o de pago) 3233/CBM-130294
AUTORES / AUTHORS: - Catarino R; Coelho A; Nogueira A; Araujo A; Gomes M; Lopes C; Medeiros R
INSTITUCIÓN / INSTITUTION: - Molecular Oncology GRP CI, Medical Oncology Department, Portuguese Institute of Oncology, Porto, Portugal. raquelcatarino@yahoo.com
RESUMEN / SUMMARY: - Cyclin D1 (CCND1) is a key regulatory protein of the cell cycle. The purpose of our study was to assess the role of CCND1 genetic variants influencing the genetic susceptibility of non-small cell lung cancer (NSCLC). We conducted a study of 1234 individuals, including 892 controls and 342 cases. Individuals carrying two G-alleles have a 2-fold increased risk for the development of NSCLC and the waiting time for onset of NSCLC in these patients was 2 years earlier in comparison with other individuals. Our results may be important in contributing to the knowledge of the mechanisms involved in lung carcinogenesis.
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[757]
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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[758]
TÍTULO / TITLE: - Key factors influencing lung cancer survival in northern Italy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Epidemiol. 2013 Mar 16. pii: S1877-7821(13)00028-3. doi: 10.1016/j.canep.2013.02.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canep.2013.02.005
AUTORES / AUTHORS: - Mangone L; Minicozzi P; Vicentini M; Giacomin A; Caldarella A; Cirilli C; Falcini F; Giorgi Rossi P; Sant M
INSTITUCIÓN / INSTITUTION: - Statistical, Quality and Clinical Studies Unit, IRCCS Arcispedale Santa Maria Nuova, Viale Umberto I 50, 42123 Reggio Emilia, Italy. Electronic address: Lucia.Mangone@asmn.re.it.
RESUMEN / SUMMARY: - Aim: Lung cancer is a major cause of cancer death worldwide. The aims of this study were to analyze presentation, treatment and survival for lung cancer in northern Italy, and identify factors influencing survival. Methods: A total of 1180 lung cancer cases diagnosed in four north Italian cancer registries (Biella, Modena, Reggio Emilia, Romagna) in 2003-2005 were analyzed. Information on morphology, stage, diagnostic examinations, chemotherapy, radiotherapy, and surgical treatment was collected from clinical records. Three-year relative survival and relative excess risks of death were estimated. Results: Overall, 10% of cases were stage I, 50% stage IV, and 12% stage unknown. Romagna - where sophisticated diagnostic examinations were performed more often - had proportionately more microscopically verified cases and resected cases than Biella. Romagna had also high proportions of cases given chemotherapy and radiotherapy. Three-year survival was 14%, range 10% (Biella) to 19% (Romagna); 69% for stage I, 3% for stage IV. Stage I survival was higher in Romagna (82%) than Reggio Emilia and Biella (60-61%) but for operated stage I cases, survival was similar (88%) in Romagna and Biella. The fully adjusted model showed a higher risk of death in Biella (1.23, 95%CI 1.02-1.48) than Modena (reference). Conclusions: Stage and surgery are key factors influencing survival. Centralizing lung cancer treatment to improve diagnostic work-up may improve outcomes.
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[759]
TÍTULO / TITLE: - Surgery for lung adenocarcinoma with smokers’ polycythemia: a case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Res Notes. 2013 Feb 1;6:38. doi: 10.1186/1756-0500-6-38.
●● Enlace al texto completo (gratuito o de pago) 1186/1756-0500-6-38
AUTORES / AUTHORS: - Sugiura Y; Nemoto E; Shinoda H; Nakamura N; Kaseda S
INSTITUCIÓN / INSTITUTION: - National Hospital Organization, Kanagawa National Hospital, Pulmonary and Thoracic Surgery, 666-1 Ochiai, Hadano, Kanagawa, 257-8585, Japan. yasoos@hotmail.com
RESUMEN / SUMMARY: - BACKGROUND: Smoking is a cause of cancer and polycythemia. Therefore, surgeons who treat patients with cancer may also encounter patients with polycythemia. However, few cases of surgical patients with polycythemia have been reported; in particular, a surgical case involving smokers’ polycythemia has never been reported. We herein report a patient with lung cancer and smokers’ polycythemia who successfully underwent lobectomy with control of hematocrit based on a modified formula in the perioperative period. CASE PRESENTATION: A 67-year-old man underwent abdominoperineal resection for rectal carcinoma in June 2008. A ground glass opacity had been identified in the upper lobe of the right lung and was gradually enlarging. In March 2012, bronchoscopic cytology for investigation of the mass revealed non-small cell lung cancer, suggesting primary lung non-small cell carcinoma (T1bN0M0, Stage IA). When he was referred to our hospital for surgery, his complete blood count showed a red blood cell level of 6.50x106/muL, hemoglobin of 21.0 g/dL, and hematocrit of 60.1%. The hematologists’ diagnosis was secondary polycythemia due to heavy smoking (smokers’ polycythemia) because the white blood cell and platelet counts were within normal limits and the erythropoietin was not increased. We calculated the appropriate phlebotomy and infusion volumes based on a formula that we modified. After 550 g of blood was phlebotomized to reduce the hematocrit to approximately 55%, video-assisted right lung upper lobectomy with lymph node dissection was performed in April 2012. The hematocrit was maintained at <50% postoperatively, and the patient was uneventfully discharged on postoperative day 7. The predictive hematocrit and measured hematocrit were very closely approximated in this case. CONCLUSION: We experienced a patient with smokers’ polycythemia who underwent right upper lobectomy for adenocarcinoma. The findings in this case report are meaningful for surgeons treating cancer patients because there are few reports discussing the perioperative care of surgical patients with polycythemia.
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[760]
TÍTULO / TITLE: - A case report of lung cancer in a horse trainer caused by exposure to respirable crystalline silica: an exposure assessment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Saf Health Work. 2013 Mar;4(1):71-4. doi: 10.5491/SHAW.2013.4.1.71. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 5491/SHAW.2013.4.1.71
AUTORES / AUTHORS: - Yoon JH; Kim B; Choi BS; Park SY; Kwag HS; Kim IA; Jeong JY
INSTITUCIÓN / INSTITUTION: - Occupational Lung Disease Institute, Korea Workers’ Compensation and Welfare Service, Ansan, Korea.
RESUMEN / SUMMARY: - Here, we present a case of lung cancer in a 48-year-old male horse trainer. To the best of our knowledge, this is the first such case report to include an exposure assessment of respirable crystalline silica (RCS) as a quartz. The trainer had no family history of lung cancer. Although he had a 15 pack/year cigarette-smoking history, he had stopped smoking 12 years prior to his diagnosis. For the past 23 years, he had performed longeing, and trained 7-12 horses per day on longeing arena surfaces covered by recycled sands, the same surfaces used in race tracks. We investigated his workplace RCS exposure, and found it to be the likely cause of his lung cancer. The 8-hour time weight average range of RCS was 0.020 to 0.086 mg/m(3) in the longeing arena. Horse trainers are exposed to RCS from the sand in longeing arenas, and the exposure level is high enough to have epidemiological ramifications for the occupational risk of lung cancer.
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[761]
TÍTULO / TITLE: - A case of malignant peritoneal mesothelioma revealed with limitation of PET-CT in the diagnosis of thoracic metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Dis. 2013 Feb;5(1):E11-6. doi: 10.3978/j.issn.2072-1439.2012.08.19.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.08.19
AUTORES / AUTHORS: - Saraya T; Yokoyama T; Ishii H; Tanaka Y; Tsujimoto N; Ogawa Y; Sohara E; Nakajima A; Inui T; Sayuki H; Fujiwara M; Oka T; Kawachi R; Goya T; Takizawa H; Goto H
INSTITUCIÓN / INSTITUTION: - Departments of Respiratory Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka City, Tokyo, Japan;
RESUMEN / SUMMARY: - A 47-year-old man was referred to our hospital because of a 2-month history of dry cough, 2-kg weight loss, and a feeling of abdominal fullness. The PET-CT scan depicts the intense standard uptake values (SUVs) of the anterior and subphrenic lymphnodes, and intraperitoneal cavity, especially in the omentum, while, no uptake was found in the pleural cavity. Based on the pathological findings of the open lung biopsy specimens, he was diagnosed with malignant peritoneal mesothelioma of epithelioid type with thoracic metastasis. The present case demonstrated the some of the limitations of PET-CT in the diagnosis of malignant mesothelioma, which failed to detect pleural involvement despite aggressive invasion by this tumor.
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[762]
TÍTULO / TITLE: - Lipopolysaccharide Enhances Mouse Lung Tumorigenesis: A Model for Inflammation-Driven Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet Pathol. 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1177/0300985813476061
AUTORES / AUTHORS: - Melkamu T; Qian X; Upadhyaya P; O’Sullivan MG; Kassie F
INSTITUCIÓN / INSTITUTION: - University of Minnesota, Minneapolis, MN.
RESUMEN / SUMMARY: - The association between pulmonary inflammation and lung cancer is well established. However, currently there are no appropriate models that recapitulate inflammation-related lung cancer in humans. In the present study, we examined, in 2 tumor bioassays, enhancement by bacterial lipopolysaccharide (LPS) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Mice that were treated with NNK alone developed 29.6 +/- 9.8 and 36.2 +/- 4.1 lung tumors per mouse in experiments 1 and 2, respectively. Chronic intranasal instillation of LPS to NNK-treated mice increased the multiplicity of lung tumors to 47.3 +/- 16.1 and 51.2 +/- 4.8 lung tumors per mouse in experiments 1 and 2, corresponding to a significant increase by 60% and 41%, respectively. Moreover, administration of LPS to NNK-pretreated mice significantly increased the multiplicity of larger tumors and histopathologically more advanced lesions (adenoma with dysplasia and adenocarcinoma), macrophage recruitment to the peritumoral area, and expression of inflammation-, cell proliferation-, and survival-related proteins. Overall, our findings demonstrated the promise of the NNK-LPS-A/J mice model to better understand inflammation-driven lung cancer, dissect the molecular pathways involved, and identify more effective preventive and therapeutic agents against lung cancer.
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[763]
TÍTULO / TITLE: - A retrospective study: platinum-based induction chemotherapy combined with gemcitabine or paclitaxel for stage IIB-IIIA central non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg Oncol. 2013 Mar 21;11(1):76.
●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-76
AUTORES / AUTHORS: - Lv C; Ma Y; Wu N; Yan S; Zheng Q; Sun Y; Li S; Fang J; Yang Y
RESUMEN / SUMMARY: - BACKGROUND: Several encouraging phase III clinical trials have evaluated platinum-based induction chemotherapy against stage IIB-IIIA non-small-cell lung cancer (NSCLC). Chemotherapy efficacy was assessed using common regimens in this retrospective analysis. METHODS: From 2007 to 2011, the clinical records of stage IIB-IIIA NSCLC patients undergoing surgery after neoadjuvant chemotherapy were reviewed. Gathered data were tested for significance and variables impacting survival were assessed by univariate and Cox regression analyses. RESULTS: Overall, 84% of patients were male and 93% had central disease. Platinum-based chemotherapy protocols with gemcitabine or paclitaxel gave an overall response rate of 55% (45/82) and 6.1% pathological complete response (5/82). Clinical response was unassociated with regimen or histology, while more pneumonectomies were performed in the stable compared to partial response disease group (P =0.040). Postoperative mortality was 1.2% (1/82), and complications, unassociated with regimen or histology, were atelectasis (26.8%) and supraventricular arrhythmias (13.4%). Right-sided procedures appeared to increase the incidence of bronchopleural fistula (P =0.073). The median disease-free survival time was 18 months and median overall survival time was not reached. Disease-free survival rates at one, two, and three years were 54%, 47%, and 33%, while the overall survival rate was 73%, 69%, and 59%, respectively. Disease-free survival predictors were radiographic response and mediastinal lymphadenopathy before chemotherapy (P =0.012 and 0.002, respectively). CONCLUSIONS: Two cycles of platinum-based chemotherapy with gemcitabine or paclitaxel is efficacious for patients with stage IIB-IIIA central disease. Patients achieving clinical response had improved disease-free survival times, while those with mediastinal lymphadenopathy had a higher postoperative recurrence risk.
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[764]
TÍTULO / TITLE: - Coordinate direct input of both KRAS and IGF1 receptor to activation of PI 3-kinase in KRAS mutant lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0446
AUTORES / AUTHORS: - Molina-Arcas M; Hancock DC; Sheridan C; Kumar MS; Downward J
INSTITUCIÓN / INSTITUTION: - 1London Research Institute, Cancer Research UK.
RESUMEN / SUMMARY: - Using a panel of non-small cell lung cancer (NSCLC) lines, we show here that MEK and RAF inhibitors are selectively toxic for the KRAS mutant genotype, while PI 3-kinase (PI3K), AKT and mTOR inhibitors are not. IGF1 receptor (IGF1R) tyrosine kinase inhibitors also show selectivity for KRAS mutant lung cancer lines. Combinations of IGF1R and MEK inhibitors resulted in strengthened inhibition of KRAS mutant lines and also showed improved effectiveness in autochthonous mouse models of Kras induced NSCLC. PI3K pathway activity is dependent on basal IGF1R activity in KRAS mutant, but not wild-type, lung cancer cell lines. KRAS is needed for both MEK and PI3K pathway activity in KRAS mutant, but not wild-type, lung cancer cells, while acute activation of KRAS causes stimulation of PI3K dependent upon IGF1R kinase activity. Coordinate direct input of both KRAS and IGF1R is thus required to activate PI3K in KRAS mutant lung cancer cells.
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[765]
TÍTULO / TITLE: - African american health disparities in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin J Oncol Nurs. 2013 Apr 1;17(2):180-6. doi: 10.1188/13.CJON.180-186.
●● Enlace al texto completo (gratuito o de pago) 1188/13.CJON.180-186
AUTORES / AUTHORS: - Green PM; Guerrier-Adams S; Okunji PO; Schiavone D; Smith JE
INSTITUCIÓN / INSTITUTION: - College of Nursing and Allied Health Sciences, Howard University, Washington, DC.
RESUMEN / SUMMARY: - Lung cancer is a leading cause of cancer-related deaths in the United States and globally. African Americans experience significant differences in lung cancer incidence and mortality. Smoking is the single greatest risk for lung cancer, making smoking cessation programs a potentially fruitful approach for reducing the risk of lung cancer. Despite clinical practice guidelines that prompt nurses to advise patients to quit smoking, only a small percentage of nurses do so. Minority patients are less likely than Whites to receive smoking cessation advice. This article discusses recent findings on the pathophysiology and risks for lung cancer. The literature on smoking cessation research is examined to determine the features of successful cessation interventions. Recommendations are offered for enhancing tobacco cessation efforts in nursing practice, education, and research.
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[766]
TÍTULO / TITLE: - Diagnostic value of endobronchial and endoscopic ultrasound-guided fine needle aspiration for accessible lung cancer lesions after non-diagnostic conventional techniques: a prospective study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 19;13(1):130.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-130
AUTORES / AUTHORS: - Bugalho A; Ferreira D; Eberhardt R; Dias SS; Videira PA; Herth FJ; Carreiro L
RESUMEN / SUMMARY: - BACKGROUND: Lung cancer diagnosis is usually achieved through a set of bronchoscopic techniques or computed tomography guided-transthoracic needle aspiration (CT-TTNA). However these procedures have a variable diagnostic yield and some patients remain without a definite diagnosis despite being submitted to an extensive workup. The aim of this study was to evaluate the efficacy and cost of linear endobronchial (EBUS) and endoscopic ultrasound (EUS) guided fine needle aspiration (FNA), performed with one echoendoscope, for the diagnosis of suspicious lung cancer lesions after failure of conventional procedures. METHODS: One hundred and twenty three patients with an undiagnosed but suspected malignant lung lesion (paratracheal, parabronchial, paraesophageal) or with a peripheral lesion and positron emission tomography positive mediastinal lymph nodes who had undergone at least one diagnostic flexible bronchoscopy or CT-TTNA attempt were submitted to EBUS and EUS-FNA. Patients with endobronchial lesions were excluded. RESULTS: Of the 123 patients, 88 had a pulmonary nodule/mass and 35 were selected based on mediastinal PET positive lymph nodes. Two patients were excluded because an endobronchial mass was detected at the time of the procedure. The target lesion could be visualized in 121 cases and FNA was performed in 118 cases. A definitive diagnosis was obtained in 106 cases (87.6%). Eighty-eight patients (72.7%) had non-small cell lung cancer, 15 (12.4%) had small cell lung cancer and metastatic disease was found in 3 patients (2.5%). The remaining 15 negative cases were subsequently diagnosed by surgical procedures. Twelve patients (9.9%) had a malignant tumor and in 3 (2.5%) a benign lesion was found. The overall sensitivity, specificity, positive and negative predictive values of EBUS and EUS-FNA to diagnose malignancy were 89.8%, 100%, 100% and 20.0% respectively. The diagnostic accuracy was 90.1% in a population with 97.5% prevalence of cancer. The ultrasonographic approach avoided expensive surgical procedures and significantly reduced costs (p < 0.001). CONCLUSIONS: Linear EBUS and EUS-FNA are able to improve the diagnostic yield of suspicious lung cancer lesions after non-diagnostic conventional techniques. These techniques, performed with one scope, can be offered to patients with accessible lesions as an intermediate step for diagnosis since they may avoid more invasive procedures and hence reduce costs.
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[767]
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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[768]
TÍTULO / TITLE: - Blocking NRG1 and other ligand-mediated Her4 signaling enhances the magnitude and duration of the chemotherapeutic response of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Sci Transl Med. 2013 Feb 6;5(171):171ra18. doi: 10.1126/scitranslmed.3004438.
●● Enlace al texto completo (gratuito o de pago) 1126/scitranslmed.3004438
AUTORES / AUTHORS: - Hegde GV; de la Cruz CC; Chiu C; Alag N; Schaefer G; Crocker L; Ross S; Goldenberg D; Merchant M; Tien J; Shao L; Roth L; Tsai SP; Stawicki S; Jin Z; Wyatt SK; Carano RA; Zheng Y; Sweet-Cordero EA; Wu Y; Jackson EL
INSTITUCIÓN / INSTITUTION: - Department of Discovery Oncology, Genentech Inc., South San Francisco, CA 94080, USA.
RESUMEN / SUMMARY: - Although standard chemotherapies are commonly used to treat most types of solid tumors, such treatment often results in inadequate response to, or relapse after, therapy. This is particularly relevant for lung cancer because most patients are diagnosed with advanced-stage disease and are treated with frontline chemotherapy. By studying the residual tumor cells that remain after chemotherapy in several in vivo non-small cell lung cancer models, we found that these cells have increased levels of human epidermal growth factor receptor (HER) signaling due, in part, to the enrichment of a preexisting NRG1(HI) subpopulation. Neuregulin 1 (NRG1) signaling in these models can be mediated by either the HER3 or HER4 receptor, resulting in the differential activation of downstream effectors. Inhibition of NRG1 signaling inhibits primary tumor growth and enhances the magnitude and duration of the response to chemotherapy. Moreover, we show that inhibition of ligand-mediated Her4 signaling impedes disease relapse in cases where NRG1 inhibition is insufficient. These findings demonstrate that ligand-dependent Her4 signaling plays an important role in disease relapse.
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[769]
TÍTULO / TITLE: - Ascertaining an Appropriate Diagnostic Algorithm Using EGFR Mutation-Specific Antibodies to Detect EGFR Status in Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59183. doi: 10.1371/journal.pone.0059183. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059183
AUTORES / AUTHORS: - Jiang G; Fan C; Zhang X; Dong Q; Wang L; Liu Y; Dai S; Yang L; Zhang Y; Yu J; Wang E
INSTITUCIÓN / INSTITUTION: - Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
RESUMEN / SUMMARY: - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation status is the most valuable indicator in the screening of non-small-cell lung cancer (NSCLC) patients for tyrosine kinase inhibitor (TKI) therapy. Accurate, rapid and economical methods of detecting EGFR mutations have become important. The use of two mutation-specific antibodies targeting the delE746-A750 mutation in exon 19 and L858R mutation in exon 21 makes this task possible, but the lack of consensually acceptable criteria for positive results limits the application of this antibody based mutation detection. METHODS: We collected 399 specimens from NSCLC patients (145 resection specimens, 220 biopsy specimens, and 34 cytology specimens) whose EGFR mutation status had been detected by TaqMan PCR assay. Immunohistochemical (IHC) analyses using EGFR mutation-specific antibodies were employed for all samples. After staining and scoring, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated in accordance with different levels of positive grades in comparison with the results of PCR-based assay. RESULTS: In IHC-based analyses, 144 cases were scored 0, 104 cases were scored 1+, 103 cases were scored 2+, and 48 cases were scored 3+. With the molecular-based results were set as the “gold standard”, the prevalence of mutation was 6.94% (10/144), 23.08% (24/104), 67.96% (70/103) and 100% (48/48), respectively, for samples with scores 0, 1+, 2+ and 3+. When score 3+ was considered positive, the specificity and PPV were 100%; if only score 0 was considered negative, 93.06% NPV was obtained. CONCLUSION: Patients with score 3+ have a perfect PPV (100%), and may accept TKI treatment directly without any molecular-based assays. Patients with score 0 had high NPV (93.06%), which could reach 97.22% when the detection of total EGFR was applied. However, samples with score 1+ or 2+ are unreliable and need further verification of EGFR mutation status by molecular-based assays.
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[770]
TÍTULO / TITLE: - Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nanoscale Res Lett. 2013 Feb 9;8(1):66. doi: 10.1186/1556-276X-8-66.
●● Enlace al texto completo (gratuito o de pago) 1186/1556-276X-8-66
AUTORES / AUTHORS: - Jiang L; Li X; Liu L; Zhang Q
INSTITUCIÓN / INSTITUTION: - Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China. bmezqq@163.com.
RESUMEN / SUMMARY: - Oral chemotherapy is a key step towards ‘chemotherapy at home’, a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-alpha-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer.
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[771]
TÍTULO / TITLE: - A rare malignant tumor of scalp in a 3-month-old Taiwanese infancy: case report of primitive myxoid mesenchymal tumor of infancy with molecular study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Mol Morphol. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1007/s00795-013-0032-1
AUTORES / AUTHORS: - Su TC; Hwang MJ; Li CF; Wang SC; Lee CH; Chen CJ
INSTITUCIÓN / INSTITUTION: - Department of Surgical Pathology, Changhua Christian Hospital, 135 Nanxiao Street, Changhua, Taiwan.
RESUMEN / SUMMARY: - Primitive myxoid mesenchymal tumor of infancy is an extremely rare and recently recognized soft tissue tumor entity with a tendency for multiple recurrences. Only ten cases have been described in the literature and most cases are reported in Western countries. This tumor ranges in size from 2 to 15 cm and is characterized microscopically by a diffuse growth of primitive cells in a myxoid background with focal fascicles or a herringbone pattern. In this study, we describe a primitive myxoid mesenchymal tumor of infancy on the scalp of a 3-month-old Taiwanese boy. The histology showed typical morphology and the tumor cells showed vimentin and CD99 immunoreactivities. The translocation t(12,15)(p13;q25) was not found by fluorescence in situ hybridization. After complete surgical excision, no recurrence was noted during an 18-month follow-up.
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[772]
TÍTULO / TITLE: - Nicotinic Receptor beta2 Determines NK Cell-Dependent Metastasis in a Murine Model of Metastatic Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57495. doi: 10.1371/journal.pone.0057495. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057495
AUTORES / AUTHORS: - Hao J; Shi FD; Abdelwahab M; Shi SX; Simard A; Whiteaker P; Lukas R; Zhou Q
INSTITUCIÓN / INSTITUTION: - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
RESUMEN / SUMMARY: - Cigarette smoke exposure markedly compromises the ability of the immune system to protect against invading pathogens and tumorigenesis. Nicotine is a psychoactive component of tobacco products that acts as does the natural neurotransmitter, acetylcholine, on nicotinic receptors (nAChRs). Here we demonstrate that natural killer (NK) cells strongly express nAChR beta2. Nicotine exposure impairs the ability of NK cells to kill target cells and release cytokines, a process that is largely abrogated by nAChR beta2 deficiency. Further, nicotinic suppression of NF-kappaB-induced transcriptional activity in NK cells is dependent on nAChR beta2. This nAChR subtype also plays a large role in the NK cell-mediated control of melanoma lung metastasis, in a murine lung metastasis model exposed to nicotine. Our findings suggest nAChR beta2 as a prominent pathway for nicotine induced impairment of NK cell functions which contributes to the occurrence of smoking-related pathologies.
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[773]
TÍTULO / TITLE: - Fatal pneumonitis associated with postoperative intensity-modulated radiotherapy in lung cancer: Case report and review.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):714-716. Epub 2012 Nov 30.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1053
AUTORES / AUTHORS: - Hu Y; Li J; Su X
INSTITUCIÓN / INSTITUTION: - Department of Oncology, The First People’s Hospital of Jingzhou, Jingzhou, Hubei 434000, P.R. China.
RESUMEN / SUMMARY: - Radiation pneumonitis (RP) is the most significant complication of acute treatment-related toxicities in lung cancer. Intensity-modulated radiotherapy (IMRT) with inverse planning enables us to achieve the desired dose distribution. However, there are many high-risk procedures associated with lung irradiation, including chemotherapy and surgery. We report a case of fatal treatment-related pneumonitis, where the patient had undergone postoperative IMRT for lung cancer. Following completion of radiotherapy, the patient developed progressive dyspnea. A chest computed tomography (CT) scan revealed the presence of diffuse reticular interstitial processes and honeycombing in both lungs. The fibrotic change in both lungs in a transverse view was compatible with low-dose irradiation of non-target organs at risk. Acute radiation pneumonitis was diagnosed. For patients receiving postoperative IMRT, low-dose irradiation volumes should be considered for lungs, as well as strict dose-volume histogram (DVH) parameters.
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[774]
TÍTULO / TITLE: - p73 expression is associated with cellular chemosensitivity in human non-small cell lung cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):583-587. Epub 2012 Nov 19.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1035
AUTORES / AUTHORS: - Liu K; Zhuang X; Mai Z
INSTITUCIÓN / INSTITUTION: - Department of Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
RESUMEN / SUMMARY: - p73 is a member of the p53 tumor suppressor protein family and induces apoptosis in tumor cells that lack functional p53. It has been demonstrated that methylation of CpG islands in the promoter and exon 1 region may result in silencing of the p73 gene. The aim of this study was to investigate the correlation between p73 gene expression and chemosensitivity in non-small cell lung cancer (NSCLC) cell lines. The expression of the p73 transcript in six NSCLC cell lines was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The methylation status in these cell lines was determined by methylation-specific PCR (MSP) analysis. An in vitro demethylation assay was conducted using the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine (5-aza-dC). Restored expression of p73 in the human lung squamous cell carcinoma cell line C57, both at the mRNA and protein level, was investigated by RT-PCR and immunohistochemistry, respectively. A colony formation assay was used to measure the surviving fraction of the C57 cell line. Transcript silencing of the p73 gene in the six NSCLC cell lines was observed and related to aberrant methylation. The expression of the p73 transcript and protein in the C57 cell line was restored by 5-aza-dC. The surviving fraction for colony formation in C57 cells pre-treated with 5-aza-dC was 0.059+/-0.006, which was significantly different from that of the control group (0.12+/-0.008; P<0.05). Our data demonstrated a significant correlation between expression of p73 and cellular chemosensitivity in NSCLC.
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[775]
TÍTULO / TITLE: - Utility of serum DNA and pyrosequencing for the detection of EGFR mutations in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Genet. 2013 Mar 8. pii: S2210-7762(13)00016-1. doi: 10.1016/j.cancergen.2013.01.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cancergen.2013.01.005
AUTORES / AUTHORS: - Akca H; Demiray A; Yaren A; Bir F; Koseler A; Iwakawa R; Bagci G; Yokota J
INSTITUCIÓN / INSTITUTION: - Department of Medical Biology, School of Medicine, Pamukkale University, Denizli, Turkey. Electronic address: hakca@pau.edu.tr.
RESUMEN / SUMMARY: - Mutations in the EGFR gene are critical determinants of treatment with EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) patients. DNA isolation from tumor samples usually requires surgery; therefore, we wanted to isolate DNA from circulating tumor cells by using the serum of NSCLC patients. This protocol was recently published. DNA was isolated from the serum of 52 Turkish NSCLC patients and their EGFR mutation status was examined by pyrosequencing. EGFR mutations were detected in 25 of the 52 patients (48.1%): 17 patients with delE746-A750, 2 with delE747-A750insP, and 6 with L858R. All mutations detected by pyrosequencing were confirmed by dideoxy sequencing, and the presence of the same mutations in the tumors was verified by using paraffin embedded tissues of all the patients. Mutations were detected more frequently in adenocarcinomas (24 of 36, 66.7%) than in squamous cell carcinomas (1 of 16, 6.3%) (P < 0.001). These results confirm the utility of serum DNA and pyrosequencing for the detection of EGFR mutations in patients with advanced NSCLC.
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[776]
TÍTULO / TITLE: - Efficacy of hypofractionated radiotherapy for nasal tumours in 38 dogs (2005-2008).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Small Anim Pract. 2013 Feb;54(2):80-6. doi: 10.1111/jsap.12024.
●● Enlace al texto completo (gratuito o de pago) 1111/jsap.12024
AUTORES / AUTHORS: - Fujiwara A; Kobayashi T; Kazato Y; Yayoshi N; Fujita M
INSTITUCIÓN / INSTITUTION: - Department of Veterinary Radiology, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: To evaluate the efficacy of hypofractionated radiotherapy for canine nasal tumours, including the improvement in clinical signs, rate of complications and assessment of prognostic factors. METHODS: Medical records of 38 dogs with malignant nasal tumours were reviewed, and those treated with a weekly schedule of hypofractionated radiotherapy were included in the study. Acute and late side effects were defined as complications noted either within 1 month or after 6 months of irradiation, respectively. Progression-free interval and overall survival were calculated using the Kaplan-Meier method. Log-rank test and Cox proportional hazard model were also performed. RESULTS: Clinical signs improved in 30 of 36 dogs. Acute complications were seen in 28 of 36 dogs and were considered manageable. Late complications were observed in 17 of 30 dogs that survived 6 months or longer, but severe side effects were not observed. The median progression-free interval and overall survival was 245 days (95% CI: 127-512 days) and 512 days (95% CI: 203-820 days), respectively. Age, breed and presence of dyspnoea were negatively correlated with overall survival. CLINICAL SIGNIFICANCE: These results suggest that hypofractionated radiotherapy could be a viable option for the treatment of nasal tumours in dogs that are not candidates for conventional multi-fractionated radiotherapy.
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[777]
TÍTULO / TITLE: - Diagnostic value of tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Feb 13. doi: 10.1002/cncy.21283.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21283
AUTORES / AUTHORS: - Hsieh TC; Huang WW; Lai CL; Tsao SM; Su CC
INSTITUCIÓN / INSTITUTION: - Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
RESUMEN / SUMMARY: - BACKGROUND: Cytology fails to detect neoplastic cells in approximately 40% to 50% of malignant pleural effusions (PEs), which commonly accompany lung adenocarcinomas. The diagnostic accuracy of various tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions (LAC-CNPEs) has been poor. The current study attempted to maximize diagnostic efforts in distinguishing LAC-CNPEs from benign PEs. METHODS: PE samples were collected from 74 patients with lung adenocarcinoma with associated cytologically positive (41 patients) and negative (33 patients) PEs, and from 99 patients with benign conditions including tuberculosis (26 patients), pneumonia (28 patients), congestive heart failure (25 patients), and cirrhosis (20 patients). The authors evaluated the diagnostic sensitivity and optimal cutoff points for the tumor markers HER2/neu, CYFRA 21-1, and carcinoembryonic antigen (CEA) to distinguish LAC-CNPEs from benign PEs. RESULTS: Mean levels of HER2/neu, CYRFA 21-1, and CEA were found to be significantly higher in LAC-CNPEs compared with benign PEs (P = .0050, P = .0039, and P < .0001, respectively). The cutoff points for HER2/neu, CYFRA 21-1, and CEA were optimally set at 3.6 ng/mL, 60 ng/mL, and 6.0 ng/mL, respectively. Their sensitivities ranged from 12.1%, to 30.3%, to 63.6%, respectively. CEA combined with CYFRA 21-1 increased diagnostic sensitivity to 66.7%. The false-positive rates of these markers in benign PEs were 6.1%, 2.0%, and 0%, respectively. CONCLUSIONS: The combination of CEA with CYFRA 21-1 appears to provide the best differentiation between LAC-CNPEs and benign PEs to date using 2 tumor markers, and allows for the early diagnosis and early treatment of approximately two-thirds of affected patients. Cancer (Cancer Cytopathol) 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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[778]
TÍTULO / TITLE: - Multiple Marker Detection in Peripheral Blood for NSCLC Diagnosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57401. doi: 10.1371/journal.pone.0057401. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057401
AUTORES / AUTHORS: - Ulivi P; Mercatali L; Casoni GL; Scarpi E; Bucchi L; Silvestrini R; Sanna S; Monteverde M; Amadori D; Poletti V; Zoli W
INSTITUCIÓN / INSTITUTION: - Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.
RESUMEN / SUMMARY: - BACKGROUND: Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC). METHODS: 100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method. RESULTS: Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15-11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75-13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71-4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01-1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90-0.97, with sensitivity and specificity over 90%. CONCLUSIONS: Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer.
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[779]
TÍTULO / TITLE: - Stereotactic body radiotherapy using gated radiotherapy with real-time tumor-tracking for stage I non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 21;8:69. doi: 10.1186/1748-717X-8-69.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-69
AUTORES / AUTHORS: - Inoue T; Katoh N; Onimaru R; Shimizu S; Tsuchiya K; Suzuki R; Sakakibara-Konishi J; Shinagawa N; Oizumi S; Shirato H
INSTITUCIÓN / INSTITUTION: - Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. ronimaru@pop.med.hokudai.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: To clarify the clinical outcomes of two dose schedule of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) using a real-time tumor-tracking radiation therapy (RTRT) system in single institution. METHODS: Using a superposition algorithm, we administered 48 Gy in 4 fractions at the isocenter in 2005-2006 and 40 Gy in 4 fractions to the 95% volume of PTV in 2007-2010 with a treatment period of 4 to 7 days. Target volume margins were fixed irrespective of the tumor amplitude. RESULTS: In total, 109 patients (79 T1N0M0 and 30 T2N0M0). With a median follow-up period of 25 months (range, 4 to 72 months), the 5-year local control rate (LC) was 78% and the 5-year overall survival rate (OS) was 64%. Grade 2, 3, 4, and 5 radiation pneumonitis (RP) was experienced by 15 (13.8%), 3 (2.8%), 0, and 0 patients, respectively. The mean lung dose (MLD) and the volume of lung receiving 20 Gy (V20) were significantly higher in patients with RP Grade 2/3 than in those with RP Grade 0/1 (MLD p = 0.002, V20 p = 0.003). There was no correlation between larger maximum amplitude of marker movement and larger PTV (r = 0.137), MLD (r = 0.046), or V20 (r = 0.158). CONCLUSIONS: SBRT using the RTRT system achieved LC and OS comparable to other SBRT studies with very low incidence of RP, which was consistent with the small MLD and V20 irrespective of tumor amplitude. For stage I NSCLC, SBRT using RTRT was suggested to be reliable and effective, especially for patients with large amplitude of tumor movement.
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[780]
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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[781]
TÍTULO / TITLE: - Differential Expression of the RANKL/RANK/OPG System Is Associated with Bone Metastasis in Human Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58361. doi: 10.1371/journal.pone.0058361. Epub 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058361
AUTORES / AUTHORS: - Peng X; Guo W; Ren T; Lou Z; Lu X; Zhang S; Lu Q; Sun Y
INSTITUCIÓN / INSTITUTION: - Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China.
RESUMEN / SUMMARY: - BACKGROUND: Human non-small cell lung cancer (NSCLC) patients exhibit a high propensity to develop skeletal metastasis, resulting in excessive osteolytic activity. The RANKL/RANK/OPG system, which plays a pivotal role in bone remodeling by regulating osteoclast formation and activity, is of potential interest in this context. MATERIALS AND METHODS: Reverse transcriptase polymerase chain reaction, western blotting, and immunohistochemical analysis were used to examine the expression of RANKL, RANK, and OPG in human NSCLC cell lines with different metastatic potentials, as well as in 52 primary NSCLC samples and 75 NSCLC bone metastasis samples. In primary NSCLC patients, the expression of these proteins was correlated with clinicopathological parameters. Recombinant human RANKL and transfected RANKL cDNA were added to the PAa cell line to evaluate the promoter action of RANKL during the process of metastasis in vitro and in vivo. RESULTS: Up-regulated RANKL, RANK, and OPG expression and increased RANKL:OPG ratio were detected in NSCLC cell lines and in tumor tissues with bone metastasis, and were correlated with higher metastatic potential. The metastatic potential of NSCLC in vitro and in vivo, including migration and invasion ability, was significantly enhanced by recombinant human RANKL and the transfection of RANKL cDNA, and was impaired after OPG was added. The increased expression of RANKL and OPG correlated with tumor stage, lymph node metastasis, and distant metastasis. CONCLUSIONS: Differential expression of RANKL, RANK, and OPG is associated with the metastatic potential of human NSCLC to skeleton, raising the possibility that the RANKL/RANK/OPG system could be a therapeutic target for the treatment of metastatic NSCLC patients.
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[782]
TÍTULO / TITLE: - Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Mar 12;14(3):5806-16. doi: 10.3390/ijms14035806.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14035806
AUTORES / AUTHORS: - Liang YW; Chang CC; Hung CM; Chen TY; Huang TY; Hsu YC
INSTITUCIÓN / INSTITUTION: - Department of Emergency Medicine, Chi-Shan Hospital, Department of Health, Executive Yuan, Kaohsiung 84274, Taiwan. d8702008@tmu.edu.tw.
RESUMEN / SUMMARY: - Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.
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[783]
TÍTULO / TITLE: - Pathway analysis for genome-wide association study of lung cancer in han chinese population.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57763. doi: 10.1371/journal.pone.0057763. Epub 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057763
AUTORES / AUTHORS: - Zhang R; Zhao Y; Chu M; Wu C; Jin G; Dai J; Wang C; Hu L; Gou J; Qian C; Bai J; Wu T; Hu Z; Lin D; Shen H; Chen F
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology and Biostatistics and Ministry of Education (MOE) Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
RESUMEN / SUMMARY: - Genome-wide association studies (GWAS) have identified a number of genetic variants associated with lung cancer risk. However, these loci explain only a small fraction of lung cancer hereditability and other variants with weak effect may be lost in the GWAS approach due to the stringent significance level after multiple comparison correction. In this study, in order to identify important pathways involving the lung carcinogenesis, we performed a two-stage pathway analysis in GWAS of lung cancer in Han Chinese using gene set enrichment analysis (GSEA) method. Predefined pathways by BioCarta and KEGG databases were systematically evaluated on Nanjing study (Discovery stage: 1,473 cases and 1,962 controls) and the suggestive pathways were further to be validated in Beijing study (Replication stage: 858 cases and 1,115 controls). We found that four pathways (achPathway, metPathway, At1rPathway and rac1Pathway) were consistently significant in both studies and the P values for combined dataset were 0.012, 0.010, 0.022 and 0.005 respectively. These results were stable after sensitivity analysis based on gene definition and gene overlaps between pathways. These findings may provide new insights into the etiology of lung cancer.
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[784]
TÍTULO / TITLE: - Isolated pineal region metastasis from lung adenocarcinoma with obstructive hydrocephalus: a case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Case Rep. 2013 Mar 14;7(1):71.
●● Enlace al texto completo (gratuito o de pago) 1186/1752-1947-7-71
AUTORES / AUTHORS: - Nemoto K; Aoshiba K; Itoh M; Semba S; Tsuji T; Adachi H; Nakamura H
RESUMEN / SUMMARY: - INTRODUCTION: Although the brain is a common site of metastasis from lung cancer, pineal region metastasis from lung adenocarcinoma is rare. Most cases of pineal metastases are asymptomatic, and are diagnosed by autopsy. Therefore, the management of pineal region tumors remains controversial. Here, we present a rare case of lung carcinoma presenting with pineal region metastasis and obstructive hydrocephalus as the first manifestation of the lung adenocarcinoma. CASE PRESENTATION: A 63-year-old Japanese woman was referred to our hospital for treatment of a tumor of the pineal region associated with hydrocephalus. On admission, she was found to have a mass in her right lung on a chest radiograph. During the preoperative investigation, the patient began to show a progressively worsening level of altered consciousness. Therefore, neuroendoscopic surgery was performed as an emergency procedure, which resulted in improvement of the hydrocephalus and diagnosis of adenocarcinoma. A systematic investigation revealed adenocarcinoma of her right lung as the primary lesion. She was treated by a platinum-based chemotherapy regime. Stereotactic radiation to the pineal region was undertaken concurrently. After completion of the chemotherapy, the primary lesion and pineal region metastasis showed good partial response. CONCLUSION: The prognosis of pineal region metastasis is extremely poor, and only three patients with metastatic pineal region metastasis from lung cancer who were treated by chemotherapy have been reported. We performed neuroendoscopic surgery to obtain resolution of the obstructive hydrocephalus and the definite histological diagnosis. This resulted in improvement of the general condition of the patient, and the patient could be treated by chemotherapy and radiotherapy. We strongly believe that neuroendoscopic surgery was a good option in this case. This case report suggests that in the presence of an isolated pineal region tumor, metastasis should be considered a possible diagnosis, and careful examination for systemic malignant disease will be needed.
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[785]
TÍTULO / TITLE: - Lung Cancer and Paraneoplastic Neurologic Syndromes. Case Report and Review of the Literature.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Feb 1. pii: S1525-7304(12)00265-3. doi: 10.1016/j.cllc.2012.11.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.11.008
AUTORES / AUTHORS: - Rossato M; Zabeo E; Burei M; Cecchin D; Guzzardo V; Fassina A; Vettor R
INSTITUCIÓN / INSTITUTION: - Department of Medicine, DIMED, University of Padova, Padova, Italy. Electronic address: marco.rossato@unipd.it.
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[786]
TÍTULO / TITLE: - Cases presenting to orthopedists with manifestations of lung cancer on skeletal radiographs.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Orthop Surg Traumatol. 2013 Apr;23(3):273-9. doi: 10.1007/s00590-012-0984-1. Epub 2012 Apr 4.
●● Enlace al texto completo (gratuito o de pago) 1007/s00590-012-0984-1
AUTORES / AUTHORS: - Ichinohe K; Ushio T; Ookawa Y; Sugiyama M; Ishihara M
INSTITUCIÓN / INSTITUTION: - Department of Radiotherapy, Fukuroi Municipal Hospital, 2515-1 Kunou, Fukuroi, Shizuoka, Japan, koya@moon.odn.ne.jp.
RESUMEN / SUMMARY: - The value of cervical spine or shoulder radiography has been established for the detection of Pancoast tumors. However, for the detection of lung cancers other than Pancoast tumors, the value of these skeletal radiographies has not been assessed. The aim of our study was to determine how many patients first presented to orthopedists with manifestations of lung cancer on skeletal radiographs and to present several cases for illustration. From the registry of the pathology department of our hospital, we identified 345 lung cancer patients diagnosed histologically over 10 years. From these patients, we selected 310 who had no previous history of malignancies at histological diagnosis of lung cancer. The study population consisted of individuals from the selected patients who had presented once or more to orthopedists at our hospital for any reason, at up to 2 years prior to histological diagnosis of lung cancer. For the study population, all radiological examinations performed by the orthopedists were reviewed by radiologists. The study population included 46 patients constituting 14.8 % (46/310) of the selected patients. Of these 46 patients, 37 (80.4 %) received 97 skeletal radiographies. Reviewing these skeletal radiographies disclosed lung tumors on 13 in 11 (11/46, 23.9 %) of the patients. We found that more than 10 % of lung cancer patients with no previous history of malignancies had presented to orthopedists on one or more occasions, at up to 2 years before histological diagnosis, and that approximately 25 % of these patients had manifestations of lung cancer on skeletal radiographs.
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[787]
TÍTULO / TITLE: - Intensity-modulated stereotactic body radiotherapy for stage I non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):840-844. Epub 2012 Dec 18.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1082
AUTORES / AUTHORS: - Kim MJ; Yeo SG; Kim ES; Min CK; Se An P
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang;
RESUMEN / SUMMARY: - This study aimed to investigate the clinical outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). A prospective database of 16 consecutive patients receiving SBRT for pathologically-proven and peripherally-located stage I NSCLC was reviewed. Fifteen patients were medically inoperable and one patient refused to undergo surgery. The median age of the patients was 76 years (range, 69-86). Treatment planning used four-dimensional computed tomography and fixed-field IMRT (n=11) or volumetric-modulated arc therapy (VMAT; n=5). The SBRT scheme was 48 Gy in four fractions (n=9) or 55 Gy in five fractions (n=7), delivered on consecutive days. The overall response rate at 6 months was 78.6%, including a complete response in three (21.4%) patients and a partial response in eight (57.1%). Three patients (21.4%) demonstrated a stable disease status. The median follow-up time was 14 months (range, 6-20) for the surviving patients. One patient developed local failure at 11 months, while another suffered from regional failure in a subcarinal lymph node at 4 months. Two patients did not survive within the first 6 months; one patient died during salvage chemotherapy for mediastinal lymph node metastasis and the other succumbed to a cause unrelated to lung cancer. The Kaplan-Meier estimates of local failure-free, progression-free and overall survival rates at 18 months were 91.0, 85.2 and 87.5%, respectively. The toxicity was mild; no severe (grade >/=3) toxicity was identified. IMRT-based (including VMAT) delivery of SBRT for patients with stage I NSCLC demonstrated favorable responses and local control without severe toxicity.
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[788]
TÍTULO / TITLE: - Non small cell carcinoma metastasis to meningioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Korean Neurosurg Soc. 2013 Jan;53(1):43-5. doi: 10.3340/jkns.2013.53.1.43. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 3340/jkns.2013.53.1.43
AUTORES / AUTHORS: - Kim KH; Hong EK; Lee SH; Yoo H
INSTITUCIÓN / INSTITUTION: - Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - “Tumor-to-tumor” metastasis is a rare event; meningioma has been reported as the most common primary intracranial tumor to harbor cancer metastases. Several hypotheses have been previously proposed to explain this occurrence, but the exact mechanism by which these metastases develop into meningiomas is not yet understood. Magnetic resonance imaging and spectroscopy have been valuable diagnostic tools, but preoperative diagnosis of metastasis to meningioma remains highly difficult. We present a case report of a metastasis of non-small cell lung cancer into an intracranial meningioma.
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[789]
TÍTULO / TITLE: - In Chemotherapy for Lung Cancer, Sometimes Less is More.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Natl Compr Canc Netw. 2013 Mar 1;11(3):232-5.
AUTORES / AUTHORS: - Roeland E; Loprinzi C; Moynihan TJ; Smith TJ; Temel J
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[790]
TÍTULO / TITLE: - Predictive and prognostic value of LPS-stimulated cytokine secretion in metastatic non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1021-5
AUTORES / AUTHORS: - Vlachostergios PJ; Gioulbasanis I; Ghosh S; Tsatsanis C; Papatsibas G; Xyrafas A; Hatzidaki E; Vasiliou C; Kamposioras K; Agelaki S; Margioris AN; Nasi D; Georgoulias V; Papandreou CN
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, Biopolis, Larissa, 41110, Greece, pvlacho@med.uth.gr.
RESUMEN / SUMMARY: - OBJECTIVE: Cancer patients usually develop malnutrition which may alter their innate immune system integrity. The aim of this study was to investigate the clinical relevance of chemokine response after lipopolysaccharide (LPS)-stimulation in metastatic non-small cell lung cancer (NSCLC). METHODS: Blood samples from metastatic NSCLC patients were incubated with LPS before the onset of systemic therapy. Interleukin (IL)-6 and IL-8 levels at baseline and after LPS-stimulation were measured and the fold change compared to baseline levels was evaluated as the stimulation index for each cytokine per patient. Results were correlated with sex, age, smoking status, histologic subtype, performance status (PS), albumin, Mini Nutritional Assessment (MNA) status and clinical outcomes. RESULTS: Totally 103 patients were evaluated. Mean (+/-SD) stimulation index was 37.6 (+/-57.8) for IL-6 and 76.7 (+/-133.4) for IL-8. The disease control rate after first-line chemotherapy was 44/80 (55 %) and the mean (+/-SD) progression-free survival (PFS) and overall survival (OS) were 4.2 (+/-3.9) and 9.2 (+/-1.1) months, respectively. MNA, PS, albumin, IL-6 and IL-8 stimulation indices were univariately associated with PFS and OS. IL-8 stimulation index emerged as an independent predictor of both PFS and OS, along with PS, and albumin levels. CONCLUSION: The extent of IL-6 and IL-8 stimulation after ex vivo induction with LPS is an important predictor of clinical outcome in metastatic NSCLC patients.
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[791]
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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[792]
TÍTULO / TITLE: - Simulated microgravity alters the metastatic potential of a human lung adenocarcinoma cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - In Vitro Cell Dev Biol Anim. 2013 Mar;49(3):170-7. doi: 10.1007/s11626-013-9581-9. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s11626-013-9581-9
AUTORES / AUTHORS: - Chang D; Xu H; Guo Y; Jiang X; Liu Y; Li K; Pan C; Yuan M; Wang J; Li T; Liu C
INSTITUCIÓN / INSTITUTION: - Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Beijing, 100853, China.
RESUMEN / SUMMARY: - Simulated microgravity (SM) has been implicated in affecting diverse cellular pathways. Although there is emerging evidence that SM can alter cellular functions, its effect in cancer metastasis has not been addressed. Here, we demonstrate that SM inhibits migration, gelatinolytic activity, and cell proliferation of an A549 human lung adenocarcinoma cell line in vitro. Expression of antigen MKI67 and matrix metalloproteinase-2 (MMP2) was reduced in A549 cells stimulated by clinorotation when compared with the 1xg control condition, while overexpression of each gene improves ability of proliferation and migration, respectively, under SM conditions. These findings suggest that SM reduced the metastatic potential of human lung adenocarcinoma cells by altering the expression of MKI67 and MMP2, thereby inhibiting cell proliferation, migration, and invasion, which may provide some clues to study cancer metastasis in the future.
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[793]
TÍTULO / TITLE: - Malignant pleural mesothelioma diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tuberc Respir Dis (Seoul). 2013 Feb;74(2):74-8. doi: 10.4046/trd.2013.74.2.74. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 4046/trd.2013.74.2.74
AUTORES / AUTHORS: - Kang B; Kim MA; Lee BY; Yoon H; Oh DK; Hwang HS; Choi C
INSTITUCIÓN / INSTITUTION: - Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - A 61-year-old woman came to the hospital with dyspnea and pleural effusion on chest radiography. She underwent repeated thoracentesis, transbronchial lung biopsy, bronchoalveolar lavage, and thoracoscopic pleural biopsy with talc pleurodesis, but diagnosis of her was uncertain. Positron emission tomography showed multiple lymphadenopathies, so she underwent endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes. Here, we report a case of malignant pleural mesothelioma that was eventually diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. This is an unusual and first case in Korea.
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[794]
TÍTULO / TITLE: - Migration of implanted markers for image-guided lung tumor stereotactic ablative radiotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Appl Clin Med Phys. 2013 Mar 4;14(2):4046. doi: 10.1120/jacmp.v14i2.4046.
AUTORES / AUTHORS: - Hong JC; Eclov NC; Yu Y; Rao AK; Dieterich S; Le QT; Diehn M; Sze DY; Loo BW Jr; Kothary N; Maxim PG
INSTITUCIÓN / INSTITUTION: - Stanford University. peter.maxim@stanford.edu.
RESUMEN / SUMMARY: - The purpose of this study was to quantify postimplantation migration of percutaneously implanted cylindrical gold seeds (“seeds”) and platinum endovascular embolization coils (“coils”) for tumor tracking in pulmonary stereotactic ablative radiotherapy (SABR). We retrospectively analyzed the migration of markers in 32 consecutive patients with computed tomography scans postimplantation and at simulation. We implanted 147 markers (59 seeds, 88 coils) in or around 34 pulmonary tumors over 32 procedures, with one lesion implanted twice. Marker coordinates were rigidly aligned by minimizing fiducial registration error (FRE), the root mean square of the differences in marker locations for each tumor between scans. To also evaluate whether single markers were responsible for most migration, we aligned with and without the outlier causing the largest FRE increase per tumor. We applied the resultant transformation to all markers. We evaluated migration of individual markers and FRE of each group. Median scan interval was 8 days. Median individual marker migration was 1.28 mm (interquartile range [IQR] 0.78-2.63 mm). Median lesion FRE was 1.56 mm (IQR 0.92-2.95 mm). Outlier identification yielded 1.03 mm median migration (IQR 0.52-2.21 mm) and 1.97 mm median FRE (IQR 1.44-4.32 mm). Outliers caused a mean and median shift in the centroid of 1.22 and 0.80 mm (95th percentile 2.52 mm). Seeds and coils had no statistically significant difference. Univariate analysis suggested no correlation of migration with the number of markers, contact with the chest wall, or time elapsed. Marker migration between implantation and simulation is limited and unlikely to cause geometric miss during tracking.
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[795]
TÍTULO / TITLE: - (18)F-misonidazole PET imaging of hypoxia in micrometastases and macroscopic xenografts of human non-small cell lung cancer: a correlation with autoradiography and histological findings.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Nucl Med Mol Imaging. 2013;3(2):142-53. Epub 2013 Mar 8.
AUTORES / AUTHORS: - Huang T; Civelek AC; Zheng H; Ng CK; Duan X; Li J; Postel GC; Shen B; Li XF
INSTITUCIÓN / INSTITUTION: - Department of Radiology, the 4th Hospital of Harbin Medical University Harbin, Heilongjiang, China ; Key Laboratory of Molecular Imaging, College of Heilongjiang Province Harbin, Heilongjiang, China ; Department of Diagnostic Radiology, University of Louisville School of Medicine Louisville, Kentucky USA.
RESUMEN / SUMMARY: - The objective of this study was to determine whether (18)F-misonidazole could detect hypoxia in macroscopic and microscopic tumors in mice. In nude mice, subcutaneous xenografts and peritoneal metastases were generated utilizing human non-small cell lung cancer A549 and HTB177 cells. Animals were co-injected with (18)F-misonidazole, pimonidazole and bromodeoxyuridine, and tumor perfusion was assessed by Hoechst 33342 injection. The intratumoral distribution of (18)F-misonidazole was determined by micro-PET scan and autoradiography. Pimonidazole, bromodeoxyuridine and Hoechst 33342 were detected by immunohistochemistry on the autoradiography sections. Submillimeter micrometastases found to be severely hypoxic. In both peritoneal metastases and subcutaneous xenografts models, PET images displayed significant (18)F-misonidazole uptake, and its distribution was non-uniform in these macroscopic subcutaneous tumors. In frozen sections, digital autoradiography and immunohistochemistry revealed similar distributions of (18)F-misonidazole, pimonidazole and glucose transporter-1, in both microscopic and macroscopic tumors. Bromodeoxyuridine stained-positive proliferative regions were well perfused, as judged by Hoechst 33342, and displayed low (18)F-misonidazole accumulation. (18)F-misonidazole uptake was low in tumor stroma and necrotic zones as well. Microscopic non-small cell lung cancer metastases are severely hypoxic. (18)F-misonidazole PET is capable to image hypoxia noninvasively not only in macroscopic tumors but also in micrometastases growing in mice. Accordingly, (18)F-misonidazole may be a promising agent to detect the burden of micrometastatic diseases.
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[796]
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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[797]
TÍTULO / TITLE: - VEGF and TSP1 levels correlate with prognosis in advanced non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-013-1020-6
AUTORES / AUTHORS: - Fleitas T; Martinez-Sales V; Vila V; Reganon E; Mesado D; Martin M; Gomez-Codina J; Montalar J; Reynes G
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Hospital Clinico Universitario de Valencia, Avda Blasco Ibanez 17, 46010, Valencia, España, tfleitask@gmail.com.
RESUMEN / SUMMARY: - PURPOSE: There is a need for biomarkers that may help in selecting the most effective anticancer treatments for each patient. We have investigated the prognostic value of a set of angiogenesis, inflammation and coagulation markers in patients treated for advanced non-small cell lung cancer. PATIENTS AND METHODS: Peripheral blood samples were obtained from 60 patients before first line platinum-based chemotherapy +/- bevacizumab, and after the third cycle of treatment. Blood samples from 60 healthy volunteers were also obtained as controls. Angiogenesis, inflammation and coagulation markers vascular endothelial growth factor (VEGF), their soluble receptors 1 (VEGFR1) and 2 (VEGFR2), thrombospondin-1 (TSP-1), interleukin-6 (IL6), sialic acid (SA) and tissue factor (TF) were quantified by ELISA. RESULTS: Except for TSP-1, pre- and post-treatment levels of all markers were higher in patients than in controls (p < 0.05). There was a positive and significant correlation between VEGF and VEGFR2 before treatment. VEGF also correlated with inflammatory markers IL-6 and SA. Moreover, there was a positive and significant correlation between levels of VEGFR1 and TF. Decreased levels of TSP-1 and increased levels of VEGF were associated with shorter survival. Bevacizumab significantly modified angiogenesis parameters and caused a decrease of VEGF and an increase of TSP-1. CONCLUSION: Angiogenesis, inflammation and coagulation markers were increased in NSCLC patients. Increased levels of VEGF and low levels of TSP-1 correlated with a poor prognosis.
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[798]
TÍTULO / TITLE: - Prognostic value of LIPC in non-small cell lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Feb 15;12(4):543-4. doi: 10.4161/cc.23677. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 4161/cc.23677
AUTORES / AUTHORS: - Alifano M; Damotte D
INSTITUCIÓN / INSTITUTION: - Deparment of Thoracic Surgery, Hopitaux Universitaires Paris Centre, AP-HP, Universite Paris Descartes, Paris, France. marco.alifano@htd.aphp.fr
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[799]
TÍTULO / TITLE: - The management of skin toxicity during erlotinib in advanced non-small cell lung cancer: how much does it cost?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cutan Ocul Toxicol. 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 3109/15569527.2013.765444
AUTORES / AUTHORS: - Giuliani J; Marzola M
INSTITUCIÓN / INSTITUTION: - Palliative Care Unit, Mater Salutis Hospital , Legnago (VR) , Italy and.
RESUMEN / SUMMARY: - Abstract Introduction: The aim of this study is to estimate the costs for the foreseeable management of skin toxicity (papulo-pustular reactions) in patients treated with erlotinib for non-small cell lung cancer (NSCLC) in order to value the direct medical economical impact. No studies like the above have been published until now. Materials and methods: We retrospectively analyzed all consecutive patients with NSCLC treated with erlotinib at Clinical Oncology Unit of University Hospital of Ferrara, Italy from June 2007 to May 2011. We evaluated severity and median duration of papulo-pustular reactions for each grade and we identified costs for the different therapeutic interventions. Results: We evaluated 25 patients. Median time follow-up was 18.65 months (range 5.69-88.36). Finally, follow-up 7 patients (28.0%) were alive with metastases and 18 patients (72.0%) were deceased. Nineteen patients (76.0%) developed papulo-pustular reactions: 2 patients (10.5%) mild rash, 11 patients (57.9%) moderate rash and 6 patients (31.6%) severe rash; no case of hospitalization was observed. Median duration of mild rash was 97 days (costs-range: 157.7-452.2 euro), median duration of moderate rash was 89 days (costs-range: 438.7-1035.6 euro) and median duration of severe rash was 34 days (costs-range: 460.3-1057.2 euro). Conclusions: Our experience, though the analysis of not selected case study, showed that management of skin toxicities related to erlotinib is not so expensive, especially for low grade; therefore, we also recommended to give particular attention to low grade of toxicities for reducing progression to high grade and consequent risk of hospitalization, which really impact on costs.
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[800]
TÍTULO / TITLE: - Secondary reactive oxygen species production after PDT during pulmonary tumor growth in sera of nude mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Photodiagnosis Photodyn Ther. 2013 Feb;10(1):62-71. doi: 10.1016/j.pdpdt.2012.05.004. Epub 2012 Jun 27.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pdpdt.2012.05.004
AUTORES / AUTHORS: - Douillard S; Rozec B; Bigot E; Aillet L; Patrice T
INSTITUCIÓN / INSTITUTION: - Departement Laser, Hopital Laennec, CHU de Nantes, 44093 Nantes, France.
RESUMEN / SUMMARY: - Photodynamic therapy (PDT), mediated by a sensitizer exposed to light to produce singlet oxygen (O), induces tumor responses varying from one person to another. Cancer growth induces oxidative stress at any step of its development from induction to treatment, which could also modify response to PDT. After the initial amount of O delivered, secondary oxidative species (SOS) are also generated inducing additional damages. Using an in vitro assay we saw variations among mice strains concerning their serum capability to generate SOS after O production. Nude mice had a higher capability to generate SOS as compared to the non mutated strain. Capability to generate SOS evolved during growth of orthotopically-grafted pulmonary cancers (A549), with either values corrected for hemolysis or not. Immediately after graft SOS production decreased, then increased again, reaching a plateau phase after 10 days which lasted for 20 days and finally increased steeply during the last phase of tumor growth, preceding cachexia and death. This profile differed profoundly from the one observed after heterotopic tumor grafts for which hemolysis induced artifacts masking important variations in SOS production. Our results demonstrate experimentally a relationship between the general health status of an individual, cancer progression and serum capability to generate SOS during PDT. These findings could explain some PDT failures as well as some unexpected successes on large tumors and should be taken into account when determining treatment parameters. They may also explain why different effects are observed on different experimental models with similar sensitizers.
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[801]
TÍTULO / TITLE: - NSCLC Brain Metastases Respond to Erlotinib and Radiation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar;3(3):OF8. doi: 10.1158/2159-8290.CD-RW2013-024. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-RW2013-024
RESUMEN / SUMMARY: - Erlotinib plus whole-brain radiotherapy improves survival in NSCLC patients with brain metastases.
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[802]
TÍTULO / TITLE: - A novel method for finding non-small cell lung cancer diagnosis biomarkers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Med Genomics. 2013;6 Suppl 1:S11. doi: 10.1186/1755-8794-6-S1-S11. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1186/1755-8794-6-S1-S11
AUTORES / AUTHORS: - Tran QN
INSTITUCIÓN / INSTITUTION: - Department of Computer Science, Lamar University, USA. qntran@lamar.edu
RESUMEN / SUMMARY: - BACKGROUND: One of the most common causes of worldwide cancer premature death is non-small cell lung carcinoma (NSCLC) with a very low survival rate of 8%-15%. Since patients with an early stage diagnosis can have up to four times the survival rate, discovering cost-effective biological markers that can be used to improve the diagnosis and prognosis of the disease is an important clinical challenge.In the last few years, significant progress has been made to address this challenge with identified biomarkers ranging from 5-gene signatures to 133-gene signatures. However, A typical molecular sub-classification method for lung carcinomas would have a low predictive accuracy of 68%-71% because datasets of gene-expression profiles typically have tens of thousands of genes for just few hundreds of patients. This type of datasets create many technical challenges impacting the accuracy of the diagnostic prediction. RESULTS: We discovered that a small set of nine gene-signatures (JAG1, MET, CDH5, ABCC3, DSP, ABCD3, PECAM1, MAPRE2 and PDF5) from the dataset of 12,600 gene-expression profiles of NSCLC acts like an inference basis for NSCLC lung carcinoma and hence can be used as genetic markers. This very small and previously unknown set of biological markers gives an almost perfect predictive accuracy (99.75%) for the diagnosis of the disease the sub-type of cancer. Furthermore, we present a novel method that finds genetic markers for sub-classification of NSCLC. We use generalized Lorenz curves and Gini ratios to overcome many challenges arose from datasets of gene-expression profiles. Our method discovers novel genetic changes that occur in lung tumors using gene-expression profiles. CONCLUSIONS: While proteins encoded by some of these gene-signatures (e.g., JAG1 and MAPRE2) have been showed to involve in the signal transduction of cells and proliferation control of normal cells, specific functions of proteins encoded by other gene-signatures have not yet been determined. Hence, this work opens new questions for structural and molecular biologists about the role of these gene-signatures for the disease.
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[803]
TÍTULO / TITLE: - Diagnostic Value of Circulating microRNAs for Lung Cancer: A Meta-Analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genet Test Mol Biomarkers. 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1089/gtmb.2012.0370
AUTORES / AUTHORS: - Shen Y; Wang T; Yang T; Hu Q; Wan C; Chen L; Wen F
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Biotherapy of China, Division of Pulmonary Diseases, Department of Respiratory Medicine, West China Hospital of Sichuan University , Chengdu, China .
RESUMEN / SUMMARY: - Background: Lung cancer is a leading cause of cancer mortality, and it shows a high incidence worldwide. Circulating microRNAs have been proposed as diagnostic indicators of lung cancer, but inconsistent results in the literature have prevented their widespread use in diagnosis. The present meta-analysis aimed to systematically evaluate the diagnostic accuracy of circulating microRNAs for lung cancer. Methods: Several research databases were searched systematically for studies of the accuracy of circulating microRNAs as diagnostic indicators of lung cancer. Results from different studies were pooled using random-effects models. Summary receiver operating characteristic (SROC) curves were used to assess the overall performance of microRNA-based assays. Results: Thirteen publications were included in the meta-analysis. The following summary estimates were obtained for the performance of circulating microRNAs in lung cancer diagnosis: sensitivity, 0.85 (95% confidence intervals [CI]: 0.83-0.87); specificity, 0.84 (95% CI: 0.81-0.86); positive likelihood ratio, 5.23 (95% CI: 3.75-7.29); negative likelihood ratio, 0.20 (95% CI: 0.14-0.27); and diagnostic odds ratio, 31.77 (95% CI: 16.98-59.42). The SROC curve indicated a maximum joint sensitivity and specificity of 0.85, with an area under the curve of 0.92. Conclusion: Circulating microRNAs show significant potential as diagnostic markers of lung cancer. The results of this meta-analysis justify larger, more rigorous studies to confirm such a diagnostic role.
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[804]
TÍTULO / TITLE: - Computer-aided diagnosis systems for lung cancer: challenges and methodologies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Biomed Imaging. 2013;2013:942353. doi: 10.1155/2013/942353. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/942353
AUTORES / AUTHORS: - El-Baz A; Beache GM; Gimel’farb G; Suzuki K; Okada K; Elnakib A; Soliman A; Abdollahi B
INSTITUCIÓN / INSTITUTION: - BioImaging Laboratory, Department of Bioengineering, University of Louisville, Louisville, KY 40292, USA.
RESUMEN / SUMMARY: - This paper overviews one of the most important, interesting, and challenging problems in oncology, the problem of lung cancer diagnosis. Developing an effective computer-aided diagnosis (CAD) system for lung cancer is of great clinical importance and can increase the patient’s chance of survival. For this reason, CAD systems for lung cancer have been investigated in a huge number of research studies. A typical CAD system for lung cancer diagnosis is composed of four main processing steps: segmentation of the lung fields, detection of nodules inside the lung fields, segmentation of the detected nodules, and diagnosis of the nodules as benign or malignant. This paper overviews the current state-of-the-art techniques that have been developed to implement each of these CAD processing steps. For each technique, various aspects of technical issues, implemented methodologies, training and testing databases, and validation methods, as well as achieved performances, are described. In addition, the paper addresses several challenges that researchers face in each implementation step and outlines the strengths and drawbacks of the existing approaches for lung cancer CAD systems.
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[805]
TÍTULO / TITLE: - Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56333. doi: 10.1371/journal.pone.0056333. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056333
AUTORES / AUTHORS: - Kayser G; Csanadi A; Otto C; Plones T; Bittermann N; Rawluk J; Passlick B; Werner M
INSTITUCIÓN / INSTITUTION: - Institute of Pathology, University Hospital Freiburg, Freiburg, Germany. gian.kayser@uniklinik-freiburg.de
RESUMEN / SUMMARY: - Histological subclassification of non-small cell lung cancer (NSCLC) has growing therapeutic impact. In advanced cancer stages tissue specimens are usually bioptically collected. These small samples are of extraordinary value since molecular analyses are gaining importance for targeted therapies. We therefore studied the feasibility, diagnostic accuracy, economic and prognostic effects of a tissue sparing simultaneous multi-antibody assay for subclassification of NSCLC. Of 265 NSCLC patients tissue multi arrays (TMA) were constructed to simulate biopsy samples. TMAs were stained by a simultaneous bi-color multi-antibody assay consisting of TTF1, Vimentin, p63 and neuroendocrine markers (CD56, chromogranin A, synaptophysin). Classification was based mainly on the current proposal of the IASLC with a hierarchical decision tree for subclassification into adenocarcinoma (LAC), squamous cell carcinoma (SCC), large cell neuroendocrine carcinoma (LCNEC) and NSCLC not otherwise specified. Investigation of tumor heterogeneity showed an explicit lower variation for immunohistochemical analyses compared to conventional classification. Furthermore, survival analysis of our combined immunohistochemical classification revealed distinct separation of each entity’s survival curve. This was statistically significant for therapeutically important subgroups (p = 0.045). As morphological and molecular cancer testing is emerging, our multi-antibody assay in combination with standardized classification delivers accurate and reliable separation of histomorphological diagnoses. Additionally, it permits clinically relevant subtyping of NSCLC including LCNEC. Our multi-antibody assay may therefore be of special value, especially in diagnosing small biopsies. It futher delivers substantial prognostic information with therapeutic consequences. Integration of immunohistochemical subtyping including investigation of neuroendocrine differentiation into standard histopathological classification of NSCLC must, therefore, be considered.
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[806]
TÍTULO / TITLE: - Ulcerative cutaneous lesions synchronously present with the diagnosis of primary lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Med. 2013;2013:136564. doi: 10.1155/2013/136564. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/136564
AUTORES / AUTHORS: - Shaheen K; Alraiyes AH; Baibars M; Paintsil A; Alraies MC
INSTITUCIÓN / INSTITUTION: - Department of Hospital Medicine, Institute of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH 44195, USA.
RESUMEN / SUMMARY: - The percentage of patients with lung cancer that develop skin metastases is low. The diagnosis is usually made using clinical information and skin biopsy in patients with suspicious skin lesions and history of smoking or lung cancer. The prognosis for patients having lung cancer with skin metastasis is very poor. We describe findings in a 70-year-old man with lung cancer with skin metastases. Interestingly, multiple skin lesions were the first manifestation of the underlying lung cancer. The prognosis for patients having lung cancer with skin metastasis is thus very poor.
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[807]
TÍTULO / TITLE: - Identification of driver mutations in lung cancer: first step in personalized cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Mar;8(1):3-14. doi: 10.1007/s11523-013-0263-z. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0263-z
AUTORES / AUTHORS: - Planchard D
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology (Thoracic Unit), Institut-Gustave-Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France, David.PLANCHARD@igr.fr.
RESUMEN / SUMMARY: - Non-small cell lung cancer (NSCLC) has recently been associated with interesting molecular characteristics that have important implications in carcinogenesis and response to targeted therapies. Targeted therapies, if given to a patient subpopulation enriched by the presence of relevant molecular targets, can often abrogate cell signaling that perpetuates cancer progression. For instance, several molecular alterations have been defined as “driver mutations,” such as mutations in EGFR and EML4-ALK fusion gene. Other key signaling pathways have also been identified as novel targets for lung cancer treatment. These first steps towards personalized medicine represent a shift in the management of NSCLC. Indeed, NSCLC should no longer be viewed as one common generic tumor but rather as a collection of more rare diseases with different biological behaviors and different sensitivities to targeted treatments. We are now clearly entering an era of personalized medicine for NSCLC cancers, and the development of molecular profiling technologies to assess DNA provides the potential to tailored medical care.
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[808]
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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[809]
TÍTULO / TITLE: - Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Feb 13. doi: 10.1002/cncy.21281.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21281
AUTORES / AUTHORS: - Mitiushkina NV; Iyevleva AG; Poltoratskiy AN; Ivantsov AO; Togo AV; Polyakov IS; Orlov SV; Matsko DE; Novik VI; Imyanitov EN
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
RESUMEN / SUMMARY: - BACKGROUND: Although the molecular analysis of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in archived lung cancer tissues is relatively well established, the genetic testing of cytological material has not yet become a routine. METHODS: The current study used cell samples that were obtained by bronchial brushing, transthoracic needle aspiration, or biopsy imprint preparation between 1993 and 2008. Islets of malignant cells were visually located on the archived cytological slides, lysed in situ by a drop of sodium dodecyl sulfate-containing buffer, and subjected to the standard DNA and RNA extraction. Examination of paraffin-embedded tissue blocks (resection specimens or biopsy material) from the same patients was performed in parallel. RESULTS: A total of 75 cytological/histological lung adenocarcinoma sample pairs underwent polymerase chain reaction analysis for the EGFR mutation. Two cytological samples and 1 morphological sample failed to produce DNA. Concordance for the wild-type and mutation status was observed in 54 of 72 and 14 of 72 informative pairs, respectively; 3 pairs and 1 pair, respectively, had mutation only in the cytological or histological material. The discrepancies could be explained by the failure to ensure a high percentage of lung cancer cells in the analyzed samples or, alternatively, by the genuine intratumoral molecular heterogeneity of some neoplasms. RNA extraction followed by reverse transcriptase-polymerase chain reaction analysis for the EML4-ALK translocation was performed for 44 EGFR mutation-negative sample pairs; failures were observed for 2 cytological and 6 histological specimens. All informative pairs were concordant either for the norm (32 of 36 pairs) or for the presence of EML4-ALK gene fusion (4 of 36 pairs). CONCLUSIONS: Archived cytological slides appear to be well suited both for EGFR and ALK analysis. Cancer (Cancer Cytopathol) 2013; © 2013 American Cancer Society.
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[810]
TÍTULO / TITLE: - The impact of decreasing cutoff values for maximal oxygen consumption (VO(2)max) in the decision-making process for candidates to lung cancer surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Dis. 2013 Feb;5(1):12-8. doi: 10.3978/j.issn.2072-1439.2012.12.04.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.12.04
AUTORES / AUTHORS: - Rocco G; Gatani T; Di Maio M; Meoli I; La Rocca A; Martucci N; La Manna C; Stefanelli F
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery and Oncology, Division of Thoracic Surgery and Service of Physiopathology, National Cancer Institute, Naples, Italy; ; Division of Respiratory Physiopathology, Monaldi Hospital, Naples, Italy.
RESUMEN / SUMMARY: - BACKGROUND: Maximal oxygen consumption (VO(2)max) is considered a decisive test for risk prediction in patients with borderline cardiopulmonary reserve. Guidelines have adopted decreasing VO(2)max cut-off values to define operability within acceptable mortality and morbidity limits. We wanted to investigate how the adoption of decreasing VO(2)max cut-off-values assessment contributed to better select lung surgery candidates. METHODS: One hundred and nineteen consecutive surgical candidates have been prospectively analyzed as a sample population. Preoperative work-up included spirometry and transfer factor (DLco); irrespective of the spirometric values, these patients were subjected to VO(2)max assessment. Surgical eligibility was decided by the same surgeon throughout the series. In the postoperative period, overall mortality and the occurrence of any, major or minor complications was recorded and graded according to the Common Terminology Criteria for Adverse Events v.4.3. RESULTS: Three arbitrary cut-offs were introduced at 15, 14 and 12 mL(.)kg(-1) (.)min(-1). Notably, 15 and 12 mL(.)kg(-1) (.)min(-1) correlated with percentage VO(2)max values of 50% and 35% of predicted (P<0.0001 and 0.0079), respectively. Accordingly, the patients were subdivided into groups in which the prevalence of postoperative morbidity was recorded. The groups were homogeneous as to age, BMI, preoperative absolute and percentage FEV1 and DLco. In the Cox proportionate-hazards multivariate analysis, VO(2)max less than 35% (P=0.0017) and CTCAE >2 (P=0.0457) emerged as significant predictors of survival after surgery. Conversely on logistic regression analysis, age over 70 years (P=0.03) and pneumonectomy (P=0.001), but not VO(2)max cut-off values, were significant predictors of major (CTCAE >2) morbidity. CONCLUSIONS: Since VO(2)max is increasingly used to contribute to risk prediction for the individual patient, surgeons need to be advised that the concept of a definitive, generalized cut-off value for VO(2)max is probably a contradiction in terms. Patient-specific VO(2)max values are more likely to contribute to risk assessment since they may reflect the primarily affected component among the determinants of maximal oxygen consumption. Whether patient-specific VO(2)max should be routinely used by surgeons to define operability for borderline patients needs further evaluation.
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[811]
TÍTULO / TITLE: - Down-regulation of canonical and up-regulation of non-canonical wnt signalling in the carcinogenic process of squamous cell lung carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57393. doi: 10.1371/journal.pone.0057393. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057393
AUTORES / AUTHORS: - Bartis D; Csongei V; Weich A; Kiss E; Barko S; Kovacs T; Avdicevic M; D’Souza VK; Rapp J; Kvell K; Jakab L; Nyitrai M; Molnar TF; Thickett DR; Laszlo T; Pongracz JE
INSTITUCIÓN / INSTITUTION: - Department of Medical Biotechnology, Institute of Immunology and Biotechnology, Medical School, University of Pecs, Pecs, Hungary ; Department of Medicine, Medical School, University of Birmingham, Birmingham, United Kingdom.
RESUMEN / SUMMARY: - The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of beta-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future.
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[812]
TÍTULO / TITLE: - Selumetinib: a promising pharmacologic approach for KRAS-mutant advanced non-small-cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Future Oncol. 2013 Feb;9(2):167-77. doi: 10.2217/fon.12.198.
●● Enlace al texto completo (gratuito o de pago) 2217/fon.12.198
AUTORES / AUTHORS: - Metro G; Chiari R; Baldi A; De Angelis V; Minotti V; Crino L
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori 1, 06156 Perugia, Italy.
RESUMEN / SUMMARY: - Selumetinib is a potent and selective inhibitor of MEK1 and 2 that is currently being clinically developed for the treatment of several human malignancies. Initially administered as free-base suspension, a more convenient Hyd-sulfate capsule formulation has recently been developed. Phase I studies revealed that acneiform dermatitis was the dose-limiting toxicity of both the free-base and capsule formulation given two-times a day at the maximum tolerated doses of 100 and 75 mg, respectively, with the capsule formulation resulting into a significantly higher drug bioavailability. Importantly, as a MEK inhibitor, selumetinib could be particularly effective in tumors with a hyperactivated Ras/Raf/MEK/ERK pathway, which might be the case of KRAS-mutant non-small-cell lung cancers (NSCLCs). Accordingly, a recent randomized Phase II study evaluating docetaxel plus selumetinib or placebo in KRAS-mutant pretreated advanced NSCLC patients has demonstrated a significant improvement in terms of response rate, progression-free survival and patient-reported outcomes in favor of the combination arm. These positive results support further clinical evaluation of selumetinib in NSCLC, and confirmatory ongoing and future trials will assess its role according to KRAS-mutation status and in combination regimens with other targeted agents.
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[813]
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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[814]
TÍTULO / TITLE: - Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pharm Biol. 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 3109/13880209.2012.761242
AUTORES / AUTHORS: - Kalpana Deepa Priya D; Gayathri R; Gunassekaran GR; Murugan S; Sakthisekaran D
INSTITUCIÓN / INSTITUTION: - Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras , Chennai, Tamil Nadu , India.
RESUMEN / SUMMARY: - Abstract Context: Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties. Objective: The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9 micromol/mouse/day) against B(a)P (100 mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice. Materials and methods: Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H(2)O(2)) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c. Results: SFN treatment was found to decrease the H(2)O(2) production (p < 0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p < 0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p < 0.01) and Bax (p < 0.001), respectively. Caspase-3 activity was also enhanced (p < 0.001) which leads to DNA fragmentation in SFN treated groups. Conclusion: Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.
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[815]
TÍTULO / TITLE: - Multigenic nature of the mouse pulmonary adenoma progression 1 locus.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Genomics. 2013 Mar 6;14:152. doi: 10.1186/1471-2164-14-152.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2164-14-152
AUTORES / AUTHORS: - Dassano A; Noci S; Galbiati F; Colombo F; Trincucci G; Pettinicchio A; Dragani TA; Manenti G
INSTITUCIÓN / INSTITUTION: - Department of Predictive and Preventive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Via Amadeo 42, Milan, 20133, Italy. tommaso.dragani@istitutotumori.mi.it.
RESUMEN / SUMMARY: - BACKGROUND: In an intercross between the SWR/J and BALB/c mouse strains, the pulmonary adenoma progression 1 (Papg1) locus on chromosome 4 modulates lung tumor size, one of several measures of lung tumor progression. This locus has not been fully characterized and defined in its extent and genetic content. Fine mapping of this and other loci affecting lung tumor phenotype is possible using recombinant inbred strains. RESULTS: A population of 376 mice, obtained by crossing mice of the SWR/J strain with CXBN recombinant inbred mice, was treated with a single dose of urethane and assayed for multiplicity of large lung tumors (N2lung). A genome-wide analysis comparing N2lung with 6364 autosomal SNPs revealed multiple peaks of association. The Papg1 locus had two peaks, at rs3654162 (70.574 Mb, -logP=2.8) and rs6209043 (86.606 Mb, -logP=2.7), joined by an interval of weaker statistical association; these data confirm the presence of Papg1 on chromosome 4 and reduce the mapping region to two stretches of ~6.8 and ~4.2 Mb, in the proximal and distal peaks, respectively. The distal peak included Cdkn2a, a gene already proposed as being involved in Papg1 function. Other loci possibly modulating N2lung were detected on chromosomes 5, 8, 9, 11, 15, and 19, but analysis for linkage disequilibrium of these putative loci with Papg1 locus suggested that only those on chromosomes 11 and 15 were true positives. CONCLUSIONS: These findings suggest that Papg1 consists, most likely, of two distinct, nearby loci, and point to putative additional loci on chromosomes 11 and 15 modulating lung tumor size. Within Papg1, Cdkn2a appears to be a strong candidate gene while additional Papg1 genes await to be identified. Greater knowledge of the genetic and biochemical mechanisms underlying the germ-line modulation of lung tumor size in mice is relevant to other species, including humans, in that it may help identify new therapeutic targets in the fight against tumor progression.
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[816]
TÍTULO / TITLE: - Induction of cytokines and growth factors by rapamycin in the microenvironment of brain metastases of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):953-958. Epub 2013 Jan 15.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1135
AUTORES / AUTHORS: - Kim SH; Lee JE; Yang SH; Lee SW
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Yonsei University College of Medicine, Seodaemun-gu, Seoul;
RESUMEN / SUMMARY: - The association between rapamycin and astrocytes in a tumor-bearing mouse model with brain metastases of non-small cell lung cancer (NSCLC) was investigated. For in vitro experiments, NCI-H358, a human lung adenocarcinoma cell line, was co-cultured with immortalized astrocytes, and treated with rapamycin, an mTOR inhibitor. We evaluated the expression of interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in tumor cells in vivo. Rapamycin is cytotoxic in vitro; however, co-culturing tumor cells and astrocytes induced tumor cell survival. IL-1, IL-3, IL-6, TNF-alpha, TGF-beta, PDGF, MCP-1 and MIP-1 expression were higher in rapamycin-treated mice compared to the control group, however, IGF-1 expression was lower. Notably, treatment with rapamycin before inoculating tumor cells affected cytokine expression in the tumor microenvironment. We suggest that growth factors and cytokines in the tumor microenvironment play a role in the survival of cancer cells in brain metastases.
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[817]
TÍTULO / TITLE: - Targeted Inhibition of the Molecular Chaperone Hsp90 Overcomes ALK Inhibitor Resistance in Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-12-0440
AUTORES / AUTHORS: - Sang J; Acquaviva J; Friedland JC; Smith DL; Sequeira M; Zhang C; Jiang Q; Xue L; Lovly CM; Jimenez JP; Shaw AT; Doebele RC; He S; Bates RC; Camidge DR; Morris SW; El-Hariry I; Proia DA
INSTITUCIÓN / INSTITUTION: - 1Synta Pharmaceuticals Corp., Lexington; 2Massachusetts General Hospital Cancer Center, Boston, Massachusetts; Departments of 3Pathology and 4Oncology, St. Jude Children’s Research Hospital, Memphis; 5Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine; 6Insight Genetics, Nashville; 7Morris Laboratories/HealthChart LLC, Memphis, Tennessee; and 8Division of Medical Oncology, University of Colorado Cancer Center, Aurora, Colorado.
RESUMEN / SUMMARY: - EML4-ALK gene rearrangements define a unique subset of patients with non-small cell lung carcinoma (NSCLC), and the clinical success of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib in this population has become a paradigm for molecularly targeted therapy. Here, we show that the Hsp90 inhibitor ganetespib induced loss of EML4-ALK expression and depletion of multiple oncogenic signaling proteins in ALK-driven NSCLC cells, leading to greater in vitro potency, superior antitumor efficacy, and prolonged animal survival compared with results obtained with crizotinib. In addition, combinatorial benefit was seen when ganetespib was used with other targeted ALK agents both in vitro and in vivo. Importantly, ganetespib overcame multiple forms of crizotinib resistance, including secondary ALK mutations, consistent with activity seen in a patient with crizotinib-resistant NSCLC. Cancer cells driven by ALK amplification and oncogenic rearrangements of ROS1 and RET kinase genes were also sensitive to ganetespib exposure. Taken together, these results highlight the therapeutic potential of ganetespib for ALK-driven NSCLC.
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[818]
TÍTULO / TITLE: - Thoracic computed tomography findings in malignant mesothelioma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Iran J Radiol. 2012 Nov;9(4):209-11. doi: 10.5812/iranjradiol.8764. Epub 2012 Nov 20.
●● Enlace al texto completo (gratuito o de pago) 5812/iranjradiol.8764
AUTORES / AUTHORS: - Tamer Dogan O; Salk I; Tas F; Epozturk K; Gumus C; Akkurt I; Levent Ozsahin S
INSTITUCIÓN / INSTITUTION: - Department of Chest Diseases, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey.
RESUMEN / SUMMARY: - BACKGROUND: Malignant pleural mesothelioma (MPM) is an uncommon neoplasm. MPM occurs more frequently in patients born or living in certain villages of Turkey. OBJECTIVES: We aimed to review radiological findings of MPM. PATIENTS AND METHODS: We reviewed the CT findings in 219 biopsy-proven MPM patients admitted to our clinic between 1993 and 2008. RESULTS: The most common CT findings included pleural thickening (n=197, 90%) classified as diffuse (n=138, 63%), nodular (n=49, 22%) and mass-type (n=16, 7%). Pleural effusion was found in 173 patients (79%), involvement of the interlobar fissures in 159 (73%), mediastinal pleural involvement in 170 (78%), volume contraction in 142 (65%), mediastinal shift in 102 (47%) and mediastinal lymphadenopathy in 54 (25%). CONCLUSION: MPM may present with diverse radiological features. Pleural thickening and pleural effusion were the most frequent radiological findings. Thoracic CT scans might be assessed more cautiously in patients with environmental exposure to asbestos.
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[819]
TÍTULO / TITLE: - Automated Delineation of Lung Tumors from CT Images Using a Single Click Ensemble Segmentation Approach.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pattern Recognit. 2013 Mar 1;46(3):692-702.
●● Enlace al texto completo (gratuito o de pago) 1016/j.patcog.2012.10.005
AUTORES / AUTHORS: - Gu Y; Kumar V; Hall LO; Goldgof DB; Li CY; Korn R; Bendtsen C; Velazquez ER; Dekker A; Aerts H; Lambin P; Li X; Tian J; Gatenby RA; Gillies RJ
INSTITUCIÓN / INSTITUTION: - Department of Imaging, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612. USA.
RESUMEN / SUMMARY: - A single click ensemble segmentation (SCES) approach based on an existing “Click&Grow” algorithm is presented. The SCES approach requires only one operator selected seed point as compared with multiple operator inputs, which are typically needed. This facilitates processing large numbers of cases. Evaluation on a set of 129 CT lung tumor images using a similarity index (SI) was done. The average SI is above 93% using 20 different start seeds, showing stability. The average SI for 2 different readers was 79.53%. We then compared the SCES algorithm with the two readers, the level set algorithm and the skeleton graph cut algorithm obtaining an average SI of 78.29%, 77.72%, 63.77% and 63.76% respectively. We can conclude that the newly developed automatic lung lesion segmentation algorithm is stable, accurate and automated.
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[820]
TÍTULO / TITLE: - Loss of the Keratin Cytoskeleton Is Not Sufficient to Induce Epithelial Mesenchymal Transition in a Novel KRAS Driven Sporadic Lung Cancer Mouse Model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57996. doi: 10.1371/journal.pone.0057996. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057996
AUTORES / AUTHORS: - Konig K; Meder L; Kroger C; Diehl L; Florin A; Rommerscheidt-Fuss U; Kahl P; Wardelmann E; Magin TM; Buettner R; Heukamp LC
INSTITUCIÓN / INSTITUTION: - Institute of Pathology, University of Cologne, Cologne, Germany.
RESUMEN / SUMMARY: - Epithelial-to-mesenchymal transition (EMT), the phenotypical change of cells from an epithelial to a mesenchymal type, is thought to be a key event in invasion and metastasis of adenocarcinomas. These changes involve loss of keratin expression as well as loss of cell polarity and adhesion. We here aimed to determine whether the loss of keratin expression itself drives increased invasion and metastasis in adenocarcinomas and whether keratin loss leads to the phenotypic changes associated with EMT. Therefore, we employed a recently described murine model in which conditional deletion of the Keratin cluster II by Cre-recombinase leads to the loss of the entire keratinmultiprotein family. These mice were crossed into a newly generated Cre-recombinase inducible KRAS-driven murine lung cancer model to examine the effect of keratin loss on morphology, invasion and metastasis as well as expression of EMT related genes in the resulting tumors. We here clearly show that loss of a functional keratin cytoskeleton did not significantly alter tumor morphology or biology in terms of invasion, metastasis, proliferation or tumor burden and did not lead to induction of EMT. Further, tumor cells did not induce synchronously expression of vimentin, which is often seen in EMT, to compensate for keratin loss. In summary, our data suggest that changes in cell shape and migration that underlie EMT are dependent on changes in signaling pathways that cause secondary changes in keratin expression and organization. Thus, we conclude that loss of the keratin cytoskeleton per se is not sufficient to causally drive EMT in this tumor model.
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[821]
TÍTULO / TITLE: - Mouse model for ROS1-rearranged lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56010. doi: 10.1371/journal.pone.0056010. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056010
AUTORES / AUTHORS: - Arai Y; Totoki Y; Takahashi H; Nakamura H; Hama N; Kohno T; Tsuta K; Yoshida A; Asamura H; Mutoh M; Hosoda F; Tsuda H; Shibata T
INSTITUCIÓN / INSTITUTION: - Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
RESUMEN / SUMMARY: - Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22-q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer.
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[822]
TÍTULO / TITLE: - Mouse models for lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Oncol. 2013 Apr;7(2):165-77. doi: 10.1016/j.molonc.2013.02.010. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2013.02.010
AUTORES / AUTHORS: - Kwon MC; Berns A
INSTITUCIÓN / INSTITUTION: - Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - Lung cancer is a devastating disease and a major therapeutic burden with poor survival rates. It is responsible for 30% of all cancer deaths. Lung cancer is strongly associated with smoking, although some subtypes are also seen in non-smokers. Tumors in the latter group are mostly adenocarcinomas with many carrying mutations in the epidermal growth factor receptor (EGFR). Survival statistics of lung cancer are grim because of its late detection and frequent local and distal metastases. Although DNA sequence information from tumors has revealed a number of frequently occurring mutations, affecting well-known tumor suppressor genes and proto-oncogenes, many of the driver mutations remain ill defined. This is likely due to the involvement of numerous rather infrequently occurring driver mutations that are difficult to distinguish from the very large number of passenger mutations detected in smoking-related lung cancers. Therefore, experimental model systems are indispensable to validate putative driver lesions and to gain insight into their mechanisms of action. Whereas a large fraction of these analyzes can be performed in cell cultures in vitro, in many cases the consequences of the mutations have to be assessed in the context of an intact organism, as this is the context in which the Mendelian selection process of the tumorigenic process took place and the advantages of particular mutations become apparent. Current mouse models for cancer are very suitable for this as they permit mimicking many of the salient features of human tumors. The capacity to swiftly re-engineer complex sets of lesions found in human tumors in mice enables us to assess the contribution of defined combinations of lesions to distinct tumor characteristics such as metastatic behavior and response to therapy. In this review we will describe mouse models of lung cancer and how they are used to better understand the disease and how they are exploited to develop better intervention strategies.
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[823]
TÍTULO / TITLE: - Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model; Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Immune Netw. 2012 Dec;12(6):269-76. doi: 10.4110/in.2012.12.6.269. Epub 2012 Dec 31.
●● Enlace al texto completo (gratuito o de pago) 4110/in.2012.12.6.269
AUTORES / AUTHORS: - Baek S; Lee SJ; Kim MJ; Lee H
INSTITUCIÓN / INSTITUTION: - Office of Biomedical Professors, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
RESUMEN / SUMMARY: - The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either CD34(+) hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-beta secretion were higher in SDC but CCR7 expression, IFN-gamma and IL-10 secretion were higher in MoDC. The proportion of CD11c(+)CD8a(+) cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-gamma secreting CD8(+) T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.
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[824]
TÍTULO / TITLE: - Regional differences in incidence of malignant mesothelioma in Denmark.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dan Med J. 2013 Mar;60(3):A4592.
AUTORES / AUTHORS: - Skammeritz E; Omland O; Hansen J; Johansen JP
INSTITUCIÓN / INSTITUTION: - Skovfaldet 2º, 8200 Aarhus N, Denmark. ellenskammeritz@gmail.com.
RESUMEN / SUMMARY: - INTRODUCTION: The incidence of malignant mesothelioma (MM) in Denmark has been rising rapidly since the 1950s. The aim of this study was to determine temporal developments of MM incidence and survival in Denmark as a whole and in the individual regions. MATERIAL AND METHODS: Data from the Danish Cancer Registry were used. Cases of MM of the pleura, peritoneum and pericardium occurring in the 1943-2009 period were included. National and regional incidence rates were calculated, age-standardised and stratified by various variables. Survival was calculated using Kaplan Meier plot. RESULTS: The total national incidence of MM for men has been rising throughout the period and reached its maximum of 1.76 in 2008-2009. For women, the incidence rate has remained relatively steady, with a maximum of 0.5 in 1973-1977. Since the late 1980s, the Region of Northern Jutland has had the highest male incidence rate. The difference in relative risk for men in the Region of Southern Denmark and the Region of Northern Jutland was 1.53 in 2008-2009, and the relative risk of developing MM in the Region of Northern Jutland for the entire period collectively compared with Denmark as a whole was 1.38. No notable regional difference exists for women. Survival has improved for both men and women, but remains poor with a median survival of 12.5 months for men and 13.3 months for women in 2008-2009. CONCLUSION: The national MM incidence for men continues to increase, perhaps showing a slight tendency towards deceleration in the most recent decade. A clear long-term effect of the Danish asbestos ban has not yet occurred. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
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[825]
TÍTULO / TITLE: - Alternative processing of the u2 small nuclear RNA produces a 19-22nt fragment with relevance for the detection of non-small cell lung cancer in human serum.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e60134. doi: 10.1371/journal.pone.0060134. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0060134
AUTORES / AUTHORS: - Mazieres J; Catherinne C; Delfour O; Gouin S; Rouquette I; Delisle MB; Prevot G; Escamilla R; Didier A; Persing DH; Bates M; Michot B
INSTITUCIÓN / INSTITUTION: - Service de Pneumologie, Hopital Larrey, CHU de Toulouse, Universite de Toulouse III (Paul Sabatier), Toulouse, France.
RESUMEN / SUMMARY: - RNU2 exists in two functional forms (RNU2-1 and RNU2-2) distinguishable by the presence of a unique 4-bases motif. Detailed investigation of datasets obtained from deep sequencing of five human lung primary tumors revealed that both forms express at a high rate a 19-22nt fragment (miR-U2-1 and -2) from its 3’ region and contains the 4-bases motif. Deep sequencing of independent pools of serum samples from healthy donors and lung cancer patients revealed that miR-U2-1 and -2 are pervasively processed in lung tissue by means of endonucleolytic cleavages and stably exported to the blood. Then, microarrays hybridization experiments of matched normal/tumor samples revealed a significant over-expression of miR-U2-1 in 14 of 18 lung primary tumors. Subsequently, qRT-PCR of miR-U2-1 using serum from 62 lung cancer patients and 96 various controls demonstrated that its expression levels identify lung cancer patients with 79% sensitivity and 80% specificity. miR-U2-1 expression correlated with the presence or absence of lung cancer in patients with chronic obstructive pulmonary disease (COPD), other diseases of the lung - not cancer, and in healthy controls. These data suggest that RNU2-1 is a new bi-functional ncRNA that produces a 19-22nt fragment which may be useful in detecting lung cancer non-invasively in high risk patients.
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[826]
TÍTULO / TITLE: - Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Res. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0437-T
AUTORES / AUTHORS: - Chaudhri VK; Salzler GG; Dick SA; Buckman MS; Sordella R; Karoly ED; Mohney R; Stiles BM; Elemento O; Altorki NK; McGraw TE
INSTITUCIÓN / INSTITUTION: - Weill Cornell Medical College.
RESUMEN / SUMMARY: - Cancer cells undergo a metabolic reprogramming but little is known about metabolic alterations of other cells within tumors. We use mass spectrometry-based profiling and a metabolic pathway-based systems analysis to compare 21 primary human lung tumor cancer-associated fibroblast lines (CAFs) to “normal” fibroblast lines (NFs) generated from adjacent non-neoplastic lung tissue. CAFs are pro-tumorigenic, although the mechanisms by which CAFs support tumors have not been elucidated. We have identified several pathways whose metabolite abundance globally distinguished CAFs from NFs, suggesting that metabolic alterations are not limited to cancer cells. In addition, we found metabolic differences between CAFs from high and low glycolytic tumors that might reflect distinct roles of CAFs related to the tumor’s glycolytic capacity. One such change was an increase of dipeptides in CAFs. Dipeptides primarily arise from the breakdown of proteins. We found in CAFs an increase in basal macroautophagy which likely accounts for the increase in dipeptides. Furthermore, we demonstrate a difference between CAFs and NFs in the induction of autophagy promoted by reduced glucose. In sum, our data suggest increased autophagy may account for metabolic differences between CAFs and NFs and may play additional as yet undetermined roles in lung cancer.
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[827]
TÍTULO / TITLE: - A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55596. doi: 10.1371/journal.pone.0055596. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055596
AUTORES / AUTHORS: - Kim SC; Jung Y; Park J; Cho S; Seo C; Kim J; Kim P; Park J; Seo J; Kim J; Park S; Jang I; Kim N; Yang JO; Lee B; Rho K; Jung Y; Keum J; Lee J; Han J; Kang S; Bae S; Choi SJ; Kim S; Lee JE; Kim W; Kim J; Lee S
INSTITUCIÓN / INSTITUTION: - Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
RESUMEN / SUMMARY: - BACKGROUND: Deep sequencing techniques provide a remarkable opportunity for comprehensive understanding of tumorigenesis at the molecular level. As omics studies become popular, integrative approaches need to be developed to move from a simple cataloguing of mutations and changes in gene expression to dissecting the molecular nature of carcinogenesis at the systemic level and understanding the complex networks that lead to cancer development. RESULTS: Here, we describe a high-throughput, multi-dimensional sequencing study of primary lung adenocarcinoma tumors and adjacent normal tissues of six Korean female never-smoker patients. Our data encompass results from exome-seq, RNA-seq, small RNA-seq, and MeDIP-seq. We identified and validated novel genetic aberrations, including 47 somatic mutations and 19 fusion transcripts. One of the fusions involves the c-RET gene, which was recently reported to form fusion genes that may function as drivers of carcinogenesis in lung cancer patients. We also characterized gene expression profiles, which we integrated with genomic aberrations and gene regulations into functional networks. The most prominent gene network module that emerged indicates that disturbances in G2/M transition and mitotic progression are causally linked to tumorigenesis in these patients. Also, results from the analysis strongly suggest that several novel microRNA-target interactions represent key regulatory elements of the gene network. CONCLUSIONS: Our study not only provides an overview of the alterations occurring in lung adenocarcinoma at multiple levels from genome to transcriptome and epigenome, but also offers a model for integrative genomics analysis and proposes potential target pathways for the control of lung adenocarcinoma.
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[828]
TÍTULO / TITLE: - Changes in the Secretory Profile of NSCLC-Associated Fibroblasts after Ablative Radiotherapy: Potential Impact on Angiogenesis and Tumor Growth.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Transl Oncol. 2013 Feb;6(1):66-74. Epub 2013 Feb 1.
AUTORES / AUTHORS: - Hellevik T; Pettersen I; Berg V; Bruun J; Bartnes K; Busund LT; Chalmers A; Bremnes R; Martinez-Zubiaurre I
INSTITUCIÓN / INSTITUTION: - Department of Oncology, University Hospital of Northern Norway, Tromso, Norway.
RESUMEN / SUMMARY: - In the context of radiotherapy, collateral effects of ablative doses of ionizing radiation (AIR) on stromal components of tumors remains understudied. In this work, cancer-associated fibroblasts (CAFs) isolated from freshly resected human lung tumors were exposed to AIR (1x 18 Gy) and analyzed for their release of paracrine factors. Inflammatory mediators and regulators of angiogenesis and tumor growth were analyzed by multiplex protein assays in conditioned medium (CM) from irradiated and non-irradiated CAFs. Additionally, the profile of secreted proteins was examined by proteomics. In functional assays, effects of CAF-CM on proliferative and migratory capacity of lung tumor cells (H-520/H-522) and human umbilical vein endothelial cells (HUVECs) and their tube-forming capacity were assessed. Our data show that exposure of CAFs to AIR results in 1) downregulated release of angiogenic molecules such as stromal cell-derived factor-1, angiopoietin, and thrombospondin-2 (TSP-2); 2) upregulated release of basic fibroblast growth factor from most donors; and 3) unaffected expression levels of hepatocyte growth factor, interleukin-6 (IL-6), IL-8, IL-1beta, and tumor necrosis factor-alpha. CM from irradiated and control CAFs did not affect differently the proliferative or migratory capacity of tumor cells (H-520/H-522), whereas migratory capacity of HUVECs was partially reduced in the presence of irradiated CAF-CM. Overall, we conclude that AIR mediates a transformation on the secretory profile of CAFs that could influence the behavior of other cells in the tumor tissue and hence guide therapeutic outcomes. Downstream consequences of the changes observed in this study merits further investigations.
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[829]
TÍTULO / TITLE: - Late recurrence of benign multicystic peritoneal mesothelioma complicated with an incisional hernia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Surg. 2013;2013:903795. doi: 10.1155/2013/903795. Epub 2013 Mar 7.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/903795
AUTORES / AUTHORS: - Canbay E; Ishibashi H; Sako S; Kitai T; Nishino E; Yonemura Y
INSTITUCIÓN / INSTITUTION: - NPO to Support Peritoneal Dissemination Treatment, 1-26, Harukimotomachi, Kishiwada City, Osaka 596-0032, Japan ; Department of General Surgery, Kishiwada Tokushukai Hospital, 4-27-1 Kamori-Cho, Kishiwada City, Osaka 596-8522, Japan ; Department of General Surgery, Kocaeli-Derince Education and Research Hospital, Kocaeli 41900, Turkey.
RESUMEN / SUMMARY: - Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease arising from the peritoneal mesothelium. Here, we report a 57-year-old woman admitted to our unit with an incisional hernia fifteen years later following her first operation due to BMPM. Computerized tomography demonstrated a cystic appearing mass with intraabdominal extension in hernia sac. The patient underwent en bloc resection of the mass and hernia repair. An immunohistochemical analysis of the mass confirmed the recurrence of BMPM. Our case supports that BMPM has slowly progressive nature and can recur with complicated incisional hernia long time after primary resection. Diagnosis and long-term followup are crucial for clarifying the characteristics of this disease.
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[830]
TÍTULO / TITLE: - Antibody repertoire in paraneoplastic cerebellar degeneration and small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e60438. doi: 10.1371/journal.pone.0060438. Epub 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0060438
AUTORES / AUTHORS: - Sabater L; Hoftberger R; Boronat A; Saiz A; Dalmau J; Graus F
INSTITUCIÓN / INSTITUTION: - Service of Neurology, Hospital Clinic, Universitat de Barcelona and Institut d Investigacio Biomedica August Pi i Sunyer (IDIBAPS), Barcelona, España.
RESUMEN / SUMMARY: - The goal of this study is to determine whether patients with paraneoplastic cerebellar degeneration (PCD) and small-cell lung cancer (SCLC) have a specific repertoire of antibodies, if SOX1 antibodies (SOX1-ab) can predict the presence of SCLC, and if antibodies to cell surface antigens occur in this syndrome. Antibody analysis was done using immunohistochemistry on rat brain, immunoblot with recombinant antigens, screening of cDNA expression libraries, and immunolabeling of live neurons in 39 patients with PCD and SCLC. VGCC-ab were measured by RIA, and SOX1-ab, Hu-ab, and ZIC4-ab by immunoblot. Lambert-Eaton myastenic syndrome (LEMS) was present in 10 of 23 patients with electrophysiological studies. At least one antibody was detected in 72% of patients. The individual frequencies were: 49% SOX1-ab, 44% VGCC-ab, 31% Hu-ab, and 13% ZIC4-ab. SOX1-ab occurred in 76% of patients with VGCC-ab and 27% of those without VGCC-ab (p = 0.0036). SOX1-ab were not found in 39 patients with sporadic late-onset cerebellar ataxia, 23 with cerebellar ataxia and glutamic acid decarboxylase antibodies, and 73 with PCD and cancer types other than SCLC (31 without onconeural antibodies, 25 with Yo-ab , 17 with Tr-ab). Five patients (13%) had antibodies against unknown neuronal cell surface antigens but none of them improved with immunotherapy. One serum immunoreacted against the axon initial segment of neurons and another serum against ELKS1, a protein highly expressed in the cerebellum that interacts with the beta4-subunit of the VGCC. In conclusion, 72% of patients with PCD and SCLC had one or more antibodies that indicate the presence of this tumor. In these patients, VGCC-ab and SOX1-ab occur tightly associated. SOX1-ab are predictors of SCLC in ataxia patients with a specificity of 100% and sensitivity of 49%. Unlike limbic encephalitis with SCLC, antibodies to cell surface antigens other than VGCC-ab, are infrequent and do not predict response to treatment.
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[831]
TÍTULO / TITLE: - Synthesis and characterization of some novel fatty acid analogues: a preliminary investigation on their activity against human lung carcinoma cell line.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lipids Health Dis. 2013 Mar 28;12(1):45.
●● Enlace al texto completo (gratuito o de pago) 1186/1476-511X-12-45
AUTORES / AUTHORS: - Jubie S; Dhanabal P; Afzal Azam M; Muruganantham N; Kalirajan R; Elango K
RESUMEN / SUMMARY: - BACKGROUND: Preparation of some novel heterocyclic compounds with long alkyl and alkenyl chain of cytotoxic activity. METHOD: Gamma linolenic acid, a poly unsaturated fatty acid and stearic acid, a saturated fatty acid were isolated from the microalga Spirulina platensis. Some novel gamma linolenic acid and stearic acid analogues having 1,3,4-oxadiazole and 1,2,4-triazole were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Cytotoxicity of these compounds was evaluated by the growth inhibition of A-549 cells in-vitro. RESULTS: Compound 1 and 3 showed comparable cytotoxicity against the human lung carcinoma A-549 cell lines.
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[832]
TÍTULO / TITLE: - The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 15;13:77. doi: 10.1186/1471-2407-13-77.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-77
AUTORES / AUTHORS: - Shingyoji M; Iizasa T; Higashiyama M; Imamura F; Saruki N; Imaizumi A; Yamamoto H; Daimon T; Tochikubo O; Mitsushima T; Yamakado M; Kimura H
INSTITUCIÓN / INSTITUTION: - Division of Thoracic Diseases, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba, 260-8717, Japan. mshingyoji@chiba-cc.jp.
RESUMEN / SUMMARY: - BACKGROUND: We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. METHODS: Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). RESULTS: High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. CONCLUSIONS: These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer.
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[833]
TÍTULO / TITLE: - Nutrition Habits, Physical Activity, and Lung Cancer: An Authoritative Review.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lung Cancer. 2013 Jan 30. pii: S1525-7304(12)00267-7. doi: 10.1016/j.cllc.2012.12.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cllc.2012.12.002
AUTORES / AUTHORS: - Koutsokera A; Kiagia M; Saif MW; Souliotis K; Syrigos KN
INSTITUCIÓN / INSTITUTION: - Amalia Fleming General Hospital, Athens, Greece.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer death worldwide. Because of high incidence rates and low survival rates, it is important to study the risk factors that may help prevent the disease from developing. It has been well established that cigarette smoking is the most important risk factor for lung cancer. Nonetheless it is likely that there are other modifiable risk factors that would assist in the prevention of lung cancer. Research on factors such as nutrition and physical activity and their influence on lung cancer has been carried out for nearly 3 decades. A systematic review in the MEDLINE database of published studies was conducted, focusing on systematic reviews, meta-analyses, and large prospective studies. The association between physical activity and lung cancer has been conflicting. Among the researched studies, 10 showed an inverse association, whereas 11 reported no association. A meta-analysis that was conducted from 1996 to October 2003 showed that leisure physical activity (LPA) prevents lung cancer. Data from 11 cohort and case-control studies showed an inverse relationship between fruit and vegetable consumption and lung cancer. Evidence from case-control studies suggests a positive association between meat intake and risk of lung cancer, although several more recent studies have presented doubts about these findings. The possible association of physical activity, nutrition, and the risk of lung cancer development remains controversial. Further prospective studies should be conducted to determine the potential influence of these 2 risk factors.
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[834]
TÍTULO / TITLE: - Successful pneumonectomy for invasive pulmonary aspergillosis and advanced non-small cell-lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - British Medical J (BMJ). Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista bmj.com/search.dtl
●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Mar 14;2013. pii: bcr2012007925. doi: 10.1136/bcr-2012-007925.
●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007925
AUTORES / AUTHORS: - Minesaki S; Koyama N; Ishida H; Kobayashi K
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka-shi, Saitama, Japan.
RESUMEN / SUMMARY: - Aspergillus spp. is a pathogenic fungus in patients with malignancy, immunosuppression or respiratory diseases, and invasive pulmonary aspergillosis (IPA) caused by its infection is an aggressive and often lethal disorder. We report a case of non-small-cell lung cancer (NSCLC) where pneumonectomy concomitantly enabled radical cure of the underlying disease and IPA against which different antifungal drugs had been ineffective. In a patient with locally advanced NSCLC that progressed despite chemoradiation, radiation pneumonitis and subsequently cavitary disease developed following the administration of corticosteroids. Based upon the isolation of Aspergillus spp. from sputum, a diagnosis of IPA was made and since the latter was refractory to multiple antifungal drugs, pneumonectomy was undertaken which resulted in successful treatment of both NSCLC and IPA. Surgical intervention should be considered as a therapeutic option for IPA complicating NSCLC that is refractory to medical management.
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[835]
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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[836]
TÍTULO / TITLE: - Erlotinib resistance in lung cancer: current progress and future perspectives.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Pharmacol. 2013;4:15. doi: 10.3389/fphar.2013.00015. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 3389/fphar.2013.00015
AUTORES / AUTHORS: - Tang J; Salama R; Gadgeel SM; Sarkar FH; Ahmad A
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine Detroit, MI, USA.
RESUMEN / SUMMARY: - Lung cancer is the most common cancer in the world. Despite modern advancements in surgeries, chemotherapies, and radiotherapies over the past few years, lung cancer still remains a very difficult disease to treat. This has left the death rate from lung cancer victims largely unchanged throughout the past few decades. A key cause for the high mortality rate is the drug resistance that builds up for patients being currently treated with the chemotherapeutic agents. Although certain chemotherapeutic agents may initially effectively treat lung cancer patients, there is a high probability that there will be a reoccurrence of the cancer after the patient develops resistance to the drug. Erlotinib, the epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitor, has been approved for localized as well as metastatic non-small cell lung cancer where it seems to be more effective in patients with EGFR mutations. Resistance to erlotinib is a common observation in clinics and this review details our current knowledge on the subject. We discuss the causes of such resistance as well as innovative research to overcome it. Evidently, new chemotherapy strategies are desperately needed in order to better treat lung cancer patients. Current research is investigating alternative treatment plans to enhance the chemotherapy that is already offered. Better insight into the molecular mechanisms behind combination therapy pathways and even single molecular pathways may help improve the efficacy of the current treatment options.
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[837]
TÍTULO / TITLE: - Morphologic analysis of pulmonary neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Korean J Pathol. 2013 Feb;47(1):16-20. doi: 10.4132/KoreanJPathol.2013.47.1.16. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 4132/KoreanJPathol.2013.47.1.16
AUTORES / AUTHORS: - Lee SS; Kang M; Ha SY; An J; Roh MS; Ha CW; Han J
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Gachon University School of Medicine, Incheon, Korea.
RESUMEN / SUMMARY: - BACKGROUND: Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis. METHODS: Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes. RESULTS: The mean nuclear area was 0.318+/-0.101 microm(2) in typical carcinoid tumors, 0.326+/-0.119 microm(2) in atypical carcinoid tumors, 0.314+/-0.107 microm(2) in small cell carcinomas, and 0.446+/-0.145 microm(2) in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268+/-0.600 microm in typical carcinoid tumors, 2.408+/-0.680 microm in atypical carcinoid tumors, 2.158+/-0.438 microm in small cell carcinomas, and 3.247+/-1.276 microm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001). CONCLUSIONS: Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.
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[838]
TÍTULO / TITLE: - Paraneoplastic neurological syndrome as an initial indicator of small cell carcinoma of the lung.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - British Medical J (BMJ). Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista bmj.com/search.dtl
●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Feb 6;2013. pii: bcr2012008432. doi: 10.1136/bcr-2012-008432.
●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008432
AUTORES / AUTHORS: - Porto L; Miranda M; Gomes A; Andre R; Rodrigues B
INSTITUCIÓN / INSTITUTION: - Internal Medicine Department, Centro Hospitalar Tondela-Viseu, Viseu, Portugal. leneaporto@gmail.com
RESUMEN / SUMMARY: - Paraneoplastic syndromes are indirect manifestations of cancer due to functional peptides/hormones produced by a tumour, or due to cross reactivity between tumour and host antigens. Here the case of a 58-year-old woman presenting with ataxia, paraesthesia and subacute and progressive loss of vision is reported. The patient exhibited strong serum positivity for anti-Hu and anti-CV2 antibodies, and a chest CT scan showed a hypodense nodule in proximity of the right upper lobe bronchus and an enlarged ipsilateral paratracheal lymph node that was not visible on a lung x-ray. Histopathological examination of a biopsy specimen from this lymph node showed that small cell carcinoma of the lung was present. The patient’s deficits were subsequently diagnosed as three coexisting paraneoplastic neurological syndromes (PNSs): subacute cerebellar ataxia, sensory neuropathy and retinopathy, respectively. Although rare, PNSs can be the first manifestations of cancer, and their rapid recognition facilitates an early treatment.
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[839]
TÍTULO / TITLE: - Nonsmall cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Respir Rev. 2013 Mar 1;22(127):33-6. doi: 10.1183/09059180.00007012.
●● Enlace al texto completo (gratuito o de pago) 1183/09059180.00007012
AUTORES / AUTHORS: - Sculier JP
INSTITUCIÓN / INSTITUTION: - Universite Libre de Bruxelles (ULB), Institut Jules Bordet, Service des Soins Intensifs et Urgences Oncologiques, Brussels, Belgium.
RESUMEN / SUMMARY: - The objective of this review is to report the Clinical Year in Review proceedings in the field of nonsmall cell lung cancer that were presented at the 2012 European Respiratory Society Congress in Vienna, Austria. Various topics were reviewed, including epidemiology, screening, diagnosis, treatment, prognosis, and palliative and end of life care.
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[840]
TÍTULO / TITLE: - Tracheal replacement for primary tracheal cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Opin Otolaryngol Head Neck Surg. 2013 Apr;21(2):171-7. doi: 10.1097/MOO.0b013e32835e212b.
●● Enlace al texto completo (gratuito o de pago) 1097/MOO.0b013e32835e212b
AUTORES / AUTHORS: - Haag JC; Jungebluth P; Macchiarini P
INSTITUCIÓN / INSTITUTION: - Division of Ear, Nose, and Throat, Department of Clinical Science, Intervention and Technology (CLINTEC), Advanced Center of Translational Regenerative Medicine, Karolinska Institutet, University Hospital, Stockholm, Sweden.
RESUMEN / SUMMARY: - PURPOSE OF REVIEW: To summarize the so far applied clinical methods of tracheal replacement, comparing pros and cons of conventional and tissue-engineered approaches. RECENT FINDINGS: Several strategies have been most recently described to replace the trachea-like aortic homografts, allotransplantation, and tissue engineering. Allotransplantation requires lifelong immunosuppression and this may be ethically questioned being not a lifesaving procedure. Tissue-engineered tracheal transplantation has been clinically applied using biological or bioartificial tubular or bifurcated scaffolds reseeded with mesenchymal stromal cells, and bioactive molecules boosting regeneration and promoting neovascularization. SUMMARY: Tracheal tissue engineering may be a promising alternative to conventional allotransplantation in adults and children. Different methods have been developed and are currently under active clinical investigation, and await long-term results.
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[841]
TÍTULO / TITLE: - Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Oncol. 2013;2013:240164. doi: 10.1155/2013/240164. Epub 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/240164
AUTORES / AUTHORS: - Storey R; Joh J; Kwon A; Jenson AB; Ghim SJ; Kloecker GH
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
RESUMEN / SUMMARY: - Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV’s possible etiologic link to NSCLC by evaluating an immune response to HPV’s oncogene, E7, in patients with NSCLC. Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive. Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC.
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[842]
TÍTULO / TITLE: - Phenotypes and karyotypes of human malignant mesothelioma cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58132. doi: 10.1371/journal.pone.0058132. Epub 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058132
AUTORES / AUTHORS: - Relan V; Morrison L; Parsonson K; Clarke BE; Duhig EE; Windsor MN; Matar KS; Naidoo R; Passmore L; McCaul E; Courtney D; Yang IA; Fong KM; Bowman RV
INSTITUCIÓN / INSTITUTION: - UQ Thoracic Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia ; Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Queensland, Australia.
RESUMEN / SUMMARY: - BACKGROUND: Malignant mesothelioma is an aggressive tumour of serosal surfaces most commonly pleura. Characterised cell lines represent a valuable tool to study the biology of mesothelioma. The aim of this study was to develop and biologically characterise six malignant mesothelioma cell lines to evaluate their potential as models of human malignant mesothelioma. METHODS: Five lines were initiated from pleural biopsies, and one from pleural effusion of patients with histologically proven malignant mesothelioma. Mesothelial origin was assessed by standard morphology, Transmission Electron Microscopy (TEM) and immunocytochemistry. Growth characteristics were assayed using population doubling times. Spectral karyotyping was performed to assess chromosomal abnormalities. Authentication of donor specific derivation was undertaken by DNA fingerprinting using a panel of SNPs. RESULTS: Most of cell lines exhibited spindle cell shape, with some retaining stellate shapes. At passage 2 to 6 all lines stained positively for calretinin and cytokeratin 19, and demonstrated capacity for anchorage-independent growth. At passage 4 to 16, doubling times ranged from 30-72 hours, and on spectral karyotyping all lines exhibited numerical chromosomal abnormalities ranging from 41 to 113. Monosomy of chromosomes 8, 14, 22 or 17 was observed in three lines. One line displayed four different karyotypes at passage 8, but only one karyotype at passage 42, and another displayed polyploidy at passage 40 which was not present at early passages. At passages 5-17, TEM showed characteristic features of mesothelioma ultrastructure in all lines including microvilli and tight intercellular junctions. CONCLUSION: These six cell lines exhibit varying cell morphology, a range of doubling times, and show diverse passage-dependent structural chromosomal changes observed in malignant tumours. However they retain characteristic immunocytochemical protein expression profiles of mesothelioma during maintenance in artificial culture systems. These characteristics support their potential as in vitro model systems for studying cellular, molecular and genetic aspects of mesothelioma.
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[843]
TÍTULO / TITLE: - Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers—a potential determinant of susceptibility to multiple malignancies.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Clin Exp Pathol. 2013;6(3):395-410. Epub 2013 Feb 15.
AUTORES / AUTHORS: - Arai H; Okudela K; Oshiro H; Komitsu N; Mitsui H; Nishii T; Tsuboi M; Nozawa A; Noishiki Y; Ohashi K; Inui K; Masuda M
INSTITUCIÓN / INSTITUTION: - Yokohama City University Medical Center, Yokohama, Japan. hiromasa@jg7.so-net.ne.jp
RESUMEN / SUMMARY: - The present study evaluated the potential clinicopathologic significance of elevated microsatellite alteration at selected tetra-nucleotide (EMAST) in non-small cell lung cancer (NSCLC). Sixty-five NSCLCs (19 squamous cell carcinomas, 39 adenocarcinomas, one adenosquamous cell carcinoma, and 6 large cell carcinomas) were examined for EMAST in the ten selected tetra-nucleotide markers. Traditional microsatellite instability (MSI) in the five mono- or di-nucleotide markers of the Bethesda panel was also examined, and compared with EMAST. The incidence of EMAST was higher than that of traditional MSI, as 64.6% (42/65) and 12.3% (8/65) tumors respectively exhibited EMAST and traditional MSI in at least one marker. EMAST and traditional MSI appear to occur independently, as no significant association in their incidence was found (Fisher’s exact test, P = 0.146). Subjects who exhibited EMAST in two or more markers had a significantly higher incidence of history of other malignant neoplasms (42.9% [9/21]), compared to those with less than two markers (16.3% [7/43] (Chi-square test, P = 0.021)). Taken together, impairment of molecular machinery for maintaining stable replication of the tetra-nucleotide-repeating regions, which would differ from machinery for mono- or di-nucleotide-repeating regions, may elevate susceptibility to NSCLCs and certain neoplastic diseases. Elucidation of the potential molecular mechanism of EMAST is expected to lead to a discovery of a novel genetic background determining susceptibility to NSCLC and other multiple neoplasms. This is the first report describing a clinicopathologic significance of EMAST in NSCLC.
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[844]
TÍTULO / TITLE: - MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Death Dis. 2013 Mar 14;4:e544. doi: 10.1038/cddis.2013.71.
●● Enlace al texto completo (gratuito o de pago) 1038/cddis.2013.71
AUTORES / AUTHORS: - Grosso S; Doyen J; Parks SK; Bertero T; Paye A; Cardinaud B; Gounon P; Lacas-Gervais S; Noel A; Pouyssegur J; Barbry P; Mazure NM; Mari B
INSTITUCIÓN / INSTITUTION: - 1] Institut de Pharmacologie Moleculaire et Cellulaire (IPMC), Centre National de la Recherche Scientifique, CNRS UMR 7275, Sophia Antipolis, France [2] University of Nice Sophia-Antipolis, Nice, France.
RESUMEN / SUMMARY: - The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional mode of hypoxia-inducible factor (HIF)-dependent transcriptional regulation, involving modulation of a specific set of micro RNAs (miRNAs), including miR-210, has emerged. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. Therefore, we hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed a non-small cell lung carcinoma (NSCLC)-derived cell line (A549) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). The miR-210-expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. Cells were subjected to radiation levels ranging from 0 to 10 Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of radioresistance as control cells in hypoxia. Under hypoxia, pmiR-210 cells showed a low mortality rate owing to a decrease in apoptosis, with an ability to grow even at 10 Gy. This miR-210 phenotype was reproduced in another NSCLC cell line (H1975) and in HeLa cells. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we have shown that genomic double-strand breaks (DSBs) foci disappear faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells removed the radioresistant phenotype, showing that this mechanism is dependent on HIF-1. In conclusion, miR-210 appears to be a component of the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could be used by tumor cells in conditions where reoxygenation has occurred and suggests that strategies targeting miR-210 could enhance tumor radiosensitization.
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[845]
TÍTULO / TITLE: - Targeted Resequencing Reveals ALK Fusions in Non-Small Cell Lung Carcinomas Detected by FISH, Immunohistochemistry, and Real-Time RT-PCR: A Comparison of Four Methods.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:757490. doi: 10.1155/2013/757490. Epub 2013 Jan 20.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/757490
AUTORES / AUTHORS: - Tuononen K; Sarhadi VK; Wirtanen A; Ronty M; Salmenkivi K; Knuuttila A; Remes S; Telaranta-Keerie AI; Bloor S; Ellonen P; Knuutila S
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Haartman Institute, University of Helsinki, P.O. Box 21 (Haartmaninkatu 3), 00014 Helsinki, Finland.
RESUMEN / SUMMARY: - Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements occur in a subgroup of non-small cell lung carcinomas (NSCLCs). The identification of these rearrangements is important for guiding treatment decisions. The aim of our study was to screen ALK gene fusions in NSCLCs and to compare the results detected by targeted resequencing with results detected by commonly used methods, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcription-PCR (RT-PCR). Furthermore, we aimed to ascertain the potential of targeted resequencing in detection of ALK-rearranged lung carcinomas. We assessed ALK fusion status for 95 formalin-fixed paraffin-embedded tumor tissue specimens from 87 patients with NSCLC by FISH and real-time RT-PCR, for 57 specimens from 56 patients by targeted resequencing, and for 14 specimens from 14 patients by IHC. All methods were performed successfully on formalin-fixed paraffin-embedded tumor tissue material. We detected ALK fusion in 5.7% (5 out of 87) of patients examined. The results obtained from resequencing correlated significantly with those from FISH, real-time RT-PCR, and IHC. Targeted resequencing proved to be a promising method for ALK gene fusion detection in NSCLC. Means to reduce the material and turnaround time required for analysis are, however, needed.
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[846]
TÍTULO / TITLE: - Synergistic interaction between cisplatin and PARP inhibitors in non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Mar 15;12(6):877-83. doi: 10.4161/cc.24034. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 4161/cc.24034
AUTORES / AUTHORS: - Michels J; Vitale I; Senovilla L; Enot DP; Garcia P; Lissa D; Olaussen KA; Brenner C; Soria JC; Castedo M; Kroemer G
INSTITUCIÓN / INSTITUTION: - U848; INSERM; Villejuif, France; Institut Gustave Roussy; Villejuif, France; Faculte de Medecine; Universite Paris Sud/Paris XI; Le Kremlin Bicetre, France.
RESUMEN / SUMMARY: - The antineoplastic agent cis-diammineplatinum(II) dichloride (cisplatin, CDDP) is part of the poorly effective standard treatment of non-small cell lung carcinoma (NSCLC). Here, we report a novel strategy to improve the efficacy of CDDP. In conditions in which CDDP alone or either of two PARP inhibitors, PJ34 hydrochloride hydrate or CEP 8983, used as standalone treatments were inefficient in killing NSCLC cells, the combination of CDDP plus PJ34 or that of CDDP plus CEP 8983 were found to kill a substantial fraction of the cells. This cytotoxic synergy could be recapitulated by combining CDDP and the siRNA-mediated depletion of the principal PARP isoform, PARP1, indicating that it is mediated by on-target effects of PJ34 or CEP 8983. CDDP and PARP inhibitors synergized in inducing DNA damage foci, mitochondrial membrane permeabilization leading to cytochrome c release, and dissipation of the inner transmembrane potential, caspase activation, plasma membrane rupture and loss of clonogenic potential in NSCLC cells. Collectively, our results indicate that CDDP can be advantageously combined with PARP inhibitors to kill several NSCLC cell lines, independently from their p53 status. Combined treatment with CDDP and PARP inhibitors elicits the intrinsic pathway of apoptosis.
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[847]
TÍTULO / TITLE: - Oligometastases/Oligo-recurrence of lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pulm Med. 2013;2013:438236. doi: 10.1155/2013/438236. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/438236
AUTORES / AUTHORS: - Niibe Y; Chang JY; Onishi H; Salama J; Hiraki T; Yamashita H
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Kanagawa, Sagamihara 252-0374, Japan.
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[848]
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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[849]
TÍTULO / TITLE: - Development of a biosensor for detection of pleural mesothelioma cancer biomarker using surface imprinting.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57681. doi: 10.1371/journal.pone.0057681. Epub 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057681
AUTORES / AUTHORS: - Mathur A; Blais S; Goparaju CM; Neubert T; Pass H; Levon K
INSTITUCIÓN / INSTITUTION: - Department of Chemical and Biological Sciences, Polytechnic Institute of NYU, Brooklyn, New York, United States of America.
RESUMEN / SUMMARY: - Hyaluronan-linked protein 1 (HAPLN1) which has been shown to be highly expressed in malignant pleural mesotheliomas (MPM), was detected in serum using an electrochemical surface-imprinting method. First, the detection method was optimized using Bovine serum albumin (BSA) as a model protein to mimic the optimal conditions required to imprint the similar molecular weight protein HAPLN1. BSA was imprinted on the gold electrode with hydroxyl terminated alkane thiols, which formed a self-assembled monolayer (SAM) around BSA. The analyte (BSA) was then washed away and its imprint (empty cavity with shape-memory) was used for detection of BSA in a solution, using electrochemical open-circuit potential method, namely potentiometry. Factors considered to optimize the conditions include incubation time, protein concentration, limit of detection and size of electrode. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to confirm selectivity of imprints. With the obtained imprinting control parameters, HAPLN1 was imprinted in duplicate and the detection of spiked HAPLN1 was successfully conducted in serum.
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[850]
TÍTULO / TITLE: - A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Mar 21;12(8).
AUTORES / AUTHORS: - Edmond V; Merdzhanova G; Gout S; Brambilla E; Gazzeri S; Eymin B
INSTITUCIÓN / INSTITUTION: - INSERM; U823; Equipe 2 Bases Moleculaires de la Progression des Cancers du Poumon; Grenoble, France; Universite Joseph Fourier; Institut Albert Bonniot; Grenoble, France.
RESUMEN / SUMMARY: - The transcription factor E2F1 belongs to the E2F family and plays a crucial role during cell cycle progression and apoptosis. Ser/Arg-Rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. We previously identified the SR protein SRSF2 as a new transcriptional target of E2F1 and demonstrated that both proteins cooperate to induce apoptosis in non-small cell lung carcinoma. In this study, we postulated that SRSF2 is also involved in the proliferative functions of E2F1. Using IHC, we first demonstrate that SRSF2 and its phosphorylated form (P-SRSF2) are overexpressed in neuroendocrine lung tumors that are highly proliferative tumors expressing high levels of E2F1. Importantly, we show a direct correlation between cyclin E, an E2F1-target gene controlling S phase, and P-SRSF2 proteins levels (p = 0.0083), suggesting a role of SRSF2 in E2F1-mediated cellular proliferation. Accordingly, using neuroendocrine lung carcinoma cell lines, we demonstrate that SRSF2 is a cell cycle-regulated protein involved in entry and progression into S phase. We also provide evidence that SRSF2 interacts with E2F1 and stimulates its transcriptional control of cell cycle target genes such as cyclin E. Finally, we show that inhibition of AKT signaling pathway prevents SRSF2 phosphorylation and activity toward E2F1 transcriptional function. Taken together, these results identify a new role of SRSF2 in the control of cell cycle progression and reinforce the functional link between SRSF2 and E2F1 proteins.
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[851]
TÍTULO / TITLE: - Klotho sensitizes human lung cancer cell line to cisplatin via PI3k/Akt pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57391. doi: 10.1371/journal.pone.0057391. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057391
AUTORES / AUTHORS: - Wang Y; Chen L; Huang G; He D; He J; Xu W; Zou C; Zong F; Li Y; Chen B; Wu S; Zhao W; Wu J
INSTITUCIÓN / INSTITUTION: - Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
RESUMEN / SUMMARY: - Klotho was first identified in 1997 and has been considered as an anti-aging gene. Emerging evidence demonstrates that klotho has a close relationship with cancers, including lung cancer, breast cancer, etc, by inhibiting the proliferation and promoting apoptosis of cancer cells. Cisplatin has been the most widely used drug in the first-line chemotherapy. However, the increase in cisplatin-resistant cancer cells has become a major obstacle in clinical management of cancers. In our study, we for the first time demonstrated that klotho could attenuate the resistance of lung cancer to cisplatin based chemotherapy and the apoptosis of the resistant cells with klotho overexpression was markedly increased. However, klotho knockdown cells showed enhanced resistance to chemotherapy. Further analysis showed that inhibition of PI3K/Akt pathway with specific inhibitor (LY294002) attenuated the promotive effects on cancer growth following interfering with klotho shRNA. Moreover, we demonstrated that klotho modulated the resistance to cisplatin in a xenograft nude mice model. These observations suggested that klotho could improve the resistance of lung cancer cells to chemotherapy and may serve as a potential target for the gene therapy of lung cancers resistant to cisplatin based chemotherapy.
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[852]
TÍTULO / TITLE: - Right lower lobectomy eight years after left pneumonectomy for a second primary lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cardiothorac Surg. 2013 Mar 15;8:46. doi: 10.1186/1749-8090-8-46.
●● Enlace al texto completo (gratuito o de pago) 1186/1749-8090-8-46
AUTORES / AUTHORS: - Liu Y; Cui P; Yang Z; Zhang P; Guo R; Shao G
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, First Hospital of Jilin University, Changchun, Jilin Province, 130021, PR of China. guoguangshao@sohu.com.
RESUMEN / SUMMARY: - Lobectomy for second primary lung cancer in a patient with previous pneumonectomy is seldom done because most such patients either have inadequate pulmonary reserve or metastatic disease at other sites. This is different than when this type of surgery is done for benign disease where the lobe to be resected is already non functional. We report a case where successful right lower lobectomy for a second primary lung cancer was carried out in a 53 year old man who had had a left pneumonectomy eight years before. We conclude that, although this type of approach can be worthwhile, surgeons must be cautious and selective before doing so.
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[853]
TÍTULO / TITLE: - Synovial metastasis from lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Proc (Bayl Univ Med Cent). 2013 Jan;26(1):25-7.
AUTORES / AUTHORS: - Levine HR; Tingle E; Carter B; Dockery D
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Baylor University Medical Center at Dallas.
RESUMEN / SUMMARY: - Intraarticular masses are infrequently encountered in clinical practice; however, the differential diagnosis can be broad. Neoplasia, both benign and malignant, and proliferative processes are the most common etiologies. We present a case of metastatic disease in the synovium in a patient with a history of lung cancer. Lung carcinoma is the most common primary malignancy to metastasize to synovial tissue, and the knee joint is the most common joint to be affected.
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[854]
TÍTULO / TITLE: - Lung cancer associated with neurofibromatosis type I.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Radiol. 2013;2013:869793. doi: 10.1155/2013/869793. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/869793
AUTORES / AUTHORS: - Oikonomou A; Mikroulis D; Mintzopoulou P; Lukman L; Prassopoulos P
INSTITUCIÓN / INSTITUTION: - Department of Radiology, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
RESUMEN / SUMMARY: - Lung cancer associated with neurofibromatosis type I is considered very rare, and only a few case reports have been described in the literature. There is some evidence that a genetic linkage between neurofibromatosis and carcinogenesis in the lung may exist. We present a 42-year-old female, lifetime nonsmoker with a known history of neurofibromatosis type I, free of respiratory symptoms, who underwent a low-dose HRCT of the lungs to investigate any occult interstitial lung changes. A solitary ill-defined nodule of a ground-glass opacity was detected incidentally in the middle lobe with no associated lymphadenopathy or metastatic disease. Several thin-walled lung cysts were also seen in the lower lobes. Histological analysis of the nodule after middle lobectomy revealed well-differentiated adenocarcinoma. The patient did not receive systemic chemotherapy or radiotherapy. She was free of disease on 18-month followup.
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[855]
TÍTULO / TITLE: - Pulmonary metastasis of a papillary thyroid carcinoma and primary lung adenocarcinoma: two coincident carcinomas at the same location.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Feb 16;8:26. doi: 10.1186/1746-1596-8-26.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-26
AUTORES / AUTHORS: - Xue L; Luan Z; Liu Y; Zou S; Jiang J; Wu N; Lu N; Lin D
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. nlu03@126.com.
RESUMEN / SUMMARY: - Tumor-to-tumor metastasis is a fairly rare phenomenon. The lung cancers are the most common donors, but are exceedingly rare as recipients. Here we report a case of a lung adenocarcinoma acting as the recipient of papillary thyroid carcinoma, with multiple spreading foci of the two cancers in the lung simultaneously. The morphology and immunohistochemisty (Napsin-A, Thyroglobulin) are very important in differential diagnosis of lung primary adenocarcinoma and metastatic papillary thyroid carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/2069496615891134.
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[856]
TÍTULO / TITLE: - Nucleotide and phylogenetic analysis of human papillomavirus types 6 and 11 isolated from recurrent respiratory papillomatosis in Brazil.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Infect Genet Evol. 2013 Mar 1;16C:282-289. doi: 10.1016/j.meegid.2012.12.033.
●● Enlace al texto completo (gratuito o de pago) 1016/j.meegid.2012.12.033
AUTORES / AUTHORS: - de Matos RP; Sichero L; Mansur IM; do Bonfim CM; Bittar C; Nogueira RL; Kupper DS; Valera FC; Nogueira ML; Villa LL; Calmon MF; Rahal P
INSTITUCIÓN / INSTITUTION: - UNESP - Sao Paulo State University, IBILCE, Institute of Bioscience, Language & Literature and Exact Science, Department of Biology, Rua Cristovao Colombo 2265, Bairro Jardim Nazareth, CEP 15054-010, Sao Jose do Rio Preto, Sao Paulo, Brazil. Electronic address: renatapram@hotmail.com.
RESUMEN / SUMMARY: - There are few studies about the distribution of natural molecular variants of low-risk HPVs. Our aim was to evaluate the E6 early gene variability among HPV-6 and HPV-11 isolates detected in recurrent respiratory papillomatosis (RRP) samples obtained in a cohort of Brazilian patients. We also performed a phylogenetic analysis in order to compare nucleotide sequences identified in our study with previously reported isolates from different anatomic sites (laryngeal papillomas, genital warts, cervical cancer and anal swabs) obtained from other parts of the world to determine the phylogenetic relationships of variants detected in Brazil. The complete coding region of the E6 gene of 25 samples was cloned and sequenced: 18 isolates of HPV-6 (72%) and 7 isolates of HPV-11 (28%). A total of four different HPV-6 genomic variants and two HPV-11 genomic variants was identified. It was not possible to correlate specific variants with disease severity. Phylogenetic trees for both HPV types were constructed enclosing both E6 sequences detected in our study and formerly published sequences. In both phylogenetic trees, the sequences from Brazil did not group together. We could not establish a geographical association between HPV-6 or HPV-11 variants, unlike HPV-16 and HPV-18.
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[857]
TÍTULO / TITLE: - Automatic Segmentation of Lung Carcinoma Using 3D Texture Features in 18-FDG PET/CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Imaging. 2013;2013:980769. doi: 10.1155/2013/980769. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/980769
AUTORES / AUTHORS: - Markel D; Caldwell C; Alasti H; Soliman H; Ung Y; Lee J; Sun A
INSTITUCIÓN / INSTITUTION: - Medical Physics Unit, University of McGill, Montreal, QC, Canada H3A 0G4.
RESUMEN / SUMMARY: - Target definition is the largest source of geometric uncertainty in radiation therapy. This is partly due to a lack of contrast between tumor and healthy soft tissue for computed tomography (CT) and due to blurriness, lower spatial resolution, and lack of a truly quantitative unit for positron emission tomography (PET). First-, second-, and higher-order statistics, Tamura, and structural features were characterized for PET and CT images of lung carcinoma and organs of the thorax. A combined decision tree (DT) with K-nearest neighbours (KNN) classifiers as nodes containing combinations of 3 features were trained and used for segmentation of the gross tumor volume. This approach was validated for 31 patients from two separate institutions and scanners. The results were compared with thresholding approaches, the fuzzy clustering method, the 3-level fuzzy locally adaptive Bayesian algorithm, the multivalued level set algorithm, and a single KNN using Hounsfield units and standard uptake value. The results showed the DTKNN classifier had the highest sensitivity of 73.9%, second highest average Dice coefficient of 0.607, and a specificity of 99.2% for classifying voxels when using a probabilistic ground truth provided by simultaneous truth and performance level estimation using contours drawn by 3 trained physicians.
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[858]
- CASTELLANO -
TÍTULO / TITLE:Histoplasmose simulando neoplasia primaria de pulmao ou metastases pulmonares.
TÍTULO / TITLE: - Histoplasmosis mimicking primary lung cancer or pulmonary metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Bras Pneumol. 2013 Feb;39(1):63-68.
AUTORES / AUTHORS: - Dall Bello AG; Severo CB; Guazzelli LS; Oliveira FM; Hochhegger B; Severo LC
INSTITUCIÓN / INSTITUTION: - Laboratorio de Micologia, Irmandade Santa Casa de Misericordia de Porto Alegre, Porto Alegre, RS, Brasil.
RESUMEN / SUMMARY: - OBJECTIVE: To describe the main clinical and radiological characteristics of patients with histoplasmosis mimicking lung cancer. METHODS: This was a retrospective descriptive study based on the analysis of the medical records of the 294 patients diagnosed with histoplasmosis between 1977 and 2011 at the Mycology Laboratory of the Santa Casa Sisters of Mercy Hospital of Porto Alegre in the city of Porto Alegre, Brazil. The diagnosis of histoplasmosis was established by culture, histopathological examination, or immunodiffusion testing (identification of M or H precipitation bands). After identifying the patients with macroscopic lesions, as well as radiological and CT findings consistent with malignancy, we divided the patients into two groups: those with a history of cancer and presenting with lesions mimicking metastases (HC group); and those with no such history but also presenting with lesions mimicking metastases (NHC group). RESULTS: Of the 294 patients diagnosed with histoplasmosis, 15 had presented with lesions mimicking primary neoplasia or metastases (9 and 6 in the HC and NHC groups, respectively). The age of the patients ranged from 13 to 67 years (median, 44 years). Of the 15 patients, 14 (93%) presented with pulmonary lesions at the time of hospitalization. CONCLUSIONS: The clinical and radiological syndrome of neoplastic disease is not confined to malignancy, and granulomatous infectious diseases must therefore be considered in the differential diagnosis.
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[859]
TÍTULO / TITLE: - Fibrosing mediastinitis mimicking bronchogenic carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Thorac Dis. 2013 Feb;5(1):E5-7. doi: 10.3978/j.issn.2072-1439.2012.07.03.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2072-1439.2012.07.03
AUTORES / AUTHORS: - Koksal D; Bayiz H; Mutluay N; Koyuncu A; Demirag F; Dagli G; Berktas B; Berkoglu M
INSTITUCIÓN / INSTITUTION: - Chest Diseases Clinic, Ataturk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey.
RESUMEN / SUMMARY: - Fibrosing mediastinitis is a rare but benign disorder characterized by an excessive fibrotic reaction in the mediastinum which can result in compromise of airways, great vessels, and other mediastinal structures. In this paper we presented a patient with fibrosing mediastinitis mimicking bronchogenic carcinoma. The patient was a 32-year-old diabetic male admitting with cough and hemoptysis. There was a right hilar mass and multiple mediastinal conglomerated lymph nodes on chest computed tomography. Positron emission tomography with computed tomography (PET/CT) scan demonstrated increased fluorodeoxyglucose (FDG) uptake at the right hilar mass lesion and mediastinal lymph nodes. Fiberoptic bronchoscopy showed mucosal distortion of right upper lobe. Pathologic examination of the mucosal biopsy revealed inflammation. Endobronchial ultrasound guided transbronchial needle and cervical mediastinoscopic lymph node biopsies were undiagnostic. Diagnostic thoracotomy confirmed the diagnosis fibrosing mediastinitis. Administration of six months of systemic corticosteroid and antituberculous therapy was not beneficial. In conclusion, despite being a rare clinical entity, fibrosing mediastinitis should be kept in mind in the differential diagnosis of mediastinal mass lesions of unknown etiology. The diagnosis is exceptionally difficult in the presence of atypical radiological findings. The treatment is particularly challenging without any proven effective therapy.
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[860]
TÍTULO / TITLE: - Automated localization and segmentation of lung tumor from PET-CT thorax volumes based on image feature analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Conf Proc IEEE Eng Med Biol Soc. 2012;2012:5384-7. doi: 10.1109/EMBC.2012.6347211.
●● Enlace al texto completo (gratuito o de pago) 1109/EMBC.2012.6347211
AUTORES / AUTHORS: - Cui H; Wang X; Feng D
INSTITUCIÓN / INSTITUTION: - Biomedical and Multimedia Information Technology (BMIT) research group, School of Information Technologies, The University of Sydney, Australia. hcui7511@uni.sydney.edu.au
RESUMEN / SUMMARY: - Positron emission tomography - computed tomography (PET-CT) plays an essential role in early tumor detection, diagnosis, staging and treatment. Automated and more accurate lung tumor detection and delineation from PET-CT is challenging. In this paper, on the basis of quantitative analysis of contrast feature of PET volume in SUV (standardized uptake value), our method firstly automatically localized the lung tumor. Then based on analysing the surrounding CT features of the initial tumor definition, our decision strategy determines the tumor segmentation from CT or from PET. The algorithm has been validated on 20 PET-CT studies involving non-small cell lung cancer (NSCLC). Experimental results demonstrated that our method was able to segment the tumor when adjacent to mediastinum or chest wall, and the algorithm outperformed the other five lung segmentation methods in terms of overlapping measure.
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[861]
TÍTULO / TITLE: - A mathematical model for microRNA in lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e53663. doi: 10.1371/journal.pone.0053663. Epub 2013 Jan 24.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0053663
AUTORES / AUTHORS: - Kang HW; Crawford M; Fabbri M; Nuovo G; Garofalo M; Nana-Sinkam SP; Friedman A
INSTITUCIÓN / INSTITUTION: - Mathematical Biosciences Institute, Ohio State University, Columbus, Ohio, United States of America.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer-related deaths worldwide. Lack of early detection and limited options for targeted therapies are both contributing factors to the dismal statistics observed in lung cancer. Thus, advances in both of these areas are likely to lead to improved outcomes. MicroRNAs (miRs or miRNAs) represent a class of non-coding RNAs that have the capacity for gene regulation and may serve as both diagnostic and prognostic biomarkers in lung cancer. Abnormal expression patterns for several miRNAs have been identified in lung cancers. Specifically, let-7 and miR-9 are deregulated in both lung cancers and other solid malignancies. In this paper, we construct a mathematical model that integrates let-7 and miR-9 expression into a signaling pathway to generate an in silico model for the process of epithelial mesenchymal transition (EMT). Simulations of the model demonstrate that EGFR and Ras mutations in non-small cell lung cancers (NSCLC), which lead to the process of EMT, result in miR-9 upregulation and let-7 suppression, and this process is somewhat robust against random input into miR-9 and more strongly robust against random input into let-7. We elected to validate our model in vitro by testing the effects of EGFR inhibition on downstream MYC, miR-9 and let-7a expression. Interestingly, in an EGFR mutated lung cancer cell line, treatment with an EGFR inhibitor (Gefitinib) resulted in a concentration specific reduction in c-MYC and miR-9 expression while not changing let-7a expression. Our mathematical model explains the signaling link among EGFR, MYC, and miR-9, but not let-7. However, very little is presently known about factors that regulate let-7. It is quite possible that when such regulating factors become known and integrated into our model, they will further support our mathematical model.
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[862]
TÍTULO / TITLE: - EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Feb 23;13(1):19. doi: 10.1186/1475-2867-13-19.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-19
AUTORES / AUTHORS: - Satoh M; Takemura Y; Hamada H; Sekido Y; Kubota S
INSTITUCIÓN / INSTITUTION: - Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan. kubota.s787@gmail.com.
RESUMEN / SUMMARY: - Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. We studied whether a green tea polyphenol, epigallocathechin-3-gallate (EGCG), could induce cell death in five human mesothelioma cell lines. We found that EGCG induced apoptosis in all five mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism. EGCG induced reactive oxygen species (ROS), and impaired the mitochondrial membrane potential. As treatment with ROS scavengers, catalase and tempol, significantly inhibited the EGCG-induced apoptosis, ROS is considered to be responsible for the EGCG-induced apoptosis. Further, we found that EGCG induced autophagy, and that when autophagy was suppressed by chloroquine, the EGCG-induced cell death was enhanced. Taken together, these results suggest that EGCG has a great potential for the treatment of mesothelioma by inducing apoptosis and autophagy.
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[863]
TÍTULO / TITLE: - Modeling NSCLC Progression: Recent Advances and Opportunities Available.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - AAPS J. 2013 Apr;15(2):542-50. doi: 10.1208/s12248-013-9461-y. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1208/s12248-013-9461-y
AUTORES / AUTHORS: - Suleiman AA; Nogova L; Fuhr U
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology, University Hospital of Cologne, Gleueler Strasse 24, 50931, Cologne, Germany, ahmed.suleiman@uk-koeln.de.
RESUMEN / SUMMARY: - Non-small cell lung cancer (NSCLC) is one of the leading causes of death around the world with an estimated 5-year relative survival rate of 16% at diagnosis. Development of drugs treating NSCLC is not easy, and the success rate for an anticancer treatment to pass through the whole clinical development process is as low as 5%. Modeling and simulation lend themselves as tools which can potentially streamline drug development. A critical component of the models developed is a description of how the disease progresses over time and how a treatment would affect its trajectory. Our aim was to review the literature to present the models and growth functions which have been used for describing NSCLC dynamics, and how anticancer treatments can affect such dynamics, both in animals and in humans. Only a limited set of models were identified for such a purpose. Most of the models which have been used were descriptive of tumor growth, yet there were attempts to account for the underlying processes, especially in animals where it is more feasible to collect data needed for developing such models. Moreover, we discuss how modeling and simulation can aid in decision making across the different stages of drug development. Based on some encouraging results from trials of other cancer types where modeling tumor dynamics has played an important role, we propose further exploration of NSCLC using model-based techniques and further use of these techniques in designing and evaluating NSCLC trials.
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[864]
TÍTULO / TITLE: - Involvement of STAT3 in immune evasion during lung tumorigenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncoimmunology. 2013 Jan 1;2(1):e22653.
●● Enlace al texto completo (gratuito o de pago) 4161/onci.22653
AUTORES / AUTHORS: - Kida H; Ihara S; Kumanogoh A
INSTITUCIÓN / INSTITUTION: - Department of Respiratory Medicine, Allergy and Rheumatic Diseases; Osaka University Graduate School of Medicine; Suita, Osaka, Japan.
RESUMEN / SUMMARY: - In a recent study, we have shown that STAT3 expressed by tumor cells blunts antitumor immunity during carcinogen-induced lung tumorigenesis. STAT3 inhibits the production of pro-inflammatory chemokines and MHC Class I chain-related gene A. In contrast, STAT3 promotes the expression of MHC class I molecules. Consequently, STAT3 promotes tumor cell resistance to NK cell-mediated cytotoxicity.
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[865]
TÍTULO / TITLE: - Inhibition of TWIST1 Leads to Activation of Oncogene-Induced Senescence in Oncogene Driven Non-Small Cell Lung Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Res. 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0456
AUTORES / AUTHORS: - Burns TF; Dobromilskaya I; Murphy SC; Gajula RP; Thiyagarajan S; Chatley SN; Aziz K; Cho YJ; Tran PT; Rudin CM
INSTITUCIÓN / INSTITUTION: - The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine.
RESUMEN / SUMMARY: - A large fraction of non-small cell lung cancers (NSCLC) are dependent on defined oncogenic driver mutations. Although targeted agents exist for EGFR- and EML4-ALK-driven NSCLC, no therapies target the most frequently found driver mutation, KRAS. Furthermore, acquired resistance to the currently targetable driver mutations is nearly universally observed. Clearly a novel therapeutic approach is needed to target oncogene driven NSCLC. We recently demonstrated that the basic helix-loop-helix transcription factor Twist1 cooperates with mutant Kras to induce lung adenocarcinoma in transgenic mouse models and that inhibition of Twist1 in these models led to Kras-induced senescence. In the current study, we examine the role of TWIST1 in oncogene driven human NSCLC. Silencing of TWIST1 in KRAS mutant human NSCLC cell lines resulted in dramatic growth inhibition and either activation of a latent oncogene-induced senescence program or in some cases, apoptosis. Similar effects were observed in EGFR mutation driven and c-Met amplified NSCLC cell lines. Growth inhibition by silencing of TWIST1 was independent of p53 or p16 mutational status and did not require previously defined mediators of senescence, p21 and p27, nor could this phenotype be rescued by overexpression of SKP2. In xenograft models, silencing of TWIST1 resulted in significant growth inhibition of KRAS mutant, EGFR mutant and c-Met amplified NSCLC. Remarkably, inducible silencing of TWIST1 resulted in significant growth inhibition of established KRAS mutant tumors. Together these findings suggest that silencing of TWIST1 in oncogene driver dependent NSCLC represents a novel and promising therapeutic strategy.
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[866]
TÍTULO / TITLE: - Study on invadopodia formation for lung carcinoma invasion with a microfluidic 3D culture device.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56448. doi: 10.1371/journal.pone.0056448. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056448
AUTORES / AUTHORS: - Wang S; Li E; Gao Y; Wang Y; Guo Z; He J; Zhang J; Gao Z; Wang Q
INSTITUCIÓN / INSTITUTION: - Graduate School of Dalian Medical University, Dalian, People’s Republic of China.
RESUMEN / SUMMARY: - Invadopodia or invasive feet, which are actin-rich membrane protrusions with matrix degradation activity formed by invasive cancer cells, are a key determinant in the malignant invasive progression of tumors and represent an important target for cancer therapies. In this work, we presented a microfluidic 3D culture device with continuous supplement of fresh media via a syringe pump. The device mimicked tumor microenvironment in vivo and could be used to assay invadopodia formation and to study the mechanism of human lung cancer invasion. With this device, we investigated the effects of epidermal growth factor (EGF) and matrix metalloproteinase (MMP) inhibitor, GM6001 on invadopodia formation by human non-small cell lung cancer cell line A549 in 3D matrix model. This device was composed of three units that were capable of achieving the assays on one control group and two experimental groups’ cells, which were simultaneously pretreated with EGF or GM6001 in parallel. Immunofluorescence analysis of invadopodia formation and extracellular matrix degradation was conducted using confocal imaging system. We observed that EGF promoted invadopodia formation by A549 cells in 3D matrix and that GM6001 inhibited the process. These results demonstrated that epidermal growth factor receptor (EGFR) signaling played a significant role in invadopodia formation and related ECM degradation activity. Meanwhile, it was suggested that MMP inhibitor (GM6001) might be a powerful therapeutic agent targeting invadopodia formation in tumor invasion. This work clearly demonstrated that the microfluidic-based 3D culture device provided an applicable platform for elucidating the mechanism of cancer invasion and could be used in testing other anti-invasion agents.
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[867]
TÍTULO / TITLE: - Lung cancer: how to face the revolution?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Mar;8(1):1-2. doi: 10.1007/s11523-013-0265-x. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0265-x
AUTORES / AUTHORS: - Morere JF; Penault-Llorca F
INSTITUCIÓN / INSTITUTION: - Oncology Department, Paul Brousse Hospital, Villejuif, France, jean-francois.morere@pbr.aphp.fr.
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[868]
TÍTULO / TITLE: - Lung cancer: OPTIMAL results for erlotinib in NSCLC.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Clin Oncol. 2013 Mar 19. doi: 10.1038/nrclinonc.2013.45.
●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2013.45
AUTORES / AUTHORS: - Hutchinson L
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[869]
TÍTULO / TITLE: - Efficacy study of CyberKnife stereotactic radiosurgery combined with CIK cell immunotherapy for advanced refractory lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Exp Ther Med. 2013 Feb;5(2):453-456. Epub 2012 Nov 19.
●● Enlace al texto completo (gratuito o de pago) 3892/etm.2012.818
AUTORES / AUTHORS: - Wang YY; Wang YS; Liu T; Yang K; Yang GQ; Liu HC; Wang SS; Yang JL
INSTITUCIÓN / INSTITUTION: - School of the Integration of Traditional and Western Medicine, Binzhou Medical University, Yantai, Shandong 264003;
RESUMEN / SUMMARY: - CyberKnife (CK), hypofractionated stereotactic radiosurgery, is a preferred option for the treatment of advanced refractory lung cancer which is usually inoperable. Cytokine-induced killer (CIK) cell immunotherapy has a marked radiosensitization effect which aids the elimination of residual tumor cells in distant areas. The main purpose of the present study was to evaluate the clinical efficacy of CK alone and combined with CIK cell therapy for advanced refractory lung cancer. In one year, 22 patients with advanced lung cancer underwent CK therapy at a CyberKnife Center. Of these patients, 11 received CIK cell therapy before or after the CK therapy course. The median prescribed dose in the combined CK and CIK group was 35 Gy (mean, 33.8+/-5.0 Gy) with a median number of fractions of 5. The median dose for patients who underwent CK alone was 35 Gy (mean, 35.2+/-6.0 Gy). CIK cell therapy was administered according to the condition of each patient, generally 2 continuous therapeutic sessions in 2 months. The median follow-up period was 3 months. The preliminary curative efficiency rate was 81.82% for patients who underwent CK/CIK and 72.73% for those who received CK alone, according to radiographic re-examination (P>0.05). The median improvement in the Karnofsky scores of the CK/CIK group was 20 (18+/-10.51) compared with 10 (8.6+/-11.85) for those who underwent CK alone (P<0.05). The median expression of carcinoembryonic antigen (CEA) before and after treatment was 40.81 and 12.21 ng/ml, respectively, for the CK/CIK group compared with 39.04 and 26.36 ng/ml for CK alone. The median percentage of phenotype expression of the CIK cells (CD3(+)/CD8(+) and CD3(+)/CD56(+)) in the patients who underwent CK/CIK was recorded as 64.35% (57.08+/-16.94%) and 15.27% (18.80+/-7.00%), respectively, prior to transfusion. The preliminary results of the present study suggest that CK combined with CIK cell immunotherapy improved the short-term outcomes of patients for curative efficacy, Karnofsky scores, tumor marker levels and immune status compared with alternative CK treatments, although further studies are required.
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[870]
TÍTULO / TITLE: - Lung cancer epigenetics: emerging biomarkers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomark Med. 2013 Feb;7(1):49-58. doi: 10.2217/bmm.12.111.
●● Enlace al texto completo (gratuito o de pago) 2217/bmm.12.111
AUTORES / AUTHORS: - Balgkouranidou I; Liloglou T; Lianidou ES
INSTITUCIÓN / INSTITUTION: - Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, 15771 Athens, Greece.
RESUMEN / SUMMARY: - Lung cancer is the leading cause of cancer-related deaths worldwide, and the 5-year survival rate is still very poor due to the scarcity of effective tools for early detection. The discovery of highly sensitive and specific biomarkers highlighting pathological changes early enough to allow clinical intervention is therefore of great importance. In the last decade, epigenetics and particularly research on DNA methylation have provided important information towards a better understanding of lung cancer pathogenesis. Novel and promising molecular biomarkers for diagnosis and prognosis of lung cancer are continuously emerging in this area, requiring further evaluation. This process includes extensive validation in prospective clinical trials before they can be routinely used in a clinical setting. This review summarizes the evidence on epigenetic biomarkers for lung cancer, focusing on DNA methylation.
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[871]
TÍTULO / TITLE: - Cisplatin for small cell lung cancer: Associated publications in Science Citation Index Expanded.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):684-688. Epub 2012 Nov 15.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1029
AUTORES / AUTHORS: - Ho YS; Nakazawa K; Sato S; Tamura T; Kurishima K; Satoh H
INSTITUCIÓN / INSTITUTION: - Trend Research Centre, Asia University, Taichung 41354, Taiwan ;
RESUMEN / SUMMARY: - This study was conducted to explore a bibliometric approach to quantitatively assess current research trends in cisplatin-containing chemotherapy for small cell lung cancer (SCLC), using related literature in the Science Citation Index Expanded database from 1992 to 2011. Articles were analyzed by the scientific output and research performances of countries and institutions. The distribution of key words in the article title and author-selected keywords were used to evaluate research trends. It was observed that the number of articles devoted to cisplatin-containing chemotherapy for SCLC did not increase with time. The USA and Japan were the top two countries with the highest number of articles devoted to cisplatin-containing chemotherapy for SCLC. In both countries, the number of articles did not increase with time, and a decreasing trend was identified in the USA over the last 10 years. This study demonstrates trends in cisplatin-containing chemotherapy for SCLC. The clinical application of novel drugs is required for successful SCLC treatment.
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[872]
TÍTULO / TITLE: - Respiratory epithelial adenomatoid hamartoma originating from nasal septum.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Exp Otorhinolaryngol. 2013 Mar;6(1):45-7. doi: 10.3342/ceo.2013.6.1.45. Epub 2011 Nov 29.
●● Enlace al texto completo (gratuito o de pago) 3342/ceo.2013.6.1.45
AUTORES / AUTHORS: - Park IH; Lee HC; Lee HM
INSTITUCIÓN / INSTITUTION: - Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - Respiratory epithelial adenomatoid hamartoma (REAH) is a rare benign lesion in nasal cavity. We report two cases of REAH of the nasal cavity arising from nasal septum. The etiology of REAH is unknown although inflammation may induce gland proliferation observed in hamartomas. One of our cases was associated with nasal polyposis. REAH is a self-limiting disease, so it is important to differentiate REAH from other pathologic process, including inverted papilloma and low-grade adenocarcinoma. The treatment of choice is complete excision through a conservative approach.
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[873]
TÍTULO / TITLE: - Effects of different sequences of pulmonary artery and vein ligations during pulmonary lobectomy on blood micrometastasis of non-small cell lung cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):463-468. Epub 2012 Nov 9.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1022
AUTORES / AUTHORS: - Song PP; Zhang W; Zhang B; Liu Q; DU J
INSTITUCIÓN / INSTITUTION: - Institute of Oncology, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan 250021; ; Department of Thoracic Surgery, Shandong Tumor Hospital, Jinan 250117, P.R. China.
RESUMEN / SUMMARY: - The aim of this study was to investigate the effects of different sequences of pulmonary artery and vein ligations during lobectomy on blood micrometastasis of non-small cell lung cancer (NSCLC). Cytokeratin 19 (CK19)/adhesion molecule CD44v6 mRNA were used as markers. A total of 30 NSCLC patients undergoing pulmonary lobectomy were randomly divided into pulmonary artery (PA)-first and pulmonary vein (PV)-first groups according to the order of artery or vein ligation (15 cases in each). Fluorescent quantitative-RT-PCR (FQ-RT-PCR) was used to detect the mRNA expression of CK19 and CD44v6 in pulmonary venous blood at the early and late periods during surgery, and DeltaCt values were calculated. Meanwhile, the peripheral blood samples from 10 healthy volunteers were selected as the control. DeltaCt values of CD44v6 and CK19 of NSCLC groups at the early period during surgery were 7.83+/-1.70 and 10.76+/-2.74, while those of the control group were 9.17+/-1.04 and 12.76+/-2.36. The expression of CD44v6 and CK19 genes in venous blood of NSCLC groups was significantly higher than that of the control group (P<0.05). In addition, the DeltaCt values of CD44v6 and CK19 in the early and late periods during surgery in the PA-first group were 7.92+/-1.97 vs. 5.67+/-2.11 (P= 0.008) and 11.21+/-3.14 vs. 8.60+/-4.02 (P= 0.05), respectively. The expression of CD44v6 and CK19 in the late period were both significantly higher than those in the early period, while neither the DeltaCt value of CD44v6 nor that of CK19 in the early vs. late periods in the PV-first group exhibited statistically significant differences (7.95+/-1.91 vs. 7.74+/-2.10 and 10.60+/-3.15 vs. 10.30+/-2.98) (P<0.05). Surgical manipulation itself may stimulate the occurrence of blood micrometastasis and the ligation of the PV first during surgery may help prevent blood micrometastasis.
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[874]
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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[875]
TÍTULO / TITLE: - Screening: Improved model for lung cancer detection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Clin Oncol. 2013 Apr;10(4):183. doi: 10.1038/nrclinonc.2013.39. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1038/nrclinonc.2013.39
AUTORES / AUTHORS: - Hutchinson L
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