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Cancer Pharmacogenomics.

December 2012 - January 2013


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TÍTULO / TITLE:  - Lapatinib plus capecitabine for brain metastases in patients with human epidermal growth factor receptor 2-positive advanced breast cancer: a review of the anatolian society of medical oncology (ASMO) experience.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Onkologie. 2012;35(12):740-5. doi: 10.1159/000345040. Epub 2012 Oct 31.

            ●● Enlace al texto completo (gratuito o de pago) 1159/000345040

AUTORES / AUTHORS:  - Cetin B; Benekli M; Oksuzoglu B; Koral L; Ulas A; Dane F; Turker I; Kaplan MA; Koca D; Boruban C; Yilmaz B; Sevinc A; Berk V; Isikdogan A; Uncu D; Harputluoglu H; Coskun U; Buyukberber S

INSTITUCIÓN / INSTITUTION:  - Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey. caretta06@hotmail.com

RESUMEN / SUMMARY:  - BACKGROUND: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). PATIENTS AND METHODS: A total of 203 patients with HER2+ MBC, who had progressed  after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. All patients were treated with the combination of lapatinib (1,250 mg/day continuously) and capecitabine (2,000 mg/m(2) on days 1-14 of a 21-day cycle). RESULTS: The median follow-up was 10.5 months (range 1-38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval  (CI) 5-9), with a median overall survival of 13 months (95% Cl 9-17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3-4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. CONCLUSION: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.




TÍTULO / TITLE:  - Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Br J Cancer. 2013 Jan 15;108(1):64-71. doi: 10.1038/bjc.2012.504.

            ●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2012.504

AUTORES / AUTHORS:  - Hirst TC; Vesterinen HM; Sena ES; Egan KJ; Macleod MR; Whittle IR

INSTITUCIÓN / INSTITUTION:  - Division of Clinical Neurosciences, University of Edinburgh, FU204, Chancellor’s  Building, Royal Infimary of Edinburgh, Little France Crescent, Edinburgh, EH16 4SA, UK.

RESUMEN / SUMMARY:  - Background:Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the  role of in vivo glioma models in predicting clinical efficacy.Methods:We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias.Results:We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74-2.03) and reduced tumour volume by 50.4% (41.8-58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of  between-study heterogeneity, and there was evidence of a significant publication  bias.Conclusion:These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental in vivo glioma studies of temozolomide differ  from those of other glioma therapies in their consistent efficacy and successful  translation into clinical medicine.




TÍTULO / TITLE:  - Prognostic role of hormone receptors in ovarian cancer: a systematic review and meta-analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Int J Gynecol Cancer. 2013 Jan;23(1):25-33. doi: 10.1097/IGC.0b013e3182788466.

            ●● Enlace al texto completo (gratuito o de pago) 1097/IGC.0b013e3182788466

AUTORES / AUTHORS:  - Zhao D; Zhang F; Zhang W; He J; Zhao Y; Sun J

INSTITUCIÓN / INSTITUTION:  - *Department of Minimally Invasive Gynecologic Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine; and daggerInstitutes for Advanced Interdisciplinary Research and double daggerSchool of Life Science,  East China Normal University, Shanghai, PR China.

RESUMEN / SUMMARY:  - OBJECTIVE: The aim of this study was to summarize the global predicting role of hormone receptors for survival in ovarian cancer. METHODS: Eligible studies were  identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall or progression-free/disease-free/relapse-free survival in patients with elevated levels of estrogen receptor (ER), progesterone receptor (PR), or human epidermal  growth factor receptor 2 (HER2) with those in patients with lower levels. Studies were pooled, and combined hazards ratios (HRs) of ER, PR, and HER2 for survival were calculated, respectively. RESULTS: A total of 35 studies were included for meta-analysis (23 for ER, 19 for PR, and 8 for HER2). For overall survival, the pooled HR of PR reached 0.88 [95% confidence interval (CI), 0.82-0.95], which means that elevated PR level could significantly indicate better survival. In contrast, elevated levels of HER2 could predict worse outcome with an HR of 1.41  (95% CI, 1.05-1.89). Increased level of ER was not significantly prognostic (HR,  0.94; 95% CI, 0.87-1.01). For progression-free survival/disease-free survival/recurrence-free survival, elevated PR level also had predictive value for better outcome with a pooled HR of PR of 0.80 (95% CI, 0.67-0.95). Oppositely, elevated HER2 level could predict poorer outcome with an HR of 1.55 (95% CI, 1.11-2.16). Estrogen receptor failed to predict outcome with an HR of 0.90 (95% CI, 0.78-1.03). CONCLUSIONS: In patients with ovarian cancer, elevated  level of PR predicted favorable survival, and elevated level of HER2 was associated with worse survival.




TÍTULO / TITLE:  - Lung cancer genotype-based therapy and predictive biomarkers: present and future.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Pathol Lab Med. 2012 Dec;136(12):1482-91. doi: 10.5858/arpa.2012-0508-RA.

            ●● Enlace al texto completo (gratuito o de pago) 5858/arpa.2012-0508-RA

AUTORES / AUTHORS:  - Cagle PT; Allen TC

INSTITUCIÓN / INSTITUTION:  - Department of Pathology & Genomic Medicine, The Methodist Hospital, Houston, Texas, USA. pcagle@tmhs.org

RESUMEN / SUMMARY:  - CONTEXT: The advent of genotype-based therapy and predictive biomarkers for lung  cancer has thrust the pathologist into the front lines of precision medicine for  this deadly disease. OBJECTIVE: To provide the clinical background, current status, and future perspectives of molecular targeted therapy for lung cancer patients, including the pivotal participation of the pathologist. DATA SOURCES: Data were obtained from review of the pertinent peer-reviewed literature. CONCLUSIONS: First-generation tyrosine kinase inhibitors have produced clinical response in a limited number of non-small cell lung cancers demonstrated to have  activating mutations of epidermal growth factor receptor or anaplastic lymphoma kinase rearrangements with fusion partners. Patients treated with first-generation tyrosine kinase inhibitors develop acquired resistance to their  therapy. Ongoing investigations of second-generation tyrosine kinase inhibitors and new druggable targets as well as the development of next-generation genotyping and new antibodies for immunohistochemistry promise to significantly expand the pathologist’s already crucial role in precision medicine of lung cancer.




TÍTULO / TITLE:  - XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in  colorectal cancer: a meta-analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Cancer Chemother Pharmacol. 2013 Jan 9.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2067-8

AUTORES / AUTHORS:  - Ye F; Liu Z; Tan A; Liao M; Mo Z; Yang X

INSTITUCIÓN / INSTITUTION:  - Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China.

RESUMEN / SUMMARY:  - PURPOSE: Genetic variations are related to individual differences of DNA repair ability and drug metabolism, which can greatly influence prognosis of antineoplastic agents, such as oxaliplatin. The aim was to explore the influences of X-ray repair cross-complementing 1(XRCC1) and Glutathione S-transferase P1 (GSTP1) genetic variants on prognosis of oxaliplatin-based chemotherapy in colorectal cancer patients. METHODS: We performed a meta-analysis including 13 original studies with a total number of 1,234 patients in advanced or metastatic  colorectal cancer. Tumor responses [complete response, partial response, stable disease (SD) and progressive disease (PD)] and progression-free survival were estimated. RESULTS: Our results showed that XRCC1 Arg399Gln polymorphism was significantly associated with tumor chemotherapy when SD or PD was considered as  non-response [risk ratio (RR) = 1.29; 95 % confidence intervals (CI): 1.05-1.60;  P = 0.02]. No significant association was found between GSTP1 Ile105 Val polymorphism and tumor response (RR = 0.63; 95 % CI: 0.35-1.14; P = 0.13). In addition, our results also showed that there was no significant association between XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes and hazard ratio for progression-free survival (Hazards ratio = 1.04 and 1.92; 95 % CI: 0.75-1.43 and  0.62-1.37; P = 0.826 and 0.677, respectively). CONCLUSION: In our meta-analysis,  XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for oxaliplatin-based chemotherapy in colorectal cancer, and the results still need further confirmation.




TÍTULO / TITLE:  - Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Ann Oncol. 2013 Jan 20.

            ●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mds645

AUTORES / AUTHORS:  - Azim HA Jr; Michiels S; Zagouri F; Delaloge S; Filipits M; Namer M; Neven P; Symmans WF; Thompson A; Andre F; Loi S; Swanton C

INSTITUCIÓN / INSTITUTION:  - Breast Cancer Translational Research Laboratory (BCTL), J.C. Heuson , Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium.

RESUMEN / SUMMARY:  - BackgroundWe critically evaluated the available evidence on genomic tests in breast cancer to define their prognostic ability and likelihood to determine treatment benefit.DesignIndependent evaluation of six genomic tests [Oncotype Dx, MammaPrint(®), Genomic Grade Index, PAM50 (ROR-S), Breast Cancer Index, and EndoPredict] was carried out by a panel of experts in three parameters: analytical validity, clinical validity, and clinical utility based on the principles of the EGAPP criteria.Panel statementsThe majority of the working group members found the available evidence on the analytical and clinical validity of Oncotype Dx and MammaPrint(®) to be convincing. None of the genomic tests demonstrated robust evidence of clinical utility: it was not clear from the current evidence that modifying treatment decisions based on the results of a given genomic test could result in improving clinical outcome.ConclusionsThe IMPAKT 2012 Working Group proposed the following recommendations: (i) a need to develop models that integrate clinicopathologic factors along with genomic tests; (ii) demonstration of clinical utility should be made in the context of a prospective randomized trial; and (iii) the creation of registries for patients who are subjected to genomic testing in the daily practice.




TÍTULO / TITLE:  - Rheumatoid factor as predictor of response to abatacept, rituximab and tocilizumab in rheumatoid arthritis: Systematic review and meta-analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Semin Arthritis Rheum. 2013 Jan 2. pii: S0049-0172(12)00279-X. doi: 10.1016/j.semarthrit.2012.11.007.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.semarthrit.2012.11.007

AUTORES / AUTHORS:  - Maneiro RJ; Salgado E; Carmona L; Gomez-Reino JJ

INSTITUCIÓN / INSTITUTION:  - Rheumatology Unit, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, España. Electronic address: joseramon.maneiro.fernandez@sergas.es.

RESUMEN / SUMMARY:  - OBJECTIVE: To identify if rheumatoid factor (RF) is predictor of response to rituximab (RTX), abatacept (ABT), and tocilizumab (TCZ) in rheumatoid arthritis (RA). METHODS: Systematic review and meta-analysis of clinical trials and observational studies based on a sensitive search. Meta-regression was used to explore causes of heterogeneity. Unpublished data of clinical trials provided by  the authors were also included. RESULTS: The electronic search captured 3221 references and 422 meeting abstracts. By hand search, four additional articles were also identified. A total of 23 studies meet the purpose of the study and were included in the review. RF positivity at starting predicts better ACR20 [OR, 1.95 (1.24, 3.08)], ACR50 [OR, 5.38 (2.50, 11.60)] and EULAR response [OR, 3.52 (1.66, 7.45)] in 14 studies with RTX, and better ACR20 [OR, 1.51 (1.21, 1.90)] in 6 studies with TCZ. In 3 studies with ABT, no association was found between response and RF [OR 1.36 (0.97, 1.90)]. No asymmetries in the funnel plots or significant variables were found in the meta-regression. CONCLUSION: In RA, RF positivity predicts better response to RTX and TCZ but not to ABT.




TÍTULO / TITLE:  - Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: A  meta-analysis of randomized controlled trials.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Breast. 2013 Jan 5. pii: S0960-9776(12)00252-4. doi: 10.1016/j.breast.2012.12.008.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.breast.2012.12.008

AUTORES / AUTHORS:  - Yang B; Shi W; Yang J; Liu H; Zhao H; Li X; Jiao S

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, General Hospital of Chinese PLA, Beijing 100853, China.

RESUMEN / SUMMARY:  - BACKGROUND: While chemotherapy significantly improves the prognosis of breast cancer patients, it also damages otherwise healthy organs, such as the ovaries. Gonadotropin-releasing hormone (GnRH) agonists may have a protective effect against chemotherapy-induced ovarian toxicity in premenopausal women being treated for breast cancer; however, studies of its clinical efficacy have reported conflicting results. OBJECTIVES: This meta-analysis was designed to assess the collective data from previous studies of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian toxicity in premenopausal women with breast cancer. METHODS: Electronic literature databases (Cochrane Library, Medline, and Embase) were searched for relevant randomized controlled trials (RCTs) published prior to April 2012. Only RCTs that compared GnRH agonists plus chemotherapy to chemotherapy alone for premenopausal  women with breast cancer were selected. A random-effects model was used to calculate the risk ratios (RRs) for premature ovarian failure (POF) within one year after chemotherapy treatment and rates of resumed menses and spontaneous pregnancy during the follow-up period after cessation of treatment. RESULTS: Five RCTs composed of 528 patients (GnRH agonist combination, n = 274; chemotherapy alone, n = 254) were included in the meta-analysis. Significantly fewer women treated with GnRH agonist experienced post-chemotherapy POF, yielding a RR of 0.40 (vs. chemotherapy alone, 95% confidence interval [CI] 0.21-0.75). In contrast, both treatment groups experienced similar rates of resumed menses (RR = 1.31, 95% CI 0.93-1.85) and spontaneous pregnancy (RR = 0.96, 95% CI 0.20-4.56).  CONCLUSION: Concurrent administration of GnRH agonists during chemotherapy treatment of breast cancer in premenopausal women appears to protect against chemotherapy-related POF in the first year after treatment, but appears to have no effect on resumed menses or spontaneous pregnancy rates.




TÍTULO / TITLE:  - Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Eur J Cancer Care (Engl). 2013 Jan 18. doi: 10.1111/ecc.12043.

            ●● Enlace al texto completo (gratuito o de pago) 1111/ecc.12043

AUTORES / AUTHORS:  - Almenar Cubells D; Bosch Roig C; Jimenez Orozco E; Alvarez R; Cuervo JM; Diaz Fernandez N; Sanchez Heras AB; Galan Brotons A; Giner Marco V; Codes M De Villena M

INSTITUCIÓN / INSTITUTION:  - Medical Oncology Service, Hospital Universitario Dr Peset, Valencia.

RESUMEN / SUMMARY:  - We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no  reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for >/=7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8),  and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.




TÍTULO / TITLE:  - The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Target Oncol. 2013 Jan 16.

            ●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0257-x

AUTORES / AUTHORS:  - Petrelli F; Borgonovo K; Barni S

INSTITUCIÓN / INSTITUTION:  - Oncology Unit, Azienda Ospedaliera Treviglio, UO Oncologia, Piazzale Ospedale 1,  24047, Treviglio, Bergamo, Italy, faupe@libero.it.

RESUMEN / SUMMARY:  - Skin rash is an early and frequent phenomenon during treatment with anti-epidermal growth factor receptor monoclonal antibodies. The objective of this review is to assess the predictive value of skin rash in patients with advanced colorectal cancer treated with cetuximab and panitumumab. We searched PubMed and ASCO Meetings for publications reporting the correlation of skin rash  with survival and/or response rate. Hazard ratios (HRs) with 95 % confidence intervals for progression and/or survival, and/or risk ratios (RRs) for response  rate in patients with rash were obtained from publications and pooled in a meta-analysis. Fourteen publications (for a total of 3,833 patients) were included in this meta-analysis. The occurrence of skin toxicity represents a predictive factor for survival (HR 0.51; p < 0.00001) and progression (HR 0.58; p < 0.00001). Similarly, patients who developed moderate or severe rash had an increased chance of response (35 vs 13 %; RR 2.23, p < 0.00001). The occurrence of skin rash during treatment with cetuximab and panitumumab represents a significant predictor of the efficacy of these drugs. The hypothesis that, in patients who lack substantial skin toxicity, this treatment is not beneficial and requires early discontinuation deserves further study.



TÍTULO / TITLE:  - Clinicopathological Significance of Plasminogen Activator Inhibitor-1 Promoter 4G/5G Polymorphism in Breast Cancer: A Meta-analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Arch Med Res. 2013 Jan 3. pii: S0188-4409(12)00341-4. doi: 10.1016/j.arcmed.2012.12.002.

            ●● Enlace al texto completo (gratuito o de pago) 1016/j.arcmed.2012.12.002

AUTORES / AUTHORS:  - Lee JH; Kim Y; Choi JW; Kim YS

INSTITUCIÓN / INSTITUTION:  - Department of Pathology, Korea University Ansan Hospital, Ansan, Republic of Korea.

RESUMEN / SUMMARY:  - BACKGROUND AND AIMS: Plasminogen activator inhibitor type 1 (PAI-1) is associated with poor prognosis in breast cancer. Transcriptional expression of the PAI-1 can be controlled by PAI-1 promoter 4G/5G polymorphism. However, the significance of  PAI-1 promoter 4G/5G polymorphism in breast cancer patients is contentious. To address this controversy, we conducted a meta-analysis for the relationships between PAI-1 promoter polymorphism and clinicopathological characteristics of breast cancer. METHODS: Relevant published studies were identified using a search of PubMed, Embase, and the ISI Web of Science. The effect sizes of PAI-1 promoter 4G/5G polymorphism on breast cancer risk, lymph node metastasis, histologic grade, and overall survival were calculated by odds ratio (OR) or hazard ratio. The effect sizes were combined using a random-effects model. RESULTS: Individuals with 4G/4G genotype had a higher risk of breast cancer than those with the combined 4G/5G and 5G/5G genotypes (OR = 1.388; p = 0.031). Breast cancer patients with the 5G/5G genotype displayed lymph node metastasis more than patients with either the combined other genotypes (OR = 1.495; p = 0.027) or with the 4G/4G genotype (OR = 1.623; p = 0.018). However, the PAI-1 promoter 4G/5G polymorphism was not associated with histological grade or overall survival. CONCLUSIONS: PAI-1 promoter 4G/5G polymorphism is associated with a relatively increased risk of breast cancer development and lymph node metastasis.




TÍTULO / TITLE:  - Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Prostate Cancer: a Systematic Review with Meta-analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(11):5665-9.

AUTORES / AUTHORS:  - Wang K; Peng HL; Li LK

INSTITUCIÓN / INSTITUTION:  - Department of Urology, Xinqiao Hospital, Third Military Medical Universit,, Chengdu, China E-mail : lilongk@hotmail.com.

RESUMEN / SUMMARY:  - Background: The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has involvement in cancer pathogenesis, progression and metastasis.  However, the prognostic value of VEGF in patients with prostate cancer remains controversial. Objectives: The aim of our study was to evaluate the prognostic value of VEGF in prostate cancer, and summarise the results of related research on VEGF. Methods: In accordance with an established search strategy, 11 studies with 1,529 patients were included in our meta-analysis. The correlation of VEGF-expression with overall survival and progression-free survival was evaluated by hazard ratio, either given or calculated. Results: The studies were categorized by introduction of the author, demographic data in each study, prostate cancer-relatived information, VEGF cut-off value, VEGF subtype, methods  of hazard ratio (HR) estimation and its 95% confidence interval (CI). High VEGF-expression in prostate cancer is a poor prognostic factor with statistical significance for OS (HR=2.32, 95%CI: 1.40-3.24). However, high VEGF-expression showed no effect on poor PFS (HR=1.30, 95%CI: 0.88-1.72). Using Begg’s, Egger’s test and funnel plots, we confirmed lack of publication bias in our analysis. Conclusion: VEGF might be regarded as a prognostic maker for prostate cancer, as  supported by our meta-analysis. To achieve a more definitive conclusion enabling  the clinical use of VEGF in prostate cancer, we need more high-quality interventional original studies following agreed research approaches or standards.




TÍTULO / TITLE:  - Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Asian Pac J Cancer Prev. 2012;13(10):5177-82.

AUTORES / AUTHORS:  - Qi WX; Shen Z; Lin F; Sun YJ; Min DL; Tang LN; He AN; Yao Y

INSTITUCIÓN / INSTITUTION:  - Department of Oncology, Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China.

RESUMEN / SUMMARY:  - PURPOSE: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitor monotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3  or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neurotoxicity in  EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. CONCLUSION: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR- TKI monotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.




TÍTULO / TITLE:  - The induction of the apoptosis of cancer cell by sonodynamic therapy: a review.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Chin J Cancer Res. 2012 Dec;24(4):368-73. doi: 10.3978/j.issn.1000-9604.2012.08.03.

            ●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.1000-9604.2012.08.03

AUTORES / AUTHORS:  - Bai WK; Shen E; Hu B

INSTITUCIÓN / INSTITUTION:  - Department of Ultrasound In Medicine, Shanghai Jiao tong University Affiliated 6th People’s Hospital, Shanghai Institute of Ultrasound In Medicine, Shanghai 200233, China; ; Department of Ultrasound In Medicine, Shandong University Affiliated Qian Fo Shan Hospital, Ji Nan 250014, China.

RESUMEN / SUMMARY:  - Ultrasound can be used not only in the examination, but also in the therapy, especially in the therapy of cancer, which has got effect in the treatment. Sonodynamic therapy is an experimental cancer therapy which uses ultrasound to enhance the cytotoxic effects of drugs known as sonosensitizers. It has been tested in vitro and in vivo. The ultrasound could penetrate the tissue and cell under some of conditions which directly changes the cell membranes permeability,  thereby allowing the delivery of exogenous molecules into the cells in some degree. Ultrasound could inhibit the proliferation or induce the apoptosis of the cancer cell in vitro or in vivo. Recent research indicated low frequency and low  intensity ultrasound could induce cells apoptosis, and which could be strengthened by sonodynamic sensitivities, microbubbles, chemotherapeutic drugs and so on. Most kinds of ultrasound suppressed the proliferation of cancer cell through inducing the apoptosis of cancer cell. The mechanism of apoptosis is not  clear. In this review, we will focus on and discuss the mechanisms of the induction of the apoptosis of cancer cell by ultrasound.



TÍTULO / TITLE:  - Pulmonary and peritoneal tuberculosis associated with tumor necrosis factor-alpha inhibitor use: a case report and review of the literature.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Case Rep Pulmonol. 2012;2012:598634. doi: 10.1155/2012/598634. Epub 2012 Dec 4.

            ●● Enlace al texto completo (gratuito o de pago) 1155/2012/598634

AUTORES / AUTHORS:  - Tipirneni N; Siegel MO

INSTITUCIÓN / INSTITUTION:  - Division of Infectious Diseases, George Washington University Medical Center, 2150 NW Pennsylvania Avenue, Washington, DC 20037, USA.

RESUMEN / SUMMARY:  - The association between the use of tumor necrosis factor-alpha inhibitors and the increased risk of granulomatous infections, especially tuberculosis, has been well documented. Given the rapidly expanding list of inflammatory conditions for  which tumor necrosis factor-alpha inhibitors are receiving FDA approval, the incidence of tuberculosis in this patient population has increased. Despite heightened awareness by physicians, the diagnosis of tuberculosis can remain challenging, given that extrapulmonary sites of infection are more frequently involved. We present a case of pulmonary and peritoneal tuberculosis in a gentleman being treated with a tumor necrosis factor-alpha inhibitor and discuss  the diagnostic challenges of establishing the diagnosis.



TÍTULO / TITLE:  - Quantitative prediction of integrase inhibitor resistance from genotype through consensus linear regression modeling.

RESUMEN / SUMMARY:  - Enlace al Resumen / Link to its Summary

REVISTA / JOURNAL:  - Virol J. 2013 Jan 3;10:8. doi: 10.1186/1743-422X-10-8.

            ●● Enlace al texto completo (gratuito o de pago) 1186/1743-422X-10-8

AUTORES / AUTHORS:  - Van der Borght K; Verheyen A; Feyaerts M; Van Wesenbeeck L; Verlinden Y; Van Craenenbroeck E; van Vlijmen H

INSTITUCIÓN / INSTITUTION:  - Tibotec-Virco, Beerse, Belgium. kvdborgh@its.jnj.com.

RESUMEN / SUMMARY:  - ABSTRACT: BACKGROUND: Integrase inhibitors (INI) form a new drug class in the treatment of HIV-1 patients. We developed a linear regression modeling approach to make a quantitative raltegravir (RAL) resistance phenotype prediction, as Fold Change in IC50 against a wild type virus, from mutations in the integrase genotype. METHODS: We developed a clonal genotype-phenotype database with 991 clones from 153 clinical isolates of INI naive and RAL treated patients, and 28 site-directed mutants.We did the development of the RAL linear regression model in two stages, employing a genetic algorithm (GA) to select integrase mutations by consensus. First, we ran multiple GAs to generate first order linear regression models (GA models) that were stochastically optimized to reach a goal  R2 accuracy, and consisted of a fixed-length subset of integrase mutations to estimate INI resistance. Secondly, we derived a consensus linear regression model in a forward stepwise regression procedure, considering integrase mutations or mutation pairs by descending prevalence in the GA models. RESULTS: The most frequently occurring mutations in the GA models were 92Q, 97A, 143R and 155H (all 100%), 143G (90%), 148H/R (89%), 148K (88%), 151I (81%), 121Y (75%), 143C (72%),  and 74M (69%). The RAL second order model contained 30 single mutations and five  mutation pairs (p < 0.01): 143C/R&97A, 155H&97A/151I and 74M&151I. The R2 performance of this model on the clonal training data was 0.97, and 0.78 on an unseen population genotype-phenotype dataset of 171 clinical isolates from RAL treated and INI naive patients. CONCLUSIONS: We describe a systematic approach to derive a model for predicting INI resistance from a limited amount of clonal samples. Our RAL second order model is made available as an Additional file for calculating a resistance phenotype as the sum of integrase mutations and mutation pairs.