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Caparica R.,University of Sao Paulo | de Castro G.,University of Sao Paulo | Gil-Bazo I.,University of Navarra | Caglevic C.,Fundacion Arturo Lopez Perez | And 6 more authors.
Critical Reviews in Oncology/Hematology | Year: 2016

B-Raf mutations occur in about 1-2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warranted to validate these findings. Enrollment of these patients in clinical trials is an interesting strategy to offer a potentially more effective and less toxic targeted therapy. © 2016 Elsevier Ireland Ltd.

Horvath E.,University for Development | Silva C.,University for Development | Fasce G.,Fundacion Arturo Lopez Perez | Ferrari C.,University of Connecticut | And 3 more authors.
American Journal of Roentgenology | Year: 2012

OBJECTIVE. The purpose of this study was to assess the parallel artery and vein sign at color Doppler breast ultrasound as a predictor of the benign nature of breast masses. SUBJECTS AND METHODS. A prospective study was performed to identify evidence of a parallel artery and vein in breast lesions consecutively biopsied with a 14-gauge needle under ultrasound guidance. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and 95% CIs for the parallel artery and vein sign were calculated. RESULTS. The parallel artery and vein sign was identified in 142 of the 1074 masses (13.2%). The specificity for benignity was 99.3% (CI 95%, 98.3-100.0%); sensitivity, 17.6% (CI 95%, 15.0-20.3%); positive predictive value, 99.0% (CI 95%, 96.7-100); negative predictive value, 30.0% (CI 95%, 27.0-32.9); positive likelihood ratio, 24.7 (CI 95%, 21.2-28.7); and negative likelihood ratio, 0.83 (CI 95%, 0.80-0.86). Among masses found to have the parallel artery and vein sign, all BI-RADS ultrasound category 3 and 95.1% of BI-RADS 4 lesions were determined to be benign. CONCLUSION. Although the parallel artery and vein sign is an uncommon finding, it has a significant association with benign pathologic results (96.5%) with a positive likelihood ratio of 24.7. The presence of this color Doppler ultrasound finding in breast masses in BI-RADS ultrasound categories 3 and 4 reinforces the benign nature and may allow follow-up rather than biopsy in the care of some patients. © American Roentgen Ray Society.

Murray N.P.,Simon Bolivar University of Venezuela | Murray N.P.,Institute Bio Oncologia | Murray N.P.,Major University | Calaf G.M.,University of Tarapaca | And 8 more authors.
Oncology Reports | Year: 2010

Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer deaths. The serum prostate specific antigen (PSA) is the only biomarker routinely used in screening. The aim of this study was to develop a system to test the presence of circulating prostate cells in men without a diagnosis of prostate cancer in relation with age, serum PSA levels and prostate biopsy by determining the co-expression of several markers such as CD82, HER-2 and matrix metalloproteinase 2 (MMP-2). For this purpose mononuclear cells were separated from blood using differential centrifugation and then prostate cells were identified by using standard immunocytochemical method. Results indicated that among 409 men screened for prostate cancer 16.6% were positive for circulating prostate cells. Cells were positive for MMP-2 and HER-2 in 100 and 14.3% of cases, respectively, without an association with age or PSA levels. However, CD82 protein expression was associated with older age and low grade tumors. It can be concluded that the study of circulating prostate cells with various markers could be a useful complementary screening test for prostate cancer in men with increased PSA level.

OBJECTIVES: Serum prostate specific an-tigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of can-cer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable re-sults, but it could be a useful complementa-ry screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. To evaluate the diagnostic yield of the detection of mCPC as a complementary PC screening test in a po-pulation fulfilling criteria for a prostate biopsy for sus-picion of PC. METHODS: A prospective screening study of consecuti-ve patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0ng/ml, PSA velocity >0.35ng/ml/year and/or DRE suspi-cious for cancer. Patients fulfilling inclusion criteria had blood taken for mCPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-histochemical staining with anti-PSA and anti-P504S was used to detect mCPC. Both cytologist and pathologist were blinded to the results of the biopsy, mCPC results and clinical de-tails. The diagnostic yield of the presence or absence of mCPC was evaluated; the prostate biopsy was classi-fied as cancer or no-cancer. RESULTS: 228 men participated, with a mean age of 66.8 ± 8.8 years and a median serum PSA of 5.15ng/ml. 28.6% of the biopsies were positive for PC, and mCPC were detected in 31.0% of all cases. Sensibility, specifici-ty and negative predictive value were 86.2%, 90.8% and 94.3% respectively. The negative and positive like-lihood ratios were 9.36 and 0.15. In men with a PSA <4.0ngml, 13.3% had cancer detected on biopsy, with a sensibility and specificity for mCPC detection of 83.3% and 84.6% and negative predictive value of 97.1%. All the mCPC determinations were interpretable. There were 9 false negative cases, all with small low grade tumors. CONCLUSIONS: The use of mCPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, including patients with a serum PSA <4.0ng/ml.

Sternberg C.N.,San Camillo and Forlanini Hospitals | Hawkins R.E.,University of Manchester | Wagstaff J.,South West Wales Cancer Institute | Salman P.,Fundacion Arturo Lopez Perez | And 10 more authors.
European Journal of Cancer | Year: 2013

Background: In this randomised phase III study (VEG105192; NCT00334282), pazopanib previously demonstrated statistically and clinically meaningful improvement of progression-free survival versus placebo in patients with advanced/metastatic renal cell carcinoma (mRCC). Final overall survival (OS) and updated safety results are now reported. Methods: Treatment-naive or cytokine-pretreated mRCC patients (n = 435) stratified and randomised (2:1) to pazopanib 800 mg daily or placebo, were treated until disease progression, death or unacceptable toxicity. Upon progression, placebo patients could receive pazopanib through an open-label study. Final OS in the intent-to-treat population was analysed using a stratified log-rank test. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighted (IPCW) analyses were performed post-hoc to adjust for crossover. Findings: The difference in final OS between pazopanib- and placebo-treated patients was not statistically significant (22.9 versus 20.5 months, respectively; hazard ratio [HR] = 0.91; 95% confidence interval [CI], 0.71-1.16; one-sided P =.224). Early and frequent crossover from placebo to pazopanib and prolonged duration of crossover treatment confounded the OS analysis. In IPCW analyses, pazopanib decreased mortality (HR = 0.504; 95% CI, 0.315-0.762; two-sided P =.002). Similar, albeit non-significant, results were obtained in RPSFT analyses (HR = 0.43; 95% CI, 0.215-1.388; two-sided P =.172). Since the last cutoff, cumulative exposure to pazopanib increased by 30%. The pazopanib safety profile showed no new safety signals or changes in the type, frequency and severity of adverse events. Interpretation: Although no significant difference in OS was observed in this study, extensive crossover from placebo to pazopanib confounded final OS analysis. Post-hoc analyses adjusting for crossover suggest OS benefit with pazopanib treatment for mRCC patients. © 2013 Elsevier Ltd. All rights reserved.

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