Browsing by Author "Fraga, A."
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- Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity-a pilot studyPublication . Cheng, Y.; Monteiro, C.; Matos, A.; You, J.; Fraga, A.; Pereira, C.; Catalán, V.; Rodríguez, A.; Gómez-Ambrosi, J.; Frühbeck, G.; Ribeiro, R.; Hu, P.Background: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m-2) and normal weight (NW, BMI < 25 kg m-2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling. Results: Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion. Conclusions: Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.
- Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancerPublication . Fraga, A.; Ribeiro, R.; Coelho, A.; Vizcaíno, J.; Coutinho, H.; Lopes, J.; Príncipe, P.; Lobato, C.; Lopes, C.; Medeiros, R.Background In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms. Methods Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray. DNA was isolated from peripheral blood and used to genotype functional polymorphisms at the corresponding genes (HIF1A +1772 C > T, rs11549465; CA9 + 201 A > G; rs2071676; LOX +473 G > A, rs1800449; KDR – 604 T > C, rs2071559). Results Immunohistochemistry analyses disclosed predominance of positive CAIX and VEGFR2 expression in epithelial cells of prostate carcinomas compared to nodular prostate hyperplasia (P = 0.043 and P = 0.035, respectively). In addition, the VEGFR2 expression score in prostate epithelial cells was higher in organ-confined and extra prostatic carcinoma compared to nodular prostate hyperplasia (P = 0.031 and P = 0.004, respectively). Notably, for LOX protein the immunoreactivity score was significantly higher in organ-confined carcinomas compared to nodular prostate hyperplasia (P = 0.015). The genotype-phenotype analyses showed higher LOX staining intensity for carriers of the homozygous LOX +473 G-allele (P = 0.011). Still, carriers of the KDR−604 T-allele were more prone to have higher VEGFR2 expression in prostate epithelial cells (P < 0.006). Conclusions Protein expression of hypoxia markers (VEGFR2, CAIX and LOX) on prostate epithelial cells was different between malignant and benign prostate disease. Two genetic polymorphisms (LOX +473 G > A and KDR−604 T > C) were correlated with protein level, accounting for a potential gene-environment effect in the activation of hypoxia-driven pathways in prostate carcinoma. Further research in larger series is warranted to validate present findings.
- mHealth in Urology: A Review of Experts' Involvement in App DevelopmentPublication . Pereira-Azevedo, N.; Carrasquinho, E.; Cardoso-Oliveira, E.; Cavadas, V.; Osório, L.; Fraga, A.; Castelo-Branco, M.; Roobol, M.Smartphones are increasingly playing a role in healthcare and previous studies assessing medical applications (apps) have raised concerns about lack of expert involvement and low content accuracy. However, there are no such studies in Urology. We reviewed Urology apps with the aim of assessing the level of participation of healthcare professionals (HCP) and scientific Urology associations in their development.
- Rotterdam Prostate Cancer Risk Calculator: Development and Usability Testing of the Mobile Phone AppPublication . Pereira-Azevedo, N.; Osório, L.; Fraga, A.; Roobol, M.BACKGROUND: The use of prostate cancer screening tools that take into account relevant prebiopsy information (ie, risk calculators) is recommended as a way of determining the risk of cancer and the subsequent need for a prostate biopsy. This has the potential to limit prostate cancer overdiagnosis and subsequent overtreatment. mHealth apps are gaining traction in urological practice and are used by both practitioners and patients for a variety of purposes. OBJECTIVE: The impetus of the study was to design, develop, and assess a smartphone app for prostate cancer screening, based on the Rotterdam Prostate Cancer Risk Calculator (RPCRC). METHODS: The results of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) study were used to elaborate several algorithms that allowed the risk of prostate cancer to be estimated. A step-by-step workflow was established to ensure that depending on the available clinical information the most complete risk model of the RPCRC was used. The user interface was designed and then the app was developed as a native app for iOS. The usability of the app was assessed using the Post-Study System Usability Questionnaire (PSSUQ) developed by IBM, in a group of 92 participants comprising urologists, general practitioners, and medical students. RESULTS: A total of 11 questions were built into the app, and, depending on the answers, one of the different algorithms of the RPCRC could be used to predict the risk of prostate cancer and of clinically significant prostate cancer (Gleason score ≥7 and clinical stage >T2b). The system usefulness, information quality, and interface quality scores were high-92% (27.7/30), 87% (26.2/30), and 89% (13.4/15), respectively. No usability problems were identified. CONCLUSIONS: The RPCRC app is helpful in predicting the risk of prostate cancer and, even more importantly, clinically significant prostate cancer. Its algorithms have been externally validated before and the usability score shows the app's interface is well designed. Further usability testing is required in different populations to verify these results and ensure that it is easy to use, to warrant a broad appeal, and to provide better patient care.
- What about vaginal extraction of the kidney? results of an online surveyPublication . Cabral, J.; Braga, I.; Branco, F.; Cavadas, V.; Fraga, A.; Silva-Ramos, M.PURPOSE: We aimed to characterize surgeons opinion about the vaginal extraction of the kidney after transperitoneal laparoscopic nephrectomy. Matherial and Methods: A 9-item questionnaire was published online (Survey Monkey TM) and publicized via email to a multidisciplinary pool of surgeons in Portugal. Data was collected and statistical analysis was performed using IBM SPSS Statistics, Version 21.0. RESULTS: Three hundred and fifty nine inquiries were sent, 154 surgeons completed the questionnaires (response rate of 43.0%). Fifty five point eight percent of the participants would choose the transvaginal approach for themselves or for a close relative. The most stated arguments were a better cosmesis (29.0%) expectancy of lower post operative pain (26.0%) and lower rate of incisional hernias (23.0%). Defenders of the transabdominal procedure justified with an expectancy of lower complication rate (39%), namely impairment of sexual function and fertility (22%). The female gender and the familiarity with transvaginal surgery were the stronger predictors of the option for this approach (70.6% vs 48.5%; p=0,016 and 85.3% vs 46.6%; p <0.001 respectively). CONCLUSIONS: Contrasting with similar surveys published on transvaginal NOTES, the vaginal specimen extraction after conventional laparoscopic nephrectomy was fairly accepted by the inquired surgeons.