Avelino Fraga

Universidade do Porto

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Ricardo Ribeiro

Maastricht University

Vítor Cavadas

Hospital de Santo António

Rui Medeiros

Portuguese League Against Epilepsy

Cátia Monteiro

University of Aveiro

Miguel Silva‐Ramos

Universidade do Porto

Mariana Madanelo

Hospital de Santo António

Sofia Mesquita

Hospital de Santo António

F. Pina

Universidade do Porto

Javier Gómez‐Ambrosi

Clinica Universidad de Navarra

Luís Osório

Hospital de Santo António

Cooperative Institutions

Universidade do Porto

Centro Hospitalar do Porto

Hospital de Santo António

IPO Porto

Instituto Português de Oncologia Francisco Gentil

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto

University of Lisbon

University College London

Universidade de São Paulo

Hospital de São João

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Tumor Cell-educated Periprostatic Adipose Tissue Acquires an Aggressive Cancer-promoting Secretory Profile

Cellular Physiology and Biochemistry (2012)

Ricardo Ribeiro Cátia Monteiro Virgínia Cunha Andreia S. Azevedo Maria José Oliveira

Background/Aims: The microenvironment produces important factors that are crucial to prostate cancer (PCa) progression. However, the extent to which the cancer cells stimulate periprostatic adipose tissue (PPAT) to produce these proteins is largely unknown. Our purpose was to determine whether PCa cell-derived factors influence PPAT metabolic activity. Methods: Primary cultures of human PPAT samples from PCa patients (adipose tissue organotypic explants and primary stromal vascular fraction, SVF) were stimulated with conditioned medium (CM) collected from prostate carcinoma (PC3) cells. Cultures without CM were used as control. We used multiplex analysis and ELISA for protein quantification, qPCR to determine mitochondrial DNA (mtDNA) copy number and zymography for matrix metalloproteinase activity, in order to evaluate the response of adipose tissue explants and SVFs to PC3 CM. Results: Stimulation of PPAT explants with PCa PC3 CM induced adipokines associated with cancer progression (osteopontin, tumoral necrosis factor alpha and interleukin-6) and reduced the expression of the protective adipokine adiponectin. Notably, osteopontin protein expression was 13-fold upregulated. Matrix metalloproteinase 9 activity and mitochondrial DNA copy number were higher after stimulation with cancer CM. Stromovascular cells from PPAT in culture were not influenced by tumor-derived factors. Conclusion: The modulation of adipokine expression by tumor CM indicates the pervasive extent to which tumor cells command PPAT to produce factors favorable to their aggressiveness.

Osteopontin

10.1159/000337604

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Citations (76)

VE61 Robot-assisted partial nephrectomy with HugoTM RAS system in a Horseshoe kidney

European Urology Open Science (2024)

Sofia Mesquita Paulo Príncipe Diana Aguiar de Sousa Avelino Fraga Miguel Silva‐Ramos

Horseshoe kidney

10.1016/s2666-1683(24)00843-7

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A hint for the obesity paradox and the link between obesity, perirenal adipose tissue and Renal Cell Carcinoma progression

Scientific Reports (2022)

Preza Fernandes Pedro Passos Miguel Mendes-Ferreira Adriana R. Rodrigues Alexandra Gouveia

Increasing evidence supports a role for local fat depots in cancer outcomes. Despite the robust positive association of obesity with renal cell carcinoma (RCCa) diagnosis, increased adiposity is inversely related to RCCa oncological outcomes. Here, we sought to ascertain whether imagiologically assessed local fat depots associate with RCCa progression and survival and account for this apparent paradox. A retrospective cohort of renal carcinoma patients elective for nephrectomy (n = 137) were included. Beyond baseline clinicopathological characteristics, computed tomography (CT)-scans at the level of renal hilum evaluated areas and densities of different adipose tissue depots (perirenal, subcutaneous, visceral) and skeletal muscle (erector spinae, psoas and quadratus lumborum muscles) were analyzed. Univariate and multivariable Cox proportional hazards models were estimated following empirical analysis using stepwise Cox regression. Age, visceral adipose tissue (VAT) area and body mass index (BMI) predicted tumour-sided perirenal fat area (R2 = 0.584), which presented upregulated UCP1 expression by 27-fold (P = 0.026) and smaller adipocyte areas, compared with subcutaneous depot. Multivariate analyses revealed that increased area of perirenal adipose tissue (PRAT) on the contralateral and tumour side associate with improved progression-free survival (HR = 0.3, 95CI = 0.1-0.8, P = 0.019) and overall survival (HR = 0.3, 95CI = 0.1-0.7, P = 0.009). PRAT measurements using CT, might become a possible tool, well correlated with other measures of obesity such as VAT and BMI, that will improve determination of obesity and contribute to assess the risk for disease progression and mortality in renal cancer patients. Present data supports the obesity paradox in RCCa, assumed that larger PRAT areas seem to protect from disease progression and death.

Obesity paradox

10.1038/s41598-022-24418-9

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Citations (7)

Additional file 14: of Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study

Figshare (2018)

Yan Cheng Cátia Monteiro Andreia Matos Jiaying You Avelino Fraga

Table S12. GO molecular function analysis of the overlapping genes. GO molecular function analyses for the 14 overlapping genes. (XLSX 13 kb)

Epigenome

Profiling (computer programming)

10.6084/m9.figshare.6153110

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Mini-incision Living Donor Nephrectomy and Trans-peritoneal Laparoscopic Nephrectomy: Will There Be a Place for New Evidence?

Transplantation Proceedings (2019)

Diogo Nunes‐Carneiro André Marques-Pinto Isaac Braga João Cabral Manuela Almeida

Acute tubular necrosis

10.1016/j.transproceed.2019.01.044

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Extracorporeal shock wave lithotripsy: Retrospective Study on Possible Predictors of Treatment Success and Revisiting the Role of Non-contrast-enhanced Computer Tomography in Kidney and Ureteral Stone Disease

Research Square (Research Square) (2024)

Beatriz Oliveira Bernardo Teixeira Martinha Magalhães Nuno Vinagre Vítor Cavadas

Abstract Background Extracorporeal shock wave lithotripsy (ESWL) is a safe and efficient treatment option for urinary stone disease. The overall stone-free rate (SFR) varies significantly. This study aimed to assess the influence of stone size, location, stone density, and skin-to-stone distance (SSD), on the outcome of ESWL. We assessed whether pre-treatment non-contrast-enhanced CT scan (NCCT) confers significant advantages compared to kidney-ureter-bladder film (KUB) only. Methods We reviewed the medical records of 307 cases (165 men, 142 women) with renal and ureteral stones treated consecutively at our institution with ESWL between 2020 and 2023. 44 of these underwent a NCCT. The outcome of ESWL was defined in two ways: visible stone fragmentation on KUB, and the need for further treatment. Results Overall success of fragmentation was 85% (261 patients). 61% of patients (n = 184) didn’t need any further treatment. Stone size and location correlated significantly with treatment outcomes regarding the need for further treatment (p = 0,004) and stone fragmentation (p = 0,016), respectively. Unlike mean SSD (p = 0,462), the mean attenuation value (MAV) significantly correlated with the need for retreatment (p = 0,016). MAV seems to be a better predictor of treatment success (AUC of the ROC curve: 0,729), compared to stone size (AUC: 0,613). The difference between groups (with and without NCCT) in both treatment outcomes did not reach statistical significance. Conclusion During decision-making, information regarding SSD and MAV can be useful in more dubious scenarios. However, it appears that their inclusion doesn’t provide substantial advantages when compared to relying solely on KUB.

10.21203/rs.3.rs-4124036/v1

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Genetic Polymorphism in EGF Is Associated with Prostate Cancer Aggressiveness and Progression-Free Interval in Androgen Blockade–Treated Patients

Clinical Cancer Research (2008)

Ana Luísa Teixeira Ricardo Ribeiro Diana Cardoso Daniela Pinto Francisco S. N. Lobo

Abstract Purpose: Most prostate cancer patients develop resistance to androgen deprivation treatment, resulting in hormone resistance. Epidermal growth factor (EGF) activates several pro-oncogenic intracellular pathways inducing proliferation, differentiation, and tumorigenesis in epithelial cells. The EGF-EGF receptor pathway seems to be especially relevant in hormone-resistant prostate cancer stage. A single nucleotide polymorphism G>A in +61 locus of EGF gene has been described, in which A homozygous carriers express significantly less EGF protein compared with G allele carriers. Our purpose was to investigate the potential prognostic and predictive role of EGF functional genetic variant +61 G>A in prostate cancer patients submitted to androgen blockade therapy (ABT). Experimental Design: We conducted a case-control study in prostate cancer patients treated with ABT (n = 123) and in healthy controls without evidence of cancer (n = 152). Cumulatively, a follow-up study (median follow-up, 37 months) was undertaken to evaluate response to ABT therapy in prostate cancer patients. EGF +61 G>A genotypes were detected by PCR-RFLP. Results: We found increased risk in G carriers, after age-adjusted regression analysis, for being diagnosed with Gleason ≥7 and with metastatic disease compared with control group (CG; age-adjusted odds ratio, 3.37, P = 0.004 and age-adjusted odds ratio, 2.61, P = 0.043, respectively). Kaplan-Meier survival analysis and log-rank test showed an influence of EGF +61 G>A polymorphism in time to relapse during ABT (P = 0.018). Conclusions: EGF functional polymorphism may contribute to earlier relapse in ABT patients, supporting the involvement of EGF as an alternative pathway in hormone-resistant prostatic tumors. Furthermore, our results lend support to EGF-EGF receptor pathway as an additional therapeutic target during hormonal treatment.

10.1158/1078-0432.ccr-07-5119

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Citations (44)

Interleukin-6 functional polymorphism influences susceptibility and has a predictive factor in prostate cancer patients receiving androgen blockade therapy

European Journal of Cancer Supplements (2008)

Andreia S. Azevedo R. Ribeiro Avelino Fraga F. Pina Francisco S. N. Lobo

10.1016/s1359-6349(08)71346-6

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Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study

Clinical Epigenetics (2018)

Yan Cheng Cátia Monteiro Andreia Matos Jiaying You Avelino Fraga

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. 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. 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.

CpG site

Epigenome

10.1186/s13148-018-0490-3

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Rotterdam Prostate Cancer Risk Calculator: Development and Usability Testing of the Mobile Phone App

JMIR Cancer (2017)

Nuno Pereira‐Azevedo Luís Osório Avelino Fraga Monique J. Roobol

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.

Overdiagnosis

Calculator

Mobile phone

10.2196/cancer.6750

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Citations (52)