Browsing by Author "Santos, PB"
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- Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?Publication . Santos, PB; Patel, H; Henrique, R; Félix, AProstate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.
- Oncocitoma renal: tem a URO-TC utilidade no diagnóstico histológico?Publication . Dores, J; Kronenberg, P; Santos, PB; Ferreira, S; Gomes, FCIntrodução: Ao longo dos últimos anos, a crescente utilização de exames imagiológicos, nomeadamente ecografia e tomografia computorizada (TC), traduziu-se num aumento do diagnóstico incidental de tumores renais, sobretudo pequenas massas renais (<4 cm). O conhecimento de que até 30% destas massas podem ser benignas, entre elas os oncocitomas, levou á procura de métodos de diagnóstico mais eficazes, de forma a evitar situações de sobretratamento e de forma a tornaram-se decisões terapêuticas mais fundamentadas. Objectivos: Analisar retrospectivamente uma série de tumores renais histologicamente comprovados, nomeadamente oncocitomas e carcinomas de células renais (CCR), e verificar se existem diferenças morfológicas e/ou nos padrões de captação de contraste através da URO-TC. Material e métodos: Identificámos todos os tumores renais entre 2004-2015 com o diagnóstico histológico de oncocitoma e de CCR. Estes resultados foram obtidos por biopsia do tumor renal, tumorectomia/nefrectomia parcial ou nefrectomia radical. Registámos e comparámos as características morfológicas e os padrões de captação de contraste na fase nefrográfica com medição de unidades de Hounsfield (HU) dos oncocitomas e dos CCR (células claras), selecionados de acordo com a dimensão (aprox. idêntica á dos oncocitomas) e obtidos na sequência de tumorectomia renal ou nefrectomia radical. Resultados: Identificaram-se 16 CCR e 31 oncocitomas, dos quais 15 foram excluídos por não termos acesso ás imagens de TC no sistema informático. A dimensão média dos oncocitomas foi 3,7 cm (1,8 – 14) e a dos CCR 3,5 cm (1,9 – 8,4). A atenuação de contraste média dos oncocitomas e dos CCR na fase sem contraste foi de 33 HU e 32 HU, respectivamente. Na fase nefrográfica, a captação média de contraste para os oncocitomas foi de 47,5 HU e 47,4 HU para os CCR. Na fase nefrográfica, a diferença de atenuação entre os oncocitomas e o parênquima renal normal foi 43,5 HU e a diferença de atenuação entre os CCR e o parênquima renal normal foi 59,7 HU. Estes resultados foram estatisticamente significativos (p<0,05). Não se identificaram outras alterações na fase excretora da TC, nem diferenças relevantes de carácter morfológico, nomeadamente nos contornos das lesões, presença de calcificações, ou de cicatriz central. Conclusões: Na avaliação imagiológica por URO-TC, nomeadamente na fase nefrográfica, parece existir uma tendência para maior isodensidade dos oncocitomas em relação ao parênquima renal normal. Este achado poderá contribuir para uma melhor decisão terapêutica, na medida em que nos pode direccionar para uma biópsia de confirmação em detrimento da excisão cirúrgica.
- Prostate stem cell antigen - novel biomarker and therapeutic target?Publication . Santos, PB; Patel, HRProstate stem cell antigen gene was originally identified through an analysis of genes upregulated in the human prostate cancer LAPC-4 xenograft model. PSCA was named inaccurately since it is not a marker for a stem cell population nor is it exclusively expressed in the prostate. The function of PSCA in normal cellular processes or carcinogenesis is currently unknown.
- The inflammation-related biomarker CXCR7 independently predicts patient outcome after radical prostatectomyPublication . Santos, PB; Lobo, J; Félix, A; Silva, F; Manso, RT; Costa, J, et al.INTRODUCTION: The influence of inflammation on prostate tumor carcinogenesis is currently much better known than with its role in prostate cancer (CaP) progression. We evaluated the prognostic value of epigenetic (HDAC1, HDAC4, H3Ac) and inflammation-related (CXCR4, CXCR7, CXCL12) biomarkers immunoexpression, in radical prostatectomy specimens, from 2 cohorts of CaP patients with long term follow-up. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded radical prostatectomy specimens were obtained from the pathology archives of Prof. Doutor Fernando Fonseca Hospital, in Amadora, Portugal and Portuguese Oncology Institute of Porto, in Porto, Portugal, and tissue microarrays were assembled. It was achieved a set of 234 patients submitted to radical retropubic prostatectomy between January 2000 and December 2005. Immunohistochemistry was used for evaluation of protein expression of epigenetic and inflammation-related markers. Nuclear staining was assessed using digital image analysis. Study outcomes included disease-specific survival and disease-free survival (DFS). Statistical analysis was tabulated using SPSS version 23.0. Hazard ratios (HRs) and survival curves were estimated using Cox-regression and Kaplan-Meyer models, respectively. Statistical significance was set at P < 0.05. RESULTS: Complete follow-up data was available for 234 patients and median follow-up time was 164 [11-218] months. Patients with higher CXCR4 immunoexpression experienced significantly worse disease-specific survival compared to patients with low expression (HR = 1.016, 95% CI: 1.002-1.031). The same happened with CXCL12 (HR = 0.546 95% CI: 0.322-0.926) and H3Ac (HR = 1.015, 95% CI: 1.001c1.029). In what concerns to DFS, patients with higher expression of CXCR4 and CXCR7 were significantly more prone to experience disease recurrence (HR = 1.003, 95% CI: 1.000-1.005 and HR = 1.111, 95% CI:1.032-1.196, respectively). When adjusted to pTStage and WHO Grade Groups, CXCR7 maintained independent impact on DFS (HR = 1.119, 95% CI: 1.032-1.214). CONCLUSIONS: The interplay between inflammation and epigenetics and its impact in CaP outcome deserves further studies in the future. CXCR7 shows an independent predictor for worse DFS after radical prostatectomy, and could provide important prognostic information for patient management after radical prostatectomy.
- Ultrassonografia doppler em andrologiaPublication . Coelho, M; Cardoso, AP; Santos, PB