GABRIEL ARANTES GALVAO DIAS DOS SANTOS
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Cholesterol Triggers Nuclear Co-Association of Androgen Receptor, p160 Steroid Coactivators, and p300/CBP-Associated Factor Leading to Androgenic Axis Transactivation in Castration-Resistant Prostate Cancer(2022) PIMENTA, R.; CAMARGO, J. A.; CANDIDO, P.; GHAZARIAN, V.; GONçALVES, G. L.; GUIMARãES, V. R.; ROMãO, P.; CHIOVATTO, C.; MIOSHI, C. M.; SANTOS, G. A. dos; SILVA, I. A.; BIRBRAIR, A.; SROUGI, M.; NAHAS, W. C.; LEITE, K. R.; VIANA, N. I.; REIS, S. T.Background/Aims: Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo. Methods: Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA. Results: Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3 and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group. Conclusion: Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype. © 2022 Cell Physiol Biochem Press GmbH & Co KG. All rights reserved.
- Evaluation of AR, AR-V7, and p160 family as biomarkers for prostate cancer: insights into the clinical significance and disease progression(2024) PIMENTA, Ruan; MALULF, Feres Camargo; ROMAO, Poliana; CAETANO, Giovana Vilas Boas; SILVA, Karina Serafim da; GHAZARIAN, Vitoria; SANTOS, Gabriel A. dos; GUIMARAES, Vanessa; SILVA, Iran Amorim; CAMARGO, Juliana Alves de; RECUERO, Saulo; MELAO, Barbara V. Lima Aguiar; ANTUNES, Alberto Azoubel; SROUGI, Miguel; NAHAS, William; LEITE, Katia R. M.; REIS, Sabrina T.Purpose To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. Methods The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. Results The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001). Conclusion Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools.
- Digital application developed to evaluate functional results following robot-assisted radical prostatectomy* App for prostate cancer(2020) FARIA, Leandro F.; REIS, Sabrina T.; LEITE, Katia R.; CRUZ, Jose Arnaldo Shiomi da; PIMENTA, Ruan; I, Nayara Viana; AMARAL, Gabriela Q.; SANTOS, Gabriel A. G. D.; ILIAS, Daniel; FAKHOURI, Felipe; XAVIER, Geraldo; SROUGI, Miguel; PASSEROTTI, Carlo CamargoIntroduction: Mobile applications (""apps"") developed for smartphones and tablets are increasingly used in healthcare, allowing remote patient support or promoting self-health care. Prostate cancer (PC) screening allows for early-stage PC diagnosis, resulting in high rates of curative procedures such as radical prostatectomy. The main complications following surgery are urinary incontinence and erectile dysfunction. However, the exact numbers related to these morbidities are often missing due to brief interviews during consultations in the medical office. Therefore, the aim of this study was to create an app to determine whether response rates to preand post-surgical PC questionnaires will increase. Methods: The app was built using the IONIC framework system and provided to patients through a prospective randomized study. We included 100 patients divided into two groups: 1. first group used the app (n = 50); and 2. second group responded via validated printed questionnaires (control group) (n = 50). All patients received discharge counseling to respond to the questionnaires 1, 3, 6 and 12 months after the procedure. The app group received verbal guidance on how monitoring would occur, received an SMS containing a username and password providing access to the system and received reminder alerts to respond to the questionnaires. Results: The new app is called UroHealth and is available for download in the Apple App Store or at www.urohealth.com.br . When we evaluated the response rates, we found that 42.9% of the patients answered the preoperative questionnaire in the app group, while 16% responded in the control group (p = 0.003). By the end of the follow-up, we found that 24.5% of the patients answered the questionnaire in the app group, while 4% responded in the control group (p = 0.003). Conclusion: This app enabled almost 6 times more patients to answer long-term follow-up questions after surgical procedures, providing high-quality information regarding morbidity related to treatment. Although our initial results indicate that this app may become a useful tool in obtaining more frequent and realistic answers, thus helping to improve surgical techniques, other ways of reaching the patient should be tested to achieve higher response rates.
- Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model(2023) PIMENTA, Ruan; CAMARGO, Juliana A.; GONCALVES, Guilherme L.; GHAZARIAN, Vitoria; CANDIDO, Patricia; GUIMARAES, Vanessa R.; ROMAO, Poliana; CHIOVATTO, Caroline; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; NAHAS, William C.; LEITE, Katia R.; PESSOA, Ana Flavia Marcal; VIANA, Nayara I.; REIS, Sabrina T.BackgroundPreviously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia.Methods and resultsIn vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 & mu;g/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation.ConclusionOur results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.
- Robotically assisted laparoscopic radical prostatectomy induces lower tissue trauma than radical retropubic prostatectomy(2021) QUINTO, Denise; REIS, Sabrina T.; ZAMPOLLI, Lucca Juvele; PIMENTA, Ruan; GUIMARAES, Vanessa R.; VIANA, Nayara I.; SANTOS, Gabriel A. dos; GIMENEZ, Mario P.; LEITE, Katia R.; ZAMPOLLI, Hamilton; CRUZ, Jose Arnaldo S. da; SROUGI, Miguel; PASSEROTTI, Carlo C.To compare tissue trauma between Retropubic Radical Prostatectomy and Robotically Assisted Laparoscopic Radical Prostatectomy by inflammatory mediators. Serum samples from 40 patients submitted to RALP and 20 patients submitted to RRP were withdrawn at four different time points. The cytokines IL-4, IL-8, IL-6, IL-1B, IL-10 and TNF-alpha were detected using ELISA/Multiplex assays and xMAP-Luminex (R). With both techniques, IL-10 and IL-6 were higher in T4 than in T1-T3 (p = 0.001). IL-10 and IL-6 were higher in T4 in open surgery than in robotic surgery (p = 0.000 andp = 0.001, respectively). Compared with both groups, IL-6 and IL-10 were higher in T4 in open surgery than in robotic surgery. Thus, we can postulate that RALP causes less tissue trauma than classical RRP, as indicated by the more limited increase in inflammatory mediators such as IL-6 and IL-10.