JOSE PONTES JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- High CD39 expression is associated with the non-muscle-invasive phenotype of human bladder cancer(2021) FERREIRA, J. M.; MATHEUS, L. H. G.; ALMEIDA, R. V. S. de; MELO, P. A. de Souza; LEITE, K. R. M.; MURTA, C. B.; CLARO, J. F. de Almeida; CAMACHO, C. P.; PONTES-JúNIOR, J.; Dellê H.Background: An accurate prediction of progression is critical to define the management of bladder cancer (BC). The ectonucleotidases CD39 and CD73 play strategic roles in calibrating purinergic signals via an extracellular balance between ATP and adenosine. The altered expression of these enzymes plays a potential role in tumor invasion and metastasis, therefore, has been proposed to be used for prognosis of solid tumor. In BC this is not yet clear. Objective: This study aimed to evaluate CD39 and CD73 expression in a cohort of patients with non-muscle-invasive (NMI) and muscle-invasive (MI) BC regard to its association with clinicopathological features. Materials and Methods: Retrospective clinical follow-up data and primary urothelial BC specimens of 162 patients were used (87 from patients who underwent transurethral resection and 75 from cystectomized patients). Tissue microarrays were constructed, and immunohistochemistry for CD39 and CD73 was performed to make associations with clinicopathological data. Results: Overall, 96 were NMI (59.3%) and 66 MI (40.7%). CD39 immunoreactivity in BC cells was found in 72% of the cases, while CD73 was found in 97%. High CD39 expression alone was more frequent in NMI BC (p < 0.001), while CD73 expression was not powerful to predict the stage of BC. The association of both markers confirmed that only CD39 has potential in BC prognosis. Conclusions: The altered expression of CD39 presented herein supports the idea that this ectonucleotidase may be involved in bladder tumorigenesis. High expression of CD39 in tumor cells is correlated with the early stage of BC. Copyright: © 2021 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Consensus on Prostate Cancer Treatment of Localized Disease With Very Low, Low, and Intermediate Risk: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC)(2021) LUZ, Murilo de Almeida; GUIMARAES, Gustavo Cardoso; NARDI, Aguinaldo Cesar; POMPEO, Alexandre Saad Feres Lima; SARKIS, Alvaro Sadek; NOWIER, Amr; POMPEO, Antonio Carlos Lima; JR, Archimedes Nardozza; JR, Ari Adamy; CARNEIRO, Arie; SALVAJOLI, Bernardo Peres; BENIGNO, Bruno Santos; JR, Celso Heitor de Freitas; CHADE, Daher Cezar; ANGOTTI, Clarissa; PALHARES, Daniel Moore Freitas; OTERO, Danilo Armando Citarella; SILVA NETO, Deusdedit Cortez Vieira da; CARVALHAL, Eduardo Franco; GIL, Erlon; ARRUDA, Fernando Freire de; KORKES, Fernando; LEMOS, Gustavo Caserta; CARVALHAL, Gustavo Franco; CARVALHO, Icaro Thiago de; GIMPEL, Ivan Federico Pinto; CHAMBO, Jose Luis; JR, Jose Pontes; RIBEIRO FILHO, Leopoldo Alves; NOGUEIRA, Lucas Mendes; WROCLAWSKI, Marcelo Langer; FREITAS, Marcelo Roberto Pereira; ARAP, Marco Antonio; SADI, Marcus Vinicius; BULBUL, Muhammad; COELHO, Rafael Ferreira; GADIA, Rafael; KHAULI, Raja B.; REIS, Rodolfo Borges Dos; ROJAS, Rodrigo Antonio Ledezma; GUIMARAES, Roger Guilherme; ALDOUSARI, Saad; FERRIGNO, RobsonPURPOSE A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.
conferenceObject PROSPECTIVE RANDOMIZED TRIAL COMPARING OPEN TO LAPAROSCOPIC PARTIAL NEPHRECTOMY (NCT01809119)(2021) SAWCZYN, Guilherme; GUGLIELMETTI, Giuliano; RODRIGUES, Gilberto; CARDILLI, Leonardo; CORDEIRO, Mauricio; NEVES, Luis; PONTES, Jose; FAZOLI, Arnaldo; COELHO, Rafael; SROUGI, Miguel; NAHAS, William- Reply to: Axel Heidenreich. Still Unanswered: The Role of Extended Pelvic Lymphadenectomy in Improving Oncological Outcomes in Prostate Cancer. Eur Urol 2021;79:605-6(2021) LESTINGI, Jean F. P.; GUGLIELMETTI, Giuliano B.; TRINH, Quoc-Dien; COELHO, Rafael F.; JR, Jose Pontes; BASTOS, Diogo A.; CORDEIRO, Mauricio D.; SARKIS, Alvaro S.; FARAJ, Sheila F.; MITRE, Anuar I.; SROUGI, Miguel; NAHAS, William C.
- Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial(2021) LESTINGI, Jean F. P.; GUGLIELMETTI, Giuliano B.; TRINH, Quoc-Dien; COELHO, Rafael F.; PONTES, Jose Jr Jr; BASTOS, Diogo A.; CORDEIRO, Mauricio D.; SARKIS, Alvaro S.; FARAJ, Sheila F.; I, Anuar Mitre; SROUGI, Miguel; NAHAS, William C.Background: The role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs). Objective: To determine whether EPLND has better oncological outcomes than limited PLND (LPLND. Design, setting and participants: This was a prospective, single-center phase 3 trial in patients with intermediate-or high-risk clinically localized PCa. Intervention: Randomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally. Outcome measurements and statistical analysis: The primary endpoint was biochemi-cal recurrence & ndash;free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND. Results and limitations: In total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63 & ndash;1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17 & ndash;1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3 & ndash;5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14 & ndash;0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study. Conclusion: This RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analy-sis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3 & ndash;5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP. Patient summary: In this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.
- Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis(2021) FURUYA, Tatiane Katsue; MURTA, Claudio Bovolenta; CARRASCO, Alexis German Murillo; UNO, Miyuki; SICHERO, Laura; VILLA, Luisa Lina; CARDILLI, Leonardo; COELHO, Rafael Ferreira; GUGLIELMETTI, Giuliano Betoni; CORDEIRO, Mauricio Dener; LEITE, Katia Ramos Moreira; NAHAS, William Carlos; CHAMMAS, Roger; JR, Jose PontesSimple Summary: As there are still no biomarkers reported in clinical practice in penile cancer (PeC), we aimed to investigate and validate molecular signatures based on miRNA and mRNA profiles to identify molecular drivers and pathways involved in PeC tumorigenesis. We found eight DEmiRs and 37 DEGs comparing tumoral tissues (TT) paired with non-neoplastic tissues (NNT) of PeC patients. Four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) were identified as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. Furthermore, we performed an analysis of miRNA-mRNA interaction and found disruption in the dynamics of the regulation of eight pairs during tumor development that have never been described in PeC. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis. Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.
- Early Effects of High-intensity Focused Ultrasound (HIFU) Treatment for Prostate Cancer on Fecal Continence and Anorectal Physiology(2021) ALMEIDA, Renato Vasconcelos Souza de; SILVINO, Jose Ricardo Cruz; KALIL, Jamile Rosario; JR, Vitor Lazarini dos Santos; SOUZA, Vinicius Meneguette Gomes de; JR, Jose Pontes; GUGLIELMETTI, Giuliano Betoni; SANCHEZ-SALAS, Rafael Ernesto; CLARO, Joaquim Francisco de Almeida; MURTA, Claudio BovolentaOBJECTIVE To evaluate high-intensity focused ultrasound (HIFU) effects on anorectal physiology and fecal continence or constipation, and on quality of life (QoL). METHODS We prospectively evaluated 26 patients with localized prostate cancer who underwent HIFU. The Rome III criteria for functional constipation, the Cleveland Clinic Florida Fecal Incontinence Score, and the Fecal Incontinence QoL Score questionnaires were answered before and after treatment. Anorectal manometry was used to evaluate resting and squeezing pressures, sustained contraction, paradoxical puborectalis contraction, rectal sensation, and rectal capacity. RESULTS Thirteen patients underwent hemiablation and 13 underwent whole-gland ablation. There was no difference between groups regarding the Rome III criteria for functional constipation results. The Cleveland Clinic Florida Fecal Incontinence Score results showed that 3 (11.5%) of patients had mild fecal incontinence before HIFU and 5 (19.2%) had it afterward (P = .625). No patients reported poor QoL due to fecal incontinence in the Fecal Incontinence QoL Score. Anorectal manometry demonstrated no decrease in resting pressure after treatment (P = .299), while squeezing pressure significantly increased from 151.87 to 167.91 mm Hg (P = .034). The number of patients with normal sustained contraction remained the same (20 [77%]). Paradoxical puborectalis contraction was seen in 12 (46%) of the patients before the procedure and in 13 (50%) after (P = .713). Improvement in sensory parameters was not significant: first sense changed from 73.46 to 49.71 mL (P = .542) and first urge from 98.27 to 82.88 mL (P = .106). Rectal capacity had a nonsignificant decrease from 166.15 to 141.15mL (P = .073). CONCLUSION HIFU did not cause significant changes in anorectal physiology. Fecal incontinence or constipation after HIFU was not observed via validated questionnaires. (c) 2020 Elsevier Inc.
- Treatment of Localized and Locally Advanced, High-Risk Prostate Cancer: A Report From the First Prostate Cancer Consensus Conference for Developing Countries(2021) KHAULI, Raja; FERRIGNO, Robson; GUIMARAES, Gustavo; BULBULAN, Muhammad; USON JUNIOR, Pedro Luiz Serrano; SALVAJOLI, Bernardo; PALHARES, Daniel Moore Freitas; RACY, Douglas; GIL, Erlon; ARRUDA, Fernando Freire de; LEMOS, Gustavo Caserta; CARVALHAL, Gustavo Franco; CARVALHO, Icaro Thiago de; MARTINS, Igor Austin Fernandes; GIMPEL, Ivan Frederico Pinto; SALVAJOLI, Joao Victor; CHAMBO, Jose Luis; PONTES JUNIOR, Jose; RIBEIRO FILHO, Leopoldo Alves; NOGUEIRA, Lucas; FREITAS, Marcelo Roberto Pereira; WROCLAWSKI, Marcelo; ARAP, Marco Antonio; SADI, Marcus Vinicius; COELHO, Rafael; GADIA, Rafael; ROJA, Rodrigo Antonio Ledezma; HANRIOT, Rodrigo de Moraes; BARONI, Ronaldo; ZEQUI, Stenio; NAHAS, William Carlos; ALFER JUNIOR, Wladimir; MALUF, Fernando CotaitPURPOSE To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.
- Reply to Alberto Briganti, Giorgio Gandaglia, Markus Graefen, Steven Joniau, R. Jeffrey Karnes, and Francesco Montorsi's Letter to the Editor re: Jean FP Lestingi, Giuliano B. Guglielmetti, Quoc-Dien Trinh, et al. Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Eur Urol 2021;79:595-604. Time for a Change? Clinically Meaningful Reasons Why We Will Continue Performing Extended Pelvic Lymph Node Dissection in Selected Patients with Prostate Cancer(2021) LESTINGI, Jean F. P.; Quoc-Dien Trinh; COELHO, Rafael F.; PONTES JR., Jose; BASTOS, Diogo A.; NAHAS, William C.