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
6 resultados
Resultados de Busca
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- Adhesion molecules of detrusor muscle cells are influenced by a hypercholesterolemic diet or bladder outlet obstruction in a wistar rat model(2013) PONTES-JUNIOR, Jose; NUNES, Ricardo Luis Vita; REIS, Sabrina Thalita dos; OLIVEIRA, Luiz Carlos N. de; VIANA, Nayara; LEITE, Katia Ramos Moreira; BRUSCHINI, Homero; SROUGI, MiguelBackground: Cell adhesion molecules (CAMs) are essential for maintaining tissue integrity by regulating intercellular and cell to extracellular matrix interactions. Cadherins and catenins are CAMs that are located on the cell membrane and are important for adherens junction (AJ) function. This study aims to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO) promotes structural bladder wall modifications specific to alterations in the expression of cadherins and catenins in detrusor muscle cells. Methods: Forty-five 4-week-old female Wistar rats were divided into the following three groups: group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25% cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas group 2 underwent a partial BOO procedure that included a suture tied around the urethra. Six weeks later, all rats had their bladders removed, and previous exams were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and alpha-, beta-and gamma-catenins were evaluated by immunohistochemistry with a semiquantitative analysis. Results: Wistar rats fed a HCD (group 3) exhibited a significant increase in LDL cholesterol levels (p=0.041) and body weight (p=0.017) when compared to both groups that were fed a normal diet in a ten-week period. We found higher beta- and gamma-catenin expression in groups 2 and 3 when compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p = 0.002). Conclusions: A HCD in Wistar rats promoted, in addition to higher body weight gain and increased serum LDL cholesterol levels, overexpression of beta- and gamma-catenin in the detrusor muscle cells. Similar finding was observed in the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated rats. These findings may be associated with bladder dysfunctions that occur under such situations.
- Can Single Positive Core Prostate Cancer at biopsy be Considered a Low-Risk Disease after Radical Prostatectomy?(2013) SILVA, Ricardo Kupka da; DALL'OGLIO, Marcos Francisco; SANT'ANA, Alexandre Crippa; PONTES JUNIOR, Jose; SROUGI, MiguelPurpose: Single positive core in a prostate biopsy is usually associated with indolent prostate cancer (PCa) and is one of the active surveillance (AS) inclusion criteria. We investigated whether single positive core PCa at biopsy could define an archetype of low-risk disease. Materials and Methods: A total of 1320 consecutive patients were enrolled. Among them, 249 patients with single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed. Results: Out of the 249 patients, 172 (69.0%) had pathological findings >= pT2c and 87 (34.9%) had an undergraded Gleason Score (GS) based on the biopsy. Positive surgical margins (PSMs), extraprostatic extension (EPE) and seminal vesicle invasion (SVI) were found in 20.8%, 10.0% and 6.0% of patients, respectively. In a comparative analysis, we found that the PSA level, prostate weight and number of cores at biopsy are essential to correctly predict an indolent PCa. A total of 125 patients (67.3%) with nonpalpable tumors became high-risk tumors (pT2c-T3). Analyzing only nonpalpable tumors with a GS of 6 at biopsy (156 patients), we noted that 106 (67.9% of cT1) progressed from cT1c to pT2c-pT3. Conclusions: Single core PCa have clinically significant disease in the Radical Prostatectomy specimens, with considerable rates of overgrading for the GS, pT2c-pT3, PSMs, EPE and SVI. The treatment plan must be evaluated individually for patients with single core PCa and must take into account other prognostic factors when determining whether a patient should be managed with AS.
- The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer(2013) REIS, Sabrina T.; TIMOSZCZUK, Luciana S.; PONTES-JUNIOR, Jose; VIANA, Nayara; SILVA, Iran A.; DIP, Nelson; SROUGI, Miguel; LEITE, Katia R. M.OBJECTIVE: The aim of this study is to verify the expression of proteins that are controlled by miR-let7c, 100 and 218 using immunohistochemistry in tissue microarray representative of localized and metastasized the lymph nodes and bone prostate cancer. METHODS: To verify the expression of proteins that are controlled by miR-let7c (C-MYC, BUB1, RAS) 100 (SMARCA5, RB) and 218 (LAMB3) and cell proliferation (Ki-67) we used immunohistochemistry and computerized image system ImageJ MacBiophotonics in three tissue microarrays representative of localized prostate cancer and lymph node and bone metastases. miRNA expression was evaluated by qRT-PCR using 60 paraffin blocks to construct the tissue microarray representative of localized disease. RESULTS: RAS expression was increased in localized prostate cancer and bone metastases compared to the lymph nodes (p = 0.017). RB showed an increase in expression from localized prostate cancer to lymph node and bone metastasis (p = 0.036). LAMB3 was highly expressed in localized and lymph node metastases (p<0.001). Cell proliferation evaluated by Ki-67 showed an increase from localized prostate cancer to metastases (p<0.001). We did not found any relationship between C-MYC (p = 0.253), BUB1 (p = 0.649) and SMARCA5 (p = 0.315) protein expression with prognosis or tumor behavior. CONCLUSION: We found that the expression of RAS, RB, LAMB3 and Ki-67 changed in the different stages of prostate cancer. Furthermore, we confirmed the overexpression of the miRNAs let7c, 100 and 218 in localized prostate cancer but failed to show the control of protein expression by the putative controller miRNAs using immunohistochemistry.
- Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray(2013) ZERATI, Marcelo; LEITE, Katia R. M.; PONTES-JUNIOR, Jose; SEGRE, Cesar Camara; REIS, Sabrina Thalita; SROUGI, Miguel; DALL'OGLIO, Marcos FranciscoIntroduction: The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods: This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop (R) software. Results: The mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). Conclusion: Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.
- Perineural invasion detection in prostate biopsy is related to recurrence-free survival in patients submitted to radical prostatectomy(2013) KATZ, Betina; SROUGI, Miguel; DALL'OGLIO, Marcos; NESRALLAH, Adrian J.; SANT'ANNA, Alexandre C.; PONTES JR., Jose; ANTUNES, Alberto A.; REIS, Sabritia T.; VIANA, Nayara; SANUDO, Adriana; CAMARA-LOPES, Luiz H.; LEITE, Katia R. M.Objective: Perineural invasion (PNI) is detected in almost 20% of prostate biopsies and has been related to worse prognostic factors in radical prostatectomy (RP) specimens and lower disease-free survival rates. The aim of this study was to evaluate the importance of PNI during periods of extended prostate biopsies and to determine the value of this preoperative parameter as a predictor of pathologic findings in surgical specimens and in biochemical recurrence. Materials and methods: Between 2001 and 2009, 599 prostate biopsies and their respective RP specimens were examined in our laboratory. The RP specimens were always examined completely. The mean age of the patients was 61 years, and the mean PSA was 6.4 ng/mL. The mean and median number of biopsy cores obtained was 14.4 and 14, respectively. PNI was identified in 105 biopsies (17.5%). We studied the ability of PNI in prostate biopsies to determine the tumor stage in surgical specimens and the relationship of PNI with biochemical recurrence during a mean follow-up time of 51.4 months. Results: The presence of PNI in prostate biopsies was observed in older patients (63 vs. 61 years old, P = 0.008). All of the prognostic factors determined for the RP specimens were significantly worse in patients with PNI compared with those without PNI. PNI was strongly associated with a higher pathologic stage (87% specificity, 40% sensitivity, odds ratio 4.8). Stage pT3 prostatic cancer was determined in 46 (43.8%) of 105 patients with PNI on biopsy compared to 69 (14%) of 494 patients without PNI (P = 0.01). Fifty-six (19.6%) patients had a biochemical recurrence, and PNI correlated significantly with PSA recurrence. A Kaplan-Meier analysis revealed a significant difference in recurrence-free survival between patients with and without PNI (45% vs. 53%, respectively, P = 0.021, log-rank test = 0.19). Conclusion: PNI is an important morphologic preoperative predictor of the pathologic stage as well as biochemical recurrence and must always be mentioned when adenocarcinoma is diagnosed on prostate biopsies.
- Correlation between Beta1 integrin expression and prognosis in clinically localized prostate cancer(2013) PONTES-JUNIOR, Jose; REIS, Sabrina Thalita; BERNARDES, Felipe S.; OLIVEIRA, Luiz C. N.; BARROS, Erika Aparecida Felix de; DALL'OGLIO, Marcos Francisco; TIMOSCZUK, Luciana M. S.; RIBEIRO-FILHO, Leopoldo A.; SROUGI, Miguel; LEITE, Katia R. M.Integrins are transmembrane glycoprotein receptors that regulate cell-matrix interactions, thus functioning as sensors from the environment. They also act as cell adhesion molecules that are responsible for the maintenance of the normal epithelial phenotype. Some studies have reported a correlation between carcinogenesis and changes in integrin expression, especially beta 1 integrin, however its role in prostate cancer (PC) is unclear. The aim of our study was to evaluate the expression of beta 1 integrin in localized PC and to correlate the pattern of expression with recurrence after surgical treatment. Methods For this case-control study, we retrospectively selected surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Recurrence was defined as a PSA level exceeding 0.2ng/mL after surgery, and the median follow-up was 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two samples from each tumor. We employed a semiquantitative analysis and considered a case as positive when the expression was strong and diffusely present. Results: There was a loss of 11 cases during the tissue micro array assembling. beta 1 expression was positive in 79 of the 100 evaluated cases (79%). The univariate and multivariate analyses showed that the negative expression of beta 1 integrin was associated with biochemical recurrence (p = 0.047) and time to recurrence after radical prostatectomy (p = 0.023). When beta 1 was negative, the odds ratio for recurrence was 2.78 times higher than that observed in the positive cases [OR = 2.78, p = 0.047, IC 95% (1.01-7.66)]. Conclusions: The loss of beta 1 integrin immune expression was correlated with biochemical recurrence in patients treated with radical prostatectomy for localized PC.