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
13 resultados
Resultados de Busca
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- Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer(2012) REIS, Sabrina Thalita; LEITE, Katia Ramos M.; PIOVESAN, Luis Felipe; PONTES-JUNIOR, Jose; VIANA, Nayara Izabel; ABE, Daniel Kanda; CRIPPA, Alexandre; MOURA, Caio Martins; ADONIAS, Sanarelly Pires; SROUGI, Miguel; DALL'OGLIO, Marcos FranciscoBackground: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.
- The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior(2015) LEITE, Katia R. M.; MORAIS, Denis Reis; FLOREZ, Manuel Garcia; REIS, Sabrina T.; ISCAIFE, Alexandre; VIANA, Nayara; MOURA, Caio M.; SILVA, Iran A.; KATZ, Betina S.; PONTES JR., Jose; NESRALLAH, Adriano; SROUGI, MiguelBackground: The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. Methods: The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. Results: MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5 alpha-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5 alpha-dihydrotestosterone. Conclusion: Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.
- Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer(2015) REIS, Sabrina Thalita dos; VIANA, Nayara Izabel; ISCAIFE, Alexandre; PONTES-JUNIOR, Jose; DIP, Nelson; ANTUNES, Alberto Azoubel; GUIMARAES, Vanessa Ribeiro; SANTANA, Isaque; NAHAS, William Carlos; SROUGI, Miguel; LEITE, Katia Ramos MoreiraIntroduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
- PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis(2015) LEITE, Katia R. M.; REIS, Sabrina T.; PONTES JUNIOR, Jose; ZERATI, Marcelo; GOMES, Daniel de Oliveira; CAMARA-LOPES, Luiz H.; SROUGI, MiguelBackground: PD-L1 is a glycoprotein from the family of T-cell co-stimulatory molecules that are constitutively expressed by macrophages. Aberrant expression of PD-L1 is observed in human cancers associated with inhibition of the tumor-directed T-cell immune response. There are few reports in the literature evaluating PD-L1 expression in association to prognosis specifically in renal cell cancer clear cell type (RCC-CC). Methods: Immunohistochemistry using a PD-L1 polyclonal antibody was performed on a tissue microarray (TMA) that contained 115 surgical specimens of RCC-CC. Cases were classified based on the absence or presence of staining intensity in the cytoplasm and membranes of the tumor cells. Statistical analysis was used to determine the association of PD-L1 expression with classic prognostic factors and tumor recurrence. Results: PD-L1 expression was positive in 56.5 % of tumors. The univariate analysis showed a correlation between PD-L1 expression and nuclear Fuhrman grade (p = 0.021) and microvascular tumor embolization (p = 0.039). One hundred and four patients were monitored for a mean time of 115.7 months. Seventeen patients (16.3 %) suffered tumor recurrence. Negative outcomes were associated with higher nuclear grade tumors, PD-L1 expression, and the presence of microvascular invasion. Conclusion: Our findings confirm that PD-L1 expression is an important prognostic factor in RCC-CC.
- MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer(2011) REIS, Sabrina Thalita; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; SOUSA-CANAVEZ, Juliana Moreira de; DALL'OGLIO, Marcos Francisco; PASSEROTTI, Carlo C.; ABE, Daniel Kanda; CRIPPA, Alexandre; CRUZ, Jose Arnaldo Shiomi da; TIMOSZCZUK, Luciana M. S.; SROUGI, Miguel; LEITE, Katia R. M.Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9 and its specific inhibitors, TIMP-1 and RECK, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome in prostate cancer (PC). Methods: MMP-9, TIMP-1, and RECK expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79 patients with clinically localized PC submitted to radical prostatectorny (RP). Frozen benign prostatic tissue from another 10 men with prostate cancer, also submitted to RP, was analyzed to determine if the profile of gene expression was maintained. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). Results: In the tumor samples, MMP-9 was overexpressed by 9.2 times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times, respectively). Overexpression of MMP-9 was significantly related to PSA levels above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9 was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and RECK, in contrast to their underexpression in tumor samples. Conclusion: Our results show that MMP-9 is overexpressed and its negative regulators are underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the carcinogenesis process. Additionally, we noticed a relationship between MMP-9 overexpression and increased levels of PSA, an important prognostic factor. In benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained because the expression of its negative regulators is preserved.
- Tgf-beta 1 expression as a biomarker of poor prognosis in prostate cancer(2011) REIS, Sabrina Thalita dos; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; SOUSA-CANAVEZ, Juliana Moreira de; ABE, Daniel Kanda; CRUZ, Jose Arnaldo Shiomi da; DALL'OGLIO, Marcos Francisco; CRIPPA, Alexandre; PASSEROTTI, Carlo Camargo; RIBEIRO-FILHO, Leopoldo A.; VIANA, Nayara Izabel; SROUGI, Miguel; LEITE, Katia Ramos MoreiraOBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-beta 1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-beta 1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of 11 patients with benign prostate hyperplasia. The expression levels of TGF-beta 1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-beta 1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-beta 1, a higher expression level was found in patients with Gleason scores >= 7 when compared to patients with Gleason scores <7 (p = 0.002). Among the 26 cases of TGF-beta 1 overexpression, 92.3% had poor prognostic features. CONCLUSIONS: TGF-beta 1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-beta 1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-beta 1 in prostate carcinogenesis.
- Indoleamine 2,3-dioxygenase expression in the prognosis of the localized prostate cancer(2020) FERREIRA, Janaina Mendes; DELLE, Humberto; CAMACHO, Cleber Pinto; ALMEIDA, Robson Jose; REIS, Sabrina Thalita; MATOS, Yves Silva Teles; LIMA, Amanda M. Ramos; LEITE, Katia Ramos Moreira; PONTES-JUNIOR, Jose; SROUGI, MiguelBackground Indoleamine 2,3-dioxygenase (IDO1) is an enzyme that acts as an immunomodulatory molecule. It is found in several types of cancer where it seems to be associated with tumor escape due to its immunosuppressive mechanisms. However, the role of IDO1 expression in prostate cancer (PC) is unclear. The aim of our study was to evaluate the expression of IDO1 in localized PC and to correlate with the classic prognostic factor and recurrence after surgical treatment. Methods We retrospectively evaluated surgical specimens from 111 patients with localized PC, who underwent radical prostatectomy. Recurrence was defined as a prostate specific antigen (PSA) level exceeding 0.2 ng/mL postoperatively, and the follow-up was 123 months. IDO1 expression was evaluated by immunohistochemistry in 72 cases of which 42 (58%) had biochemical recurrence. Results Lower IDO1 expression was associated with higher Gleason score (p = 0.022) and PSA levels (p = 0.042). The multivariate analyses revealed that the loss of IDO1 and higher PSA were independently associated with biochemical recurrence. The chance of recurrence was increased by 85% in patients with lower IDO1 [OR = 0.15;p = 0.009 CI 95% (0.038-0.633)] and increased by 5.5 times in patients with higher PSA [OR = 5.51;p = 0.012 CI 95% (1.435-21.21)]. The recurrence-free survival curve also demonstrates that lower IDO1 was associated with lower time to biochemical recurrence (p = 0.0004). Conclusion The loss of IDO1 expression was associated with increased chance of biochemical recurrence, higher PSA, and a Gleason score in localized PC.
- 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.
- Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer(2015) LEITE, Katia R. M.; REIS, Sabrina T.; VIANA, Nayara; MORAIS, Denis R.; MOURA, Caio M.; SILVA, Iran A.; PONTES JR., Jose; KATZ, Betina; SROUGI, MiguelThe search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip (R) miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.
- miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer(2012) REIS, Sabrina Thalita; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; DALL'OGLIO, Marcos Francisco; DIP, Nelson; PASSEROTTI, Carlo Camargo; ROSSINI, Guilherme Ayres; MORAIS, Denis Reis; NESRALLAH, Adriano Joao; PIANTINO, Camila; SROUGI, Miguel; LEITE, Katia R.Background: Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line. Materials and methods: To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR). Results: The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025). Conclusions: Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.