BRUNO ZILBERSTEIN
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
32 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 32
- Characterization of oncogene suppressor marker expression in patients with submucosal gastric carcinoma(2018) MORON, Roberson A.; JACOB, Carlos Eduardo; BRESCIANI, Claudio Jose Caldas; SIMOES, Kleber; ALVES, Venancio Avancini Ferreira; IRYA, Kyoshi; GAMA-RODRIGUES, Joaquim; CECCONELLO, Ivan; LONGATTO-FILHO, Adhemar; ZILBERSTEIN, BrunoThe aim of the present study was to determine the clinical significance of p53 and p21(ras) p21(wafl), p27(kip1) and p16(ink4a) expression in cases of early gastric cancer. A total of 81 patients who had undergone gastrectomy with D2 lymphadenectomy between 1971 and 2004 were retrospectively investigated. The immunohistochemical expression of p21ras, p53, p21waf1.cip1, p27kip1 and p16ink4a in the tissues was evaluated. In normal, metaplastic and tumoral mucosa, p53 was positive in 53, 87.3, and 87.1% of the cases, respectively. In the same tissues, p21ras was positive in 85.3, 86 and 96.8%, respectively. Positivity for p16ink4a was detected in 46.3, 91.1 and 86% of the cases, respectively, whereas p27kip1 was positive in 60, 94.7 and 95.3%, and p21wafl/ cip1 was positive in 32.4, 72.7 and 71.4% of the cases, respectively. All the tumors were positive for p53. Tumors with lymph node invasion presented with overexpression (+ 4) of p53 in 47% of the cases vs. 17% of patients who did not have lymph node involvement. Therefore, higher expression of p53, p21ras and p21wafl/ cip1 in the tumor exhibited a statistically significant association with lymph node involvement.
- Imagine a world without cancer(2014) BRUECHER, Bjoern L. D. M.; LYMAN, Gary; HILLEGERSBERG, Richard van; POLLOCK, Raphael E.; LORDICK, Florian; YANG, Han-Kwang; USHIJIMA, Toshikazu; YEOH, Khay-Guan; SKRICKA, Tomas; POLKOWSKI, Wojciech; WALLNER, Grzegorz; VERWAAL, Vic; GAROFALO, Alfredo; D'UGO, Domenico; ROVIELLO, Franco; STEINAU, Hans-Ulrich; WALLACE, Timothy J.; DAUMER, Martin; MAIHLE, Nitah; III, Thomas J. Reid; DUCREUX, Michel; KITAGAWA, Yuko; KNUTH, Alexander; ZILBERSTEIN, Bruno; STEELE, Scott R.; JAMALL, Ijaz S.Background: Since the ""War on Cancer"" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. Discussion: Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor-and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient's own results. As combined strategies may be outcome-orientated and integrate tumor-, patient-as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. Summary: Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer.
- Gastric Remnant Carcinosarcoma: Case Report and Review of the Literature(2021) RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; MELLO, Evandro Sobroza de; ALMEIDA, Jose Luiz; ZILBERSTEIN, Bruno; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan
- Carnoy's solution increases the number of examined lymph nodes following gastrectomy for adenocarcinoma: a randomized trial(2016) DIAS, Andre Roncon; PEREIRA, Marina Alessandra; MELLO, Evandro Sobroza; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; RIBEIRO JUNIOR, UlyssesPathological examination of a minimum of 16 lymph nodes is recommended following surgery for gastric adenocarcinoma, despite this a longer survival is expected when 30 or more lymph nodes are examined. Small lymph nodes are difficult to identify, and fat-clearing solutions have been proposed to improve this, but there is no evidence of their clinical benefit. Fifty D2 subtotal gastrectomy specimens were randomized for fixation in Carnoy's solution (CS) or 10 % neutral buffered formalin (NBF), with subsequent fat dissection. After dissection, the residual fat from the NBF group, instead of being discarded, was immersed in CS and dissected again. Data from 25 D2 subtotal gastrectomies performed before the study were also analyzed. The mean number of examined lymph nodes was 50.4 and 34.8 for CS and NBF, respectively (p < 0.001). Missing lymph nodes were found in all cases from the residual fat group (mean of 16.9), and in eight of them (32 %) metastatic lymph nodes were present; this allowed the upstaging of two patients. Lymph nodes in the CS group were smaller than those in the NBF group (p = 0.01). The number of retrieved lymph nodes was similar among the NBF and Retrospective groups (p = 0.802). Compared with NBF, CS increases lymph node detection following gastrectomy and allows a more accurate pathological staging. No influence of the research protocol on the number of examined lymph nodes was observed.
- Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients(2013) MARTINHO, Olga; SIMOES, Kleber; LONGATTO-FILHO, Adhemar; JACOB, Carlos Eduardo; ZILBERSTEIN, Bruno; BRESCIANI, Claudio; GAMA-RODRIGUES, Joaquim; CECCONELLO, Ivan; ALVES, Venancio; REIS, Rui ManuelGastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in similar to 83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in similar to 56% of primary tumors and in similar to 90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker.
- Schistosomiasis Misleading Gastric Cancer Treatment(2020) RAMOS, Marcus Fernando Kodama Pertille; DUARTE, Vinicius Campos; PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi de; SCHMERLING, Claudia Kliemann; ZILBERSTEIN, Bruno; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan
conferenceObject Liver Irradiation Increases Relapse-Free Survival in Adjuvant Gastric Cancer Treatment(2013) VASCONCELOS, K.; CHEN, A. T. C.; HONG, C. B. C.; NAKAZATO, D.; STELKO, G.; HOFF, P. M. G.; TAKEDA, F. R.; ZILBERSTEIN, B.; RIBEIRO JUNIOR, U.; NADALIN, W.- Gastric cancer with microsatellite instability displays increased thymidylate synthase expression(2022) PEREIRA, Marina A.; DIAS, Andre R.; RAMOS, Marcus F. K. P.; CARDILI, Leonardo; MORAES, Rafael D. R.; ZILBERSTEIN, Bruno; NAHAS, Sergio C.; MELLO, Evandro S.; JR, Ulysses RibeiroBackground Gastric cancer (GC) with microsatellite instability (MSI) is a less aggressive disease and associated with resistance to 5-fluorouracil (5-FU)-based chemotherapy (CMT). Thymidylate synthase (TS) is inhibited by 5-FU, and another potential mediator of therapeutic resistance to 5-FU. Therefore, we aimed to analyze the association between MSI and TS expression in GC, and its impact on disease outcomes. Methods We retrospectively evaluated GC who underwent D2-gastrectomy. MSI and TS were analyzed by immunohistochemistry. We also investigated p53 expression, PD-L1 status, and tumor-infiltrating lymphocytes (CD4 and CD8). Results Out of 284 GC, 60 (21.1%) were MSI. Median TS-score for all cases was 16.5. TS expression was significantly higher in MSI compared to microsatellite-stable (MSS; p < 0.001). Considering both status, GC were classified in four groups: 167 (58.8%) MSS + TS-low; 57 (20.1%) MSS + TS-High; 24 (8.5%) MSI + TS-low; and 36 (12.7%) MSI + TS-high. MSI + TS-high group had less advanced pTNM stage, higher CD8+T cells levels (p < 0.001) and PD-L1 positivity (p < 0.001). Normal p53 expression was related to MSI GC (p < 0.001). Improved survival was observed in MSI + TS-high, but no survival benefit was seen with CMT. Conclusion MSI GC was associated with high TS levels, which may explain therapeutic resistance to 5-FU. Additionally, MSI + TS-high showed better survival, but without improvement with CMT.
- Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer(2022) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; MORAES, Rafael Dyer Rodrigues de; RIBEIRO, Renan Ribeiro E.; ALVES, Venancio Avancini Ferreira; ZILBERSTEIN, Bruno; MELLO, Evandro Sobroza de; JR, Ulysses RibeiroObjective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune -related score.Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC).Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival.Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.
conferenceObject Clinicopathological Characteristics and Prognostic Value of HER2, PD-L1 and MSI Expression in Curative Resectable Gastric Cancer Patients(2019) PEREIRA, M. A.; RAMOS, M. F.; FARAJ, S. F.; DIAS, A. R.; CIRQUEIRA, C. D.; CHARRUF, A. Z.; PERROTTA, F. S.; MELLO, E. S.; ZILBERSTEIN, B.; CECCONELLO, I.; YAGI, O. K.; ALVES, V. A.; JUNIOR, U. R.