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Apoptosis in urologic tumors

Grant number: 11/09720-0
Support type:Regular Research Grants
Duration: August 01, 2011 - July 31, 2013
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Flávio de Oliveira Lima
Grantee:Flávio de Oliveira Lima
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers: Carlos Márcio Nóbrega de Jesus ; João Lauro Viana de Camargo ; José Carlos Souza Trindade Filho

Abstract

Urological neoplasm are a major cause of morbidity and mortality in occident, and they have a high frequency in Brazil, mainly in south and south eastern states (Health Ministry; Ministério da Saúde, http:// www. datasus.gov.br). Prostate cancer, for example, is the most common neoplasm of man and the second cause of death, following lung cancer. Prostatic cancer incidence in Brazil for 2008 was 49.530 new cases. Apoptosis (programmed cell death) is an efficient physiological mechanism for cell suicide that is important for growth and cell differentiation processes in multicellular animals, controlling the number of cells and organ size. One of the striking characteristics of the great majority of cancers is their progressive resistance to apoptosis. morphological alterations observed in apoptosis are induced by the action of the caspases, especially by caspase-3. The inhibitors of apoptosis proteins (IAPs) are a family of molecular inhibitors of apoptosis, and they act by directly blocking cleaved caspase-3 (XIAP) or the protein SMAC/DIABLO, an antagonist. The inhibition of XIAP activity or the increase of SMAC activity might improve the therapeutic response of the patients. In this work we will evaluate the immunoexpression of IAPs and SMAC in prostatic carcinoma and urological tumors in general, and we will correlate the results with Apoptotic Index (AI), cellular proliferation, p53 protein immunoexpression and patient survival rate. TMA paraffin blocks will be make with prostatic cancer tissue initially, of patients operated at Hospital das Clinicas da Faculdade de Medicina de Botucatu. Sections of 4 µm will be processed by immunohistochemistry for survivin, XIAP, cIAP-1, cIAP-2 and SMAC, and the immunoexpression scores obtained. They will be correlated between each other and with the AI obtained by anti-cleaved caspase-3 and anti-cleaved cytokeratin-18 antibodies, the cellular proliferation index, p53 protein immunoexpression and patient survival data. (AU)