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Oxidative Stress Analysis and Urothelial Cancer Stem Cells Features in the Urinary Bladder Cancer of Rats submitted to Bacillus Calmette-Guerin and Staphylococcus Enterotoxin B Immunotherapies

Grant number: 11/18441-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2012
Effective date (End): December 31, 2012
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Wagner José Fávaro
Grantee:Mariana Anteghini Castilho
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The high frequency of recurrence of bladder cancer (BC) and its heterogeneous presentation prompted us to suppose that cancer stem cells (CSCs) could be involved in the development of this kind of tumor. CSCs constitute a rare population of undifferentiated tumorigenic cells responsible for tumor initiation, maintenance, and spreading. Recently, there has been increased interest in research of the role of free radicals in carcinogenesis and the role of antioxidant materials in the prevention, treatment, and alleviation of therapy related side effects of cancer. Intravesical Bacillus Calmette-Guerin therapy is considered the most successful treatment for superficial bladder cancer. However, undesirable effects of BCG were noted. The Staphylococcal Enterotoxin B (SEB) is a potential candidate to intravesical therapy of bladder cancer, despite having doubts about this topic. Thus, the aims of the hereby study are to characterize and to compare the molecular and morphological effects of the BCG and SEB treatments in the BC of rats induced experimentally, as well as to characterize the CSCs. Fifty female Fisher 344 rats were anesthetized and 10 of them received 0.3 ml dose of saline (Control group). Other 40 rats received 1.5 mg/kg dose of n-methyl-n-nitrosourea, intravesically every other week, on weeks 0, 2, 4, 6. After MNU treatment, the 40 rats were divided into 4 groups: The MNU group received the same treatment as the Control group for 6 weeks; The BCG group received 106 CFU dose of BCG for 6 weeks; The SEB group received 10 mg/Kg dose of SEB intravesically for 6 weeks and The BCG-SEB group received simultaneous BCG and SEB treatments. After 6 weeks of treatment, all urinary bladders were collected for histopathological, immunological and Western Blotting analyses.