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Histopathological and Molecular Analyses of Bacillus Calmette-Guerin Intravesical Immunotherapie Associated with Aerobic Exercise in Non-Muscle Invasive Bladder Cancer.

Grant number: 12/20997-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2013
Effective date (End): January 31, 2014
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:José Carlos Souza Trindade Filho
Grantee:Flávia Bessi Constantino
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


The high frequency of recurrence of bladder cancer (BC) could be related to low effects of current therapies on the mechanisms of tissue repair, angiogenesis and antioxidant enzymes. Intravesical Bacillus Calmette-Guerin (BCG) therapy is considered the most successful treatment for superficial bladder cancer. Although intravesical BCG immunotherapy treatment can reduce the risk of recurrence and progression, its use is limited by the adverse effect profile and intolerance that occurs in 20% of patients. Scientific evidences suggest that environmental factors, lifestyle and, mainly physical exercise can reduce the incidence of cancer and may slow tumor growth by 50%. Given the strategic role of new therapeutic modalities and the need for specific studies in the field of urothelial carcinogenesis, there is the aerobic exercise, which opens new perspectives in the treatment of some cancers, including the urothelial cancer. Thus, the aims of the study are to characterize and to compare the histopathological and molecular effects of the intravesical BCG immunotherapie associated with aerobic exercise in the BC of rats chemically induced, as well as to establish the effects of these therapeutic strategies concerning the cellular repair pathways, angiogenesis and antioxidant enzymes. Sixty female Fisher 344, 7 week old, will be used. For induction of BC, 40 animals will be anesthetized and will receive 1.5 mg/kg dose of n-methyl-n-nitrosourea (MNU), intravesically every other week for 8 weeks (a total of 4 doses). The other 20 animals that will not receive MNU, will be considered as Control group (Group 1) and Control-Physical Exercise group (Group 2). Two weeks after the last dose of MNU, the animals will be divided into six groups (10 animals per group): Control group (Group 1) will receive 0.3 mL dose of 0.9% physiological saline, intravesically for 8 weeks; Control-Physical Exercise group (Group 2): will submitted to aerobic exercise protocol (swimming) for 8 weeks; MNU group (Group 3): will receive the same treatment as Group 1; MNU-BCG group (Group 4): will receive 106 CFU (40mg) dose of BCG, intravesically for 8 weeks; MNU-Physical Exercise (Group 5): will receive the same treatment as Group 2; MNU-Physical Exercise-BCG group (Group 6): will receive the same treatment as Group 2 and Group 4. After 18 weeks of treatment, all bladders will be collected for histopathological and immunological.