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Assessment of c-Myc activation in the treatment of urothelial carcinoma in rats with Bacillus Calmette-Guerin and Nitazoxanide with oral and intravesical association

Grant number: 17/15679-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2018
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Medicine - Surgery
Principal researcher:Leonardo Oliveira Reis
Grantee:Eduardo Riccetto
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Background: Therapies with combined drugs have indicated better efficiency in the treatment of urothelial carcinomas. The anthelmintic drug Nitazoxanide (NTZ) has shown promising results of anti-tumor and immunomodulatory action, which makes it a suitable candidate for combined therapies with the Bacillus Calmette-Guérin. Aims: To characterize and compare c-Myc activation between therapies with BCG, NTZ and lack of treatment on rats with urothelial carcinoma.Methodology: 50 rats of the Fischer 344 breed will be used in the study. UC will be induced with 4 intravesical instilations of N-methyl-N-nitrosurea, 15 days apart form each other. Animals will then be allocated into one of 5 study groups: Control Group (0,3 mL of saline solution at 0,9% concentration); BCG group (intravesical BCG at 106 UFC - 1mg); NTZ group (intravesical instillation of 400mg/kg of NTZ); BCG+NTZ group 1 (intravesical BCG at 106 UFC - 1mg and); BCG+NTZ group 2 (intravesical BCG at 106 UFC - 1mg and oral 400mg/kg of NTZ). The groups will be treated until the 16th week after the beginning of the experiment, at which point, the animals will be euthanized and urinary bladders will be collected for immunohistochemical (IHC) analysis of c-Myc activation. Predicted results: We expect to demonstrate the correlation between the reduction of c-Myc activation in IHC and the use of oral or intravesical NTZ in combination with BCG therapy. (AU)

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