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Effects of nickel and platinum complexes derived from Schiff base versus immunotherapy using Bacillus Calmette-Guerin (BCG) in the progression of non-muscle invasive bladder cancer (NMIBC)

Grant number: 13/04708-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2013
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Wagner José Fávaro
Grantee:Mirian Yoshiko Matsumoto
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Low effectiveness of treatments and the high rates of non-muscle-invasive urinary bladder cancer (NMIBC) can be caused by low effects of these therapies on mechanisms of tissue repair, reactive oxygen species (ROS) and angiogenesis. Immunotherapy with BCG (Bacille Calmette-Guerin) associated with transurethral resection (TUR) is currently the most effective treatment for NMIBC. However, side effects of varying strengths is associated with the use of BCG, from mild irritative symptoms to severe systemic reaction, that contributes to the cessation of treatment, in addition the rate of recurrence increases up to 30% after treatment. Thus, the development of new therapies for the treatment of NMIBC those are more effective and have fewer side effects than the conventional therapies are highly relevant. Therefore, there is a constant search for the development of new molecules or the improvement over existing drugs used to treat cancers like NMIBC. These facts imply the development of new drugs, like metal complexes derived from Schiff bases that are versatile and have anti-cancer activity offering a new perspective to combat some types of cancers, including NMIBC. This project aims to conduct a systematic study involving the development of complexes derived from Schiff bases and test the applicability of these complexes in the treatment of NMIBC. The synthesized compounds will be characterized by optical, chromatographic and spectroscopic techniques. Cell culture tests will reveal cytotoxicity of these synthesized compounds. Cells will be grown at 37°C in a 5% CO2 in air atmosphere. The cytotoxicity will be determined by counting after incubation time, in phosphate buffer medium. These studies involving cell culture aim to exploit the potential of the metal complexes as antitumor agents. We will use the Fischer 344 rat to induce NMIBC. For induction of NMIBC, the animals will be chemically induced to cancer through a dose of 1.5 mg/Kg of N-methyl-N-nitrosourea (MNU) dissolved in sodium citrate (1M pH 6.0) at 15 days (weeks 0, 2, 4, 6) total of 4 doses. Two weeks after the last dose of MNU, the animals will be examined by cystography to evaluate the occurrence of tumor and subsequently treated for 6 weeks with BCG or compounds derived from Schiff bases. After the period of treatment, the animals will be euthanized and the urinary bladders collected and analyzed for histopathological, immunohistochemistry e Western Blotting. It is expected to obtain more effective therapy with fewer side effects and that can supplement or replace traditional therapies such as BCG. Besides the expected scientific / technological progress, the project will contribute to the realization of fundamental research and advanced, that will occur with publications in specialized journals, and based on ability to train specialized human resources. Finally, the implementation of this project will provide integration between researchers from different areas and different institutions. (AU)

Filed patent(s) as a result of this research project

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020170047245 - Universidade Estadual de Campinas (UNICAMP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - March 2017, 09