Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-28T19:56:24Z No. of bitstreams: 1 DIS_ANA_HELENA_BRETANHA_LOPES_TORT_COMPLETO.pdf: 1228563 bytes, checksum: 1ae15f2eb2fe5ed55580c78c418cb7be (MD5) / Made available in DSpace on 2016-06-28T19:56:24Z (GMT). No. of bitstreams: 1 DIS_ANA_HELENA_BRETANHA_LOPES_TORT_COMPLETO.pdf: 1228563 bytes, checksum: 1ae15f2eb2fe5ed55580c78c418cb7be (MD5) Previous issue date: 2016-02-15 / Gliomas are primary tumors of the central nervous system that are associated with a high mortality rate; they course with an average survival rate of 2 years after the diagnosis. Less than 5 % of glioma patients survive more than five years after diagnosis, even those treated with state of the art protocols, which include surgery, radiotherapy and chemotherapy. Tumors result from impairments of intracellular signaling pathways, including the p38/MAPK pathway, which, are responsible to control of cell proliferation and tumorigenesis, among other cellular responses. The goal of the present work was to investigate the effects of ML3403, an inhibitor of p38/MAPK, on the viability and proliferation of glioma cells, and to assess its effect when combined with bevacizumab (BVZ). BVZ already used in the clinical setting as anadjuvant for treating gliomas. It is a monoclonal antibody against VEGF-A receptor and thus reduces the signaling involved in tumor angiogenesis. U138 and U251 glioma cells were treated with ML3403 (0.1 to 200 ?M) and BVZ (1 to 200 ?g/mL) and later assessedfor cell viability, by MTT method and proliferation by cell counting. The results demonstrate that treatment with ML3403 reduces glioma cell viability and proliferation. Co-treatment with BVZ does not present any significant effect. The use of p38/MAPK inhibitors may constitute an interesting treatment against glioma progression. / Por serem tumores prim?rios localizados no sistema nervoso central, os gliomas apresentam altas taxas de mortalidade com sobrevida m?dia de dois anos. Menos de 5% dos pacientes com gliomas sobrevivem mais de cinco anos ap?s o diagn?stico, mesmo com os tratamentos mais avan?ados, os quais envolvem cirurgia, radia??o e quimioterapia. Os tumores resultam de diferentes defeitos em vias de sinaliza??o intracelulares, incluindo a via p38/MAPK. Entre as respostas celulares mediadas pela fam?lia de p38/MAPK, destaca-se a regula??o da produ??o do fator de crescimento endotelial vascular (VEGF). O objetivo deste trabalho foi investigar os efeitos de ML3403, um inibidor da p38/MAPK, sobre a viabilidade das c?lulas de glioma, e avaliar o seu efeito combinado com bevacizumab (BVZ). O BVZ, j? utilizado na cl?nica como adjuvante no tratamento de gliomas, ? um anticorpo monoclonal contra o receptor de VEGF-Ae reduz a sinaliza??o envolvida no processo de angiog?nese tumoral. As c?lulas de gliomas U138MG e U251MG foram tratadas com ML3403 (0,1 a 200?M) e BVZ (1 a 200 ?g/mL)e avaliadas para viabilidade celular, atrav?s do m?todo do MTT e prolifera??o celular, atrav?s da contagem do n?mero de c?lulas. Os resultados obtidos demonstraram redu??o da viabilidade e prolifera??o celular ap?s o tratamento com ML3403. O co-tratamento com BVZ n?o apresentou efeito aditivo. A utiliza??o de inibidores da via de sinaliza??o p38/MAPK pode ser considerada como um tratamento promissor na diminui??o do crescimento de gliomas.