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Doctoral Thesis
DOI
10.11606/T.87.2012.tde-06062012-114304
Document
Author
Full name
Rafael de Oliveira Andrette
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Arruda Neto, Joao Dias de Toledo (President)
Folgueira, Maria Aparecida Azevedo Koike
Jorge, Soraia Attie Calil
Menck, Carlos Frederico Martins
Segreto, Helena Regina Comodo
Title in Portuguese
Efeito de campos elétricos exógenos em células tumorais - utilização em quimioterapia de células melanocíticas B16F10.
Keywords in Portuguese
Biofísica
Biologia molecular
Física molecular
Oncologia
Quimioterapia
Abstract in Portuguese
Neste trabalho exploramos a possibilidade interferir no processo de reparação das neoplasias, expondo-as simultaneamente a campos elétricos estáticos (CEE) e quimioterápicos. Os resultados combinados do CEE com Etoposídeo induziram um aumento expressivo na mortalidade celular, reduzindo a IC50 do Etoposídeo de 0,49 mmol para 0,20 mmol na linhagem tumoral B16F10, e de 0,46 mmol para 0,15 mmol nas células de fibroblasto FN1. Quantificou-se um aumento médio de 15% na apoptose, via Caspase 3, dobrando-se os valores obtidos isoladamente ao Etoposídeo. A detecção da apoptose e necrose via Anexina V/PI revelou um aumento de 20 para 40% na mortalidade com o tratamento combinado. O tratamento combinado do campo elétrico com o quimioterápico Etoposídeo indica a ocorrência de uma interferência seletiva no mecanismo de reparo para danos do tipo DSB, neutralizando a sinalização de reparo.
Title in English
Exogenous electric fields effects in tumoral cells - use in chemotherapy of melanocytic cells B16F10.
Keywords in English
Biophysics
Chemotherapy
Molecular biology
Molecular physics
Oncology
Abstract in English
The possibility of therapeutic usage of electric fields as complementary intervention in cancer treatment, by means of simultaneous exposure of tumors to chemotherapy and static electric fields (SEF) is investigated and addressed in this work. The combined results of SEF with Etoposide induced a substantial increase of cell deaths, reducing Etoposide IC50 from 0.49 mmol to 0.20 mmol in the tumor strain B16F10, and from 0.46 mmol to 0.15 mmol in the fibroblast cells FN1. An apoptosis average increase of 15%, via Caspase 3, the sole application of Etoposide, in these same times, doubled the apoptosis. Detection of apoptosis and necrosis via Annexine V/PI exhibited cell death increase from 20% to 40% when combined with electric field exposure. The combined treatment of electric field with the chemotherapyc Etoposide indicates the existence of a selective interference in the repairing mechanism for DSB damages, neutralizing in this way the repair signaling.
 
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Publishing Date
2012-07-06
 
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