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Master's Dissertation
DOI
10.11606/D.42.2013.tde-17062013-111916
Document
Author
Full name
Lílian Rêgo de Carvalho
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Ibañez, Olga Célia Martinez (President)
Barbuto, Jose Alexandre Marzagao
Goldberg, Anna Carla Renata Krepel
Title in Portuguese
Inflamação e câncer hepático e pulmonar em camundongos selecionados para máxima ou mínima resposta inflamatória aguda.
Keywords in Portuguese
Camundongos
Carcinógenos químicos
Imunogenética
Inflamação
Neoplasias hepática
Neoplasias pulmonares
Abstract in Portuguese
A inflamação é um componente essencial presente no microambiente tumoral, sendo relacionada a muitos tipos de câncer, como o de pulmão e de fígado. O objetivo foi estudar a influência de fatores genéticos relacionados à inflamação no desenvolvimento do câncer através da análise da progressão tumoral em camundongos AIRmax e AIRmin, geneticamente selecionados para máxima ou mínima resposta inflamatória. Os carcinomas foram induzidos pela injeção de Uretana ou DEN. 32 semanas após dose, a maioria dos AIRmax apresentaram tumores hepáticos, enquanto AIRmin foram resistentes. O contrário aconteceu com câncer de pulmão: todos os AIRmin foram acometidos e poucos AIRmax apresentaram pequenas lesões. As proteínas de fase aguda IL-6, TNFa e IL-1b são importantes nesse processo, pois tiveram aumento de produção em órgãos alvo horas após injeção. Esses resultados sugerem que um grupo de loci gênicos controla a resposta inflamatória e a susceptibilidade/resistência a diversos tipos de câncer e ressaltam o papel específico de células locais no controle da imunidade ao tumor.
Title in English
Inverse susceptibility to hepatic and lung cancer in mouse lines selected according to the acute inflammatory response.
Keywords in English
Chemical carcinogens
Hepatic neoplasms
Immunogenetics
Inflammation
Lung neoplasms
Mice
Abstract in English
Inflammatory components are an essential part of the tumor microenvironment being crucial in some types of cancer. Our objective was to study the influence of genetic factors relevant to inflammatory response regulation on cancer development by the comparative analysis of carcinogen-induced liver and lung tumors in AIRmax and AIRmin mouse strains, genetically selected for maximum and minimum inflammatory responsiveness. The carcinomas were induced by the injection of Urethane or DEN. 32 weeks after treatment, most AIRmax had liver tumors whereas AIRmin mice were resistant. The inverse occured in lungs: all AIRmin were affected and the incidence in AIRmax was 27.3%. The acute phase proteins IL-6, TNFa and IL-1b seem to be important in this process, with increased production in target organs hours after drug injection. These results provide a demonstration that a group of genes controls the inflammatory response and susceptibility or resistance to different types of cancers and also highlight the specific role of local cells in the control of tumor immunity.
 
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Publishing Date
2013-10-02
 
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