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Study of the effect of silencing differentially overexpressed genes in center and periphery glioblastoma cells using siRNA

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Resumo:Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a poor median overall survival time of 14,6 months under standard therapy. Part of GBM aggressiveness could be explained by the presence of infiltrative malignant cells localized beyond the margins of the tumor, which seem to be resistant to post-surgical chemotherapy. Previous work done in our lab, resulting from microarray analysis of 12-paired primary cultures derived from patient tumor biopsies, revealed that cells derived from both the core and the periphery of GBM tumor constitute two different entities, morphologically and biologically. In this study we specifically investigated the effect of inhibiting differently overexpressed genes in both center and periphery cells. Silencing of FZD3, FGFR1, ID4, GLI3, SMAD6, MAP3K1, ADAM17, CTNNB1, CD40, STAT6, HSP27, PDGFRB, HMGA2, CLIC4 and PTGER4 with specific siRNA oligonucleotides were done in this study. We observed that some genes could be particularly important for the proliferation of a specific cell population. Our results could be relevant in exploring new promising druggable molecular targets for future GBM therapies.
Autores principais:Neto, Carlos Olavo de Oliveira
Assunto:Glioblastoma Brain tumor siRNA Gene silencing Center cells Periphery cells Mestrado Integrado - 2014
Ano:2014
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
Descrição
Resumo:Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a poor median overall survival time of 14,6 months under standard therapy. Part of GBM aggressiveness could be explained by the presence of infiltrative malignant cells localized beyond the margins of the tumor, which seem to be resistant to post-surgical chemotherapy. Previous work done in our lab, resulting from microarray analysis of 12-paired primary cultures derived from patient tumor biopsies, revealed that cells derived from both the core and the periphery of GBM tumor constitute two different entities, morphologically and biologically. In this study we specifically investigated the effect of inhibiting differently overexpressed genes in both center and periphery cells. Silencing of FZD3, FGFR1, ID4, GLI3, SMAD6, MAP3K1, ADAM17, CTNNB1, CD40, STAT6, HSP27, PDGFRB, HMGA2, CLIC4 and PTGER4 with specific siRNA oligonucleotides were done in this study. We observed that some genes could be particularly important for the proliferation of a specific cell population. Our results could be relevant in exploring new promising druggable molecular targets for future GBM therapies.