Gene expression alterations in central nervous system neoplasms with EGFR amplification

Detalhes bibliográficos
Autor(a) principal: Moedas, Marco Filipe Semião
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/1510
Resumo: Tese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de Ciências
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spelling Gene expression alterations in central nervous system neoplasms with EGFR amplificationBiologia celularExpressão genéticaTumores do sistema nervoso centralTeses de mestradoTese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de CiênciasCentral Nervous System (CNS) Neoplasms are characterized by their cell of origin and their histopathological features. Tumors of glial cell origin (Gliomas) are the most frequent, with Glioblastoma Multiforme (GBM) rising as the most common. GBM tumors of grade IV accordingly with the World Health Organization (WHO), are generally lethal, with a median survival time of 4.9 months, and their most striking histopathological features are the high degree of vascularization and necrosis. The most common genetic alterations in GBM are the amplification, overexpression and mutation of the EGFR gene, and the deletion of the long arm of chromosome 10, where, among others, the PTEN gene is located. These genes are related, respectively, with the activation and inhibition of pathways like the MAPK cascade, the PIP-mediated signaling and STAT signaling which are involved in cellular proliferation and inhibition of apoptosis. Deregulation of these pathways renders them the logical target for inhibition of growth and proliferation of tumoral cells, and some anti-EGFR therapies have been tried, but with relatively poor success. The goal of this work is to analyse the genetic expression of the genes that make up the EGFR-activated signaling pathways in gliomas, and identify those molecules where targeted intervention would make sense in such a way that cellular proliferation would cease, and differentiation and apoptosis would be induced. Tumor samples (n=100) were characterized by Multiplex Ligation-dependent Amplification (MLPA) and Chromosomal Comparative Genomic Hybridization (cGGH). Further analysis of tumors samples (n=15) was done by using Gene Expression Arrays GeneChip® HuGene 1.0ST and data analysis softwares Partek Genomics Suite and Ingenuity Pathway Analysis, in order to determine the expression values of the various genes that make up the EGFR-activated signaling pathways. This allowed us to identify a particular pathway that appears to have its components constantly overexpressed, the STAT signaling pathway, mainly through the STAT3 gene. The STAT3 protein is activated by various receptors and is implicated in tumorigenesis and immune evasion, and as such, may be a suitable target for anti-neoplasic therapies.Resumo largado em português disponível no documentoRoque, LúciaCorreia, Maria do CéuRepositório da Universidade de LisboaMoedas, Marco Filipe Semião2010-07-27T08:58:46Z20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdftext/xmlhttp://hdl.handle.net/10451/1510enghttp://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000576055info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-20T17:02:32Zoai:repositorio.ul.pt:10451/1510Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T17:02:32Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Gene expression alterations in central nervous system neoplasms with EGFR amplification
title Gene expression alterations in central nervous system neoplasms with EGFR amplification
spellingShingle Gene expression alterations in central nervous system neoplasms with EGFR amplification
Moedas, Marco Filipe Semião
Biologia celular
Expressão genética
Tumores do sistema nervoso central
Teses de mestrado
title_short Gene expression alterations in central nervous system neoplasms with EGFR amplification
title_full Gene expression alterations in central nervous system neoplasms with EGFR amplification
title_fullStr Gene expression alterations in central nervous system neoplasms with EGFR amplification
title_full_unstemmed Gene expression alterations in central nervous system neoplasms with EGFR amplification
title_sort Gene expression alterations in central nervous system neoplasms with EGFR amplification
author Moedas, Marco Filipe Semião
author_facet Moedas, Marco Filipe Semião
author_role author
dc.contributor.none.fl_str_mv Roque, Lúcia
Correia, Maria do Céu
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Moedas, Marco Filipe Semião
dc.subject.por.fl_str_mv Biologia celular
Expressão genética
Tumores do sistema nervoso central
Teses de mestrado
topic Biologia celular
Expressão genética
Tumores do sistema nervoso central
Teses de mestrado
description Tese de mestrado, Biologia (Biologia Molecular Humana), 2009, Universidade de Lisboa, Faculdade de Ciências
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-01-01T00:00:00Z
2010-07-27T08:58:46Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/1510
url http://hdl.handle.net/10451/1510
dc.language.iso.fl_str_mv eng
language eng
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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