Establishment of a Glioblastoma Zebrafish Xenograft Model

Detalhes bibliográficos
Autor(a) principal: Fontes, Márcia Catarina Oliveira
Data de Publicação: 2021
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10451/53814
Resumo: Tese de mestrado, Biologia Evolutiva e do Desenvolvimento, Universidade de Lisboa, Faculdade de Ciências, 2022
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spelling Establishment of a Glioblastoma Zebrafish Xenograft Modelglioblastomaxenógrafos de peixe-zebramicroambiente tumoralquimioterapiapembrolizumabTeses de mestrado - 2022Departamento de Biologia AnimalTese de mestrado, Biologia Evolutiva e do Desenvolvimento, Universidade de Lisboa, Faculdade de Ciências, 2022Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor. Despite years of research, patients’ prognosis is still very poor. The current therapeutic options are scarce and consist of surgery, radiotherapy and chemotherapy with Temozolomide (TMZ). Immunotherapy holds promise in treating GBM, however the particular immunosuppressive microenvironment of GBM constitutes a major challenge. Not only is it urgent to find new approaches but also to predict which patients will benefit or not from the available therapies. Recently, my host laboratory has shown that zebrafish xenografts can reveal different therapeutic responses and are suited to study cancer hallmarks such as angiogenesis, metastasis and the innate tumor microenvironment (TME). The present project had the major goal of developing a glioblastoma zebrafish xenograft model, as a first step towards a future personalized approach in glioblastoma. Using a human glioblastoma cell line, U87MG, I generated subcutaneous (PVS) and orthotopic (brain) zebrafish xenografts. Tumor hallmarks and treatment response were analyzed by single-cell confocal imaging. We also screened the major therapeutic options present in the guidelines and showed that U87MG-GBM orthotopic xenografts show sensitivity to all therapies. However, the combination of radiotherapy and TMZ was the most efficient. Characterization of the TME revealed a prevalence of a pro-tumoral environment (M2-like macrophages) and reduced infiltration of neutrophils in the brain. Finally, we challenged our model with pembrolizumab immunotherapy and showed a significant induction of cell death and tumor shrinkage in a non-cell autonomous manner. Pembrolizumab treatment led to drastic decrease in macrophage recruitment. Since macrophages have been shown to be crucial for tumor survival and maintenance, we suggest that pembrolizumab mechanism of action can rely on impairment on macrophage infiltration.Fior, Rita, 1977-Lopes, CarlaRepositório da Universidade de LisboaFontes, Márcia Catarina Oliveira2022-07-18T10:45:47Z202220212022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/53814TID:202994457engmetadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:48:08Zoai:repositorio.ulisboa.pt:10451/53814Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:25:10.360649Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Establishment of a Glioblastoma Zebrafish Xenograft Model
title Establishment of a Glioblastoma Zebrafish Xenograft Model
spellingShingle Establishment of a Glioblastoma Zebrafish Xenograft Model
Fontes, Márcia Catarina Oliveira
glioblastoma
xenógrafos de peixe-zebra
microambiente tumoral
quimioterapia
pembrolizumab
Teses de mestrado - 2022
Departamento de Biologia Animal
title_short Establishment of a Glioblastoma Zebrafish Xenograft Model
title_full Establishment of a Glioblastoma Zebrafish Xenograft Model
title_fullStr Establishment of a Glioblastoma Zebrafish Xenograft Model
title_full_unstemmed Establishment of a Glioblastoma Zebrafish Xenograft Model
title_sort Establishment of a Glioblastoma Zebrafish Xenograft Model
author Fontes, Márcia Catarina Oliveira
author_facet Fontes, Márcia Catarina Oliveira
author_role author
dc.contributor.none.fl_str_mv Fior, Rita, 1977-
Lopes, Carla
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Fontes, Márcia Catarina Oliveira
dc.subject.por.fl_str_mv glioblastoma
xenógrafos de peixe-zebra
microambiente tumoral
quimioterapia
pembrolizumab
Teses de mestrado - 2022
Departamento de Biologia Animal
topic glioblastoma
xenógrafos de peixe-zebra
microambiente tumoral
quimioterapia
pembrolizumab
Teses de mestrado - 2022
Departamento de Biologia Animal
description Tese de mestrado, Biologia Evolutiva e do Desenvolvimento, Universidade de Lisboa, Faculdade de Ciências, 2022
publishDate 2021
dc.date.none.fl_str_mv 2021
2022-07-18T10:45:47Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/53814
TID:202994457
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identifier_str_mv TID:202994457
dc.language.iso.fl_str_mv eng
language eng
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instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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