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Master's Dissertation
DOI
10.11606/D.42.2015.tde-10042015-120110
Document
Author
Full name
Matthew Thomas Ferreira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Colquhoun, Alison (President)
Chammas, Roger
Lopes, Marilene Hohmuth
Title in English
Analysis of how the production and activity of PGD2 affects glioma cell lines.
Keywords in English
Cancer
Eicosanoids
Glioblastoma
Opposing roles
PGD2
PGE2
Prostaglandin
Abstract in English
The World Health Organization classifies glioblastoma (GBM) as a type IV astrocytoma, making it one of the most fatal tumors that exists. Despite the advances in chemotherapy, surgery, and radiation treatments that improve a patients length of survival, the overall trajectory of the disease remains unchanged. It has been shown that GBM cells produce significant levels of prostaglandins, including prostaglandin D2 (PGD2). PGD2 possesses pro- and anti-tumorigenic properties. Hence, a more complete understanding of PGD2 activity in GBM could yield more effective treatments against GBM. Through techniques like RT-PCR, immunohistochemistry, and HPLC tandem mass spectrometry, we were able to confirm the presence of the PGD2 synthesis in GBM cell lines. We treated GBM cell lines with various concentrations of exogenous PGD2 over 72 hours and observed its effects on cell count, apoptosis, mitosis and viability. Our results suggest that PGD2 possesses contradictory functions in GBM depending on concentration (mM PGD2 vs. nM PGD2) and receptor activation.
Title in Portuguese
Análise de como a produção e atividade de PGD2 afetam linhagens de glioma.
Keywords in Portuguese
Câncer
Eicosanoides
Glioblastoma
Papeis opostos
PGD2
PGE2
Prostaglandina
Abstract in Portuguese
A Organização Mundial de Saúde classifica glioblastoma (GBM) como um astrocitoma tipo IV, fazendo uns dos tumores mais fatais que existe. A pesar dos avanços em quimioterapia, cirurgia e radioterapia que melhoram a longevidade de sobrevivência, a trajetória geral da doença permanece imutável. Tem sido demonstrado que células de GBM produzem níveis significativos de prostaglandinas, incluindo prostaglandina D2 (PGD2). PGD2 possui propriedades pro- e anti-tumorigenicos. Então, um entendimento mais completo da atividade de PGD2 em GBM pode gerar tratamentos mais efetivos. Através de técnicas como RT-PCR, imunohistoquimicas e HPLC espectrometria de massa em tandem, conseguimos confirmar a presença da síntese de PGD2 em linhagens de GBM. Tratamos linhagens de GBM com concentrações variáveis de PGD2 exógeno durante 72 horas e observamos seus efeitos na contagem de células, apoptose, mitose e viabilidade. Nossos resultados sugerem que PGD2 possui funções opostas em GBM dependendo em concentração (mM PGD2 vs. nM PGD2) e ativação de receptores.
 
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Publishing Date
2015-04-10
 
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