Role of p110δ in the treatment of glioblastoma multiforme with temozolomide

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Role of p110δ in the treatment of glioblastoma multiforme with temozolomide


Author: Mok, Wing Hei
Title: Role of p110δ in the treatment of glioblastoma multiforme with temozolomide
Degree: M.Sc.
Year: 2013
Subject: Phosphoinositides.
Antineoplastic agents.
Glioblastoma multiforme -- Treatment.
Gliomas -- Treatment.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: ix, 61 leaves : col. ill. ; 30 cm.
Language: English
InnoPac Record:
Abstract: Despite advanced treatments such as surgical excisions or chemo-and radiotherapies to treat malignant gliomas, survival rates had not been satisfactory. Debulking and surgical removal of the tumour mass is limiting, as extensive removal of cancerous tissue would result in loss of normal neurological functions. Some malignant gliomas are also known to be resistant to most available chemotherapeutic drugs. A widely used drug Temozolomide is introduced and known to be effective in treating gliomas with its tolerable side effects and favourable toxicity profile, by disrupting the cell’s DNA repair mechanism, directing to cell death. Yet, in malignant gliomas, they are also cell death resistant. Therefore, another method is proposed to enhance cell cycle arrest and cell death by the addition of small interfering RNA sequences - siRNA. Upon binding to genes that are essential for cell survival and metabolism, these genes are 'knockdown', wiping out the functionality of these genes. Therefore, targeting an important cell regulatory gene and sensitizing the cells to an apoptotic drug would likely inhibiting cancer cell growth. This study evaluates the effects of p110δ gene (apoptosis-inducing), transcribed by PIK3CD, knockdown on Glioblastoma multiforme (GBM), a type of apoptosis resistant malignant glioma, after autophagic Temozolomide treatment (autophagy-inducing), while comparing that to Temozolomide treatment alone. Results demonstrated that p110δ is essential for cell proliferation, and Temozolomide is effective in inhibiting cell survival. However, when used in combination, there was only a slight additive effect observed, in terms of cell proliferation and cell survival.

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