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The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas

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Title: The Combination of Histone Deacetylase Inhibitors and Oncolytic Viruses for the treatment of High-grade Gliomas
Author: Syed, Zafir
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Bridle, Byram
Abstract: Survival of patients with high-grade gliomas is dismal. Oncolytic viruses (OV) and histone deacetylase inhibitors (HDIs) represent revolutionary approaches to treating cancers, with minimal toxic side-effects. This study assessed the viability of human and murine glioma cell lines following treatment with OVs and/or HDIs. Maraba virus (MG1) proved to be a potent OV in glioma cells. The potential to combine MG1 with HDIs to enhance efficacy was explored. A variety of combinations with additive effects were achieved. Notably, four HDIs synergized with MG1 in two of six cell lines. Also tested was the hypothesis that OVs enhance the sensitivity of glioma cells to HDI-mediated cytotoxicity via ligation of Toll-like receptors (TLR). Therefore, TLR agonists were tested in combination with HDIs but results supported the null hypothesis. Surprisingly, the TLR3 agonist poly (I:C) attenuated MG1-mediated cytotoxicity, suggesting that TLR3-blockade may promote viral oncolysis. However, blocking TLR3 had no benefit.
URI: http://hdl.handle.net/10214/8291
Date: 2014-08
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