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Hyper-radiosensitization Induced by the Histone Deacetylase Inhibitor Vorinostat, in glioblastoma

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2010
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dissertation
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Glioblastoma is an aggressive form of brain cancer that limits patients to an average survival of 12 months after diagnosis [9]. Long term survival is limited by an inability to completely eradicate glioblastomas even with high dose radiation. Glioblastoma's aggressiveness allows it to regenerate rapidly if even trace amounts of the cancerous cells are alive [9]. Even when combined with drugs such as temozolomide current standards of care call for partial brain radiation of 60 Gy [10]. Such high doses have detrimental effects on patients to include extreme nausea, skin damage, hair loss, general malaise, and links have been found to reduction in life expectancy [9]. In order to reduce these adverse effects, drugs that induce radiosensitization such as Vorinostat (SAHA), are key to furthering cancer research. By inducing a conformational change to a more open form in chromatin structure, HDAC inhibitors could sensitize cancer cells to radiation treatments that are harmful to the brain.

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University of Maryland in Baltimore. Molecular Medicine. M.S. 2010
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