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- W2886408766 abstract "The MYC oncogene is associated with aggressive forms of the pediatric brain tumor medulloblastoma. MYC promotes oncogenesis in part by altering cellular glucose and glutamine metabolism. We hypothesized that MYC-driven medulloblastoma would be sensitive to the glutamine metabolic inhibitor 6-diazo-5-oxo-l-norleucine (DON). In MYC-driven medulloblastoma cell lines, 10uM DON treatment increases apoptosis by up to 280% (p 0.4), suggesting that DON was inhibiting asparaginase synthetase, the enzyme that transfers the ammonia group from glutamine to aspartate to generate asparagine. We hypothesized that DON efficacy could be enhanced by asparaginase (ASNase), an enzyme that breaks down asparagine into aspartate and ammonia. ASNase is a commonly used therapy in pediatric patients with leukemia and lymphoma. In MYC-driven medulloblastoma cell lines, treatment with low-dose DON or ASNase as single agents did not significantly increase apoptosis by cleaved caspase-3 immunofluoresence or cleaved-PARP western blot. The combination of low-dose DON and ASNase increased apoptosis by up to 577% (p Citation Format: Allison R. Hanaford, Brad Poore, Jesse Alt, Barbara Slusher, Charles G. Eberhart, Eric H. Raabe. In vivo metabolomics reveals a potentially potent combination therapy for MYC-driven medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3484." @default.
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- W2886408766 date "2018-07-01" @default.
- W2886408766 modified "2023-10-14" @default.
- W2886408766 title "Abstract 3484:In vivometabolomics reveals a potentially potent combination therapy for MYC-driven medulloblastoma" @default.
- W2886408766 doi "https://doi.org/10.1158/1538-7445.am2018-3484" @default.
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