By a News Reporter-Staff News Editor at Clinical Trials Week -- Investigators publish new report on Biotechnology. According to news reporting originating in Baltimore, Maryland, by NewsRx journalists, research stated, "Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from ?-ketoglutarate by the mutant enzyme. 2-HG is an 'oncometabolite' that competitively inhibits ?-KG dependent dioxygenases resulting in various widespread cellular changes including abnormal hypermethylation of genomic DNA and suppression of cellular differentiation. Despite the growing understanding of IDH mutant gliomas, the development of effective therapies has proved challenging in part due to the scarcity of endogenous mutant in vivo models."
The news reporters obtained a quote from the research from the Johns Hopkins University School of Medicine, "Here we report the generation of an endogenous IDH1 anaplastic astrocytoma model which rapidly grows in vivo, produces 2-HG and exhibits DNA hypermethylation. Using this model, we have demonstrated the preclinical efficacy and mechanism of action of the FDA approved demethylating drug 5-azacytidine in vivo. Long term administration of 5-azacytidine resulted in reduction of DNA methylation of promoter loci, induction of glial differentiation, reduction of cell proliferation and a significant reduction in tumor growth. Tumor regression was observed at 14 weeks and subsequently showed no signs of re-growth at 7 weeks despite discontinuation of therapy."
According to the news reporters, the research concluded: "These results have implications for clinical trials of demethylating agents for patients with IDH mutated gliomas."
For more information on this research see: 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft. Oncotarget, 2013;4(10):1737-47 (see also Biotechnology).
Our news correspondents report that additional information may be obtained by contacting A. Borodovsky, Dept. of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Additional authors for this research include V. Salmasi, S. Turcan, A.W. Fabius, G.S. Baia, C.G. Eberhart, J.D. Weingart, G.L. Gallia, S.B. Baylin, T.A. Chan and G.J Riggins.
Keywords for this news article include: Biotechnology, Glioma, Maryland, Genetics, Oncology, Baltimore, Xenograft, United States, Xenotransplantion, North and Central America, Clinical Trials and Studies.
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