17 Jan Keywords: bicarbonate, dichloroacetate, glioma, hyperpolarized 13C therapies and metabolic modulation, with improved ef- fectiveness have. Metabolic Modulation of Glioblastoma with Dichloroacetate (DCA) can reverse this cancer-specific metabolic and mitochondrial remodeling in glioblastoma. Metabolic modulation of glioblastoma with dichloroacetate. Authors: ED. Michelakis, G Sutendra, P Dromparis, L. C. Webster, A Haromy, E Niven, C. Maguire.
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Metabolic Modulation of Glioblastoma with Dichloroacetate | サイエンス誌
Malignant gliomas in adults. Log in through your institution Log in via OpenAthens. This metabolic remodeling is accompanied by mitochondrial hyperpolarization. Based on these results, a limited effect of DCA on glioblastoma or brain metastases could be hypothesized Dichloroacetate should be considered with platinum-based chemotherapy in iwth tumors rather than as a single agent in advanced non-small cell lung cancer Edward B.
Dcihloroacetate to my folders. Dunbar et al was a phase I trial to evaluate safety and tumor response to DCA treatment in 13 patients with high grade glioma and two patients with brain metastasis from adenocarcinoma of the uterus and the lung. Dichloroacetate, an inhibitor of pyruvate dehydrogenase kinase, shifts metabolism away from aerobic glycolysis in glioblastoma tumor cells and may have clinical efficacy in patients.
Association of reactive oxygen species levels and radioresistance in cancer stem cells Maximilian DiehnRobert W.
Metabolic Modulation of Glioblastoma with Dichloroacetate
Topics Discussed in This Paper. J Clin Pharmacol ; Readers are strongly advised to discuss the information with their physician.
Immunology Dangerous liaisons in anaphylaxis.
Dichloroacetate causes reversible demyelination in vitro: Analysis of diculoroacetate metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo.
Solid tumors, including the aggressive primary brain cancer glioblastoma multiforme, develop resistance to cell death, in part as a result of a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis.
Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology Gopinath SutendraEvangelos D Michelakis Front. Based on this phase I trial an effect of DCA in the treatment of advanced and treatment refractory solid tumors can neither be supported nor negated The dose-limiting toxicity was a dose-dependent, reversible peripheral neuropathy, and there was no hematologic, hepatic, renal, or cardiac toxicity.
Metabolic Modulation of Glioblastoma with Dichloroacetate. Agbenyega T, et al.
Case reports Strum et al. References Publications referenced by this paper. Cancer Chemother Pharmacol ; Metabolic modulation of glioblastoma with dichloroacetate.
The dose-limiting toxicity was mosulation dose-dependent, reversible peripheral neuropathy, and there was no hematologic, hepatic, renal, or cardiac toxicity. J Cancer Res Clin Oncol ; Drug Metab Rev ; Diculoroacetate of clinical efficacy were present at a dose that did not cause peripheral neuropathy and at serum concentrations of DCA sufficient to inhibit the target enzyme of DCA, pyruvate dehydrogenase kinase II, which was highly expressed in all glioblastomas.
Pharmacogenetic considerations with dichloroacetate dosing. From This Paper Figures, tables, and topics from this paper.
Science 9 November VolIssue DCA therapy also inhibited the hypoxia-inducible factor-1alpha, promoted p53 activation, and suppressed angiogenesis both in vivo and in vitro. A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate DCA in patients with advanced solid tumors.
The best objective response until termination of the study was a stable disease in one patient after eight weeks. Solid tumors, including the aggressive primary brain cancer glioblastoma multiforme, develop resistance to cell death, in part as a result of a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. Generate a file for use with external citation management software.