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Dallas, TX, United States

Pichumani K.,Advanced Imaging Research Center | Mashimo T.,Simmons Cancer Center | Vemireddy V.,Annette rauss Center For Neuro Oncology | Kovacs Z.,Advanced Imaging Research Center | And 6 more authors.
Neurochemistry International | Year: 2016

13C-enriched compounds are readily metabolized in human malignancies. Fragments of the tumor, acquired by biopsy or surgical resection, may be acid-extracted and 13C NMR spectroscopy of metabolites such as glutamate, glutamine, 2-hydroxyglutarate, lactate and others provide a rich source of information about tumor metabolism in situ. Recently we observed 13C-13C spin-spin coupling in 13C NMR spectra of lactate in brain tumors removed from patients who were infused with [1,2-13C]acetate prior to the surgery. We found, in four patients, that infusion of 13C-enriched acetate was associated with synthesis of 13C-enriched glucose, detectable in plasma. 13C labeled glucose derived from [1,2-13C]acetate metabolism in the liver and the brain pyruvate recycling in the tumor together lead to the production of the 13C labeled lactate pool in the brain tumor. Their combined contribution to acetate metabolism in the brain tumors was less than 4.0%, significantly lower than the direct oxidation of acetate in the citric acid cycle in tumors. © 2016.

Mashimo T.,Southwestern Medical Center | Mashimo T.,Simmons Comprehensive Cancer Center | Mashimo T.,Annette rauss Center For Neuro Oncology | Pichumani K.,Advanced Imaging Research Center | And 34 more authors.
Cell | Year: 2014

Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using 13C-NMR analysis of brain tumors resected from patients during infusion of 13C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-13C]acetate and can do so while simultaneously oxidizing [1,6-13C]glucose. The tumors do not oxidize [U-13C]glutamine. In vivo oxidation of [1,2-13C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth. © 2014 Elsevier Inc. All rights reserved.

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