Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology. To investigate this hypothesis, we performed 31 P-MRS imaging in mouse xenograft models of four human gliomas, one of which harbored the IDH1-R132H mutation.31 P-MR spectra from the IDH1-mutant tumor displayed a pattern distinct from that of the three IDH1 wild-type tumors, characterized by decreased levels of phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated tumors by 31 P highresolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro 31 P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters phospholipid metabolism in gliomas involving phosphoethanolamine and glycerophosphocholine. These new noninvasive biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant glioma. Cancer Res; 74(17); 4898-907. Ó2014 AACR.
A linear code C is said to be a complementary-dual code (an LCDThis paper is to identify few classes of LCD quasi-cyclic (QC) codes. A sufficient condition for a ρ-generator QC code C is given under which C is an LCD code. Another sufficient condition is given for maximal 1-generator codes. We provide two necessary and sufficient conditions for a maximal 1-generator QC code C satisfying certain constraints to be an LCD code. It is shown that unlike cyclic codes, a maximal 1-generator index-2 QC code is reversible if and only if it is a self-dual code. Several classes of LCD QC codes are introduced.
This article reviews the methodological aspects of detecting low-abundant J-coupled metabolites via 1D spectral editing techniques and 2D nuclear magnetic resonance (NMR) methods applied in vivo, in humans, with a focus on the brain. A brief explanation of the basics of J-evolution will be followed by an introduction to 1D spectral editing techniques (e.g., J-difference editing, multiple quantum coherence filtering) and 2D-NMR methods (e.g., correlation spectroscopy, J-resolved spectroscopy). Established and recently developed methods will be discussed and the most commonly edited J-coupled metabolites (e.g., neurotransmitters, antioxidants, onco-markers, and markers for metabolic processes) will be briefly summarized along with their most important applications in neuroscience and clinical diagnosis.
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