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lung, tissues, tumor, cancer, analysis, metabolites, noncancerous, article, google, scholar, nmr, cycle, human, cas, pubmed, table, metabolic, krebs, pyruvate, tissue, lactate, expression, data, fig, figure, patients, metabolite, enrichment, gene, patterns, glucose, cells, tocsy, fan, gcms, hsqc, metabolism, mass, extracts, glu, clabeled, isotopomers, full, labeled, cell, ala, asp, isotopomer, patient, lane,

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n-methyl-n-[tert-butyldimethylsilyl]trifluoroacetamide 2-dimethyl-2-silapentane-5-sulfonate sodium salt flood-tolerant rice coleoptiles biosynthetically-related 13c-labeled metabolites article download pdf pseudo-molecular ion cluster inducible 6-phosphofructo-2-kinase/fructose-2 multi-capillary columns coupled 13c-isotopomer-based metabolomic analysis glucose-stimulated insulin secretion small-cell lung cancer spin-spin coupling patterns infusing [u-13c]-glc 13c satellite cross-peaks small-cell lung cancers full size image hepatic pyruvate-carboxylase activity acquiring 13c-isotopomer data real-time quantitative pcr [u-13c-glc] infusion tumor-specific metabolic alterations unlabeled pre-existing oaa pc-induced anaplerotic flux α-tubulin image density mass spectrometry-based metabolomics 13c-labeled mass isotopomers [u-13c]-glucose tracer teresa wm fan delineate 13c-labeled oaa glutathione-s-transferase gsh 1h-13c hsqc analysis 13c-3-gln 13c-3-glu-gssg isotopomer-based metabolomic analysis metabolite &13c-isotopomer profiling enhancing energy metabolism lung cancer metabolism major 13c-labeled metabolite 13c-enriched metabolite content hong gao & donald total correlation spectroscopy real-time pcr analysis real-time pcr data metabolomics-edited transcriptomics analysis [13c3]-asp mass isotopomer privacy choices/manage cookies authors’ original file human lung cancer open tubular column α-tubulin protein band high interfering background

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         headline:Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM)
         description:Metabolic perturbations arising from malignant transformation have not been systematically characterized in human lung cancers in situ. Stable isotope resolved metabolomic analysis (SIRM) enables functional analysis of gene dysregulations in lung cancer. To this purpose, metabolic changes were investigated by infusing uniformly labeled 13C-glucose into human lung cancer patients, followed by resection and processing of paired non-cancerous lung and non small cell carcinoma tissues. NMR and GC-MS were used for 13C-isotopomer-based metabolomic analysis of the extracts of tissues and blood plasma. Many primary metabolites were consistently found at higher levels in lung cancer tissues than their surrounding non-cancerous tissues. 13C-enrichment in lactate, Ala, succinate, Glu, Asp, and citrate was also higher in the tumors, suggesting more active glycolysis and Krebs cycle in the tumor tissues. Particularly notable were the enhanced production of the Asp isotopomer with three 13C-labeled carbons and the buildup of 13C-2,3-Glu isotopomer in lung tumor tissues. This is consistent with the transformations of glucose into Asp or Glu via glycolysis, anaplerotic pyruvate carboxylation (PC), and the Krebs cycle. PC activation in tumor tissues was also shown by an increased level of pyruvate carboxylase mRNA and protein. PC activation – revealed here for the first time in human subjects – may be important for replenishing the Krebs cycle intermediates which can be diverted to lipid, protein, and nucleic acid biosynthesis to fulfill the high anabolic demands for growth in lung tumor tissues. We hypothesize that this is an important event in non-small cell lung cancer and possibly in other tumor development.
         datePublished:2009-06-26T00:00:00Z
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            Cancer Research
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      headline:Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM)
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         Cancer Research
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      name:Department of Chemistry, University of Louisville, Louisville, USA
      name:James Graham Brown Cancer Center, University of Louisville, Louisville, USA
      name:Center for Regulatory and Environmental Analytical Metabolomics (CREAM), University of Louisville, Louisville, USA
      name:Department of Chemistry, University of Louisville, Louisville, USA
      name:James Graham Brown Cancer Center, University of Louisville, Louisville, USA
      name:Center for Regulatory and Environmental Analytical Metabolomics (CREAM), University of Louisville, Louisville, USA
      name:Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Egypt
      name:Department of Chemistry, University of Louisville, Louisville, USA
      name:Center for Regulatory and Environmental Analytical Metabolomics (CREAM), University of Louisville, Louisville, USA
      name:James Graham Brown Cancer Center, University of Louisville, Louisville, USA
      name:Department of Surgery, University of Louisville, Louisville, USA
      name:James Graham Brown Cancer Center, University of Louisville, Louisville, USA
      name:Center for Regulatory and Environmental Analytical Metabolomics (CREAM), University of Louisville, Louisville, USA

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