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  • Quantitative measurement of organic acids in tissues from gastric cancer patients indicates increased glucose metabolism in gastric cancer.

Quantitative measurement of organic acids in tissues from gastric cancer patients indicates increased glucose metabolism in gastric cancer.

PloS one (2014-06-10)
Hoon Hur, Man Jeong Paik, Yi Xuan, Duc-Toan Nguyen, In-Hye Ham, Jisoo Yun, Yong Kwan Cho, Gwang Lee, Sang-Uk Han
ABSTRACT

The levels of organic acids representing metabolic pathway end products are important indicators of physiological status, and may be associated with metabolic changes in cancer. The aim of this study is to investigate the levels of organic acids in cancerous and normal tissues from gastric cancer patients and to confirm the role of metabolic alterations in gastric carcinogenesis. Organic acids in normal and cancerous tissues from forty-five patients with gastric adenocarcinoma were investigated by gas chromatography-mass spectrometry in selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We analysed the significant differences in the levels of organic acids in normal and cancer tissues and investigated the correlation of these levels in cancer tissues with clinicopathological features. The levels of Krebs cycle components, including α-ketoglutaric acid, succinic acid, fumaric acid, malic acid and oxaloacetic acid, were significantly increased in cancer tissues compared to normal tissues. In addition, the levels of glycolytic products, including pyruvic acid and lactic acid, as well as the levels of ketone bodies, including 3-hydroxybutyric acid, were also significantly increased in cancer tissues compared to normal tissues. The levels of ketone bodies in cancer tissues with differentiated histology and in intestinal-type cancer tissues were significantly increased. The organic acid profiling analysis described here may be a generally useful clinical tool for understanding the complexity of metabolic events in gastric adenocarcinoma, and organic acids may have potential as metabolic markers for the future discovery of diagnostic and therapeutic modalities.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Oxaloacetic acid, ≥97% (HPLC)
Sigma-Aldrich
cis-Aconitic acid, ≥98%
Supelco
Lactic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Oxaloacetic acid, powder, suitable for hybridoma
Sigma-Aldrich
Oxaloacetic acid, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97% (HPLC)
Sigma-Aldrich
Lactic acid, 88%, FCC
Sigma-Aldrich
Lactic acid, natural, ≥85%
Sigma-Aldrich
Lactic acid, meets USP testing specifications
Sigma-Aldrich
Methoxyamine hydrochloride, 98%
Sigma-Aldrich
tert-Butylchlorodimethylsilane solution, 50 wt. % in toluene
Sigma-Aldrich
Diethyl ether, puriss., contains ~5 mg/L 2,6-di-tert.-butyl-4-methylphenol as stabilizer, meets analytical specification of Ph. Eur., BP, ≥99.5% (GC)
Supelco
Residual Solvent - Toluene, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Ethyl acetate, analytical standard
Sigma-Aldrich
Pyruvic acid, 98%
Sigma-Aldrich
Pyruvic acid, 95%
Sigma-Aldrich
DL-Malic acid, meets analytical specification of FCC, E296, 99-100.5% (alkalimetric)
Sigma-Aldrich
Pyruvic acid, ≥97%, FG
USP
Malic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
tert-Butyldimethylsilyl chloride, reagent grade, 97%
Supelco
Dichloromethane, analytical standard
Sigma-Aldrich
Dichloromethane, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains 50-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, puriss., meets analytical specification of Ph. Eur., NF, ≥99% (GC)
Supelco
Succinic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Supelco
Malic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Fumaric Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
Succinic acid, BioReagent, BioRenewable, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Succinic acid, purum p.a., ≥99.0% (T)