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LongText Report for: Shingyoji_2004_Cancer.Sci_95_537

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Irinotecan is an active cytotoxic agent for various cancers, and is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) in vivo. Although the primary metabolic site is in the liver, ex vivo studies have proven that irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. The present study attempted to elucidate the in vitro conversion efficiency in human plasma, and to examine possible inter-individual variability and its clinical significance. Plasma samples were taken from 57 patients with lung cancer, 3 patients with benign pulmonary diseases and 9 healthy volunteers. After addition of 157 mM irinotecan to plasma, time courses of SN-38 concentration, measured by high-performance liquid chromatography (HPLC), were investigated. All subjects showed linear increase in SN-38 concentration during the first 60-min period, followed by a plateau. Mean and standard deviation of the conversion rate in the first 60 min were 515.9 +/- 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097. Although most of the subjects showed comparable conversion rates, 3 subjects had significantly higher conversion rates. In conclusion, the results of this study suggest that the enzyme activity of CCE in human plasma may show inter-individual variability. 

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Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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