| http://purl.uniprot.org/citations/17640957 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17640957 | http://www.w3.org/2000/01/rdf-schema#comment | "Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Using 21 single nucleotide polymorphisms (SNPs), including 4 nonsynonymous SNPs, 100C>T (Arg(34)Trp, *2), 424G>A (Val(142)Met, *3), 1A>T (Met(1)Leu, *5), and 617G>A (Arg(206)His, *6), and a SNP at the splice acceptor site of intron 8 (IVS8-2A>G, *4), 20 haplotypes were identified in 262 Japanese subjects. In 176 Japanese cancer patients who received irinotecan, associations of CES2 haplotypes and changes in a pharmacokinetic parameter, (SN-38 + SN-38G)/CPT-11 area under the plasma concentration curve (AUC) ratio, were analyzed. No significant association was found among the major haplotypes of the *1 group lacking nonsynonymous or defective SNPs. However, patients with nonsynonymous SNPs, 100C>T (Arg(34)Trp) or 1A>T (Met(1)Leu), showed substantially reduced AUC ratios. In vitro functional characterization of the SNPs was conducted and showed that the 1A>T SNP affected translational but not transcriptional efficiency. These findings are useful for further pharmacogenetic studies on CES2-activated prodrugs."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.org/dc/terms/identifier | "doi:10.1124/dmd.107.015339"xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Akasawa A."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Matsumoto K."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Saito Y."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Yoshida T."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Saito H."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Sawada J."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Yamamoto N."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Kamatani N."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Kaniwa N."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Minami H."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Ohtsu A."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Ozawa S."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Sai K."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Saijo N."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Shirao K."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Kim S.R."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Jinno H."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/author | "Tanaka-Kagawa T."xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/name | "Drug Metab Dispos"xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/pages | "1865-1872"xsd:string |
| http://purl.uniprot.org/citations/17640957 | http://purl.uniprot.org/core/title | "Haplotypes and a novel defective allele of CES2 found in a Japanese population."xsd:string |