title: Expression of genes for 5-FU-metabolizing enzymes and response to irinotecan plus 5-FU-leucovorin in colorectal cancer.
abstract: BACKGROUND
  5-Fluorouracil (5-FU) is initially catabolized by dihydropyrimidine dehydrogenase. Thymidylate synthase (TS) is the target enzyme of 5-FU. In addition, activation of 5-FU to form various nucleotides via three pathways requires phosphorylation by orotate phosphoribosyltransferase, thymidine phosphorylase and uridine phosphorylase, respectively. The aim of this study was to assess the predictive value of the expression of these genes in patients receiving irinotecan plus 5-FU/leucovorin therapy (IFL) for colorectal cancer.
  
  
  METHODS
  Twenty-seven patients with metastatic, or recurrent colorectal cancer were studied. Enzyme gene expression was measured in primary tumors by the real-time reverse transcription PCR method.
  
  
  RESULTS
  The TS mRNA level was significantly higher in the responders than in the non-responders (p=0.0409).
  
  
  CONCLUSIONS
  The effect of IFL therapy may be determined by the extent of TS mRNA expression. It is suggested that assay of TS mRNA may be useful for predicting the effect of intravenous regimens such as FOLFIRI.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-5-7Asahimachi Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Noda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Maeda
authors.forename: Toru
authors.initials: T
authors.lastname: Inoue
authors.forename: Tamahiro
authors.initials: T
authors.lastname: Nishihara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nishiguchi
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000077146:Irinotecan; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D014543:Uridine Phosphorylase; D013939:Thymidine Phosphorylase; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin