title: Roles of thymidylate synthase and dihydropyrimidine dehydrogenase in tumor progression and sensitivity to 5-fluorouracil in human gastric cancer.
abstract: BACKGROUND
  The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated.
  
  
  METHODS
  TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay.
  
  
  RESULTS
  There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465).
  
  
  CONCLUSIONS
  These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.
authors.affiliation: Department of Surgery 1, Iwate Medical University, Morioka, Japan. mterashi@iwate-med.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Terashima
authors.forename: T
authors.initials: T
authors.lastname: Irinoda
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Nakaya
authors.forename: A
authors.initials: A
authors.lastname: Takagane
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Yonezawa
authors.forename: K
authors.initials: K
authors.lastname: Oyama
authors.forename: T
authors.initials: T
authors.lastname: Inaba
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Takechi
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017024:Chemotherapy, Adjuvant; D042943:Dihydrouracil Dehydrogenase (NADP); D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D011237:Predictive Value of Tests; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil