title: Thymidylate synthase and dihydropyrimidine dehydrogenase expressions in gallbladder cancer.
abstract: BACKGROUND
  Although 5-Fluorouracil (5-FU) is widely used in chemotherapeutic treatment for gallbladder cancer, there is little evidence of its effectiveness. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are the major determinants of individual sensitivity to 5-FU, and the impact of TS and DPD expression on prognosis and 5-FU efficacy has been studied in gastrointestinal carcinomas.
  
  
  METHODS
  TS and DPD enzymatic activities in frozen samples of 7 gallbladder cancer tissues and immunohistochemical TS and DPD protein expressions in 53 resected gallbladder cancers were evaluated.
  
  
  RESULTS
  The DPD activity of gallbladder cancers was significantly higher than that of gastric and colon cancers (p=0.041). TS and DPD protein expressions increased in pT2 and pT3 cases compared to those in pT1 cases, and cases both with high TS and DPD expressions had a worse prognosis than both low TS and DPD expressions. However, TS and DPD expressions were not independent prognostic factors.
  
  
  CONCLUSIONS
  TS and DPD protein expressions in gallbladder cancers were frequently high in pT2 and pT3 gallbladder cancers and control of high TS or DPD levels may be important for advanced gallbladder cancer therapy.
authors.affiliation: Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kobe, Japan. ajiki@med.kobe-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ajiki
authors.forename: Kenro
authors.initials: K
authors.lastname: Hirata
authors.forename: Taro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Horiuchi
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Fujita
authors.forename: Kazuto
authors.initials: K
authors.lastname: Habara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamigaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000201:enzymology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D005260:Female; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000096:biosynthesis*
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase