title: Role of thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumour progression and sensitivity to doxifluridine in gastric cancer patients.
abstract: This study was designed to investigate the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) on tumour progression and sensitivity to 5'-deoxy-5-fluorouridine (5'-DFUR). Tumour tissue was obtained from surgically resected samples from 93 patients with primary gastric cancer. Tumour TP and DPD expression levels were determined by the enzyme-linked immunosorbent assay (ELISA) system and compared with several clinicopathological factors and in vitro sensitivity to 5'-DFUR. DPD showed no correlation with any clinicopathological factors. However, the TP level was significantly correlated with the depth of tumour, lymphatic invasion and venous invasion. In comparison with 5'-DFUR sensitivity, there was a weak inverse correlation between the DPD level and the sensitivity to 5'-DFUR (r(s)=-0.361). Furthermore, the TP/DPD ratio showed a significant correlation with 5'-DFUR sensitivity (r(s)=0.634). In a subgroup of patients with postoperative 5'-DFUR administration, the survival rate was significantly better in patients with a high TP/DPD ratio (n=8) than in those with low TP/DPD ratio (n=14) (P=0.0140). These results suggest that sensitivity to 5'-DFUR is predictable by measurement of both TP and DPD levels.
authors.affiliation: Department of Surgery 1, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan. mterashi@fmu.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Terashima
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: A
authors.initials: A
authors.lastname: Takagane
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Araya
authors.forename: T
authors.initials: T
authors.lastname: Irinoda
authors.forename: H
authors.initials: H
authors.lastname: Yonezawa
authors.forename: T
authors.initials: T
authors.lastname: Nakaya
authors.forename: K
authors.initials: K
authors.lastname: Oyama
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP); D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000502:physiology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000502:physiology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; C025034:doxifluridine