title: Expression levels of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in patients with gastrointestinal cancer.
abstract: BACKGROUND
  Thymidine phosphorylase (TP) is a key enzyme involved in pyrimidine nucleoside metabolism. Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of 5-fluorouracil (5-FU). These are important enzymes in the pyrimidine salvage pathway and are considered to be key enzymes for determining the prognosis of patients with gastrointestinal cancer. In the present study, TP and DPD were quantified and evaluated in gastric and colorectal cancer.
  
  
  METHODS
  In 111 cases of malignancy, including 30 gastric cancers and 81 colorectal cancers, the expression levels of both TP and DPD in fresh-frozen samples from either tumor or adjacent normal tissue were quantified using enzyme-linked immunosorbent assay (ELISA). The relationships between TP or DPD expression levels in tumor tissues or adjacent normal tissues and clinicopathological factors were evaluated.
  
  
  RESULTS
  The TP expression levels in gastric or colorectal tumor tissues were found to be significantly higher than those in the adjacent normal tissue. Although the DPD expression levels in gastric tumor tissue were significantly higher than those in adjacent normal tissue, the DPD expression levels in colorectal tumor tissue were nearly identical to those in the adjacent normal tissue. The DPD expression levels in gastric tumor tissues were significantly higher than those in colorectal tumor tissues. The TP expression levels correlated significantly with the DPD expression levels in tumor or adjacent normal tissues. The DPD expression levels in tumor tissues significantly correlated with those in adjacent normal tissue.
  
  
  CONCLUSIONS
  The difference in DPD expressions between gastric and colorectal cancer tissues may reflect the organ specificity of the carcinomas and a difference in chemotherapeutic sensitivity to 5-FU or its analogs. The correlation between TP and DPD expression levels suggests the existence of a common regulatory pathway.
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kita-Kyushu 807-8555, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Inoue
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagashima
authors.forename: Takefumi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Kentarou
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Kadowaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shibao
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tsurudome
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sako
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000096:biosynthesis*
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase