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2003 Fiscal Year Final Research Report Summary

STUDIES OF POSTOPERATIVE ADJUVANT CHEMOTHERAPY BASED ON THE PREDICTION OF EFFICACY OF 5-FU-BASED CHEMOTHERAPY FOR GASTRIC CANCER.

Research Project

Project/Area Number 12671199
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

NABEYA Yoshihiro  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT, 大学院・医学研究院, 助手 (40322028)

Co-Investigator(Kenkyū-buntansha) SHIMADA Hideaki  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER, 大学院・医学研究院, 講師 (20292691)
GUNJI Yoshio  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究院, 助教授 (60241957)
OCHIAI Takenori  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (80114255)
MATSUBARA Hisahiro  CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER, 大学院・医学研究院, 講師 (20282486)
Project Period (FY) 2000 – 2003
Keywords5-FU / thymidylate synthase (TS) / dihydropyrimidine dehydrogenase (DPD) / thymidine phosphorylase (TP) / GASTRIC CANCER / HISTOLOGICAL EFFECT / DRUG SENSITIVITY
Research Abstract

[Purpose and methods] The tumoral activity of thymidylate synthase (TS) or dihydropyrimidine dehydrogenase (DPD), the metabolizing enzyme of 5-fluorouracil (5-FU), has reportedly been related to either the sensitivity to 5-FU or the prognosis of the patient. However, possible changes in the activity of such 5-FU-metabolizing enzymes resulting from an exposure of cancer cells to 5-FU may also affect the cellular response to 5-FU. In the present study, we measured the tumoral mRNA expressions of TS/DPD in gastric cancer patients before and after preoperative chemotherapy with UFT (comprising 5-FU prodrug tegafur and uracil at a ratio of 1:4), and aimed to clarify whether such TS/DPD mRNA expression levels could be correlated with the histological efficacy of UFT. In another experimental study, we examined possible perturbations in the activity of 5-FU-metabolizing enzymes during an exposure of gastric cancer cells to 5-FU, and the association with sensitivity to 5-FU was investigated. [Results] The tumoral TS and DPD levels were found to be altered by 5-FU treatment in both of gastric cancer patients and cultured gastric cancer cells. In the clinical study, the low DPD mRNA level before administration of UFT correlated with the favorable histological effect, while the TS mRNA level did not correlate with the histological effect in each case. In the experimental study, either elevation of TS total/inhibition rate or low level of DPD during 5-FU exposure was associated with sensitivity to 5-FU in cultured gastric cancer cells. [Significance] The different alterations in the TS and DPD levels induced by 5-FU exposure may be a critical response defining the sensitivity or resistance for 5-FU in gastric cancer cells, while the molecular mechanisms of such alterations have yet to be elucidated.

  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Nabeya, Y., et al.: "Is an alteration in the activity of 5-FU-metabolizing enzymes a critical response to 5-FU treatment in esophageal/gastric cancer cell lines? Implications for 5-FU sensitivity."Proc.Am.Assoc.Cancer Res.. 44. 4599 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nabeya, Y., et al.: "Is an alteration in the activity of 5-FU-metabolizing enzymes a critical response to 5-FU treatment in esophageal/gastric cancer cell lines? Implications for 5-FU sensitivity."Proc.Am.Assoc.Cancer Res. (1st ed.). 44. 4599 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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