• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of cytidine deaminase as a parameter for anticancer drug sensitivity in the tailor-made therapy

Research Project

Project/Area Number 13671673
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionJichi Medical School

Principal Investigator

MORITA Tatsuo  Jichi Medical University, Dept. of Urology, Associate Professor, 医学部, 助教授 (40200422)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordscytidine deaminase / anticancer drug / sensitivity
Research Abstract

Objctive: Cytidine deaminase (CDD) is involved in the metabolism of new pyrimidine analogues, capecitabine (N^4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine ) and gemcitabine (2',2'-difluorodeoxycytidine: dFdC). The purpose of present study is to directly examine the role of CDD in tumor cells themselves in mediating the sensitivity to capecitabine as compared with gemcitabine. Methods: Human bladder cancer cell line T24 was transfected with human CDD2 cDNA by the lipofectin method. Results: Transfection of CDD2 cDNA did not change the levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) but increased the CDD activity significantly (p<0.01). Forced expression of CCD made T24 sensitive to 5'-deoxy-5-fluorocyidine (5'DFCR) in vitro and capecitabine in vivo, but resistant to gemitabine both in vitro and in vivo. Tetrahydrouridine (THU), a specific CDD inhibitor, abrogated the changes in the in-vitro sensitivity to 5'DFCR and gemcitabine by transfection of CDD2 cDNA. Transfection of CDD2 cDNA resulted in significant increase in cellular 5-fluorouracil (5FU) level (p<0.01) and inhibition of TS activity (p<0.01) after treatment with 5'DFCR in vitro. Conclusion: The present study clearly showed direct evidence for the contribution of CDD in tumor cells themselves to the sensitivities to capecitabine and gemcitabine.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (1 results)

All Other

All Publications (1 results)

  • [Publications] Tatsio Morita: "Forced expression of cytidine deaminase confers sensitivity to capecitabine"ONCOLOGY, in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi