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A study on the molecular diagnosis of antifolate resistance in leukemia cells : Establishment of anti-folate-resistant cell line and elucidation of molecular mechanisms of resistance

Research Project

Project/Area Number 07672502
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionTokai University

Principal Investigator

MIYACHI Hayato  Tokai University School fo Medicine, Department of Clinical Pathology, Associate Professor, 医学部, 助教授 (20174196)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Keywordsanti-folate / resistance / methotrexate / CB3717 / leukemia / gene
Research Abstract

Antifolate resistant cell lines were established to elucidate molecular mechanisms of resistance. Effects of reduced or oxidized folates on the development of methotrexate (MTX) or N^<10>-propargyl-5,8-dideazafolic (CB3717) acid resistance were examined. An approximately 60-fold MTX-resistant CCRF-CEM developed in pteroylglutamic acid (PGA) was resistant to MTX by virtue of decreased membrance transport of the drug. Further enhancement of MTX resistance resulted in selection of an approximately 5000-fold MTX resistance as noted by increased dihydrofolate reductase (DHFR) due to gene amplification. An approximately 140-fold and subsequently 1500-fold MTX-resistant subline developed in leucovorin were resistant to MTX by virtue of increased DHFR due to gene amplification. Approximately 200-fold CB3717-resistant MOLT-3 sublines developed in PGA or leucovorin had decreased membrance transport. Only CB3717-resistant subline developed in PGA had increased thymidylate synthase due to gene amplification. Membrane transport defective anti-folate-resistant sublines showed collateral sensitivity to trimeterxate, which was reduced in the presence of leucovorin, suggesting collateral sensitivity to TMQ was caused by intracellular folate defficiency.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Miyachi Hayato,et al.: "Amplification of the thymidylate synthase gane in an N^<10>-propargy1-5,8-de deaqafalic-acid-resistant human leukema,MOLT-3,clereloped in PGA,but not in leucon" J.Cancer-Res.Clin Oncol. 122. 9659-664 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayato Miyachi, et al: "Amplification of the thymidylate synthase gene in an N^<10>-propargyl-5,8-dideazafolic-acid-resistant human leukemia MOLT-3 cell line developed in pteroylglutamic acid, but not in leucovorin." J Cancer Res Clin Oncol. 122. 659-664 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyachi Hayato,etal: "Amplification of the thymidylate synthase gene in an N^<10>-propargyl-5,8-dideaza folic-acid-resistant human leukemid,MOLT-3 developed in R6A,but notin leu解読不可" J.Cancer Res.Clin.Oncol. 122. 659-664 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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