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A NEW DELIVERY SYSTEM FOR 5-FLUOROURACIL USING PRODRUG AND CONVERTING ENZYME

Research Project

Project/Area Number 12671700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionShinshu University

Principal Investigator

KOMURASAKI Yusuke  Shinshu University Hosital, Department of Ophthalmology, Lecturer, 医学部・附属病院, 講師 (90303479)

Co-Investigator(Kenkyū-buntansha) KURIMOTO Yasuo  Shinshu University, Department of Ophthalmology, Lecturer, 医学部, 講師 (50293519)
SHIBUKI Hiroto  Shinshu University, Department of Ophthalmology, Assistant, 医学部, 助手 (70313864)
YOSHIMURA Nagahisa  Shinshu University, Department of Ophthalmology, Professor, 医学部, 教授 (70211662)
AKIMOTO Masayuki  Shinshu University, Department of Ophthalmology, Assistant, 医学部, 助手 (90303453)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Keywords5-fluorouracil / 5-fluorocytosine / cytosine deaminase / adenoviral vector / gene therapy / filtering surgery / 緑内障
Research Abstract

Aims. To evaluate a new delivery system of 5-fluorouracil ( 5-FU ) using 5-fluorocytosine ( 5-FC ) as a prodrug and cytosine deaminase induced in vitro and in vivo.
Methods. Fibroblastic cells from rabbit Tenon's capsule were cultured. The cells were exposed to 5-FU arid 5-FC with or without cytosine deaminase induced by recombinant adenovirus. In vitro study, cell proliferation and DNA synthesis were assessed by MTS, BrdU assay. The effect of 5-FC removal after the treatment of 5-FC and cytosine deaminase induction was also assayed.
In vivo study, cells with or without cytosine deaminase induction were transplanted into subconjunctival space of mice, followed by eye drops of 1,000 μg/ml of 5-FC three times a day. The mice were sacrificed at day1, 5, and 10, then the cells transplanted were evaluated.
Results. Cell proliferation was inhibited by exposure to 5-FU as dose dependent manner, however up to 1 ,000 μg/ml of 5-FC did not affect cell proliferation. Cell proliferation was inhibited by exposure to 5-FC as time dependent manner with induction of cytosine deaminase following infection of recombinant adenovirus. When 5-FC was removed three or six days after the treatment, the cells grew again. The effect was reproduced in vivo model of subconjunctival cellular proliferation although 5-FC was administrated as eye drops. There were no cases having corneal erosion.
Conclusion. In this study we showed cell proliferation was inhibited by co-exposure of 5-FC and cytosine deaminase. This new delivery system may merit in control delivery of 5-FU after filtering surgery.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Akimoto M, et al.: "A new delivery system for 5-fluorouracil using prodrug and converting enzyme"British Journal of Ophthalmology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akimoto,Masayuki et Al.: "A NEW DELIVERY SYSTEM FOR 5-FLUOROURACIL USING PRODRUG AND CONVERTING ENZYME"British Journal of Ophthalmology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akimoto M, et al.: "A new delivery system for 5-fluorouracil using prodrug and converting enzyme"British Journal of Ophthalmology. (in press).

    • Related Report
      2001 Annual Research Report

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

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