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Anti-tumor effect of alkylating pyrrole-imidazole polyamide targeting rhabdomyosarcoma specific fusion gene PAX3-FOXO1

Research Project

Project/Area Number 15K10930
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionNihon University

Principal Investigator

FURUYA Takeshi  日本大学, 医学部, 助教 (20568539)

Co-Investigator(Kenkyū-buntansha) 杉藤 公信  日本大学, 医学部, 研究医員 (10328750)
藤原 恭子  日本大学, 医学部, 助教 (40595708)
越永 從道  日本大学, 医学部, 教授 (70205376)
植草 省太  日本大学, 医学部, 専修医 (70746338)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords医学 / 臨床外科学 / 小児腫瘍学 / 横紋筋肉腫 / ピロール・イミダゾール・ポリアミド / CBI / 融合遺伝子
Outline of Final Research Achievements

Alveolar rhabdomyosarcoma (ARMS) is one of the typical subtypes of rhabdomyosarcoma (RMS), and is characterized by a frequent chromosomal translocation. This translocation results in the formation of fusion gene including PAX3-FOXO1, which possess tumor promoting functions. In the present study, we have synthesized pyrrole-imidazole polyamides (PIP) recognizing PAX3-FOXO1 fusion site and conjugated them with alkylating agent chlorambucil. That molecule (Rhab-ChB1) could specifically bind to DNA with PAX3-FOXO1 fusion site sequence, but not to negative control DNA. Rhab-ChB1 showed strong growth suppressing effect, not only on fusion gene positive cells, but also on fusion gene negative cells. Flow cytometry analysis elucidated that the treatment with Rhab-ChB 1 provoked G2/M arrest. Since the effective concentration of Rhab-ChB1 was almost 100 times lower than that of ChB itself, Rhab-ChB1 may be developed as a new effective alkylating agent.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (2 results)

All 2017 2016

All Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Development of pyrrole-imidazole polyamide targeting rhabdomyosarcoma2017

    • Author(s)
      藤原恭子
    • Organizer
      新規バイオ医薬ピロール・イミダゾール(PI)ポリアミドの創薬開発シンポジウム
    • Place of Presentation
      日本大学桜門会館
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト胞巣型横紋筋肉腫におけるPAX3-FOXO1を標的としたアルキル化Pyrrole-Imidazole Polyamideの抗腫瘍効果の検討2016

    • Author(s)
      渡邉揚介
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場・リーガロイヤルホテル(大阪府大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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