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Poteitial new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor

Research Project

Project/Area Number 25462618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

TAKENAGA MITSUKO  聖マリアンナ医科大学, 医学(系)研究科(研究院), 准教授 (10236490)

Co-Investigator(Kenkyū-buntansha) OHTA YUKI  聖マリアンナ医科大学, 医学部, 助教 (60387066)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsKSP阻害 / キネシンモータータンパク / 細胞周期 / ヒト卵巣がん細胞 / アポトーシス / KSP / キネシンモータータンパク質 / 抗がん剤 / ヒト卵巣がん
Outline of Final Research Achievements

Among synthetic kinesin spindle protein (KSP) inhibitor compounds, KPYB10602, a six-member lactam-fused carbazole derivative was the most potent in vitro against cell growth of human ovarian cancer, A2780. KPYB10602 caused dose-dependent suppression of tumor growth in vivo. Mitotic arrest due to KPYB10602 was confirmed in vitro, and was characterized by inhibition of securin degradation. Apoptosis after mitotic arrest was associated with an increase in the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2. Increase of reactive oxygen species (ROS) and caspase pathway were also involved. Furthermore, KPYB10602 caused little neurotoxicity in vivo. Therefore, KPYB10602 could be a promising candidate as an anti-tumor agent with reduced adverse events for treating human ovarian cancer.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2013 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor2015

    • Author(s)
      Takenaga, M., Yamamoto, Y., Takeuchi T., Ohta, Y., Tokura, Y., Hamaguchi, A., Asai, D., Nakashima, H., Oishi, S., and Fujii, N.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 463 Issue: 3 Pages: 222-228

    • DOI

      10.1016/j.bbrc.2015.05.029

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 新規合成KSP阻害剤のヒト卵巣がんに対する抗腫瘍効果2016

    • Author(s)
      武永美津子, 竹内智起, 山本有貴, 都倉享恵, 新美純, 濱口明美, 太田有紀, 淺井大輔, 大石真也, 中島秀喜, 藤井信孝.
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 凍結脂肪組織からの組織幹細胞の単離と研究利用の試み2016

    • Author(s)
      太田有紀, 武永美津子, 大滝正訓, 渡辺実, 武半優子, 飯利太朗, 松本直樹
    • Organizer
      第15回日本再生医療学会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 癌細胞に対する新規KSP阻害薬の効果2015

    • Author(s)
      太田有紀, 武永美津子, 大滝正訓, 渡辺実, 武半優子, 飯利太朗, 松本直樹.
    • Organizer
      第36回日本臨床薬理学会
    • Place of Presentation
      京王プラザ(東京都・新宿区)
    • Year and Date
      2015-12-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] インジェクタブル人工エラスチンゲルによる抗HIVペプチドのデポ製剤化2015

    • Author(s)
      淺井大輔, 金本大成, 寺久保繁美, Ashutosh Chilkoti, 武永美津子,中島秀喜.
    • Organizer
      第37回日本バイオマテリアル学会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] PGE1含有徐放製剤(Nano PGE1)のアジュバント関節炎に対する作用2015

    • Author(s)
      武永美津子, 石原務, 新美純, 濱口明美, 太田有紀, 水島徹
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎の門ヒルズフォーラム(東京都・港区)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Nano PGE1の慢性炎症に対する作用2015

    • Author(s)
      武永美津子, 石原務, 新美純, 濱口明美, 太田有紀, 水島徹.
    • Organizer
      第31回日本DDS学会
    • Place of Presentation
      京王プラザ(東京都・新宿区)
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規KSP阻害剤の抗腫瘍効果に関する研究2013

    • Author(s)
      武永美津子, 竹内智起, 都倉享恵, 濱口明美, 山本有貴, 太田有紀, 淺井大輔, 中島秀喜, 大石真也, 藤井信孝.
    • Organizer
      第29回日本DDS学会
    • Place of Presentation
      京都;京都テルサ
    • Related Report
      2013 Research-status Report
  • [Book] DDSキャリア作製プロトコル集(丸山一雄監修)2015

    • Author(s)
      武永美津子 五十嵐理慧 水島徹
    • Total Pages
      262
    • Publisher
      株式会社シーエムシー出版
    • Related Report
      2015 Annual Research Report
  • [Remarks] 聖マリアンナ医科大学 難病治療研究センター

    • URL

      http://www.marianna-u.ac.jp/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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