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Drug development for infantile hemangioma through manipulation of the ubiquitin E3 ligase complex

Research Project

Project/Area Number 18K15718
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionEhime University

Principal Investigator

Kagajo Mari  愛媛大学, 医学部附属病院, 医員 (40527511)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords血管腫 / 血管新生阻害剤 / アプタマー / 血管新生阻害 / CBF1アプタマー / 血管新生 / CBF1 / CUL3 / CUL3型ユビキチンE3 / 血管内皮細胞 / ヘマンジオーマ / ユビキチンE3
Outline of Final Research Achievements

Excessive cell proliferation of endothelial cells as well as abnormal angiogenesis cause hemangioma. The inhibition of angiogenesis, thus, would be a therapeutic option of hemangioma. To data, most anti-angiogenic drugs only target vascular endothelial growth factor (VEGF) or its receptors. In this study, making use of the exponential enrichment (SELEX), we developed 15 single-stranded deoxyribonucleic acid (ssDNA) aptamers capable of binding to CBF1 with high affinity (Kd; 10-300 nM), named as Apt-1 to Apt-15. Among them, Apt-3, inhibited angiogenesis through the activation of Notch signaling in vitro. Apt-3 may contribute to the development of a novel angiogenic inhibitor.

Academic Significance and Societal Importance of the Research Achievements

血管腫 (ヘマンジオーマ)は、血管内皮細胞の異常増殖が原因で乳幼児期に発症する。肝臓等の臓器に腫瘍形成が見られる重症例では、外科的手術や肝移植などが必要となる。また、皮膚に腫瘍が形成される軽症例では容姿に影響を与え、患者のQuality of Lifeを低下させる。しかし、その特異的な薬物治療法は確立されていない。本研究が開発した血管新生阻害活性を有するCBF1結合DNAアプタマーはヘマンジオーマを含めた血管新生関連疾患の新しい治療薬のシーズとなる可能性を秘めている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Development of Human CBF1-Targeting Single-Stranded DNA Aptamers with Antiangiogenic Activity In Vitro2020

    • Author(s)
      Tezuka-Kagajo Mari、Maekawa Masashi、Ogawa Atsushi、Hatta Yoshiko、Ishii Eiichi、Eguchi Mariko、Higashiyama Shigeki
    • Journal Title

      Nucleic Acid Therapeutics

      Volume: 30 Issue: 6 Pages: 365-378

    • DOI

      10.1089/nat.2020.0875

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Development of human CBF1-targeting single-stranded DNA aptamers as angiogenic inhibitors.2020

    • Author(s)
      Mari Tezuka-Kagajo, Yoshiko Hatta, Masashi Maekawa, Atsushi Ogawa, Minenori Ishimae, Mariko Eguchi and Shigeki Higashiyama
    • Organizer
      第79回日本癌学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] CBF1結合核酸分子およびその用途2020

    • Inventor(s)
      東山繁樹・小川敦司・前川大志・八田佳子・加賀城真理
    • Industrial Property Rights Holder
      東山繁樹・小川敦司・前川大志・八田佳子・加賀城真理
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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