Project/Area Number |
18K15718
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Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
|
Research Institution | Ehime 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.
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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。
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