| Project/Area Number |
20K16077
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 薬剤性腎障害 / 医療ビッグデータ解析 / ドラッグリポジショニング / 病態モデル解析 / 医療ビッグデータ |
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| Outline of Research at the Start |
抗がん剤による薬剤性腎障害のコントロールが患者のQOL向上、治療継続、予後改善のための重要な課題であると言える。しかし、現状の予防法では、完全に腎障害を抑えることはできないため、新たな予防法や予防薬の開発が求められている。本研究では、既存薬の新たな薬効を見出すドラッグリポジショニング手法を用いて、大規模医療情報データベース、創薬ツール、遺伝子発現データベースなどのデータベース解析と基礎研究、臨床研究を融合させた新規的な手法を活用して、抗がん剤による薬剤性腎障害の発症機序に立脚した予防戦略の開発を目指す。
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| Outline of Final Research Achievements |
Cisplatin is effective in many types of carcinoma. However, high rates of renal injury are a clinical problem. On the other hand, new prophylaxis methods are needed, as the prevention methods currently used in clinical practice do not completely prevent renal injury. Therefore, the aim of this study was made to explore prophylactic agents with high potential for clinical application. Cascade Eye, a drug discovery AI, LINCS, a gene expression database, and FAERS, a large adverse drug reaction reporting database, were used to identify drugs that can prevent cisplatin-induced kidney injury in clinical practice.
Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、医療ビッグデータ解析、細胞実験、動物実験を組み合わせた研究手法により、現在も臨床で使用されている脂質異常症治療薬であるフェノフィブラートが臨床応用可能性の高いシスプラチン誘発腎障害予防薬となる可能性を示した。
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