| Project/Area Number |
16K08921
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
猶本 良夫 川崎医科大学, 医学部, 教授 (00237190)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 薬剤性消化管粘膜障害 / 5-アミノレブリン酸 / オルガノイド / heme oxygenase-1 / 5‐アミノレブリン酸 / プロバイオティクス / 薬剤性消化管障害 / 医薬品副作用・薬物相互作用 |
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| Outline of Final Research Achievements |
We utilized organoid culture established from mouse intestinal epithelium, and focused on the study of 5-aminolevulinic acid (5-ALA)-mediated protective effect on a damage to the intestinal mucosa by anticancer drugs.
In two-dimensional culture with commercially available rat intestinal epithelial cells, 5-ALA treatment could induce heme oxygenase-1 (HO-1), a major survival signal molecule that responds to oxidative stress. Under the treatment with SN-38, an active metabolite of a popular anticancer drug CPT-11 (Irinotecan), which is known to injure intestinal mucosa, the addition of 5-ALA could maintain the expression of HO-1 in rat intestinal epithelial cells but not without 5-ALA. We also observed the similar phenomenon in mouse intestinal organoid. Furthermore, 5-ALA treatment could reduce a chance of cell death by SN-38 treatment in this culture setting, suggesting that 5-ALA can be a potential supportive reagent against anticancer drug-induced damage to intestinal mucosa.
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| Academic Significance and Societal Importance of the Research Achievements |
化学療法における5-ALAの腸管粘膜保護効果については理論的に妥当であるものの未だ報告がなかったため、本研究における5-ALAの消化管粘膜保護作用の研究成果には新規性を有する。故に、近い将来に化学療法に対する新規支持療法として臨床応用が期待される。
さらに、5-ALA合成能を高めたプロバイオティクス製剤創出に向けての新たな研究・開発へのステップを踏み出すことが可能となれば、実臨床の観点からも画期的である。5-ALAと既存のプロバイオティクス製剤との併用療法、すなわちシンバイオティクスを考案することができれば、社会的意義へつながるものと期待される。
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