| Project/Area Number |
18K15079
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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 49020:Human pathology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Hori Yumiko 大阪大学, 医学系研究科, 助教 (60528785)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | リンパ管異常 / リンパ管奇形 / mTOR / シロリムス / 難治性リンパ管異常 / ｍTOR阻害薬 |
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| Outline of Final Research Achievements |
The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. However, little is known about the expression of mTOR pathway components in lymphatic anomalies. Here we investigated the expression pattern of mTOR pathway components and their phosphorylated forms (mTOR, p-mTOR, 4EBP1, p-4EBP1, S6K1 and p-S6K1) in normal lymphatic vessels and lymphatic anomalies using immunohistochemistry.
In this study, we described expression pattern of mTOR pathway components in lymphatic anomalies and related diseased. A detailed protein expression analysis of mTOR-pathway components may shed light on their roles in lymphatic anomalies, and lead to predicting the clinical prognosis of sirolimus treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
難治性リンパ管異常に対してmTOR阻害剤であるシロリムスが著効した例があり、本邦でも薬事承認を目指した第Ⅲ相医師主導治験が行われたが、どのような機序で治療効果が得られるのか、またどのような症例において治療効果が得られやすいのかなど、詳細は明らかになっていない。
本研究では、シロリムス治療が行われた症例の組織検体を使用して、mTOR関連タンパクの免疫染色を行った。この検討の結果、シロリムスの治療効果に関与する因子が明らかとなり、免疫染色による簡便な治療効果予測につながる。
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