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Analysis of mTOR Pathway Expression in Lymphatic malformation and Related diseases

Research Project

Project/Area Number 18K15079
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionOsaka University

Principal Investigator

Hori Yumiko  大阪大学, 医学系研究科, 助教 (60528785)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
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)
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
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.

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。

Report

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

    (3 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Analysis of mTOR pathway expression in lymphatic malformation and related diseases.2020

    • Author(s)
      Hori Y, Ozeki M, Hirose K, Matsuoka K, Matsui T, Kohara M, Tahara S, Toyosawa S, Fukao T, Morii E.
    • Journal Title

      Pathology International

      Volume: - Issue: 6 Pages: 323-329

    • DOI

      10.1111/pin.12913

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 血管腫・血管奇形の病理診断2019

    • Author(s)
      堀由美子
    • Organizer
      第16回日本血管腫血管奇形学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] リンパ管異常症におけるmTOR関連蛋白発現の免疫組織学的検討2019

    • Author(s)
      堀由美子、松岡健太郎、森井英一
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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