| Project/Area Number |
20K07640
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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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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
Ito Tatsuya 札幌医科大学, 医学部, 助教 (10516636)
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| Co-Investigator(Kenkyū-buntansha) |
高澤 啓 札幌医科大学, 医学部, 准教授 (00593021)
竹政 伊知朗 札幌医科大学, 医学部, 教授 (50379252)
信岡 隆幸 札幌医科大学, 医学部, 講師 (50404603)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 胃癌 / claudin-18.2 / 薬物療法 / 分子生物学的研究 / 分子標的治療 / Claudin-18.2 / 浸潤 / 転移 / 発現調節機構 |
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| Outline of Research at the Start |
胃癌切除標本および胃癌細胞株を用いて胃癌におけるClaudin-18.2の発現調節機構を解明することで、すでに研究が進みつつあるClaudin-18.2抗体療法の臨床応用の一助とするとともに、胃癌浸潤転移能獲得におけるメカニズムの解析による胃癌病態解明を目的とする。
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| Outline of Final Research Achievements |
The aim of this study was to elucidate the expression status and regulatory mechanisms of claudin-18.2 in gastric cancer, targeting the claudin-18.2 protein, which is specifically expressed in gastric mucosa, for antibody therapy. First, we examined the differences in claudin-18.2 expression between primary and metastatic lesions of gastric cancer. As a result, it was found that approximately half of the gastric cancers expressing claudin-18.2 maintained claudin-18.2 expression in metastatic lesions as well. On the other hand, the remaining half showed reduced or lost expression. In gastric cancers expressing claudin-18.2, favorable expression was also observed in the leading edge of the tumor, suggesting a correlation between claudin-18.2 expression and the surrounding microenvironment, as well as the acquisition of metastatic potential.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究期間中に胃癌に対するclaudin-18.2を用いた抗体療法の臨床試験の結果が複数報告され、本邦においても本治療の承認が得られた。一方でclaudin-18.2発現調節機構や、癌における機能については不明である。本研究ではこれらの端緒に触れるも、全貌の解明には至っていない。しかし我々は過去の研究も踏まえ、claudin-18.2蛋白の細胞内局在がこれらを解決する重要な点と考えるとともに、これは実際の治療応用に際しても重要な点になると考ええている。現在、本研究はcell lineを用いた研究に発展・進行中である。
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