Studies on thyorid cancer pathogenesis using mouse models
| Project/Area Number |
19K09028
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAGAYAMA Yuji 長崎大学, 原爆後障害医療研究所, 教授 (30274632)
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| Co-Investigator(Kenkyū-buntansha) |
蔵重 智美 長崎大学, 原爆後障害医療研究所, 客員研究員 (60568955)
嶋村 美加 長崎大学, 原爆後障害医療研究所, 助教 (90736406)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 甲状腺がん / TSH受容体 / オートファジー / インバースアゴニスト / マウスモデル / 遺伝子改変 / 逆作動薬 / キナーゼ阻害剤 |
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| Outline of Research at the Start |
当研究室で樹立した上記モデルや今後さらに目的に合わせた新規開発モデルを用いて；
(i) 逆作動薬を用いた新規治療法：逆作動薬効果を有する抗体及び低分子化合物による治療の可能性
(ii) キナーゼ阻害剤の作用機序の解析：キナーゼ阻害剤の作用機序の解析とバイオマーカーの検索
(iii) オートファジーの研究：オートファジーの生理学的機能と標的阻害の効果
を問う。
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| Outline of Final Research Achievements |
Thyroid cancer is the most common endocrine cancer and has been on the increase worldwide in recent years. Animal models are useful for understanding the pathogenesis of thyroid cancer and for research on the development of new treatment methods. In this study, using the mouse model that faithfully recapitulates the pathogenesis of human thyroid cancer that we have recently established, we investigated (i) the possibility of treatment with antibodies and small molecules that have a reverse agonist effect, (ii) the mechanism of action of kinase inhibitors is mainly inhibition of angiogenesis, (iii) the physiological activity of autophagy is related to (iii) physiological activity of autophagy is important for thyroid cell survival and maintenance of homeostasis, and although autophagy deficiency itself does not promote thyroid carcinogenesis, deficiency of autophagy promotes the development of thyroid cancer caused by mutant BRAF.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は，世界的に増加傾向にあり，放射線での誘発がチェルノブイリから福島まで問題となっている甲状腺がんの新規治療法として逆作動薬（抗体及び低分子化合物）が有効であること，最近導入されたキナーゼ阻害剤の作用機序が実は主に血管新生阻害であること，オートファジーが甲状腺では腫瘍抑制的に作用していることを新規に見出したもので，甲状腺がんの病態から現状の治療法の作用機序，さらには将来の新規治療薬までを幅広く網羅した研究であり，甲状腺腫瘍学の進展に貢献すること大であると考える．
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Graves ' disease.2020
Author(s)
Davies TF, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M, Eckstein AK, Green AS, Kahaly GJ.
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Journal Title
Nature Review Disease Primers
Volume: 6 (1)
Issue: 1
Pages: 52-52
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Graves ' disease.2020
Author(s)
Davies TF, Andersen S, Latif R, Nagayama Y, Barbesino G, Brito M, Eckstein AK, Green AS, Kahaly GJ.
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Journal Title
Nat Rev Dis Primers
Volume: in press
Related Report
Peer Reviewed / Open Access
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