• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Studies on thyorid cancer pathogenesis using mouse models

Research Project

Project/Area Number 19K09028
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionNagasaki University

Principal Investigator

NAGAYAMA Yuji  長崎大学, 原爆後障害医療研究所, 教授 (30274632)

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)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
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)
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
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。

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.

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.

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (24 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Int'l Joint Research] Al Farabi Kazakh National University(カザフスタン)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Icahn School of Medicine at Mount Sinai(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Characterization of metabolic reprogramming by metabolomics in the oncocytic thyroid cancer cell line XTC.UC1.2023

    • Author(s)
      Kurashige T, Shimamura M, Hamada K, Matsuse M, Mitsutake N, Nagayama Y.
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 149-160

    • DOI

      10.1038/s41598-023-27461-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Effect of Long-Term Inorganic Iodine on Intrathyroidal Iodothyronine Content and Gene Expression in Mice with Graves' Hyperthyroidism2023

    • Author(s)
      Uchida Toyoyoshi、Shimamura Mika、Taka Hikari、Kaga Naoko、Miura Yoshiki、Nishida Yuya、Nagayama Yuji、Watada Hirotaka
    • Journal Title

      Thyroid

      Volume: 33 Issue: 3 Pages: 330-337

    • DOI

      10.1089/thy.2022.0496

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Re-evaluation of the role of autophagy in thyroid cancer treatment2022

    • Author(s)
      Kazakova D, Shimamura M, Kurashige T, Hamada K, Nagayama Y.
    • Journal Title

      Endocrine Journal

      Volume: 69 Issue: 7 Pages: 847-862

    • DOI

      10.1507/endocrj.EJ22-0017

    • NAID

      130008162464

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MIEAP and ATG5 are tumor suppressors in a mouse model of BRAFV600E-positive thyroid cancer2022

    • Author(s)
      Hamada Koichiro、Kurashige Tomomi、Shimamura Mika、Arakawa Hirofumi、Nakamura Yasuyuki、Nagayama Yuji
    • Journal Title

      Frontiers in Endocrinology

      Volume: 13 Pages: 932754-932754

    • DOI

      10.3389/fendo.2022.932754

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thyrotropin receptor antagonists and inverse agonists, and their potential application to thyroid diseases2022

    • Author(s)
      Nagayama Y, Nishihara E
    • Journal Title

      Endocrine Journal

      Volume: 69 Issue: 11 Pages: 1285-1293

    • DOI

      10.1507/endocrj.EJ22-0391

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reprogramming of cellular metabolism and its therapeutic applications in thyroid cancer2022

    • Author(s)
      Nagayama Y, Hamada K
    • Journal Title

      Metabolites

      Volume: 12 Issue: 12 Pages: 1214-1214

    • DOI

      10.3390/metabo12121214

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid2021

    • Author(s)
      Matsuyama M, Shichijo K, Matsuda K, Fujimoto N, Kondo H, Miura S, Kurashige T, Nagayama Y, Nakashima M.
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 19096-19096

    • DOI

      10.1038/s41598-021-98481-z

    • NAID

      120007175565

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy and thyroid cancer.2020

    • Author(s)
      Nagayama Y
    • Journal Title

      Jounal of Cancer Metastasis and Treatment

      Volume: 7 Pages: 6-6

    • DOI

      10.20517/2394-4722.2020.114

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Causative role for defective expression of mitochondria-eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors.2020

    • Author(s)
      Mussazhanova Z, Shimamura M, Kurashige T, Ito M, Nakashima M, Nagayama Y
    • Journal Title

      Cancer Sci.

      Volume: 111 Issue: 8 Pages: 2814-2823

    • DOI

      10.1111/cas.14501

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Nature Review Disease Primers

      Volume: 6 (1) Issue: 1 Pages: 52-52

    • DOI

      10.1038/s41572-020-0184-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Commentary: Excessive iodine promotes pyroptosis of thyroid follicular epithelial cells in Hashimoto's thyroiditis through the ROS-NF-κB-NLRP3 pathway.2020

    • Author(s)
      Ngayama Y
    • Journal Title

      Frontier Endocrinololgy - Thyroid Endocrinology

      Volume: - Pages: 00581-00581

    • DOI

      10.3389/fendo.2020.00581

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Re-evaluation of the effect of iodine on thyroid cell survival and function with PCCL3 and Nthy-ori 3-1 cells.2020

    • Author(s)
      Kurashige T, Shimamura M, Nagayama Y.
    • Journal Title

      Journal of Endocrine Society

      Volume: 4 (11) Issue: 11

    • DOI

      10.1210/jendso/bvaa146

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Acceleration of BRAFV600E-mediated thyroid carcinogenesis by TGFβ signal deficiency.2020

    • Author(s)
      Shimamura M, Kurashige T, Kuatov R, Nagayama Y.
    • Journal Title

      Endocrine

      Volume: in press Issue: 3 Pages: 571-577

    • DOI

      10.1007/s12020-020-02298-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Nat Rev Dis Primers

      Volume: in press

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice2019

    • Author(s)
      Kurashige Tomomi、Nakajima Yasuyo、Shimamura Mika、Matsuyama Mutsumi、Yamada Masanobu、Nakashima Masahiro、Nagayama Yuji
    • Journal Title

      Endocrinology

      Volume: 160 Issue: 9 Pages: 2085-2092

    • DOI

      10.1210/en.2019-00312

    • NAID

      120006988409

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] eterogenous nature of gene expression patterns in BRAF-like papillary thyroid carcinomas with BRAFV600E.2019

    • Author(s)
      Nagayama Y, Mishima H
    • Journal Title

      Endocrine

      Volume: 66 Issue: 3 Pages: 607-613

    • DOI

      10.1007/s12020-019-02063-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 甲状腺オンコサイトーマの病態研究-ミトコンドリア品質管理機構と甲状腺腫瘍-2022

    • Author(s)
      永山雄二
    • Organizer
      原爆後障害研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 甲状腺オンコサイトーマにおけるmitochondria eating protein (MIEAP)の発現・機能2021

    • Author(s)
      永山雄二、Mussazhanova Zhanna、嶋村美加、中島正洋
    • Organizer
      第5回放射線災害・医科学研究拠点カンファランス
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 三宅賞受賞記念講演:甲状腺オンコサイトーマの研究2021

    • Author(s)
      永山雄二
    • Organizer
      第64回日本甲状腺学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 甲状腺癌マウスモデル研究2020

    • Author(s)
      永山雄二
    • Organizer
      第32回日本内分泌外科学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Autophagy in the thyroid2019

    • Author(s)
      Nagayama Y
    • Organizer
      Asia Oceania Thyroid Association
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Radiation-induced thyroid cancer; comparison Nagasaki/Hiroshima, Chernobyl and Fukushima.2019

    • Author(s)
      Nagayama Y
    • Organizer
      The NASHIM seminar
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi