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Establishment of individualized therapy for pituitary tumors using organoid culture

Research Project

Project/Area Number 17K19684
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Internal medicine of the bio-information integration and related fields
Research InstitutionKobe University

Principal Investigator

Takahashi Yutaka  神戸大学, 医学研究科, 准教授 (70301281)

Research Collaborator Yamada Shozo  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords下垂体腫瘍 / オルガノイド / 創薬 / ハイスループットスクリーニング
Outline of Final Research Achievements

We aimed to establish pituitary tumor in vitro model using organoid culture methods. Upon these models, we can clarify the pathogenesis of the tumor and screen drugs based on the individualized approaches. Thus far, we have optimized the culture conditions using 67 pituitary tumors and cell lines. As a result, we have been able to cultivate more than 3 months with hormone secretion with proliferation for one month in the tumor. Interestingly, organoid culture methods abled the cell line to recover the responsiveness to the stimuli and drugs. We are further optimizing the protocol and aiming more useful organoid model.

Academic Significance and Societal Importance of the Research Achievements

脳腫瘍の中でも頻度が高い下垂体腫瘍には、薬剤抵抗性を示す腫瘍もしばしば見られる。このような薬剤抵抗性腫瘍に対する創薬は喫緊の課題であるが、適切なin vitroモデルが存在しないことが大きな障害になっている。これまでの研究の結果、初代培養系では2週間以上のホルモン分泌能の維持が困難であるところを、1ヶ月の増殖および3ヶ月のホルモン分泌能の維持が可能になった。また下垂体腫瘍細胞株の三次元培養系では形質の回復と薬剤反応性がみられ、ハイスループットスクリーニグによる腫瘍特性に合わせた創薬の基盤が確立された。これらの成果をさらに発展することにより難治性下垂体腫瘍の画期的な創薬を目指す。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2019 2018 2017 Other

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Invited: 16 results) Book (7 results) Remarks (2 results)

  • [Journal Article] IgG4-related hypophysitis in patients with autoimmune pancreatitis2019

    • Author(s)
      Kanie Keitaro、Bando Hironori、Iguchi Genzo、Shiomi Hideyuki、Masuda Atsuhiro、Fukuoka Hidenori、Nishizawa Hitoshi、Fujita Yasunori、Sakai Arata、Kobayashi Takashi、Shiomi Yuuki、Yoshida Kenichi、Matsumoto Ryusaku、Suda Kentaro、Kodama Yuzo、Ogawa Wataru、Takahashi Yutaka
    • Journal Title

      Pituitary

      Volume: 22 Issue: 1 Pages: 54-61

    • DOI

      10.1007/s11102-018-00930-y

    • NAID

      120006767933

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Essential Role of SIRT1 in Hypothalamic-Pituitary Axis2018

    • Author(s)
      Yamamoto Masaaki、Takahashi Yutaka
    • Journal Title

      Frontiers in Endocrinology

      Volume: 9 Pages: 605-605

    • DOI

      10.3389/fendo.2018.00605

    • NAID

      120006534501

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolated adrenocorticotropic hormone deficiency as a form of paraneoplastic syndrome2018

    • Author(s)
      Bando Hironori、Iguchi Genzo、Kanie Keitaro、Nishizawa Hitoshi、Matsumoto Ryusaku、Fujita Yasunori、Odake Yukiko、Yoshida Kenichi、Suda Kentaro、Fukuoka Hidenori、Tanaka Keiko、Ogawa Wataru、Takahashi Yutaka
    • Journal Title

      Pituitary

      Volume: 21 Issue: 5 Pages: 480-489

    • DOI

      10.1007/s11102-018-0901-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of preoperative pasireotide therapy on invasive octreotide-resistant acromegaly2018

    • Author(s)
      Yamamoto Reina、Robert Shima Kosuke、Igawa Hirobumi、Kaikoi Yuka、Sasagawa Yasuo、Hayashi Yasuhiko、Inoshita Naoko、Fukuoka Hidenori、Takahashi Yutaka、Takamura Toshinari
    • Journal Title

      Endocrine Journal

      Volume: 65 Issue: 10 Pages: 1061-1067

    • DOI

      10.1507/endocrj.EJ17-0487

    • NAID

      130007501515

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple salivary cortisol measurements are a useful tool to optimize metyrapone treatment in patients with Cushing’s syndromes treatment; case presentations.2018

    • Author(s)
      Yoshida K, Fukuoka H, Odake Y, Nakajima S, Tachibana M, Ito J, Hosokawa Y, Yamada T, Miura H, Suematsu N, Matsumoto R, Bando H, Suda K, Nishizawa H, Iguchi G, Ogawa W, Takahashi Y
    • Journal Title

      Front Endocrinol

      Volume: 8 Pages: 375-375

    • DOI

      10.3389/fendo.2017.00375

    • NAID

      120006382334

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Factors correlated with serum insulin-like growth factor-I levels in health check-up subjects.2018

    • Author(s)
      Matsumoto R, Koga M, Kasayama S, Fukuoka H, Iguchi G, Odake Y, Yoshida K, BandoH, Suda K, Nishizawa H, Takahashi M, Ogawa W, Takahashi Y
    • Journal Title

      Growth Horm IGF Res.

      Volume: in press Pages: 55-60

    • DOI

      10.1016/j.ghir.2018.01.003

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypothalamic-pituitary germinoma presenting as generalized hypohidorosis.2017

    • Author(s)
      Fukunaga A, Tajima S, Sasayama T, Tanaka K, Takahashi Y, Nishigori C
    • Journal Title

      Eur J Dermotol.

      Volume: 27 Issue: 3 Pages: 297-299

    • DOI

      10.1684/ejd.2017.2975

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel thymoma-associated autoimmune disease: Anti-PIT-1 antibody syndrome.2017

    • Author(s)
      Bando H, Iguchi G, Okimura Y, Odake Y, Yoshida K, Matsumoto R, Suda K, Nishizawa H, Fukuoka H, Mokubo A, Tojo K, Maniwa Y, Ogawa W, Takahashi Y.
    • Journal Title

      Sci Rep.

      Volume: 20 Issue: 1 Pages: 43060-43067

    • DOI

      10.1038/srep43060

    • NAID

      120005997120

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cross-sectional prevalence of pancreatic cystic lesions in patients with acromegaly, a single-center experience2017

    • Author(s)
      Odake Yukiko、Fukuoka Hidenori、Yamamoto Masaaki、Arisaka Yoshifumi、Konishi Junya、Yoshida Kenichi、Matsumoto Ryusaku、Bando Hironori、Suda Kentaro、Nishizawa Hitoshi、Iguchi Genzo、Yamada Shozo、Ogawa Wataru、Takahashi Yutaka
    • Journal Title

      Pituitary

      Volume: 20 Issue: 5 Pages: 509-514

    • DOI

      10.1007/s11102-017-0810-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Insulin Secretion and Insulin Sensitivity Before and After Surgical Treatment of Pheochromocytoma or Paraganglioma2017

    • Author(s)
      Komada Hisako、Hirota Yushi、So Anna、Nakamura Tomoaki、Okuno Yoko、Fukuoka Hidenori、Iguchi Genzo、Takahashi Yutaka、Sakaguchi Kazuhiko、Ogawa Wataru
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 102 Issue: 9 Pages: 3400-3405

    • DOI

      10.1210/jc.2017-00357

    • NAID

      120006554638

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Two Cases of Atezolizumab-Induced Hypophysitis2017

    • Author(s)
      Kanie Keitaro、Iguchi Genzo、Bando Hironori、Fujita Yasunori、Odake Yukiko、Yoshida Kenichi、Matsumoto Ryusaku、Fukuoka Hidenori、Ogawa Wataru、Takahashi Yutaka
    • Journal Title

      Journal of the Endocrine Society

      Volume: 2 Issue: 1 Pages: 91-95

    • DOI

      10.1210/js.2017-00414

    • NAID

      120006767927

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 下垂体機能低下症を呈する新たな疾患の発見と発症機序の解明2019

    • Author(s)
      高橋 裕
    • Organizer
      第29回日本間脳下垂体腫瘍学会 大阪
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 機能性下垂体腺腫Update2019

    • Author(s)
      高橋 裕
    • Organizer
      第29回日本間脳下垂体腫瘍学会 大阪
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Immunotherapy-induced Pituitary Damage2019

    • Author(s)
      Takahashi Y
    • Organizer
      the 16th International Pituitary Congress
    • Related Report
      2018 Annual Research Report
  • [Presentation] 下垂体機能低下症を呈する新たな疾患の発見と発症機序の解明2018

    • Author(s)
      高橋 裕
    • Organizer
      第18回日本内分泌学会北陸支部学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 日常診療からいかに新しい疾患を見出すのか?2018

    • Author(s)
      高橋 裕
    • Organizer
      第28回臨床内分泌代謝Update
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 下垂体機能低下症を呈する新たな疾患の発見と発症機序の解2018

    • Author(s)
      高橋 裕
    • Organizer
      第91回内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 機能性下垂体腫瘍薬物療法Update2018

    • Author(s)
      高橋 裕
    • Organizer
      第91回内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 下垂体update 機能性下垂体腫瘍の病理と薬物治療2018

    • Author(s)
      高橋 裕
    • Organizer
      第22回日本内分泌病理学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Pituitary autoimmunity: a journey for the discovery of novel diseases2018

    • Author(s)
      Takahashi Y
    • Organizer
      18th International Congress of Endocrinology
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] プレゼンの奥義を伝授します(教育講演)2017

    • Author(s)
      高橋 裕
    • Organizer
      第90回日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 内分泌学の面白さを若手にどのように伝えるのか2017

    • Author(s)
      高橋 裕
    • Organizer
      第90回日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 中枢性甲状腺機能低下症を呈する新たな疾患の発見とその機序の解明2017

    • Author(s)
      高橋 裕
    • Organizer
      第60回日本甲状腺学会学術総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 先端巨大症の新たな病態と治療戦略(ランチョンセミナー)2017

    • Author(s)
      高橋 裕
    • Organizer
      第21回日本臨床内分泌病理学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 下垂体機能低下症を呈する新たな疾患の発見と機序の解明2017

    • Author(s)
      高橋 裕
    • Organizer
      第17回北海道支部内分泌集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 間脳下垂体疾患診療におけるパールとピットフォール2017

    • Author(s)
      高橋 裕
    • Organizer
      第27回臨床内分泌代謝Update
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] The essential role of GH/IGF-I in liver.2017

    • Author(s)
      Takahashi Y.
    • Organizer
      the 15th International Pituitary Congress
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Country perspective of acromegaly in Japan.2017

    • Author(s)
      Takahashi Y.
    • Organizer
      8th European Meeting on the Management of Acromegaly
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] 内分泌機能検査実施マニュアル改訂第3版2018

    • Author(s)
      高橋 裕
    • Total Pages
      109
    • Publisher
      診断と治療社
    • Related Report
      2018 Annual Research Report
  • [Book] 医学書院2018

    • Author(s)
      高橋 裕
    • Total Pages
      2160
    • Publisher
      今日の治療指針
    • Related Report
      2018 Annual Research Report
  • [Book] 今日の疾患辞典2018

    • Author(s)
      高橋 裕
    • Total Pages
      300
    • Publisher
      プレシジョン
    • Related Report
      2018 Annual Research Report
  • [Book] 内分泌症候群(第3版)2018

    • Author(s)
      高橋 裕
    • Total Pages
      561
    • Publisher
      日本臨床
    • Related Report
      2018 Annual Research Report
  • [Book] Frontiers in Hormone Research2017

    • Author(s)
      Iguchi G, Bando H, Takahashi Y
    • Total Pages
      180
    • Publisher
      Karger
    • ISBN
      9783318060140
    • Related Report
      2017 Research-status Report
  • [Book] Advances in Medicine and Biology2017

    • Author(s)
      Iguchi G, Takahashi Y
    • Total Pages
      262
    • Publisher
      Nova Science
    • ISBN
      9781536108354
    • Related Report
      2017 Research-status Report
  • [Book] 今日の治療指針2018年度版2017

    • Author(s)
      高橋 裕
    • Total Pages
      2192
    • Publisher
      医学書籍社
    • ISBN
      9784260032339
    • Related Report
      2017 Research-status Report
  • [Remarks] 神戸大学医学部糖尿病内分泌内科神経内分泌グループ

    • URL

      http://www.med.kobe-u.ac.jp/im2/doctor/activity/acti-04.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 神戸大学大学院医学研究科 糖尿病内分泌内科学 神経内分泌グループ

    • URL

      http://www.med.kobe-u.ac.jp/im2/doctor/activity/acti-04.html

    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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