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Development of novel therapy for intractable pituitary adenomas focused on functional control of hormone secretion targeting insulin secretion regulatory gene in the tumor cells

Research Project

Project/Area Number 16K10760
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionKumamoto University

Principal Investigator

Yano Shigetoshi  熊本大学, 医学部附属病院, 非常勤診療医師 (60332871)

Co-Investigator(Kenkyū-buntansha) 秀 拓一郎  北里大学, 医学部, 准教授 (40421820)
篠島 直樹  熊本大学, 医学部附属病院, 助教 (50648269)
魏 范研  熊本大学, 大学院生命科学研究部(医), 准教授 (90555773)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords下垂体腺腫 / CDKAL1 / 先端巨大症 / ホルモン分泌 / インスリン / 小胞体ストレス / チオメチル化修飾 / cdkal1 / 難治性
Outline of Final Research Achievements

In order to clarify the hormone secretion mechanism of pituitary tumor which causes intractable acromegaly, we tried to elucidate the function of insulin regulatory protein "CDKAL1" in pituitary tumor cells.
CDKAL1 was expressed in various pituitary tumor samples removed by surgery. Expression level of mRNA and protein of CDKAL1 was significantly lower in growth hormone secreting tumors than nonfunctioning tumors. Mechanical suppression of cdkal1 gene expression caused elevation of intracellular calcium level and resulted in increased secretion of growth hormone. These results indicate that functional decline of CDKAL1 is involved in the abnormal secretion of hormones in growth hormone secreting pituitary adenomas.

Academic Significance and Societal Importance of the Research Achievements

難治性下垂体腺腫におけるホルモン分泌のメカニズムはいまだ明らかでないため、あらたな治療法がほとんどない。本研究は糖尿病でよく研究されているインスリン調節遺伝子の作用を下垂体腺腫細胞で確認し、少なくとも成長ホルモン分泌調節に関与していることを明らかにした。この機能制御をさらに詳しく解明していけば腫瘍の治療抵抗性の指標、あるいは予後の指標を設定することができるであろう。さらにこの遺伝子を生体内で制御することができれば、難治性下垂体腺腫に対する新たな治療法を構築することが期待でき、長期にわたる治療で苦しむ患者の利益に大いに資することが期待できる研究である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Usefulness of Oblique Coronal Computed Tomography and Magnetic Resonance Imaging in the Endoscopic Endonasal Approach to Treat Skull Base Lesions2018

    • Author(s)
      Yano Shigetoshi、Shinojima Naoki、Kitajima Mika、Uetani Hiroyuki、Hide Takuichiro、Mukasa Akitake
    • Journal Title

      World Neurosurgery

      Volume: 113 Pages: e10-e19

    • DOI

      10.1016/j.wneu.2018.01.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surgical Outcomes of Endoscopic Endonasal Skull Base Surgery of Craniopharyngiomas Evaluated According to the Degree of Hypothalamic Extension.2017

    • Author(s)
      Yano S, Hide T, Shinojima N.
    • Journal Title

      World Neurosurg.

      Volume: Apr;100 Pages: 288-296

    • DOI

      10.1016/j.wneu.2017.01.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Reply to "Craniopharyngioma: Surgical Outcome as Related to the Degree of Hypothalamic Involvement".2017

    • Author(s)
      Yano S, Hide T, Shinojima N.
    • Journal Title

      World Neurosurg.

      Volume: Aug;104 Pages: 1011-1013

    • DOI

      10.1016/j.wneu.2017.03.040

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraoperative Scoring System to Predict Postoperative Remission in Endoscopic Endonasal Transsphenoidal Surgery for Growth Hormone-Secreting Pituitary Adenomas.2017

    • Author(s)
      Yano S, Shinojima N, Kawashima J, Kondo T, Hide T.
    • Journal Title

      World Neurosurg.

      Volume: Sep;105 Pages: 375-385

    • DOI

      10.1016/j.wneu.2017.05.162

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and complications of endoscopic skull base surgery for giant pituitary adenomas.2017

    • Author(s)
      Yano S.*, Hide T., Shinojima N.
    • Journal Title

      World Neurosurg

      Volume: 99 Pages: 533-542

    • DOI

      10.1016/j.wneu.2016.12.068

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quality of Life and Clinical Features of Long-Term Survivors Surgically Treated for Pediatric Craniopharyngioma.2016

    • Author(s)
      Yano S.*, Kudo M., Hide T., Shinojima N., Makino K., Nakamura H., Kuratsu J.
    • Journal Title

      World Neurosurg

      Volume: 85 Pages: 153-162

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneous regression of nonfunctioning pituitary macroadenoma: A case report.2016

    • Author(s)
      Kameno K., Yano S.*, Shinojima N., Kuratsu J.
    • Journal Title

      Interdisciplinary Neurosurgery: Advanced Techniques and Case Management

      Volume: 5 Pages: 45-47

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 巨大下垂体腺腫に対する経鼻内視鏡手術の有用性と合併症対策2016

    • Author(s)
      矢野茂敏、秀 拓一郎、篠島直樹、倉津純一
    • Journal Title

      日本内分泌学会雑誌

      Volume: 92 Pages: 60-62

    • Related Report
      2016 Research-status Report
  • [Presentation] 下垂体腺腫におけるtRNA転写後修飾を介した成長ホルモン産生の制御2019

    • Author(s)
      武末吉広、魏 范研、篠島直樹、矢野茂敏、武笠晃丈、富澤 一仁
    • Organizer
      第29回日本間脳下垂体腫瘍学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 下垂体腺腫摘出術後の視機能悪化原因分析2017

    • Author(s)
      矢野茂敏、篠島直樹、秀 拓一郎
    • Organizer
      第27回日本間脳下垂体腫瘍学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頭蓋底手術どこまでできるか、経鼻的内視鏡下頭蓋底手術はどこまで開頭術に迫れるか2017

    • Author(s)
      矢野茂敏、篠島直樹、秀 拓一郎
    • Organizer
      第37回日本脳神経外科コングレス総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 内視鏡下下垂体腺腫摘出術における 安全な摘出を目指した術中確認項目の有用性検証2017

    • Author(s)
      矢野茂敏、篠島直樹、秀 拓一郎、武笠晃丈
    • Organizer
      第22回日本脳腫瘍の外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 今更だけど下垂体腫瘍は本当に内視鏡がいいのか、それとも顕微鏡なのか?-内視鏡術者の立場より―2017

    • Author(s)
      矢野茂敏
    • Organizer
      第76回日本脳神経外科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 内視鏡下経鼻的経蝶形骨洞アプローチにおける術前CT, MRIのoblique coronal imagingの有用性2017

    • Author(s)
      矢野茂敏 、篠島直樹 、秀 拓一郎 、武笠晃丈 、上谷浩之 、北島美香
    • Organizer
      第76回日本脳神経外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頭蓋咽頭腫に対する経鼻的内視鏡下頭蓋底手術の進歩2016

    • Author(s)
      矢野茂敏、秀 拓一郎、篠島直樹
    • Organizer
      第21回日本脳腫瘍の外科学会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 3D ビデオセッション 2:基本手技と適応 経鼻的内視鏡下頭蓋底手術2016

    • Author(s)
      矢野茂敏
    • Organizer
      第36回日本脳神経外科コングレス総会
    • Place of Presentation
      大阪市
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Real time evalution of perfusion value by ICG endoscopy in endoscopic skull base surgery2016

    • Author(s)
      Yano S, Hide T, Shinojima N, Kuratsu J
    • Organizer
      ENDOCHICAGO
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2016-05-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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