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Basic research of mechanism of malignant pheochromocytoma

Research Project

Project/Area Number 23591889
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

HARA Hisato  筑波大学, 医学医療系, 教授 (80189688)

Co-Investigator(Kenkyū-buntansha) TAKEKOSHI Kazuhiro  筑波大学, 医学医療系, 教授 (40261804)
ISHII Kiyoaki  筑波大学, 医学医療系, 助教 (80419150)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords褐色細胞腫 / mTOR / mTOR
Research Abstract

This research was performed to explore the malignant potential of phechromocytoma and the mechanism of effect of molecular targetted therapy. We examined that Rat pheochromocytoma cell line PC12 was treated with mTOR inhibitor and Sunitinib. Antiproliferative effect and the increase of apoptosis effect was showed.
We demonstrated that sunitinib significantly increased the levels of LC3-II.Following sunitinib treatment, immunofluorescent imaging revealed a marked increased punctate LC3-II distribution.Inhibition of autophagy by siRNAs targeting Atg13 or by pharmacological inhibition with ammonium chloride, enhanced both sunitinib-induced apoptosis and anti-proliferation. Inhibition of autophagy may be a promising therapeutic option for improving the anti-tumor effect of sunitinib.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (10 results)

All 2014 2013 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (5 results)

  • [Journal Article] Inhibition of Autophagy Enhances Sunitinib-Induced Cytotoxicity in Rat Pheochromocytoma PC12 cells2013

    • Author(s)
      Tatsuhiko Ikeda, Kiyo-aki Ishii, Yuria Saito, Masahiro Miura, Aoi Otagiri, Yasushi Kawakami, Hitoshi Shimano, Hisato Hara, Kazuhiro Takekoshi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 121 Issue: 1 Pages: 67-73

    • DOI

      10.1254/jphs.12158FP

    • NAID

      10031147588

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sunitinib inhibits catecholamine synthesis and secretion in pheochromocytoma tumor cells by blocking vegf receptor 2 via plc-7-related pathways2012

    • Author(s)
      Yuichi Aita, Kiyo-aki Ishii, Yuria Saito, Tatsuhiko Ikeda, Yasushi Kawakami, Hitoshi Shimano, Hisato Hara, Kazuhiro Takekoshi
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 303 Issue: 8 Pages: E1006-E1014

    • DOI

      10.1152/ajpendo.00156.2012

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identical germline mutations in the TMEM127 gene in two unrelated Japanese patients with bilateral pheochromocytoma2012

    • Author(s)
      Takeichi, N.
    • Journal Title

      Clini Endocrinol.

      Volume: 77 Issue: 5 Pages: 707

    • DOI

      10.1111/j.1365-2265.2012.04421.x

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sunitinib induces apoptosis in pheochromocytoma tumor cells by inhibiting VEGFR2/Akt/mTOR/S6K1 pathways through modulation of Bcl-2 and BAD2012

    • Author(s)
      Saito Y, et al.
    • Journal Title

      American Journal of Physiology Endocrinology and Metabolism

      Volume: 302 Issue: 6 Pages: 615

    • DOI

      10.1152/ajpendo.00035.2011

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of autophagy enhances sunitinib-induced cytotoxicity in rat pheochromocytoma PC12 cells.2012

    • Author(s)
      Ikeda Tatsuhiko
    • Journal Title

      J Pharmacol Sci.

      Volume: 121(1) Pages: 67-73

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ラット褐色細胞腫細胞PC12においてスニチニブによるアポトーシス作用はオートファジー抑制により亢進する2014

    • Author(s)
      池田達彦、石井清朗、竹越一博、島野仁、原尚人
    • Organizer
      日本外科学会
    • Place of Presentation
      京都
    • Year and Date
      2014-04-04
    • Related Report
      2013 Final Research Report
  • [Presentation] mTORC1およびmTORC2阻害のラット褐色細胞腫細胞に対する作用機序の検討2013

    • Author(s)
      池田達彦、石井清朗、竹越一博、島野仁、原尚人
    • Organizer
      日本内分泌外科学会
    • Place of Presentation
      山形
    • Year and Date
      2013-05-23
    • Related Report
      2013 Final Research Report
  • [Presentation] mTOR阻害薬のラット褐色細胞腫細胞に対する作用機序の解明2011

    • Author(s)
      池田達彦、石井清朗、竹越一博、島野仁、原尚人
    • Organizer
      日本内分泌外科学会
    • Place of Presentation
      東京
    • Year and Date
      2011-07-07
    • Related Report
      2013 Final Research Report
  • [Presentation] mTOR阻害薬のラット褐色細胞腫細胞に対する作用機序の解明2011

    • Author(s)
      池田達彦
    • Organizer
      第23回日本内分泌外科学会総会
    • Place of Presentation
      ホテルオークラ(東京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] mTORC1およびmTORC2阻害のラット褐色細胞腫細胞に対する作用機序の検討

    • Author(s)
      池田達彦
    • Organizer
      日本内分泌外科学会
    • Place of Presentation
      山形
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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