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2013 Fiscal Year Final Research Report

Basic research of mechanism of malignant pheochromocytoma

Research Project

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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
Keywords褐色細胞腫 / 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.

  • Research Products

    (7 results)

All 2014 2013 2012 2011

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (3 results)

  • [Journal Article] Inhibition of autophagy enhances sunitinib-induced cytotoxicity in rat pheochromocytoma PC12 cells2012

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

      J Pharmacol Sci

      Volume: 121(1) Pages: 67-73

    • DOI

      10.1254/jphs.12158FP

    • Peer Reviewed
  • [Journal Article] Sunitinib inhibits catecholamine synthesis and secretion in pheochromocytoma tumor cells by blocking VEGF receptor 2 via PLC-γ-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

    • DOI

      10.1152/ajpendo.00156.2012

  • [Journal Article] Identical germline mutations in the TMEM127 gene in 2 unrelated Japanese patients with bilateral pheochromocytoma2012

    • Author(s)
      Naomi Takeichi, Sanae Midorikawa, Atsushi Watanabe, Banyar Than Naing, Hideki Tamura, Toshiko Kano, Hitoshi Sugihara, Sumiko Nissato, Yuria Saito, Yuichi Aita, Kiyo-aki Ishii, Takehito Igarashi, Yasushi Kawakami, Hisato Hara, Tatsuhiko Ikeda, Kazuo Shimizu, Shinichi Suzuki, Hitoshi Shimano, Masashi Kawamoto, Takashi Shimada, Tsuyoshi Watanabe, Shinichi Oikawa, Kazuhiro Takekoshi
    • Journal Title

      Clinical Endocrinology

    • DOI

      10.1111/j.1365-2265.2012.04421.x

    • 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)
      Yuria Saito, Yuko Tanaka, Yuichi Aita, Kiyo-aki Ishii, Tatsuhiko Ikeda, Kazumasa Isobe, Yasushi Kawakami, Hitoshi Shimano, Hisato Hara, Kazuhiro Takekoshi
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 302(6) Pages: E615 25

    • DOI

      10.1152/ajpendo.00035.2011

    • 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
  • [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
  • [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

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Published: 2015-07-16   Modified: 2015-07-29  

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