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Development of a novel therapy by targeting Warburg effect of gliomas.

Research Project

Project/Area Number 23592149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionMiyagi Cancer Center Research Institute

Principal Investigator

YAMASHITA YOUZI  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (30420045)

Co-Investigator(Kenkyū-buntansha) SHIMA Hiroshi  地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療 法研究部, 部長 (10196462)
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsグリオーマ / 解糖系 / ワールブルグ効果 / PKM / スプライシング / 解糖系酵素 / 腫瘍マーカー
Research Abstract

Pre-mRNA splicing of gene encoding pyruvate kinase M (PKM), a glycolytic enzyme, was dys-regulated, so that expression of PKM isoforms switches from normal- to tumor-type in human glioma. This aberrant splicing was associated with increased levels of a splicing modulator. Experiments using cell-lines showed that suppression of the splicing regulator results in partial restoration of expression of a normal-type PKM isoform. Additionally, we developed mice that transduced with a reporter gene enabling us to live-image PKM splicing regulation.

Report

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

    (26 results)

All 2014 2013 2012 2011

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (11 results)

  • [Journal Article] Hiroshi Shima, Masafumi Taniwaki,Ryoji Yamaguche, and Kazuhiro Morishita、Loss of NDRG2 expression activates PI3K-AKTsignalling via PTEN phosphorylation in ATLL and other cancers2014

    • Author(s)
      Shingo Nakahata
    • Journal Title

      Nature Communications

      Volume: 5巻 Pages: 3393-3393

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Loss of NDRG2 expression activates PI3K-AKTsignalling via PTEN phosphorylation in ATLL and other cancers2014

    • Author(s)
      Shingo Nakahata 他17名、Hiroshi Shima, Masafumi Taniwaki, Ryoji Yamaguche, and Kazuhiro Morishita
    • Journal Title

      Nature Communications

      Volume: 5 Pages: 3393-3393

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological analysis of nine consecutive central nervous system primitive neuroectodermal tumors in a single institute.2013

    • Author(s)
      Aizawa-Kohama M、ほか7名
    • Journal Title

      Brain Tumor Pathol

      Volume: 30 Pages: 15-27

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons2012

    • Author(s)
      Takahashi K、Shima H
    • Journal Title

      J Biol Chem

      Volume: 287巻 Pages: 14816-14826

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel function of MKP-5/DUSP10, a phosphatase for stress-activated kinases, on ERK dependent gene expression, and up-regulation of its gene expression in colon carcinomas2012

    • Author(s)
      Nomura M、Yamashita Y、Shima H
    • Journal Title

      Oncol Rep

      Volume: 28巻 Pages: 931-936

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Safety and feasibility of convection-enhanced delivery of nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain2012

    • Author(s)
      Sugiyama S、Yamashita Y
    • Journal Title

      Neurol Res

      Volume: 34巻 Pages: 581-587

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological analysis of nine consecutive central nervous system primitive neuroectodermal tumors in a single institute2012

    • Author(s)
      Aizawa-Kohama M、Yamashita Y
    • Journal Title

      Brain Tumor Pathol

      Volume: 30巻 Pages: 15-27

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IDH 1/2 gene status defines the prognosis a nd molecular profiles in patients with grade III gliomas2012

    • Author(s)
      Shibahara I、Yamashita Y
    • Journal Title

      Int J Clin Oncol

      Volume: 17巻 Pages: 551-561

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons2012

    • Author(s)
      Takahashi K、ほか7名
    • Journal Title

      J Biol Chem.

      Volume: 287 Pages: 14816-14826

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel function of MKP-5/DUSP10, a phosphatase for stress-activated kinases, on ERK dependent gene expression, and up-regulation of its gene expression in colon carcinomas2012

    • Author(s)
      Nomura M、ほか10名
    • Journal Title

      Oncol Rep

      Volume: 28 Pages: 931-936

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Safety and feasibility of convection-enhanced delivery of nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain.2012

    • Author(s)
      Sugiyama S、ほか8名
    • Journal Title

      Neurol Res

      Volume: 34 Issue: 6 Pages: 581-7

    • DOI

      10.1179/1743132812y.0000000050

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas.2012

    • Author(s)
      Shibahara I、ほか10名
    • Journal Title

      Int J Clin Oncol

      Volume: 17 Issue: 6 Pages: 551-61

    • DOI

      10.1007/s10147-011-0323-2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel function of MKP-5/DUSP10, a phosphatase for stress-activated kinases, on ERK dependent gene expression, and up-regulation of its gene expression in colon carcinomas2012

    • Author(s)
      Yoji Yamashita,Nobuhiro Tanuma
    • Journal Title

      Oncology Reports

      Volume: 未定

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons2012

    • Author(s)
      Hiroshi Shima
    • Journal Title

      J. Biol. Chem.

      Volume: 未定

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression2011

    • Author(s)
      Yoji Yamashita,Nobuhiro Tanuma
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 352 Pages: 155-162

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Generation of knock-in mice to dissect isoform-specific roles for each splicing isoform of pyruvate kinase M in vivo2013

    • Author(s)
      松本祥子、坂本良美、野村美有樹、田中遼大、盛田麻美、伊藤しげみ、椎葉健一、野村栄樹、片倉隆一、山下洋二、佐藤郁郎、渡邊利雄、島礼、田沼延公
    • Organizer
      第36回分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-05
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] ノックインモデルを用いた、ピルビン酸キナーゼM(PKM)アイソフォームの機能解析2013

    • Author(s)
      坂本良美、渡邊利雄、野村美有樹、山下洋二、椎葉健一、佐藤郁郎、佐藤雅美、島礼、田沼延公
    • Organizer
      第72回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Ptprz gene encoding a transmembrene-type protein phosphatase is up-regulated by Sox-2 in glioma2013

    • Author(s)
      Yoji Yamashita, Nobuhiro Tanuma, Ichiro Shibahara, Yukihiro Sonoda, Masayuki Kanamori,Ryuta Saito, Toshihiro Kumabe, Teiji Tominaga, Hiroshi Shima, Ryuichi Katakura
    • Organizer
      AACR ANNUAL MEETING 2013
    • Place of Presentation
      Washington,DC
    • Year and Date
      2013-04-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Ptprz gene encoding a transmembrene-type protein phosphatase is up-regulated by Sox-2 in glioma.2013

    • Author(s)
      Yoji Yamashita,Nobuhiro Tanuma,Ichiro Shibahara,Yukihiro Sonoda,Masayuki Kanamori,Ryuta Saito,Toshihiro Kumabe,Teiji Tominaga,Hiroshi Shima,Ryuichi Katakura
    • Organizer
      AACR ANNUAL MEETING 2013
    • Place of Presentation
      Washington,DC
    • Related Report
      2013 Annual Research Report
  • [Presentation] ノックインモデルを用いた、ピルビン酸キナーゼM(PKM)アイソフォームの機能解析2013

    • Author(s)
      坂本良美、渡邊利雄、野村美有樹、山下洋二、椎葉健一、佐藤郁郎、佐藤雅美、島礼、田沼延公
    • Organizer
      第72回日本癌学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] A mouse model incapable of switching PKM isoforms2012

    • Author(s)
      田沼延公、山下洋二、島礼、渡邊利雄
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-20
    • Related Report
      2013 Final Research Report
  • [Presentation] A mouse model incapable of switching PKM isoforms2012

    • Author(s)
      Tanuma N、ほか3名
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] リン酸化によるスプライシング装置タンパク Sap155/Sf3b1 制御機構2012

    • Author(s)
      島礼
    • Organizer
      日本プロテインホスファターゼ研究会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] PP6c 遺伝子は胚の初期発生時期に必須である2012

    • Author(s)
      島礼
    • Organizer
      日本プロテインホスファターゼ研究会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] Protein Phosphatases in human Glioma Samples2011

    • Author(s)
      Hiroshi Shima
    • Organizer
      The first Japan-Taiwan Bilateral Conference on Protein Phosphatases
    • Place of Presentation
      Okazaki
    • Related Report
      2011 Research-status Report
  • [Presentation] 「グリオーマにおけるピルビン酸キナーゼM(PKM)スプライシングのスイッチ機構」2011

    • Author(s)
      山下洋二,島礼
    • Organizer
      日本脳神経外科学会 第70回学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2011 Research-status Report

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

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