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嫌気性微小環境に応答する難治性消化器癌幹細胞の新しい転写制御機構の解明と創薬応用

Publicly Offered Research

Project AreaIntegrative Research on Cancer Microenvironment Network
Project/Area Number 25112708
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

石井 秀始  大阪大学, 医学(系)研究科(研究院), 特任教授(常勤) (10280736)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords癌 / ゲノム / 発現制御 / 薬学 / 臨床
Outline of Annual Research Achievements

癌微小環境の新しい研究:治療抵抗性癌幹細胞内pyruvate kinase[PKM2]の『非代謝性機能』が関わる新しい癌悪性化機構の解明と創薬応用を明確な出口戦略として設定するために、PKM2の代謝性機能から『非代謝性機能』に注目して研究を進めた。前年度に引き続き今年度は解糖系酵素の非代謝性機能に注目してPKM2の下流でエピゲノムの同体を分子論的に究明した。微小環境に応答する難治性消化器癌の分子病態を究明し、革新的な創薬のための基盤を構築した。【創薬】2つの創薬標的(核移行・核内)のうち、この段階では核移行に焦点を当てて、Cell Imaging Systemでsemi-HTS(High-Throughput-Screening)した。【核内転写制御】核内PKM2複合対が結合するDNA配列をゲノムワイドで明らかにし、データベースと照合して核内PKM2下流の遺伝子を同定した。【創薬】核内PKM2が標的プロモーター結合の人工的制御をPOCとして、阻害剤、デコイをスクリーニングした。以上より難治癌の転移に関わる癌代謝とエピゲノムの関連性を分子論的に究明した。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (20 results)

All 2014 2013

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (7 results)

  • [Journal Article] Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen.2014

    • Author(s)
      Yoshioka Y, Kosaka N, Konishi Y, Ohta H, Okamoto H, Sonoda H, Nonaka R, Yamamoto H, Ishii H, Mori M, Furuta K, Nakajima T, Hayashi H, Sugisaki H, Higashimoto H, Kato T, Takeshita F, Ochiya T.
    • Journal Title

      Nature Communications

      Volume: 5 Issue: 1 Pages: 3591-3591

    • DOI

      10.1038/ncomms4591

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] LZTS1 downregulation confers paclitaxel resistance and is associated with worse prognosis in breast cancer.2014

    • Author(s)
      Lovat, F., Ishii, H., Schiappacassi, M., Fassan, M., Barbareschi, M., Galligioni, E., Gasparini, P., Baldassarre, G., Croce, CM., Vecchione, A.
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 970-977

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma.2014

    • Author(s)
      Fukusumi T, Ishii H, Konno M, Yasui T, Nakahara S, Takenaka Y, Yamamoto Y, Nishikawa S, Kano Y, Ogawa H, Hasegawa S, Hamabe A, Haraguchi N, Doki Y, Mori M, Inohara H.
    • Journal Title

      Br J Cancer

      Volume: 111(3) Issue: 3 Pages: 506-514

    • DOI

      10.1038/bjc.2014.289

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer.2014

    • Author(s)
      Hasegawa S, Eguchi H, Nagano H, Konno M, Tomimaru Y, Wada H, Hama N, Kawamoto K, Kobayashi S, Nishida N, Koseki J, Nishimura T, Gotoh N, Ohno S, Yabuta N, Nojima H, Mori M, Doki Y, Ishii H.
    • Journal Title

      Br. J. Cancer

      Volume: 111 Issue: 8 Pages: 1572-80

    • DOI

      10.1038/bjc.2014.454

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combined evaluation of hexokinase 2 and phosphorylated pyruvate dehydrogenase-E1alpha in invasive front lesions of colorectal tumors predicts cancer metabolism and patient prognosis2014

    • Author(s)
      Hamabe, A. Yamamoto, H. Konno, M. Uemura, M. Nishimura, J. Hata, T. Takemasa, I. Mizushima, T. Nishida, N. Kawamoto, K. Koseki, J. Doki, Y. Mori, M. Ishii, H.
    • Journal Title

      Cancer Science

      Volume: 105 Issue: 9 Pages: 1100-8

    • DOI

      10.1111/cas.12487

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of pyruvate kinase M2 in transcriptional regulation leading to epithelial-mesenchymal transition2014

    • Author(s)
      Hamabe, A. Konno, M. Tanuma, N. Shima, H. Tsunekuni, K. Kawamoto, K. Nishida, N. Koseki, J. Mimori, K. Gotoh, N. Yamamoto, H. Doki, Y. Mori, M. Ishii, H.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 111 Issue: 43 Pages: 15526-31

    • DOI

      10.1073/pnas.1407717111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cancer Stem Cells of the Digestive System.2014

    • Author(s)
      Colvin, S. H., Nishida, N., Koseki, J., Konno, M., Kawamoto, K., Tsunekuni, K., Doki, Y., Mori, M., Ishii, H.
    • Journal Title

      Jpn. J. Clin. Oncol.

      Volume: 44 Issue: 12 Pages: 1141-1149

    • DOI

      10.1093/jjco/hyu146

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SSEA-3 as a novel amplifying cancer cell surface marker in colorectal cancers.2013

    • Author(s)
      Suzuki, Y., Haraguchi, N., Takahashi, H., Uemura, M., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Ishii, H., Doki, Y., Mori, M., Yamamoto, H.
    • Journal Title

      Int. J. Oncol.

      Volume: 42 Pages: 161-167

    • DOI

      10.3892/ijo.2012.1713

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Depletion of Jarid1b induces cellular senescence in human colorectal cancer.2013

    • Author(s)
      Ohta, K., Haraguchi, N., Kano, Y., Kagawa, Y., Konno, M., Nishikawa, S., Hamabe, A., Hasegawa, S., Ogawa, H., Fukusumi, T., Uemura, M., Nishimura, J., Hata, T., Takemasa, I., Nishimura, T., Noguchi, Y., Ozaki, M., Kudo, T., Sakai, D., Satoh, T., Fukami, M., Ishii, M., Yamamoto, H., Doki, Y., Mori, M., Ishii, H.
    • Journal Title

      Intern. J. Oncol.

      Volume: 42 Issue: 4 Pages: 1212-1218

    • DOI

      10.3892/ijo.2013.1799

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth.2013

    • Author(s)
      Kano, Y., Konno, M., Ohta, K., Haraguchi, N., Nishikawa, S., Kagawa, Y., Hamabe, A., Hasegawa, S., Ogawa, H., Fukusumi, T., Noguchi, Y., Ozaki, M., Kudo, T., Sakai, D., Satoh, T., Ishii, M., Mizohata, E., Inoue, T., Mori, M., Doki, Y., Ishii, H.
    • Journal Title

      Mol.Clin. Oncol.

      Volume: 1 Issue: 4 Pages: 753-757

    • DOI

      10.3892/mco.2013.127

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of in vivo administration of reprogramming factors in the mouse liver.2013

    • Author(s)
      6) Tomokuni, A., Eguchi, H., Hoshino, H., Dewi, DL., Nishikawa, S., Kano, Y., Miyoshi, N., Tojo, A., Kobayashi, S., Gotoh, N., Hinohara, K., Fusaki, N., Saito, T., Suemizu, H., Wada, H., Kobayashi, S., Marubashi, S., Tanemura, M., Doki, Y., Mori, M.,et.al.
    • Journal Title

      Oncol Lett.

      Volume: 6 Issue: 2 Pages: 323-328

    • DOI

      10.3892/ol.2013.1418

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy.2013

    • Author(s)
      Nishikawa, S., Konno, M., Hamabe, A., Hasegawa, S., Kano, Y., Ohta, K., Fukusumi, T., Sakai, D., Kudo, T., Haraguchi, N., Satoh, T., Takiguchi, S., Mori, M., Doki,Y., Ishii, H.
    • Journal Title

      Int. J. Oncol.

      Volume: 42 Issue: 4 Pages: 1437-1442

    • DOI

      10.3892/ijo.2013.1837

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD49f-positive cell population efficiently enriches colon cancer-initiating cells.2013

    • Author(s)
      Haraguchi, N., Ishii, H., Mimori, K., Ohta, K., Uemura, M., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Yamamoto, H., Doki, Y., Mori, M.
    • Journal Title

      Int J Oncol.

      Volume: 43 Issue: 2 Pages: 425-430

    • DOI

      10.3892/ijo.2013.1955

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Innovative drug discovery for intractable cancer stem cells2014

    • Author(s)
      石井秀始
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] 難治性消化器癌に対する革新的治療法2014

    • Author(s)
      石井秀始、土岐祐一郎、森正樹
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 創薬標的としての癌幹細胞エピゲノム代謝2014

    • Author(s)
      石井秀始
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Innvovative Medicine for Gastrointestinal Cancer Stem Cells2014

    • Author(s)
      石井秀始
    • Organizer
      第52回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 難治性消化器癌に対する革新的医療技術の創出2013

    • Author(s)
      石井秀始、土岐 祐一郎、森 正樹
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 癌幹細胞研究の現状と展望2013

    • Author(s)
      石井秀始
    • Organizer
      第23回日本サイトメトリー学会学術集会
    • Place of Presentation
      日本医科大学橘桜会館(東京都)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 難治性消化器癌を克服する新しい創薬展開2013

    • Author(s)
      石井秀始
    • Organizer
      第23回日本サイトメトリー学会学術集会
    • Place of Presentation
      日本医科大学橘桜会館(東京都)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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