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Molecular targeted cancer therapy with HDAC inhibitors

Research Project

Project/Area Number 19590148
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionNagasaki University

Principal Investigator

OZAKI Keiichi  Nagasaki University, 大学院・医歯薬学総合研究科, 准教授 (50252466)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsオーダーメード医療 / ヒストン脱アセチル化酵素阻害剤 / がん分子標的療法 / ERK / 活性酸素 / ERK-MAPキナーゼ / PI3キナーゼ / シグナル遮断剤 / vヒストン脱アセチル化酵素 / MEK阻害剤
Research Abstract

ERK-MAPキナーゼ経路という細胞増殖に必須な経路の異常かつ恒常的活性化のみられるがん細胞では、その経路遮断薬であるMEK阻害剤と新しい抗がん剤であるヒストン脱アセチル化酵素(HDAC)阻害剤との併用によって、相乗的な抗がん作用が発現する。その細胞死増強効果は、ミトコンドリア傷害と抗酸化酵素の発現抑制が連動し、致死的な活性酸素の蓄積に至ることで発現した。さらに、ヌードマウスに移植したヒト癌細胞に対しても、併用による相乗効果が劇的に認められ、これらは今後のHDAC阻害剤を用いた癌治療において重要な知見となる。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (25 results)

All 2009 2008 2007

All Journal Article (12 results) (of which Peer Reviewed: 10 results) Presentation (13 results)

  • [Journal Article] Blockade of constitutively activated ERK signaling enhances cytotoxicity of microtubule-destabilizing agents in tumor cells2009

    • Author(s)
      S. Tanimura, A. Uchiyama, K. Watanabe, M. Yasunaga, Y. Inada, T. Kawabata, K. Iwashita, K. Ozaki and M. Kohno
    • Journal Title

      Biochem. Biophys. Res. Commun 378

      Pages: 650-655

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of constitutively activated ERK signaling enhances cytotoxicity of microtubule-destabilizing agents in tumor cells2009

    • Author(s)
      Tanimura, S., et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 378

      Pages: 650-655

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞内シグナル伝達経路の選択的遮断を基盤としたがん治療戦略2008

    • Author(s)
      尾崎恵一, 谷村進, 河野通明
    • Journal Title

      ファルマシア 44巻

      Pages: 219-224

    • Related Report
      2008 Final Research Report
  • [Journal Article] Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross-resistance to a wide range of DNA-damaging agents2008

    • Author(s)
      K. Ozaki, F. Futaba, M. Tanaka, T. Sakamoto, S. Tanimura and M. Kohno
    • Journal Title

      Cancer Sci. 99

      Pages: 376-384

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross-resistance to a wide range of DNA-damaging agents.2008

    • Author(s)
      Ozaki, K., et al.
    • Journal Title

      Cancer Sci. 99

      Pages: 376-384

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞内シグナル伝達経路の選択的遮断を基盤としたがん治療戦略2008

    • Author(s)
      尾崎恵一, 他
    • Journal Title

      ファルマシア 44

      Pages: 219-224

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross-resistance to a wide range of DNA-damaging agents2008

    • Author(s)
      Ozaki, K.
    • Journal Title

      Cancer Sci. 99

      Pages: 376-384

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anticancerdrugs upregulate HspBP1 and therby antagonize the prosurvival function of Hsp70 in tumor cells2007

    • Author(s)
      S. Tanimura, A. Hirano, J. Hashizume, M. Yasunaga, T. Kawabata, K. Ozaki and M. Kohno
    • Journal Title

      J. Biol. Chem 282

      Pages: 35430-35439

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of the phosphatidylinositol-3-kinase Akt signaling pathway enhances induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the pathway is constitutively activated2007

    • Author(s)
      Y. Fujiwara, Y. Hosokawa, K. Watanabe, S. Tanimura, K. Ozaki and M. Kohno
    • Journal Title

      Mol. Cancer Ther 6

      Pages: 1133-1142

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeted molecular strategies for cancer therapy based on the blockade of oncogenic pathways in human tumor cells2007

    • Author(s)
      K. Ozaki
    • Journal Title

      J. Pharm. Soc.Japan 127

      Pages: 983-991

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Targeted molecular strategies for cancer therapy based on the blockade of oncogenic pathways in human tumor cells2007

    • Author(s)
      Ozaki, K.
    • Journal Title

      Yakugaku Zasshi 127

      Pages: 983-991

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of the phosphatidylinositol-3-kinase-Akt signaling pathway enhances induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the pathway is constitutively activated2007

    • Author(s)
      Fujiwara, Y.
    • Journal Title

      Mol.Cancer Ther. 6

      Pages: 1133-1142

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Blockade of constitutively activated ERK signaling enhances cytotoxicity of HDAC inhibitors in tumor cells2009

    • Author(s)
      T. Sakamoto, K. Ozaki, N. Baba, K. Fujio, S. Tanimura, M. Kohno
    • Organizer
      The Second Asian Symposium on Pharmaceutical Sciences in Nagasaki
    • Place of Presentation
      長崎
    • Related Report
      2008 Final Research Report
  • [Presentation] PI3キナーゼ/Akt経路遮断剤とドキソルビシの併用による細胞死誘導増強 : セラミドの関与2008

    • Author(s)
      積佳江, 尾崎惠一, 坂野 喜子, 河野通明
    • Organizer
      Biochemistry and Molecular Biology 2008
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular mechanisim via which solid tumors become chemoresistant under hypoxic conditions2008

    • Author(s)
      尾崎恵一, 田中将人, 河野通明
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular mechanism for the enhanced cell death induced by the combination of HDAC inhibitors and MEK inhibitors2008

    • Author(s)
      坂元利彰, 尾崎恵一, 河野通明
    • Organizer
      第67回日本癌学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] Molecular mechanism for the enhanced cell death induced by the combination of HDAC inhibitors and MEK inhibitors2008

    • Author(s)
      坂元利彰, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] HDAC阻害剤とMEK阻害剤の併用による細胞死誘導の分子機構2007

    • Author(s)
      尾崎 恵一
    • Organizer
      第24回 日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2007-12-08
    • Related Report
      2007 Annual Research Report
  • [Presentation] Effective chemotherapeutic strategies for the treatment of lung adenocarcinoma cells harboring EGFR mutation2007

    • Author(s)
      尾崎 恵一
    • Organizer
      第65回 日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] PI3キナーゼ/Akt経路遮断剤とドキソルビシの併用による細胞死誘導増強-セラミドの関与2007

    • Author(s)
      積佳江, 尾崎惠一, 河野通明
    • Organizer
      第24回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] 低酸素環境下における癌細胞の抗癌剤耐性獲の分子機構2007

    • Author(s)
      田中将人, 尾崎惠一, 河野通明
    • Organizer
      第24回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] HDAC阻害剤とMEK阻害剤の併用による細胞死誘導の分子機構2007

    • Author(s)
      坂元利彰, 馬場伸幸, 尾崎惠一, 河野通明
    • Organizer
      第24回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] Effective chemotherapeutic strategies for the treatment of lung adenocarcinoma cells harboring EGFR mutation2007

    • Author(s)
      尾崎惠一, 小杉正生, 坂元利彰, 河野通明
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Targeting the ERK signaling pathway in cancer therapy2007

    • Author(s)
      河野通明, 谷村進, 尾崎惠一
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Blockade of the PI3K-Akt pathway selectively enhances induction of apoptosis by microtubule-destabilizing agents2007

    • Author(s)
      藤原雄介, 渡邊一石, 谷村進, 尾崎惠一, 河野通明
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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