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Discovery and development of antitumor drugs focused on the molecular clock of dedifferentiation and apoptosis during carcinogenesis

Research Project

Project/Area Number 21390047
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

OHDO Shigehiro  九州大学, 大学院・薬学研究院, 教授 (00223884)

Co-Investigator(Kenkyū-buntansha) KOYANAGI Satoru  九州大学, 大学院・薬学研究院, 准教授 (60330932)
NAOYA Matsunaga  九州大学, 大学院・薬学研究院, 助教 (10432915)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords体内時計 / がん / 分化 / アポトーシス / 創薬
Research Abstract

Circadian clock systems have been related in cell cycle and carcinogenesis. Theexpression of molecular clock genes is altered in cancer patients. However, the influenceof an alteration of molecular clock works during carcinogenesis has not been investigatedyet. In this study, the hepatocarcinogenesis by diethylnitrosoamine(DEN) in mice wasinhibited by the down-regulation of cellular dedifferentiation related genes expression. These findings suggest that the control of cellular dedifferentiation related genesexpression is important in carcinogenesis.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (26 results)

All 2012 2011 2010 2009

All Journal Article (14 results) (of which Peer Reviewed: 5 results) Presentation (12 results)

  • [Journal Article] Stress-regulated transcription factor ATF4 promotes neoplastic transformation by suppressing expression of the INK4a/ARF cell senescence factors2012

    • Author(s)
      Horiguchi M, Koyanagi S, Okamoto A, Suzuki SO, Matsunaga N, Ohdo S.
    • Journal Title

      Cancer Res

      Volume: 72(2) Pages: 395-401

    • Related Report
      2011 Final Research Report
  • [Journal Article] Stress-regulated transcription factor ATF4 promotes neoplastic transformation by suppressing expression of the INK4a/ARF cell senescence factors2012

    • Author(s)
      Horiguchi M, et al
    • Journal Title

      Cancer Research

      Volume: 72(2) Issue: 2 Pages: 395-401

    • DOI

      10.1158/0008-5472.can-11-1891

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of CLOCK on cytotoxicity induced by diethylnitrosamine in mouse primary hepatocytes2011

    • Author(s)
      Matsunaga N, Kohno Y, Kakimoto K, Hayashi A, Koyanagi S, Ohdo S.
    • Journal Title

      Toxicology

      Volume: 280(3) Pages: 144-151

    • Related Report
      2011 Final Research Report
  • [Journal Article] Molecular basis of chronopharmaceutics2011

    • Author(s)
      Ohdo S, Koyanagi S, Matsunaga N, Hamdan A.
    • Journal Title

      J Pharm Sci

      Volume: 100(9) Pages: 3560-3576

    • Related Report
      2011 Final Research Report
  • [Journal Article] Influence of CLOCK on cytotoxicity induced by diethylnitrosamine in mouse primary hepatocytes.2011

    • Author(s)
      Matsunaga N, et al.
    • Journal Title

      Toxicology

      Volume: 280(3) Pages: 144-151

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia-response plasmid vector producing bcl-2 shRNA enhances the apoptotic cell death of mouse rectum carcinoma2010

    • Author(s)
      Fujioka T, Matsunaga N, Okazaki H, Koyanagi S, Ohdo S.
    • Journal Title

      J Pharmacol Sci

      Volume: 113(4) Pages: 353-361

    • NAID

      10027746067

    • Related Report
      2011 Final Research Report
  • [Journal Article] Glucocorticoid-dependent expression of O(6)-methylguanine-DNA methyltransferase gene modulates dacarbazine-induced hepatotoxicity in mice2010

    • Author(s)
      Horiguchi M, Kim J, Matsunaga N, Kaji H, Egawa T, Makino K, Koyanagi S, Ohdo S.
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 333(3) Pages: 782-787

    • Related Report
      2011 Final Research Report
  • [Journal Article] Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice2010

    • Author(s)
      Okazaki F, Matsunaga N, Okazaki H, Utoguchi N, Suzuki R, Maruyama K, Koyanagi S, Ohdo S.
    • Journal Title

      Cancer Res

      Volume: 70(15) Pages: 6238-6246

    • Related Report
      2011 Final Research Report
  • [Journal Article] Chronotherapeutic strategy : Rhythm monitoring, manipulation and disruption2010

    • Author(s)
      Ohdo S.
    • Journal Title

      Adv Drug Deliv Rev

      Volume: 62(9-10) Pages: 859-875

    • Related Report
      2011 Final Research Report
  • [Journal Article] Chronopharmacological strategies : Intraand inter-individual variability of molecular clock2010

    • Author(s)
      Ohdo S, Koyanagi S, Matsunaga N.
    • Journal Title

      Adv Drug Deliv Rev

      Volume: 62(9-10) Pages: 885-897

    • Related Report
      2011 Final Research Report
  • [Journal Article] Glucocorticoid-dependent expression of O(6)-methylguanine-DNA methyltransferase gene modulates dacarbazine-induced hepatotoxicity in mice.2010

    • Author(s)
      Horiguchi M, et al.
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 333(3) Pages: 782-787

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice.2010

    • Author(s)
      Okazaki F, et al.
    • Journal Title

      Cancer Res

      Volume: 70(15) Pages: 6238-6246

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clock gene mutation modulates the cellular sensitivity to genotoxic stress through altering the expression of N-methylpurine DNA glycosylase gene2009

    • Author(s)
      Kim J, Matsunaga N, Koyanagi S, Ohdo S.
    • Journal Title

      Biochem Pharmacol

      Volume: 78(8) Pages: 1075-1082

    • Related Report
      2011 Final Research Report
  • [Journal Article] Clock gene mutation modulates the cellular sensitivity genotoxic stress through altering the expression N-methylpurine DNA glycosylase gene2009

    • Author(s)
      Kim J., et al.
    • Journal Title

      Biochem.Pharmacol. 78(8)

      Pages: 1075-1082

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 時間薬理による副作用低減.シンポジウム「副作用低減のための新しい薬理学的アプローチ」(オーガナイザー:植田真一郎、大石了三)2011

    • Author(s)
      大戸茂弘、小柳悟、松永直哉
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] 分子時計を基盤にした時間治療.シンポジウム「生命現象を担う生体分子に着目した創薬と臨床応用」(オーガナイザー:荒牧弘範、前仲勝実)2011

    • Author(s)
      大戸茂弘、小柳悟、松永直哉
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2011 Final Research Report
  • [Presentation] 創薬・育薬を指向した時間薬剤学的研究2010

    • Author(s)
      大戸茂弘
    • Organizer
      特別講演第28回製剤設計研究会
    • Place of Presentation
      東京薬科大学
    • Year and Date
      2010-10-23
    • Related Report
      2011 Final Research Report
  • [Presentation] 創薬・育薬を指向した時間薬剤学的研究2010

    • Author(s)
      大戸茂弘、小柳悟、松永直哉
    • Organizer
      第47回薬剤学懇談会研究討論会「新技術・新素材が切り拓く薬剤開発」岐阜県飛騨高山
    • Place of Presentation
      高山グリーンホテル、天領閣
    • Year and Date
      2010-06-24
    • Related Report
      2011 Final Research Report
  • [Presentation] 分子時計を基盤にした創薬・育薬2010

    • Author(s)
      大戸茂弘
    • Organizer
      第5回DDS熊本シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2010-02-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 時間薬理学とは.シンポジウム「時間薬理学と時間栄養学による新しい治療戦略の開拓」(オーガナイザー:柴田重信、大戸茂弘)2010

    • Author(s)
      大戸茂弘、小柳悟、松永直哉
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] 癌の時間治療と今後の展望.シンポジウム「体内時計を利用した創薬から治療戦略まで」(オーガナイザー:柴田重信、守屋孝洋)2010

    • Author(s)
      大戸茂弘、小柳悟、松永直哉
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Related Report
      2011 Final Research Report
  • [Presentation] 体内時計の分子機構を基盤にした薬物投与設計.シンポジウム1「薬物療法を支える基礎研究と臨床研究の糸口、進め方と成果の活用」(オーガナイザー:家入一郎、大戸茂弘)2010

    • Author(s)
      小柳悟、松永直哉、大戸茂弘
    • Organizer
      医療薬学フォーラム2010第18回クリニカルファーマシーシンポジウム
    • Place of Presentation
      広島
    • Related Report
      2011 Final Research Report
  • [Presentation] 時間治療による薬物治療の最適化.特別講演2009

    • Author(s)
      大戸茂弘
    • Organizer
      第24回長崎DDS研究会
    • Place of Presentation
      長崎
    • Year and Date
      2009-12-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 薬物・栄養投与の時間治療学的戦略~体内時計の分子機構を基盤として~.特別講演2009

    • Author(s)
      大戸茂弘
    • Organizer
      日本薬学会主催第10回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular clock mechanisms of drug metabolism.2009

    • Author(s)
      Ohdo S, Matsunaga N, Koyanagi S.
    • Organizer
      Symposium"Functional genomics"16th International Conference on Cytochrome P450
    • Place of Presentation
      Japan(Okinawa)
    • Related Report
      2011 Final Research Report
  • [Presentation] 抗がん剤の時間薬理.シンポジウム4「PK/PD解析から見た抗がん剤の効果・副作用」(オーガナイザー:鈴木洋史、桂敏也)2009

    • Author(s)
      大戸茂弘、松永直哉、小柳悟
    • Organizer
      医療薬学フォーラム2009第17回クリニカルファーマシーシンポジウム
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2017-07-26  

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