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Development of an individualized therapy for establishing the optimal dosage by analysis of pharmacological gene

Research Project

Project/Area Number 19590149
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HAMADA Akinobu  Kumamoto University, 医学部・附属病院, 准教授 (00322313)

Co-Investigator(Kenkyū-buntansha) 齋藤 秀之  熊本大学, 医学部附属病院, 教授 (40225727)
川口 辰哉  熊本大学, 医学部附属病院, 准教授 (50244116)
松本 充博  熊本再春荘病院, 呼吸器科, 部長 (70253755)
Co-Investigator(Renkei-kenkyūsha) SAITO Hideyuki  熊本大学, 医学部・附属病院, 教授 (40225727)
KAWAGUCHI Tatsuya  熊本大学, 医学部・附属病院, 准教授 (50244116)
MATSUMOTO Mitsuhiro  熊本大学, 医学部・附属病院, 准教授 (70253755)
SASAKI Ji-ichiro  熊本大学, 医学部・附属病院, 助教 (60419637)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsオーダーメード医療 / 個別投与設計 / 抗悪性腫瘍薬 / 薬理遺伝学
Research Abstract

抗癌薬個別投与設計に有用と考えられる体内動態に影響を与える因子の探索を行った。アムルビシンに影響する薬物輸送タンパクとしてP糖タンパク質であることを明らかにした。イマチニブの体内動態と投与量に影響を与える因子に体表面積が関与することを明らかにした。エルロチニブの皮膚毒性と体内動態にP糖タンパク質の遺伝多型が影響することを明らかにした。本研究により、抗癌薬においても体内動態を制御する遺伝子群の解析が体内動態の個人間変動の解明に有効であることを示した。

Report

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

    (28 results)

All 2009 2008 2007

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (18 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Relationship between an effective dose of imatinib2009

    • Author(s)
      Kawaguchi T, Hamada A, Hirayama C, Nakashima R, Nambu T, Yamakawa Y, Watanabe H, Horikawa H, Mitsuya H, Saito H
    • Journal Title

      body surface area, and trough drug levels in patients with chronic myeloid leukemia (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of oral administered S-1 on the pharmacokinetics of SN-38, irinotecan active metabolite, in patients with advanced colorectal cancer.2009

    • Author(s)
      Yokoo K, Hamada A, Tazoe K, Sasaki Y, Saito H
    • Journal Title

      Ther Drug Monit (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of oral administered S-1 0n the pharmacokinetics of SN-38, irinotecan active metabolite, in patients with advanced colorectal cancer.2009

    • Author(s)
      Yokoo K
    • Journal Title

      Ther Drug Monit in press

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between an effective dose of imatinib, body surface area. and trough drug levels in patients with chronic myeloid leukemia.2009

    • Author(s)
      Kawaguchi T
    • Journal Title

      Int J Hematol (In press)

    • NAID

      10025161955

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of P-glycoprotein in accumulation and cytotoxicity of amrubicin and amrubicinol in MDR1 gene-transfected LLC-PK1 cells and human A549 lung adenocarcinoma cells2008

    • Author(s)
      Hira A, Watanabe H, Maeda Y, Yokoo K, Sanematsu E, Fujii J, Sasaki J, Hamada A, Saito H
    • Journal Title

      Biochem Pharmacol 75

      Pages: 973-980

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Constitutive overexpression of P-glycoprotein, rather than breast cancer resistance protein or organic cation transporter 1, contributes to acquisition of imatinib-resistance in K562 cells2008

    • Author(s)
      Hirayama C, Watanabe H, Nakashima R, Nanbu T, Hamada A, Kuniyasu A, Nakayama H, Kawaguchi T, Saito H
    • Journal Title

      Pharm Res 25

      Pages: 827-835

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of P-glycoprotein in accumulation and cytotoxicity of amrubicin and amrubicinol in MDR1 gene-transfected LLC-PK1 cells and human a549 lung adenocarcinoma cells2008

    • Author(s)
      Hira A
    • Journal Title

      Biochem Pharmacol 75

      Pages: 973-980

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of P-glycoprotein in accumulation and cytotoxicity of amrubicin and amrubicinol in MDR1 gene-transfected LLC-PK1 cells and human A549 lung adenocarcinoma cells2007

    • Author(s)
      Hira A
    • Journal Title

      Biochem Pharmacol 75

      Pages: 973-980

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Constitutive overexpression of P-glycoprotein, rather than breast cancer resistance protein or organic cation transporter 1, contributes to acquisition of imatinib-resistance in K562 cells2007

    • Author(s)
      Hirayama C
    • Journal Title

      Pharm Res 25

      Pages: 827-835

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 慢性骨髄性白血病治療薬イマチニブの血中濃度と至適投与量の関連2009

    • Author(s)
      濱田哲暢
    • Organizer
      日本臨床腫瘍学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-03-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] 慢性骨髄性白血病治療薬イマチニブの血中濃度と至適投与量の関連2009

    • Author(s)
      濱田哲暢, 川口辰哉, 平山知恵, 中島麗子, 南部健, 山川裕司, 堀川健太郎, 齋藤秀之
    • Organizer
      第7回日本臨床腫瘍学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] 非小細胞肺癌患者におけるエルロチニブの薬物動態変動ならびに毒性との相関解析試験2009

    • Author(s)
      佐々木治一郎、濱田哲暢、岩本範博、稲葉恵、岸裕人、浦田真紀、牛島淳、佐伯祥、山下明寿、千場博、齋藤秀之、興梠博次
    • Organizer
      第7回日本臨床腫瘍学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] 日本人におけるカルボプラチンの臨床薬理学的検討とカルバートの式の妥当性2009

    • Author(s)
      下方智也、安田宜成、河田健司、濱田哲暢、齋藤秀之、松尾清一、近藤征史、今泉和良、長谷川好規、安藤雄一
    • Organizer
      第7回日本臨床腫瘍学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] イマチニブ治療中の慢性骨髄性白血病患者における細胞内および血中薬物濃度相関解析2008

    • Author(s)
      中島麗子
    • Organizer
      日本臨床薬理学会
    • Place of Presentation
      東京
    • Year and Date
      2008-12-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] 日本人における慢性骨髄性白血病治療薬イマチニブの母集団薬物動態解析2008

    • Author(s)
      山川裕司
    • Organizer
      日本臨床薬理学会
    • Place of Presentation
      東京
    • Year and Date
      2008-12-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] Therapeutic efficacy of imatinib at a reduced dose to relieve adverse effects were equivalent to the standard dose in chronic myeloid leukemia patients.2008

    • Author(s)
      Akinobu Hamada
    • Organizer
      米国癌学会
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2008-04-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] K562細胞におけるBCR-ABL非依存的活性化ERKのimatinib抵抗性獲得への寄与2008

    • Author(s)
      南部健, 中川亜衣子, 川口辰哉, 荒木令江, 濱田哲暢, 齋藤秀之
    • Organizer
      第2回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] Characteristics of chronic-phase CML patients having durable cytogenetic response to low-dose imatinib2008

    • Author(s)
      Kawaguchi T, Hamada A, Nakashima R, Horikawa K, Ishihara S, Saito H, Hiroaki Mitsuya
    • Organizer
      American Society of Hematology 50th Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] イマチニブ治療中の慢性骨髄性白血病患者における細胞内および血中薬物濃度の相関解析2008

    • Author(s)
      中島麗子, 南部健, 平山知絵, 濱田哲暢, 川口辰哉, 齋藤秀之
    • Organizer
      第29回日本臨床薬理学会年会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation]2008

    • Author(s)
      山川裕司, 中島麗子, 平山知絵, 濱田哲暢, 川口辰哉, 満屋裕明, 齋藤秀之
    • Organizer
      日本人における慢性骨髄性白血病治療薬イマチニブ(IM)の母集団薬物動態解析
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Therapeutic efficacy of imatinib at a reduced dose to relieve adverse effects was equivalent to the standard dose in chronic myeloid leukemia patients2008

    • Author(s)
      Hamada A, Kawaguchi T, Nakajima R, Hirayama C, Nanbu T, Watanabe H, Saito H
    • Organizer
      American Association for Cancer Research 99th Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] 慢性骨髄性白血病細胞におけるメシル酸イマチニブ耐性獲得機序の解析2007

    • Author(s)
      南部 健
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] 塩酸アムルビシンと塩酸イリノテカン併用における薬物動態学的検討2007

    • Author(s)
      前田 友紀子
    • Organizer
      日本臨床薬理学会
    • Place of Presentation
      宇都宮
    • Year and Date
      2007-12-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] イマチニブ (IM) 抵抗性白血病細胞株K562-IMにおけるABCトランスポータ及び有機カチオントランスポータの発現・機能解析に基づくIM耐性獲得機序の解明2007

    • Author(s)
      南部 健
    • Organizer
      生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2007-11-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] 塩酸アムルビシンと塩酸イリノテカン併用における薬物動態学的検討2007

    • Author(s)
      前田友紀子, 實松絵美子, 濱田哲暢, 齋藤秀之
    • Organizer
      第28回日本臨床薬理学会年会
    • Place of Presentation
      宇都宮
    • Related Report
      2008 Final Research Report
  • [Presentation] イマチニブ(IM)抵抗性白血病細胞株K562-IMにおけるABCトランスポータ及び有機カチオントランスポータの発現・機能解析に基づくIM耐性獲得機序の解明2007

    • Author(s)
      南部健, 平山知絵, 渡邊博志, 中島麗子, 濱田哲暢, 國安明彦, 中山仁, 川口辰哉, 齋藤秀之
    • Organizer
      第29回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      仙台
    • Related Report
      2008 Final Research Report
  • [Presentation] S-1投与によるラット肝breast cancer resistance protein (Bcrp)の発現亢進と塩酸イリノテカン(CPT-11)体内動態変動2007

    • Author(s)
      横尾浩司, 濱田哲暢, 渡邊博志, 今井智之, 藤本裕美, 佐々木裕, 齋藤秀之
    • Organizer
      第29回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      仙台
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] エルロチニブの副作用又は薬効を判定する方法2009

    • Inventor(s)
      濱田哲暢、佐々木治一郎、齋藤秀之、興梠博次
    • Industrial Property Rights Holder
      国立大学法人熊本大学
    • Industrial Property Number
      2009-116385
    • Filing Date
      2009-05-13
    • Related Report
      2008 Final Research Report

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

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