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Individualization of Immunosuppressive Therapy Using Pharmacodynamics, Immunology and Molecular Biology

Research Project

Project/Area Number 20591517
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNagoya University

Principal Investigator

KUZUYA Takafumi  Nagoya University, 医学部附属病院, 副部長 (00444406)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Takaaki  名古屋大学, 大学院・医学系研究科, 教授 (70314010)
HANEDA Masataka  名古屋大学, 大学院・医学系研究科, 講師 (50436995)
KODERA Yasuhiro  名古屋大学, 大学院・医学系研究科, 准教授 (10345879)
IWASAKI Kenta  名古屋大学, 大学院・医学系研究科, 助教 (10508881)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords免疫抑制薬 / 薬力学 / IL-2 / 細胞増殖抑制効果 / 免疫卸制薬 / CFSE / Bリンパ球 / PCNA / インターロイキン2 / real-time RT-PCR / IC50値
Research Abstract

To optimize immunosuppressive treatment in individual patients, many biomarkers have been proposed, but there has been very little information about association to clinical outcome data. The most effective immunosuppressive strategies in organ transplantation are based on the inhibition of IL-2 signal by calcineurin inhibitiors and we first evaluated the inhibition of IL-2 mRNA production for each patient by using RT-PCR method. Then we examined individual T-cell sensitivity to each immunosuppressive agent (cyclosporine, tacrolimus, mycophenolic acid, predonisolone) using flow cytometry with CFSE labeling. Patients with high sensitivity to cyclosporine tended to experience viral reactivation. Pretransplant pharmacodynamics could provide useful information on optimal and safe immunosuppressive therapy.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (31 results)

All 2010 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 9 results) Presentation (18 results) Remarks (1 results)

  • [Journal Article] Evaluation of IL-2 mRNA in Whole Blood as a Parameter for Monitoring Cyclosporine Pharmacodynamics2009

    • Author(s)
      Takafumi Kuzuya, Takaaki Kobayashi, Akio Katayama, Takaharu Nagasaka, Yuko Miwa, Kazuharu Uchida, Akimasa Nalao
    • Journal Title

      Biological Pharmaceutical Bulletin 32

      Pages: 604-608

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation Index for PCNA mRNA in Peripheral Blood as Immune Function Monitoring after Renal Transplantation2009

    • Author(s)
      Misao Niwa, Yuko Miwa, Takafumi Kuzuya, Kenta Iwasaki, Masataka Haneda, Tsuneo Ueki, Akio Katayama, Takahisa Hiramitsu, Norihiko Goto, Takaharu Nagasaka, Yoshihiko Watarai, Kazuharu Uchida, Akimasa Nakao, Takaaki Kobayashi
    • Journal Title

      Transplantation 87

      Pages: 1411-1414

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pretransplant Pharmacodynamic Analysis of Immunosuppressive Agents using CFSE-based T Cell Proliferation Assay2009

    • Author(s)
      Yoko Kurata, Marina Kato, Takafumi Kuzuya, Yuko Miwa, Kenta Iwasaki, Masataka Haneda, Katsuo Amioka, Yoshihiko Watarai, Kazuharu Uchida, Akimasa Nakao, Takaaki Kobayashi
    • Journal Title

      Clinical Pharmacology & Therapeutics 86

      Pages: 285-289

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacodynamicsを用いた代謝拮抗薬およびmTOR阻害薬の薬効評価2009

    • Author(s)
      水谷加代子、葛谷孝文、加藤真梨奈、倉田洋子、岩崎研太、野田幸裕、網岡克雄、山田清文、小林孝彰
    • Journal Title

      愛知県病院薬剤師会雑誌 36

      Pages: 2-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 腎移植後の免疫抑制療法の個別化2009

    • Author(s)
      葛谷孝文、加藤真梨奈、倉田洋子、片山昭男、打田和治、丹羽操、三輪祐子、岩崎研太、羽根田正隆、小林孝彰
    • Journal Title

      Organ Biology 16

      Pages: 5-11

    • Related Report
      2010 Final Research Report
  • [Journal Article] Pretransplant Pharmacodynamic Analysis of Immunosuppressive Agents Using CFSE-Based T-Cell Proliferation Assay.2009

    • Author(s)
      Kurata Yoko, et al.
    • Journal Title

      Clin. Pharmacol. Ther. 86

      Pages: 285-289

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation Index for PCNA mRNA in Peripheral Blood as Immune Function Monitoring After Renal Transplantation.2009

    • Author(s)
      Misao Niwa, et al.
    • Journal Title

      Transplantation 87

      Pages: 1411-1414

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Interleukin-2 mRNA in Whole Blood as a parameter for Monitoring Cyclosporine Pharmacodynamics.2009

    • Author(s)
      Takafumi Kuzuya, et al.
    • Journal Title

      Bio. Pharm. Bull. 32

      Pages: 604-608

    • NAID

      110007160695

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Interleukin-2 mRNA in Whole Blood as a parameter for Monitoring Cyclosporine Pharamacodynamics.2009

    • Author(s)
      Takafumi Kuzuya, et al.
    • Journal Title

      Bio. Pharm. Bull. 32(in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stimulation Index for PCNA mRNA in Peripheral Blood as Immune Function Monitoring after Renal Transplantation.2009

    • Author(s)
      Misao Niwa, et al.
    • Journal Title

      Transplantaion (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 免疫抑制薬の分子論的解析と臨床応用可能なPDモニタリングの開発2008

    • Author(s)
      倉田洋子, 網岡克雄, 加藤真梨奈, 野田幸裕, 葛谷孝文, 羽根田正隆, 長坂隆治, 打田和治, 中尾昭公, 岩崎研太, 小林孝彰
    • Journal Title

      今日の移植 21

      Pages: 602-604

    • Related Report
      2010 Final Research Report
  • [Journal Article] 免疫抑制薬の分子論的解析と臨床応用可能なPDモニタリングの開発2008

    • Author(s)
      倉田洋子, ら
    • Journal Title

      今日の移植 21

      Pages: 602-604

    • Related Report
      2008 Annual Research Report
  • [Presentation]2010

    • Author(s)
      平林彩、岩崎研太、加藤真梨奈、葛谷孝文、野田幸裕、三輪祐子、羽根田正隆、小林孝彰
    • Organizer
      日本移植学会総会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacodynamic Evaluation of Cyclosporine in B-Cell2010

    • Author(s)
      Kuzuya T., Kato M., Iwasaki K., Haneda M., Miwa Y., Kobayashi T., Uchida K., Yamada K
    • Organizer
      International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver (Canada)
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] B細胞の増殖に関わるシグナル伝達経路~シクロスポリンのB細胞に対する増殖抑制機構について2010

    • Author(s)
      平林彩, ら
    • Organizer
      日本移植学会
    • Place of Presentation
      京都
    • Related Report
      2010 Annual Research Report
  • [Presentation] リンパ球を用いた免疫抑制薬のPD解析方法の確立2009

    • Author(s)
      加藤真梨奈、倉田洋子、葛谷孝文、羽根田正隆、岩崎研太、小林孝彰、野田幸裕
    • Organizer
      日本薬学東海支部大会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-11
    • Related Report
      2010 Final Research Report
  • [Presentation] B細胞を用いた免疫抑制剤の薬力学的解析:シクロスポリンはB細胞を抑制するか?2009

    • Author(s)
      加藤真梨奈、倉田洋子、葛谷孝文、羽根田正隆、岩崎研太、野田幸裕、小林孝彰
    • Organizer
      日本移植学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞周期関連遺伝子のmRNA発現レベルによる腎移植後の免疫抑制状態の評価2009

    • Author(s)
      丹羽操、馬亮、三輪祐子、岩崎研太、羽根田正隆、渡井至彦、打田和治、片山昭男、小林孝彰
    • Organizer
      日本移植学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] 免疫抑制療法におけるT cell proliferationを指標としたPD assayの有用性2009

    • Author(s)
      倉田洋子、加藤真梨奈、葛谷孝文、岩崎研太、羽根田正隆、打田和治、中尾昭公、小林孝彰、網岡克雄
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] 腎移植患者を対象とした免疫抑制薬の薬力学的解析2009

    • Author(s)
      葛谷孝文、加藤真梨奈、倉田洋子、片山昭男、打田和治、丹羽操、三輪祐子、岩崎研太、羽根田正隆、小林孝彰
    • Organizer
      日本臨床腎移植学会
    • Place of Presentation
      千葉
    • Related Report
      2010 Final Research Report
  • [Presentation] 移植後の免疫機能モニタリング2009

    • Author(s)
      小林孝彰、丹羽操、馬亮、三輪祐子、岩崎研太、中尾昭公、羽根田正隆、葛谷孝文、植木常雄、片山昭男、平光高久、佐藤哲彦、後藤憲彦、長坂隆治、渡井至彦、打田和治
    • Organizer
      日本臨床腎移植学会
    • Place of Presentation
      千葉
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞周期関連遺伝子のmRNA発現レベルによる腎移植後の免疫抑制状態の評価.2009

    • Author(s)
      丹羽操, ら.
    • Organizer
      日本移植学会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] 腎移植後の免疫抑制療法個別化プロジェクト2008

    • Author(s)
      葛谷孝文、加藤真梨奈、倉田洋子、片山昭男、打田和治、丹羽操、三輪祐子、岩崎研太、羽根田正隆、小林孝彰
    • Organizer
      日本臓器保存生物医学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Cell proliferationを指標としたPD assayの開発2008

    • Author(s)
      倉田洋子、加藤真梨奈、葛谷孝文、中尾昭公、打田和治、小林孝彰、網岡克雄
    • Organizer
      日本移植学会総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] 免疫抑制薬の薬力学的モニタリングの開発とその有用性の検討2008

    • Author(s)
      加藤真梨奈、倉田洋子、葛谷孝文、打田和治、野田幸裕、小林孝彰
    • Organizer
      日本移植学会総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] PCNAmRNAを指標とした免疫機能モニタリングによる腎移植後の過剰免疫抑制の判定2008

    • Author(s)
      丹羽操、馬亮、三輪祐子、岩崎研太、片山昭男、打田和治、中尾昭公、小林孝彰
    • Organizer
      日本移植学会総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacodynamics(PD)を用いた代謝拮抗薬の薬効評価と個人差の解析2008

    • Author(s)
      水谷加代子、倉田洋子、加藤真梨奈、葛谷孝文、野田幸裕、小林孝彰
    • Organizer
      日本移植学会総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacodynamic Characta-ristics of Renal Transplant Resipients2008

    • Author(s)
      Kuzuya T., Kobayashi A., Katayama Y., Miwa T., Nagasaka K., Uchida K., Yamada K.
    • Organizer
      International Congress Transplantation of The Society
    • Place of Presentation
      Sydney (Australia)
    • Related Report
      2010 Final Research Report
  • [Presentation] Stimulation Index for PCNA mRNA Expression in Peripheral Blood as a Predictive Indicator of Over Immunosuppression2008

    • Author(s)
      Kobayashi T., Niwa M., Miwa Y., Katayama A., Haneda M., Kuzuya T., Nagasaka T., Ueki T., Uchida K., Nakao A.
    • Organizer
      International Congress Transplantation of The Society
    • Place of Presentation
      Sydney (Australia)
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacodynamic Characteristics of Renal Transplant Resipients.2008

    • Author(s)
      Takafumi Kuzuya, et al.
    • Organizer
      XXII International Congress of the Transplantation Society
    • Place of Presentation
      シドニー
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.nagoya-u.ac.jp/tx-immunology/TOP.html/TOP.html

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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