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Construction of improved lymphocyte transformation test based on the onset and aggravation mechanism of drug-induced liver injury

Research Project

Project/Area Number 25670068
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionChiba University

Principal Investigator

ITO Kousei  千葉大学, 薬学研究科(研究院), 教授 (30323405)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHLA / 薬剤性肝障害 / リンパ球幼弱化試験 / 共有結合 / 代謝活性化 / アダクト生成
Outline of Final Research Achievements

Drug hypersensitivity reaction is one of the categories of drug-induced liver injury (DILI). However, current clinical test such as lymphocyte transformation test (LTT) could not detect all the causative drugs with hypersensitivity reaction because the assay does not include hepatocytes that metabolize drugs and subsequently propose antigens to the lymphocytes. To overcome that shortcoming, it is needed to add hepatocytes that are endowed with metabolic enzyme activity and antigen presentation. We firstly constructed transgenic mice constitutively expressing human HLA molecule related to some kinds of DILI. In addition, adenoviruses carrying HLA to transiently express its product in mouse primary hepatocytes were constructed. It is expected that the sensitivity of current LTT assay is improved by using these novel hepatocytes tools.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (5 results)

All 2015 2014 2013

All Presentation (5 results) (of which Invited: 3 results)

  • [Presentation] ヒトにおける特異体質毒性評価を目的としたキメラ型 HLA 遺伝子導入マウスの作出2015

    • Author(s)
      1. 向後晃太郎, 青木重樹, 聡 劉, 関根秀一, 伊藤晃成
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 特異体質毒性リスク予測精度改善に向けた多面的アプローチ2015

    • Author(s)
      伊藤晃成
    • Organizer
      薬物動態談話会1月例会
    • Place of Presentation
      東京
    • Year and Date
      2015-01-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 特異体質毒性評価に利用可能なヒトーマウスキメラ型HLA遺伝子の構築2014

    • Author(s)
      向後晃太郎, 青木重樹, 関根秀一, 伊藤晃成
    • Organizer
      第 58 回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬剤性肝障害のスクリーニング系構築・メカニズム解明に向けた取組2014

    • Author(s)
      伊藤晃成
    • Organizer
      第4回 杉山特別研究室(理研)公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 薬剤性肝障害発症予測に向けた臨床・基礎からのアプローチ2013

    • Author(s)
      伊藤晃成
    • Organizer
      第30回日本TDM学会 学術大会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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