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Construction and verification of a database library of drugs and metabolites detected in formalin tissues and fixatives utilizing in silico analysis

Research Project

Project/Area Number 17K09279
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Legal medicine
Research InstitutionNippon Medical School

Principal Investigator

UEKUSA Kyoko  日本医科大学, 医学部, マネジメントサポート・スタッフ (50409215)

Co-Investigator(Kenkyū-buntansha) 石野 孔祐  日本医科大学, 医学部, 講師 (60584878)
Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsホルマリン保存 / 代謝物解析 / Q-TOF / クエチアピン / S酸化 / 酸素付加体 / 代謝物予測 / LC-QTOF / データベースライブラリ / QTOF / データベース構築 / QTOF-LC/MS / GC/MS / S酸化物 / 法医中毒学 / GC-MS
Outline of Final Research Achievements

To enhance the analysis of drugs in tissues following formalin fixation, using Q-TOF analysis software, we constructed a database library of drugs, metabolites, and other compounds detected in formalin-fixed liver and fixative.Existing Q-TOF data for fixed liver tissues from drug-positive cases were analyzed in silico to predict metabolites using ACD/Meta Sense software. Four predicted metabolites were newly used as standards for verification of unidentifiable compounds registered as estimations in Personal Compound Database Library(PCDL).Using updated PCDL, a drug and metabolite search was performed with the previous Q-TOF data. This search returned good library search scores.The predicted three types of quetiapine were identified from the product ion spectrum.
This study demonstrated the feasibility of constructing a database library to search for drugs and metabolites in formalin-fixed tissues via in silico analysis incorporating updated Q-TOF data for metabolites.

Academic Significance and Societal Importance of the Research Achievements

ヒト臓器中の法医薬毒物分析は解剖直後あるいは凍結保存した組織などで実施するのが通例であるが剖検時に薬物使用が疑われず、その後の捜査等で薬物の関与が判明し長期間経過後に薬物分析検査やその分析結果の解釈について意見を求められる場合がある。ホルマリン臓器中の薬物分析では臓器と保存液の保存期間や代謝物をも鑑みた分析が重要である。本研究ではQ-TOF分析・解析ソフトにより薬物と代謝物の検索を実施した。In silico 解析を活用し代謝物のQ-TOFデータの更新と抽出法改良によってホルマリン臓器中の薬物および代謝物の検索により有用なデータベースライブラリの構築が可能であり、法医実試料への適用を目指す。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (13 results)

  • [Journal Article] A method for determining valproic acid in human whole blood and urine via gas chromatography-mass spectrometry and small-scale inter-laboratory trial2022

    • Author(s)
      Akira Namera, Kyoko Uekusa, Takeshi Saito, Kanji Yoshimoto, Naoki Ishiuchi, Kazuhiro Murata, Masataka Nagao
    • Journal Title

      Legal Medicine

      Volume: 59 Pages: 102133-102133

    • DOI

      10.1016/j.legalmed.2022.102133

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma2020

    • Author(s)
      MINAGAWA YUKI、ISHINO KOUSUKE、WADA RYUICHI、KUDO MITSUHIRO、NAITO ZENYA、TAKESHITA TOSHIYUKI、OHASHI RYUJI
    • Journal Title

      Anticancer Research

      Volume: 40 Issue: 10 Pages: 5631-5639

    • DOI

      10.21873/anticanres.14576

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Adductome Analysis Identifies N-Nitrosopiperidine Involved in the Etiology of Esophageal Cancer in Cixian, China2019

    • Author(s)
      Totsuka Y, Lin Y, He Y, Ishino K, Sato H, Kato M, Nagai M, Elzawahry A, Totoki Y, Nakamura H, Hosoda F, Shibata T, Matsuda T, Matsushima Y, Song G, Meng F, Li D, Liu J, Qiao Y, Wei W, Inoue M, Kikuchi S, Nakagama H, Shan B
    • Journal Title

      Chemical Research in Toxicology

      Volume: 32 Issue: 8 Pages: 1515-1527

    • DOI

      10.1021/acs.chemrestox.9b00017

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Downregulation of protein disulfide-isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma2019

    • Author(s)
      Kondo R, Ishino K, Wada R, Takata H, Peng WX, Kudo M, Kure S, Kaneya Y, Taniai N, Yoshida H, Naito Z
    • Journal Title

      International Journal of Oncology

      Volume: 54 Pages: 1409-1421

    • DOI

      10.3892/ijo.2019.4710

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 2-Deoxy-D-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells2018

    • Author(s)
      Ishino K, Kudo M, Peng WX, Kure S, Kawahara K, Teduka K, Kawamoto Y, Kitamura T, Fujii T, Yamamoto T, Wada R, Naito Z
    • Journal Title

      Biochem Biophys Res Comm

      Volume: 501 Issue: 3 Pages: 668-673

    • DOI

      10.1016/j.bbrc.2018.05.041

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis2018

    • Author(s)
      Arai Hiroki、Wada Ryuichi、Ishino Kousuke、Kudo Mitsuhiro、Uchida Eiji、Naito Zenya
    • Journal Title

      International Journal of Oncology

      Volume: 52 Pages: 978-988

    • DOI

      10.3892/ijo.2018.4238

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Metabolic disorder by 2-deoxyglucose induces endoplasmic reticulum stress-related apoptosis in pancreatic cancer cells2022

    • Author(s)
      Kousuke Ishino, Mitsuhiro Kudo, Akira Matsushita, Hiroshi Yoshida, Ryuji Ohashi
    • Organizer
      第81回日本癌学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Verification of a database library of drugs and metabolites detected in formalin tissues and fixatives constructed utilizing in silico analysis2021

    • Author(s)
      Kyoko UEKUSA, Masahiko TAKINO, Kousuke ISHINO, Yoshimasa KANAWAKU
    • Organizer
      100. Jahrestagung der Deutschen Gesellschaft fur Rechtsmedizin(第100次ドイツ法医学会)
    • Related Report
      2021 Research-status Report
  • [Presentation] 膵癌細胞株において2-デオキシ-D-グルコースはヘキソサミン合成経路を介して小胞体ストレス関連細胞死を誘発する2021

    • Author(s)
      石野孔祐、工藤光洋、大橋隆治
    • Organizer
      第89回日本医科大学医学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] In silico 解析を活用し構築したホルマリン臓器中の薬物および代謝物のデ ータベースライブラリの検証2020

    • Author(s)
      植草協子、滝埜昌彦、石野孔祐、金涌佳雅
    • Organizer
      第104次日本法医学会学術全国集会
    • Related Report
      2020 Research-status Report
  • [Presentation] In silico 解析を活用したホルマリン臓器中の薬物および代謝物のデータベース検索2019

    • Author(s)
      植草協子、石野孔祐、内藤善哉、金涌佳雅
    • Organizer
      第 87 回日本医科大学医学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] QTOF解析ソフトを用いたホルマリン臓器中の薬物および代謝物の検索2018

    • Author(s)
      植草協子, 滝埜昌彦, 中園裕紀子, 石野孔祐, 林田眞喜子, 大野曜吉
    • Organizer
      第87回 日本法医学会学術関東地方集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Comprehensive screening of Aconitum alkaloids in Aconitum plants by high resolution LC-QTOF Mass Spectrometry2018

    • Author(s)
      Takino M, Hayashida M, Uekusa K, Abe H, Ohno Y
    • Organizer
      24th Congress of the International Academy of Legal Medicine (IALM) in Fukuoka 第102次日本法医学会学術全国集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵癌細胞株において2-デオキシ-D-グルコースはGFAT1リン酸化を介して小胞体ストレス関連細胞死を誘発する2018

    • Author(s)
      石野孔祐、工藤光洋、彭為霞、呉壮香、和田龍一、内藤善哉
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 質量分析データに基づくDNA付加体データベースの整備2018

    • Author(s)
      石野孔祐、前迫侑也、内藤善哉、戸塚ゆ加里
    • Organizer
      日本環境変異原学会 第47回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] トリカブト植物体のQTOF分析2017

    • Author(s)
      林田眞喜子、滝埜昌彦、安部寛子、植草協子、大野曜吉
    • Organizer
      第101次日本法医学会学術全国集会
    • Related Report
      2017 Research-status Report
  • [Presentation] バルプロ酸の簡易GC/MS分析法の開発と施設間誤差の検討2017

    • Author(s)
      奈女良昭、植草協子、林田眞喜子、斎藤剛、村田和大、大野曜吉、長尾正崇
    • Organizer
      第101次日本法医学会学術全国集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ネット通販より購入したトリカブト塊根によるアコニチン中毒症例2017

    • Author(s)
      林田眞喜子、植草協子、大野曜吉、小原 浩
    • Organizer
      日本法中毒学会第36年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 液状検体で利用可能な新規膵がん腫瘍マーカーのタンパク質網羅的探索2017

    • Author(s)
      石野孔祐、工藤光洋、彭為霞、呉壮香、河本陽子、手塚潔、藤井雄文、恩田宗彦、和田龍一、内藤善哉
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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