• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Establishment of safe and effective pediatric hematopoietic cell transplantation by pharmacokinetic analysis and metabolic enzyme activity analysis

Research Project

Project/Area Number 16K10033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKagoshima University

Principal Investigator

Kawano Yoshifumi  鹿児島大学, 医歯学域医学系, 教授 (20260680)

Co-Investigator(Kenkyū-buntansha) 児玉 祐一  鹿児島大学, 医歯学域附属病院, 講師 (20535695)
岡本 康裕  鹿児島大学, 医歯学域医学系, 准教授 (30398002)
西川 拓朗  鹿児島大学, 医歯学域附属病院, 講師 (90535725)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordscyclophosphamide / 心毒性 / acrolein / glutathione / busulfan / Aldehyde dehydrogenase 1 / シクロフォスファミド / ブスルファン / 抗がん剤 / グルタチオン / アクロレイン / 造血細胞移植術 / GST / 移植前大量化学療法 / 毒性
Outline of Final Research Achievements

4-hydroxy-cyclophosphamide (HCY) is an active metabolite of cyclophosphamide (CY). It is converted to cytotoxic metabolite acrolein. Human hepatoblastoma cell line HepG2 were exposed to HCY and the concentration of acrolein in cell culture supernatant were measured. Interestingly, the detected acrolein was higher than we expected. Furthermore, glutathione (GSH), an acrolein scavenger were reduced gradually in HepG2 cells. And then, to inhibit the production of acrolein, ALDH1 were knock downed by RNA interference. Against our expectations, the production of acrolein is not increased when ALDH1 knockdown HepG2 cells were exposed to HCY. It indicates that acrolein is not only produced directly by CY, but also is produced in another pathway.

Academic Significance and Societal Importance of the Research Achievements

Cyclophosphamide (CY)大量投与で生じる急性心筋障害はその数%が致死的であり、臨床上大きな問題である。そして、その発症機序は未だ不明でありその予防法も確立されていない。CY心毒性の主因であるacrolein産生量はその除去剤でもあるglutathionの量が関係することが示唆された。glutathion産生能の個体差が、CY心毒性発症の個体差に繋がる可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2019 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Influence of GST polymorphisms on busulfan pharmacokinetics in Japanese children.2019

    • Author(s)
      Nishikawa T, Yamaguchi H, Ikawa K, Nakayama K, Higashi E, Miyahara E, Abematsu T, Nakagawa S, Kodama Y, Tanabe T, Shigemi A, Shinkoda Y, Okamoto Y, Takeda Y, Kawano Y.
    • Journal Title

      Pediatr Int.

      Volume: - Issue: 6 Pages: 558-565

    • DOI

      10.1111/ped.13859

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Giant radiation-induced cavernous haemangioma before reduced-intensity bone marrow transplantation for acute lymphoblastic leukaemia.2019

    • Author(s)
      Saito A, Nishikawa T, Oyoshi T, Nakagawa S, Kodama Y, Yamada A, Kinoshita M, Okamoto Y, Arita K, Moritake H, Kawano Y.
    • Journal Title

      Bone Marrow Transplant.

      Volume: 54 Issue: 2 Pages: 312-315

    • DOI

      10.1038/s41409-018-0272-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of metabolites of cyclophosphamide in cardiotoxicity.2017

    • Author(s)
      Kurauchi K, Nishikawa T, Miyahara E, Okamoto Y, Kawano Y.
    • Journal Title

      BMC Res Notes.

      Volume: 14 Issue: 1 Pages: 406-406

    • DOI

      10.1186/s13104-017-2726-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal T and B cell engraftment in two cases of X-linked severe combined immunodeficiency with IgG1 gammopathy.2017

    • Author(s)
      Okano T, Nishikawa T, Watanabe E, Watanabe T, Takashima T, Yeh TW, Yamashita M, Tanaka-Kubota M, Miyamoto S, Mitsuiki N, Takagi M, Kawano Y, Mochizuki Y, Imai K, Kanegane H, Morio T.
    • Journal Title

      Clin Immunol.

      Volume: 183 Pages: 112-120

    • DOI

      10.1016/j.clim.2017.08.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persistent positive metaiodobenzylguanidine scans after autologous peripheral blood stem cell transplantation may indicate maturation of stage 4 neuroblastoma.2017

    • Author(s)
      Okamoto Y, Kodama Y, Nishikawa T, Rindiarti A, Tanabe T, Nakagawa S, Yoshioka T, Takumi K, Kaji T, Kawano Y.
    • Journal Title

      Pediatr Hematol Oncol.

      Volume: 34 Issue: 3 Pages: 157-164

    • DOI

      10.1080/08880018.2017.1348414

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Pharmacokinetics of cyclophosphamide and its metabolites in Pediatric Hematopoietic Stem Cell Transplant Recipients: A comparative study of two conditioning regimens, and one posttransplantation regimen.2017

    • Author(s)
      Nishikawa T, Ikawa K, Miyahara E, Abematsu T, Nakagawa S, Kurauchi K, Kodama Y, Tanabe T, Shinkoda Y, Okamoto Y, Kawano Y.
    • Organizer
      IATDMCT(International association of TDM and Clinical Toxicology)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウスにおける大量シクロホスファミドの薬物動態及び毒性の評価.2017

    • Author(s)
      宮原恵弥子,西川拓朗,猪川和朗,牛飼美晴,川口博明,岡本康裕,森川則文,堀内正久,河野嘉文.
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi