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Individualization of dosage for immunosuppressive drugs based on new biomarkers

Research Project

Project/Area Number 18590155
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIHARA Kiyoshi  Musashino University, Clinical Pharmaceutics, Associate Professor (00281444)

Co-Investigator(Kenkyū-buntansha) TANIGAWARA Yusuke  Musashino University, School of Medicine, Department of Pharmacy, Professor (30179832)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsOrgan Transplantation / immunosuppressive drugs / Biomarkers / Rejection / Protein Chip / Pharmacokinetics / Pharmacodynamics / Non-invasive
Research Abstract

In organ transplantation, needle biopsy of allograft is a standard test for the diagnosis of acute rejection. However, sampling errors, biopsy-associated complications, and a time-consuming process are problem. The aim of this study is to search and identify new biomarkers for allograft rejection and therapeutic effect of immunosuppressive drugs by measuring protein expression profile in peripheral blood and urine. We carried out the rat cardiac transplantation to create three models, isograft, allograft, and allograft with cyclosporine(CsA). The peripheral bloods and urine were collected to perform protein expression profiling using protein chip analysis(surface-enhanced laser desorption/ionization time of flight mass spectrometry ; SELDI-TOF MS). The cation exchange chip revealed that expression of several peptides with molecular weight of 3500, 3600, 4200, and 6500m/z increased in plasma of allograft model. The anion exchange chip revealed that expression of several proteins with molecular weight of 7000, 8000, and 9000m/z increased in plasma of allograft model. In the urine, peptides with molecular weight of 3300, 4400, and 5500m/z increased in allograft model. A comprehensive analysis of the peptides and proteins expression in peripheral blood and urine of rat organ transplantation models results in the discovery of new biomarkers, which could be applied to the therapeutic use.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 5 results) Presentation (4 results)

  • [Journal Article] Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole2008

    • Author(s)
      Mihara A, Tanigawara Y, et. al.
    • Journal Title

      Eur J Clin Pharlnacol 64

      Pages: 89-91

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastati colorectal cancer2008

    • Author(s)
      Yamada Y, Tanigawara Y., et. al.
    • Journal Title

      Br J Cancer. 25

      Pages: 1034-1038

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer.2008

    • Author(s)
      Yamada Y, Tanigawara Y, et. al.
    • Journal Title

      Br J Cancer. 98(6)

      Pages: 1034-1038

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole.2008

    • Author(s)
      Mihara A, Tanigawara Y, et. al.
    • Journal Title

      Eur J Clin Pharmacol. 64(1)

      Pages: 89-91

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients with metastatic colorectal cancer.2008

    • Author(s)
      Yamada Y, Tanigawara Y, et. al.
    • Journal Title

      Br J Caneer. 25

      Pages: 1034-1038

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole.2008

    • Author(s)
      Mihara A, Tanigawara Y, et. al.
    • Journal Title

      Eur J Chin Pharmacol. 64

      Pages: 89-91

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase II study of oxaliplatin in japanese patients with metastatic colorectal cancer refractory to fluoropyrimidines.2007

    • Author(s)
      Boku N, Tanigawara Y, et. al.
    • Journal Title

      Jpn J Clin Oncol. 37(6)

      Pages: 440-445

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] バイオマーカーによる診断と治療効果の予測2007

    • Author(s)
      三原 潔
    • Journal Title

      薬剤学:生命とくすり 67

      Pages: 188-192

    • NAID

      10019492783

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Enantioselective and highly sensitive determination of carvedilol in human plasma and whole blood after administration of the racemate using normal-phase high-performance liquid chromatography2006

    • Author(s)
      Saito M, Mihara K, et. al.
    • Journal Title

      J.Chromatogr.B Analyt.Technol.Biomed.Life Sci 843

      Pages: 73-77

    • NAID

      10025788129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus.2006

    • Author(s)
      Sato R, Tanigawara Y, et. al.
    • Journal Title

      Antimicrob Agents Chemother. 50(11)

      Pages: 3763-5769

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus.2006

    • Author(s)
      Tanigawara Y. Sato R, et. al.
    • Journal Title

      Antimicrob Agents Chemother. 50(11)

      Pages: 3754-3762

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Enantioselective and highly sensitive determination of the racemate using using normal-phase high-performance liquid chromatography.2006

    • Author(s)
      Saito M, Mihara K, et. al.
    • Journal Title

      J Chromatogr B Analyt Technol Biomed Life Sci. 843(1)

      Pages: 73-77

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Population Pharmacolinetic and Pharmacodynamic Analysis of a Class IC Antiarrhythmic, Pilsicainide, in Patients With Cardiac Arrhythmias.2006

    • Author(s)
      Ogawa R, Mihara K, et. al.
    • Journal Title

      J Clin Pharmacol. 46(10

      Pages: 59-68

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Enantioselective and highly sensitive determination of carvedilol in human plasma and whole blood after administration of the racemate using normal-phase high-performance liquid chromatography.2006

    • Author(s)
      Saito M, Mihara K, et al.
    • Journal Title

      J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 843・1

      Pages: 73-77

    • NAID

      10025788129

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pharmacokingetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus.2006

    • Author(s)
      Sato R, Tanigawara Y, et al.
    • Journal Title

      Antimicrob. Agents Chemother. 50・11

      Pages: 3763-3769

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Population pharmacokinetics of Arbekacin in patients infected with methicillin-resistant Staphylococcus aureus.2006

    • Author(s)
      Tanigawara Y., Sato R, et al.
    • Journal Title

      Antimicrob. Agents Chemother. 50・11

      Pages: 3754-3762

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 1173C>T @olymorphism in VKORC1 modulates the required warfarin dose.2006

    • Author(s)
      Kosaki K, Taniagawara Y, et al.
    • Journal Title

      Pediatr. Cardiol. 27・6

      Pages: 685-688

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Population pharmacokinetic analysis of micafungin in Japanese patients with fungal infections.2006

    • Author(s)
      Tabata K, Tanigawara Y, et al.
    • Journal Title

      Drug Metab. Pharmacokinet. 21・4

      Pages: 324-331

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Novel application of ProteinChip technology exploring acute rejection markers of rat small bowel transplantation.2006

    • Author(s)
      Yamayoshi Y, Tanigawara Y, et al.
    • Journal Title

      Transplantation 82・3

      Pages: 320-326

    • Related Report
      2006 Annual Research Report
  • [Presentation] 抗原提示細胞指向型キャリアを用いたNFκBデコイ送達に基づくラット心移植急性拒絶におけるサイトカイン産生抑制2007

    • Author(s)
      樋口 ゆり子、三原 潔, ら
    • Organizer
      日本薬剤学会第22年会
    • Place of Presentation
      さいたま市
    • Year and Date
      2007-05-23
    • Related Report
      2007 Annual Research Report
  • [Presentation] New biomarkers for acute rejection and therapeutic effect of immunosu ppressive drugs in organ transplantation2006

    • Author(s)
      Mihara K, Iketani O, Tanigawara Y
    • Organizer
      The 3rd Korea-Japan Joint Symposium on Drug Delivery and Therapy
    • Place of Presentation
      韓国、ソウル
    • Year and Date
      2006-04-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] New biomarkers for acute rejection and therapeutic effect of immunosuppressive drugs in organ transplantation.2006

    • Author(s)
      Mihara K, iketani O, Tanigawara Y
    • Organizer
      The 3rd Korea-Japan Joint Symposium on Drug Delivery and Therapy
    • Place of Presentation
      Seoul.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of AIF1, a gene marker for rejection, in peripheral blood in rat transplantation model and living-donor Liver transplantation.2006

    • Author(s)
      Ishikawa H, Mihara K, Tanigawara Y, et. al.
    • Organizer
      The 23rd Annual Meeting of The Japanese Society of Therapeutic Drug Monitoring
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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