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2006 Fiscal Year Final Research Report Summary

Development of clinical genome information systems for pharmacokinetics analysis

Research Project

Project/Area Number 16200038
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical systems
Research InstitutionThe University of Tokyo

Principal Investigator

OYAMA Hiroshi  The University of Tokyo, Faculty of Medicine, Project Professor, 医学部附属病院, 科学技術振興特任教員(特任教授) (30194640)

Co-Investigator(Kenkyū-buntansha) SASAKI Yasutsuna  Saitama Medical School, Department of Clinical Oncology, Professor, 臨床腫瘍科, 教授 (20235279)
ANDO Yuichi  Nagoya University Hospital, Department of Clinical Oncology and Chemotherapy, Assistant Professor, 医学部附属病院, 助教授 (10360083)
ONOGI Yuzo  The University of Tokyo, Faculty of Medicine, Project Associate Professor, 医学部附属病院, 科学技術振興特任教員(特任助教授) (90233593)
KOIDE Daisuke  The University of Tokyo, Faculty of Medicine, Project Associate Professor, 医学部附属病院, 科学技術振興特任教員(特任助教授) (50313143)
Project Period (FY) 2004 – 2006
Keywordspharmacokinetics / anti-cancer drug / polymorphism / individual medicine / grid computing / data base / drug adverse reaction / search
Research Abstract

We developed a clinical genome information grid search system that can extract comprehensive drug-related information from two or more life-science databases (DBs) using OGSA-WebDB technology, which is a database grid technology. The retrieval DBs are TOXINET (an adverse-drug-reaction document information DB), PharmGKB (a drug-related gene DB), Entrez Protein (a protein information DB), LSBM (a gene-expression organ DB), KEGG (a pathway-information DB), and JSNP (a single nucleotide polymorphism (SNP) information DB). The system can extract references to the newest drug responsibility genes and organs, metabolic pathway data, and protein information relevant to adverse reactions to anti-cancer or other drugs, and researchers can estimate the causal relationships between a drug responsibility gene and an adverse drug reaction. Using this, we verified the adverse drug reaction between irinotecan hydrochloride and cisplatin in combination therapy. The common pathways are the ABC transporters that are involved in the metabolism of xenobiotics by cytochrome P450, and starch and sucrose metabolism and 56 SNPs were extracted as relevant polymorphisms. A pharmacokinetics analysis algorithm for irinotecan hydrochloride was created based on clinical case data. We developed a clinical genome pharmacokinetics simulation system in which the chronological concentration change of CPT-11, SN-38, and SN-38G in each compartment can be visualized as a graph after selecting the genotype (wild-type, heterozygote, homozygote), body height, weight, and actual drug dose. It can also simulate the UGT1A1 allele type patterns of ^*28 and ^*6. We propose the system specifications for a clinical genome information-management system that includes clinical genome data, patient case data, and pharmacokinetics data. The prototype system was developed using Apache2.2.0, PHP5.1.1, MySQL5.0.18, and Java programming language on a UNIX server.

  • Research Products

    (12 results)

All 2006 Other

All Journal Article (12 results)

  • [Journal Article] Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer.2006

    • Author(s)
      Araki K, Fujita K, Ando Y, Nagashima F, Yamamoto W, Endou H, Miya T, Kodama K, Narabayashi M, Sasaki Y
    • Journal Title

      Cancer Sci. 97

      Pages: 1255-1259

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel single nucleotide polymorphism of UGT1A7 gene in Japanese.2006

    • Author(s)
      Fujita K, Ando Y, Nagashima F, Yamamoto W, Endo H, Kodama K, Araki K, Miya T, Narabayashi M, Sasaki Y
    • Journal Title

      Drug Metab Pharmacokinet. 21

      Pages: 75-78

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel single nucleotide polymorphism of UGT1A9 gene in Japanese.2006

    • Author(s)
      Fujita K, Ando Y, Nagashima F, Yamamoto W, Endo H, Kodama K, Araki K, Miya T, Narabayashi M, Sasaki Y
    • Journal Title

      Drug Metab Pharmacokinet. 21

      Pages: 79-81

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pharmacogenetic approach for cancer treatment-tailored medicine in practice.2006

    • Author(s)
      Hasegawa Y, Ando Y, Ando M, Hashimoto N, Imaizumi K, Shimokata K
    • Journal Title

      Ann N Y Acad. Sci. 1086

      Pages: 223-232

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Screening for adverse reactions to irinotecan treatment using the Invader?2006

    • Author(s)
      Hasegawa Y, Ando Y, Shimokata K
    • Journal Title

      UGT1A1 Molecular Assay Expert Rev Mol Diagn. 6

      Pages: 527-533

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer.2006

    • Author(s)
      Araki K, Fujita K, Ando Y, Nagashima F, Yamamoto W, Endou H, Miya T, Kodama K, Narabayashi M, Sasaki Y.
    • Journal Title

      Cancer Sci 97

      Pages: 1255-9

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel single nucleotide polymorphism of UGT1A7 gene in Japanese.2006

    • Author(s)
      Fujita K, Ando Y, Nagashima F, Yamamoto W, Endo H, Kodama K, Araki K, Miya T, Narabayashi M, Sasaki Y.
    • Journal Title

      Drug Metab Pharmacokinet. 21

      Pages: 75-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel single nucleotide polymorphism of UGT1A9 gene in Japanese.2006

    • Author(s)
      Fujita K, Ando Y, Nagashima F, Yamamoto W, Endo H, Kodama K, Araki K, Miya T, Narabayashi M, Sasaki Y.
    • Journal Title

      Drug Metab Pharmacokinet. 21

      Pages: 79-81

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pharmacogenetic approach for cancer treatment -- tailored medicine in practice.2006

    • Author(s)
      Hasegawa Y, Ando Y, Ando M, Hashimoto N, Imaizumi K, Shimokata K.
    • Journal Title

      Ann N Y Acad Sci 1086

      Pages: 223-232

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Screening for adverse reactions to irinotecan treatment using the Invader? UGT1A12006

    • Author(s)
      Hasegawa Y, Ando Y, Shimokata K.
    • Journal Title

      Molecular Assay Expert Rev Mol Diagn 6

      Pages: 527-533

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1^*6 is associated with reduced glucuronidase activity for SN-38 in Japanese patients with cancer.

    • Author(s)
      Fujita K, Ando Y, Nagashima F, Yamamoto W, Eodo H, Araki K, Kodama K, Miya T, Narabayashi M, Sasaki Y
    • Journal Title

      Cancer Chemother Pharmacol (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1*6 is associated with reduced glucuronidase activity for SN-38 in Japanese patients with cancer.

    • Author(s)
      Fujita K, Ando Y, Nagashima F, Yamamoto W, Eodo H, Araki K, Kodama K, Miya T, Narabayashi M, Sasaki Y.
    • Journal Title

      Cancer Chemother Pharmacol (in press)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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