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ESTABLISHMENT OF PERSONALIZED CHEMOTHERAPY OF LUNG CANCER APPLYING PHARMACOGENOMICS

Research Project

Project/Area Number 14370196
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNagoya University

Principal Investigator

SHIMOKATA Kaoru  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10022906)

Co-Investigator(Kenkyū-buntansha) HASEGAWA Yoshinori  Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20270986)
SEKIDO Yoshitaka  Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (00311712)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥10,700,000 (Direct Cost: ¥10,700,000)
Keywordscancer / chemotherapy / tailor-made therapy / polymorphism / enzyme / clinical study / irinotecan / テーラード療法
Research Abstract

Although irinotecan is widely used as an anticancer drug, it causes unpredictably severe, occasionally fatal toxicity of leukopenia or diarrhea. Irinotecan is metabolized to form active SN-38,which is further conjugated and detoxified by UDP-glucuronosyltransferase1A1(UGT1A1) enzyme. Genetic polymorphism of the UCT1A1 would affect an interindivisual variation of the toxicity by irinotecan via the alternation of bioavailability of SN-38. We investigated whether the variant UGT1A1 genotypes would be at higher risk for severe toxicity by imotcan. We suggested that determination of the UGT1A1 genotypes might be clinically useful for predicting severe toxicity by irinotecan in cancer patients.
We studied the relationship between genetic polymorphisms of the UGT1A7 gene and irinotecan toxicity in Japanese cancer patients. The results suggested that determination of UGT1A7 genotypes would not be useful for predicting severe toxicity of irinotecan.
We proposed phase 1 study of irinotecan according to the polymorphism of UGT1A1^*28. The Ethical Committee and IRB in the Nagoya University approved the clinical study. When there are homo-or hetero-polymorphism of UGT1A1^*28,the dose of irinotecan was decreased at half level, and no severe side effects were not observed. Determination of polymorphism of UGT1A1^*28,prior irinotecan chemotherapy would be useful.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Ando M: "Genetic polymorphisms of the UDP-glucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients."Japanese Journal of Cancer Research. 93. 591-597 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando Y: "Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan."Therapeutic Drug Monitoring. 24. 111-116 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchiyama M: "Loss of heterozygosity of chromosome 12P does not correlate with KRAS mutation in non-small cell lung cancer."International Journal of Cancer. 107. 962-969 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Usami N: "β-catenin inhibits cell growth of a malignant mesothelioma cell line, NCL-H28, with a 3p21.3 homozygous deletion"Oncogene. 22. 7922-7930 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato M: "The expression of DNA methyltransferases and methyl-CpG-binding proteins is not associated with the methylation status of p14ARF, p16INK4a and RASSF1A in human lung cancer cell lines."Oncogene. 21. 4822-4829 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekido Y: "Establishment of a large cell lung cancer cell line (Y-ML-1B) producing granulocyte colony-stimulating factor."Cancer Genetics and Cytogenetics. 137. 33-42 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando M.: "Genetic polymorphisms of the UDP-glucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients."Japanese Journal of Cancer Research. 93. 591-597 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ando Y.: "Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan."Therapeutic Drug Monitoring. 24. 111-116 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchiyama M.: "Loss of heterozygosity of chromosome 12P does not correlate with KRAS mutation non-small cell lung cancer."International Journal of Cancer. 107. 962-969 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Usami N.: "βcatenin inhibits cell growth of a malignant mesothelioma cell line, NCL-H28,with a 3p21.3 homozygous deletion."Oncogene. 22. 7922-7930 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato M.: "The expression of DNA methyltransferases and methyl-CpG-binding proteins is not associated with the methylation status of p14ARF, p16INK4a and RASSF1A in human lung cancer cell lines."Oncogene. 21. 4822-4829 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sekido Y.: "Establishment of a large cell lung cancer cell line (Y-ML-IB) producing granulocyte colony-simulating factor."Cancer Genetics and Cytogenetics. 137. 33-42 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchiyama M: "Loss of heterozygosity of chromosome 12P does not correlate with KRAS mutation in non-small cell lung cancer."International Journal of Cancer. 107. 962-969 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Usami N: "β-catenin inhibits cell growth of a malignant mesothelioma cell line, NCL-H28, with a 3p21.3 homozygous deletion"Oncogene. 22. 7922-7930 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ando M: "Genetic polymorphisms of the UDP-glucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients"Japanese Joumal of Cancer Research. 93. 591-597 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ando Y: "Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan."Therapeutic Drug Monitoring. 24. 111-116 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aoshima T: "Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency : A coinpound heterozygote with 103-121del and 1460T>A of the ALDH5A1 gene"Human Heredity. 53. 42-44 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura S: "Simultaneous detection of methylenetetrahydrofolate reductase gene polymorphisms, C677T and A1298C, by melting curve analysis with LightCycler"Analytical Biochemistry. 306. 340-343 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato M: "The expression of DNA methyltransferases and methyl-CpG-binding proteins is not associated with the methylation status of p14ARF, p16INK4a and RASSFIA in human lung cancer cell lines"Oncogene. 21. 4822-4829 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sekido Y: "Establishment of a large cell lung cancer cell line (Y-ML-1B) producing granulocyte colony-stimulating factor"Cancer Genetics and Cytogenetics. 137. 33-42 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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