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Relationship between Topoisomerase I gene mutation in patients with lung cancer and the effect of irinotecan hydrochloride

Research Project

Project/Area Number 15590826
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KOBAYASHI Hirosuke  Kitasato University, School of Allied Health Sciences, Prof., 医療衛生学部, 教授 (70153632)

Co-Investigator(Kenkyū-buntansha) MASUDA Noriyuki  Kitasato University, School of Medicine, Prof., 医学部, 教授 (70145465)
TANAKA Naohiko  Kitasato University, School of Medicine, Assistant Prof., 医学部, 助手 (20316954)
MITSUFUJI Hisashi  Kitasato University, School of Medicine, Assistant Prof., 医学部, 助手 (40260856)
今崎 貴生  北里大学, 医学部, 助手 (90265588)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsmalignancy / polymorphism / lung cancer / chemotherapy agent / drug resistance / drug toxicity
Research Abstract

In this study, polymorphisms of topoisomerase I (TOP I), carboxylesterase 1&2 (CES 1&2) and UDP-glucuronosyltransferase 1A1(UGT1A1), which are all related to the resistance and metabolism of chemotherapy agent irinotecan (CPT-11), were investigated in Japanese volunteers, and the polymorphism of TOP I in lung cancer tissue was also investigated, in an attempt to contribute to tailor-made treatment of cancers.
In this study, following findings were obtained.
1)No polymorphism in exons of TOP I, which are reported to be related to CPT-11 resistance, was observed in Japanese adults as well as in untreated lung cancer tissues.
2)In 2 out of 126 specimen, heterozygous mutation was detected in CES 2 exons. CES 2 converts CPT-11 to SN38 in cancer cells, where SN38 is known to be toxic in cancer cells. This mutation rate is very low, and will not contribute much to the difference in effectiveness of CPT-11 to cancer cells in patients.
3)There were several polymorphisms detected in CES 1 exons. CES 1 converts CPT-l1 to SN38 in liver cells. This mutation rate is very high, and is considered to contribute to the difference in toxicity in patients..
4)The homozygous mutation in UGT1A1*28 was 2% in the subjects in this study. UGT1A1 is known to make SN38 soluble form by conjugating it with glucuronic acid, and this mutation is known to enhance the toxicity of SN38. It is suspected that the toxicity related to this enzyme activity is seldom in Asian population except Indians, compared to American, European and African population.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005 2004 2003 Other

All Journal Article (18 results)

  • [Journal Article] Biweekly therapy for non-small cell lung cancer using cisplatin, paclitaxel and gemcitabine.2006

    • Author(s)
      Tanaka N, Honma K, Masubuchi T, Tanimura S, Yokoba M, Mitsufuji H, 他
    • Journal Title

      Kitasato Med J 35(In press)

    • NAID

      110006406012

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biweekly therapy for non-small cell lung cancer using cisplatin, paclitaxel and gemcitabine.2006

    • Author(s)
      Tanaka N, Honma K, Masubuchi T, Tanimura S, Yokoba M, Mitsufuji H, Shimane M, Arai S, Yanase N, Yamamoto H
    • Journal Title

      Kitasato Med J 35(in press)

    • NAID

      110006406012

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drug interaction between gefinitib and warfarin.2005

    • Author(s)
      Onoda S, Mitsufuji H, 他, Tanaka N, Kobayashi H, Masuda N
    • Journal Title

      Jpn J Clin Oncol 35

      Pages: 478-482

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drug interaction between gefinitib and warfarin.2005

    • Author(s)
      Onoda S, Mitsufuji H, Yanase N, Ryuge S, Kato E, Wada M, Ishii K, Hagiri S, Yamamoto M, Yokoba M, Yanaihara T, Kubota M, Takada N, Katagiri M, Abe T, Tanaka N, Kobayashi H, Masuda N
    • Journal Title

      Jpn J Clin Oncol 35(8)

      Pages: 478-482

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Local and systemic expression of inducible nitric oxide synthase in comparison with that of cyclooxygenase-2 in rat carrageenin-induced pleurisy.2005

    • Author(s)
      Fujisawa H, Nakagawa S, Ohkubo Y, Matsui M, Yamaguchi S, Kawamura M, Hatanaka K, Kawakubo Y, Hiramoto Y, Kobayashi H, Harada Y
    • Journal Title

      Nitric Oxide-Biol Chem 12

      Pages: 80-88

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Electromagnetic Interference of Implantable Unipolar Cardiac Pacemakers by an Induction Oven.2005

    • Author(s)
      Hirose M, Hida M, Sato E, Kokubo K, Nie M, Kobayashi H
    • Journal Title

      PACE 28

      Pages: 540-548

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characteristics of auditory alarms for medical equipment and future issues.2005

    • Author(s)
      Hirose M, Sato E, Taguchi M, Kokubo K, Kobayashi H, Watanabe S
    • Journal Title

      Journal of Clinical Engineering 30

      Pages: 208-213

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Drug interaction between gefinitib and warfarin.2005

    • Author(s)
      Onoda S, Mitsufuji H, Yanase N, Ryuge S, Kato E, Wada M, Ishii K, Hagiri S, Yamamoto M, Yokoba M, Yanaihara T, Kubota M, Takada N, Katagiri M, Abe T, Tanaka N, Kobayaahi H, Masuda N
    • Journal Title

      Jpn J Clin Oncol 35

      Pages: 478-482

    • Related Report
      2005 Annual Research Report
  • [Journal Article] IL-10 induces inhibitory C/EBP through STAT-3 and represses HIV-1 transcription in Macrophages2005

    • Author(s)
      Tanaka N, Hoshino Y, Gold J, Hoshino S, Martiniuk F, Kurata T, Pine R, Levy D, Rom WN, Weiden M
    • Journal Title

      Am.J.Respir.Cell Mol.Biol 33

      Pages: 406-411

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nitric oxide generated by iNOS reduces deformability of Lewis lung carcinoma cell.2004

    • Author(s)
      Igawa S, Hayash I, Tanaka, N, Hiruma H, Majima M, Kawakami T, Hirose M, Masuda N, Kobayashi H
    • Journal Title

      Cancer Sci. 94

      Pages: 342-347

    • NAID

      10013722547

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differences in p02 peaks of a murine fibrosarcoma between carbon-ion and X-ray irradiation.2004

    • Author(s)
      Fukawa, T., Takematsu, K., Oka, K., Koike, S., Ando, K., Kobayashi, H., Tanishita K.
    • Journal Title

      J. Radiat. Res. 45

      Pages: 303-308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nitric oxide generated by iNOS reduces deformability of Lewis lung carcinoma cell.2004

    • Author(s)
      Igawa S, Hayashi I, Tanaka N, Hiruma H, Majima M, Kawakami T, Hirose M, Masuda N, Kobayashi H
    • Journal Title

      Cancer Sci. 94

      Pages: 342-347

    • NAID

      10013722547

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differences in pO2 peaks of a murine fibrosarcoma between carbon-ion and X-ray irradiation.2004

    • Author(s)
      Fukawa T, Takematsu K, Oka K, Koike S, Ando K, Kobayashi H, Tanishita K
    • Journal Title

      J.Radiat.Res. 45

      Pages: 303-308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.2003

    • Author(s)
      Negoro S, Masuda N, 他
    • Journal Title

      Br J Cancer 88

      Pages: 335-341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A phase II study of topotecan in patients with small-cell lung cancer.2003

    • Author(s)
      Takeda K., Negoro S., Sawa T., Nakagawa K., Kawahara M., Isobe T., Kudoh S., Masuda N., 他
    • Journal Title

      Clinical Lung Cancer 4

      Pages: 224-228

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.2003

    • Author(s)
      Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M
    • Journal Title

      Br J Cancer 88

      Pages: 335-341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A phase II study of topotecan in patients with small-cell lung cancer.2003

    • Author(s)
      Takeda K, Negoro S, Sawa T, Nakagawa K, Kawahara M, Isobe T, Kudoh S, Masuda N., Niitani H, Fukuoka M
    • Journal Title

      Clinical Lung Cancer 4

      Pages: 224-228

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biweekly therapy for non-small cell lung cancer using cisplatin, paclitaxel and gemcitabine

    • Author(s)
      Tanaka N, Honma K, Masubuchi T, Tanimura S, Yokoba M, Mitsufuji H, Shimane M, Arai S, Yanase N, Yamamoto H
    • Journal Title

      Kitasato Med.J (in press)

    • NAID

      110006406012

    • Related Report
      2005 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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