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Detection of the cytochrome P450 enzyme in lung cancer may be useful for cancer screening

Research Project

Project/Area Number 16590492
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

OYAMA Tsunehiro  University of Occupational and Environmental Health, Japan, School of Medicine, Associate professor, 医学部, 助教授 (00309965)

Co-Investigator(Kenkyū-buntansha) KAWAMOTO Toshihiro  University of Occupational and Environmental Health, Japan, School of Medicine, Professor, 医学部, 教授 (60177748)
SUGIO Kenji  University of Occupational and Environmental Health, Japan, School of Medicine, Associate professor, 医学部, 助教授 (70235927)
ISSE Toyohi  University of Occupational and Environmental Health, Japan, School of Medicine, Assistant professor, 医学部, 講師 (80341494)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordslung cancer / CytochromeP450 / tumor marker
Research Abstract

[Introduction] The cytochrome P450 (CYP) is associated with tumor development and progression as well as activation of anti-cancer prodrugs and their metabolic clearance. Recently, some CYPs, in particular enzymes of the CYP3A subfamily (CYP3A4, CYP3A5, and CYP3A7), have been found to play a role in the metabolism of many anticancer drugs. CYP3A not only inactivates major anticancer drugs, such as tamoxifen, taxol and vinca alkaloids, but also activates major anticancer prodrugs, such as cyclophosphamide and ifosphamide. For the better management of lung cancer, it is essential to understand the roles of CYPs and the relationships between their expression and the clinical feature of individual lung cancers. In this study, we investigate the expression of four CYPs (CYP1A1, CYP2A6, CYP2E1 and CYP3A) in 78 non-small cell lung cancer (NSCLC) and their relationships to each other, tumor p53 expression, and clinical features of the patients.
[Materials and Methods] We examined CYPs and p53 i … More mmunoreactivities in 78 Japanese patients with NSCLC who underwent surgical resection at UOEH after obtaining appropriate informed consent. Histological typing of the tumors was performed according to the WHO classification (adenocarcinoma ; 48 cases, squamous cell carcinoma ; 30 cases). Immunohistochemical staining (IHC) of 78 NSCLC was performed by the LSAB (labelled streptavidine biotin) method. CYPs and p53 expression was determined as positive when more than 10% of tumor cells were stained. The p53 mutations in 48 adenocarcinomas were sequenced by the dideoxy chain termination method using an ABI 373A DNA Sequencer (Applied Biosystems).
[Results] The CYP1A1, CYP2A6, CYP2E1 and CYP3A positive rates in 48 adenocarcinomas were 43.8% (21/48), 45.8% (22/48), 39.6% (19/48) and 39.6% (19/48), respectively, although there was no CYPs positive cases in 30 squamous cell carcinomas. The CYPs positive rates in female adenocarcinoma were higher than those in male adenocarcinoma. The CYPs positive rates in early adenocarcinoma were higher than those in advanced adenocarcinoma. The CYPs positive rates in well and moderately differentiated adenocarcinoma were higher than those in poorly differentiated adenocarcinoma. There were positive relationships among CYP1A1, CYP2E1 and Cyp3A expressions in adenocarcinoma. The CYPs expression in adenocarcinoma was independent of tumor p53 alterations.
[Conclusions] Our results suggest that better understanding of CYP expression in tumors should be useful and essential, 1) to investigate the mechanism of carcinogenesis, 2) to apply CYP expression as tumor marker, 3) to use the knowledge of CYP expression for molecular targeting therapy, 4) for selection of anti-cancer drug. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (26 results)

All 2006 2005 2004

All Journal Article (24 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Evidence-based prevention (EBP) : a review of cytochrome P450 expression in the bronchial epithelium and new approach to lung cancer prevention.2006

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Environ Health Prev Med 11

      Pages: 97-101

    • NAID

      10017480275

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Smoking cessation program and CYP2A6 polymorphism.2006

    • Author(s)
      Ozaki S, et al.
    • Journal Title

      Front Biosci 11

      Pages: 2590-2597

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] The methylation status and protein expression of CDH1, p16(INK4A), and fragile histidine triad in nonsmall cell lung carcinoma : epigenetic silencing, clinical features, and prognostic significance.2006

    • Author(s)
      Nakata S, et al.
    • Journal Title

      Cancer 106

      Pages: 2190-2199

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking.2006

    • Author(s)
      Sugio S, et al.
    • Journal Title

      Br J Cancer 94

      Pages: 896-903

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Epidermal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese.2006

    • Author(s)
      Uramoto H, et al.
    • Journal Title

      Lung Cancer 51

      Pages: 71-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] p53R2, p53 inducible ribonucleotide reductase gene, correlated with tumor progression of non-small cell lung cancer.2006

    • Author(s)
      Uramoto H, et al.
    • Journal Title

      Anticancer Res 26

      Pages: 983-988

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Evidence-based prevention (EBP) : a review of cylochrome P450 expression in the bronchial epithelium and new approach to lung cancer prevention.2006

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Environ Health Prev Med 11

      Pages: 97-101

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The methylation status and protein expression of CDH1,p16(INK4A), and fragile histidine triad in nonsmall cell lung carcinoma : epigenetic silencing, clinical features, and prognostic significance.2006

    • Author(s)
      Nakata S, et al.
    • Journal Title

      Cancer 106

      Pages: 2190-2199

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Epidemal growth factor receptor mutations are associated with gefitinib sensitivity in non-small cell lung cancer in Japanese.2006

    • Author(s)
      Uramoto H, et al.
    • Journal Title

      Lung Cancer 51

      Pages: 71-77

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immunohistochemical evaluation of cytochrome p450 (CYP) and p53 in breast cancer.2005

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Front Biosci 10

      Pages: 1156-1161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tissue-distribution of aldehyde dehydrogenase 2 and effects of the aldh2 gene-disruption on the expression of enzymes involved in alcohol metabolism.2005

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Front Biosci 10

      Pages: 6905-6911

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Molecular Genetic Tumor Markers in Non-Small Cell Lung Cancer.2005

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 1193-1196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Expression levels of hepatic cytochrome P450 enzymes in Aldh2-deficient mice following ethanol exposure : a pilot study.2005

    • Author(s)
      Kim YD, et al.
    • Journal Title

      Arch Toxicol 79

      Pages: 192-195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer.2005

    • Author(s)
      Morita, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 1193-1196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Y box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer.2005

    • Author(s)
      Yoshimatsu, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 3437-3443

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Expression of deltaNp63 in squamous cell carcinoma of the esophagus.2005

    • Author(s)
      Morita, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 3533-3539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer2005

    • Author(s)
      Morita, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 1193-1196

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Y box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer2005

    • Author(s)
      Yoshimatsu, et al.
    • Journal Title

      Anticancer Res 25

      Pages: 3437-3443

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immunohistochemical evaluation of cytochrome p450(CYP) and p53 in breast cancer.2005

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Front Biosci 10

      Pages: 1156-1161

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer.2005

    • Author(s)
      Morita, et al.
    • Journal Title

      Front Biosci 10

      Pages: 2319-2324

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of cytochromeP450 in tumor tissues and its association with cancer development.2004

    • Author(s)
      Oyama T, et al.
    • Journal Title

      Front Biosci 9

      Pages: 1967-1976

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Low expression of polypeptide GaINAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma : impact on poor prognosis and early recurrence.2004

    • Author(s)
      Gu CD, et al.
    • Journal Title

      Brit J Cancer 90

      Pages: 436-442

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene.2004

    • Author(s)
      Kim YD, et al.
    • Journal Title

      Environ Res 94

      Pages: 262-266

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma : impact on poor prognosis and early recurrence.2004

    • Author(s)
      Gu CD, et al.
    • Journal Title

      Brit J Cancer 90

      Pages: 436-442

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 悪性腫瘍の診断方法2004

    • Inventor(s)
      小山倫浩
    • Industrial Property Rights Holder
      小山倫浩
    • Filing Date
      2004-10-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 悪性腫瘍の診断方法2004

    • Inventor(s)
      小山倫浩, 安元公正, 杉尾賢二
    • Industrial Property Rights Holder
      小山倫浩, 安元公正, 杉尾賢二
    • Filing Date
      2004-10-27
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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