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2006 Fiscal Year Final Research Report Summary

Inflammatory response in the non-small cell lung tissue and its regulation for cancer treatment

Research Project

Project/Area Number 15591479
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKyushu University

Principal Investigator

YOSHINO Ichiro  Kyushu University, Department of Surgery and Science, Graduate School of Medical Sciences, 助教授 (40281547)

Project Period (FY) 2003 – 2006
KeywordsMacrophage-migration inhibitory factor / lung cancer / inflammatory cytokines / benzo(a) pyren / lung carcinogenesis / epithelial-mesenchymal transition / tobacco smoke
Research Abstract

Exp. 1:
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine derived from T cells and the pituitary gland. However, several types of solid cancers also secrete MIF, and this factor has been suggested to play an important role in carcinogenesis and the progression of malignancy. In this study, we quantified MIF mRNA expression of non-small cell lung cancer (NSCLC) tissues, and examined its relationship with clinicopathologic factors.
Method: MIF mRNAs of both tumor and normal tissues were quantified by a real-time monitoring reverse transcription polymerase chain reaction in 59 patients with NSCLC. The relationship between the grade of MIF expression and clinicopathologic factors such as smoking history, cell type, stage, and prognosis was examined to investigate the clinical significance of intratumoral expression of MIF.
Results: The mean copy number of MIF mRNA per 0.08 μg of total mRNA in tumor tissues was 144078.00, whereas that of normal lung tissue was 25438.46 … More (p< 0.0001). The amounts of MIF proteins revealed by a Western blot analysis were well correlated with those of the corresponding mRNAs. Male patients and heavy smokers showed significantly higher expression of MIF. And patients with squamous cell carcinomas showed a higher expression of MIF mRNA than other subjects. In squamous cell carcinoma patients, higher expression of MIF mRNA was significantly associated with unfavorable prognosis (p=0.0142).
In a lung cancer cell line, PC9, tobacco smoke solution or benzo(a) pyrene induced MIF protein at a time-dependent manner.
Conclusions : The general intratumoral expression and close relation to smoking suggested that MIF might contribute to tumorigenesis in the lung.
Exp. 2
From the results of the Exp. 1, it was suggested that cigarette smoke induced inflammatory cytokines such as MIF, and clinical survey of relationship between smoking status and postoperative prognosis in patients with non-small cell lung cancer.
Methods: Lung adenocarcinoma cell lines (A549) were exposed to benzo(a)pyrene (B(a)P) for 24 weeks, and morphology, proliferative activity, and gene expression profiles were analyzed.
Results: Although no apparent morphologic changes were observed, the B(A)P-exposed A549 exhibited enhanced proliferative activity in 1 % bovine serum medium, and dramatic changes in expression levels were observed in a large number of genes. Of them, epithelial-to-mesenchymal transition (EMT)-related genes such as migration stimulating factor, plasminogen activator-inhibitor, twist, transforming growth factor-beta, and basic fibroblast growth factor. Most enhanced expression levels remained 8 weeks after the retrieval of B(A)P in culture.
Conclusions: B(a)P, which is one of the strongest carcinogens included in tobacco smoke, can induce EMT-related genes in lung cancer cells. This results indicate tobacco enhanced multiple factors including inflammatory cytokines (TGF-beta) and may drive malignant potential of lung cancer. Less

  • Research Products

    (12 results)

All 2007 2006 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Induction of epithelial-mesenchymal transition-related genes by benzo(a)pyrene in lung cancer2007

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      Cancer 110

      Pages: 369-374

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Impact of smoking status on the biological behavior of lung cancer2007

    • Author(s)
      Yoshino I, Maehara Y
    • Journal Title

      Surg Today 37

      Pages: 725-734

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction of epithelial-mesenchymal transition-related genes by benzo(a) pyrene in lung cancer.2007

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      Cancer 110

      Pages: 369-374

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impact of smoking status on the biological behavior of lung cancer.2007

    • Author(s)
      Yoshino I, Maehara Y.
    • Journal Title

      Surg Today 37

      Pages: 725-734

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Smoking status as a prognostic factor in patients with stage pulmonary adenocarcinoma2006

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      Ann Thorac Surg 81:1189-1193, 2006 81

      Pages: 1189-1193

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Smoking status as a prognostic factor in patients with stage I pulmonary adenocarcinoma.2006

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      Ann Thorac Sung 81

      Pages: 1189-1193

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glycolytic potential of non-small cell lung cancer:implication of anaerobic glycolysis on malignant potential2005

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      J CIin Oncol 24suppli.

      Pages: 9634

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glycolytic potential of non-small cell lung cancer : implication of anaerobic glycolysis on malignant potential2005

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      J Clin Oncol 24s

      Pages: 9634

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of p27 by S-phase kinase-associated protein 2 is associated with aggressiveness in non-small cell lung cancer2004

    • Author(s)
      Yoshino I, et. al.
    • Journal Title

      J.C.lin.Oncol. 22

      Pages: 4165-73

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of p27 by S-phase kinase-associated protein 2 is associated with aggressiveness in non-small cell lung cancer.2004

    • Author(s)
      Osoegawa, A., Yoshino. I. Tanaka, S., Sugio, K., Kameyama, T., Yamaguchi, M., Maehara, Y.
    • Journal Title

      J. Clin. Oncol. 22

      Pages: 4165-4173

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of Rho C is associated with invasiveness in non-small cell lung cancer2003

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

      Clin Cancer Res 9

      Pages: 5282-5286

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of Rho C is associated with invasiveness in non-small cell lung cancer.2003

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

      Clin Cancer Res 9

      Pages: 5282-5286

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

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Published: 2010-02-04  

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