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Genetic analyzes in lung carcinogenesis and early diagnosis for lung cancer

Research Project

Project/Area Number 07457300
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKYUSHU UNIVERSITY (1996-1997)
University of Occupational and Environmental Health, Japan (1995)

Principal Investigator

SUGIO Kenji  KYUSHU UNIVERSITY Faculty of Medicine, Assistant Professor, 医学部, 助手 (70235927)

Co-Investigator(Kenkyū-buntansha) USHIJIMA Chie  Faculty of Medicine, Research Associate, 医学部, 医員
TSUKAMOTO Shuichi  Kyushu Dental Univ.Research Associate, 助手
SAKADA Takashi  Kyushu Dental Univ.Research Associate, 助手
大崎 敏弘  産業医科大学, 医学部, 助手 (70248574)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsLung cancer / Multi-step carcinogenesis / Tumor suppressor gene / Oncogene / Genetic diagnosis / p16 / p53 / p27 / 前癌病変 / 分子生物学 / サイトケラチン
Research Abstract

1) Genetic alteration in precursor lesions of lung cancer
In lung adenocarcinoma, 3p and 9p allele loss occur at the earliest (hyperplasia) stages, and ras mutations occur at the time of non-invasive cancer (carcinoma in situ), which suggested that ras mutations might correlate tumor progression.
2) Genetic alteration in lung cancer and its clinical significance
(1) In non-small cell lung cancer (NSCLC), the frequency of ras mutation was 7%, p53 was 36%, and 3p allelic loss was 46%. The LOH of 3p was a poor prognostic factor in adenocarcinoma. Multivariate analysis showed that ras and p53 mutations were independent unfavorable prognostic factors in early stage of NSCLC.
(2) Immunohistochemical analyzes of p53, p16, Rb, and p27 showed that alternative expression of both p53 and p27 was prognostic factor in adenocarcinoma, and alternative expression of p27 was prognostic factor in squamous cell carcinoma. The accumulation of these alternative gene expressions suggested tumor progression.
3) Early detection of cancer cells for recurrence
(1) The detection of occult micro metastases in the mediastinal lymph nodes with monoclonal antibodies to cytokeratin can be used to predict and early relapse in patients with stage I NSCLC.
(2) Micrometastatic cancer cells were frequently present in bone marrow of patients with operable NSCLC and may be a significant predictor of eqrly recurrence.
Further evaluation of these methods may be useful in identifying patients with NSCLC who are most likely to benefit from adjuvant chemotherapy.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Kishimoto Y, et al.: "Frequent loss of the short arm of chromosome 9 in resected non-small cell lung cancers from Japanese patients and its association with squamous cell carcinoma." Journal of Cancer Research Clinical Oncology. 121. 291-296 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kishimoto Y, et al.: "Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers." Jornal of National Cancer Institute. 87. 1224-1229 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsudomi T, et al.: "p53 nuclear immunostaining and gene mutations in non-small cell lung cancer and their effects on patient survival." Annals of Oncology. 6. S9-S13 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hung J, et al.: "Allele-specific chromosome 3p deletion occur at an early stage in the pathogenesis of lung carcinoma." JAMA. 273. 558-563 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoue T, et al.: "The relationship between the immunodetection of transforming growth factor-β in lung adenocarcinoma and longer survival rates." Surgical Oncology. 4. 51-57 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inoue T, et al.: "Glutathion S transferase pi is a powerful indicator in chemotherapy of human lung squamous cell carcinoma." Respiration. 62. 223-227 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松尾 賢二、他.: "顕微鏡切片からのPCR." 実験医学. 15. 706-710 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松尾 賢二、他.: "肺がんにおける微小転移診断" 最新医学. 52. 2667-2673 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugio K,et al.: "High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso (2-hydroxypropy1) (2-oxopropy) amino in the pancreas of female Syrian hamsters." Carcinogenesis. 17. 303-309 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsudomi T,et al.: "Loss of heterozygosity at 3p in non-small cell lung cancer and its prognostic implication." Clinical Cancer Research. 2. 1185-1189 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Osaki T,et al.: "Increased levels of serum intercellular adhesion molecule-1 (ICAM-1) in patients with non-small cell lung cancer." Surgical Oncology. 5(3). 107-113 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugio K,et al.: "K-ras mutation and allelic loss at 5q and 18q in the development of human pancreatic cancers." International Journal of Pancreatology. 21. 205-217 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fukuyama Y,et al.: "K-ras and p53 mutations are an independent unfavorable prognostic indicator in patients with non-small cell lung cancer." British Journal of Cancer. 75. 1125-1130 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Maruyama R,et al.: "Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer." Journal of Thoracic and Cardiovasc Surgery. 114. 535-543 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oyama T,et al.: "Cytochrome P450 2E1 polymorphism as a risk factor for lung cancer : In relation to p53 gene mutation." Anticancer Research. 17. 583-588 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oyama T,et al.: "p53 mutation of lung cancer are not significantly affected by CYP1A1 or GSTM1 polymorphisms." International Journal of Oncology. 11. 305-309 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oyama T,et al: "Proliferating cell nuclear antigen and argyrophilic nucleolar organizer regions in patients with thymic disease." Oncology report. 4. 1201-1205 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ogami A,et al.: "Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer." Annals of Thoracic Surgery. 64. 363-367 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dobashi K,et al.: "Micrometastatic p53-positive cells in the lymph nodes of non-small-cell lung cancer." Journal of Thoracic Cardiovascular Surgery. 114. 339-346 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugio K,et al.: "K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers." International Journal of Pancreatology. 21. 205-217 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukuyama Y,et al.: "K-ras and p53 mutations are an independent unfavorable prognostic indicator in patients with non-small cell lung cancer." British Journal of Cancer. 75. 1125-1130 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Maruyama R,et al: "Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer." Journal of Thoracic and Cardiovasc Surgery. 114. 535-543 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oyama T,et al: "Proliferating cell nuclear antigen and argyrophilic nucleolar organizer regions in patients with thymic disease." Oncology report. 4. 1201-1205 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ogami A,et al.: "Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer." Annals of Thoracic Surgery. 64. 363-367 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Dobashi K,et al.: "Micrometastatic p53-positive cells in the lymph nodes of non-small-cell lung cancer." Journal of Thoracic Cardiovascular Surgery. 114. 339-346 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tetsuya Mitsudomi,et al.: "Loss of heterozygosity at 3p in non-small cell lung cancer and its prognostic implication" Clinical Cancer Reserch. 2. 1185-1189 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasuro Fukuyama,et al.: "K-ras and p53 mutatations are an independent unfavorable prognostic indicator in patients with non-small cell lung cancer" British J Cancer. (発売予定).

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsunehiro Oyama,et al.: "Chromosome P450 2E1 polymorphism as a risk factor for lung cancer:In relation to p53 gene mutation" Anticancer Research. (発売予定).

    • Related Report
      1996 Annual Research Report
  • [Publications] Yosuke Kishimoto: "Allele-Specific Loss in Chromosome 9p Loci in Preneoplastic Lesions Accompanying Non-Small-Cell Lung Cancers" Journal of the National Cancer Institute. 87. 1224-1229 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tetsuya Mitsudomi: "p53 nuclear immunostaining and gene mutations in non-small-cell lung cancer and their effects on patient survival" Annals of Oncology. 6. 9-13 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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