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The analysis and a molecular staging protocol using reliable markers in predicting the prognosis of patients with lung cancer

Research Project

Project/Area Number 10557125
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Thoracic surgery
Research InstitutionTazuke Kofukai Medical Research Institute

Principal Investigator

TAKI Toshihiko  Tazuke Kofukai Medical Research Institute, 医学研究所・第5研究部, 主幹 (60135605)

Co-Investigator(Kenkyū-buntansha) MITSUDOMI Tetsuya  Aichi Cancer Center, 胸部外科, 部長 (70209807)
MIYAKE Masayuki  Tazuke Kofukai Medical Research Institute, 医学研究所・第5研究部, 部長 (90250076)
中村 吉昭  財団法人 田附興風会, 医学研究所第2研究部, 研究員 (50281605)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥8,400,000 (Direct Cost: ¥8,400,000)
Keywordsmetastasis / cancer / MRP-1 / CD9 / KAI1 / CD82 / p53 / K-ras / p16 / bcl-2
Research Abstract

A molecular staging protocol using reliable markers is of importance in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) and for instituting their appropriate post-surgical treatment. We analyzed tumor tissues from 296 NSCLC patients. The DNA and mRNA were extracted from frozen specimens, and then polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exons 5 to 8, and mutations of K-ras at exon 1. Mutations of p53 gene occurred in 36.5% of patients, and mutations of the K-ras gene occurred in 8.8%. To determine MRP-1/CD9 gene and KAI1/CD82 gene expression, which have been postulated to be metastasis suppressor genes, we have applied quantitative RT-PCR. We found that 114 patients (38.5%) had MRP-1/CD9-reduced tumors, and that 216 patients (72.9%) had KAI1/CD82-reduced tumors. In addition, the immunohistochemical analysis for p16 protein was performed. One hundred … More seven carcinomas (36.1%) were classified as p16 negative. P16-negative tumors in squamous cell carcinomas were significantly more than those in adenocarcinomas (P=0.039). Moreover, immunohistochemistry was performed to evaluate bcl-2 and bax expression, One hundred fifteen carcinomas (38.9%) were bcl-2-positive and 213 carcinomas (80.0%) were bax-positive, However, there was no difference in bcl-2 expression in relation to p53 status. On the other hand, tumors with structural mutations of p53 had significantly lower expression of bax than those with wild-type p53 (P=0.0026). In contrast, tumors with mutations of the loop-sheet-helix motif of p53 had significantly higher expression of bax than those with wild-type p53 (P=0.0236). The frequency of a bcl-2/bax ratio of 【greater than or equal】1 was significantly lower in tumors with mutations of the loop-sheet-helix motif than that in tumors with wild-type p53 (P=0.0240). Mutations of the loop-sheet-helix motif of p53 were correlated with overexpression of bax, while other mutations of p53 were correlated with low levels of bax expression. This variation in pattern of bax expression in relation to mutant p53 might reflect the biological behavior of tumors in patients with bcl-2-positive NSCLCs. Up to date, there was no significant difference in survival according to these tumor markers status and further examination are needed to establish whether they are indeed of practical utility as prognostic predictors. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(57 results)

All Other

All Publications

  • [Publications] Adachi, M., et al.: "Reduced integrin α3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung"Journal of Clinical Oncology. 16. 1060-1067 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Adachi, M., et al.: "A Novel staging protocol for non-small cell lung cancers accrding to MRP-1/CD9 and KAI1/CD82 gene expression"Journal of Clinical Oncology. 16. 1397-1406 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang, C., et al.: "Mutation in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer"Oncogene. 16. 2469-2477 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang, C., et al.: "Mutations of p53 and K-ras genes as prognostic factor ofr non-small cell lung cancer"International Journal of Oncology. 12. 553-563 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yagita, M., et al.: "Thrapy-related leukemia and myelodysplasis following oral administration of etoposide for recurrent breast cancer"International Journal of Oncology. 13. 91-96 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sho, M., et al.: "Transmembrane 4 supefamily as a prognostic factor in pancreatic cancer"International Journal of Cancer. 79. 509-516 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higashiyama, M., et al.: "KAI1/CD82 expression in non-small cell lung carcinoma is a novel, favorable prognostic factor"Cancer. 83. 466-474 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang, C., et al.: "Correlation of reduction in MPR-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients"American Journal of Pathology. 153. 973-983 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inufusa, H., et al.: "Correlation of prognosis of breast cancer patients and expression of Ley which acts as a confacotr of tumor procoagulan"International Journal of Oncology. 13. 481-487 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 足立匡司: "肺癌治療における分子生物学的診断の意義-自験例(TM4SFの研究)を交えて"臨床外科. 53. 835-841 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 三宅正幸: "モノクローナル抗体の作成"外科. 60. 1567-1570 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida, s., et al.: "Montility-related Protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis un oesophageal squamous cell carcinoma"British Journal of Cancer. 79. 1168-1173 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda, n., et al.: "Prognostic significance of angiogenesis in human pancreatic cancer"British Journal of Cancer. 79. 1553-1563 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 三宅匡司: "Transmembrane 4 Super Family (TM4SF) と肺癌"分子呼吸器病. 3. 12-18 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyake, M., et al.: "a novel molecular staging protocol for non-small cell lung cancer"Oncogene. 18. 2397-2404 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, C., et al.: "Involvement of Galectin-3 expression in colorectal cancer progression and metastasis"International Journal of Oncology. 15. 143-148 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang, C., et al.: "Overexpression of Bax associated with mutations in the Loop-Sheet-Helix Motif of p53"American Journal of Pathology. 155. 955-965 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yang, S-Z., et al.: "Adraimycin activates E-cadherin-mediatedb cell-cell adhesion in human breast cancer"International Journal of Oncology. 15. 1109-1115 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang, C., et al.: "p16 protein expression is associated with a poor prognosis in sqamous cell carcinoma of the lung"British Journal of Cancer. 82. 374-380 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higashiyama, Y., et al.: "Natural autoanibody to MUC1 is a prognostic indicator for non-small cell lung cancer"American Journal of Reapiratory and Critical Care Medicine. 161. 589-594 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Adachi, M., et al.: "Significance of integrin α5 gene expression as a prognostic factor in node negative non-small cell lung cancer"Clinical Cancer Research. 15. 96-101 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hamada, H., et al.: "A novel monclonal antibody, H9, directed against the core protein of MUC1 Mucin"Oncology Report. 7. 225-232 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konishi, T., et al.: "The K-ras gene regulates vasclar endothelial growth factor gene expression in non-small cell lung cancers"International Journal of Oncology. 16. 501-511 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Adachi,M., Taki,T., Konishi,T., Huang,C., Higashiyama,M., Doi,O., Tsuji,T., and Miyake,M.: "Reduced Integrin α3 Expression as a Factor of Poor Prognosis of Patients with Adenocarcinoma of the Lung"J. Clin Oncol.. 16. 1060-1067 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Adachi,M., Taki,T., Konishi,T., Huang,C., Higashiyama,M., and Miyake,M.: "Novel Staging Protocol for Non-small Cell Lung Cancers According to MRP-1/CD9 and KAI1/CD82 Gene Expression"J. Clin Oncol.. 16. 1397-1406 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang,C., Taki,T., Adachi,M., Konishi,T., Higashiyama, M., and Miyake,M.: "Mutations in Exon 7 and 8 of p53 as Poor Prognostic Factors in Patients with Non-small Cell Lung Cancer"Oncogene. 16. 2469-2477 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang,C., Taki,T., Adachi,M., Konishi,T., Higashiyama, M., Kinoshita,M., Hamada,T., and Miyake,M.: "Mutations of p53 and K-ras Genes as Prognostic Factors for Non-small Cell Lung Cancer"Int. J. Oncol.. 12. 553-563 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yagita,M., Ieki,Y., Onishi,R., Huang,C., Adachi,M., Horiike,S., Konaka,Y., Taki,T., and Miyake,M.: "Therapy-related Leukemia and Myelodysplasia Following Oral Administration of Etoposide for Recurrent Breast Cancer"Int. J. Oncol.. 13. 91-96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sho,M., Adachi,M., Taki,T., Hashida,H., Konishi,T., Huang,C., Ikeda,N., Nakajima,Y., Kanehiro,H., Hisanaga,M., Nakano,H., and Miyake,M.: "Transmembrane 4 Superfamily as a Prognostic Factor in Pancreatic Cancer"Int. J. Cancer. 79. 509-516 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Higashiyama,M., Kodama,K., Yokouchi,H., Takami,K., Adachi,M., Taki,T., Ishiguro,S., Nakamori,S., Yoshie,O., and Miyake,M.: "KAI1/CD82 Expression in Non-small Cell Lung Carcinoma Is a Novel, Favorable Prognostic Factor"Cancer. 83. 466-474 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang,C., Kohno,N., Ogawa,E., Adachi,M., Taki,T., and Miyake,M.: "Correlation of Reduction in MRP-1/CD9 and KAI1/CD82 Expression with Recurrences in Breast Cancer Patients"Am. J. Pathol.. 153. 973-983 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inufusa,H., Nakatani,Y., Adachi,T., Wakano,T., Nakajima,A., Nakamura,M., Suzuki,M., Ando,O., Kurimoto,M., Miyake,M., Shindo,K., and Yasutomi,M.: "Correlation of Prognosis of Breast Cancer Patients and Expression of Ley Which Acts as a Cofactor of Tumor Procoagulant"Int. J. Oncol.. 13. 481-487 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uchida,S., Shimada,Y., Watanabe,G., Li,Z-G., Hong T., Miyake,M., and Imamura,M.: "Motility-related Protein (MRP-1/CD9) and KAI1/CD82 Expression Inversely Correlate with Lymph Node Metastasis in Oesophageal Squamous Cell Carcinoma"Brit. J. Cancer. 79. 1168-1173 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda,N., Adachi,M., Taki,T., Huang,C., Hashida,H., Takabayashi,A., Sho,M., Nakajima,Y., Kanehiro,H., Hisanaga,M., Nakano,H., and Miyake,M.: "Prognostic Significance of Angiogenesis in Human Pancreatic Cancer"Brit. J. Cancer. 79. 1553-1563 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyake,M., Adachi,M., Huang,C., Higashiyama,M., Kodama,K., and Taki,T.: "A Novel Molecular Staging Protocol for Non-small Cell Lung Cancer"Oncogene. 18. 2397-2404 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura,M., Inufusa,H., Adachi,T., Aga,M., Kurimoto,M., Nakatani,Y., Wakano,T., Nakajima,A., Hida,J-I., Miyake,M., Shindo,K., and Yasutomi,M.: "Involvement of Galectin-3 Expression in Colorectal Cancer Progression and Metastasis"Int. J. Oncol.. 15. 143-148 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang,C., Kohno,N., Inufusa,H., Kodama,K., Taki,T., and Miyake,M.: "Overexpression of Bax Associated with Mutations in the Loop-Sheet-Helix Motif of p53"Am. J. Pathol.. 155. 955-965 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yang,S-Z., Kohno,N., Kondo,K., Yokoyama,A., Hamada,H., Hiwada,K., and Miyake,M.: "Adriamycin Activates E-cadherin-mediated Cell-cell Adhesion in Human Breast Cancer Cells"Int. J. Oncol.. 15. 1109-1115 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang,C., Taki,T., Higashiyama,M., Kohno,N., and Miyake,M.: "p16 Protein Expression Is Associated with a Poor Prognosis in Squamous Cell Carcinoma of the Lung"Brit. J. Cancer. 82. 374-380 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirasawa,Y., Kohno,N., Yokoyama,A., Kondo,K., Hiwada,K., and Miyake,M.: "Natural Autoantibody to MUC1 Is a Prognostic Indicator for Non-Small Cell Lung Cancer"Am. J. Respir. Crit. Care Med.. 161. 589-594 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Adachi,M., Taki,T., Higashiyama,M., Kohno,N., Inufusa,H., and Miyake,M.: "Significance of Integrin α5 Gene Expression as a Prognostic Factor in Node Negative Non-small Cell Lung Cancer"Clin. Cancer Res.. 6. 96-101 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hamada,H., Kohno,N., Yokoyama,A., Kondo,K., Yang,S-Z., Hiwada,K., Watanabe,K., and Miyake,M.: "A Novel Monoclonal Antibody, H9, Directed against the Core Protein of MUC1 Mucin"Oncol. Report.. 7. 225-232 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konishi,T., Huang,C.-L., Adachi,M., Taki,T., Inufusa,H., Kodama,K., Kohno,N., and Miyake,M.: "The K-ras gene regulates vascular endothelial growth factor gene expression in non-small cell lung cancers"Int. J. Oncol.. 16. 501-511 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda N.et al.: "Prognostic Significance of Angiogenesis in Human Pancreatic Cancer"British Journal of Cancer. 79. 1564-1571 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyake M.et al.: "A Novel Molecular Staging Protocol for Non-small Cell Lung Cancer"Journal of Clinical Oncology. 18. 2397-2404 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Huang C.et al.: "Overexpression of Bax Associated with Mutations in the Loop-Sheet-Helix Motif of p53"American Journal of Pathology. 155. 955-965 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Huang C.et al.: "p16 Protein Expression Is Associated with a Poor Prognosis in Squamous Cell Carcinoma of the Lung"British Journal of Cancer. 82. 374-380 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Adachi M.et al.: "Significance of Integrin α5 Gene Expression as a Prognostic Factor in Node Negative Non-small Cell Lung Cancer"Clinical Cancer Research. 6. 96-101 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Konishi T.et al.: "The K-ras Gene Regulates Vascular Endothelial Growth Factor Gene Expression in Non-small Cell Lung Cancer"International Journal of Oncology. 16. 501-511 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三宅正幸: "肺がんにおける糖鎖抗原の発現,がんの浸潤・転移 基礎研究の臨床応用"北島政樹(医学書院). 8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三宅正幸: "Key Word 1999-2000 呼吸器疾患"山木戸道郎,日和田邦男,小倉剛(先端医学社). 2 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Adachi M.et al.: "Reduced integrin α3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung" Journal of Clinical Oncology. 16. 1060-1067 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Adachi M.et al.: "Novel staging protocol for non-small cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression" Journal of Clinical Oncology. 16. 1397-1406 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Huang C.et al.: "Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer" Oncogene. 16. 2469-2477 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sho M.et al.: "Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer" International Journal of Cancer. 79. 509-516 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Higashiyama M.et al.: "KAI1/CD82 expression in non-small cell lung carcinoma is a novel, favorable prognostic factor" Cancer. 83. 466-474 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Huang C.et al.: "Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients" American Journal of Pathology. 153. 973-983 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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