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Analysis of factors associated with tumor angiogenesis in non-small cell lung cancer and evaluation of effects of antiangiogenetic agents

Research Project

Project/Area Number 13671393
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KAMEYAMA kotaro  Kagawa Medical University, 2nd Dept. Surgery, Research Associate, 医学部, 助手 (20284375)

Co-Investigator(Kenkyū-buntansha) YAMAUCHI akira  Kagawa Medical University, Dept. Cell Regulation, Professor, 医学部, 客員教授 (00291427)
YOKOMISE hiroyasu  Kagawa Medical University, 2nd Dept. Surgery, Professor, 医学部, 教授 (80231728)
HUANG cheng-long  Kagawa Medical University, 2nd Dept. Surgery, Associate professor, 医学部, 助教授 (10271511)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsangiogenesis / angiogenic factor / angiostatic factor / antiangiogenic agent
Research Abstract

In order to clarify the mechanism of tumor angiogenesis in non-small cell lung cancer (NSCLC), we performed a study on angiogenesis in relation to various angiogenic factors and angiostatic factors in NSCLCs. We evaluated gene expression by quantitative RT-PCR using surgically resected tumor specimens, and protein expression by immunohistochemistry using paraffin embedded specimens. In addition, we evaluated the intratumoral microvessel density (IMD) using the anti-CD34 antibody staining. The present study demonstrated that tumor angiogenesis is one of the significant prognostic factors in NSCLCs. In particular, the IMD of adenocasimas was significantly higher than that of squamous cell carcinomas, and the survival rate of patients with adenocarcinomas was significantly lower than that of patients with squamous cell carcinomas. With respect to intratumoral expression of various angiogenic factors and angiostatic factors, three factors, vascular endothelial growth factor-A (VEGF-A), int … More erleukin-8, and N-cadherin, have been proven to play an important role in angiogenesis in NSCLCs. Human lung cancer cell lines, such as A549 and MAC10, have positive expression of VEGF-A and interleukin-8, but negative expression of platelate derived-endothelial growth factor. In a clinical study of NSCLCs, 51.9% of carcinomas had positive expression of VEGF-A, 45.2% of carcinomas had positive expression of interleukin-8, and 30.7% of carcinomas had positive expression of N-cadherin. Among these factors, VEGF-A expression status was also associated with nodal mestasis, and was one of the independent prognostic factors in NSCLC patients. These results suggested the intratumoral VEGF-A expression is associated with not only angiogenesis but also tumor growth. Furthermore, using spontaneous metastatic models of nude mice after transplantation of cancer cell lines and tumor tissues, we evaluated the effectiveness of antiangiogeneic agents, such as TNP470 and CGS27023A. TNP470 suppressed both tumor growth and lung metastasis. On the other hand, CGS27023 suppressed only lung metastasis, not tumor growth. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] 亀山耕太郎, 他: "Pulmonary embolism after lung resection : diagnosis and treatment"Annals of Thoracic Surgery. (掲載予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 中島 尊, 亀山耕太郎, 他: "N-cadherin expression associated with angiogenesis in non-small cell lung cancer patients"British Journal of Cancer. (掲載予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 岡本 卓, 亀山耕太郎, 他: "Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine trasheomalacia : a preliminary report"ASAIO Journal. 49・1. 63-69 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 亀山耕太郎, 他: "Problems related to TNM staging : patients with stage III non-small cell lung cancer"Journal of Thoracic and Cardiovascular Surgery. 124・3. 503-510 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 亀山耕太郎, 他: "Induction chemotherapy before operation for multiple endobronchial squamous cell carcinoma of the lung"Annals of Thoracic Surgery. 74・4. 1008-1010 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 劉 大革, 亀山耕太郎, 他: "Topoisomerase II alpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients"Cancer. 94・8. 2239-2247 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 桝屋大輝, 亀山耕太郎, 他: "The intratumoral expression of vascular endothelial growth factor and interleukin-8 associated with angiogenesis in nonsmall cell lung carcinoma patients"Cancer. 92・10. 2628-2638 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 劉 大革, 亀山耕太郎, 他: "E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer"Annals of Thoracic Surgery. 71・3. 949-955 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameyama K, et al.: "Pulmonary embolism after lung resection diagnosis and treatment"Annals of Thoracic Surgery. in-press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakashima T, Kameyama K, et at.: "N-cadherin expression associated with angiogenesis in non-small cell lung cancer patients"British Journal of Cancer. in-press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamoto T, Kameyama K, et al.: "Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine tracheomalacia: a preliminary report"ASAIO Journal. 49(1). 63-69 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameyama K, et al.: "Problems related to TNM staging: patients with stage III non-small cell lung cancer"Journal of Thracic and Cadiovascular Surgery. 124(3). 503-510 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kameyama K, et al.: "Induction chemotherapy before operation for multiple endobronchial squamous cell carcinoma of the lung"Annals of Thoracic Surgery. 74(4). 1008-1010 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Liu D, Kameyama K, et al.: "Topoisomerase II alpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients"Cancer. 94(8). 2239-2247 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masuya D, Kameyama K, et al.: "The intratumoral expression of vascular endothelial growth factor and interleukin-8 associated with angiogenesis in non-small cell lung carcinoma patients"Cancer. 92(10). 2628-2638 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Liu D, Kameyama K, et al.: "E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer"Annals of Thoracic Surgery. 71(3). 949-955 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 亀山耕太郎, 他: "Pulmonary embolism after lung resection : diagnosis and treatment"Annals of Thoracic Surgery. (掲載予定).

    • Related Report
      2002 Annual Research Report
  • [Publications] 中島 尊, 亀山耕太郎, 他: "N-cadherin expression associated with angiogenesis in non-small cell lung cancer patients"British Journal of Cancer. (掲載予定).

    • Related Report
      2002 Annual Research Report
  • [Publications] 岡本 卓, 亀山耕太郎: "Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine trasheomalacia : a preliminary report"ASAIO Journal. 49・1. 63-69 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 亀山耕太郎, 他: "Problems related to TNM staging : patients with stage III non-small cell lung cancer"Journal of Thoracic and Cardiovascular Surgery. 124・3. 503-510 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 亀山耕太郎, 他: "Induction chemotherapy before operation for multiple endobronchial squamous cell carcinoma of the lung"Annals of Thoracic Surgery. 74・4. 1008-1010 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 劉 大革, 亀山耕太郎, 他: "Topoisomerase II alpha gene expression is regulated by the p53 suppressor gene in nonsmall cell lung carcinoma patients"Cancer. 94・8. 2239-2247 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 劉 大革, 他: "E-cadherin expression associated with differentiation and prognosis in non-small cell lung cancer patients"Annals of Thoracic Surgery. 71・3. 949-955 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 桝屋大輝, 他: "The intratumoral expression of vascular endothelial growth factor and interleukin-8 assocaited with angiogenesis in nonsmall cell lung carcinoma patients"Cancer. 92・10. 2628-2638 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 劉 大革, 他: "Tpoisomerase II alpha gene expression is regulated by p53 tumor suppressor gene in non-small cell lung cancer patients"Cancer. (掲載予定).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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