| 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)
|
|---|
| 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)
|
|---|
| 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
|
