| Project/Area Number |
15390411
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Hyogo College of Medicine (2004)
Kyoto University (2003) |
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Principal Investigator |
HASEGAWA Seiki Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (10252438)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Hiromi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (90167205)
TANAKA Fumihiro Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (10283673)
NODA Makoto Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (30146708)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | RECK / Lung cancer / Prognostic factor / Angiogenesis / MMP / Gene therapy / VEGF |
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| Research Abstract |
Purpose : To assess the clinical significance of expression of RECK in non-small cell lung cancer(NSCLC), and to estimate whether the elevated expression of RECK by gene transfer has the potential for effective treatment for NSCLC.
Methods : 1)We analyzed the expression of RECK using immunohistochemistry, Western blot and real-time PCR in resected NSCLC and compared these data with other clinical and pathological features of the cases. 2)We analyzed the relationship between RECK expression and angiogenic factors, including matrix metalloproteinases(MMPs) and vascular endothelial growth factor(VEGF), in stable and transient expression of RECK in vitro. Also, we estimated the correlation between RECK expression and tumor angiogenesis or survival in a mice xenograft model. 3)We investigated the efficacy of RECK gene therapy using a nonviral vector in mouse xenograft model.
Results : First, we have demonstrated the clinical significance of RECK expression in NSCLC as follows : I)RECK express
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ion was reduced in tumor tissues as compared to that in normal lung tissues and 2)enhanced RECK expression was correlated with a favorable prognosis for the inhibition of tumor angiogenesis. A subset analysis demonstrated that the prognostic significance is evident not in early-stage disease but in advanced-stage disease. RECK expression was positively correlated with VEGF,MMP-2,and MMP-14 expression. Next, we estimated in vitro cell growth using stable cells expressing RECK. In vitro cell growth showed no differences among stable transfected lung cancer cell lines. Regarding subcutaneous tumor xenograft, however, tumor progression of RECK expressing tumor was significantly suppressed as compared with that of vector alone. In addition, immunostaining showed that micro-vessel density was reduced in RECK expressing tumor. Third, our study demonstrated that a treatment by RECK gene transfer using the novel nonviral liposome vector can suppress tumor growth of mice bearing NSCLC by decreased tumor angiogenesis.
Conclusions : These results strongly suggest that RECK can be a new target in the diagnosis and treatment of NSCLC, and it will provide a feasible strategy for antiangiogenic gene therapy of NSCLC. Less
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