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Title   다형성 교모세포종에서 아데노바이러스매개 Antisense - VEGF 를 이용한 신생혈관형성 억제 유전자 요법 ( Antiangiogenesis Gene Therapy Using Adenovirus - mediated Antisense - VEGF in Glioblastoma Multiforme )
Publicationinfo   2000 Jan; 032(04): 764-775.
Key_word   Antiangiogenesis, Gene therapy, Adenovirus, Vascular endothelial growth factor, Glioma
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Abstract   Purpose: Vascular endothelial growth factor (VEGF) is a major positive effector of angiogenesis. We investigated the mechanism of tumor growth inhibition by adenoviral transfer of antisense-VEGF in glioma and the role of VEGF for in vivo growth of human glioma cells according to the stage of the tumor growth. Materials and Methods: Replication-deficient adenoviral vector containing the VEGF cDNA in an antisense orientation (Ad5CMV- αVEGF) were constructed to increase the in vivo applicability of antisense sequence. The effect of Ad5CMV- gVEGF was studied in vitro and in vivo with human glioma cell line U-87 MG. Immunohistochemical staining of the subcutaneous tumor with anti-VEGF antibody and CD34 antibody were performed to compare VEGF protein expression and the microvessel count respectively. Results: The growth curve of U-87 MG cells treated with Ad5CMV- αVEGF remained as same as that of mock-infected and Ad5(d1312)-infected U-87 MG cells in vitro, suggesting that Ad5CMV- a VEGF does not have direct cytotoxic effect. The growth of subcutaneous human glioma xenografts was inhibited by early intratumoral injection of Ad5CMV- pVEGF. Immuno- histochemical staining of tumors showed that VEGF protein expression and mean microvessel counts were decreased in early Ad5CMV- a VEGF treatment group. Conclusion: The efficient down-regulation of VEGF produced by tumor cells using Ad5CMV- αVEGF in early stage of glioma growth has an antitumor effect in vivo through antiangiogenic mechanism.
저 자   임석아(Seock A Im),김정수(Jeong Soo Kim),남은미(Eun Mi Nam),이순남(Soon Nam Lee)