RRC ID 64038
著者 Yamanaka R, Zullo SA, Ramsey J, Onodera M, Tanaka R, Blaese M, Xanthopoulos KG.
タイトル Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus.
ジャーナル Cancer Gene Ther
Abstract Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.
巻・号 8(10)
ページ 796-802
公開日 2001-10-1
DOI 10.1038/sj.cgt.7700367
PMID 11687903
MeSH Animals Brain Neoplasms / blood supply Brain Neoplasms / therapy* Brain Neoplasms / virology Cells, Cultured Collagen / blood Collagen / genetics* Endostatins Endothelium, Vascular / metabolism* Endothelium, Vascular / virology Female Gene Expression Gene Transfer Techniques Genetic Therapy / methods* Genetic Vectors / administration & dosage Humans Melanoma, Experimental / blood supply Melanoma, Experimental / therapy* Melanoma, Experimental / virology Mice Mice, Inbred C57BL Mice, Nude Neovascularization, Pathologic / therapy* Peptide Fragments / blood Peptide Fragments / genetics* Reverse Transcriptase Polymerase Chain Reaction Semliki forest virus / physiology* Survival Rate
IF 4.534
リソース情報
ヒト・動物細胞 B16