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 |