Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases.

Details

Serval ID
serval:BIB_16169
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Sauter B.V., Martinet O., Zhang W.J., Mandeli J., Woo S.L.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
2000
Volume
97
Number
9
Pages
4802-4807
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Inhibition of angiogenesis has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in the large-scale production of the antiangiogenic proteins. This limitation may be resolved by in vivo delivery and expression of the antiangiogenic genes. We have constructed a recombinant adenovirus that expresses murine endostatin that is biologically active both in vitro, as determined in endothelial cell proliferation assays, and in vivo, by suppression of angiogenesis induced by vascular endothelial growth factor 165. Persistent high serum levels of endostatin (605-1740 ng/ml; mean, 936 ng/ml) were achieved after systemic administration of the vector to nude mice, which resulted in significant reduction of the growth rates and the volumes of JC breast carcinoma and Lewis lung carcinoma (P < 0.001 and P < 0.05, respectively). In addition, the endostatin vector treatment completely prevented the formation of pulmonary micrometastases in Lewis lung carcinoma (P = 0.0001). Immunohistochemical staining of the tumors demonstrated a decreased number of blood vessels in the treatment group versus the controls. In conclusion, the present study clearly demonstrates the potential of vector-mediated antiangiogenic gene therapy as a component in cancer therapy.
Keywords
Adenoviridae, Animals, Antineoplastic Agents/toxicity, Cell Division/drug effects, Cloning, Molecular, Collagen/biosynthesis, Collagen/genetics, Endostatins, Endothelium, Vascular/cytology, Endothelium, Vascular/drug effects, Female, Fibroblast Growth Factor 2/pharmacology, Gene Transfer Techniques, Genetic Therapy/methods, Genetic Vectors, Humans, Liver/metabolism, Lung Neoplasms/blood supply, Lung Neoplasms/drug therapy, Mammary Neoplasms, Experimental/blood supply, Mammary Neoplasms, Experimental/drug therapy, Mice, Mice, Inbred BALB C, Neoplasm Metastasis/prevention & control, Neovascularization, Pathologic/prevention & control, Peptide Fragments/biosynthesis, Peptide Fragments/genetics, Tumor Cells, Cultured, Umbilical Veins
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2007 12:09
Last modification date
20/08/2019 12:45
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