Source:http://linkedlifedata.com/resource/pubmed/id/15723303
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2005-5-18
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| pubmed:abstractText |
Recombinant adeno-associated viruses (rAAV) have become the vector of choice for many gene therapy protocols. rAAVs have a number of attractive features including long-term transgene expression and the ability to transduce both dividing and non-dividing cells. We have shown previously the anti-cancer role of tissue factor pathway inhibitor-2 (TFPI-2), a matrix-associated serine protease inhibitor, in human glioblastomas. As a result of our present study, in which 0.8-kb fragment of human TFPI-2 was cloned into the adeno-associated viral vectors (rAAA-TFPI-2), rAAV-TFPI-2 infection of SNB19 cells significantly increased TFPI-2 as determined by Western blotting. As assessed by spheroid and Matrigel assays, infection of SNB19 cells with rAAV-TFPI-2 significantly reduced migration and invasion in a dose-dependent manner. Tumor spheroids infected with rAAV-TFPI-2 and co-cultured with fetal rat brain aggregates did not invade rat brain aggregates, whereas 90-95% of the mock and AAV-CMV infected cells invaded rat brain aggregates. In vitro angiogenesis studies (tumor cells co-cultured with endothelial cells or endothelial cells seeded on matrigel) showed reduction of capillary-like structure formation in rAAV-TFPI-2-treated cells as compared to parental and mock-transfected cells. In in vivo angiogenesis results demonstrated the formation of microvessels in SNB19 parental cells and this formation was inhibited when the SNB19 cells were infected with rAAV-TFPI-2. Further, we observed a large reduction of tumor growth in SNB19 cells treated with rAAV-TFPI-2 virus injected intracerebrally when compared to controls. Our study demonstrates that rAAV-TFPI-2-mediated gene therapy offers a novel tool for the treatment of brain tumors.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
|
| pubmed:issn |
0020-7136
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2005 Wiley-Liss, Inc.
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| pubmed:issnType |
Print
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| pubmed:day |
20
|
| pubmed:volume |
115
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
998-1005
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15723303-Animals,
pubmed-meshheading:15723303-Cell Movement,
pubmed-meshheading:15723303-Cell Proliferation,
pubmed-meshheading:15723303-Dependovirus,
pubmed-meshheading:15723303-Genetic Vectors,
pubmed-meshheading:15723303-Glioblastoma,
pubmed-meshheading:15723303-Glycoproteins,
pubmed-meshheading:15723303-Humans,
pubmed-meshheading:15723303-Mice,
pubmed-meshheading:15723303-Mice, Nude,
pubmed-meshheading:15723303-Neoplasm Invasiveness,
pubmed-meshheading:15723303-Neoplasm Transplantation,
pubmed-meshheading:15723303-Neovascularization, Pathologic,
pubmed-meshheading:15723303-Tumor Cells, Cultured
|
| pubmed:year |
2005
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| pubmed:articleTitle |
Recombinant adeno-associated virus (rAAV) expressing TFPI-2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line.
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| pubmed:affiliation |
Program of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria, IL 61656, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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