Source:http://linkedlifedata.com/resource/pubmed/id/16230403
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
20
|
| pubmed:dateCreated |
2005-10-18
|
| pubmed:abstractText |
Oncolytic adenoviruses exhibiting tumor-selective replication are promising anticancer agents. Insertion and expression of a transgene encoding tissue inhibitor of metalloproteinase-3 (TIMP-3), which has been reported to inhibit angiogenesis and tumor cell infiltration and induce apoptosis, may improve the antitumor activity of these agents. To assess the effects of TIMP-3 gene transfer to glioma cells, a replication-defective adenovirus encoding TIMP-3 (Ad.TIMP-3) was employed. Ad.TIMP-3 infection of a panel of glioma cell cultures decreased the proliferative capacity of these cells and induced morphologic changes characteristic for apoptosis. Next, a conditionally replicating adenovirus encoding TIMP-3 was constructed by inserting the TIMP-3 expression cassette into the E3 region of the adenoviral backbone containing a 24-bp deletion in E1A. This novel oncolytic adenovirus, AdDelta24TIMP-3, showed enhanced oncolytic activity on a panel of primary cell cultures and two glioma cell lines compared with the control oncolytic virus AdDelta24Luc. In vivo inhibition of matrix metalloproteinase (MMP) activity by AdDelta24TIMP-3 was shown in s.c. glioma xenografts. The functional activity of TIMP-3 was imaged noninvasively using a near-IR fluorescent MMP-2-activated probe. Tumoral MMP-2 activity was significantly reduced by 58% in the AdDelta24TIMP-3-treated tumors 24 hours after infection. A study into the therapeutic effects of combined oncolytic and antiproteolytic therapy was done in both a s.c. and an intracranial model for malignant glioma. Treatment of s.c. (U-87MG) or intracranial (U-87deltaEGFR) tumors with AdDelta24TIMP-3 and AdDelta24Luc both significantly inhibited tumor growth and prolonged survival compared with PBS-treated controls. However, expression of TIMP-3 in the context of AdDelta24 did not significantly affect the antitumor efficacy of this oncolytic agent.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0008-5472
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| pubmed:author |
pubmed-author:CaretteJan EJE,
pubmed-author:ChioccaE AntonioEA,
pubmed-author:DirvenClemens M FCM,
pubmed-author:GerritsenWinald RWR,
pubmed-author:GianniDavideD,
pubmed-author:IdemaSanderS,
pubmed-author:LamfersMartine L MML,
pubmed-author:QuaxPaul H APH,
pubmed-author:SchagenFrederik H EFH,
pubmed-author:TungChing-HsuanCH,
pubmed-author:Van BeusechemVictor WVW,
pubmed-author:VandertopW PeterWP
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
65
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
9398-405
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:16230403-Adenoviridae,
pubmed-meshheading:16230403-Animals,
pubmed-meshheading:16230403-Cell Growth Processes,
pubmed-meshheading:16230403-Cell Line, Tumor,
pubmed-meshheading:16230403-Gene Transfer Techniques,
pubmed-meshheading:16230403-Glioma,
pubmed-meshheading:16230403-Humans,
pubmed-meshheading:16230403-Matrix Metalloproteinase 2,
pubmed-meshheading:16230403-Mice,
pubmed-meshheading:16230403-Mice, Nude,
pubmed-meshheading:16230403-Tissue Inhibitor of Metalloproteinase-3,
pubmed-meshheading:16230403-Virus Replication,
pubmed-meshheading:16230403-Xenograft Model Antitumor Assays
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Tissue inhibitor of metalloproteinase-3 expression from an oncolytic adenovirus inhibits matrix metalloproteinase activity in vivo without affecting antitumor efficacy in malignant glioma.
|
| pubmed:affiliation |
Department of Neurosurgery, Division of Gene Therapy, VU University Medical Center, Amsterdam, The Netherlands. M.Lamfers@vumc.nl
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
|