Source:http://linkedlifedata.com/resource/pubmed/id/16136163
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2006-1-6
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| pubmed:abstractText |
Pharmacological control is a desirable safety feature of oncolytic adenoviruses (oAdV). It has recently been shown that oAdV replication may be controlled by drug-dependent transcriptional regulation of E1A expression. Here, we present a novel concept that relies on tamoxifen-dependent regulation of E1A activity through functional linkage to the mutated hormone-binding domain of the murine estrogen receptor (Mer). Four different E1A-Mer chimeras (ME, EM, E(DeltaNLS)M, MEM) were constructed and inserted into the adenoviral genome under control of a lung-specific surfactant protein B promoter. The highest degree of regulation in vitro was seen for the corresponding oAdVs Ad.E(DeltaNLS)M and Ad.MEM, which exhibited an up to 100-fold higher oAdV replication in the presence as compared with the absence of 4-OH-tamoxifen. Moreover, destruction of nontarget cells was six- and 13-fold reduced for Ad.E(DeltaNLS)M and Ad.MEM, respectively, as compared with Ad.E. Further investigations supported tamoxifen-dependent regulation of Ad.E(DeltaNLS)M and Ad.MEM in vivo. Induction of Ad.E(DeltaNLS)M inhibited growth of H441 lung tumors as efficient as a control oAdV expressing E1A. E(DeltaNLS)M and the MEM chimeras can be easily inserted into a single vector genome, which extends their application to existing oAdVs and strongly facilitates in vivo application.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxytamoxifen,
http://linkedlifedata.com/resource/pubmed/chemical/Adenovirus E1A Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tamoxifen
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0969-7128
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
13
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
173-86
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16136163-Adenocarcinoma,
pubmed-meshheading:16136163-Adenovirus E1A Proteins,
pubmed-meshheading:16136163-Animals,
pubmed-meshheading:16136163-Cytopathogenic Effect, Viral,
pubmed-meshheading:16136163-Female,
pubmed-meshheading:16136163-Gene Expression Regulation,
pubmed-meshheading:16136163-Gene Therapy,
pubmed-meshheading:16136163-Genetic Engineering,
pubmed-meshheading:16136163-HeLa Cells,
pubmed-meshheading:16136163-Humans,
pubmed-meshheading:16136163-Lung Neoplasms,
pubmed-meshheading:16136163-Mice,
pubmed-meshheading:16136163-Mice, Nude,
pubmed-meshheading:16136163-Receptors, Estrogen,
pubmed-meshheading:16136163-Recombinant Proteins,
pubmed-meshheading:16136163-Tamoxifen,
pubmed-meshheading:16136163-Transcription, Genetic,
pubmed-meshheading:16136163-Tumor Cells, Cultured,
pubmed-meshheading:16136163-Virus Replication
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| pubmed:year |
2006
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| pubmed:articleTitle |
Tamoxifen-regulated adenoviral E1A chimeras for the control of tumor selective oncolytic adenovirus replication in vitro and in vivo.
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| pubmed:affiliation |
Department of Cardiology and Pneumology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|