Source:http://linkedlifedata.com/resource/pubmed/id/11407910
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2001-6-15
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| pubmed:abstractText |
Ototoxicity is a major dose-limiting side effect of cisplatin (DDP) administration due to its propensity to induce destruction of hair cells and neurons in the auditory system. Previous studies demonstrated that TrkC-expressing spiral ganglion neurons (SGN) are protected from the cytotoxic effects of DDP by localized delivery of the trophic factor neurotrophin-3 (NT-3). Successful in vivo implementation of such a therapy requires the development of an efficient gene delivery vehicle for expression of NT-3 within the cochlea. To this end, we constructed a herpes simplex virus (HSV) amplicon vector that expressed a c-Myc-tagged NT-3 chimera (HSVnt-3myc). Helper virus-free vector stocks were initially evaluated in vitro for their capacity to direct expression of NT-3 mRNA and protein. Transduction of cultured murine cochlear explants with HSVnt-3myc resulted in production of NT-3 mRNA and protein up to 3 ng/ml as measured over a 48-h period in culture supernatants. To determine whether NT-3 overexpression could abrogate DDP toxicity, cochlear explants were transduced with HSVnt-3myc or a murine intestinal alkaline phosphatase-expressing control vector, HSVmiap, and then exposed to cisplatin. HSVnt-3myc-transduced cochlear explants harbored significantly greater numbers of surviving SGNs than those infected with control virus. These data demonstrate that amplicon-mediated NT-3 transduction can attenuate the ototoxic action of DDP on organotypic culture. The potency of NT-3 in protecting spiral ganglion neurons from degeneration suggests that in vivo neurotrophin-based gene therapy may be useful for the prevention and/or treatment of hearing disorders.
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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
|
| pubmed:month |
Jun
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| pubmed:issn |
1525-0016
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
3
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
958-63
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11407910-Animals,
pubmed-meshheading:11407910-Blotting, Western,
pubmed-meshheading:11407910-Cell Death,
pubmed-meshheading:11407910-Cisplatin,
pubmed-meshheading:11407910-Cochlea,
pubmed-meshheading:11407910-Cytomegalovirus,
pubmed-meshheading:11407910-DNA Primers,
pubmed-meshheading:11407910-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:11407910-Genes, myc,
pubmed-meshheading:11407910-Hearing Disorders,
pubmed-meshheading:11407910-Immunoenzyme Techniques,
pubmed-meshheading:11407910-Neurites,
pubmed-meshheading:11407910-Neurons,
pubmed-meshheading:11407910-Neurotrophin 3,
pubmed-meshheading:11407910-Recombinant Fusion Proteins,
pubmed-meshheading:11407910-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11407910-Simplexvirus,
pubmed-meshheading:11407910-Spiral Ganglion
|
| pubmed:year |
2001
|
| pubmed:articleTitle |
HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage.
|
| pubmed:affiliation |
Division of Otolaryngology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|