Source:http://linkedlifedata.com/resource/pubmed/id/15280909
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2004-7-28
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pubmed:abstractText |
Soft-tissue sarcomas are mesenchymal tumors that respond poorly to systemic chemotherapy. Suicide gene therapy may be an alternative treatment strategy. Here we show a high susceptibility of human sarcoma cell lines for recombinant adeno-associated virus 2 (rAAV-2) suicide vectors: connective tissue sarcoma (HS-1), fibrosarcoma (HT-1080), Ewing sarcoma (RD-ES), Askin tumor (SK-N-MC), rhabdomyosarcoma (A-204) and soft-tissue sarcoma (WSKL-1). Several vectors containing the thymidine kinase (TK) gene under the control of either the cytomegalovirus promoter or the elongation-factor 1 alpha (EF1alpha) promoter were cloned and tested. Higher expression levels of the transgene were observed in the sarcoma lines when using the EF1alpha-suicide gene-containing vectors. A complete eradication of rAAV-2-EF1alpha-TK/eGFP (TK/enhanced green fluorescent protein fusion gene)-transduced tumor cells was shown following exposure to ganciclovir (2.5 microg/ml) in vitro, while at this dose level > 90% of mock-transduced tumor cells survived. Xenotransplantation tumor models (intraperitoneal, subcutaneous) for the human sarcoma cell line HS-1 were established in nonobese diabetic/severe-combined immunodeficient mice. Mice transplanted with rAAV-2-EF1alpha-TK/eGFP-transduced and ganciclovir-exposed tumor cells survived > 5 months while in the nontransduced group all mice had died approximately 1 month after inoculation. These data hold promise for further development of rAAV-2-based suicide gene therapy of sarcomas.
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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 |
Aug
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pubmed:issn |
0929-1903
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
577-84
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15280909-Animals,
pubmed-meshheading:15280909-Cell Line, Tumor,
pubmed-meshheading:15280909-Cytomegalovirus,
pubmed-meshheading:15280909-Dependovirus,
pubmed-meshheading:15280909-Ganciclovir,
pubmed-meshheading:15280909-Gene Therapy,
pubmed-meshheading:15280909-Genes, Transgenic, Suicide,
pubmed-meshheading:15280909-Genetic Vectors,
pubmed-meshheading:15280909-Humans,
pubmed-meshheading:15280909-Mice,
pubmed-meshheading:15280909-Mice, Inbred NOD,
pubmed-meshheading:15280909-Mice, SCID,
pubmed-meshheading:15280909-Peptide Elongation Factor 1,
pubmed-meshheading:15280909-Promoter Regions, Genetic,
pubmed-meshheading:15280909-Sarcoma,
pubmed-meshheading:15280909-Thymidine Kinase,
pubmed-meshheading:15280909-Xenograft Model Antitumor Assays
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pubmed:year |
2004
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pubmed:articleTitle |
Suicide gene therapy of sarcoma cell lines using recombinant adeno-associated virus 2 vectors.
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pubmed:affiliation |
Department of Radiation Oncology, Universitätsklinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68135, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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