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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1995-4-27
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pubmed:abstractText |
KYM-1D4 cells are a subline derived from a human rhabdomyosarcoma which are highly sensitive to TNF-mediated cytotoxicity. They were selected for this study because they express human TNF-R and are therefore a more relevant target for comparing the potential therapeutic value of human TNF-inhibitory agents than the usual murine cell lines. Two recombinant soluble TNF-R-IgG fusion proteins, one containing p55 TNR-R, the other containing p75 TNF-R, and a recombinant monomeric soluble p55 TNF-R were all found to block the cytotoxicity generated by human TNF-alpha and LT as well as also murine TNF. The p55 TNF-R-IgG fusion protein (p55-sf2) was the most effective of the antagonists tested, requiring an equimolar, (based on a monomeric configuration of TNF-alpha) or a 3-fold higher (based on a trimeric configuration of TNF-alpha) molar concentration to inhibit the cytotoxicity mediated TNF-alpha by 50%. p55-sf2 was also as effective at inhibiting the cytotoxicity mediated by LT or murine TNF in the KYM-1D4 assay. In contrast, the monomeric soluble p55 TNF-R was the least effective inhibitor, requiring a > 4000-fold higher molar concentration than p55-sf2 to achieve a similar degree of protection. The fusion proteins, particularly p55-sf2, may be useful as human therapeutic agents, as at low concentrations they can prevent both TNF-alpha-mediated and LT-mediated effects on human cells. As TNF-R-IgG fusion proteins also block the action of murine TNF in vitro, they may also be useful in the investigation of murine models of human inflammatory disease.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1043-4666
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
616-23
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7893970-Animals,
pubmed-meshheading:7893970-Antibodies, Monoclonal,
pubmed-meshheading:7893970-CHO Cells,
pubmed-meshheading:7893970-Cell Line,
pubmed-meshheading:7893970-Cell Survival,
pubmed-meshheading:7893970-Cricetinae,
pubmed-meshheading:7893970-Humans,
pubmed-meshheading:7893970-Immunoglobulin G,
pubmed-meshheading:7893970-Kinetics,
pubmed-meshheading:7893970-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:7893970-Recombinant Fusion Proteins,
pubmed-meshheading:7893970-Rhabdomyosarcoma,
pubmed-meshheading:7893970-Transfection,
pubmed-meshheading:7893970-Tumor Cells, Cultured,
pubmed-meshheading:7893970-Tumor Necrosis Factor-alpha
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pubmed:year |
1994
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pubmed:articleTitle |
TNF receptor fusion proteins are effective inhibitors of TNF-mediated cytotoxicity on human KYM-1D4 rhabdomyosarcoma cells.
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pubmed:affiliation |
Kennedy Institute of Rheumatology, Hammersmith, London, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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