Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-4-25
pubmed:abstractText
The use of TNF-mutants that are selective agonists of the TNF-R55 is one strategy that is being explored to broaden the therapeutic margin of TNF. Several problems still have to be overcome before they can be used in clinical trials. Regarding the sensitizing effect of some infections and some tumours, we identified IFN-gamma as a mediator in BCG- but not in tumour-induced sensitization. In both models, the vessel wall is most probably the key tissue as alpha-LFA-1 antibodies could protect against lethality. Studies in primates showed that an unexpected feature, namely, the longer half-life of such mutants, might interfere with this strategy. Recent observations also indicate that the mechanism of tolerance-induction, another way to separate antitumour and toxic effects of TNF, might reside in the functional ablation of the TNF-R75. Using IL-60/0 knockout mice, we could not find any causal role for IL-6 in TNF-mediated lethality, this in contrast to results obtained previously with neutralizing antibodies. Finally, we identified the acute phase protein alpha 1-acid glycoprotein as a protein with protective properties towards TNF-induced lethality and liver damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0092-6213
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Receptor-selective mutants of tumour necrosis factor in the therapy of cancer: preclinical studies.
pubmed:affiliation
Laboratory of Molecular Biology, Gent University, Belgium.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't