Linked Life Data

17922877

Source:http://linkedlifedata.com/resource/pubmed/id/17922877

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-11-5
pubmed:abstractText
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, which is being developed as an anti-tumour agent due to its selective toxicity to tumour cells, induces apoptosis by binding to two membrane-bound receptors, TRAIL-R1 and TRAIL-R2. Clinical trials have been initiated with various preparations of TRAIL as well as agonistic monoclonal antibodies to TRAIL-R1 and TRAIL-R2. Previously we reported that prior treatment of primary chronic lymphocytic leukaemia (CLL) cells with histone deacetylase inhibitors was required to sensitize CLL cells to TRAIL and, using various receptor-selective TRAIL mutant ligands, we demonstrated that CLL cells signalled to apoptosis primarily through TRAIL-R1. Some, but not all, agonistic TRAIL-receptor antibodies require cross-linking in order to induce apoptosis. The present study demonstrated that CLL cells can signal to apoptosis through the TRAIL-R2 receptor, but only after cross-linking of the agonistic TRAIL-R2 antibodies, LBY135 and lexatumumab (HGS-ETR2). In contrast, signalling through TRAIL-R1 by receptor-selective ligands or certain agonistic antibodies, such as mapatumumab (HGS-ETR1), occurs in the absence of cross-linking. These results further highlight important differences in apoptotic signalling triggered through TRAIL-R1 and TRAIL-R2 in primary tumour cells. Such information is clearly important for the rational optimisation of TRAIL therapy in primary lymphoid malignancies, such as CLL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1365-2141
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
568-77
pubmed:meshHeading
pubmed-meshheading:17922877-Aged, pubmed-meshheading:17922877-Aged, 80 and over, pubmed-meshheading:17922877-Antibodies, Monoclonal, pubmed-meshheading:17922877-Apoptosis, pubmed-meshheading:17922877-Cell Communication, pubmed-meshheading:17922877-Cell Line, Tumor, pubmed-meshheading:17922877-Cross-Linking Reagents, pubmed-meshheading:17922877-Drug Interactions, pubmed-meshheading:17922877-Ephrins, pubmed-meshheading:17922877-Female, pubmed-meshheading:17922877-Humans, pubmed-meshheading:17922877-Hydroxamic Acids, pubmed-meshheading:17922877-Leukemia, Lymphocytic, Chronic, B-Cell, pubmed-meshheading:17922877-Male, pubmed-meshheading:17922877-Middle Aged, pubmed-meshheading:17922877-Receptors, TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:17922877-TNF-Related Apoptosis-Inducing Ligand
pubmed:year
2007
pubmed:articleTitle
TRAIL signals to apoptosis in chronic lymphocytic leukaemia cells primarily through TRAIL-R1 whereas cross-linked agonistic TRAIL-R2 antibodies facilitate signalling via TRAIL-R2.
pubmed:affiliation
MRC Toxicology Unit, University of Leicester, Leicester, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't