Linked Life Data

9533769

Source:http://linkedlifedata.com/resource/pubmed/id/9533769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-4-15
pubmed:abstractText
We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system. Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')2 anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis. Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis. The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases. Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-14
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system.
pubmed:affiliation
Hematology/Oncology, University Children's Hospital, Ulm, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't