Linked Life Data

9652375

Source:http://linkedlifedata.com/resource/pubmed/id/9652375

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1998-9-16
pubmed:abstractText
Drug activity patterns in 10 human tumor cell lines representing defined mechanisms of drug resistance, including cell lines with high expression of P-glycoprotein and multidrug resistance associated protein (MRP), have previously been used for prediction of mechanism of drug action. In the present study, this cell line panel was analyzed for cellular accumulation of the fluorescent probe calcein/AM [4'5'-bis(N,N-bis (carboxymethyl) aminomethyl) fluorescein acetoxymethyl ester] and compared with drug response patterns of 20 standard chemotherapeutic drugs. According to degree of correlation with the ability to exclude calcein/AM, topoisomerase II inhibitors and tubulin actives were at the top of the list although the correlations were of lower magnitude than those obtained from the drug response patterns of mechanistically similar drugs. There was a significant relationship between the rank-order of drugs based on correlation with calcein/AM accumulation and Pgp/MRP mediated drug resistance suggesting that compounds being substrates for these pumps were identified. In simulated drug response profiles, the impact of Pgp and MRP expressing cell lines on the mechanistic prediction was found to be marginal. The results indicate that the differential molecular function/expression in the cell line panel may identify drugs interacting with specific biochemical pathways. Furthermore, the presence of cell lines overexpressing drug efflux mechanisms in the panel do not significantly influence the mechanistic predictions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
346
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
315-22
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Relationship between cytotoxic drug response patterns and activity of drug efflux transporters mediating multidrug resistance.
pubmed:affiliation
Division of Clinical Pharmacology, University Hospital, Uppsala, Sweden. sumeer.dhar@klinfarm.uu.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't