Linked Life Data

14633719

Source:http://linkedlifedata.com/resource/pubmed/id/14633719

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2003-11-24
pubmed:abstractText
Cancer cell adhesion confers a transient, de novo drug-resistant phenotype referred to as cell adhesion-mediated drug resistance (CAM-DR). In this report, we extend the CAM-DR phenotype to primary specimens from patients with myeloma, providing further evidence that CAM-DR is a viable clinical form of drug resistance. To examine mechanisms of cellular resistance to melphalan, we compared genotypic and phenotypic profiles of acquired and de novo melphalan resistance in an isogenic human myeloma cell line. Acquired melphalan resistance (8226/LR5) was associated with decreased drug-induced DNA damage and a complex gene expression profile showing that genes involved in the Fanconi anemia DNA repair pathway are increased in the LR5 cells compared with drug-sensitive or adherent cells. In contrast, cells adhered to fibronectin accumulate similar amounts of DNA damage compared with drug-sensitive cells but are protected from melphalan-induced mitochondrial perturbations and caspase activation. Levels of the proapoptotic protein Bim were significantly reduced in adherent cells. Gene expression changes associated with de novo resistance were significantly less complex compared with acquired resistance, but a significant overlap in gene expression was noted involving cholesterol synthesis. We propose that myeloma cell adhesion promotes a form of de novo drug resistance by protecting cells from melphalan-induced cytotoxic damage and that this transient protection allows cells to acquire a more permanent and complex drug resistance phenotype associated with a reduction in drug induced DNA damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7900-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Genotypic and phenotypic comparisons of de novo and acquired melphalan resistance in an isogenic multiple myeloma cell line model.
pubmed:affiliation
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, at The University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't