Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-7-17
pubmed:abstractText
Resistance of tumor cells to multiple structurally unrelated cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The "classical" MDR phenotype is the result from decreased cellular drug accumulation mediated by the adenosine triphosphate binding cassette (ABC)-transporter MDR1/P-glycoprotein (MDR1/P-gp, ABCB1) encoded by the human MDR1 gene. Inhibition of the drug extrusion activity of MDR1/P-gp by low-molecular weight pharmacologically active compounds as a method to reverse MDR in patients suffering on malignant diseases has been studied capaciously, but the clinical results have generally been disappointing. Thus, experimental therapeutic strategies to reverse MDR are under extensive investigation. These strategies included gene therapeutic approaches with antisense oligonucleotides (ODNs), ribozymes, or DNAzymes and, most recently, the application of the RNA interference (RNAi) technology. RNAi is a physiological double stranded RNA-triggered mechanism resulting in gene-silencing in a sequence-specific manner. Transient RNAi can be attained by application of small interferring RNAs (siRNAs), whereas a stable RNAi-mediated gene-silencing can be achieved by transfection of mammalian cells with short hairpin RNA (shRNA) encoding expression cassettes localized on plasmid or viral vectors. Transient and stable RNAi strategies were applied to overcome MDR1/P-gp-mediated MDR in different in vitro models derived from various neoplastic tissue and will be come up for discussion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1389-4501
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
813-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
MDR1/P-glycoprotein (ABCB1) as target for RNA interference-mediated reversal of multidrug resistance.
pubmed:affiliation
Charité Campus Mitte, Institute of Pathology, Schumannstr. 20/21, D-10117 Berlin, Germany. hermann.lage@charite.de
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't