Linked Life Data

8900868

Source:http://linkedlifedata.com/resource/pubmed/id/8900868

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-1-28
pubmed:abstractText
Manifold mechanisms of resistance can be expressed by malignancies. Profound information on this aspect is a prerequisite for comprehensive individual chemotherapy. Based on both morphological and functional findings, the diagnosis of P-Glycoprotein (P-Gp) mediated Multidrug Resistance (MDR) can be verified. In order to describe minimum criteria for conclusive diagnosis, morphological and biochemical findings (Immunocytochemistry, RT-PCR, ultrastructural and Laser-Scan microscopy) and functional data (cytostatic drug transport, proliferation) were correlated in tumor cell lines of the MDR phenotype as opposed to cells with atypical resistance. Frequently, single features of MDR are found in atypical, P-Gp negative resistance. Accumulation deficits for mitoxantrone based on vesicular drug transport were found in P-Gp negative gastric carcinoma cell line EPG85-257RNOV. Nocodazole blocked microtubule formation which is essential for vesicle transfer from perinuclear regions to the periphery of the cytosol. Cytochalasin blocked exocytosis of drug containing vesicles. MDR modulators were ineffective. Alternatively, P-Gp mediated drug extrusion and exocytosis of drug containing vesicles may constitute complementary mechanisms of resistance. In gastric carcinoma cells EPG85-257DAU, MDR modulators do increase cytosolic daunorubicin load, but drug binding to nuclear target sites is still inhibited due to drug containment within vesicles. To complicate matters, MDR modulators may be functional even in MDR negative cells, as shown in a panel of melanoma cell lines. Data show that conclusive diagnosis of P-Gp-mediated MDR should be based on more than one experimental approach including immunocytochemistry, a sensitive assay such as RT-PCR and--whenever feasible--a functional test.
pubmed:language
ger
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0031-7144
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
171-6
pubmed:dateRevised
2007-1-29
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
[Morphological and functional features of cytostatic drug resistance and the effects of MDR modulators].
pubmed:affiliation
Abteilung Allgemeine Pharmakologie, Universität Hamburg, Germany.
pubmed:publicationType
Journal Article, English Abstract