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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2006-7-17
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pubmed:abstractText |
Multidrug resistance (MDR) due to over-expression of the MDR1 (ABCB1) gene and its P-glycoprotein (Pgp) product is an obstacle in the treatment of hematological malignancies. In this study, we have evaluated the potency of KT-5720 to reverse Pgp-dependent MDR in vitro and in vivo. KT-5720 (but not its close derivatives, K252a and K252b) reversed multidrug resistance of LM1/MDR cell line at non-toxic concentrations and increased accumulation of rhodamine 123 (Rh123). KT-5720 significantly reversed MDR1-dependent resistance of primary malignant cells from patients with chronic myelogenous leukemia in blast crisis (CML-BC) and advanced multiple myeloma (MM). Moreover, KT-5720 (at 5 mg/kg) sensitized the bone marrow of MDR1 transgenic mice model towards daunorubicin (at 8 mg/kg) without general toxic effects. Therefore, KT-5720 can be considered as candidate for combination therapy in various hematological malignancies where Pgp activity is a major impediment for cure.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0145-2126
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1151-8
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16542724-Animals,
pubmed-meshheading:16542724-Antibiotics, Antineoplastic,
pubmed-meshheading:16542724-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:16542724-Blast Crisis,
pubmed-meshheading:16542724-Carbazoles,
pubmed-meshheading:16542724-Cell Line, Tumor,
pubmed-meshheading:16542724-Daunorubicin,
pubmed-meshheading:16542724-Drug Resistance, Neoplasm,
pubmed-meshheading:16542724-Drug Screening Assays, Antitumor,
pubmed-meshheading:16542724-Enzyme Inhibitors,
pubmed-meshheading:16542724-Humans,
pubmed-meshheading:16542724-Indoles,
pubmed-meshheading:16542724-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:16542724-Mice,
pubmed-meshheading:16542724-Mice, Inbred BALB C,
pubmed-meshheading:16542724-Mice, Transgenic,
pubmed-meshheading:16542724-Multiple Myeloma,
pubmed-meshheading:16542724-P-Glycoprotein,
pubmed-meshheading:16542724-Pyrroles
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pubmed:year |
2006
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pubmed:articleTitle |
In vitro and in vivo reversal of MDR1-mediated multidrug resistance by KT-5720: implications on hematological malignancies.
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pubmed:affiliation |
Laboratory of Molecular Immunobiology, Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel. hgalski@sheba.health.gov.il
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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