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rdf:type |
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lifeskim:mentions |
umls-concept:C0023473,
umls-concept:C0038250,
umls-concept:C0062068,
umls-concept:C0243077,
umls-concept:C0389995,
umls-concept:C0667301,
umls-concept:C0935989,
umls-concept:C1332710,
umls-concept:C1551336,
umls-concept:C1552913,
umls-concept:C2348480
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pubmed:issue |
8
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pubmed:dateCreated |
2007-7-19
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pubmed:abstractText |
Evidence from cell line-based studies indicates that rho-kinase may play a role in the leukaemic transformation of human cells mediated by the BCR/ABL tyrosine kinase, manifest clinically as chronic myeloid leukaemia (CML). We therefore employed two separate inhibitors, Y-27632 and fasudil, to inhibit the activity of rho-kinase against ex vivo CD34(+) cells collected from patients with CML. We compared the effects of rho-kinase inhibition in those cells with the effects of direct inhibition of BCR/ABL using the specific inhibitor imatinib. We found that inhibition of rho-kinase inhibited the effective proliferation, and reduced survival of CML progenitor cells. When combined with imatinib, rho-kinase inhibition added to the anti-proliferative and pro-apoptotic effects of the BCR/ABL inhibitor. Our studies may indicate therapeutic benefit in some cases for the combination of rho-kinase inhibitors with imatinib.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Bcr-Abl tyrosine kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/fasudil,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0887-6924
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1708-14
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17554385-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:17554385-Amides,
pubmed-meshheading:17554385-Antigens, CD34,
pubmed-meshheading:17554385-Cell Proliferation,
pubmed-meshheading:17554385-Drug Synergism,
pubmed-meshheading:17554385-Enzyme Inhibitors,
pubmed-meshheading:17554385-Fusion Proteins, bcr-abl,
pubmed-meshheading:17554385-Humans,
pubmed-meshheading:17554385-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17554385-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:17554385-Piperazines,
pubmed-meshheading:17554385-Protein Kinase Inhibitors,
pubmed-meshheading:17554385-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17554385-Protein-Tyrosine Kinases,
pubmed-meshheading:17554385-Pyridines,
pubmed-meshheading:17554385-Pyrimidines,
pubmed-meshheading:17554385-Stem Cells,
pubmed-meshheading:17554385-Tumor Cells, Cultured,
pubmed-meshheading:17554385-rho-Associated Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
The rho-kinase inhibitors Y-27632 and fasudil act synergistically with imatinib to inhibit the expansion of ex vivo CD34(+) CML progenitor cells.
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pubmed:affiliation |
Division of Laboratory and Regenerative Medicine, Stopford Building, Manchester, UK. john.burthem@cmmc.nhs.uk
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pubmed:publicationType |
Journal Article
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