Linked Life Data

15805287

Source:http://linkedlifedata.com/resource/pubmed/id/15805287

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-4-4
pubmed:abstractText
Taxol may contribute to intrinsic chemoresistance by activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) cytoprotective pathway in human cancer cell lines and tumors. We have previously shown additivity between Taxol and the MEK inhibitor, U0126 in human cancer cell lines. Here, the combination of Taxol with an orally bioavailable MEK inhibitor, CI-1040, was evaluated in human lung tumors heterotransplanted into nude mice. Unlike xenograft models that are derived from cells with multiple genetic alterations due to prolonged passage, heterotransplanted tumor models are more clinically relevant. Combined treatment with both drugs resulted in inhibition of tumor growth in all models and tumor regressions in three of four models tested, supporting our previous observation that Taxol's efficacy is potentiated by MEK inhibition. Concurrent administration was superior to intermittent dosing. Pharmacodynamic assessments of tumors indicated that suppression of MEK was associated with induction of S473 phosphorylated Akt and reduced proliferation in the combination groups relative to single agents, in addition to suppression of fibroblast growth factor-mediated angiogenesis and reduced expression of vascular endothelial growth factor. These findings are significant and indicate that this combination may have broad therapeutic applications in a diverse range of lung tumors with different intrinsic chemosensitivities.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2854-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15805287-Animals, pubmed-meshheading:15805287-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:15805287-Benzamides, pubmed-meshheading:15805287-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:15805287-Cell Line, Tumor, pubmed-meshheading:15805287-Drug Synergism, pubmed-meshheading:15805287-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:15805287-Fibroblast Growth Factors, pubmed-meshheading:15805287-Humans, pubmed-meshheading:15805287-Immunoblotting, pubmed-meshheading:15805287-Lung Neoplasms, pubmed-meshheading:15805287-Mice, pubmed-meshheading:15805287-Mice, Nude, pubmed-meshheading:15805287-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:15805287-Neovascularization, Pathologic, pubmed-meshheading:15805287-Paclitaxel, pubmed-meshheading:15805287-Xenograft Model Antitumor Assays
pubmed:year
2005
pubmed:articleTitle
Enhancement of the therapeutic efficacy of taxol by the mitogen-activated protein kinase kinase inhibitor CI-1040 in nude mice bearing human heterotransplants.
pubmed:affiliation
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. mcdaid@aecom.yu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't