Linked Life Data

15231672

Source:http://linkedlifedata.com/resource/pubmed/id/15231672

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-7-2
pubmed:abstractText
Vascular endothelial growth factor (VEGF) is a key angiogenic factor in a variety of solid tumors, making it one of the most attractive therapeutic targets. VEGF promotes the proliferation, survival, and differentiation of vascular endothelial cells by stimulating autophosphorylation and activation of VEGF receptor-2 (VEGFR-2, fetal liver kinase-1, and kinase insert domain-containing receptor). We developed fluorescence-based, quantitative methods to measure total VEGFR-2, VEGFR-2 phosphorylation, apoptosis, and microvessel density and size within whole tumor cross-sections using a laser scanning cytometer. Using these methods, we characterized the effects of DC101, a blocking antibody specific for murine VEGFR-2, on orthotopic human 253J-BV bladder tumors growing in nude mice. Basal levels of receptor phosphorylation were heterogeneous, with approximately 50% of endothelial cells positive for phosphorylated VEGFR-2 at baseline. DC101 therapy resulted in a 50% decrease in overall VEGFR-2 phosphorylation and a 15-fold and 8-fold increase in endothelial cell (CD31-positive) and tumor cell apoptosis, respectively. DC101 also decreased overall tumor microvessel density, but it mostly affected smaller CD105-negative microvessels located in the periphery of the tumor. Intriguingly, anti-VEGFR-2 therapy resulted in increased mean vessel size and an increase in overall VEGFR-2 levels. Increases in total VEGFR-2 levels were localized to the tumor core and were associated with increased expression of the oxygen-sensitive transcription factor, hypoxia inducible factor-1alpha. These data suggest that VEGFR inhibitors preferentially target discrete populations of tumor endothelial cells associated with the smaller peripheral blood vessels. Thus, agents that target a single receptor (e.g., VEGFR-2) may not be sufficient to completely inhibit tumor angiogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4601-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15231672-Animals, pubmed-meshheading:15231672-Antibodies, Monoclonal, pubmed-meshheading:15231672-Antibody Specificity, pubmed-meshheading:15231672-Apoptosis, pubmed-meshheading:15231672-Carcinoma, Transitional Cell, pubmed-meshheading:15231672-Humans, pubmed-meshheading:15231672-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:15231672-Male, pubmed-meshheading:15231672-Mice, pubmed-meshheading:15231672-Mice, Inbred BALB C, pubmed-meshheading:15231672-Mice, Nude, pubmed-meshheading:15231672-Neovascularization, Pathologic, pubmed-meshheading:15231672-Phosphorylation, pubmed-meshheading:15231672-Transcription Factors, pubmed-meshheading:15231672-Urinary Bladder Neoplasms, pubmed-meshheading:15231672-Vascular Endothelial Growth Factor Receptor-2, pubmed-meshheading:15231672-Xenograft Model Antitumor Assays
pubmed:year
2004
pubmed:articleTitle
Regional effects of an antivascular endothelial growth factor receptor monoclonal antibody on receptor phosphorylation and apoptosis in human 253J B-V bladder cancer xenografts.
pubmed:affiliation
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. dardavis@mdanderson.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't