Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-2-3
pubmed:abstractText
The potential for avoiding acquired resistance to therapy has been proposed as one compelling theoretical advantage of antiangiogenic therapy based on the normal genetic status of the target vasculature. However, previous work has demonstrated that tumors may resume growth after initial inhibition if antiangiogenic blockade is continued for an extended period. The mechanisms of this recurrent growth are unclear. In these studies, we characterized molecular changes in vasculature during apparent resumption of xenograft growth after initial inhibition by vascular endothelial growth factor blockade, "metronome" topotecan chemotherapy, and combined agents in a xenograft murine model of human Wilms' tumor. Tumors that grew during antiangiogenic blockade developed as viable clusters surrounding strikingly remodeled vessels. These vessels displayed significant increases in diameter and active proliferation of vascular mural cells and expressed platelet-derived growth factor-B, a factor that functions to enhance vascular integrity via stromal cell recruitment. In addition, remodeled vessels were marked by expression of ephrinB2, required for proper assembly of stromal cells into vasculature. Thus, enhanced vascular stability appears to characterize tumor vessel response to chronic antiangiogenesis, features that potentially support increased perfusion and recurrent tumor growth.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36-42
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14757844-Animals, pubmed-meshheading:14757844-Antineoplastic Agents, pubmed-meshheading:14757844-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:14757844-Ephrin-B2, pubmed-meshheading:14757844-Female, pubmed-meshheading:14757844-Fluorescein Angiography, pubmed-meshheading:14757844-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:14757844-Humans, pubmed-meshheading:14757844-In Situ Hybridization, pubmed-meshheading:14757844-Mice, pubmed-meshheading:14757844-Mice, Nude, pubmed-meshheading:14757844-Microscopy, Fluorescence, pubmed-meshheading:14757844-Neoplasm Proteins, pubmed-meshheading:14757844-Neoplasm Recurrence, Local, pubmed-meshheading:14757844-Neovascularization, Pathologic, pubmed-meshheading:14757844-Proto-Oncogene Proteins c-sis, pubmed-meshheading:14757844-Receptor, Platelet-Derived Growth Factor beta, pubmed-meshheading:14757844-Topotecan, pubmed-meshheading:14757844-Transplantation, Heterologous, pubmed-meshheading:14757844-Tumor Markers, Biological, pubmed-meshheading:14757844-Vascular Endothelial Growth Factor A, pubmed-meshheading:14757844-Wilms Tumor
pubmed:year
2004
pubmed:articleTitle
Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis.
pubmed:affiliation
Division of Pediatric Surgery, Columbia University College of Physicians and Surgeons, 3959 Broadway, BHN 214, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't