Acute vascular disruption by @entity25218 in an orthotopic model of @entity1 XXXX .

@entity1 @entity135 @entity13212 @entity137 @entity548 @entity39 @entity5 @entity957 @entity25218 @entity2279
The sustenance of most solid @entity5 including @entity135 ( @entity135 ) is strongly dependent on the presence of a functioning vascular network. In this study, we examined the acute effects of a @entity5 vascular disrupting agent (VDA), @entity25218 ( @entity25218 ; @entity25218 ), in an orthotopic model of @entity1 HNC. Noninvasive magnetic resonance imaging (MRI) was used to monitor the vascular response of orthotopic FaDu xenografts to VDA therapy. @entity5 showed a marked but heterogeneous pattern of enhancement after contrast agent injection on serial T1-weighted (T1W) MR images. After VDA treatment, @entity13212 and T1W MRI revealed evidence of @entity548 and lack of functioning vessels (enhancement) within the @entity5 . Quantitative estimates of relative vascular volume also showed a significant (P < .01) reduction in @entity25218 -treated @entity5 24 hours after therapy compared with untreated controls. Histology and immunostaining of untreated orthotopic FaDu @entity5 revealed poorly differentiated @entity957 histology with distinctly visible @entity2279 (+) endothelial cells. In sharp contrast, minimal @entity2279 staining with irregular endothelial fragments and faint outlines of blood vessels were seen in @entity25218 -treated @entity5 sections. @entity2279 immunostaining and histology also highlighted the selectivity of vascular damage and tissue @entity39 after VDA therapy with no evidence of @entity137 observed in normal salivary gland, heart, liver, and skeletal muscle tissues. Together, our results demonstrate a potent and selective vascular disruptive activity of @entity25218 in an orthotopic HNC model. Further evaluation into its antitumor effects alone and in combination with other agents is warranted.
