Angiogenesis permeability

Reliable markers are needed to monitor the activity of antiangiogenic dtugs. Circulating endothelial cells and their progenitor subset are a potential candidate, as is MRI dynamic measurement of vascular permeability/ flow in response to angiogenesis inhibitors, but neither has been clinically validated. 

PPl (8) and its pyrazolopyrimidine analog PP2 (9) [99-108] were first described as potent inhibitors of SFKs with marked selectivity versus ZAP-70, JAK2, EGF-R, and PKA kinases. PPl provided an early key inhibitor of Src kinase to enable determination of its roles in VEGF-mediated angiogenesis and vascular permeability, Src-driven human breast cancer cell lines with respect to both heregulin-dependent or independent growth, and Src-related,... 

Mechanism of Action-. A selective vascular endothelial growth factor (VEGF) antagonize that selectively binds and activates receptors located on the surface of vascular endothelial cells. Therapeutic Effect Blocks angiogenesis and vascular permeability and inflammation which contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD). 

Blockade of angiogenesis is useful in tumor therapy (Ferrara and Kerbel 2005 Menakuru et al. 2008). Over the last decade, the most extensively examined proan-giogenic molecule has been VEGF, a secreted protein that, through activation of tyrosine kinase receptors, promotes key events in angiogenesis that include increases in vascular permeability, and stimulation of endothelial cell proliferation and migration (Ferrara 2003). 

Dvorak Hp Nagy JA, Feng D, et al, Vascular permeability factor/zascular endothelial growth factor and the significance of microvascular permeability in angiogenesis, Curr Topics Microbiol Immunol 1999 237 97-132,... 

Corada, M., Zanetta, L., Orsenigo, F., Breviario, F., Lampugnani, M. G., et al. 2002. A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. Blood 100 905-911. 

Eliceiri, B. P., Paul, R., Schwartzberg, P. L., Hood, J. D., Leng, J., and Cheresh, D. A. 1999. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol. Cell. 4 915-924. 

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