[PDF][PDF] Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin
R Satchi-Fainaro, R Mamluk, L Wang, SM Short… - Cancer cell, 2005 - cell.com
R Satchi-Fainaro, R Mamluk, L Wang, SM Short, JA Nagy, D Feng, AM Dvorak, HF Dvorak…
Cancer cell, 2005•cell.comAngiogenesis inhibitors, such as TNP-470 and the nontoxic HPMA copolymer-TNP-470
(caplostatin), are emerging as a class of anticancer drugs. We report that TNP-470 and
caplostatin inhibit vascular hyperpermeability of tumor blood vessels as well as that induced
in mouse skin by different mediators. Treatment with TNP-470 or angiostatin for 3 days was
sufficient to reduce permeability of tumor blood vessels, delayed-type hypersensitivity, and
pulmonary edema induced by IL-2. TNP-470 also inhibited VPF/VEGF-induced …
(caplostatin), are emerging as a class of anticancer drugs. We report that TNP-470 and
caplostatin inhibit vascular hyperpermeability of tumor blood vessels as well as that induced
in mouse skin by different mediators. Treatment with TNP-470 or angiostatin for 3 days was
sufficient to reduce permeability of tumor blood vessels, delayed-type hypersensitivity, and
pulmonary edema induced by IL-2. TNP-470 also inhibited VPF/VEGF-induced …
Summary
Angiogenesis inhibitors, such as TNP-470 and the nontoxic HPMA copolymer-TNP-470 (caplostatin), are emerging as a class of anticancer drugs. We report that TNP-470 and caplostatin inhibit vascular hyperpermeability of tumor blood vessels as well as that induced in mouse skin by different mediators. Treatment with TNP-470 or angiostatin for 3 days was sufficient to reduce permeability of tumor blood vessels, delayed-type hypersensitivity, and pulmonary edema induced by IL-2. TNP-470 also inhibited VPF/VEGF-induced phosphorylation of VEGFR-2, calcium influx, and RhoA activation in endothelial cells. These results identify an activity of TNP-470, that of inhibiting vessel hyperpermeability. This activity likely contributes to TNP-470's antiangiogenic effect and suggests that caplostatin can be used in the treatment of cancer and inflammation.
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