Author/Authors :
Ronit Satchi-Fainaro، نويسنده , , Ronit and Mamluk، نويسنده , , Roni and Wang، نويسنده , , Ling and Short، نويسنده , , Sarah M. and Nagy، نويسنده , , Janice A. and Feng، نويسنده , , Dian and Dvorak، نويسنده , , Ann M. and Dvorak، نويسنده , , Harold F. and Puder، نويسنده , , Mark and Mukhopadhyay، نويسنده , , Debabrata and Folkman، نويسنده , , Judah، نويسنده ,
Abstract :
Summary
enesis 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.
