Journal
CANCER CELL
Volume 7, Issue 3, Pages 251-261Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2005.02.007
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Funding
- NCI NIH HHS [P01 CA45548, R01 CA064481, R01 CA37395] Funding Source: Medline
- NHLBI NIH HHS [HL70567, HL072178] Funding Source: Medline
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Angiogenesis inhibitors, such as TNP-470 and the nontoxic HIPMA 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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