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    Cancer Cell. 2005 Mar;7(3):251-61.

    Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin.

    Satchi-Fainaro R, Mamluk R, Wang L, Short SM, Nagy JA, Feng D, Dvorak AM, Dvorak HF, Puder M, Mukhopadhyay D, Folkman J.

    Children's Hospital Boston and Harvard Medical School, Vascular Biology Program, Department of Surgery, 1 Blackfan Circle, Karp Family Research Laboratories, Floor 12, Boston, Massachusetts 02115, USA.

    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.

    PMID: 15766663 [PubMed - indexed for MEDLINE]

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