TY - JOUR
T1 - Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin
AU - Satchi-Fainaro, Ronit
AU - Mamluk, Roni
AU - Wang, Ling
AU - Short, Sarah M.
AU - Nagy, Janice A.
AU - Feng, Dian
AU - Dvorak, Ann M.
AU - Dvorak, Harold F.
AU - Puder, Mark
AU - Mukhopadhyay, Debabrata
AU - Folkman, Judah
N1 - Funding Information:
We thank the Fulbright and the Rothschild Foundations (R.S.-F.), the National Institutes of Health (NIH) (research grant R01 CA064481 to R.S.-F. and J.F.), and the Breast Cancer Research Foundation for their financial support. This work is also partly supported by NIH research grants P01 CA45548 and R01 CA37395 (J.F.) and HL70567 and HL072178 (D.M.). The excellent technical assistance of Amy E. Birsner, Rachel W. Winter, and Ludmila M. Dobesova-Flores is acknowledged. We thank Kristin Gullage for photography and graphic art. We thank Shay Soker, Akiko Mammoto, and Sui Huang for useful discussions and Steven A. Rosenberg for the generous gift of IL-2.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20244381828&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2005.02.007
DO - 10.1016/j.ccr.2005.02.007
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AN - SCOPUS:20244381828
SN - 1535-6108
VL - 7
SP - 251
EP - 261
JO - Cancer Cell
JF - Cancer Cell
IS - 3
ER -
