Angiogenesis inhibitor TNP-470 inhibits murine cutaneous wound healing.

作者: Scott A. Klein , Sheldon J. Bond , Subhas C. Gupta , Oraib A. Yacoub , Gary L. Anderson

DOI: 10.1006/JSRE.1998.5551

关键词:

摘要: Background.TNP-470 (AGM-1470) is a potent inhibitor of angiogenesis with potential therapeutic applications in neoplastic and angio-proliferative diseases. This study evaluated its effect on cutaneous wound healing murine dorsal excisional model. Materials methods.Full-thickness wounds (1.60 cm2) were created the dorsum homozygous/hairless mice (7 to 9 weeks). Wound areas measured alternate days for 16 days. Experimental groups consisted (1) TNP-470 administered doses 0.05, 0.5, 5.0 mg/kg Days 0, 2, 4 or 0 through 6; (2) (5.0 mg/kg) coadministered minocycline (4.0 10 4; (3) 4) topical basic fibroblast growth factor (bFGF) 1.0 μg/wound 1, 2. Hematoxylin eosin staining was used compare experimental control wounds. Results.TNP-470 administration significantly decreased dose-dependent manner versus controls (P< .05). The concentration yielded greatest by maintaining an average area 20.4% greater than marked delay H&E staining. Alternate-day dosing as effective consecutive day administration. Minocycline did not augment inhibition TNP-470. Coadministration bFGF eliminated any rate-altering upon resulted similar controls. Conclusion.Therapy induces significant healing. may be exploited use situations where excessive debilitating. Topical application can overcome TNP-470-induced inhibition.

参考文章(21)
T A Mustoe, J E Tarpley, G F Pierce, G M Fox, D Yanagihara, A Thomason, Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair. American Journal of Pathology. ,vol. 140, pp. 1375- 1388 ,(1992)
H. Kim Lyerly, [edited by] David C. Sabiston, Sabiston's Essentials of Surgery ,(1987)
Jack L Arbiser, Angiogenesis and the skin: A primer Journal of the American Academy of Dermatology. ,vol. 34, pp. 486- 497 ,(1996) , 10.1016/S0190-9622(96)90444-2
Harold Brem, Judah Folkman, Analysis of experimental antiangiogenic therapy Journal of Pediatric Surgery. ,vol. 28, pp. 445- 451 ,(1993) , 10.1016/0022-3468(93)90246-H
Donald Ingber, Takeshi Fujita, Shoji Kishimoto, Katsuichi Sudo, Tsuneo Kanamaru, Harold Brem, Judah Folkman, Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature. ,vol. 348, pp. 555- 557 ,(1990) , 10.1038/348555A0
Michael S O'Reilly, Harold Brem, Judah Folkman, Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470 Journal of Pediatric Surgery. ,vol. 30, pp. 325- 330 ,(1995) , 10.1016/0022-3468(95)90583-9
Masami Kusaka, Katsuichi Sudo, Takeshi Fujita, Shogo Marui, Fumio Itoh, Donald Ingber, Judah Folkman, Potent anti-angiogenic action of AGM-1470 : comparison to the fumagillin parent Biochemical and Biophysical Research Communications. ,vol. 174, pp. 1070- 1076 ,(1991) , 10.1016/0006-291X(91)91529-L
Erle E. Peacock, Wound contraction and scar contracture. Plastic and Reconstructive Surgery. ,vol. 62, pp. 600- 601 ,(1978) , 10.1097/00006534-197810000-00020
W.Thomas Lawrence, Robert F. Diegelmann, Growth factors in wound healing. Clinics in Dermatology. ,vol. 12, pp. 157- 169 ,(1994) , 10.1016/0738-081X(94)90266-6