Analysis of experimental antiangiogenic therapy.
Angiogenesis is a fundamental process by which new blood vessels are formed. Progressive tumor growth necessitates the continuous induction of new capillary blood vessels which converge upon the tumor. Suppression of tumor growth can be accomplished with the use of antiangiogenesis agents. AGM-1470 is a potent angiogenesis inhibitor in vitro and in vivo. In mouse studies, AGM-1470 has suppressed the growth and neovascularization induced by four murine tumors resulting in a 55% to 77% decrease in tumor growth. In these mice significant toxicity did not result from AGM-1470 therapy. AGM-1470 administered systemically to C57BI/6 male mice for 20 to 28 days inhibited the growth of: (1) Lewis lung carcinoma resulting in a T/C (treatment/control = mean tumor volume of treated/mean tumor volume of control) of 0.38 +/- 0.03 (P < .001); (2) colon adenocarcinoma 38 resulting in a T/C of 0.23 +/- 0.02 (P < .001); and (3) fibrosarcoma 105 resulting in a T/C of 0.31 +/- 0.05 (P < .001). To determine if antiangiogenic therapy was equally effective in mice of both sexes and in immunodeficient animals, we tested AGM-1470 in the treatment of fibrosarcoma 105 in both female mice and nude mice. For female mice T/C was 0.24 +/- 0.06 (P < .001). For nude mice T/C was 0.27 +/- 0.06 (P < .001). These results demonstrate that AGM-1470 suppresses the growth of a variety of different tumors. Furthermore, the antitumor effect of AGM-1470 therapy is independent of the immune system and sex.
Brem
H
H
Department of Surgery, Children's Hospital, Boston, MA 02115.
Folkman
J
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001835:Body Weight; D003106:Colon / Q000098:blood supply*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003510:Cyclohexanes; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016867:Immunocompromised Host; D008168:Lung / Q000098:blood supply*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*; D012737:Sex Factors
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol