Inhibition of growth and angiogenesis of human neurofibrosarcoma by heparin and hydrocortisone.

A human neurofibrosarcoma was removed at surgery from a patient with neurofibromatosis and implanted into the subrenal capsule of female nude mice (nu/nu). A solid tumor grew and was transferred to 78 additional mice for this study. The animals were randomly assigned to one of four groups: 1) control, 27 animals; 2) oral heparin (200 or 500 U/ml), 17 animals; 3) oral hydrocortisone (0.3 mg/ml), 10 animals; or 4) oral heparin (200, 500, or 1000 U/ml) with hydrocortisone (0.3 mg/ml), 24 animals. After 10 days of treatment, the animals were sacrificed and the tumor size and degree of neovascularization were compared to the pretreatment data. Heparin treatment alone stimulated angiogenesis and resulted in tumor growth greater than in the control group (p less than 0.001). Administration of hydrocortisone alone caused a minimal reduction in tumor growth and had a minimal effect on angiogenesis (p less than 0.05 vs. control group). In contrast, heparin administered with hydrocortisone inhibited both angiogenesis and tumor growth (p less than 0.001 vs. control group). These studies suggest that angiogenesis modulators are worthy of further study as feasible means of treating human neurofibrosarcoma.