Inhibition of angiogenesis and growth of human nerve-sheath tumors by AGM-1470.
The effectiveness of AGM-1470, a potent, fungal-derived inhibitor of angiogenesis, in suppressing the neovascularization and growth of human Schwann cell tumors was tested in six schwannomas, seven neurofibromas, and one neurofibrosarcoma. Tumor fragments from surgical specimens were implanted into the subrenal capsule of 348 nude mice (nu/nu). Seven days after implantation, the tumors were measured and vascularity was graded. The animals were then randomly assigned to one of two groups, to receive either saline (control group) or systemic AGM-1470 treatment. After 2 to 6 weeks of treatment, tumor size and degree of vascularity were recorded. In the six different schwannomas implanted into 138 mice, the average vascular grade in the control group after 2 weeks of treatment increased from 2.2 to 3.2 (+1.0), while in the AGM-1470-treated group it decreased from 2.2 to 1.7 (-0.5) (p < 0.01). In the seven different neurofibromas implanted into 158 mice, the change in the average vascular grade in control and AGM-1470-treated animals was +0.5 and -1.0, respectively (p < 0.01). In the one neurofibrosarcoma implanted into 52 mice, the change in average vascular grade in each group during the 6-week treatment period was +1.9 and -1.0, respectively (p < 0.01). Neurofibrosarcoma growth after 6 weeks of AGM-1470 treatment was only 8.5% of the growth found in the control animals (p < 0.01). This study determined that AGM-1470 is effective in inhibiting angiogenesis and the growth of human nerve-sheath tumors.
Takamiya
Y
Y
Neurosurgical Oncology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston.
Friedlander
R M
RM
Brem
H
H
Malick
A
A
Martuza
R L
RL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D003510:Cyclohexanes; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009442:Neurilemmoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009455:Neurofibroma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol