The angiogenesis inhibitor TNP-470 reduces the growth rate of human neuroblastoma in nude rats.
A new animal experimental model of human neuroblastoma is described. The model involves xenotransplantation of a poorly differentiated human neuroblastoma cell line (SH-SY5Y) to the subcutaneous tissue in the hind leg of nude rats (WAG mu/rnu). Injection of 20 million cells suspended in 0.2 mL of medium in each hind leg yielded an 89% tumor take (41/46) in 23 nude rats. Tumor take was evident after 2 wk. The tumors grew exponentially and reached a volume of 5.2 +/- 1.6 mL 4 wk after transplantation. The tumor cells retained their morphologic phenotype at the ultrastructural level after transplantation and were immunohistochemically positive for neuron-specific enolase and for chromogranins A and B. Subcutaneous injections of the angiogenesis inhibitor TNP-470 (10 mg/kg of body weight) every other day gave a treated/control quotient for mean tumor volume of 0.34 after 12 d of treatment. This implies that angiogenesis inhibition may be of value as a complement to chemotherapy in the treatment of human neuroblastoma. The presented animal experimental model is designed for investigations of the effects of chemotherapy, angiogenesis inhibitors, radiotherapy, and/or surgery on the growth rate of human neuroblastoma.
Wassberg
E
E
Department of Human Anatomy, University of Uppsala, Sweden.
Påhlman
S
S
Westlin
J E
JE
Christofferson
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003510:Cyclohexanes; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009447:Neuroblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D011923:Rats, Nude; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol