The angiogenesis inhibitor TNP-470 reduces the growth rate of human neuroblastoma in nude rats

Pediatr Res. 1997 Mar;41(3):327-33. doi: 10.1203/00006450-199703000-00004.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use*
  • Autonomic Nervous System Diseases / drug therapy*
  • Autonomic Nervous System Diseases / pathology
  • Cell Survival / drug effects
  • Cyclohexanes
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Electron
  • Neovascularization, Pathologic / drug therapy*
  • Neuroblastoma / blood supply
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Rats
  • Rats, Nude
  • Sesquiterpenes / therapeutic use*
  • Transplantation, Heterologous


  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol