title: Arginine deiminase and other antiangiogenic agents inhibit unfavorable neuroblastoma growth: potentiation by irradiation.
abstract: In spite of aggressive therapy, children suffering from neuroblastoma have a poor prognosis. Therapeutic failure is most often observed in neuroblastomas with unfavorable features, including amplification/over-expression of the N-myc oncogene, rapid growth, effective angiogenesis and/or the tendency to metastasize. Here, we have used cultured human neuroblastoma cells with such features and we have examined whether antiangiogenic agents alone or in combination with tumor irradiation inhibit their angiogenesis and growth in vivo. We report that antiangiogenic agents (arginine deiminase, SU5416 and DC101) inhibit in vivo growth of neuroblastomas with unfavorable properties and that these effects are potentiated by simultaneous irradiation. Combination of either agent with irradiation leads to a reduction in the absolute number of tumor vessels and of perfused tumor vessels. Combination of arginine deiminase or DC101 with irradiation does not increase tumor hypoxia. Our data demonstrate for the first time that arginine deiminase suppresses the growth of unfavorable experimental neuroblastomas and that this effect is potentiated by irradiation. We suggest that antiangiogenesis alone or in combination with established therapeutic regimen may improve the outcome of unfavorable neuroblastomas in a clinical setting.
authors.affiliation: Department of Hematology, Oncology and Endocrinology, Children's Hospital, University of Essen, Essen, Germany.
authors.forename: Hong
authors.initials: H
authors.lastname: Gong
authors.forename: Christoph
authors.initials: C
authors.lastname: Pöttgen
authors.forename: Georg
authors.initials: G
authors.lastname: Stüben
authors.forename: Werner
authors.initials: W
authors.lastname: Havers
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke
authors.forename: Lothar
authors.initials: L
authors.lastname: Schweigerer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D015687:Cell Hypoxia; D003131:Combined Modality Therapy; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006867:Hydrolases / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib; D011505:Protein-Tyrosine Kinases; D006867:Hydrolases; C019723:arginine deiminase