title: CHS 828 inhibits neuroblastoma growth in mice alone and in combination with antiangiogenic drugs.
abstract: CHS 828 is a new chemotherapeutic drug, a pyridyl cyanoguanidine. CHS 828 has low toxicity and lacks known patterns of multidrug resistance. Here we report that oral, daily treatment with CHS 828 reduced the growth of SH-SY5Y human neuroblastoma tumors in male NMRI nu/nu mice by 82% without apparent toxicity. CHS 828 induced complete tumor regression for at least 5 weeks in four of nine animals (44%). Combination therapy with CHS 828 and the antiangiogenic drugs TNP-470 or SU5416 decreased neuroblastoma growth by a further 10 and 3%, respectively. Combination therapy induced tumor regression at d 4 with CHS plus TNP and d 6 with CHS plus SU5416, compared with d 14 with CHS 828 alone (p < 0.05), and complete tumor regression was seen in nine of 19 animals (47%). Combination treatment of CHS 828 and TNP-470 decreased the total viable tumor volume by 71% compared with treatment with CHS 828 alone. Our findings support CHS 828 as a promising new drug in treatment of childhood cancers. Furthermore, they imply efficiency of daily administration of nontoxic doses of chemotherapy, and a possible additive effect when chemotherapy is combined with angiogenesis inhibitors.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Sweden. Asa.Svensson@medcellbiol.uu.se
authors.forename: Asa
authors.initials: A
authors.lastname: Svensson
authors.forename: Ulrika
authors.initials: U
authors.lastname: Bäckman
authors.forename: Elin
authors.initials: E
authors.lastname: Jonsson
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Rolf
authors.initials: R
authors.lastname: Christofferson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003486:Cyanides / Q000008:administration & dosage / Q000627:therapeutic use*; D003510:Cyclohexanes; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009447:Neuroblastoma / Q000098:blood supply / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D003486:Cyanides; D003510:Cyclohexanes; D006146:Guanidines; D007211:Indoles; C401312:N-(6-chlorophenoxyhexyl)-N''-cyano-N''-4-pyridylguanidine; D011758:Pyrroles; D012717:Sesquiterpenes; C116890:Semaxinib; D000077609:O-(Chloroacetylcarbamoyl)fumagillol