Clinical significance of gene amplification studied in human neuroblastoma xenografts: relationship with tumor growth rate, chemotherapeutic sensitivities and levels of neuron-specific enolase.
Tumor doubling time, sensitivity to chemotherapeutic agents and concentrations of neuron-specific enolase were studied in nine human neuroblastoma xenografts, in which amplifications of N-myc, clones 8 and G21 were known; N-myc was amplified in eight, clone 8 in five and clone G21 in four of these nine xenografts. Tumor doubling time was longest in one xenograft, TNB10, which lacks the amplification of either N-myc or clone 8 or G21, and shortest in TNB1 in which all three DNA sequences are amplified with a DNA rearrangement in clone 8. No correlations were found between genomic amplification of N-myc, clones 8 and G21 and effectiveness of five chemotherapeutic drugs tested, except for cis-platinum. cis-Platinum was found to be effective on all but the one xenograft, TNB10, with the longest tumor doubling time. Concentration of neuron-specific enolase in tumor extract was lowest in TNB1 and correlated with the length of the tumor doubling time.
Tsuchida
Y
Y
Department of Surgery, National Children's Hospital, Tokyo, Japan.
Kanda
N
N
Shimatake
H
H
Kaneko
Y
Y
Notomi
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005784:Gene Amplification / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D009857:Oncogenes / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*
D000970:Antineoplastic Agents; D010751:Phosphopyruvate Hydratase