Effects of CPT-11 (a unique DNA topoisomerase I inhibitor) on a highly malignant xeno-transplanted neuroblastoma.
Although many advances have been made in the management of neuroblastoma, the prognosis of patients with advanced neuroblastoma remains poor, and constant efforts are being made to search for newer effective drugs. CPT-11 is a newly developed derivative of camptothecin and shows a unique anti-tumor activity by inhibiting DNA topoisomerase I. In this study the effects of CPT-11 on a human neuroblastoma xenograft, TNB9, were investigated according to the standard Battelle Columbus Laboratories protocol. TNB9 is one of the most malignant strains of neuroblastoma, showing a homogeneously staining resion (HSR) on chromosome 20 and 80-fold amplification of the N-myc gene. This study disclosed that CPT-11 was highly effective against TNB9. Maximum inhibition rate (IR) was 72.5% at a standard dose and 52.8% even at half the dose. No nude mouse used in this study lost weight after an administration of CPT-11. Plasma pharmacokinetics of CPT-11 administered in this experimental model were compared to that in clinical patients. Our data suggested that CPT-11 might be a promising new drug in the treatment of high-risk neuroblastoma patients and encouraged us to employ CPT-11 in the protocol of the Study Group of Japan.
Komuro
H
H
Department of Pediatric Surgery, University of Tokyo, Japan.
Li
P
P
Tsuchida
Y
Y
Yokomori
K
K
Nakajima
K
K
Aoyama
T
T
Kaneko
M
M
Kaneda
N
N
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D002890:Chromosomes, Human, Pair 20; D004264:DNA Topoisomerases, Type I / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D016259:Genes, myc; D006801:Humans; D007274:Injections, Intraperitoneal; D000077146:Irinotecan; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D059004:Topoisomerase I Inhibitors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin