Komuro H, Li P, Tsuchida Y, Yokomori K, Nakajima K, Aoyama T, Kaneko M, Kaneda N
Department of Pediatric Surgery, University of Tokyo, Japan.
Med Pediatr Oncol. 1994;23(6):487-92. doi: 10.1002/mpo.2950230607.
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.
尽管神经母细胞瘤的治疗已取得诸多进展，但晚期神经母细胞瘤患者的预后仍然很差，人们一直在不断努力寻找更新的有效药物。CPT-11是一种新开发的喜树碱衍生物，通过抑制DNA拓扑异构酶I显示出独特的抗肿瘤活性。在本研究中，根据巴特尔哥伦布实验室的标准方案，研究了CPT-11对人神经母细胞瘤异种移植瘤TNB9的作用。TNB9是神经母细胞瘤中最恶性的菌株之一，在20号染色体上显示出均匀染色区（HSR），N-myc基因扩增80倍。本研究表明CPT-11对TNB9高度有效。标准剂量下的最大抑制率（IR）为72.5%，即使在半剂量时也为52.8%。本研究中使用的裸鼠在给予CPT-11后体重均未减轻。将该实验模型中给予CPT-11后的血浆药代动力学与临床患者的进行了比较。我们的数据表明，CPT-11可能是治疗高危神经母细胞瘤患者的一种有前景的新药，并鼓励我们在日本研究小组的方案中使用CPT-11。
