拓扑替康成功治疗皮下生长的人肝母细胞瘤异种移植瘤。

Successful therapy of subcutaneously growing human hepatoblastoma xenografts with topotecan.

作者信息

Warmann S W, Fuchs J, Wilkens L, Gratz K F, von Schweinitz D, Mildenberger H

机构信息

Department of Pediatric Surgery, Medical School Hannover, Carl-Neuberg-Str.1, 30625 Hannover, Germany.

出版信息

Med Pediatr Oncol. 2001 Nov;37(5):449-54. doi: 10.1002/mpo.1228.

DOI:10.1002/mpo.1228

PMID:11745873

Abstract

BACKGROUND

Human hepatoblastoma is an infrequent liver tumor in children. Although many hepatoblastomas can be treated adequately with well-defined treatment regimens, problems still persist with advanced and non-resectable tumors; in these cases, an effective chemotherapy is necessary to improve the patients' prognosis. This underlines the need for alternative anti-tumor agents in the treatment of human hepatoblastoma. The aim of this study was to investigate the therapeutic effects of topotecan, a water-soluble camptothecin analog (topoisomerase-I-antagonist), in an in vivo model of three human hepatoblastomas xenografted subcutaneously into nude mice.

PROCEDURE

Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). Treatment with topotecan was initiated when the tumors reached a volume between 50 and 80 mm(3). A dose of 6.6 mg/kg of topotecan were given intraperitoneally every 4 days on four occasions. The tumor volume development and alpha-fetoprotein alterations were measured and statistically analyzed. After the treatment, the tumors were investigated histologically and by immunohistochemistry.

RESULTS

There was a significant reduction of tumor growth in all treated tumor xenografts vs. untreated control groups (mean relative volume 3.1 vs. 47.4; P = 0,0015-0,0079). Serum alpha-fetoprotein levels were reduced in all three cell lines, in two of them significantly (mean 44,535 kU/l vs. 228,883 kU/l; P = 0.005-0.246). Histologically, the tumor necrosis rates were higher and immunohistochemistry showed lower proliferation activities in the treated tumor xenografts vs. the control groups.

CONCLUSION

The data show that topotecan is an effective agent in the treatment of human hepatoblastoma xenografts. From these results, treatment with topotecan appears to be a promising alternative in the pre- and postoperative therapy of patients suffering from human hepatoblastoma

摘要

背景

人类肝母细胞瘤是儿童中一种罕见的肝脏肿瘤。尽管许多肝母细胞瘤可以通过明确的治疗方案得到充分治疗，但晚期和不可切除的肿瘤仍然存在问题；在这些情况下，有效的化疗对于改善患者预后是必要的。这突出了在人类肝母细胞瘤治疗中需要替代抗肿瘤药物。本研究的目的是在三种皮下移植到裸鼠体内的人类肝母细胞瘤异种移植体内模型中研究拓扑替康（一种水溶性喜树碱类似物，拓扑异构酶-I拮抗剂）的治疗效果。

程序

将来自三名儿童的肝母细胞瘤细胞悬液皮下移植到NMRI裸鼠（nu/nu）体内。当肿瘤体积达到50至80立方毫米时开始用拓扑替康治疗。每4天腹腔注射一次剂量为6.6毫克/千克的拓扑替康，共注射四次。测量并统计分析肿瘤体积的变化和甲胎蛋白的改变。治疗后，对肿瘤进行组织学和免疫组织化学研究。

结果

与未治疗的对照组相比，所有接受治疗的肿瘤异种移植瘤的肿瘤生长均显著减少（平均相对体积3.1对47.4；P = 0.0015 - 0.0079）。所有三种细胞系的血清甲胎蛋白水平均降低，其中两种显著降低（平均44535 kU/l对228883 kU/l；P = 0.005 - 0.246）。组织学上，与对照组相比，治疗后的肿瘤异种移植瘤的肿瘤坏死率更高，免疫组织化学显示增殖活性更低。