Matsusaka S, Nakasho K, Terada N, Sugihara A, Tsujimura T, Takanashi T, Uematsu K, Okamoto E, Toyosaka A
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
J Pediatr Surg. 2000 Aug;35(8):1198-204. doi: 10.1053/jpsu.2000.8726.
BACKGROUND/PURPOSE: The effect of TNP-470, an angiogenesis inhibitor, on the growth of a hepatoblastoma transplanted into nude mice was examined.
A hepatoblastoma obtained from a 3-year-old girl was serially transplanted into nude mice subcutaneously, and the transplant tumors of the seventh and eighth generations were used for experiments. Expression of various markers in the tumors was examined immunohistochemically. TNP-470 was injected subcutaneously every other day into tumor-bearing mice from 3 weeks after tumor transplantation. The proliferation of tumor cells and endothelial cells was estimated by means of the bromodeoxyuridine labeling index.
The original hepatoblastoma showed the histology of the epithelial type, consisting of both the fetal and embryonal subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti-cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors consisted of solid nests of tumor cells with numerous vascular lakes of various sizes, and showed positive staining with all antibodies that reacted positively with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and 30 mg/kg body weight suppressed the tumor growth and the increase in the serum level of AFP dose dependently. Injections of TNP-470 also suppressed the proliferation of tumor cells and endothelial cells in the tumors.
Hepatoblastomas maintained in nude mice retained the immunohistochemical characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth of hepatoblastomas transplanted into nude mice. TNP-470 may be worth investigating further as to its usefulness as a therapy for hepatoblastomas.
背景/目的：研究血管生成抑制剂TNP - 470对移植到裸鼠体内的肝母细胞瘤生长的影响。
将一名3岁女孩的肝母细胞瘤连续皮下移植到裸鼠体内，使用第七代和第八代移植瘤进行实验。通过免疫组织化学检测肿瘤中各种标志物的表达。从肿瘤移植后3周起，每隔一天给荷瘤小鼠皮下注射TNP - 470。通过溴脱氧尿苷标记指数评估肿瘤细胞和内皮细胞的增殖情况。
原发肝母细胞瘤显示为上皮型组织学，由胎儿型和胚胎型亚型组成，抗甲胎蛋白（AFP）、抗细胞角蛋白-19和多克隆抗癌胚抗原抗体以及抗人肝细胞抗体（肝细胞石蜡1）染色均呈阳性。移植瘤由肿瘤细胞的实性巢组成，伴有许多大小各异的血管湖，并且与所有与原发肝母细胞瘤呈阳性反应的抗体均呈阳性染色。以15mg和30mg/kg体重的剂量注射TNP - 470可剂量依赖性地抑制肿瘤生长和血清AFP水平的升高。注射TNP - 470还可抑制肿瘤中肿瘤细胞和内皮细胞的增殖。
在裸鼠体内维持的肝母细胞瘤保留了原发肝母细胞瘤的免疫组织化学特征，并且TNP - 470可抑制移植到裸鼠体内的肝母细胞瘤的生长。TNP - 470作为肝母细胞瘤的一种治疗方法的有效性可能值得进一步研究。
