Fuchs J, Habild G, Leuschner I, Schweinitz D V, Haindl J, Knop E
Department of Pediatric Surgery, Medical School Hannover, Germany.
Med Pediatr Oncol. 1999 Mar;32(3):209-15. doi: 10.1002/(sici)1096-911x(199903)32:3<209::aid-mpo8>3.0.co;2-0.
Hepatoblastoma is an uncommon liver tumor of infancy and early childhood. Though most patients with nonmetastatic hepatoblastomas can be cured by defining surgical strategies and chemotherapy regimes, new drugs are needed for children with advanced hepatoblastomas. The activity of paclitaxel as a new antineoplastic agent with limited experience in pediatric oncology was studied in a xenograft model.
Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). One of the primary tumors was an embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized on a liver lobe. After 4 weeks, xenografted tumor sizes reached 50-100 mm3. The xenografted tumors resembled their originals histologically and produced high levels of alpha-fetoprotein. The efficiency of paclitaxel at equitoxic doses was analyzed.
Paclitaxel produced an effect in all three hepatoblastomas. There was a significant reduction of tumor volume (P < 0.001) and alpha-fetoprotein levels after chemotherapy (P < 0.0001). The proliferation activity of the tumor cells corresponded with these results. Histologically, after treatment with paclitaxel the tumor regression was 35%-49%. The mechanism of paclitaxel action could be demonstrated by light microscopy immunohistochemistry and electron microscopy.
The preliminary results in phase I trials of solid tumors in children and the results of this study suggest that paclitaxel in phase II studies can now be entertained for patients with hepatoblastoma.
肝母细胞瘤是婴幼儿期一种罕见的肝脏肿瘤。尽管大多数非转移性肝母细胞瘤患者可通过制定手术策略和化疗方案治愈，但晚期肝母细胞瘤患儿仍需要新的药物。在异种移植模型中研究了紫杉醇作为一种在儿科肿瘤学中经验有限的新型抗肿瘤药物的活性。
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。其中一个原发性肿瘤是胚胎性多灶性肝母细胞瘤，而其他肿瘤是位于肝叶的胚胎性/胎儿性肝母细胞瘤。4周后，异种移植肿瘤大小达到50 - 100立方毫米。异种移植肿瘤在组织学上与其原发肿瘤相似，并产生高水平的甲胎蛋白。分析了等毒性剂量下紫杉醇的疗效。
紫杉醇对所有三种肝母细胞瘤均产生了作用。化疗后肿瘤体积显著减小（P < 0.001），甲胎蛋白水平显著降低（P < 0.0001）。肿瘤细胞的增殖活性与这些结果相符。组织学上，紫杉醇治疗后肿瘤消退率为35% - 49%。紫杉醇的作用机制可通过光学显微镜免疫组织化学和电子显微镜得以证实。
儿童实体瘤I期试验的初步结果以及本研究的结果表明，现在可以考虑在II期研究中对肝母细胞瘤患者使用紫杉醇。
