Fuchs J, Wenderoth M, von Schweinitz D, Haindl J, Leuschner I
Department of Pediatric Surgery, Medical School Hannover, Germany.
Cancer. 1998 Dec 1;83(11):2400-7. doi: 10.1002/(sici)1097-0142(19981201)83:11<2400::aid-cncr21>3.0.co;2-6.
Hepatoblastoma is the most common primary malignant liver tumor affecting infants and young children. Recent clinical experience with advanced hepatoblastoma shows that a reliable in vivo model to study the tumor's response to drugs is needed urgently.
Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into NMRI nude mice (nu/nu). One of the primary tumors was a embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized to one liver lobe. The xenograft tumors resembled their original tumors histologically and produced high levels of alpha-fetoprotein. The mice who received the tumors were given ifosfamide, cisplatin, doxorubicin, carboplatin, and etoposide as single agents. Thereafter, the tumor growth rate and alpha-fetoprotein levels in the animal sera were measured before and after chemotherapy and compared with the control group. After chemotherapy, the tumors were studied by conventional histology.
The tumors in the nude mice derived from the multifocal hepatoblastoma reacted minimally against four of the five cytotoxic agents, whereas cisplatin reduced the tumor volume significantly. There was a marked reduction in tumor volume in the other tumors after application of cisplatin and doxorubicin, respectively. The tumors displayed a moderate reduction in size after treatment with ifosfamide, etoposide, and carboplatin. The responses to the different cytostatic agents also corresponded with serum alpha-fetoprotein levels and mitotic rates in the tumor cells.
To the authors' knowledge, this is the first time an in vivo model for analyzing the effects of chemotherapy on hepatoblastoma has been established. The animal model may be suited for the evaluation of new drugs for the treatment of hepatoblastoma and for the investigation of multidrug resistance mechanisms in hepatoblastoma.
肝母细胞瘤是影响婴幼儿的最常见原发性肝脏恶性肿瘤。近期晚期肝母细胞瘤的临床经验表明，迫切需要一种可靠的体内模型来研究肿瘤对药物的反应。
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，而其他肿瘤是局限于一个肝叶的胚胎性/胎儿性肝母细胞瘤。异种移植肿瘤在组织学上与其原始肿瘤相似，并产生高水平的甲胎蛋白。接受肿瘤移植的小鼠分别接受异环磷酰胺、顺铂、阿霉素、卡铂和依托泊苷单药治疗。此后，在化疗前后测量动物血清中的肿瘤生长速率和甲胎蛋白水平，并与对照组进行比较。化疗后，通过常规组织学对肿瘤进行研究。
源自多灶性肝母细胞瘤的裸鼠肿瘤对五种细胞毒性药物中的四种反应极小，而顺铂显著减小了肿瘤体积。分别应用顺铂和阿霉素后，其他肿瘤的体积明显减小。用异环磷酰胺、依托泊苷和卡铂治疗后，肿瘤大小有中度减小。对不同细胞抑制剂的反应也与肿瘤细胞中的血清甲胎蛋白水平和有丝分裂率相对应。
据作者所知，这是首次建立用于分析化疗对肝母细胞瘤影响的体内模型。该动物模型可能适用于评估治疗肝母细胞瘤的新药以及研究肝母细胞瘤中的多药耐药机制。
