Establishment of a patient-derived Wilms' tumor xenograft model: A promising tool for individualized cancer therapy

Establishment of a patient-derived Wilms' tumor xenograft model: A promising tool for individualized cancer therapy
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DOI:
10.1016/j.jpurol.2013.07.009
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发表时间:
2014-02-01
影响因子:
2
通讯作者:
Kajbafzadeh, Abdol-Mohammad
Kajbafzadeh, Abdol-Mohammad
中科院分区:
医学4区
文献类型:
--
作者:
Mohseni, Mohammad-Javad;Amanpour, Saeid;Kajbafzadeh, Abdol-Mohammad

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目的:缺乏可靠预测肾母细胞瘤(WT)对抗癌药物反应的适当方法仍然是个体化癌症治疗临床实践的主要缺陷。本研究的目的是建立WT的患者来源肿瘤组织(PDTT)异种移植模型,以便根据患者的肿瘤性质选择个体化化疗方案。材料与方法:将原发性WT的肿瘤标本原位植入3只裸鼠中,4周后收获异种移植物,对20只裸鼠进行连续异位移植,分为3个实验组和1个对照组。评估了对阿霉素、放线菌素-D 和长春新碱的体外和体内化学敏感性。还应用苏木精和伊红(H&E)染色以及结蛋白、波形蛋白、肌细胞生成素和神经元特异性烯醇化酶(NSE)的免疫组织化学检查来确定异种移植物在连续移植过程中与原始肿瘤组织相比的组织学稳定性。结果:异种移植物模型成功建立。异种移植肿瘤的组织病理学特征与患者的肿瘤相似。 PDTT的早期传代表现出与原始肿瘤组织相似的化疗敏感性模式。结论:WT的PDTT异种移植物凭借其与原始患者肿瘤相比的生物稳定性,为个体化癌症治疗方案的选择提供了合适的模型。 (C) 2013 年儿科泌尿外科杂志公司。由爱思唯尔有限公司出版。保留所有权利。
Objective: Lack of appropriate approaches that reliably predict response of Wilms' tumor (WT) to anticancer agents remains a major deficiency in clinical practice of individualized cancer therapy. The aim of this study was to establish a patient-derived tumor tissue (PDTT) xenograft model of WT for individualized chemotherapeutic regimen selection in accordance with the patient's tumor nature.Material and methods: Tumor specimens of a primary WT were orthotopically implanted into three nude mice, and after 4 weeks xenografts were harvested for serial heterotopic transplantation in 20 nude mice that were divided into three experimental groups and one control group. In vitro and in vivo chemosensitivity to doxorubicin, actinomycin-D, and vincristine were evaluated. Hematoxylin and eosin (H&E) staining and immunohistochemical examination with desmin, vimentin, myogenin, and neuron-specific enolase (NSE) were also applied to determine histological stability of the xenograft during serial transplantation compared with the original tumor tissue.Results: The xenograft model was successfully established. Histopathologic characteristics of the xenograft tumors were similar to the patient's tumor. Early passage of the PDTT showed a similar chemosensitivity pattern to the original tumor tissue.Conclusions: PDTT xenograft of WT provides an appropriate model for individualized cancer therapeutic regimen selection by means of its biological stability compared with original patient's tumor. (C) 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.