Mohseni Mohammad-Javad, Amanpour Saeid, Muhammadnejad Samad, Sabetkish Shabnam, Muhammadnejad Ahad, Heidari Reza, Haddadi Mahnaz, Mazaheri Zohreh, Vasei Mohammad, Kajbafzadeh Abdol-Mohammad
Pediatric Urology Research Center, Children's Center of Excellence, Department of Pediatric Urology, Islamic Republic of Iran.
Department of Experimental Research, Cancer Research Center, Iranian Cancer Institute, Islamic Republic of Iran.
J Pediatr Urol. 2014 Feb;10(1):123-9. doi: 10.1016/j.jpurol.2013.07.009. Epub 2013 Aug 26.
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.
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.
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.
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.
缺乏可靠预测肾母细胞瘤（WT）对抗癌药物反应的合适方法仍然是个体化癌症治疗临床实践中的一个主要缺陷。本研究的目的是建立一个WT的患者来源肿瘤组织（PDTT）异种移植模型，以便根据患者肿瘤的性质选择个体化化疗方案。
将原发性WT的肿瘤标本原位植入三只裸鼠体内，4周后收获异种移植瘤，在20只裸鼠中进行连续异位移植，这些裸鼠分为三个实验组和一个对照组。评估对阿霉素、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）染色以及用结蛋白、波形蛋白、肌细胞生成素和神经元特异性烯醇化酶（NSE）进行免疫组化检查，以确定与原始肿瘤组织相比，异种移植瘤在连续移植过程中的组织学稳定性。
成功建立了异种移植模型。异种移植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学敏感性模式。
WT的PDTT异种移植通过与原始患者肿瘤相比具有生物学稳定性，为个体化癌症治疗方案的选择提供了一个合适的模型。
