1] Kidney Cancer Program, University of Texas (UT) Southwestern Medical Center, Dallas, Texas, USA. [2] Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA. [3] Department of Developmental Biology, UT Southwestern Medical Center, Dallas, Texas, USA. [4] Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas, USA.
Nat Protoc. 2014 Aug;9(8):1848-59. doi: 10.1038/nprot.2014.108. Epub 2014 Jul 10.
Traditionally, xenograft models have been used to study tumors in vivo. However, their utility is reduced by the use of tumor cell lines for implantation. Tumorgrafts (TGs; also known as patient-derived xenografts (PDXs)), which involve patient-derived tumor samples, are increasingly recognized as more representative models than traditional xenografts. Furthermore, we showed previously that renal cell carcinoma (RCC) TGs retain the histology, gene expression, DNA copy number alterations, mutations and treatment responsiveness of patient tumors. In skilled hands, implantations require ≤5 min per mouse, and TGs typically grow to 1 cm in 1-4 months. Here we outline the process of implantation of patient-derived RCC samples into the kidneys of immunodeficient mice, as well as the s.c. implantation for preclinical drug testing, including guidelines for the design and execution of drug trials. TGs have extensive applications besides therapeutic studies and may identify biomarkers and mechanisms of resistance. In addition, they may provide insights into tumor biology.
传统上，异种移植模型被用于在体内研究肿瘤。然而，由于使用肿瘤细胞系进行植入，其效用降低。肿瘤移植（TG；也称为患者来源的异种移植物（PDX））涉及患者来源的肿瘤样本，被认为比传统异种移植更具代表性。此外，我们之前表明，肾细胞癌（RCC）TG 保留了患者肿瘤的组织学、基因表达、DNA 拷贝数改变、突变和治疗反应性。在熟练的手中，每个小鼠的植入时间需要≤5 分钟，并且 TG 通常在 1-4 个月内长到 1 厘米。在这里，我们概述了将患者来源的 RCC 样本植入免疫缺陷小鼠肾脏的过程，以及用于临床前药物测试的皮下植入，包括药物试验设计和执行的指南。TG 除了治疗研究外还有广泛的应用，可能会鉴定出生物标志物和耐药机制。此外，它们可能为肿瘤生物学提供深入了解。
