In Vivo and Ex Vivo Patient-Derived Tumor Xenograft Models of Lymphoma for Drug Discovery.
In Vivo and Ex Vivo Patient-Derived Tumor Xenograft Models of Lymphoma for Drug Discovery.
复制标题
DOI：
10.1002/cpz1.96
复制
发表时间：
2021-04-01
期刊：
影响因子：
--
通讯作者：
Inghirami, Giorgio
中科院分区：
文献类型：
--
作者：
Cacciapuoti, Maria Teresa;Cappelli, Luca Vincenzo;Inghirami, Giorgio
在血液肿瘤学领域，已经取得了显着的科学进步，主要是由新技术的发现，基因组学的改进和新的体外和体内模型推动的。多个细胞系集合的建立和仪器小鼠模型的开发增强了我们发现有效治疗方法的能力。然而，忠实地模拟个体癌症的癌症模型仍然是不完美的。患者源性肿瘤异种移植物（PDTX）已成为鉴定驱动肿瘤发生的机制和测试潜在治疗干预的有力工具。认识到PDTX可以保持供体样本的许多特性，从而开发了发现和实施治疗的新策略。在这篇文章中描述的是淋巴瘤PDTX的生成和表征的协议，可用作共享程序的基础。通用协议将促进模型的利用，使公共和私人存储库的整合，并在共享平台的发展援助。© 2021 Wiley Periodicals LLC.基本方案1：原代和PDTX样品的组织处理和冷冻保存基本方案2：在免疫缺陷小鼠中进行肿瘤植入PDTX模型替代方案1：髓内股注射替代方案2：静脉内注射替代方案3：腹膜内注射支持方案1：通过流式细胞术表征PDTX支持方案2：通过PCR检测IGK、IGH和TCR重排对PDTX肿瘤进行生物学和分子表征基本方案3：收获PDTX衍生的肿瘤细胞用于离体实验基本方案4：在PDTX小鼠模型中体内测试多种化合物。
In the hemato-oncology field, remarkable scientific progress has been achieved, primarily propelled by the discovery of new technologies, improvement in genomics, and novel in vitro and in vivo models. The establishment of multiple cell line collections and the development of instrumental mouse models enhanced our ability to discover effective therapeutics. However, cancer models that faithfully mimic individual cancers are still imperfect. Patient-derived tumor xenografts (PDTXs) have emerged as a powerful tool for identifying the mechanisms which drive tumorigenesis and for testing potential therapeutic interventions. The recognition that PDTXs can maintain many of the donor samples' properties enabled the development of new strategies for discovering and implementing therapies. Described in this article are protocols for the generation and characterization of lymphoma PDTXs that may be used as the basis of shared procedures. Universal protocols will foster the model utilization, enable the integration of public and private repositories, and aid in the development of shared platforms. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Tissue handling and cryopreservation of primary and PDTX samples Basic Protocol 2: Performing tumor implant in immunocompromised mice PDTX models Alternate Protocol 1: Intra-medullary femoral injection Alternate Protocol 2: Intravenous injection Alternate Protocol 3: Intraperitoneal injection Support Protocol 1: Phenotypical characterization of PDTXs by flow cytometry Support Protocol 2: Biological and molecular characterization of PDTX tumors by PCR detection of IGK, IGH, and TCR rearrangements Basic Protocol 3: Harvesting PDTX-derived tumor cells for ex vivo experiments Basic Protocol 4: In vivo testing of multiple compounds in a PDTX mouse model.