PDX Core

项目摘要/摘要 患者衍生异种移植(PDX)核心的主要目标将是建立和表征PDX， 为了支持UCATS的两个综合研究项目的研究目标，这是一个与差异相关的研究 PDX开发和试验中心(D-PDTC)。PDX核心将负责创建和 免疫缺陷小鼠(NSG)的120种PDX模型的特征 或肺癌，并在六个地点中的任何一个被诊断：NCI指定的五个综合癌症中心 (CCC)加州大学(UC)系统(戴维斯、洛杉矶、旧金山、欧文和圣地亚哥) 和德克萨斯大学西南CCC分校。所有新建立的PDX系都将来自肿瘤 从代表种族/少数民族的患者那里获得，基于我们预期的联合集水区 为拉美裔和亚裔美国人、夏威夷原住民/太平洋岛民(AANHPI)患者提供补充。这些PDX 模型将用于生成特定个体荷瘤(PDX)小鼠的队列，以了解药物疗效和 差异研究。PDX核心将由经验丰富且有能力的 UCDCCC的共享资源(小鼠生物学共享资源[MBSR]和生物库共享 资源[BSR]。在过去的五年中，MBSR和BSR一直参与建立、维护、 表征、存储和分发来自人类患者的大量PDX模型和来自 兽医患者在专门的、高度封闭的和无病原体的传染病环境中。具体来说， 在UCaMP期间，核心植入了383个不同的肿瘤，这些肿瘤传代成功地建立了101个 大多数模特来自种族/民族有色人种社区。此外，通过 在两个阶段聘用合格和经验丰富的人员以及功能齐全且随时可用的基础设施 先前存在的共享资源，唯一计入赠款预算的成本仅限于PDX建模 此项目的服务。通过这种方式，PDX核心将成为成功开发PDX试验不可或缺的一部分 可以可行地导致临床的单一药物和药物组合的临床前测试策略 验证。PDX核心还将通过促进PDX的沉积，为PDX网络(PDXNet)做出贡献 将模型、肿瘤和数据输入到弗雷德里克国家实验室的NCI患者衍生模型库 这样我们的模型就可以与更广泛的研究社区共享，除了共享 在UCATS成员中的PDX。此外，PDX Core还将与PDXNet合作开发和 验证用于临床前测试的PDX模型的开发和特征的SOP。

PROJECT SUMMARY/ABSTRACT The primary objectives of the Patient Derived Xenograft (PDX) Core will be to establish and characterize PDXs, and to support the research aims of the two integrated research projects of UCaTS, a disparity-relevant studies PDX Development and Trials Center (D-PDTC). The PDX Core will be responsible for the creation and characterization of 120 PDX models in immune-deficient mice (NSG) from tumors of patients with either gastric or lung cancers and diagnosed at any of the six sites: The five NCI designated comprehensive cancer centers (CCC) of the University of California (UC) system (Davis, Los Angeles, San Francisco, Irvine and San Diego) and the University of Texas Southwestern CCC. All of the newly established PDX lines will be from tumors harvested frompatients representing racial/ethnic minorities based on the combined catchment areas we expect to enrich for Latino and Asian American, Native Hawaiians/Pacific Islanders (AANHPI) patients. These PDX models will be used to generate cohorts of specific individual tumor-bearing (PDX) mice for drug efficacy and disparities studies. The PDX Core will consist of the expertise and infrastructure of experienced and capable shared resources at the UCDCCC (The Mouse Biology Shared Resource [MBSR] and the Biorepository Shared Resource [BSR]. Over the last five years, the MBSR and BSR have been involved in establishing, maintaining, characterizing, storing, and distributing numerous PDX models from human patients and PetDX models from veterinary patients in dedicated, highly-contained, and infectious pathogen-free environments. Specifically, during UCaMP, the core implanted 383 distinct tumors which were passaged to successfully establish 101 models in which the majority of models were derived from racially/ethnically communities of color. Further, by engaging qualified and experienced personnel and fully functioning and readily available infrastructure in two preexisting shared resources, the only costs charged to the grant budget are limited solely to PDX modeling services for this project. In this way, the PDX Core will be integral to the successful development of PDX trial strategies for preclinical testing of single agents and drug combinations that can feasibly lead to clinical validation. The PDX Core will also contribute to the PDX Network (PDXNet) by facilitating the deposition of PDX models, tumors, and data into the NCI Patient-Derived Models Repository at the Frederick National Laboratory for Cancer Research so that our models can be shared with the wider research community in addition sharing of the PDXs among UCaTS members. In addition, the PDX Core will also work with the PDXNet to develop and validate SOPs for development and characterization of PDX models for pre-clinical testing.