Core B: Human Pancreas

摘要：斯坦福人类胰腺癌研究生物库(核心B) 斯坦福大学胰腺癌研究人类生物库(核心B)将支持人类组织和细胞 本计划项目资助项目中提出的研究，其总体目标是系统地澄清 PDAC致病的遗传驱动因素，并确定免疫系统在胰腺癌传播中的作用。 虽然许多研究将在明确的PDAC基因工程小鼠模型中进行，但一个重要的 这些研究的主题是测试和证明我们的发现与人类PDAC的相关性。有了这个 目的：1)系统地收集和储存人胰腺癌组织和血液，并 建立这些患者的临床和人口学信息登记；2)系统地收集和存储 慢性胰腺炎患者的胰腺组织和血液的临床登记 和这些患者的人口统计信息，3)提供人体组织分析的专业知识 通过组织学、免疫组织化学、流式细胞术、细胞周期图和单细胞RNAseq，以及4)有效地与 核心C为所有项目使用CODEX进行人体组织研究。该核心将通过以下方式支持项目1 人胰腺癌组织、癌前病变和慢性胰腺炎(CP)样本 评估它们在KRAS癌基因和肿瘤抑制基因中的遗传多样性。此核心将支持 项目2，通过提供患有PDAC或炎症状态(如CP)的患者的胰腺来评估免疫 和成纤维细胞亚型、IL-22/IL-22Ra1的表达模式以及在PDAC的背景下，它们与 癌症亚型和‘茎’表型。该核心将通过验证先前的观察结果来支持项目3 分析免疫细胞和免疫调节因子在小鼠PDAC模型中的作用及其与 人类PDAC的遗传亚型。此核心还将与核心C密切合作，以实现适当的人力 用于创新的基于CODEX的多参数联合检测成像的组织处理。因此， 这一研究核心将是高度整合的，并支持本计划项目赠款的总体目标。

ABSTRACT: Stanford Human Bio-bank for Pancreas Cancer Research (Core B) The Stanford Human Bio-Bank for Pancreas Cancer Research (Core B) will support human tissue and cell studies proposed in the Projects of this Program Project Grant whose overall goal is to systematically clarify the genetic drivers of PDAC pathogenesis and define the immune system's role in pancreatic cancer propagation. While many studies will be performed in defined genetically engineered mouse models of PDAC, an important theme of these studies is to test and demonstrate the relevance of our discoveries to human PDAC. With this objective, this Core will 1) Systematically collect and bank human pancreatic cancer tissues and blood, and to establish a registry of clinical and demographic information of these patients, 2) Systematically collect and bank human pancreatic tissue and blood from patients with chronic pancreatitis and to establish a registry of clinical and demographic information of these patients, 3) Provide expertise and knowledge of human tissue analysis by histology, immunohistochemistry, FACS, CyTOF, and single-cell RNASeq, and 4) Collaborate effectively with Core C to use CODEX for studies on human tissues for all Projects. This Core will support Project 1 by providing human pancreatic cancer tissue, pre-cancerous pancreatic lesions, and chronic pancreatitis (CP) samples for evaluation of their genetic diversity in the KRAS oncogene, and tumor suppressor genes. This Core will support Project 2, by providing pancreata from patients with PDAC, or inflammatory states like CP, to assess immune and fibroblast subtypes, IL-22/ IL-22RA1 expression patterns and in the context of PDAC, their association with cancer subtypes and `stemness' phenotypes. This Core will support Project 3, by validating earlier observations in mouse PDAC models by analyzing immune cells and immunomodulatory factors and their association with genetic subtypes of human PDAC. This Core will also work closely with Core C to enable appropriate human tissue processing for the innovative CO-Detection by indEXing (CODEX)-based multi-parameter imaging. Thus, this research core will be highly integrated and supportive of the overall objectives of this Program Project Grant.