Cancer Metabolism Core

新陈代谢核心 摘要 拟议的UNMC获得性抵抗治疗网络(ARTnet)中心的新陈代谢核心 胰腺癌(ACPC)将研究创新的、假设驱动的代谢和信号机制 导致胰腺导管腺癌(PDAC)获得性治疗抵抗的改变。其核心是 新陈代谢核心提供的服务将很好地融入所有三个项目。核心将提供 具有成本效益的代谢组学和数据分析支持，为所有项目提供适当的质量控制 提供代谢组学、生理分析和代谢方面的集中基础设施和专业知识 依赖项/漏洞屏幕。新陈代谢核心将有三个具体目标。基本能力 由Core提供的将包括稳态极地代谢组学和类脂组学(特定目标1)、稳定同位素 具有动力学通量分析的分解代谢组学(SIRM)(特定目标2)，以及海马胞外通量 以分析仪为基础的分析，研究细胞代谢状态的荧光分析，并确定代谢 脆弱性(具体目标3)。新陈代谢核心将参与稳态的设计和实施 极性代谢组学、类脂组学、~(13)C代谢物标记的细胞系、有机化合物和 外显体。核心还将对小鼠和人类进行稳定的极地代谢组学和脂类组学 所有项目的肿瘤组织标本。该核心还将根据需要为ACPC提供实践培训， 其他Artnet中心和其他调查人员。该核心还将为药物测量提供支持 药物在组织中的浓度和代谢以及药物的药代动力学/药效学研究。

METABOLISM CORE Abstract The metabolism core of the proposed the UNMC Acquired Resistance to Therapy Network (ARTNet) Center for Pancreatic Cancer (ACPC) will study innovative, hypothesis-driven mechanisms of metabolic and signaling alterations that contribute to acquired therapy resistance in pancreatic ductal adenocarcinoma (PDAC). The core services provided by the metabolism core will be well integrated into all the three projects. The core will offer cost-effective metabolomics and data analysis support with appropriate quality controls for all projects by providing a centralized infrastructure and expertise in metabolomics, physiological assays, and metabolic dependency/vulnerability screens. The metabolism core will have three specific aims. The basic capabilities offered by the Core will include steady-state polar metabolomics and lipidomics (Specific Aim 1), Stable Isotope Resolved Metabolomics (SIRM) with kinetic flux analysis (Specific Aim 2), and Seahorse extracellular flux analyzer-based assays, fluorescent assays to investigate the metabolic state of cells, and identifying metabolic vulnerabilities (Specific Aim 3). The Metabolism Core will participate in the design and conduct of steady-state polar metabolomics, lipidomics, 13C-metabolite labeled kinetic flux analysis with cell lines, organoids, and exosomes. The core will also perform steady-state polar metabolomics and lipidomics for mouse and human tumor tissue specimens in all the projects. The core will also provide hands-on training, as needed, for the ACPC, other ARTNet centers, and other investigators. The core will also provide support for measuring drug concentrations and metabolism in the tissues and drug pharmacokinetics/ pharmacodynamics studies.