ANALYTICAL CORE

分析核心

• 批准号: 8879964
• 负责人: PEIYING YANG
• 金额: $ 9.94万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8879964
• 关键词: Academic Medical Centers; Biological; Biological Assay; Biology; Blood; Categories; Cells; Colon Carcinoma; Complex; Detection; Development; Dilution Techniques; Dinoprostone; Eicosanoids; Electrospray Ionization; Endocannabinoids; Endometrial Carcinoma; Epoprostenol; Funding; Goals; Grant; High Pressure Liquid Chromatography; Inflammation; Instruction; Intervention; Knowledge; Laboratories; Lipids; Lipoxygenase; Liquid Chromatography; Liquid substance; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Mass Spectrum Analysis; Measures; Methods; Monitor; Mus; PTGS2 gene; Pathway interactions; Pharmaceutical Preparations; Procedures; Process; Program Research Project Grants; Prostaglandins; Publications; Research; Research Personnel; Resources; Role; Sampling; Series; Sphingolipids; Techniques; Tissues; University of Texas M D Anderson Cancer Center; Work; analytical method; animal tissue; celecoxib; design; inhibitor/antagonist; instrument; instrumentation; interest; liquid chromatography mass spectrometry; malignant breast neoplasm; novel; small molecule; stable isotope; success; tandem mass spectrometry; urinary

PROJECT SUMMARY (See instructions): The proposed Analytical Core will perform analyses of a wide variety of bioactive lipids in various mouse tissues and biological fluids for investigators in the Program Project Grant. The four projects in this PPG proposal will evaluate the role of COX-2, and associated metabolites such as PGE2 that are believed to be involved in the initiation and progression of colon, breast, and endometrial cancers. A strong advantage of the current PPG is that we will now also explore the important roles of a series of bioactive lipids including endocannabinoids and sphingolipids and their interactions with COX-2 pathways. This will require the Analytical Core to not only quantify a wide variety of prostaglandins such as PGE2 and PGE-M, but also to determine and quantify pharmacologically relevant endocannabinoids and sphingolipids in various animal tissues. These three categories of bioactive lipids will be measured predominantly by methods that involve high performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESIMS/ MS) using a stable isotope dilution technique developed by the Core Director and which has been extensively used in her laboratory. Use of eicosanoid assays by investigators involved in this PPG grant has already contributed to a number of publications that demonstrate the potential impact of these lipids on cancer development. The proposed research will enhance our understanding of the essential roles of bioactive lipids in the pathophysiological processes related to malignancy. In addition, the Core will also develop a novel LC/MS/MS method to simultaneously quantify all three classes of bioactive lipids. This will allow us to assess the interaction of bioactive lipids of interest and advance our knowledge of how the three categories of bioactive lipids are interrelated. Lastly, the Core will quantify blood and tissue levels of intervention compounds, such as the selective COX-2 inhibitor celecoxib, as well as prostaglandins, such as PGI2 and TXA2 to facilitate monitoring the pharmacologic effect of celecoxib proposed in all four projects. Thus, the overall objective of the Analytical Core is to provide sophisticated technical and analytical support that involves integration of sensitive isolation and detection procedures with the latest bioanalytical methods

项目摘要（请参阅说明）： 所提出的分析核心将对计划项目赠款的各种小鼠组织中的各种生物活性脂质和生物流体进行分析。该PPG提案中的四个项目将评估COX-2的作用，以及相关的代谢物，例如PGE2，这些代谢物被认为与结肠，乳腺癌和子宫内膜癌的起始和进展有关。当前PPG的一个强大优势是，我们现在还将探索一系列生物活性脂质的重要作用，包括内源性大麻素和鞘脂脂质及其与COX-2途径的相互作用。这将需要分析核心不仅可以量化各种各样的前列腺素，例如PGE2和PGE-M，而且还可以确定和量化各种动物组织中与药理学相关的内源性内源性大麻素和鞘脂。这三类生物活性脂质将主要通过涉及高性能液相色谱/电喷雾电离串联质谱法（LC/ESIMS/MS）的方法来测量，并使用稳定的同位素稀释技术开发的稳定的同位素稀释技术，并且已在其实验室中广泛使用。参与该PPG赠款的调查人员使用类黄花粉测定法已经为许多出版物做出了贡献，这些出版物证明了这些脂质对癌症发展的潜在影响。拟议的研究将增强我们对生物活性脂质在与恶性肿瘤有关的病理生理过程中的基本作用的理解。此外，核心还将开发一种新型的LC/MS/MS方法，以同时量化所有三类生物活性脂质。这将使我们能够评估感兴趣的生物活性脂质的相互作用，并促进我们对三类生物活性脂质如何相互关联的了解。最后，核心将量化干预化合物的血液和组织水平，例如选择性COX-2抑制剂Celecoxib，以及前列腺素（例如PGI2和TXA2），以促进监测所有四个项目中提出的Celecoxib的药理作用。 因此，分析核心的总体目标是提供复杂的技术和分析支持，涉及将敏感隔离和检测程序与最新的生物分析方法整合在一起