ANALYTICAL CORE

分析核心

基本信息

批准号：
8248362
负责人：
PEIYING YANG
金额：
$ 9.94万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2012-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8248362
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 prostaglandin M small molecule stable isotope success tandem mass spectrometry urinary

项目摘要

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（参见说明）：拟议的分析核心将为计划项目拨款的研究人员对各种小鼠组织和生物液体中的各种生物活性脂质进行分析。该 PPG 提案中的四个项目将评估 COX-2 以及相关代谢物（例如 PGE2）的作用，这些代谢物被认为与结肠癌、乳腺癌和子宫内膜癌的发生和进展有关。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（包括内源性大麻素和鞘脂）的重要作用及其与 COX-2 途径的相互作用。这将要求分析核心不仅能够量化各种前列腺素，例如 PGE2 和 PGE-M，而且还能够确定和量化各种动物组织中药理学相关的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效液相色谱/电喷雾电离串联质谱 (LC/ESIMS/MS) 的方法进行测量，使用由核心主任开发的稳定同位素稀释技术，该技术已广泛应用于她的研究中。实验室。参与 PPG 资助的研究人员使用类二十烷酸测定法已经发表了许多出版物，证明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相关的病理生理过程中的重要作用的理解。此外，Core 还将开发一种新型 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，并增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（例如选择性 COX-2 抑制剂塞来昔布）以及前列腺素（例如 PGI2 和 TXA2）的血液和组织水平，以促进监测所有四个项目中提出的塞来昔布的药理作用。因此，分析核心的总体目标是提供复杂的技术和分析支持，包括将敏感的分离和检测程序与最新的生物分析方法相集成