HR-MAS-pathologic correlation of prostate tissue markers

HR-MAS-前列腺组织标志物的病理相关性

• 批准号: 6932058
• 负责人: MARK G SWANSON
• 金额: $ 14.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6932058
• 关键词: adenocarcinoma; androgens; apoptosis; atomic absorption spectrometry; bioimaging /biomedical imaging; biomarker; cell proliferation; citrates; clinical research; disease /disorder model; gene expression; genetically modified animals; histopathology; hormone related neoplasm /cancer; human subject; immunocytochemistry; laboratory mouse; male; metabolism; neoplasm /cancer classification /staging; nuclear magnetic resonance spectroscopy; pathologic process; patient oriented research; prostate neoplasms; urinary tract imaging /visualization; zinc

DESCRIPTION (provided by applicant): This proposed research career award builds on the principal investigator's work as an NIH fellow involving the use of magnetic resonance spectroscopy for the improved characterization of prostate cancer. Prostate cancer is a disease that afflicts one in five American men; however, it is difficult to predict those cancers that will spread (metastasize) and become life threatening from those that will remain indolent. Combined Magnetic Resonance Imaging and Spectroscopic Imaging (MRI/3D-MRSI) has demonstrated the ability to: improve the localization of prostate cancer within the gland; assess the extracapsular spread of the disease; and provide a measure of therapeutic response. As an NIH postdoctoral fellow, the principal investigator used MRI/3D-MRSI to study the metabolic effects of hormone ablation therapy in prostate cancer patients, and developed high resolution magic angle spinning (HR-MAS) techniques for the analysis of ex vivo prostate cancer tissues. The goal of this study is to better characterize the metabolic changes observed in vivo by MRSI and ex vivo by HR-MAS by improving their correlation with the underlying biochemical, morphologic, and genetic changes associated with the disease. To achieve these goals, we will use multidimensional HR-MAS techniques to identify new metabolic markers which can be exploited in vivo, and diffusion based experiments to learn more about the intracellular vs. extracellular distribution of prostate metabolites. Further, we will combine our HR-MAS findings with improved pathologic analysis to more accurately correlate specific metabolic profiles with prostate tissue type. Immunohistochemical assays will be performed to correlate metabolic profiles with other markers for cellular proliferation and apoptosis. We will also investigate the impact of zinc changes on citrate metabolism by assaying zinc levels in prostate tissues by atomic absorption spectrophotometry and zinc transporter gene expression using real-time reverse-transcriptase polymerase chain reaction analysis. These methods will then be used to learn more about changes in citrate metabolism under hormone dependent and independent conditions, using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The completion of the specific aims of this study will provide the principal investigator with the additional tools needed to develop his own independent cancer imaging research program. UCSF is a leading prostate cancer research center, with an NCI-designated comprehensive cancer center and prostate SPORE program. This excellent research environment combined with the extensive research experience of the mentor will greatly facilitate the completion of the goals set out in this proposal.

描述（由申请人提供）：这项拟议的研究职业奖建立在主要研究者作为NIH研究员的工作基础上，涉及使用磁共振波谱技术改善前列腺癌的特征。 前列腺癌是一种折磨五分之一美国男性的疾病;然而，很难预测那些将扩散（转移）并从那些将保持惰性的癌症中威胁生命的癌症。 联合磁共振成像和光谱成像（MRI/3D-MRSI）已证明能够：改善前列腺癌在腺体内的定位;评估疾病的囊外扩散;并提供治疗反应的测量。 作为NIH博士后研究员，主要研究者使用MRI/3D-MRSI研究前列腺癌患者激素消融治疗的代谢效应，并开发了用于分析离体前列腺癌组织的高分辨率魔角旋转（HR-MAS）技术。 本研究的目的是更好地表征MRSI体内和HR-MAS离体观察到的代谢变化，通过改善其与疾病相关的潜在生化，形态学和遗传变化的相关性。 为了实现这些目标，我们将使用多维HR-MAS技术来识别可以在体内利用的新的代谢标志物，以及基于扩散的实验来了解更多关于前列腺代谢物的细胞内与细胞外分布的信息。 此外，我们将联合收割机结合我们的HR-MAS结果与改进的病理分析，以更准确地将特定的代谢谱与前列腺组织类型相关联。 将进行免疫组织化学测定，以将代谢特征与细胞增殖和凋亡的其他标志物相关联。 我们还将通过原子吸收分光光度法测定前列腺组织中的锌水平，并使用实时逆转录聚合酶链反应分析锌转运蛋白基因表达，研究锌变化对柠檬酸盐代谢的影响。 然后，这些方法将用于使用小鼠前列腺转基因腺癌（TRAMP）模型，更多地了解激素依赖性和非依赖性条件下柠檬酸盐代谢的变化。 完成本研究的特定目标将为主要研究者提供开发其独立癌症成像研究计划所需的额外工具。 UCSF是领先的前列腺癌研究中心，拥有NCI指定的综合癌症中心和前列腺SPORE计划。 这种优秀的研究环境与导师丰富的研究经验相结合，将极大地促进本建议书所列目标的完成。