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: 6507631
• 负责人: MARK G SWANSON
• 金额: $ 12.21万
• 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/6507631
• 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首席研究员作为 NIH 研究员的工作基础上，涉及使用磁共振波谱来改善前列腺癌的表征。 前列腺癌是一种困扰五分之一美国男性的疾病。然而，很难预测那些将扩散（转移）并威胁生命的癌症与那些保持惰性的癌症。 磁共振成像和光谱成像相结合 (MRI/3D-MRSI) 已证明能够： 改善前列腺癌在腺体内的定位；评估疾病的囊外传播；并提供治疗反应的衡量标准。 作为 NIH 博士后研究员，主要研究员使用 MRI/3D-MRSI 研究前列腺癌患者激素消融治疗的代谢影响，并开发了高分辨率魔角旋转 (HR-MAS) 技术用于分析离体前列腺癌组织。 本研究的目的是通过提高 MRSI 体内观察到的代谢变化和 HR-MAS 体外观察到的代谢变化与疾病相关的潜在生化、形态和遗传变化的相关性，更好地表征代谢变化。 为了实现这些目标，我们将使用多维 HR-MAS 技术来识别可在体内利用的新代谢标记物，并使用基于扩散的实验来了解有关前列腺代谢物的细胞内与细胞外分布的更多信息。 此外，我们将把 HR-MAS 研究结果与改进的病理分析相结合，以更准确地将特定代谢特征与前列腺组织类型相关联。 将进行免疫组织化学测定，以将代谢谱与细胞增殖和凋亡的其他标记物相关联。 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和使用实时逆转录酶聚合酶链反应分析锌转运蛋白基因表达来研究锌变化对柠檬酸代谢的影响。 然后，使用小鼠前列腺转基因腺癌​​ (TRAMP) 模型，这些方法将用于了解更多关于激素依赖和独立条件下柠檬酸代谢变化的信息。 本研究具体目标的完成将为主要研究者提供开发自己独立的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 项目。 这种优良的研究环境加上导师丰富的研究经验将极大地促进本提案所提出的目标的完成。