Racial Disparity in Bladder Cancer and Identification of Altered Metabolism in African American Compare to European Bladder Cancer

与欧洲膀胱癌相比，非裔美国人膀胱癌的种族差异以及代谢改变的鉴定

• 批准号: 9388440
• 负责人: Nagireddy Putluri
• 金额: $ 37.07万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-05 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9388440
• 关键词: Accounting; Acetylation; Acetyltransferase; Address; African American; Alcohol dehydrogenase; American; Aspartic Acid; Bioenergetics; Biological; Biological Factors; Biological Markers; Cancer Patient; Cancer cell line; Caring; Clinical; Cystectomy; Data; Development; Diagnostic; Disease; Disease Outcome; Disease Progression; Enzymes; European; Generations; Genes; Genetic; Glean; Glioma; Glutaminase; Glutamine; Hypermethylation; In Vitro; Incidence; Iron; Isocitrate Dehydrogenase; Label; Lipids; Malignant neoplasm of urinary bladder; Marital Status; Mass Spectrum Analysis; Measurement; Measures; Messenger RNA; Metabolic; Metabolic Marker; Metabolic Pathway; Metabolism; Methodology; Mitochondria; Muscle; Mutation; NAT1 gene; Occupational Exposure; Oncogenic; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Pharmaceutical Preparations; Pharmacology; Phospholipase A1; Phosphorylcholine; Pilot Projects; Positioning Attribute; Proteins; Publications; Publishing; Race; Reporting; Research; Role; SEER Program; Seminal; Smoker; Smoking; Socioeconomic Factors; Techniques; Therapeutic; Tissues; Urine; Xenobiotic Metabolism; Xenograft procedure; base; cancer health disparity; combinatorial; experience; glutaric acid; health care availability; health disparity; in vivo; inhibitor/antagonist; lecithin-retinol acyltransferase; lipid metabolism; metabolome; metabolomics; mitochondrial metabolism; mortality; prognostic; racial disparity; racial health disparity; therapeutic target; treatment strategy; triple-negative invasive breast carcinoma; tumor; tumor progression

Project Summary/Abstract It has known that bladder cancer (BCa) mortality is higher in African American patients. Disparity exists between African-American (AA) and European-American (EA), in the clinical outcome of BCa. The long-term objective of our research plan is to reduce the disproportionate effects of bladder cancer (BCa) on African American. A guiding principle of our methodology is that alterations in mitochondrial metabolites exist between African American and European American BCa and that these differences can explain, in part, BCa health disparity. In this application, we propose to use the technique of metabolomic profiling to uncover these underlying differences. To date, a metabolomic analyses aimed at understanding of bladder cancer health disparity has not been reported. We have recently published the first study describing metabolic alterations associated with bladder cancer. In preliminary studies, we have profiled the metabolome of BCa from AA and EA patients and identified a distinct AA race-specific expression pattern in mitochondrial metabolites and lipids. In this proposal, we will i) characterize the mitochondrial associated metabolites in AA and EA BCa, ii) verify the D-2HG and associated enzymes (GLS, ADHFE1, and IDH1/2) in BCa patients and establish a therapeutically targeted deregulation pathway for glutamine metabolism in AA BCa iii) assess the levels of lyso PC and PC and the function of their metabolizing enzymes PLA1A and LRAT in AA BCa. The successful completion of the proposed studies will have a significant impact in the field of Bladder cancer health disparity and metabolism. Importantly, findings from our study have the potential to reveal racially exclusive metabolic markers and therapeutic targets for BCa. Taken together, the information gleaned from this proposal could rapidly revolutionize current diagnostic, prognostic and therapeutic approaches by revealing the biological underpinnings of bladder cancer health disparity.

项目总结/摘要 据了解，膀胱癌（BCa）死亡率在非洲裔美国人患者中较高。存在差距 非裔美国人（AA）和欧洲裔美国人（EA）之间，在BCa的临床结果。长期 我们的研究计划的目标是减少膀胱癌（BCa）对非洲人的不成比例的影响。 美国人我们的方法的指导原则是线粒体代谢物的改变存在于 非洲裔美国人和欧洲裔美国人的BCa，这些差异可以部分解释BCa健康 差距在本申请中，我们建议使用代谢组学分析技术来揭示这些 潜在的差异。迄今为止，代谢组学分析旨在了解膀胱癌的健康状况， 未报告差异。我们最近发表了第一项描述代谢改变的研究， 与膀胱癌有关。在初步研究中，我们已经分析了AA和AA中BCa的代谢组， EA患者，并确定了一个独特的AA种族的线粒体代谢产物和脂质的表达模式。 在本提案中，我们将i）表征AA和EA BCa中的线粒体相关代谢物，ii）验证 BCa患者的D-2 HG和相关酶（GLS，ADHFE 1和IDH 1/2），并建立了一个 iii）评估AA BCa中谷氨酰胺代谢的治疗靶向失调途径 PC和PC及其代谢酶PLA 1A和LRAT在AA BCa.成功 完成拟议的研究将对膀胱癌健康差距领域产生重大影响 和新陈代谢。重要的是，我们的研究结果有可能揭示种族排他性的代谢 BCa的标志物和治疗靶点。总的来说，从这一建议中收集到的信息可以 通过揭示生物学特性，迅速革新当前的诊断、预后和治疗方法。 膀胱癌的治疗方法