High Kynurenine in Agressive Triple Negative African American Breast Cancer

侵袭性三阴性非裔美国乳腺癌中的高犬尿氨酸

• 批准号: 8687235
• 负责人: Arun Sreekumar
• 金额: $ 20.42万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8687235
• 关键词: Address; African American; Age; American; Aryl Hydrocarbon Receptor; Biochemical; Bioinformatics; Biological; Biometry; Breast Cancer Epidemiology; Cancer Biology; Cancer Patient; Cancer Prognosis; Cell Line; Cell Proliferation; Cells; Clinical; Data; Data Set; Development; Disease; Disease-Free Survival; Epidemiology; European; Fingerprint; Gene Expression; Gene Proteins; Gene Targeting; Genetic; Glean; Goals; HRAS gene; Healthcare; Hormonal; Immunoblotting; Incidence; Kynurenine; Lead; Light; Malignant Neoplasms; Mammary Gland Parenchyma; Mass Spectrum Analysis; Measures; Metabolic; Metabolic Pathway; Metabolism; Methodology; Molecular Profiling; Oncogenes; Outcome; Pathway interactions; Patients; Play; Pre-Clinical Model; Race; Receptor Activation; Recording of previous events; Reporting; Research; Role; Sampling; Serum; Signal Pathway; Signal Transduction; Specimen; Staging; Subgroup; Therapeutic; Tissue Sample; Tissues; Tryptophan; Woman; Work; Xenograft Model; aryl hydrocarbon receptor ligand; base; cancer health disparity; malignant breast neoplasm; member; metabolomics; outcome forecast; patient population; prognostic; public health relevance; small molecule; triple-negative invasive breast carcinoma; tumor; tumor progression

DESCRIPTION (provided by applicant): The long-term objective of our research plan is to reduce the disproportionate effects of breast cancer on African American women, especially those belonging to the Triple Negative subtype (i.e., ER-, PR- and Her2-). A guiding principle of our methodology is biochemical differences exist between TN breast cancers of African American and European American origin and that these differences can explain, in part, breast cancer health disparity. In this application, we propose characterization one such alteration in Kynurenine metabolism. High levels of the metabolites Kynurenine and Tryptophan were found in a subset of TN breast cancers, predominantly African American, with poor clinical outcome. These patients also showed higher expression of the RAS oncogene. Based on these we hypothesize that higher levels of the metabolite Kynurenine in association with RAS signaling, could lead to aggressive tumors within the African American women, having TN breast cancer. Further, we propose that characterization of the role of Kynurenine metabolism in TN African American breast cancer could help address the issue of racial disparity in breast cancer clinical outcomes.

描述（由申请人提供）：我们研究计划的长期目标是减少乳腺癌对非洲裔美国妇女的不成比例的影响，特别是那些属于三阴性亚型（即，ER-、PR-和Her 2-）。我们的方法的指导原则是非裔美国人和欧洲裔美国人的TN乳腺癌之间存在生物化学差异，这些差异可以部分解释乳腺癌健康差异。在本申请中，我们提出了犬尿氨酸代谢的一个这样的改变的表征。高水平的代谢物犬尿氨酸和色氨酸被发现在TN乳腺癌的一个子集，主要是非洲裔美国人，具有不良的临床结果。这些患者还显示RAS癌基因的较高表达。基于这些，我们假设与RAS信号传导相关的代谢物犬尿氨酸的水平较高，可能导致患有TN乳腺癌的非裔美国妇女体内的侵袭性肿瘤。此外，我们提出犬尿氨酸代谢在TN非洲裔美国人乳腺癌中的作用的表征可以帮助解决乳腺癌临床结果中的种族差异问题。