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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

基本信息

批准号：
8843400
负责人：
Arun Sreekumar
金额：
$ 17.02万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
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/8843400
关键词：
Address African American Age American Aryl Hydrocarbon Receptor Biochemical Bioinformatics Biological Biometry Breast Cancer Epidemiology Breast Cancer Patient Cancer Biology 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 Health 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 racial disparity small molecule triple-negative invasive breast carcinoma tumor tumor progression

项目摘要

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）：我们的研究计划的长期目标是减少乳腺癌对非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Her2-）的妇女。我们方法的一个指导原则是，非裔美国人和欧洲裔美国人的TN乳腺癌之间存在生化差异，这些差异可以部分解释乳腺癌健康差异。在这个应用中，我们提出表征犬尿氨酸代谢的这种改变。高水平的代谢产物犬尿氨酸和色氨酸在TN乳腺癌的一个亚群中被发现，主要是非裔美国人，临床结果不佳。这些患者也表现出RAS癌基因的高表达。基于这些，我们假设与RAS信号相关的较高水平的代谢物犬尿氨酸可能导致患有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非裔美国人乳腺癌中的作用特征可以帮助解决乳腺癌临床结果的种族差异问题。