A High Throughput Human Tumor Modeling Technology for Cancer Drug Discovery

用于癌症药物发现的高通量人体肿瘤建模技术

• 批准号: 10330116
• 负责人: Gary D Luker
• 金额: $ 16.64万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10330116
• 关键词: 3-Dimensional; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Breast Cancer Cell; Breast Cancer Model; Breast cancer metastasis; Chemopreventive Agent; Chronic Disease; Clinical Trials; Consumption; Distant Metastasis; Dyes; Engineering; Frequencies; Human; Investigation; Malignant Neoplasms; Mammary Neoplasms; Modeling; Oncogenic; Oxidants; Patient-Focused Outcomes; Phenotype; Phytochemical; Preventive; Primary Neoplasm; Process; Signal Transduction; Supplementation; Technology; Testing; breast cancer progression; cancer cell; dietary supplements; drug discovery; epithelial to mesenchymal transition; fisetin; fruits and vegetables; humanized mouse; improved outcome; metastatic process; mouse model; preclinical study; prevent; protective effect; treatment strategy; tumor; tumor growth

Project Summary Fisetin is a naturally-occurring phytochemical abundantly found in vegetables and fruits as the coloring agent. Preclinical studies have shown that fisetin offers anti-inflammatory and anti-oxidant benefits and protective effects against chronic diseases. Due to its significant benefits, consumption of fisetin as a dietary supplement is currently being studied in a clinical trial. Guided by our recent studies that showed fisetin significantly downregulates oncogenic signaling in breast cancer cells, we hypothesized that fisetin has chemopreventive effects against processes that are essential to breast cancer metastasis. Thus, using fisetin as a supplement may have preventive benefits against metastatic progression and significantly improve outcomes for patients. Because breast cancer metastasis occurs often very early and even before primary tumors are detected, preventing pro-metastatic processes is essential to improve outcomes for patients. We will test our hypothesis using our three-dimensional organotypic breast tumor model and a humanized mouse model of breast cancer, to study chemopreventive effects of fisetin on proliferation, epithelial-to-mesenchymal transition, and local invasion of cancer cells. Through phenotypic and mechanistic studies, we aim to demonstrate that fisetin supplementation will have benefits against breast tumor growth and frequencies of local and distant metastasis. In addition, our systematic studies in this project will help broaden investigations of dietary supplements as chemopreventive agents to block progression of breast cancer and other malignancies.

项目摘要 鱼腥草素是一种天然植物化学物质，大量存在于蔬菜和水果中作为着色剂。 临床前研究表明，非瑟丁具有抗炎、抗氧化和保护作用。 对慢性病的治疗效果。由于其显著的好处，食用非瑟丁作为膳食补充剂 目前正在进行临床试验研究。根据我们最近的研究，菲赛汀显著地 下调乳腺癌细胞中的致癌信号，我们假设菲斯汀具有化学预防作用 对乳腺癌转移所必需的过程的影响。因此，使用非瑟丁作为补充 可能对防止转移进展有预防作用，并显著改善患者的预后。 因为乳腺癌转移往往发生得很早，甚至在原发肿瘤被发现之前， 预防转移过程是改善患者预后的关键。我们将检验我们的假设 使用我们的三维器官型乳腺肿瘤模型和人源化的乳腺癌小鼠模型， 研究鱼腥草素对细胞增殖、上皮向间充质转化和局部的化学预防作用。 癌细胞的侵袭。通过表型和机理研究，我们的目标是证明 补充有益于抑制乳腺肿瘤的生长和局部和远处的频率。 转移。此外，我们在这个项目中的系统研究将有助于拓宽对饮食的调查。 作为化学预防药物的补充剂，以阻止乳腺癌和其他恶性肿瘤的进展。