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Oleocanthal functional food products for breast cancer recurrence control

用于控制乳腺癌复发的油橄榄功能性食品

基本信息

批准号：
10276305
负责人：
KHALID A EL SAYED
金额：
$ 5.48万
依托单位：
OLEOLIVE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10276305
关键词：
Animal Model Breast Cancer Patient Breast Cancer Prevention Consumption Data Diet Dose Effectiveness Excision Formulation Future Human Human Pathology Immunocompetent Incidence Mammary gland Molecular Target Mouse Mammary Tumor Virus Natural Products Neoadjuvant Therapy Neoplasm Metastasis Nude Mice Nutraceutical Olive oil preparation Operative Surgical Procedures Oral Outcome Paclitaxel Patients Phenols Powder dose form Preventive treatment Primary Neoplasm Recording of previous events Recurrence Regimen Signal Pathway Solid Survival Rate Taste Perception Testing Therapeutic Transgenic Mice bioactive natural products breast cancer progression cancer recurrence commercialization disorder later incidence prevention efficacy testing functional food improved malignant breast neoplasm mouse model parent grant patient subsets prevent triple-negative invasive breast carcinoma tumor

项目摘要

SUMMARY From Parent Grant (R41CA247025) Triple negative breast cancer (TNBC) represents 20% of the breast cancer (BC) cases in the US. TNBC patients have a poor recurrence-free, overall survival rate, and limited available treatment options. The Mediterranean olive oil-rich diet is documented to reduce BC incidence. (-)-Oleocanthal (OC) is a natural phenolic secoiridoid exclusively occurring in extra-virgin olive oil (EVOO) and it has shown selective anti-BC activities, including preliminary results showing prevention of recurrence of TNBC in animal models. The HGF/Met signaling pathway, a validated major OC molecular target, is likely involved in initiating aggressive and recurrent TNBC in a subset of patients. To improve taste, dissolution and stability, a solid dispersion formulation of OC (OC-X) was recently developed and characterized. We hypothesize that the EVOO powdered formulation of OC, OC-X, could be developed as a nutraceutical product to help control locoregional TNBC recurrence. This will be tested in the following Specific Aims. In the first aim, we will perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in a nude mouse model after primary tumor surgical resection. This aim will assess the efficacy of formulations in preventive, treatment, and after completion of paclitaxel neoadjuvant regimen modes. In the second aim, we will perform dose dependent studies to determine the optimal effective dose of orally administered OC-X on tumor recurrence in the MMTV-PyMT transgenic mouse model. This immune competent mouse model develops BC mimicking progression seen in human patients and will be used to assess BC recurrence (after surgical excision of early mammary gland tumors) and metastasis following treatment with OC-X. Expected outcomes: EVOO enriched in OC has been safely consumed throughout human history with increasing evidence of effectiveness against many human pathologies, including BC. Given the lack of other safe therapeutic alternatives, OC is a candidate bioactive natural product that could be safe for long-term use to prevent BC recurrence. The data generated by this project will be combined with future studies of OC-X to facilitate commercialization of OC-X as a nutraceutical product to prevent BC recurrence.

总结来自父母补助金（R41 CA 247025）三阴性乳腺癌（TNBC）占美国乳腺癌（BC）病例的20%。TNBC患者无复发率低，总生存率低，可用的治疗方案有限。地中海据记录，富含橄榄油的饮食可以减少BC的发病率。（-）-油花醛（OC）是一种天然酚类开环环烯醚萜它只存在于特级初榨橄榄油（EVOO）中，并显示出选择性的抗BC活性，包括初步结果显示在动物模型中预防TNBC复发。HGF/Met信号通路途径是一种经验证的主要OC分子靶点，可能参与启动侵袭性和复发性TNBC，一部分病人为了改善口感、溶解性和稳定性，制备了OC（OC-X）的固体分散体制剂。最近开发和鉴定的。我们假设，OC，OC-X，可以开发为营养产品，以帮助控制局部TNBC复发。这将是在以下具体目标中进行测试。在第一个目标中，我们将进行剂量依赖性研究，以确定口服给予OC-X对裸鼠模型中肿瘤复发的最佳有效剂量肿瘤手术切除该目的将评估制剂在预防、治疗和治疗后的功效。完成紫杉醇新辅助治疗方案模式。在第二个目标中，我们将进行剂量依赖性研究确定口服OC-X对MMTV-PyMT中肿瘤复发的最佳有效剂量转基因小鼠模型。这种免疫活性小鼠模型发展出BC，模拟在并将用于评估BC复发（在手术切除早期乳腺后肿瘤）和转移。预期结果：富含OC的EVOO已在整个人类历史中安全食用，越来越多的证据表明对许多人类有效。病理学，包括BC。鉴于缺乏其他安全的治疗替代品，OC是一种候选的生物活性物质，天然产品，可以安全地长期使用，以防止BC复发。这个项目产生的数据将与OC-X的未来研究相结合，以促进OC-X作为营养产品的商业化防止BC复发。