Meriva for treatment-induced inflammation and fatigue in women with breast cancer

Meriva 治疗乳腺癌女性治疗引起的炎症和疲劳

• 批准号: 8927561
• 负责人: THADDEUS PACE
• 金额: $ 19.02万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8927561
• 关键词: Address; Affect; Aftercare; Anterior uveitis; Arizona; Attention; Attenuated; Biological Factors; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer survivor; C-reactive protein; Cells; Chronic; Combination Drug Therapy; Curcumin; Data; Degenerative polyarthritis; Development; Disease; Drug Formulations; Effectiveness; Equipment and supply inventories; Exhibits; Fatigue; Food Additives; Health; Immune; Inflammation; Inflammation Mediators; Inflammatory; Interleukin-1 beta; Interleukin-6; Laboratories; Lecithin; Measures; Molecular; NF-kappa B; Nature; Non-Insulin-Dependent Diabetes Mellitus; Nuclear; Nutraceutical; Participant; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Placebos; Plants; Plasma; Property; Radiation; Radiation therapy; Randomized; Recruitment Activity; Resistance; Risk; Role; Signal Pathway; Symptoms; Testing; Tumeric; Tumor Necrosis Factor-alpha; Universities; Woman; Work; absorption; base; cancer therapy; chemotherapy; cytokine; design; improved; malignant breast neoplasm; member; novel; prevent; psychologic

DESCRIPTION (provided by applicant): This R21 proposal is designed to investigate the efficacy of Meriva, a unique formulation of the neutraceutical curcumin with enhanced absorption properties, to reduce chemotherapy and radiotherapy (XRT)-associated activation of the nuclear factor-kappa B (NF-kB) pathway in circulating peripheral blood mononuclear cells (PBMCs) in women treated for breast cancer. As many as 60% of breast cancer patients who receive radiation are known to develop fatigue, with about 30% suffering persistent fatigue several months to years after treatment completion. Fatigue therefore represents a persistent problem, even after successful completion of treatment for breast cancer. The physical, psychological, and molecular mechanisms by which patients develop fatigue are poorly understood and are most likely multi-factorial. However, one pathway that has received considerable attention is nuclear factor-kappa B (NF-kB). Our work has shown that NF-kB pathway activity in circulating immune cells is associated with the development of fatigue in patients treated with radiation. Importantly, we have also found that patients most at risk for persistent fatigue and NF-kB pathway activity are those who have received both chemotherapy and radiation for their breast cancer. We therefore believe that NF-kB represents an important target for the treatment of breast cancer-related fatigue. Curcumin, the principal component of turmeric and derived from the plant curcumin longa, has been shown to impact a number of molecular signaling pathways, including NF-kB. Although curcumin has been a food additive for centuries and is widely consumed as a neutraceutical, the effectiveness of orally administered curcumin to modulate NF-kB is believed to be severely limited by the poor absorption or curcumin. Meriva is a curcumin formulation that includes phosphatidylcholine. The combination of phosphatidylcholine with curcumin has been shown to enhance the absorption of curcumin compared to curcumin alone. As a result, Meriva represents an exciting way by which to reduce NF-kB activation and fatigue in women treated with chemotherapy and radiation for breast cancer. To date Meriva has shown considerable promise in the context of several disorders, including type-2 diabetes, osteoarthritis and chronic anterior uveitis. However, the effectiveness of Meriva to prevent and reverse fatigue in the context of breast cancer is yet to be evaluated. This proposal is designed to address this. Of note, our team members at Emory have already received an IND from FDA for the studies proposed. The major hypothesis of the current proposal is that Meriva will reduce inflammatory activation measured at the level of NF-kB as well as downstream proinflammatory cytokines in women treated for breast cancer. We also predict that Meriva will decrease fatigue symptoms, in a manner that is associated with reduced inflammation. Besides demonstrating that Meriva positively affects fatigue in women after breast cancer treatment, studies proposed here will also establish a mechanism for action for curcumin on fatigue.

描述（由申请人提供）：本 R21 提案旨在研究 Meriva 的功效，Meriva 是一种具有增强吸收特性的中性姜黄素独特配方，可减少接受乳腺癌治疗的女性循环外周血单核细胞 (PBMC) 中与化疗和放疗 (XRT) 相关的核因子-κ B (NF-kB) 通路激活 癌症。据了解，接受放射治疗的乳腺癌患者中有多达 60% 会出现疲劳，其中约 30% 的患者在治疗完成后数月至数年仍会出现持续性疲劳。因此，即使在成功完成乳腺癌治疗后，疲劳也是一个持续存在的问题。人们对患者产生疲劳的生理、心理和分子机制知之甚少，而且很可能是多因素影响的。然而，核因子 kappa B (NF-kB) 是一种备受关注的途径。我们的工作表明，循环免疫细胞中的 NF-kB 通路活性与接受放射治疗的患者疲劳的发生有关。重要的是，我们还发现，最有可能出现持续性疲劳和 NF-kB 通路活性的患者是那些接受过乳腺癌化疗和放疗的患者。因此，我们认为 NF-kB 是治疗乳腺癌相关疲劳的重要靶点。姜黄素是姜黄的主要成分，源自植物姜黄素 longa，已被证明会影响许多分子信号传导途径，包括 NF-kB。尽管姜黄素几个世纪以来一直是食品添加剂，并且作为保健品被广泛消费，但口服姜黄素调节 NF-kB 的有效性被认为因姜黄素的吸收不良而受到严重限制。 Meriva 是一种姜黄素配方，含有磷脂酰胆碱。与单独使用姜黄素相比，磷脂酰胆碱与姜黄素的组合已被证明可以增强姜黄素的吸收。因此，Meriva 代表了一种令人兴奋的方法，可以减少接受乳腺癌化疗和放疗的女性的 NF-kB 激活和疲劳。迄今为止，Meriva 在治疗多种疾病方面已显示出相当大的前景，包括 2 型糖尿病、骨关节炎和慢性前葡萄膜炎。然而，Meriva 在乳腺癌背景下预防和逆转疲劳的有效性仍有待评估。本提案旨在解决这个问题。值得注意的是，我们埃默里大学的团队成员已经收到 FDA 提出的研究的 IND。当前提案的主要假设是，Meriva 将减少接受乳腺癌治疗的女性中 NF-kB 水平以及下游促炎细胞因子水平的炎症激活。我们还预测 Meriva 将以与减少炎症相关的方式减轻疲劳症状。除了证明 Meriva 对乳腺癌治疗后女性的疲劳有积极影响外，本文提出的研究还将建立姜黄素对疲劳的作用机制。