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: 8755360
• 负责人: THADDEUS PACE
• 金额: $ 16.76万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8755360
• 关键词: Address; Affect; Aftercare; Anterior uveitis; Arizona; Attention; Attenuated; Biological Factors; Breast Cancer Treatment; C-reactive protein; Cancer Patient; Cancer Survivor; Cells; Chronic; Combination Drug Therapy; Curcumin; Data; Degenerative polyarthritis; Development; Disease; Drug Formulations; Effectiveness; Equipment and supply inventories; Exhibits; Fatigue; Food Additives; 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; public health relevance

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）：该R21提案旨在研究Meriva的功效，Meriva具有具有增强吸收特性的中性姜黄素的独特表述，以减少化学疗法和放射疗法（XRT）相关的核因子-KAPPA B（NF-KB）细胞（NF-KB）的激活，使妇女的乳腺细胞（NF-KB）的细胞在循环中的细胞（NF-KB）的细胞（PB）在循环中的细胞（PB）的细胞（pb）的细胞（pb）的细胞（ 癌症。已知多达60％的接受辐射的乳腺癌患者会出现疲劳，大约30％的人遭受治疗完成后几个月至几年的持续疲劳。因此，即使成功完成乳腺癌治疗后，疲劳也代表了一个持续的问题。患者患疲劳的身体，心理和分子机制知之甚少，很可能是多因素的。但是，核因子-kappa B（NF-KB）是一个引起大量关注的途径。我们的工作表明，循环免疫细胞中的NF-KB途径活性与接受辐射治疗的患者的疲劳发展有关。重要的是，我们还发现，持续疲劳和NF-KB途径活动的风险最高的患者是那些接受化学疗法和乳腺癌放射的患者。因此，我们认为NF-KB代表了治疗与乳腺癌相关疲劳的重要目标。姜黄素是姜黄的主要成分，并源自植物姜黄素longa，已被证明会影响包括NF-KB在内的许多分子信号通路。尽管姜黄素已经是几个世纪以来一直是一种食物添加剂，并且被广泛地作为中性化食用，但据信，口服姜黄素对调节NF-KB的有效性被认为受到较差的吸收或姜黄素的严重限制。 Meriva是一种姜黄素制剂，包括磷脂酰胆碱。与单独的姜黄素相比，磷脂酰胆碱与姜黄素的组合已显示可增强姜黄素的吸收。结果，Meriva代表了一种令人兴奋的方法，即减少接受化学疗法和乳腺癌放射治疗的女性NF-KB激活和疲劳。迄今为止，Meriva在几种疾病的背景下表现出了很大的希望，包括2型糖尿病，骨关节炎和慢性前葡萄膜炎。但是，在乳腺癌背景下，Meriva预防和逆转疲劳的有效性尚待评估。该建议旨在解决这个问题。值得注意的是，我们在埃默里（Emory）的团队成员已经收到了FDA的IND来提议的研究。当前提案的主要假设是，Meriva将减少在NF-KB水平上测得的炎症激活，以及接受治疗乳腺癌治疗的妇女的下游促炎细胞因子。我们还预测，Meriva会以与炎症减少有关的方式降低疲劳症状。除了证明Meriva在乳腺癌治疗后对妇女的疲劳产生积极影响外，此处提出的研究还将建立姜黄素在疲劳上的作用机制。