Therapeutic Efficacy of Flaxseed in the Treatment of Ovarian Cancer

亚麻籽治疗卵巢癌的疗效

• 批准号: 8510582
• 负责人: DALE B HALES
• 金额: $ 34.93万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8510582
• 关键词: 1 year old; Affect; Aging; Animal Model; Animals; Apoptotic; Bioavailable; Cessation of life; Colon Carcinoma; Consumption; Diagnosis; Diet; Dietary Fiber; Dietary Intervention; Disease; Dose; Early Diagnosis; Effectiveness; Epithelial ovarian cancer; Estrogen Antagonists; Estrogens; Etiology; Fatty Acids; Fish Oils; Flax; Foundations; Hepatotoxicity; Incidence; Inflammation; Intervention; Lignans; Linseed Oil; Lipids; Longevity; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Meat; Modality; Modeling; Molecular Target; Neoplasm Metastasis; Oils; Omega-3 Fatty Acids; Outcome; Ovarian Carcinoma; Oxidative Stress; Pathway interactions; Perimenopause; Phytoestrogens; Polyunsaturated Fatty Acids; Population; Prevention; Prevention strategy; Process; Property; Prostaglandins; Reporting; Research; Risk; Seeds; Severities; Site; Source; Staging; Surrogate Endpoint; Survival Rate; Testing; Treatment Efficacy; United States; Variant; Vegetables; Woman; alpha-Linolenic Acid; base; cancer risk; cancer therapy; commercial application; conventional therapy; dietary supplements; effective therapy; feeding; flaxseed lignan; functional food; human disease; improved; innovation; insight; interest; liver function; malignant breast neoplasm; prevent; screening

DESCRIPTION (provided by applicant): Ovarian cancer is the most lethal of the gynecological malignacies and the 5th leading cause of cance death in women. The etiology of ovarian cancer is poorly understood and there are no suitable early detection markers. Due to the late stage at which the disease is usually diagnosed the survival rate is very low and conventional treatment modalities or intervention strategies are usually ineffective. A diet which is high in meats and low in vegetables may be corellated with increased ovarian cancer incidence. An imbalance of omega 3 (OM-3FA) and omega 6 (OM-6FA) fatty acids contributes to excess cancer risk. Studies indicate that populations that consume high amounts of OM-3FA have lower incidences of breast, prostate and colon cancers than do those that consume less OM-3FA. Thus increasing the consumption of OM-3FA may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. Flaxseed is an excellent source of dietary fiber, the OM-3FA alpha-linolenic acid (ALA), and phytoestrogen lignans, which are potent anti-estrogens that have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. An effective treatment or dietary intervention that significantly reduces the progression of ovarian cancer has the potential for turning ovarian cancer into a disease that women die WITH not from. The proposed studies will test the effectiveness of a flaxseed-enriched diet in the suppression of ovarian cancer, and examine the mechanism of action of omega-3 fatty acids and enteroestrogens using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that a flaxseed enriched diet will cause a significant reduction in the severity of ovarian carcinoma in the laying hen. Furthermore, we hypothesize that dietary intervention with flaxseed results in amelioration of ovarian cancer severity due to the synergistic action of omega-3 fatty acids and phytoestrogen lignans. Identification of molecular targets whose expression is affected by flax enriched diet will provide insight into the etiology of ovarian cancer and will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women. Three Specific Aims are proposed based on the innovative used of three test diets: regular flaxseed vs. high lignan/low omega-3 fatty acid containing flaxseed (Linola) vs. flaxseed oil-derived omega-3 (high omega-3/low lignan). Aim 1) to determine the optimum dose of flaxseed; Aim 2) to evaluate the mechanism through which flaxseed reduces the severity of ovarian cancer diets containing either high lignan (Linola) or high omega-3(flaxseed oil) will b compared to regular flaxseed; and Aim 3) to evaluate the efficacy of one-year dietary intervention with these diet's on the severity of ovarian cancer in old laying hens.

描述（由申请人提供）：卵巢癌是最致命的妇科恶性肿瘤，也是女性癌症死亡的第五大原因。人们对卵巢癌的病因知之甚少，也没有合适的早期检测标志物。由于该疾病通常诊断已处于晚期，生存率非常低，传统的治疗方式或干预策略通常无效。肉类含量高、蔬菜含量低的饮食可能与卵巢癌发病率增加有关。欧米伽 3 (OM-3FA) 和欧米伽 6 (OM-6FA) 脂肪酸不平衡会导致癌症风险过高。研究表明，摄入大量 OM-3FA 的人群比摄入较少 OM-3FA 的人群乳腺癌、前列腺癌和结肠癌的发病率更低。因此，增加 OM-3FA 的摄入量可能是预防卵巢癌、增强癌症治疗和显着延长寿命的无毒方法。亚麻籽是膳食纤维、OM-3FA α-亚麻酸 (ALA) 和植物雌激素木脂素的极好来源，它们是有效的抗雌激素，已被证明在某些癌症中具有抗增殖和促凋亡活性。显着减缓卵巢癌进展的有效治疗或饮食干预有可能将卵巢癌转变为女性不会死于的疾病。拟议的研究将测试富含亚麻籽的饮食在抑制卵巢癌方面的有效性，并使用蛋鸡作为卵巢癌模型来研究 omega-3 脂肪酸和肠雌激素的作用机制。除了老年母鸡之外，没有其他自发性上皮性卵巢癌动物模型可以模仿人类疾病。我们假设富含亚麻籽的饮食将导致蛋鸡卵巢癌的严重程度显着降低。此外，我们假设，由于 omega-3 脂肪酸和植物雌激素木脂素的协同作用，亚麻籽饮食干预可改善卵巢癌的严重程度。鉴定其表达受富含亚麻的饮食影响的分子靶标将有助于深入了解卵巢癌的病因学，并将为开发基于功能性食品的饮食干预措施以预防和治疗女性卵巢癌奠定基础。基于三种测试饮食的创新使用，提出了三个具体目标：普通亚麻籽与含有亚麻籽的高木脂素/低 omega-3 脂肪酸 (Linola) 与亚麻籽油衍生的 omega-3（高 omega-3/低木脂素）。目的1）确定亚麻籽的最佳剂量；目标 2) 评估与普通亚麻籽相比，亚麻籽降低含有高木脂素 (Linola) 或高 omega-3（亚麻籽油）的卵巢癌饮食严重程度的机制；目标 3) 评估这些饮食的一年饮食干预对老年蛋鸡卵巢癌严重程度的效果。