Fish oil for the prevention and treatment of ovarian cancer

描述(申请人提供)：卵巢癌是妇科恶性肿瘤中最致命的，是女性癌症死亡的第五大原因。卵巢癌的病因知之甚少，也没有合适的早期检测标记物。由于该病通常被诊断为晚期，其存活率很低，常规治疗方式或干预策略通常无效。高肉类、低蔬菜的饮食可能与卵巢癌发病率的增加有关。Omega 3(OM-3FA)和omega 6(OM-6FA)脂肪酸的不平衡导致了额外的癌症风险。研究表明，与摄入较少OM-3FA的人群相比，摄入大量OM-3FA的人群患乳腺癌、前列腺癌和结肠癌的几率更低。因此，增加OM-3FA的摄入量可能是预防卵巢癌、加强癌症治疗和显著延长生命的一种无毒方式。鱼油是长链OM-3FA的极好来源，它已被证明在某些癌症中具有抗增殖和促凋亡活性。有效的治疗或饮食干预可以显著减缓卵巢癌的进展，但有可能将卵巢癌转变为一种女性不会死于的疾病。这项拟议的研究将测试添加鱼油的饮食在抑制和预防卵巢癌方面的有效性，并以产蛋母鸡为卵巢癌模型，研究omega-3脂肪酸的作用机制。除了衰老的母鸡，没有其他自发性上皮性卵巢癌的动物模型模仿人类的疾病。我们假设，添加鱼油的日粮将显著降低蛋鸡卵巢癌的发病率和严重程度。识别其表达受鱼油影响的分子靶点将有助于深入了解omega-3脂肪酸的作用机制，并可能为卵巢癌的病因学提供新的理解。这些研究将为开发以功能食品为基础的预防和治疗女性卵巢癌的饮食干预措施提供基础。基于对蛋鸡卵巢癌模型的创新应用，提出了两个具体的目标：目的1)通过评估鱼油对母鸡代理终点的影响，确定鱼油的最佳剂量；目的2)确定鱼油的最佳剂量在高发癌症的老年蛋鸡中抑制和预防卵巢癌的效果。

DESCRIPTION (provided by applicant): Ovarian cancer is the most lethal of the gynecological malignancies and the 5th leading cause of cancer 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 correlated 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. Fish oil is an excellent source of long chain OM-3FA which 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 fish oil supplemented diet in the suppression and prevention of ovarian cancer, and examine the mechanism of action of omega-3 fatty acids 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 fish oil supplemented diet will cause a significant reduction in the incidence and severity of ovarian carcinoma in the laying hen. Identification of molecular targets whose expression is affected by fish oil will provide insight into the mechanism of action of omega-3 fatty acids, and may provide new understanding to the etiology of ovarian cancer. These studies will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women. Two Specific Aims are proposed based on the innovative use of the laying hen model of ovarian cancer: Aim 1) to determine the optimum dose of fish oil by assessing the effects on surrogate endpoints in hens; Aim 2) to determine the effect of the optimal dose of fish oil on the suppression and prevention of ovarian cancer in old laying hens prone to high prevalence of cancer.