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，也是女性癌症死亡的第五大原因。卵巢癌的病因尚不清楚，也没有合适的早期检测标志物。由于该疾病通常诊断为晚期，生存率非常低，传统的治疗方式或干预策略通常无效。多吃肉少蔬菜的饮食可能与卵巢癌发病率增加有关。omega -3 （OM-3FA）和omega -6 （OM-6FA）脂肪酸的不平衡会增加患癌症的风险。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的摄入量可能是一种无毒的方法来预防卵巢癌，增加癌症治疗和显着延长寿命。鱼油是长链OM-3FA的极好来源，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少卵巢癌的进展，有可能使卵巢癌成为一种女性不会死于卵巢癌的疾病。本研究将以蛋鸡为卵巢癌模型，测试鱼油补充饲料对卵巢癌的抑制和预防效果，并研究omega-3脂肪酸的作用机制。除了衰老的母鸡，没有其他动物模型的自发性上皮性卵巢癌模仿人类疾病。我们假设鱼油补充饲料将显著降低蛋鸡卵巢癌的发病率和严重程度。鉴定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认识。这些研究将为开发以功能性食品为基础的饮食干预以预防和治疗女性卵巢癌提供基础。基于卵巢癌蛋鸡模型的创新使用，提出了两个具体目标：目标1)通过评估对母鸡替代终点的影响来确定鱼油的最佳剂量；目的2)确定最佳鱼油剂量对癌症高发老蛋鸡卵巢癌的抑制和预防作用。

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.