Inflammatory processes In diet-Induced pancreatic cancer promotion

有大量证据表明，富含脂肪和卡路里的西式饮食是导致肥胖的关键因素 肥胖和包括癌症在内的其他慢性疾病的发展。尽管潜在的机制 炎症可能是多方面的，在高脂饮食诱导的肥胖和 癌症。浸润性炎症细胞以及全身和局部促炎介质水平 为肿瘤的发展提供理想的微环境抗炎策略已经在许多方面得到了证明 延缓或预防癌症发展的动物模型被广泛认为是耐人寻味的 癌症预防的方法。我们的初步研究表明，高脂肪、高热量的饮食 (HFCD)在炎性微环境中的存在大大加速了发展 在胰腺癌基因工程动物模型中胰腺癌前体病变的研究进展 此外，我们之前发表的研究表明，口腔癌 给予抗炎药物延缓胰腺癌前期病变的进展 胰腺癌发生的条件性Kras小鼠模型。此外，饮食补充剂对 鱼油对小鼠胰腺癌移植瘤的抑制作用 促炎前列腺素水平。该项目的主要假设是，一个HFCD 促进胰腺癌的发展和生长。这一效应由存在所介导和加速 一个炎热的微环境。以炎症反应为靶点可能预防胰腺癌 由世界粮食计划署推动的发展。为了验证我们的假设，我们提出了以下三个具体目标。 1)确定胰腺炎症在HFCD诱导的胰腺癌中的重要性 研究进展，2)研究二十烷类化合物在HFCD诱导的胰腺癌中的重要性 开发和研究其作用机制；3)确定鱼油作为抗肿瘤药物的效果。 炎症策略，以减少胰腺癌的发展。最先进的基因工程 动物模型将被用来检验这些假设。在细胞培养中将剖析潜在的机制。 模拟胰腺癌不同发展阶段的系统。 相关性(请参阅说明)： 我们期待着证明我们的假设，即旨在抑制炎症成分的策略，例如 通过鱼油，显著延缓或阻止高脂肪、高热量饮食的促癌作用。 由于今天鱼油被广泛用作一般的促进健康的膳食补充剂，我们的研究将提供 使用鱼油预防胰腺癌的科学依据和阐明其机制。我们的 结果也可能转移到其他与肥胖相关的癌症，甚至非恶性慢性病。

There is substantial evidence that the Western-style diet, rich in fats and calories, is a critical factor in the development of obesity and other chronic diseases, including cancer. Although the underlying mechanisms are likely multi-faceted, inflammation certainly plays an important role in High Fat Diet-induced obesity and cancer. Infiltrating inflammatory cells as well as systemic and local levels of pro-inflammatory mediators provide in ideal micro-milieu for tumor development Anti-inflammatory strategies have been shown in many animal models to delay or prevent the development of cancers and are widely considered intriguing approaches for cancer prevention. Our preliminary studies have shown that a high fat, high calorie diet (HFCD) in the presence of an inflammatory micro-environment substantially accelerates the development and progression of pancreatic cancer precursor lesions in a genetically engineered animal model of pancreatic cancer development Furthermore, our previous published studies have demonstrated that oral administration of an anti-inflammatory drug delays the progression of pancreatic cancer precursor lesions in the conditional Kras mouse model of pancreatic cancer development. In addition, dietary supplementation of fish oil inhibited pancreatic cancer grov\rth in a xenograft mouse model, which was accompanied by reduced levels of pro-inflammatory prostaglandin species. The overarching hypothesis of this Project is that a HFCD promotes pancreatic cancer development and growth. This effect mediated and accelerated by the presence of an inflammatory micro-environment. Targeting the inflammatory response may prevent pancreatic cancer development promoted by the HFCD. To test our hypothesis the following three Specific Aims are proposed. 1) To determine the importance of pancreatic inflammation in HFCD-induced pancreatic cancer development, 2) to characterize the importance of eicosanoids in HFCD-induced pancreatic cancer development and investigate their mechanisms, and 3) to determine the efficacy of fish oil as an anti- inflammatory strategy to reduce pancreatic cancer development. State-of-the-art genetically engineered animal models will be utilized to test the hypotheses. Underlying mechanisms will be dissected in cell culture systems that mimic the different stages of pancreatic cancer development. RELEVANCE (See instructions): We anticipate proving our hypothesis that strategies aimed at inhibiting the inflammatory component, e.g. through fish oil, significantly delay or prevent the tumor-promoting effects of the high fat, high calohe diet. Since today fish oil is widely used as a general health-promoting dietary supplement, our studies will provide the scientific rationale for the use of fish oil to prevent pancreatic cancer and elucidate its mechanism. Our results may also be transferable to other obesity-related cancer and even non-malignant chronic diseases.