TUMOR LIPIDS AND HYPERTHERMIA/CHEMOTHERAPY

我们建议继续我们对膜基础的研究 对抗癌治疗的敏感性。此应用程序将用于 研究鱼油多不饱和脂肪酸在 癌症生物学与治疗。有证据表明，膜 Omega-3类的多不饱和化合物，它在 海洋精油，可以抑制恶性肿瘤的生长。在……里面 与之相反，omega-6级的人实际上可能会促进 成长。我们的范例是试验性地插入脂肪酸 不同的比较类别进入癌症的细胞膜 细胞。我们将同时利用饮食和组织培养模式。这个 插入相当迅速，且具有剂量依赖性(具有平台性)。这个 替代膜没有明显的主要破坏作用 基于初步证据的膜结构。这个 生化(脂质成分)和物理结果(膜 在质膜和胞内膜上的取代顺序) 都会被描绘出来。小鼠肿瘤和人肿瘤的研究 都包括在内。替代对生物(自体)的影响 更新、差异化)将被研究。最重要的是，我们 将研究饮食脂肪酸改变作为一种 癌症化疗的治疗辅助剂(阿霉素和 膜活性药物ET-18-OCH3)和热疗。临床 将追寻背景，但不会强迫。我们也会继续 我们对膜的作用机制的研究 多不饱和脂肪酸的浓缩增加了对 白血病细胞对阿霉素和这将包括一个多方面的 氧自由基与后续脂质作用的研究进展 过氧化。这些研究应该有助于理解 膜在改变的癌症生物学中的作用及其应用 将脂肪酸改变作为癌症治疗的辅助手段作为 多式联运方式。这一结果可能导致应用于 人类的癌症，因为有饮食方法可以让你 临床上的胎膜。

We propose to continue our study of the membrane basis for susceptibility to anticancer therapy. This application is to investigate the role of fish oil polyunsaturated fatty acids in cancer biology and therapy. There is evidence that membrane polyunsaturates of the omega-3 class, which are abundant in marine oils, can inhibit the growth of malignant neoplasms. In contradistinction, those of omega-6 class may actually promote growth. Our paradigm is the experimental insertion of fatty acids of various comparative classes into the membranes of cancer cells. We will utilize both dietary and tissue culture models. The insertion is fairly rapid and dose dependent (with plateau). The substituted membranes have no apparent major disruption of membrane structure based on preliminary evidence. The biochemical (lipid composition) and physical results (membrane order) of the substitution on plasma and intracellular membranes will be delineated. Studies on both a murine and human neoplasm are included. The effects of the substitution on the biology (self- renewal, differentiation) will be examined. Most importantly, we will investigate the potential of dietary fatty acid alteration as a therapeutic adjunct to cancer chemotherapy (Adriamycin and the membrane active drug ET-18-OCH3) and hyperthermia. Clinical contexts will be pursued, but not forced. We will also continue our investigation of the mechanisms by which membrane polyunsaturated fatty acid enrichment augments the sensitivity of leukemia cells to Adriamycin and this will include a multifaceted investigation of the role of oxygen radicals and subsequent lipid peroxidation. The studies should help understand the role of membranes in the altered biology of cancer, and the application of fatty acid alteration as adjunct to cancer therapy as part of a multimodal approach. The results could lead to application to human cancer since there are dietary methods for enriching membranes clinically.