PATHOPHYSIOLOGY & CHEMOTHERAPY IN PSORIASIS AND CANCER

这项建议是对皮肤病的持续研究，部分表现为 由细胞增殖异常引起的。目标是获取知识 银屑病、鱼鳞状皮肤病等的病理生理学研究 增生性皮肤病，可用于开发药理学 临床改善或治愈的方法。 表皮增殖的控制及皮外因素的影响 影响这些对照的因素将在正常、非介入和 从牛皮癣表皮中寻找牛皮癣病因的线索。这个 已知的影响表皮细胞的生物和生化因素 生理学的增殖和分化，例如牛皮癣刺激剂 生长因子和肿瘤促进剂将在几个 利用遗传易感性不受影响的实验模型 牛皮癣的皮肤。一种新的体细胞融合角质形成细胞模型 技术将被用来研究增生性表皮疾病 遗传成分。HeLa与角质形成细胞融合产生 含有牛皮癣或其他疾病基因组成的永生细胞系 遗传性表皮疾病将提供一个宝贵的新工具，以基本和 治疗性研究。通过将角质形成细胞杂交细胞接种到裸体中 小鼠，增殖和分化的功能表达 可以研究体内的异常情况。第二种新模式， 环孢素免疫抑制的大鼠，这允许长期生长的 人的皮肤，将极大地促进对 活体正常皮肤和病变皮肤。 叶酸拮抗剂和叶酸的基本细胞机制 多胺生物合成抑制剂选择性影响表皮 银屑病过程中的过度增殖将被研究开发 更安全和更有效的治疗形式的药理学方法。

This proposal is a continuing study of cutaneous disease, manifest in part by abnormalities in cell proliferation. The goals are to obtain knowledge on the pathophysiology of psoriasis, ichthyosiform dermatoses, and other hyperproliferative skin diseases, that can be used to develop pharmacologic approaches for their clinical improvement or cure. Controls of epidermal proliferation and the influence of extracutaneous factors on these controls will be studied in normal, uninvolved, and psoriatic epidermis for clues to the etiopathogenesis of psoriasis. The biological and biochemical factors known to influence epidermal cell proliferation and differentiation, e.g., psoriatic stimulants, physiologic growth factors, and tumor promoters, will be examined in several experimental models that utilize the genetically predisposed uninvolved skin of psoriasis. A new keratinocyte model employing somatic cell fusion techniques will be used to study hyperproliferative epidermal diseases with genetic components. Fusions betwen HeLa and keratinocytes to produce immortal cell lines containing the genetic makeup of psoriasis or other genetic epidermal diseases will provide a valuable new tool for basic and therapeutic studies. By innoculating the keratinocyte hybrids into nude mice, functional expression of proliferation and differentiation abnormalities in vivo can be studied. The second new model, cyclosporine-immunesuppressed rats, which permit the long-term growth of human skin, will greatly facilitate pathophysiologic investigations of normal and diseased skin in vivo. The basic cellular mechanisms by which the folic acid antagonists and inhibitors of polyamine biosynthesis selectively influence epidermal hyperproliferation in the psoriatic process will be studied to develop pharmacological approaches for safer and more effective forms of therapy.