PATHOPHYSIOLOGY & CHEMOTHERAPY IN PSORIASIS AND CANCER

这项建议是一个持续的研究皮肤疾病，表现在部分 是由细胞增殖异常引起的 目标是获得知识 银屑病、鱼鳞病样皮肤病和其他 过度增生性皮肤病，可用于开发药理学 临床改善或治愈的方法。 表皮细胞增殖的调控及皮外基质的影响 将在正常、未受累和 银屑病表皮的银屑病发病机制的线索。 的 已知影响表皮细胞的生物学和生物化学因素 增殖和分化，例如，银屑病刺激剂、生理性的 生长因子和肿瘤促进剂，将在几个 实验模型，利用遗传易感无关 牛皮癣的皮肤 一种新的角质形成细胞体细胞融合模型 技术将用于研究过度增殖性表皮疾病， 遗传成分。 HeLa和角质形成细胞之间的融合， 含有银屑病或其他遗传组成的永生细胞系 遗传性表皮疾病将提供一个有价值的新工具， 治疗研究。 通过将角质细胞杂交体接种到裸 小鼠，增殖和分化的功能表达 可以研究体内的异常。 第二种新模式， 环孢素免疫抑制大鼠，这允许长期生长的 人类皮肤，将大大促进病理生理学研究， 正常和患病的皮肤。 叶酸拮抗剂和叶酸拮抗剂的基本细胞机制 多胺生物合成的抑制剂选择性地影响表皮 将研究银屑病过程中的过度增殖， 药理学方法更安全和更有效的治疗形式。

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.