MALIGNANCY-ASSOCIATED HYPERCALCEMIA

恶性肿瘤相关性高钙血症(MAHC)由两种常见疾病引起 机制：局部溶骨性高钙血症和体液高钙血症 恶毒。这项提议几乎完全涉及幽默。 综合征，这似乎适用于大约80%的人类MAHC和 为此已经发现和/或开发了几个动物模型。 在正在进行的研究中，我们已经充分描述了人类体液综合症的特征 以及由Fisher大鼠H500间质细胞瘤引起的 以及一种新的体内小鼠鳞状细胞模型。来自人类肿瘤的材料 提取物和间质细胞条件培养液的纯化程度超过 是传统技术的20,000倍。信使核糖核酸已经制备完成 从人和动物模型肿瘤中提取并在体外和体内翻译 系统，在几个检测系统中对翻译产品进行分析。 本提案的主要目标包括：1)净化和 常规蛋白质纯化分析因子(S) 技术，使用来自各种来源的材料，2)识别 通过受体结合置换技术生成因子(S)，3)生成 常规和单抗因子(S)，4)完全 描述Fisher综合征明显完全逆转的特征 通过输注合成的PTH类似物而产生的大鼠，5)复制 实验动物的综合症和启动生理学研究，以及6) 人和动物因子(S)的分子克隆 模型肿瘤。

Malignancy-associated hypercalcemia (MAHC) results from two general mechanisms: local osteolytic hypercalcemia and humoral hypercalcemia of malignancy. This proposal deals almost exclusively with the humoral syndrome, which appears to apply in some 80% of examples of human MAHC and for which several animal models have been discovered and/or developed. In ongoing studies, we have fully characterized the human humoral syndrome as well as that resulting from the H500 Leydig cell tumor in the Fisher rat and a novel murine squamous cell model in vivo. Material from human tumor extracts and Leydig cell conditioned medium have been purified more than 20,000-fold by conventional techniques. Messenger RNA has been prepared from human and animal model tumors and translated in in vitro and in vivo systems, with assay of translation products in several detection systems. The principal goals of the present proposal include: 1) to purify and analyze the factor(s) by conventional protein purification and analytical techniques, using material from a variety of sources, 2) to identify the factor(s) by receptor binding-displacement techniques, 3) to generate conventional and monoclonal antisera to the factor(s), 4) to fully characterize the apparent complete reversal of the syndrome in the Fisher rat produced by the infusion of a synthetic PTH analog, 5) to reproduce the syndrome in experimental animals and initiate physiological studies, and 6) to pursue molecular cloning of the factor(s) from both human and animal model tumors.