MALIGNANCY-ASSOCIATED HYPERCALCEMIA

糖尿病相关性高钙血症（MAHC）的结果来自两个一般的 机制：局部溶骨性高钙血症和体液性高钙血症， 恶性肿瘤 这一建议几乎完全涉及体液 综合征，这似乎适用于约80%的人MAHC的例子， 为此已经发现和/或开发了几种动物模型。 在正在进行的研究中，我们已经充分描述了人类体液综合征的特征， 以及由Fisher大鼠中的H500 Leydig细胞瘤引起的 和一种新的鼠体内鳞状细胞模型。 人肿瘤材料 提取物和Leydig细胞条件培养基已经纯化超过 20,000倍的传统技术。 信使RNA已经被制备出来 从人和动物模型肿瘤中提取并在体外和体内翻译 系统，在几个检测系统中测定翻译产物。 本提案的主要目标包括：1）净化和 通过常规的蛋白质纯化和分析来分析因子 技术，使用来自各种来源的材料，2）确定 通过受体结合置换技术，3）产生 因子的常规和单克隆抗血清，4）完全 描述Fisher综合征的明显完全逆转 通过输注合成的PTH类似物产生的大鼠，5）以再现 实验动物综合征和启动生理学研究，以及6） 从人类和动物中进行因子的分子克隆 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.