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MALIGNANCY-ASSOCIATED HYPERCALCEMIA

恶性肿瘤相关的高钙血症

基本信息

批准号：
3152013
负责人：
Arthur Eastwood Broadus
金额：
$ 23万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1981
资助国家：
美国
起止时间：
1981-07-01 至 1987-06-30
项目状态：
已结题

项目摘要

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.

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。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Two forms of parathyroid hormone-like adenylate cyclase-stimulating protein derived from tumors associated with humoral hypercalcemia of malignancy.

两种形式的甲状旁腺激素样腺苷酸环化酶刺激蛋白，源自与恶性肿瘤体液高钙血症相关的肿瘤。

DOI：
10.1002/jbmr.5650020616
发表时间：
1987
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
0
作者：
Stewart,AF;Burtis,WJ;Wu,T;Goumas,D;Broadus,AE
通讯作者：
Broadus,AE

Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy.

DOI：
10.1016/s0021-9258(18)48217-8
发表时间：
1987-05
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
W. Burtis;T. Wu;C. Bunch;J. Wysolmerski;K. Insogna;E. C. Weir;A. Broadus;A. F. Stewart
通讯作者：
W. Burtis;T. Wu;C. Bunch;J. Wysolmerski;K. Insogna;E. C. Weir;A. Broadus;A. F. Stewart

Calcium metabolism without anguish. Understanding the body's homeostatic 'black box'.

钙代谢无痛苦。