MALIGNANCY-ASSOCIATED HYPERCALCEMIA

恶性肿瘤相关的高钙血症

• 批准号: 3155742
• 负责人: Arthur Eastwood Broadus
• 金额: $ 31.24万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3155742
• 关键词: 1,25 dihydroxycholecalciferol; adenylate cyclase; cancer complication; cyclic AMP; disease /disorder model; enzyme induction /repression; gel electrophoresis; gel filtration chromatography; genetic manipulation; high performance liquid chromatography; histiocytic lymphoma; hormone analog; hormone metabolism; human subject; hypercalcemia; immunologic assay /test; messenger RNA; molecular cloning; monoclonal antibody; neoplasm /cancer immunology; neoplastic cell; osteoclast activating factor; parathyroid hormones; radioimmunoassay; tissue /cell culture

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome. The peptide factor or factors mediating this syndrome has not been previously identified. The two most active hypotheses at present are that the factor in question is a parathyroid hormone-like peptide or a growth factor-peptide. In ongoing studies, we have 1) fully characterized a number of animal models of the humoral syndrome and have identified a similar factor as a secretary product of normal keratinocytes, 2) purified and sequenced peptides from a human and a rat tumor, with the human tumor peptide revealing an aminoterminal region of striking homology to human parathyroid hormone, 3) constructed a cDNA library from a renal human carcinoma mRNA, and 4) begun to study the actions of the tumor-derived peptide at the level of its two key target tissues, bone and kidney. The principle goals of the present proposal include: 1) to continue our purification and sequencing efforts using tumors from humans and several other species, 2) to develop polyclonal and monoclonal antibodies to the human and rat peptides, 3) to identify and sequence a fulllength cDNA and initiate a broad range of molecular projects, and 4) to expand and refine out studies of the factor's actions on bone and renal cells.

恶性肿瘤的体液性高钙血症是一种常见的 副肿瘤综合征 肽因子或调节因子 这种综合征以前没有被发现过。 两个最 目前活跃的假设是，有问题的因素是一个 甲状旁腺素样肽或生长因子肽。 在正在进行的研究中，我们1）充分描述了一些 体液综合征的动物模型，并已确定了一个 与正常角质形成细胞分泌产物相似的因子，2） 从人和大鼠肿瘤中纯化并测序的肽， 其中人肿瘤肽显示氨基末端区域 与人甲状旁腺激素具有惊人的同源性，3） 构建人肾癌cDNA文库 mRNA，和4）开始研究的行动，肿瘤衍生的 在其两个关键靶组织骨和肾的水平上， 本提案的主要目标包括：（1）继续 我们对人类肿瘤的纯化和测序工作 和其他几个物种，2）开发多克隆和单克隆 人和大鼠肽的抗体，3）鉴定和 测序全长cDNA并启动广泛的 分子项目，和4）扩大和完善了研究的 因子对骨和肾细胞的作用。