ISOLATION OF ANTI-KAPOSI'S SARCOMA FACTORS

抗卡波西肉瘤因子的分离

• 批准号: 6203469
• 负责人: Steven Birken
• 金额: $ 15.41万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6203469
• 关键词: AIDS related neoplasm /cancer; Kaposi's sarcoma; SDS polyacrylamide gel electrophoresis; analytical chemistry; angiogenesis inhibitors; antineoplastics; bioassay; chemical stability; chorionic gonadotropin; chromatography; gel filtration chromatography; gestational age; human pregnant subject; immunologic assay /test; mass spectrometry; matrix assisted laser desorption ionization; method development; peptide structure; pregnancy; protein purification; protein sequence; reversed phase chromatography; urine

Recent reports from other collaborators in this program as well as other investigators have shown that crude clinical pharmaceutical preparations of hCG approved for human injection inhibit the growth of Kaposi's Sarcoma (KS) cells in tissue culture as well as Kaposi tumors in both animal models and human patients. Factors contained within these hCG preparations are potential therapeutic reagents for patient treatment. Virtually any protein in the circulation can appear in the urine even at trace concentrations. The pharmaceutic forms of hCG for human use are produced from the urine of pregnant women but are only 35% hCG by weight. We have shown that anti-KS factors similar in size on gel filtration to those present in such clinical grades on crude hCG appear in higher concentrations in raw urine form women in the first trimester of pregnancy. During pregnancy, a wide variety of growth factors are secreted both by mother and fetus. None of the known factors tested exhibit the anti-KS activities found in commercial preparations of hCG, hCG subunits and the hCG beta core. The hypothesis of this project is that the factors responsible for these anti-KS effects (name hCG associated factors or HAF) are proteins or peptides in blood which are excreted into the urine during early pregnancy or other states. These proteins are distinct from hCG, hCGbeta, or hCGbeta core. In order to test this hypothesis, the following aims are proposed: 1. Isolate the anti-KS (HAF) proteins from the urine of women in early pregnancy in collaboration with project 1. 2. To chemically characterize the isolated HAF molecules by primary structural analysis and develop immunoassays to them. 3. To determine the precise chronological pattern of HAF excretion in early pregnancy and to investigate whether other physiological states lead to excretion of HAF to help understand the natural functions of these molecules.

该计划的其他合作者以及其他合作者的最新报告 研究人员已经表明， 批准用于人体注射的hCG抑制卡波西肉瘤的生长 (KS)组织培养中的细胞以及两种动物中的卡波西肿瘤 模型和人类患者。这些hCG制剂中包含的因素 是用于患者治疗的潜在治疗试剂。几乎任何 蛋白质在循环中可以出现在尿液中，即使在微量 浓度的生产人用hCG的药物形式， 从孕妇的尿液中提取，但按重量计只有35%的hCG。我们有 显示抗KS因子在凝胶过滤上的大小类似于那些 存在于粗hCG的这种临床分级中， 妇女在怀孕前三个月的原始尿液中的浓度 怀孕在怀孕期间，各种各样的生长因子分泌 母亲和胎儿都是如此。测试的已知因素中没有一个表现出 在hCG的商业制剂中发现的抗KS活性，hCG亚单位 和hCG β核心该项目的假设是，因素 负责这些抗KS作用（命名为hCG相关因子或HAF） 是血液中的蛋白质或肽，在尿中排泄。 早孕或其他状态。这些蛋白质不同于hCG， hCG β或hCG β核心。为了验证这一假设，以下 提出了以下目标：1.从小鼠尿中分离抗KS（HAF）蛋白， 与项目1合作，帮助早孕妇女。2.进行化学 通过一级结构分析表征分离的HAF分子， 对它们进行免疫分析。3.确定精确的时间顺序 妊娠早期HAF排泄模式，并研究是否 其他生理状态导致HAF的排泄，以帮助理解 这些分子的天然功能。