ISOLATION OF ANTI-KAPOSI'S SARCOMA FACTORS

抗卡波西肉瘤因子的分离

• 批准号: 6311552
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6311552
• 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.

来自此计划中的其他合作者以及其他人员的最新报告 调查人员表明，粗制的临床药物制剂 重组人绒毛膜促性腺激素对卡波西肉瘤生长的抑制作用 组织培养中的(KS)细胞以及两种动物的Kaposi肿瘤 模特和人类病人。这些人绒毛膜促性腺激素制剂中包含的因素 是治疗病人的潜在治疗试剂。几乎所有的 循环中的蛋白质即使在微量情况下也会出现在尿液中。 浓度。人绒毛膜促性腺激素的药剂型被生产出来 来自孕妇的尿液，但按重量计只有35%的人绒毛膜促性腺激素。我们有 表明抗KS因子在凝胶过滤中的大小与那些 目前在此类临床分级中粗hCG出现较高 怀孕前三个月妇女原始尿液中的浓度 怀孕了。在怀孕期间，各种各样的生长因子被分泌出来 母亲和胎儿都是如此。测试的已知因素中没有一个表现出 人绒毛膜促性腺激素、人绒毛膜促性腺激素商业制剂中的抗KS活性 人绒毛膜促性腺激素β核心。这个项目的假设是这些因素 对这些抗KS效应负责(命名为hCG相关因子或HAF) 血液中的蛋白质或多肽在尿液中排出 早孕或其他状态。这些蛋白质不同于hCG， HCGbeta，或hCGbeta核心。为了检验这一假设，以下是 目的：1.从猪尿液中分离抗-KS(HAF)蛋白 与1.2项目合作的早期怀孕妇女。从化学到 用一级结构分析和红外光谱对分离的HAF分子进行表征 发展对它们的免疫分析。3.确定准确的时间顺序 妊娠早期HAF排泄规律的研究 其他生理状态会导致haf的排泄，以帮助理解 这些分子的自然功能。