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.

该计划中其他合作者的最新报告以及其他 研究人员表明，粗略的临床药物制剂 批准人类注射的HCG抑制了Kaposi肉瘤的生长 （KS）组织培养和两种动物的Kaposi肿瘤中的细胞 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 循环中的蛋白质即使在痕量处也可能出现在尿液中 浓度。 HCG用于人类使用的药物形式是生产的 孕妇的尿液，但重量仅为HCG 35％。我们有 表明抗KS因子的凝胶过滤大小与那些相似的因子 在此类临床等级中存在于原油HCG上 原始尿液中的浓度在头三个月的女性 怀孕。怀孕期间，分泌多种生长因素 由母亲和胎儿。未测试的已知因素均显示 在HCG，HCG亚基的商业准备中发现的反KS活动 和HCG Beta核心。该项目的假设是因素 负责这些反KS效应（名称HCG相关因素或HAF） 是血液中的蛋白质或肽在尿液中排泄到尿液中 早期怀孕或其他州。这些蛋白质与HCG不同， HCGBETA或HCGBETA核心。为了检验这一假设，以下 提出了目的：1。将抗K（HAF）蛋白隔离在尿液中 妇女在与项目1。2合作的怀孕初期。 通过主要结构分析和 向他们开发免疫测定。 3。确定准确的时间顺序 早期怀孕的HAF排泄模式，并调查是否是否 其他生理状态导致HAF排泄，以帮助了解 这些分子的自然功能。