NCI CLINICAL INVESTIGATOR AWARD PROGRAM

NCI 临床研究者奖励计划

• 批准号: 3079493
• 负责人: ROBERT P FOGLIA
• 金额: $ 6.51万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079493
• 关键词: antiantibody; antiidiotype antibody; blocking antibody; cell migration; chorioallantoic membrane; electron microscopy; embryo /fetus antigen; gene expression; growth factor; histochemistry /cytochemistry; human tissue; immunoperoxidase; male reproductive system; mammalian embryology; mixed tissue /cell culture; monoclonal antibody; neoplastic cell; neuroblastoma; nonmammalian vertebrate embryology; ovary neoplasms; uterus neoplasms

Mullerian Inhibiting Substance (MIS), a product of the fetal testis, initiates regression of the Mullerian duct, the anlagen of the uterus, fallopian tubes and upper vagina. This fetal regressor may be used to produce a similar effect against tumors derived from cell lines which respond to MIS in utero. The goal of this particular study is to purify the MIS receptor and with this tool to localize the sites of action of MIS. Two approaches will be used. The first entails the use of purified labeled MIS to bind the MIS receptor. The second approach will be to use a blocking monoclonal antibody to develop an antiidiotypic antibody to MIS which can bind to MIS receptor. Once obtained, receptors can be localized both to the Mullerian duct itself and to other potential sites of action. Purification of MIS receptor will allow the study of the mechanism of Mullerian duct regression since it is not certain whether the receptor resides in the mesenchyme or in the epithelium. In addition, since MIS is known to suppress neoplasia, the MIS receptor may be able to serve as a "tumor marker" to which MIS tagged with a chemotherapeutic or radiomimetic agent may be delivered. After developing appropriate skills in immunology, biochemistry, tissue culture, and histochemistry, these techniques will be used to study the neuroblastoma tumor during the third year of the study. An analysis will be made of: 1) the influence and interaction of the microenvironment through which the embryonic neural crest cells migrate with the neuroblastoma by coculturing notochord and somites with tumor on the chorioallantoic membrane; 2) the migratory pattern of neuroblastoma cells transplanted into different regions of the early quail embryo. The goal of the latter study will be to: 1) identify what biologic modifiers are present in the matrix through which neural crest cells develop and through which they migrate; and 2) determine how these factors modulate the growth and development of the neuroblastoma. With this information manipulation of these modifiers or their analogues may result in a significant impairment in the growth of this tumor.

Mullerian抑制物质（MIS），胎儿睾丸的产物， 启动Mullerian管道的回归，子宫的Anlagen， 输卵管和上阴道。 该胎儿回归器可用于 对来自细胞系的肿瘤产生类似的作用 回应子宫里的MIS。 这项特定研究的目的是净化 MIS受体以及使用此工具来定位 误。 将使用两种方法。 第一个需要使用纯化 标记为MIS以结合MIS受体。 第二种方法是使用 阻断单克隆抗体以开发抗替代抗体的MIS 可以与MIS受体结合。 一旦获得，可以将受体定位 既有穆勒风管本身和其他潜在的作用部位。 MIS受体的纯化将允许研究 Mullerian管道回归，因为不确定受体是否 位于间质或上皮中。 另外，由于MIS是 已知可以抑制肿瘤的人，MIS受体可能能够充当 “肿瘤标记”用化学治疗或放射性标记标记为“肿瘤标记” 代理可以交付。 在发展了适当的免疫学，生物化学，组织之后 培养和组织化学，这些技术将用于研究 研究的第三年，神经母细胞瘤肿瘤。 分析将 由：1）微环境的影响和相互作用 胚胎神经rest细胞通过该胚胎与 神经母细胞瘤通过共培养脊索和与肿瘤在 绒毛膜膜； 2）神经母细胞瘤细胞的迁移模式 移植到早期鹌鹑胚胎的不同区域。 后一项研究的目的是：1）确定什么生物学 修饰符存在于矩阵中，神经rest细胞通过 发展并通过它们迁移； 2）确定这些因素如何 调节神经母细胞瘤的生长和发育。 与此 这些修饰符或其类似物的信息操纵可能会导致 在这种肿瘤的生长中严重损害中。