Biomarkers with Biological Function in Ovarian Carcinoma

卵巢癌中具有生物学功能的生物标志物

• 批准号: 7467974
• 负责人: AMY PATRICE SKUBITZ
• 金额: $ 28.32万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7467974
• 关键词: Adhesions; Ascites; Biological; Biological Markers; Biological Process; Biology; Blood; Blood Circulation; Blood specimen; Cell Adhesion; Cell Adhesion Molecules; Code; Detection; Drug or chemical Tissue Distribution; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Event; Gene Expression; Genes; Histocompatibility Testing; Histology; Immunohistochemistry; Liquid substance; Localized; Malignant Epithelial Cell; Molecular Weight; Monoclonal Antibodies; Morphology; Numbers; Outcome; Ovarian Carcinoma; Ovarian Tissue; Pathology; Patients; Peritoneal; Play; Proteins; Purpose; RNA Interference; Radioimmunoassay; Radioimmunoprecipitation Assay; Recurrence; Research Personnel; Role; Sampling; Screening procedure; Staging; Surface; Survival Rate; Techniques; Tissue Sample; Tissues; Treatment Protocols; Western Blotting; base; design; established cell line; human tissue; improved; innovation; novel; novel therapeutics; programs; protein expression

DESCRIPTION (provided by applicant): Ten genes that code for cell adhesion molecules have been identified by gene array analysis that are up-regulated in ovarian carcinoma tissue samples and are relatively specific to ovarian carcinoma. The objective of this project is to identify one or more cell adhesion molecule in which: (a) altered gene expression corresponds to altered protein expression, (b) protein expression is associated with patient information, and (c) the biological relevance of the molecules can be defined with respect to ovarian carcinoma. These molecules may potentially serve as early detection biomarkers or for detection of recurrence of ovarian carcinoma. In addition, these molecules may prove useful in the design of novel therapeutic regimens for ovarian carcinoma. In Aim #1, the ten cell adhesion proteins will be localized by immunohistochemistry in tissue samples of ovarian carcinoma vs. other tissue types. Their molecular weight in tissue samples will be verified by Western immunoblotting or radioimmunoprecipitation. In Aim #2, blood and ascites samples from patients with ovarian carcinoma will be screened for the presence of the proteins by Western immunoblotting or radioimmunoprecipitation. The level of each protein in the patients' circulation will be quantitated by ELISA or radioimmunoassay. Statistical analysis will be used to identify the association between tissue distribution, protein expression, and circulating levels of the proteins, and tissue histology and patient outcome/information. In Aim #3, the levels of expression of the proteins on the surface and in the spent media of fresh ovarian carcinoma patient samples and established cell lines will be quantitated. The role of these cell adhesion proteins in ovarian carcinoma cell adhesion, invasion, and aggregate formation will be elucidated by use of blocking monoclonal antibodies and RNA interference. The association between levels of expression/secretion of the cell adhesion proteins with biological functional activities and patient information will be determined.

描述（由申请人提供）：通过基因阵列分析鉴定了10个编码细胞粘附分子的基因，这些基因在卵巢癌组织样本中上调，并且对卵巢癌具有相对特异性。本项目的目的是鉴定一种或多种细胞粘附分子，其中：（a）改变的基因表达对应于改变的蛋白质表达，（B）蛋白质表达与患者信息相关，以及（c）分子的生物学相关性可以相对于卵巢癌进行定义。这些分子可能作为早期检测的生物标志物或用于检测卵巢癌的复发。此外，这些分子可能被证明是有用的，在设计新的治疗方案，卵巢癌。在目标#1中，将通过免疫组织化学在卵巢癌与其他组织类型的组织样品中定位10种细胞粘附蛋白。将通过Western免疫印迹或放射免疫沉淀法验证组织样本中的分子量。在目标#2中，将通过蛋白质免疫印迹或放射免疫沉淀来筛选来自卵巢癌患者的血液和腹水样品中蛋白质的存在。患者循环中每种蛋白质的水平将通过ELISA或放射免疫测定法定量。将使用统计分析来确定组织分布、蛋白表达和蛋白循环水平与组织组织学和患者结局/信息之间的相关性。在目标#3中，将定量新鲜卵巢癌患者样品和建立的细胞系的表面上和用过的培养基中的蛋白质的表达水平。这些细胞粘附蛋白在卵巢癌细胞粘附、侵袭和聚集形成中的作用将通过使用阻断性单克隆抗体和RNA干扰来阐明。将确定细胞粘附蛋白的表达/分泌水平与生物功能活性和患者信息之间的关联。