Glycomics Laboratory for the Development of Ovarian Cancer Biomarkers

卵巢癌生物标志物开发糖组学实验室

• 批准号: 10418619
• 负责人: KAREN L. ABBOTT
• 金额: $ 61.34万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-10 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10418619
• 关键词: Antibodies; Arkansas; Ascites; Binding; Binding Proteins; Biological Assay; Biological Markers; Biotin; Blood; C-terminal; Cancer Biology; Cancer Patient; Carbohydrates; Cell Communication; Cells; Chemoresistance; Complex; Detection; Development; Diagnosis; Disease; Elements; Enzymes; Epithelial ovarian cancer; Future; GPAA1 gene; GPI Membrane Anchors; Glycopeptides; Glycoproteins; Glycosylphosphatidylinositols; Goals; Growth; Immune; Immunoglobulin G; Label; Link; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Mass Spectrum Analysis; Medical; Methods; Monitor; Non-Malignant; Notch Signaling Pathway; Ovarian Endometrioid Adenocarcinoma; Ovary; Papillary; Pathway interactions; Peptides; Polysaccharides; Population; Prognostic Marker; Proteins; Quality of life; Recurrence; Research; Research Personnel; Role; Sampling; Science; Screening for Ovarian Cancer; Serous; Serous Cystadenocarcinoma; Serum; Side; Site; Specificity; Stage at Diagnosis; Structure; Survival Rate; Symptoms; Technology; Therapeutic Intervention; Time; Tissues; Universities; Validation; advanced disease; alpha Toxin; antibody detection; biomarker discovery; cancer biomarkers; cancer cell; cancer stem cell; carbohydrate binding protein; defined contribution; detection assay; glycosylation; glycosyltransferase; improved; laboratory development; lipid structure; medical schools; multidisciplinary; notch protein; potential biomarker; stem cell population; sugar; tumor; tumor growth; tumor microenvironment; tumor progression

ABSTRACT Ovarian cancer is a silent killer with few early symptoms and advanced disease often present at the time of diagnosis. This cancer is the most lethal of all gynecologic malignancies with over 20,000 new cases diagnosed each year. The 5 year survival rates for ovarian cancer dramatically improve when the disease is diagnosed at an earlier stage. Therefore, the long term goal of the Glycomics Laboratory for the Development of Ovarian Cancer Biomarkers is to apply the most advanced technologies toward the goal of identifying glycoprotein and glycan markers that can detect ovarian cancer early. We are a multidisciplinary team with expertise in cancer biology, glycomics, glycan array analysis, and translational glycoimmunology from investigators at the University of Arkansas for Medical Sciences (UAMS), the Complex Carbohydrate Research Center (CCRC) at the University of Georgia, and the Harvard Medical School Center for Glycoscience at Harvard University. The investigators at UAMS specialize in biomarker discovery using glycomic methods and functional studies of glycosyltransferase enzymes in ovarian cancer progression, the co-investigators at the CCRC specialize in the mass spectrometry identification of O-linked glycans present on the Notch receptor and the functional analysis of these glycans in Notch activation, and the co-investigators at Harvard specialize in the development of antibodies binding to tumor-specific glycans and the development of glycopeptide arrays. The aims of this application are (1) To develop and validate N-linked and O-linked glycoforms for the detection of ovarian cancer and (2) To discover and develop glycosylphosphatidylinositol (GPI) anchored protein glycoforms and GPI anchor binding proteins for the detection of ovarian cancer.

摘要 卵巢癌是一种沉默的杀手，早期症状很少，晚期疾病通常在发病时出现。 诊断.这种癌症是所有妇科恶性肿瘤中最致命的，有超过20，000个新病例 每年诊断。卵巢癌的5年生存率显着提高时，疾病是 早期诊断。因此，糖组学实验室的长期目标是开发 卵巢癌生物标志物的目的是应用最先进的技术， 糖蛋白和聚糖标记物可以早期检测卵巢癌。我们是一个多学科的团队， 在癌症生物学、糖组学、聚糖阵列分析和翻译糖免疫学方面的专业知识， 阿肯色州大学医学科学院（UAMS）的研究人员， 格鲁吉亚大学的研究中心（CCRC）和哈佛医学院的 哈佛大学的糖科学。UAMS的研究人员专门从事生物标志物的发现， 卵巢癌进展中糖基转移酶的糖组学方法和功能研究， CCRC的共同研究者专门从事质谱鉴定存在于 Notch受体和这些聚糖在Notch激活中的功能分析，以及 哈佛专门从事开发与肿瘤特异性聚糖结合的抗体， 糖肽阵列本申请的目的是（1）开发和验证N-连接和O-连接的 发现和开发糖基磷脂酰肌醇 (GPI)锚定蛋白糖型和GPI锚结合蛋白用于检测卵巢癌。