Glycomics Laboratory for the Development of Ovarian Cancer Biomarkers

摘要 卵巢癌是一种沉默的杀手，早期症状很少，晚期疾病通常出现在 诊断。这种癌症是所有妇科恶性肿瘤中最致命的，新发病例超过2万例。 每年都会确诊。卵巢癌的5年生存率显著提高，当疾病 在早期阶段被诊断出来。因此，糖类实验室发展的长远目标是 卵巢癌生物标志物的目的是应用最先进的技术来识别 糖蛋白和糖链标记物可以早期发现卵巢癌。我们是一个多学科团队，拥有 在癌症生物学、糖组学、糖链阵列分析和翻译糖免疫学方面的专业知识 阿肯色州医学大学(UAMS)的研究人员发现，这种复杂的碳水化合物 佐治亚大学研究中心(CCRC)和哈佛医学院研究中心 哈佛大学的血糖科学。UAMS的研究人员专门研究生物标记物的发现 卵巢癌进展过程中糖基转移酶的糖学方法和功能研究 CCRC的协查人员专门从事O-连接多糖的质谱学鉴定 Notch受体和这些多糖在Notch激活中的功能分析，以及 哈佛大学专门开发与肿瘤特异性糖链结合的抗体，并开发 糖肽阵列。本申请的目的是(1)开发和验证N-链接和O-链接 糖类化合物在卵巢癌检测中的应用及(2)糖基磷脂酰肌醇的发现和开发 (GPI)锚定蛋白糖体和GPI锚定结合蛋白检测卵巢癌。

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.