Serum Markers of Angiogenesis in von Hippel-Lindau Dise*

希佩尔-林道病血管生成的血清标志物*

• 批准号: 6891040
• 负责人: GAIL ELIZABETH TOMLINSON
• 金额: $ 7.8万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891040
• 关键词: Von Hippel Lindau syndrome; angiogenesis; biomarker; blood banks; cancer registry /resource; cancer risk; clinical research; diagnosis design /evaluation; early diagnosis; family genetics; gene mutation; genetic disorder; genetic registry /resource /referral center; genetic screening; genetic susceptibility; growth factor receptors; hematology; human subject; neoplasm /cancer diagnosis; patient oriented research; phlebotomy; serum; tumor suppressor genes; vascular endothelial growth factors

DESCRIPTION (provided by applicant): Von HippeI-Lindau disease (VHL) is a rare autosomal dominant tumor predisposition syndrome characterized by multi-system benign and malignant tumors characterized by angiogenic proliferation. Patients present at an average age of 26 years; 25-43 percent present with retinal hemangioblastoma, while 35-39 percent present with cerebellar hemangioblastoma. However, patients may be symptomatic during the first decade of life; therefore, future attempts at pre-clinical intervention will likely target both pediatric and adult populations. In this application, we take the initial steps to develop pre-clinical markers of neoptasia. We will establish a serum bank and a registry of families with Von Hippel-Lindau Disease. We hypothesize that serum levels of VEGF and its soluble receptor sVEGFR1 may be significantly different in patients genetically determined to have VHL than in mutation-negative controls. We will analyze serum from mutation-positive and age matched mutation negative individuals for levels of VEGF and sVEGF-R1. We will determine the correlation between severity of VHL disease and the serum levels of VEGF and sVEGF-R1. We will analyze serum levels in terms of mutation sub-type. As additional markers of angiogenesis become known, we will be strategically placed to perform analyses on our serum samples banked from these high-risk individuals. The establishment of a VHL registry in North Texas will also place us in an excellent position to develop clinical protocols aimed towards early detection of lesions in VHL patients.

描述（由申请人提供）： Von HippeI-Lindau 病（VHL）是一种罕见的常染色体显性肿瘤易感综合征，其特征是多系统良性和恶性肿瘤，以血管生成增殖为特征。患者平均年龄 26 岁； 25-43% 患有视网膜血管母细胞瘤，35-39% 患有小脑血管母细胞瘤。然而，患者在生命的最初十年可能会出现症状；因此，未来的临床前干预尝试可能会针对儿童和成人人群。 在此应用中，我们采取了初步步骤来开发肿瘤的临床前标志物。我们将建立一个血清库和冯·希佩尔-林道病家族登记处。我们假设，在基因确定患有 VHL 的患者中，VEGF 及其可溶性受体 sVEGFR1 的血清水平可能与突变阴性对照患者存在显着差异。我们将分析突变阳性和年龄匹配的突变阴性个体的血清中 VEGF 和 sVEGF-R1 的水平。 我们将确定 VHL 疾病的严重程度与 VEGF 和 sVEGF-R1 血清水平之间的相关性。我们将根据突变亚型分析血清水平。随着血管生成的其他标志物逐渐为人所知，我们将战略性地对从这些高风险个体中储存的血清样本进行分析。 在北德克萨斯州建立 VHL 登记处也将使我们处于有利地位，能够制定旨在早期发现 VHL 患者病变的临床方案。