Serum Markers /Angiogenesis in von Hippel-Lindau Disease

希佩尔-林道病的血清标志物/血管生成

• 批准号: 6784375
• 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/6784375
• 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遗传肿瘤易感综合征，以血管生成性增生为特征的多系统良性和恶性肿瘤为特征。患者平均年龄为26岁; 25- 43%患有视网膜血管母细胞瘤，而35- 39%患有小脑血管母细胞瘤。然而，患者可能在生命的前十年出现症状;因此，未来临床前干预的尝试可能针对儿童和成人人群。 在本申请中，我们采取初步步骤来开发neoptasia的临床前标志物。我们将建立一个血清库和一个冯希佩尔-林道病家庭登记处。我们推测，VEGF及其可溶性受体sVEGFR 1的血清水平可能是显着不同的患者基因确定有VHL比突变阴性对照。我们将分析突变阳性和年龄匹配的突变阴性个体的血清VEGF和sVEGF-R1水平。 我们将确定VHL疾病的严重程度与血清VEGF和sVEGF-R1水平之间的相关性。我们将根据突变亚型分析血清水平。随着更多的血管生成标志物的发现，我们将在战略上对这些高危个体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一个非常有利的位置，以制定旨在早期发现VHL患者病变的临床方案。