MAGIC ROUNDABOUT (MRB), A TUMOR ENDOTHELIAL MARKER

MAGIC ROUNDABOUT (MRB)，一种肿瘤内皮标志物

基本信息

批准号：
7477270
负责人：
PANKAJ K. SETH
金额：
$ 15.36万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-15 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7477270
关键词：
Adult Angioblast Angiogenesis Inhibitors Angiopoietin-2 Angiopoietins Basement membrane Binding Bioinformatics Biological Markers Blood Vessels Blood capillaries Candidate Disease Gene Cell Migration Inhibition function Cell Migration Inhibition measurement Characteristics Data Development Diabetic Retinopathy Disease Embryonic Development Endothelial Cells Endothelium Event Family Family member Fibroblast Growth Factor Fibroblast Growth Factor 2 Genes Growth Factor Hypoxia Image In Vitro Kidney Magic Magnetic Resonance Magnetic Resonance Imaging Mammary Neoplasms Metastatic Lesion Metastatic Melanoma Microarray Analysis Monitor Neoplasm Metastasis Neoplasms in Vascular Tissue Nephrectomy Numbers Pathologic Neovascularization Pattern Pericytes Phase Physiological Processes Play Population Pregnancy Principal Investigator Process Renal Cell Carcinoma Research Resolution Resources Rest Role Sampling Series Signal Transduction Site Solid Neoplasm TIE-2 Receptor Testing Therapeutic Tumor Angiogenesis Vascular Endothelial Cell Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Vascular Endothelium Wound Healing angiogenesis base capillary cell motility female reproductive system hemangioblastoma in vivo member molecular imaging novel precursor cell programs receptor reconstitution response therapeutic target tool tumor tumor growth tumor progression vasculogenesis

项目摘要

DESCRIPTION (provided by applicant): The development and application of new molecularly based therapies is of utmost important. The key to the development of such rational therapeutic approaches lies in the identification of suitable molecular markers. Though it has been long established that tumor progression is angiogenesis dependent, fundamental questions remain regarding the characteristic differences between normal and tumor endothelial cells. Thus, novel markers, which can distinguish between normal and tumor vascular endothelium, are needed. Importantly, these markers might provide potential therapeutic targets for anti-vascular therapy. Magic roundabout (MRB) is a roundabout receptor family member with endothelial cell restricted expression. Our preliminary data shows that the MRB is highly expressed in tumor endothelium and is markedly diminished or absent in normal endothelium. Therefore in specific aim 1, we propose to take advantage of MRB's tumor endothelial restricted expression to test the hypothesis that MRB expression can be used for in vivo molecular imaging of tumor endothelium. It is expected that investing our resources in developing MRB as a tumor vascular imaging target might provide a tool to monitor the efficacy of various antiangiogenic/ vascular therapies. In specific aim 2, we propose to isolate other tumor endothelium markers (TEMs) candidates from primary renal cell cancer (RCC) and assess their expression at sites of RCC metastasis. It is hoped that some of these TEMs may serve as anti-angiogenic targets for RCC metastasis therapy.

描述（由申请人提供）：新的分子疗法的开发和应用至关重要。开发这种合理治疗方法的关键在于识别合适的分子标记。尽管早已确定肿瘤进展依赖于血管生成，但关于正常内皮细胞和肿瘤内皮细胞之间的特征差异仍然存在基本问题。因此，需要能够区分正常血管内皮和肿瘤血管内皮的新标记物。重要的是，这些标志物可能为抗血管治疗提供潜在的治疗靶点。 Magic roundabout (MRB) 是一种内皮细胞限制性表达的环形受体家族成员。我们的初步数据表明，MRB 在肿瘤内皮中高表达，而在正常内皮中明显减少或不存在。因此，在具体目标1中，我们建议利用MRB的肿瘤内皮限制表达来检验MRB表达可用于肿瘤内皮的体内分子成像的假设。预计投入我们的资源开发 MRB 作为肿瘤血管成像靶点可能会提供一种工具来监测各种抗血管生成/血管疗法的功效。在具体目标 2 中，我们建议从原发性肾细胞癌 (RCC) 中分离出其他候选肿瘤内皮标志物 (TEM)，并评估它们在 RCC 转移部位的表达。希望其中一些 TEM 可以作为 RCC 转移治疗的抗血管生成靶点。