Angiogenic Factors Associated with Uveal Melanoma

与葡萄膜黑色素瘤相关的血管生成因素

基本信息

批准号：
7230981
负责人：
ARTHUR S POLANS
金额：
$ 37.66万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7230981
关键词：
Angiogenic Factor Animal Model Arachnoid mater Area Binding Biochemical Blood Vessels Cell Line Cells Cessation of life Chromosome abnormality Chromosomes Cytogenetics Development Diffusion Disease Double Minutes Down-Regulation Early Diagnosis Embryo Epithelium Equilibrium Event Eye Eye Neoplasms Eye diseases Frequencies Gene Amplification Gene Dosage Gene Expression Genes Growth Hepatic Human Human Cell Line Immunotherapy In Vitro Individual Integrins Investigation Laboratories Life Ligands Lymphatic Maintenance Malignant - descriptor Malignant Neoplasms Measures Metastatic Lesion Methods Microcirculation Micrometastasis Mutation Neoplasm Metastasis New Zealand Nude Mice Numbers Nutritional Requirements Optic Nerve Oryctolagus cuniculus Outcome Oxygen Pathway interactions Patients Pattern Phenotype Polymerase Chain Reaction Population Predisposing Factor Primary Neoplasm Process Property Regulation Regulatory Pathway Research Personnel Retrospective Studies Route Sampling Secondary to Site Source Specimen Staining method Stains Stem cells Symptoms Testing Thromboplastin Time Tissue-Specific Gene Expression Tissues Transplantation Tumor Tissue Tumor-Derived Uveal Melanoma axl receptor tyrosine kinase base cell type density established cell line immunosuppressed improved innovation insight laser capture microdissection melanocyte melanoma mortality neoplastic cell neovascular novel novel therapeutics outcome forecast perineural prognostic programs receptor receptor binding size tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): Uveal melanoma is the most prevalent ocular tumor originating in the eye. The genetic alterations underlying the disease are unknown, and there are few prognostic indicators that can be observed clinically. In addition, events leading to systemic metastases may have occurred by the time the ocular symptoms are recognized, and death due to hepatic disease often ensues. Improved methods are needed for the early detection and treatment of the disease. We hypothesize that the malignant and metastatic properties of such tumors depend in part on the expression of Cyr61 and Tissue Factor (TF) and their modulation of the tumor microcirculation. The microcirculation is comprised of pre-existing blood vessels, new or angiogenic vessels, and channels or networks owing to de-differentiated tumor cells. The expression of Cyr61 and TF will be measured as a function of each of these sources of the tumor microcirculation using methods of laser capture microdissection and Real-Time PCR. In addition, regions of chromosome 1p, encompassing the genes for both Cyr61 and TF, may be amplified and act as a predisposing factor for tumor development. Cytogenetic approaches, including FISH, will be used to determine the frequency of 1p amplification associated with uveal melanoma, and whether such occurrences correlate with prognostic tumor parameters. Finally, a novel pathway involving the receptor tyrosine kinase Axl, regulating Cyr61 expression, will be further delineated using biochemical methods and compared at sites of primary tumor and metastatic growth. These regulatory pathways may be important for the survival of long-lived micrometastases. Specific Aims include: 1. Determine the Frequency of Cyr61 and TF Gene Amplification as a Predisposing Factor for Uveal Melanoma. 2. Test Correlations Between Prognostic Tumor Parameters and the Expression of Cyr61 and TF Using Specimens of Human Uveal Melanoma. 3. Correlate the Expression of Cyr61 and TF with Patient Outcome in Specimens of Human Uveal Melanoma. 4. Evaluate the Function of Cyr61 and TF in Animal Models of Uveal Melanoma. 5. Characterize Cyr61 Modulation by Axl in Primary Uveal Melanoma and Principal Sites of Metastasis.

描述（由申请人提供）：卵巢黑色素瘤是源自眼睛的最普遍的眼部肿瘤。该疾病的遗传改变是未知的，几乎没有临床观察的预后指标。此外，可能在确认眼症状时发生的导致全身转移的事件发生，并且经常因肝病而导致的死亡。需要改进的方法来对疾病进行早期检测和治疗。我们假设这种肿瘤的恶性和转移性特性部分取决于CYR61和组织因子（TF）的表达及其对肿瘤微循环的调节。微循环由既有的血管，新或血管生成血管以及由于差异分化的肿瘤细胞的通道或网络组成。 CYR61和TF的表达将通过激光捕获微分解和实时PCR的方法来测量肿瘤微循环的每个来源的函数。此外，涵盖CYR61和TF的基因的1p染色体区域可能会被放大，并充当肿瘤发育的诱人因素。包括鱼在内的细胞遗传学方法将用于确定与卵巢黑色素瘤相关的1p扩增的频率，以及这种发生是否与预后肿瘤相关参数。最后，将使用生化方法进一步描述涉及调节CYR61表达的受体酪氨酸激酶AXL的新途径，并在原发性肿瘤和转移性生长的位点进行比较。这些调节途径对于长寿命微转移的存活可能很重要。具体目的包括： 1。确定CYR61和TF基因扩增的频率是紫veal黑色素瘤的诱发因子。 2。使用人卵巢黑色素瘤标本的预后肿瘤参数与CYR61和TF的表达之间的测试相关。 3。将CYR61和TF的表达与人卵巢黑色素瘤标本中的患者结局相关联。 4。评估CYR61和TF在紫veal瘤动物模型中的功能。 5。表征AXL在原发性卵巢黑色素瘤和转移的主要部位中通过AXL调制的特征。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Resveratrol metabolites do not elicit early pro-apoptotic mechanisms in neuroblastoma cells.

DOI：
10.1021/jf104901g
发表时间：
2011-05-11
期刊：
Journal of agricultural and food chemistry
影响因子：
6.1
作者：
Kenealey JD;Subramanian L;Van Ginkel PR;Darjatmoko S;Lindstrom MJ;Somoza V;Ghosh SK;Song Z;Hsung RP;Kwon GS;Eliceiri KW;Albert DM;Polans AS
通讯作者：
Polans AS