GROWTH FACTOR FUNCTION IN HUMAN BRAIN TUMORS

人脑肿瘤中生长因子的功能

基本信息

批准号：
3418697
负责人：
RICHARD S MORRISON
金额：
$ 19.02万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-08-05 至 1994-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3418697
关键词：
astrocytoma athymic mouse brain cell brain neoplasms fibroblast growth factor gene expression genetic markers glia glioma human subject human tissue neoplastic transformation polymerase chain reaction western blottings

项目摘要

The molecular mechanisms underlying the development of human brain neoplasms remain poorly understood, so that, advances in surgery, radiation and chemotherapy have not successfully impacted on their lethality. There is good evidence that the more malignant varieties of such tumors express multiple chromosomal abnormalities. In some tumors, genetic aberrations have been associated with alterations in growth factors or their receptors. Consistent with this finding, we have recently demonstrated that human glioma cells express high levels of basic fibroblast growth factor (bFGF), a potent mitogen and angiogenic protein. In contrast to other growth factors previously identified in human gliomas, bFGF expression in gliomas is elevated relative to its expression in other human tumor types. this proposal is aimed at testing the hypothesis that the expression of bFGF correlates with a transformed phenotype in malignant human gliomas. We will determine: 1) if bFGF expression is modified in human glioma cells relative to normal glia and other types of brain tumors, 2) if bFGF expression is directly related to the degree of malignancy in human glioma cells, and 3) if alterations in bFGF expression can effect the phenotype of normal and transformed human glial cells. bFGF expression will be studied at the RNA and protein level using polymerase chain reaction and Western blots respectively. A correlation of bFGF expression with the degree of phenotypic malignancy in gliomas could provide a prognostic marker for this tumor. Furthermore, the expression of bFGF and its receptor in glioma cells may provide a potential avenue for interrupting the lethal cycle of glioma growth and invasion.

人脑发育的分子机制人们对肿瘤仍然知之甚少，因此，手术、放射治疗方面的进步化疗尚未成功地影响其致死率。那里有力的证据表明此类肿瘤的恶性变种表达多种染色体异常。在某些肿瘤中，基因畸变与生长因子或其受体的改变有关。与这一发现一致的是，我们最近证明了人类神经胶质瘤细胞表达高水平的碱性成纤维细胞生长因子（bFGF），一种有效的有丝分裂原和血管生成蛋白。与其他增长方式相比先前在人类神经胶质瘤中发现的因子，神经胶质瘤中的 bFGF 表达相对于其在其他人类肿瘤类型中的表达升高。这该提案旨在检验 bFGF 表达的假设与人类恶性神经胶质瘤的转化表型相关。我们将确定：1) 人类神经胶质瘤细胞中的 bFGF 表达是否发生改变相对于正常神经胶质细胞和其他类型的脑肿瘤，2) 如果 bFGF 人脑胶质瘤的表达与恶性程度直接相关细胞，以及 3) bFGF 表达的改变是否会影响表型正常和转化的人类神经胶质细胞。将研究bFGF表达使用聚合酶链式反应和 Western 检测 RNA 和蛋白质水平分别印迹。 bFGF表达与程度的相关性神经胶质瘤的表型恶性肿瘤可以为此提供预后标志瘤。此外，bFGF及其受体在胶质瘤中的表达细胞可能提供中断致死循环的潜在途径神经胶质瘤的生长和侵袭。