GROWTH FACTOR FUNCTION IN HUMAN BRAIN TUMORS

人脑肿瘤中生长因子的功能

• 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
• 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

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.

人脑发展的基础的分子机制 肿瘤的理解仍然很差，因此手术的进步，辐射 化学疗法并未成功影响其致命性。 那里 是很好的证据表明，这种肿瘤的更恶性变种表达 多种染色体异常。 在某些肿瘤中，遗传像差 与生长因子或其受体的改变有关。 与这一发现一致，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）， 有效的有丝分裂原和血管生成蛋白。 与其他增长相反 先前在人神经胶质瘤中鉴定出的因素，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而言，其表达升高。 这 提案旨在检验BFGF表达的假设 与恶性的人神经胶质瘤中转化的表型相关。 我们 将确定：1）如果在人神经胶质瘤细胞中修改了BFGF表达 相对于正常的神经胶质和其他类型的脑肿瘤，2）如果BFGF 表达与人神经胶质瘤的恶性肿瘤直接相关 细胞，3）如果BFGF表达的改变会影响 正常和转化的人神经胶质细胞。 将研究BFGF表达 在RNA和蛋白质水平上使用聚合酶链反应和西部 分别是印迹。 BFGF表达与程度的相关性 神经胶质瘤中的表型恶性肿瘤可以为此提供预后标记 瘤。 此外，BFGF及其受体在神经胶质瘤中的表达 细胞可能会提供中断致命周期的潜在途径 神经胶质瘤的生长和入侵。