GLIOMAS: BIOLOGIC, MOLECULAR, AND GENETIC STUDIES

神经胶质瘤：生物学、分子和遗传学研究

• 批准号: 3094585
• 负责人: VICTOR A LEVIN
• 金额: $ 86.85万
• 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: 1992-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3094585
• 关键词: brain neoplasms; glioma; human subject; molecular oncology; neoplasm /cancer genetics; tumor suppressor genes

By studying patients with gliomas, we hope to make correlations with clinical outcome that will shed light on malignant phenotype, the propensity of some tumor types to invade and/or metastasize, the control of tumor lineage, relevant germ line mutations, and uncover potential future molecular targets for therapy. Surgical biopsy material and early passage glioma cells from patients with different adult and childhood brain tumors will be used to determine amounts of cytokine and cytokine receptors, cell proliferation, the glutathione content, expression of glutathione-S- transferases, the activity of O6-methylguanine-DNA-methyltransferase, DNA polymerase alpha and beta, topoisomerase II, and the ability of tumor cells to repair DNA interstrand crosslinks after in vitro exposure to nitrosourea and platinum compounds. We will also investigate tumor invasiveness in histologic sections and compare this with invasiveness as judged by neuroimaging studies. The suppressor gene associated with chromosome 10 will be determined. We will investigate the effect of reinsertion of EGFR, TGFalpha, and p53 genes and chromosome 10 into normal glial cells, astrocytoma, and glioblastoma cells on phenotype, alterations in expression of EGFR, FGF, and TGFbeta, tyrosine protein kinases, and nuclear c-myc and c-fos expression. These same parameters will also be studied following exposure to retinoic acid, herbimycin, and other potential differentiating agents. The extent of p53 gene alterations in tumors and in the germ line of patients and the differential expression of type I and type II NFI transcripts will be explored. Family kindreds of glioma families with cancer will also be studied to determine relevant familial and de novo germ line mutations. In addition to these laboratory studies, we will develop aggressive and innovative clinical therapeutic trials for patients with primary malignant brain tumors in order to improve total survival and enhance quality of survival.

通过研究神经胶质瘤患者，我们希望与 临床结果将揭示恶性表型 某些肿瘤类型侵袭和/或转移的倾向，控制 肿瘤谱系、相关种系突变，并揭示潜在的未来 治疗的分子靶点。 手术活检材料和早期传代 来自不同成人和儿童脑肿瘤患者的神经胶质瘤细胞 将用于确定细胞因子和细胞因子受体、细胞的量 增殖、谷胱甘肽含量、谷胱甘肽-S-表达 转移酶，O6-甲基鸟嘌呤-DNA-甲基转移酶的活性，DNA 聚合酶α和β、拓扑异构酶II和肿瘤细胞的能力 修复体外暴露于亚硝基脲后的 DNA 链间交联 和铂化合物。 我们还将研究肿瘤的侵袭性 组织学切片并将其与通过判断的侵袭性进行比较 神经影像学研究。 与10号染色体相关的抑制基因 将被确定。 我们将研究重新插入 EGFR 的效果， TGFα和p53基因和10号染色体进入正常神经胶质细胞， 星形细胞瘤和胶质母细胞瘤细胞的表型、表达变化 EGFR、FGF 和 TGFbeta、酪氨酸蛋白激酶和核 c-myc 和 c-fos表达。 下面还将研究这些相同的参数 接触视黄酸、除草霉素和其他潜在的分化剂 代理。 肿瘤和种系中 p53 基因改变的程度 患者的I型和II型NFI的差异表达 将探讨成绩单。 患有神经胶质瘤家族的家族亲属 还将研究癌症以确定相关的家族性和新发细菌 线突变。 除了这些实验室研究之外，我们还将开发 针对患有以下疾病的患者进行积极和创新的临床治疗试验 原发性恶性脑肿瘤，以提高总生存率和 提高生存质量。