GLYCOLIPIDS BRAIN TUMORS

描述：(改编自申请者摘要)总体目标 这项研究的目的是描述 巨噬细胞中的神经节苷脂和中性糖脂 会渗入实验性的小鼠脑瘤。虽然 鞘糖脂(GSLS)以前在腹膜中被研究过 巨噬细胞，之前还没有对人或小鼠的研究 关于浸润性脑瘤的巨噬细胞的GSL组成。我们的 对小鼠脑瘤的初步研究表明，宿主浸润性 巨噬细胞对GSL的总组成有很大贡献 在体内生长的实体脑瘤。拟议的研究将是 对两种实验性小鼠脑瘤进行了研究，室管膜母细胞瘤和 CT-2A。这两种肿瘤的生长行为不同，神经节苷脂 组成和浸润性巨噬细胞的数量。玻璃珠 色谱柱将用于将巨噬细胞与肿瘤细胞和非肿瘤细胞分离 肿瘤酶解离后巨噬细胞侵袭宿主细胞。 拟议的研究将涉及以下具体目标：1)A) 日本血吸虫浸润性巨噬细胞GSLS的比较分析 在大脑和皮下同时生长的两种脑瘤 C57BL/6小鼠的侧翼；2)在这些肿瘤中的类似分析 生长在SCID的侧翼(严重的联合免疫缺陷) 老鼠。这第二个目标将决定寄主遗传的影响 肿瘤浸润性巨噬细胞GSLS的研究背景。这个 GSLS的定性和定量分析将涉及HIGH 性能薄层层析和气-液色谱， 分别进行了分析。TLC免疫染色将用于定量检测 巨噬细胞富含GSLS、Asialo-GM1(GA1)和GM1b。尽管GSLS拥有 被认为是脑的分类、诊断和治疗 肿瘤中是否表达GSLS尚未确定。 肿瘤细胞或肿瘤浸润性宿主细胞。这个 拟议中的研究可以为人类的细胞起源提供新的见解 脑肿瘤相关的GSLS及环境因素在GSLS中的作用 调节肿瘤浸润性巨噬细胞的GSL组成。

DESCRIPTION: (adapted from Applicant's Abstract) The broad objective of this research is to characterize the composition of glycosphingolipids (gangliosides and neutral glycolipids) in macrophages that infiltrate experimental mouse brain tumors. Although glycosphingolipids (GSLs) were studied previously in peritoneal macrophages, there have been no previous studies in either man or mouse on the GSL composition of macrophages that infiltrate brain tumors. Our preliminary studies in mouse brain tumors suggest that host infiltrating macrophages contribute significantly to the total GSL composition of solid brain tumors growing in vivo. The proposed research will be conducted on two experimental mouse brain tumors, ependymoblastoma and CT-2A. The two tumors differ in growth behavior, ganglioside composition and in the number of infiltrating macrophages. Glass bead columns will be used to separate macrophages from tumor cells and non- macrophage host-infiltrating cells after enzymatic tumor dissociation. The proposed research will involve the following specific aims: 1) A comparative analysis of GSLs in infiltrating macrophages isolated from the two brain tumors growing in both the brain and subcutaneously in the flank of the C57BL/6 mouse; 2) A similar analysis in these tumors growing in the flank of the SCID (severe combined immune deficiency) mouse. This second aim will determine the influence of host genetic background on the GSLs of tumor-infiltrating macrophages. The qualitative and quantitative analysis of the GSLs will involve high performance thin-layer chromatography and gas-liquid chromatography, respectively. TLC immunostaining will be used to quanitate the macrophage enriched GSLs, asialo-GM1 (GA1) and GM1b. Although GSLs have been considered for the classification, diagnosis and therapy of brain tumors, it has not been established whether the GSLs are expressed in the neoplastic tumor cells or in tumor-infiltrating host cells. The proposed research can provide new insight on the cellular origin of brain tumor-associated GSLs and on the role of environmental factors in regulating the GSL composition of tumor-infiltrating macrophages.