GLYCOLIPIDS BRAIN TUMORS

描述：（改编自申请人的摘要） 这项研究的目的是描述 巨噬细胞中的鞘糖脂（神经节苷脂和中性糖脂） 渗透到实验小鼠脑肿瘤中。 虽然 鞘糖脂（GSL）先前在腹膜中进行了研究 巨噬细胞，以前没有在人或小鼠中进行过研究 对浸润脑肿瘤的巨噬细胞的GSL成分的影响。 我们 对小鼠脑肿瘤的初步研究表明， 巨噬细胞对总GSL组成有显著贡献， 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肿瘤室管膜母细胞瘤和 CT-2A 这两种肿瘤的生长行为不同，神经节苷脂 组成和浸润巨噬细胞的数量。 玻璃珠 柱将用于将巨噬细胞与肿瘤细胞分离， 在酶促肿瘤解离后，巨噬细胞宿主浸润细胞。 拟议的研究将涉及以下具体目标：1）A 在分离的浸润性巨噬细胞中GSL的比较分析 这两个脑瘤在大脑和皮下生长， C57BL/6小鼠的侧腹; 2）在这些肿瘤中的类似分析 严重联合免疫缺陷（SCID） 老鼠. 这第二个目标将决定宿主遗传的影响 肿瘤浸润性巨噬细胞GSL的背景。 的 对GSL的定性和定量分析将涉及高 高效薄层色谱和气液色谱， 分别 TLC免疫染色将用于定量 巨噬细胞富集的GSL，无唾液酸-GM1（GA1）和GM1b。 虽然GSL 被认为是脑血管病的分类、诊断和治疗 肿瘤，尚未确定GSL是否在肿瘤中表达。 肿瘤细胞或肿瘤浸润宿主细胞中。 的 拟议的研究可以提供新的见解的细胞起源， 脑肿瘤相关GSL和环境因素在 调节肿瘤浸润巨噬细胞的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.