CURE AND PREVENTION OF RAT GLIOMA AND HEPATOCARCINOMA

本项目考虑了诱导免疫原性参与免疫原性， 治疗和预防大鼠脑胶质母细胞瘤以及治疗 和肝癌的预防。 我们计划将亲代胶质瘤C6 植入大鼠大脑 肿瘤形成后，转染细胞 表达胰岛素样生长因子-I（IGF-I）反义RNA将是 直接注射到脑肿瘤中或皮下注射， 远端部位。这种治疗治愈实验建立的皮下 和脑胶质母细胞瘤的免疫反应。 因此，大脑 将通过免疫细胞化学分析肿瘤以鉴定 参与治疗的免疫系统细胞类型在三个额外的 啮齿类胶质母细胞瘤细胞系，在同基因组中建立肿瘤 动物，以确定该现象的普遍性。 的 辐射的细胞（不能分裂）可以激活 将研究其他细胞系中的免疫系统，正如它们对C6细胞所做的那样 所有其他细胞系。 反义核酸转染的胶质瘤细胞 将产生阻断IGF I型受体表达的载体 并注射以测试受体是否参与胞内分泌 致瘤性和免疫原性的潜在机制。 的 IGF-I的表达与主要的 将遵循组织相容性复合物-I（MHC-I）。 其他参与者 在免疫识别中，如细胞表面和可溶性共刺激分子 分子，将被评估。 严重联合免疫缺陷（SCID） 小鼠将植入患者淋巴细胞， 同一个捐赠者的胶质瘤 他将用这个系统来研究 表达反义IGF-1 cDNA的转染肿瘤细胞的免疫原性 第二个模型系统，肝细胞癌（由BRL-3A产生 细胞系）也将进行研究。 这些细胞表达IGF-II， 肝脏 它们将用反义附加体IGF-II转染 质粒和致瘤性以及参与免疫应答的能力 将在体内进行研究。 胰岛素样生长因子受体的潜在作用 肿瘤细胞免疫原性将通过反义基因进行评价 通过用IGF I型和II型受体双重转染进行转移。

This project considers the involvement of induced immunogenicity in the cure and prevention of rat glioblastoma in the brain as well as the cure and prevention of hepatocarcinoma. We plan to inject parental glioma C6 cells into rat brain. After the tumor is established, transfected cells expressing insulin-like growth factor-I (IGF-I) antisense RNA will be injected either directly into the brain tumor or subcutaneously at a distal site. Such treatment cures experimentally established subcutaneous and brain glioblastoma tumors via an immune response. Therefore, brain tumors will be analyzed by immunocytochemistry for the identification of the immune system cell types participating in the cure in three additional rodent glioblastoma cell lines with an established tumors in the syngeneic animal in order to determine the generality of the phenomenon. The possibility that irradiated cells (incapable of division) can activate the immune system in other cell lines as they do with C6 cells will be studied with all additional cell lines. Glioma cells transfected with antisense vector blocking the expression of IGF type-I receptor will be generated and injected to test whether the receptor participates in an intracrine mechanism(s) underlying tumorigenicity and immunogenicity. The interrelationships between the expression of IGF-I and the major histocompatibility complex-I (MHC-I) will be followed. Other participants in immune recognition, such as cell surface and soluble co-stimulatory molecules, will be assessed. Severe Combined Immune Deficiency (SCID) mice will be implanted with patients lymphocytes in mice carrying glioblastoma tumor of the same donor. This system will he used to study immunogenicity of transfected tumor cells expressing antisense IGF-I cDNA. The second model system, hepatocell carcinoma (generated by the BRL-3A cell line) will also be studied. These cells express IGF-II as does fetal liver. They will be transfected with antisense episome-based IGF-II plasmid and the tumorigenicity and ability to involve the immune response in vivo will be studied. The potential role of IGF receptors in altered tumor cell immunogenicity will be evaluated through antisense gene transfer by a double transfection with IGF type-I and type-II receptors.