课题基金 / 基金详情

CURE AND PREVENTION OF RAT GLIOMA AND HEPATOCARCINOMA

CURE AND PREVENTION OF RAT GLIOMA AND HEPATOCARCINOMA
大鼠胶质瘤和肝癌的治疗和预防
批准号:
2100536
负责人:
JOSEPH ILAN
金额:
$26.46万
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-02-15 至 1996-11-30

项目摘要

项目成果

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中文摘要
翻译
这个项目考虑了诱导免疫原性在 大鼠脑内胶质母细胞瘤的治疗与预防 和预防肝癌。我们计划给亲代胶质瘤C6注射 细胞植入大鼠脑内。肿瘤建立后,转基因细胞 表达胰岛素样生长因子-I(IGF-I)反义RNA 直接注射到脑瘤中或皮下注射 远端部位。这种治疗方法可以治愈皮下试验建立的 和脑胶质母细胞瘤通过免疫反应。因此,大脑 肿瘤将通过免疫细胞化学进行分析,以确定 参与治疗的免疫系统细胞类型在另外三个方面 啮齿类胶质母细胞瘤细胞系与已建立的肿瘤同基因 以确定动物现象的共性。这个 受辐射的细胞(不能分裂)可能会激活 将研究其他细胞系的免疫系统,就像对C6细胞所做的那样 以及所有额外的细胞系。反义基因转染的神经胶质瘤细胞 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内分泌 致瘤性和免疫原性的潜在机制(S)。这个 胰岛素样生长因子-I的表达与肝细胞癌的关系 将遵循组织相容性复合体-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,将被评估。严重联合免疫缺陷(SCID) 将患者淋巴细胞植入小鼠体内携带 同一供者的胶质母细胞瘤。这个系统将被用来研究 表达反义IGF-I基因的肿瘤细胞的免疫原性 第二个模型系统,肝癌(由BRL-3A产生 细胞系)也将被研究。这些细胞表达IGF-II,胎儿也是如此 肝脏。他们将被反义EB病毒IGF-II感染 质粒与致瘤性和参与免疫反应的能力 将在体内进行研究。胰岛素样生长因子受体在动脉粥样硬化中的潜在作用 将通过反义基因评估肿瘤细胞的免疫原性 通过IGF-I和I型-II受体的双重转染法转移。
英文摘要
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.
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GENE THERAPY FOR BRAIN TUMORS USING ANTISENSE CDNA TRANSCRIPTION GROW
  • 批准号:
    6305342
  • 项目类别:
  • 资助金额:
    $1.92万
  • 财政年份:
    1999
  • 负责人:
    JOSEPH ILAN
  • 依托单位:
GENE THERAPY FOR BRAIN TUMORS USING ANTISENSE CDNA TRANSCRIPTION GROW
  • 批准号:
    6264402
  • 项目类别:
  • 资助金额:
    $1.92万
  • 财政年份:
    1998
  • 负责人:
    JOSEPH ILAN
  • 依托单位:
GENE THERAPY FOR BRAIN TUMORS USING ANTISENSE CDNA TRANSCRIPTION GROWTH FACTOR
  • 批准号:
    6246468
  • 项目类别:
  • 资助金额:
    $1.98万
  • 财政年份:
    1997
  • 负责人:
    JOSEPH ILAN
  • 依托单位:
CURE AND PREVENTION OF RAT GLIOMA AND HEPATOCARCINOMA
  • 批准号:
    2100535
  • 项目类别:
  • 资助金额:
    $25.44万
  • 财政年份:
    1994
  • 负责人:
    JOSEPH ILAN
  • 依托单位:
海外基金