QUANTITATIVE STUDY OF IFN-G AND BRAIN TUMOR SPREAD

IFN-G 与脑肿瘤扩散的定量研究

• 批准号: 2332967
• 负责人: LOIS ALTERMAN LAMPSON
• 金额: $ 27.49万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-02-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2332967
• 关键词: antigen presenting cell; autoimmune disorder; brain neoplasms; cytotoxic T lymphocyte; disease /disorder model; glioma; image processing; immunocytochemistry; interferon gamma; laboratory rat; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplastic growth; nonhuman therapy evaluation; tissue /cell culture; tumor antigens

Advances in conventional therapies are increasingly successful in imaging and sterilizing a brain tumor mass. New approaches are needed to attack the disseminated or infiltrating tumor that remains. This has lead to renewed interest in immunotherapy as an adjunctive mode of treatment. HYPOTHESES 1. In the tumor-bearing brain, intracerebral injection of IFN-g can activate antigen-presenting cells and recruit primed helper T cells. 2 . If the T cells have been primed to tumor antigen, the resulting immune cascade can lead to the destruction of disseminated brain tumor cells. SPECIFIC AIMS I. WE WILL COMPLETE THE ANALYSIS OF IFN-g-INDUCED CHANGES IN TUMOR-FREE RATS. A. We will determine the dose-response curve for the different IFN-g-mediated effects we have previously defined in unimmunized animals. B. We will compare the IFN-g-mediated changes in rats that have been primed to neural or tumor antigens. II. DO IFN-g TREATMENT AND IMMUNIZATION WORK SYNERGISTICALLY TO CONTROL THE SPREAD OF TUMOR CELLS WITH THE BRAIN? A. We will define the effects of IFN-g treatment alone on tumor spread. B. We will define the effects of [IFN-g treatment + immunization] on tumor spread. C. We will determine whether [IFN-g treatment + immunization to tumor antigen] causes autoimmune disease. METHODS. These studies will be performed in a rat model, in vivo. Stereotactic surgery, histochemistry, immunocytochemistry, and computer-assisted image analysis will be used to establish and analyze the tumor model.

传统疗法的进步在成像方面越来越成功 以及对脑瘤块进行消毒。 需要新的方法来攻击 残留的扩散性或浸润性肿瘤。这导致 免疫疗法作为一种预防性治疗模式的新兴趣。 假设 1.在荷瘤脑中，脑内注射IFN-g可以 激活抗原呈递细胞并募集引发的辅助性T细胞。 二、如果T细胞已被致敏肿瘤抗原，则产生的免疫应答将被抑制。 免疫级联反应可导致播散性脑肿瘤的破坏 细胞 具体目标 I.我们将对IFN-γ诱导的无肿瘤细胞中的变化进行分析 大鼠 A.我们将确定不同剂量的剂量反应曲线， IFN-γ介导的影响，我们以前在未免疫的动物中定义。 B。我们将比较大鼠中IFN-γ介导的变化， 对神经或肿瘤抗原做好准备。 二. IFN-g治疗和免疫是否协同作用以控制 肿瘤细胞在大脑中的扩散？ A.我们将确定单独使用IFN-g治疗对肿瘤扩散的影响。 B。我们将定义[IFN-γ治疗+免疫]对 肿瘤扩散 C.我们将确定是否[IFN-γ治疗+免疫接种]对肿瘤 抗原]导致自身免疫性疾病。 方法. 这些研究将在大鼠体内模型中进行。 立体定向手术，组织化学，免疫细胞化学， 计算机辅助图像分析将用于建立和分析 肿瘤模型。