ALLOGENIC GLIOMA IN IMMUNE COMPETENT DOGS

描述(改编自申请人的摘要)：主要原因 神经胶质瘤患者治疗失败是复发 手术后由于这些肿瘤细胞事先侵入脑部 薄壁组织。尽管作出了积极的努力，但进展甚微。 在过去的二十年里，为了延长患者的生存时间 恶性胶质瘤。对改善管理相当重要 神经胶质瘤患者的一个重要问题是能否获得合适的动物模型。 最理想的是，这个系统将体现解剖、临床、组织病理学 分子特征与自发性人类的特征一致 疾病。申请者已经从 自发性犬星形细胞瘤。已经发明了一种技术， 测试并申请专利的是哪些胎儿对这些同种异体的免疫耐受 在狗体内可以诱导出胶质瘤细胞。这样的狗接受原位植入 同种异体胶质瘤细胞，并随后发展为颅内肿瘤 具有与人类和犬自发性相似的组织病理学特征 神经胶质瘤。该模型需要进一步完善，这将增加 它的成功率，以及定义临床终点的研究 将建立该模型作为实验性神经肿瘤学的参考： 手术切除、磁共振成像(MRI)对生长发育的研究 癌基因和抑癌基因的性质、分子遗传学分析 基因与肿瘤对当前化疗和放疗的初始反应 养生法。这样的模型将对研究新大脑的研究人员有用 从手术、化疗、放疗等学科谈肿瘤治疗 治疗、基因治疗、抗血管生成、免疫学等学科。 该项目的具体目标是：1)优化 诱导对同种异体胶质瘤细胞的免疫耐受；2)鉴定 犬脑肿瘤的临床病程，并评估是否不同 犬神经胶质瘤细胞系产生具有临床病理特征的肿瘤 并发自发性人或犬神经胶质瘤；以及3)评估 对同种异体犬脑胶质瘤常规治疗的反应，包括 手术切除、放射治疗和化疗。

DESCRIPTION (Adapted from the applicant's abstract): A primary cause for failure in the management of patients with glial neoplasms is recurrence after surgery due to prior invasion of these tumor cells into brain parenchyma. Despite aggressive efforts, very little progress has been made over the last two decades towards extending survival for patients with malignant gliomas. Of considerable importance to improvements in management of patients with gliomas is the availability of an adequate animal model. Optimally, this system would embody anatomical, clinical, histopathological and molecular features concordant with those of the spontaneous human disease. The applicants have already developed tumorigenic cell lines from spontaneously arising canine astrocytomas. A technique has been invented, tested and patented by which fetal immune tolerance to these allogenic glioma cells can be induced in dogs. Such dogs accept orthotopic implants of the allogenic glioma cells, and subsequently develop intracranial tumors with histopathological features similar to human and canine spontaneous gliomas. The model is in need of further refinements that would increase its success rate, as well as studies to define the clinical endpoints that would establish the model as a reference for experimental neuro-oncology: surgical resection, magnetic resonance imaging (MRI) studies of growth properties, molecular genetic analysis of oncogenes and tumor suppressor genes, and initial tumor response to current chemotherapy and radiation regimens. Such a model would be of use to researchers approaching new brain tumor therapy from the disciplines of surgery, chemotherapy, radiation therapy, gene therapy, antiangiogenesis, immunology, and other disciplines. The Specific Aims of the project are: 1) Optimize the success rate for induction of immune tolerance to allogenic glioma cells; 2) Characterize the clinical course of dogs with brain tumors, and assess whether different canine glioma cell lines produce tumors with clinicopathological features concurrent with spontaneous human or canine gliomas; and 3) Evaluate the response to conventional therapy of the allogenic canine glioma, including surgical resection, radiation, and chemotherapy.