IMMUNOBIOLOGY OF VIRAL INDUCED TUMORS IN EXPERIMENTAL ANIMALS

实验动物病毒诱发肿瘤的免疫生物学

• 批准号: 6243928
• 负责人: FRED LUBLIN
• 金额: $ 18.96万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243928
• 关键词: Papovaviridae; brain neoplasms; cell cycle proteins; cellular oncology; cytokine; immunity; laboratory mouse; molecular oncology; neoplasm /cancer transplantation; neoplastic growth; retinoblastoma protein; tissue /cell culture; transcription factor; transforming growth factors; tumor suppressor genes; virus related neoplasm /cancer

JC virus (JCV) is a human polyoma virus that has been associated with neurooncogenesis in several animal species. JCV can induce neural tumors in mice and hamsters as well as in nonhuman primates, e.g., owl and squirrel monkeys. In this project, we will utilize this oncogenic effect to study the immunobiology of CNS-derived tumors. There is evidence to suggest that brain tumors induce immunoregulatory abnormalities within their hosts. We plan to utilize the oncogenic potential of the human neurotropic virus (JCV) early protein, T-antigen, as a tool for inducing CNS-origin tumors. These tissues will be analyzed for their ability to induce a blood-brain barrier. The ability of these tumors to serve as immune targets will be assessed by comparing their ability to be rejected using xeno, allo, and homografts. Their immunogenicity will also be assessed by determining whether they are targeted by encephalitogenic lymphocytes, as we have demonstrated for normal astrocytes. Studies will be performed to evaluate the role of cytokines, including transforming growth factor (TGFbeta), on expression and activity of genes involved in the control of cell and tumor growth including tumor suppresses pRb, p107, and pRb2/p130, and the E2F family of key regulatory proteins in CNS tumors. Through this collaborative research we will be able to address several key questions related to the immunobiology, malignant transformation, and the cell cycle regulatory pathways of tumor cells in the CNS.

JC 病毒 (JCV) 是一种人类多瘤病毒，与 几种动物物种的神经肿瘤发生。 JCV可诱发神经肿瘤 在小鼠和仓鼠以及非人类灵长类动物中，例如猫头鹰和 松鼠猴。 在这个项目中，我们将利用这种致癌作用 研究中枢神经系统衍生肿瘤的免疫生物学。 有证据表明 表明脑肿瘤会引起体内免疫调节异常 他们的主人。 我们计划利用人类的致癌潜力 嗜神经病毒 (JCV) 早期蛋白、T 抗原，作为诱导工具 中枢神经系统起源的肿瘤。 将分析这些组织的能力 诱发血脑屏障。 这些肿瘤的能力 将通过比较免疫目标被排斥的能力来评估它们 使用异种、异体和同种移植物。 它们的免疫原性也将是 通过确定它们是否是致脑炎的目标来评估 淋巴细胞，正如我们对正常星形胶质细胞所证明的那样。 研究将 进行评估细胞因子的作用，包括转化 生长因子（TGFbeta），对参与的基因的表达和活性 细胞和肿瘤生长的控制，包括肿瘤抑制 pRb、p107、 和 pRb2/p130，以及 CNS 关键调节蛋白的 E2F 家族 肿瘤。 通过这项合作研究，我们将能够解决 与免疫生物学、恶性肿瘤相关的几个关键问题 肿瘤细胞的转化和细胞周期调控途径 中枢神经系统。