IP-10 AS AN ANGIOSTATIC FACTOR IN LUNG CANCER

IP-10 作为肺癌的血管抑制因子

• 批准号: 2010622
• 负责人: Douglas Arenberg
• 金额: $ 8.21万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-07 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2010622
• 关键词: SCID mouse; angiogenesis; angiogenesis inhibitors; antineoplastics; gene induction /repression; interferon gamma; laboratory rat; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; nonsmall cell lung cancer; transfection

DESCRIPTION (Applicant's Description): The investigators hypothesize that the angiostatic factor IP-10 is an endogenous inhibitor of tumor-derived angiogenesis. In this proposal, they will test this hypothesis by characterizing the role of IP-10 in regulating overall tumor-derived angiogenic activity in an animal model of human non-small cell lung cancer (NSCLC). They will demonstrate that underexpression of IP-10 imparts increased angiogenic activity to NSCLC cell lines. Next, they will reconstitute IP-10 production in NSCLC cell lines, thus restoring the angiostatic balance, using two methods. (1) In vitro treatment of NSCLC cells with interferon gamma (IFNgamma) to induce IP-10 expression, and (2) Gene transfer technology to indirectly (IFNgamma) or directly (IP-10) augment IP-10 expression. They will then show that IFNgamma and IP-10 gene transfected cells have reduced in vitro angiogenic activity and reduced tumorigenicity in SCID mice. Finally, they will treat established NSCLC tumors in SCID mice with locally administered IFNgamma or IP-10 and show that IFNgamma inhibits tumor growth via an IP-10 dependent increase in angiostatic activity. These studies will lead to important new information about the pathogenesis of NSCLC, and enable the Principal Investigator to acquire the necessary skills to develop into an independent investigator.

描述（申请人的描述）： 研究人员推测血管抑制因子 IP-10 是一种 肿瘤源性血管生成的内源性抑制剂。 在这项提案中，他们 将通过描述 IP-10 在调节中的作用来检验这一假设 人类动物模型中总体肿瘤衍生的血管生成活性 非小细胞肺癌（NSCLC）。 他们将证明 IP-10 的表达不足会增加 NSCLC 细胞的血管生成活性 线。 接下来，他们将在 NSCLC 细胞系中重建 IP-10 的生产， 从而使用两种方法恢复血管抑制平衡。 (1) 体外 用干扰素γ (IFNgamma) 处理 NSCLC 细胞以诱导 IP-10 (2) 间接基因转移技术 (IFNgamma) 或 直接 (IP-10) 增强 IP-10 表达。 然后他们将证明 IFNγ和IP-10基因转染细胞体外血管生成减少 活性并降低 SCID 小鼠的致瘤性。 最后，他们会治疗 通过局部施用 IFNγ 或在 SCID 小鼠中建立 NSCLC 肿瘤 IP-10 并表明 IFNgamma 通过 IP-10 依赖性抑制肿瘤生长 血管抑制活性增加。 这些研究将带来重要的新成果 有关 NSCLC 发病机制的信息，使校长能够 研究者获得发展成为独立研究者所需的技能 研究者。