TGF-beta as a key to glioma invasion

TGF-β是神经胶质瘤侵袭的关键

• 批准号: 6735545
• 负责人: LOIS ALTERMAN LAMPSON
• 金额: $ 18.79万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735545
• 关键词: antiinflammatory agents; astrocytoma; disease /disorder model; glioma; immunocytochemistry; laboratory mouse; laboratory rat; neoplasm /cancer chemotherapy; neoplasm /cancer invasiveness; neoplasm /cancer pharmacology; neoplasm /cancer transplantation; nonhuman therapy evaluation; tissue /cell culture; transforming growth factors

DESCRIPTION (provided by applicant): Invasive growth is a hallmark of astrocytoma, and a key factor in the grim prognosis for high grade tumors. This R21 application aims to block astrocytoma invasion from the time of diagnosis. This aim complements our long-standing efforts to direct migratory T cells to astrocytoma that has already invaded. This R21 project will allow us to obtain the preliminary data needed for full-scale R01 support. Two AIMS will be carried out in parallel. AIM 1. Test the hypothesis that transforming growth factor-beta 1 (TGF-beta1) is a key regulator of brain tumor invasion. AIM 2. Test the hypothesis that pharmacologic agents which affect TGF-beta1 and reduce invasion in other contexts can also reduce brain tumor invasion in vivo. The particular agent we will test here is the anti-fibrotic/anti-inflammatory drug, pirfenidone. In this amended application, we use a variety of animal models, appropriate to testing different paths of tumor invasion in the brain. We include rat glioma-derived cell lines already in active use in our laboratory; a model for brain-metastasizing breast cancer, which we have recently developed; as well as a panel of murine astrocytoma clones made to express different levels of TGF-beta1, and which may be a better mimic of single cell invasion than most rodent glioma cell lines. Methods include tissue culture, cell growth assays, immunohistochemistry, stereotactic implantation of tumor cell lines, pharmacologic treatment of tumor-bearing mice and rats. Mice and rats will be used.

描述（由申请人提供）：