EARLY DETECTION OF RADIATION-INDUCED PULMONARY TOXICITY

辐射引起的肺毒性的早期检测

• 批准号: 2097280
• 负责人: SANDRA S MC DONALD
• 金额: $ 4万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2097280
• 关键词: SDS polyacrylamide gel electrophoresis; allergic pneumonitis; alveolar macrophages; bronchoscopy; cytotoxicity; diagnosis design /evaluation; diagnostic respiratory lavage; disease /disorder model; enzyme linked immunosorbent assay; extracellular matrix proteins; fibroblast growth factor; fibroblasts; human subject; injury /disease stressor; interleukin 1; lung neoplasms; neoplasm /cancer radiation therapy; platelet derived growth factor; pulmonary fibrosis /granuloma; radiation sensitivity; radiation therapy dosage; transforming growth factors; tumor necrosis factor alpha; western blottings

An estimated 142,000 men and women died of lung cancer in 1990. The majority of patients present with locally advanced, unresectable disease for whom the 5 year survival is 5-7%. New strategies are urgently needed to improve the therapeutic ratio. Frequently, advanced non-small cell (NSC) lung cancer will produce endobronchial obstruction. High dose rate (HDR) brachytherapy combined with external beam irradiation has the advantage of providing improved localization so that the portion of the tumor most responsible for the obstruction receives the highest dose, while sparing the normal surrounding lung tissue. The lung is one of the most sensitive structures to irradiation and is a major dose-limiting organ to the delivery of optimal therapy. The acute and late effects of radiation therapy, pneumonitis and pulmonary fibrosis, are of particular concern and the ability to predict for these side effects could allow early intervention and thus, reduce the morbidity of lung cancer therapy. We propose to identify the optimal dose schedule for concurrent external radiation therapy and HDR brachytherapy in terms of symptom relief and local disease response in patients with locally advanced NSC lung cancer. Because HDR brachytherapy requires bronchoscopy, it provides a unique opportunity, via bronchoalveolar lavage (BAL), to study the effects of irradiation in vivo, and to correlate laboratory findings to date in several animal models with clinical outcome in humans. Serial BAL will provide cellular material to: identify and quantify the production of specific growth factors for fibroblasts by alveolar macrophages induced by radiation; measure production of extra cellular matrix (ECM) proteins and expression of ECM mRNA in vitro by fibroblasts in response to specific growth and inhibitory factors produced by alveolar macrophages; identify changes in cellular responses outside the radiation volume due to the release of biochemical messages from within the irradiated volume. Serum samples will be analyzed to measure the release of biochemical messages into the vascular system after irradiation as monitors/predictors of radiation injury. These laboratory findings will be correlated with each patient's clinical outcome. The information obtained could contribute significantly to our understanding of the pneumonitic and fibrotic processes secondary to lung irradiation in humans. This could enable the development of early interventions and would impact on our ability to lower the morbidity in future clinical trials for all disease sites where the lungs may be irradiated.

1990 年估计有 142,000 名男性和女性死于肺癌。 大多数患者患有局部晚期、不可切除的疾病 对于他们来说，5 年生存率为 5-7%。 迫切需要新的战略 以提高治疗率。通常，高级非小蜂窝 (NSC) 肺癌会产生支气管内阻塞。 高剂量率 (HDR) 近距离放射治疗与外束照射相结合的优点是 提供改进的定位，使肿瘤的部分最 负责阻塞的人接受最高剂量，同时保留 正常的周围肺组织。 肺是最敏感的器官之一 结构对辐射的影响，是主要的剂量限制器官 提供最佳治疗。 辐射的急性和迟发影响 肺炎和肺纤维化的治疗尤其值得关注 预测这些副作用的能力可以让我们尽早 干预，从而降低肺癌治疗的发病率。 我们 建议确定同时进行的外部治疗的最佳剂量方案 放射治疗和 HDR 近距离放射治疗在症状缓解和 局部晚期 NSC 肺癌患者的局部疾病反应。 由于 HDR 近距离放射治疗需要支气管镜检查，因此它提供了独特的 通过支气管肺泡灌洗（BAL）的机会，研究 体内辐射，并将迄今为止的实验室研究结果关联起来 几种在人类中具有临床结果的动物模型。 串行 BAL 将 提供细胞材料以：识别和量化生产 肺泡巨噬细胞诱导成纤维细胞的特异性生长因子 辐射;测量细胞外基质 (ECM) 蛋白的产生并 成纤维细胞响应特定的体外表达 ECM mRNA 肺泡巨噬细胞产生的生长和抑制因子；确认 由于辐射量之外的细胞反应发生变化 从辐照体积内释放生化信息。 血清 将分析样本以测量生化信息的释放 辐射后进入血管系统作为监测器/预测器 辐射损伤。 这些实验室结果将与每个 患者的临床结果。 获得的信息可以做出贡献 对我们对肺炎和纤维化的理解具有重要意义 人类肺部辐射的继发过程。 这可以使 早期干预措施的发展将影响我们降低风险的能力 未来临床试验中所有疾病部位的发病率 肺部可能受到辐射。