SPECIALIZED CENTER OF RESEARCH IN HYPERBARIC OXYGEN THER

描述（申请人摘要）：此申请适用于一个新项目 这代表了研究机制的多学科努力 高压氧 (HB02) 的作用、安全性和临床疗效 治疗。 HB02 疗法已被指定为免费或替代疗法 国家补充和替代医学中心的模式。 该计划由 4 个研究项目和 3 个支持核心组成，分别是 围绕以下假设： HB02 疗法将有益于头颈癌 放射治疗后必须接受重建手术的患者 因为，在药理剂量下，氧气会增强血管生成并阻碍 特定类型的细胞间粘附。四者中的共同主题 研究项目是对升高的生物学和临床反应 头颈部肿瘤、内皮细胞、巨噬细胞和细胞的环境 O2 浓度 中性粒细胞。项目 1 将开发一个手术风险预测模型 因癌症需要进行喉切除术的患者，验证模型并评估 HB02 疗法改善预后的功效。刺激血管生成 项目 1 和项目 2 均假设在 HB02 照射的组织中存在缺氧。 两个项目中的低血管性将由以下人员直接评估 通过一种新方法对活检样本进行组织病理学分析， 硝基咪唑化合物EF-5与组织的O 2 依赖性结合。项目2 将评估受辐射小鼠中 HB02 的血管生成机制 肿瘤异种移植物生长反应。项目3建议高架部分 02 的压力将减少转移性头颈部肿瘤细胞 中性粒细胞附着于肺内皮。项目4建议 HB02 增加第二信使一氧化氮的内源性产生 反过来，这可能会在本计划研究的许多应对措施中发挥作用。 科学核心是生物统计学和数据管理（核心 B）以及室和 高压设备（核心 C）。整个计划将得到以下机构的支持 行政核心（核心A）。这一协调计划将提供新的 深入了解 HB02 的机制并评估临床使用的安全性。

DESCRIPTION (Applicant's Abstract): This application is for a new program that represents a multidisciplinary effort to investigate the mechanisms of action, safety and clinical efficacy of Hyperbaric Oxygen (HB02) Therapy. HB02 herapy has been designated a complimentary or alternative modality by the National Center for Complementary and Alternative Medicine. This program consists of 4 Research Projects and 3 Support Cores which are centered on the hypothesis that: HB02 therapy will benefit head and neck cancer patients who must undergo reconstructive surgery after radiation therapy because, at pharmacological doses, oxygen augments angiogenesis and impedes specific types of intercellular adherence. Common themes within the four research projects are the biology and clinical responses to elevations in ambient 02 concentration of head and neck tumors, endothelium, macrophages and neutrophils. Project 1 will develop a predictive model for surgical risk among patients requiring laryngectomy due to cancer, validate the model and assess the efficacy of HB02 therapy for improving outcome. Stimulation of angiogenesis in irradiated tissue by HB02 is hypothesized in both Projects 1 and 2. Hypoxia and hypovascularity in both projects will be directly evaluated by histopathological analysis of biopsy samples and by a novel method, 02-dependent binding to tissues of the nitroimidazole compound EF-5. Project 2 will evaluate the mechanism for angiogenesis by HB02 in irradiated mice and tumor xenograft growth responses. Project 3 proposes that elevated partial pressures of 02 will reduce metastatic head and neck tumor cells and neutrophils from attaching to pulmonary endothelium. Project 4 proposes that HB02 increases the endogenous production of nitric oxide, a second messenger that, in turn, may play a role in many responses studied in this program. Scientific cores are Biostatistics and Data Management (Core B) and Chamber and High Pressure Equipment (Core C). The entire program will be supported by an administrative core (Core A). This coordinated program will provide new insights into mechanisms for HB02 and assess safety for clinical use.