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.
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