URINARY PGE-M, BIOMARKER OF TOBACCO-SMOKE LUNG INJURY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该建议的中心假设是，使用选择性COX-2抑制剂塞来昔布短期治疗将抑制烟草烟雾（TS）引起的尿PGE-M浓度升高至与从不吸烟者观察到的水平相当。本研究的主要目的是更好地确定吸烟和不吸烟人群中TS暴露与尿PGE-M （PGE2的主要代谢物）之间的关系，因为越来越多的证据表明前列腺素分泌失调可能有助于致癌。其次，本研究旨在确定COX-2活性对吸烟者和非吸烟者尿PGE-M水平的相对贡献，PGE-M是前列腺素产生的潜在生物标志物。我们对TS和血管生成之间的关系也很感兴趣，因为TS和PGE2一样可以诱导VEGF。因此，我们可以合理地假设，吸烟者血管生成的替代标志物可能比不吸烟者增加，而一周的塞来昔布可能会抑制血管生成。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The central hypothesis of this proposal is that short-term treatment with the selective COX-2 inhibitor celecoxib will suppress tobacco-smoke (TS) meditated elevation of urinary PGE-M concentration to levels comparable with those observed in never smokers. The primary purpose of this study is to better define the relationship between TS exposure and urinary PGE-M, the major metabolite of PGE2, in smokers and never smokers as there is increasing evidence to suggest that deregulated prostaglandin production may contribute to carcinogenesis. Secondarily, this study aims to determine the relative contribution of COX-2 activity to levels of urinary PGE-M, a potential biomaker of prostagladin production, in smokers and nonsmokers. We are also interested in the relationship between TS and angiogenesis since TS has been shown to induce VEGF as does PGE2. Therefore, it is reasonable to postulate that surrogate markers of angiogenesis may be increased in smokers compared to nonsmokers which may be suppressed by a week of celecoxib.