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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该建议的中心假设是，选择性考克斯-2抑制剂塞来昔布短期治疗将抑制烟草烟雾（TS）介导的尿PGE-M浓度升高至与从不吸烟者中观察到的水平相当。 本研究的主要目的是更好地确定TS暴露与吸烟者和从不吸烟者的尿PGE-M（PGE 2的主要代谢产物）之间的关系，因为越来越多的证据表明，前列腺素产生失调可能导致致癌作用。 其次，本研究旨在确定吸烟者和非吸烟者中考克斯-2活性对尿PGE-M水平的相对贡献，尿PGE-M是一种潜在的生物标志物，可促进前列腺素的产生。 我们也有兴趣在TS和血管生成之间的关系，因为TS已被证明诱导VEGF的PGE 2。 因此，我们有理由假设，与非吸烟者相比，吸烟者的血管生成替代标志物可能会增加，而塞来昔布治疗一周可能会抑制这种变化。

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.