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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这一建议的中心假设是，选择性COX-2抑制剂塞来昔布的短期治疗将抑制烟草烟雾(TS)干预下尿PGE-M浓度的升高，达到与从不吸烟者观察到的水平相当。这项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中PGE2的主要代谢物PGE-M之间的关系，因为越来越多的证据表明，放松调节的前列腺素产生可能有助于癌症的发生。其次，这项研究旨在确定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是产生前列腺素的潜在生物标志物。我们也对TS和血管生成之间的关系感兴趣，因为TS和PGE2一样被证明可以诱导血管生成。因此，有理由推测，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，而塞来昔布一周可能会抑制这一现象。

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.