| Epidemiological studies have shown that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin reduces the risk of esophageal, gastric, lung, and colorectal cancer, and other studies have suggested that NSAIDs can reduce tumor formation, progression, and metastasis, and inhibit angiogenesis that is essential for tumorigenesis. The key target of NSAIDs is cyclooxygenase (COX). COX is an enzyme that converts arachidonic acid (AA) to prostaglandins (PGs). It has two isoforms: COX-1 and COX-2. COX-1 is constitutively expressed in most cell types, but COX-2 expression is inducible by various stimuli. Recently, up-regulated COX-2 expression has been reported in several human carcinomas, increasing the attention to a potential role for COX-2 in tumorigenesis.; Furthermore, COX-2 has been demonstrated to inhibit apoptosis, induce angiogenesis, and modulate the immunological environment through regulation of the cytokine balance. All of these factors, when combined, strongly implicate COX-2 involvement in tumor development.; The inducible nature of the COX-2 gene and the up-regulation of COX-2 in tumors strongly suggests that it is the precise amount of COX-2 in tissues that may be an important determinant of tumor biology, influencing such factors as tumor aggressiveness, metastatic potential, drug response and thus ultimately, patients' prognosis. Furthermore, the amount of COX-2 up-regulation may also be within defined limits at various stages of tumorigenesis, thus providing a means of molecular pathology to aid in identifying those stages. While in the past quantitative measurements of molecular factors in patients' tissues were very difficult, recent advances in quantitative PCR technology (e.g., the TaqMan®) have made it feasible to perform rapid, real-time monitoring of PCR reactions with a high-throughput capacity. In this project, through the measurement of COX-2 gene expression levels, it was demonstrated that (1) up-regulated COX-2 gene expression might be an early event in the development of esophageal adenocarcinoma, (2) COX-2 gene expression can be a good prognostic factor for lung cancer, and (3) NSAIDs have a preventive effect in colorectal adenocarcinoma by reducing COX-2 gene expression. |
