AIM:The aim of this paper is to examine COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR).METHODS:Colon and rectal specimens were obtained from 26 patients with recurrent colorectal carcinomas. We examined COX-2 expression in human recurrent colorectal carcinoma tissues using immunohistochemistry and quantative real-time PCR (qPCR).RESULTS:In recurrent colorectal cancer a strong cytoplasmic and perinuclear staining of COX-2 was found. Moderate to strong immunosignals were detected in almost all of the carcinomas. We observed a strong specific staining of COX-2 in vascular endothelium. COX-2 immunoreactivity was also detected in stromal cells such as mononuclear cells, fibroblasts, and smooth muscle cells. The real-time PCR analyses demonstrated marked overexpression of the COX-2 gene in the cancer mucosa in concert with the immunohistochemistry data.CONCLUSION:We investigated COX-2 expression at the level of its protein as well as its messenger RNA in a series of recurrent colorectal cancers. These observations give additional information about the possibility that COX-2 could be involved in tumor promotion during colorectal cancer progression.

Background: Cyclooxygenase-2 (COX-2) over-expression and subsequent prostaglandin E2 (PGE2) production are frequently associated with human non-small-cell lung cancer (NSCLC) and are involved in tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that ciglitazone downregulates PGE2 in NSCLC cells.Methods: PGE2 ELISA assay and COX-2 ELISA assay were performed for measuring PGE2 and COX-2, respectively, in NSCLC. The mRNA level of COX-2 was measured by semi-quantitative RT-PCR. The transient transfection experiments were performed to measure COX-2 and peroxisome proliferator-response element (PPRE) promoter activity in NSCLC. Western blots were unitized to measure PGE synthase (PGES) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) protein expression.Results: COX-2 ELISA assays suggested that ciglitazone-dependent inhibition of PGE2 occurs through the suppression of COX-2. Ciglitazone treatment suppressed COX-2 mRNA expression and COX-2 promoter activity while upregulating PPRE promoter activity. Ciglitazone did not modify the expression of enzymes downstream of COX-2 including PGES and 15-PGDH. Utilization of a dominant-negative PPARγ showed that the suppression of COX-2 and PGE2 by ciglitazone is mediated via non-PPAR pathways.Conclusion: Taken together, our findings suggest that ciglitazone is a negative modulator of COX-2/PGE2 in NSCLC.

Previous studies by us and others established that mammary tumors induced by murine mammary tumor virus (MuMTV) could be prevented to various extents by prior vaccination with MuMTV-containing or subviral component immunogens. In this report, four predicted surface-accessible peptide regions (EP-1 to EP-4) of the major viral envelope glycoprotein (gp52) of C3H-MuMTV were tested as carrier-conjugated vaccines for the protection of Balb/c mice against a live virus challenge. With tumor incidence as an endpoint, vaccination with one of these synthetic peptides (EP-3) resulted in a significant reduction in the frequency of early onset tumors and 67% of the test animals remained tumor-free for the entire observation period (16 months). In contrast, only marginal protection was obtained by immunization with the intact glycoprotein (gp52). Immunologic interference may explain the lower protective efficacy of gp52, as compared to EP-3.

Cyclooxygenases (COX) 1 and 2 are the key enzymes of prostaglandin biosynthesis. Like in many tissues, in adult skin COX-1 is a constitutive ‘housekeeping’ enzyme, while COX-2 is induced transiently in stress situations such as tissue damage and regeneration. In human skin carcinomas and corresponding early-stage cancer lesions, permanent COX-2 expression and activation is a consistent feature. Knockout and various transgenic approaches and pharmacologic studies show strong evidence for a cause-and-effect relationship between the aberrant COX-2 activation and tumor formation. In skin epidermis, keratin 5 promoter-driven overexpression of COX-2 caused hyperplasia and dysplasia, and sensitized skin for carcinogenesis. Therefore, this model offers the unique possibility of identifying COX-2-dependent and prostaglandin-mediated molecular pathways leading to the formation and malignant progression of early-stage cancer lesions.