It was found that cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in azoxymethane induced colonic tumours, compared with specimens taken adjacent to the tumours or from the macroscopically normal intestine distant from the tumours.
The clinical implications of this biological distinction remain unknown but should be considered when assessing the efficacy of COX-2 inhibitors for chemoprevention in patients whose tumors may arise in the setting of defective DNA mismatch repair.
Immunohistochemical staining of specimens that expressed COX-1 and/or COX-2 revealed that COX-1 was localized in stromal cells adjacent to the tumor but not in tumor cells.
Interestingly, the proportion of adenocarcinoma cells with marked COX-2 expression was much greater in lymph node metastases than in the corresponding primary tumors.
This is the first description of functional COX-2 expression by NSCLC cells and the definition of a pathway whereby tumorCOX-2 expression and a high level of PGE2 production mediate profound alteration in cytokine balance in the lung cancer microenvironment.
Genetic evidence also supports a role for COX-2, since mice null for COX-2 have an 86% reduction in tumor multiplicity in a background containing a mutated APC allele.
The expression of Cox-2 was also elevated in most tumors, whereas Cox-1 was frequently expressed at lower levels in the tumor tissue than in the paired normal tissue.
Overexpression of COX-2 in cancer tissues compared with matched non-cancerous tissues was found in 70% of cases and was significantly associated with lymphatic involvement, lymph node metastasis and advanced tumor stage.
The level of COX-2 mRNA was positively correlated with the differentiation status of the tumor of origin for each cell line, COX-2 protein expression was up-regulated by epidermal growth factor when the cells were grown in absence of serum.
Both matrilysin and Cox-2 expression was increased in the mouse models and in the human colorectal cancers; however, immunohistochemistry and in situ hybridization indicated that their localization within the tumors was different.
Since gastrin is recognized as a effective gastric mitogen, it could be capable to induce COX-2, a potent tumor growth promoting and angiogenic factor, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric cancer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) in gastric cancer, 3) to assess the plasma levels, gastric lumen and tumor tissue contents of gastrin and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 in cancer tissue and intact gastric mucosa before and after HP eradication.
To investigate the role of COX-2 in UC-associated neoplasia, we assessed COX-2 protein and mRNA expression throughout the spectrum of UC-associated neoplastic lesions in four total colectomy specimens, using immunocytochemistry and a novel TaqMan reverse transcriptase-polymerase chain reaction assay.
Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%.
Because tumorCOX-2 expression appears to have a multifaceted role in conferring the malignant phenotype, COX-2 may be an important target for gene or pharmacologic therapy in NSCLC.
These findings demonstrate the functional significance rapid mRNA decay plays in controlling gene expression and show that dysregulation of these trans-acting factors can lead to overexpression of COX-2 and other angiogenic proteins, as detected in neoplasia.
Elevated levels of cyclooxygenase-2 and inducible nitric oxide synthase were observed in 74 and 91%, respectively, of tumors from Tehran as determined by immunohistochemistry, and high COX-2 expression correlated significantly with the presence of a p53 mutation in the tumor.