No abstract available.
Humans ; Peroxisome Proliferator-Activated Receptors/*metabolism ; Prostaglandin-Endoperoxide Synthase/*metabolism ; Stomach Neoplasms/*metabolism

The aim of this study was to investigate the relationship of cyclooxygenase (COX) -2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p= 0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p < 0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.
Carcinoma, Renal Cell/*metabolism/mortality/pathology ; Humans ; Kidney Neoplasms/*metabolism/mortality/pathology ; Prognosis ; Prostaglandin-Endoperoxide Synthase/*metabolism ; Protein p53/*metabolism ; Tumor Markers, Biological/*metabolism

BACKGROUND/AIMS: Gastric cancer is still the most frequently diagnosed malignancy in Korea. It has been reported that COX-2 and PPAR are involved in multi-step gastric carcinogenesis. The aim of the present study was to examine the expression of COX-2 and PPAR in gastric cancer. METHODS: A total of 75 subjects including 45 patients with gastric cancer and 30 controls were enrolled. All subjects underwent upper gastrointestinal endoscopic examination with tissue collection. mRNA extraction from the tissues and real-time PCR for COX-2, PPAR-delta, and PPAR-gamma were performed. Gastric mucosal concentration of PGE2, which is a final product of COX-2, and 15d-PGJ2, which is a ligand of PPAR-gamma, were measured by the enzyme immunoassay method. RESULTS: COX-2 mRNA expression was significantly higher in both early gastric cancer tissues (EGC, 8.32 +/- 4.84 micro gram/micro L, p<0.005) and advanced gastric cancer tissues (AGC, 8.16 +/- 2.67 micro gram/micro L, p<0.001) than in non-cancerous tissues of controls (3.46 +/- 1.72 micro gram/micro L). There was no significant difference of PPAR-delta and PPAR-gamma mRNA expression between gastric cancer tissues and controls. Mucosal PGE2 concentration was significantly higher in both EGC tissues (5.31 +/- 0.49 micro gram/mg protein, p<0.001) and AGC tissues (5.46 +/- 0.54 micro gram/mg protein, p<0.001) than in non-cancerous tissues of controls (4.22 +/- 0.8 micro gram/mg protein). There was no significant difference of 15d-PGJ2 concentration between gastric cancer tissues and controls. CONCLUSIONS: COX-2 overexpression and increased PGE2 concentration in gastric tissues may play an important role in gastric carcinogenesis. However, the role of PPAR (delta and gamma) and 15d-PGJ2 in gastric carcinogenesis is uncertain. Further studies are needed.
Adult ; Aged ; English Abstract ; Female ; Gastric Mucosa/*metabolism ; Humans ; Male ; Middle Aged ; Peroxisome Proliferator-Activated Receptors/*metabolism ; Prostaglandin-Endoperoxide Synthase/*metabolism ; Stomach Neoplasms/*metabolism

Chronic infection and inflammation have recently been implicated as important etiologic agents for atherosclerosis in general and, in particular, ischemic heart disease. Several agents have been suggested as possible candidates for the chronic inflammation including cytomegalovirus, Helicobacter pylori and Chlamydia pneumoniae. We hypothesized that a vascular infection with C. pneumoniae may induce a chronic inflammatory reaction in the host vascular tissue and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs). At first, we evaluated the relationship between C. pneumoniae infection and atherosclerosis indirectly by serologic study, and then, to confirm our hypothesis, we performed an immunohistochemical study of atherosclerotic plaques. The seropositive rate of anti-Chlamydia pneumoniae IgG was higher in the disease group (Group I, 59.8%, n = 254) than in the negative control group (Group III, 47.4%, n = 97) (p = 0.041), but the anti-Chlamydia pneumoniae IgA was not different in seropositivity between the two groups (Group I, 64.6%; Group III, 57.7%). The simultaneous seropositive rates of both IgG and IgA were 56.7% in Group I and 43.3% in Group III (p = 0.033). In subgroups without the conventional risk factors of atherosclerosis, these findings were more prominent. Furthermore, we performed immunohistochemical staining on the atherosclerotic aortic tissues obtained from patients that were seropositive to C. pneumoniae (n = 5), by using antibodies to C. pneumoniae, COX-2, and MMP-9. The immunoreactivity for COX-2 and MMP-9 increased in the atherosclerotic plaques itself, predominantly in the surrounding area of immunoreactive C. pneumoniae. These findings support our hypothesis and C. pneumoniae may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis. The present study may open a promising perspective concerning future therapeutic trials of chronic inflammation related atherogenesis under pathophysiological conditions.
Aged ; Arteriosclerosis/pathology* ; Arteriosclerosis/microbiology* ; Arteriosclerosis/metabolism ; Chlamydia Infections/complications* ; Chlamydophila pneumoniae ; Female ; Gelatinase B/metabolism ; Human ; Isoenzymes/metabolism ; Male ; Middle Age ; Prostaglandin-Endoperoxide Synthase/metabolism ; Serologic Tests*

The aim of this study was to investigate the expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with rheumatoid arthritis (RA). Synovial tissues from 9 patients with RA and 5 patients with osteoarthritis (OA) were examined for COX-1 and COX-2 expressions by immunohistochemical staining using 2 polydonal COX-1 and COX-2 antibodies. In RA synovia, synovial lining cells showed intense immunostaining for COX-1, whereas slight to moderate staining was observed in inflammatory cells, stromal fibroblast-like cells and vascular endothelial cells. There was no significant difference in COX-1 expression between RA and OA synovia. The localization of COX-2 expression dearly differed from that of COX-1 expression, being most intense in inflammatory cells. However, there was no difference in COX-1 and COX-2 expressions between RA and OA synovial tissues. Our observations support that inflammatory mechanisms modulated by COX-1 and COX-2 in chronic RA synovium might be similar to those in chronic OA synovium.
Adult ; Aged ; Arthritis, Rheumatoid/pathology ; Arthritis, Rheumatoid/enzymology* ; Cell Division ; Female ; Fibrin/metabolism ; Human ; Isoenzymes/metabolism ; Isoenzymes/biosynthesis* ; Male ; Middle Age ; Neutrophil Infiltration ; Osteoarthritis/enzymology ; Prostaglandin-Endoperoxide Synthase/metabolism ; Prostaglandin-Endoperoxide Synthase/biosynthesis* ; Stromal Cells/pathology ; Stromal Cells/enzymology ; Synovial Membrane/pathology ; Synovial Membrane/enzymology*

Methyl-beta-cyclodextrin, a cyclic oligosaccharide known for its interaction with the plasma membrane induces several events in cells including cell growth and anti-tumor activity. In this study, we have investigated the possible role of cyclooxygenase 2 (COX-2) in cell growth arrest induced by methyl-beta-cyclodextrin in Raw264.7 macrophage cells. Methyl-beta-cyclodextrin inhibited cell growth and arrested the cell cycle, and this cell cycle arrest reduced the population of cells in the S phase, and concomitantly reduced cyclin A and D expressions. Methyl-beta-cyclodextrin in a dose- and time-dependent manner, also induced COX-2 expression, prostaglandin E(2) (PGE(2)) synthesis, and COX-2 promoter activity. Pretreatment of cells with NS398, a COX-2 specific inhibitor completely blocked PGE(2) synthesis induced by methyl-beta-cyclodextrin, however inhibition on cell proliferation and cell cycle arrest was not effected, suggesting non-association of COX-2 in the cell cycle arrest. These results suggest that methyl-beta-cyclodextrin induced cell growth inhibition and cell cycle arrest in Raw264.7 cells may be mediated by cyclin A and D1 expression.
Animals ; Cell Cycle/drug effects/*physiology ; Cell Line ; Cell Proliferation/*drug effects ; Dinoprostone/*metabolism ; Dose-Response Relationship, Drug ; Isoenzymes/genetics/*metabolism ; Macrophages/cytology/*drug effects/physiology ; Mice ; Prostaglandin-Endoperoxide Synthase/genetics/*metabolism ; Research Support, Non-U.S. Gov't ; beta-Cyclodextrins/*pharmacology

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.
Animal ; Aorta/enzymology* ; Aortic Diseases/pathology ; Aortic Diseases/enzymology* ; Arteriosclerosis/pathology ; Arteriosclerosis/enzymology* ; Female ; Guinea Pigs ; Human ; Immunochemistry ; Isoenzymes/metabolism* ; Male ; Matrix Metalloproteinases/metabolism* ; Middle Age ; Prostaglandin-Endoperoxide Synthase/metabolism*

There has been no report for the expression of cyclooxygenase-2 (COX-2) and its clinicopathologic and biologic significance in ampulla of Vater cancer. This study was aimed for the clarification of COX-2 expression and its biologic roles in ampulla of Vater cancer. Fourty-six patients with ampulla of Vater cancer were enrolled and their COX-2 expression and clinicopathologic features were analyzed. The median age of patients was 60 yr and the mean duration of follow-up was 35 months (range: 14-82 months). Immunohistochemical stainings for COX-2, Ki-67, CD34 and TUNEL staining were performed. The immunoreactive COX-2 expression was present in 24 (52.2%) patients of ampulla of Vater cancer and mainly localized in cytosolic and perinuclear region. There was no significant difference in the length of survival between COX-2 postive and negative group (p=0.9420 by Log Rank test). Also, there were no significant differences of proliferation index (p=0.326), apoptotic index (p=0.764) and microvessel density (p=0.135) between COX-2 positive and negative group. Initial pTNM stage (p=0.0028 by Log Rank test) and blood transfusion over 4 pints during operation (p=0.0254 by Log Rank test) were independent prognostic factor in patients with ampulla of Vater cancer. It is suggested that immunoreactivity of COX-2 is not correlated with clinicopathologic and biologic features of ampulla of Vater cancer.
Adult ; Aged ; Ampulla of Vater*/enzymology ; Ampulla of Vater*/pathology ; Common Bile Duct Neoplasms/enzymology* ; Common Bile Duct Neoplasms/pathology* ; Female ; Human ; Immunoenzyme Techniques ; Isoenzymes/metabolism* ; Male ; Middle Aged ; Prostaglandin-Endoperoxide Synthase/metabolism* ; Statistics ; Survival Rate

Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid into prostanoids which participate in various cellular functions including apoptosis, mitogenesis, inflammation, immune modulation and differentiation. Moreover, the synthetic glucocorticoid, dexamethasone has immune modulating and anti-inflammatory effects in vivo. Recently, dexamethasone was found to enhance retinoic acid-induced neuronal differentiation. In this study, we investigated the mechanisms of dexamethasone-mediated neuronal differentiation. Immunoblotting and morphological analysis demonstrated that dexamethasone induced neuronal differentiation through COX 1 induction. This phenomenon was inhibited by indomethacin, a COX inhibitor. In addition, the addition of exogenous prostaglandin E2 (PGE2), a substance produced by the COX-mediated pathway, triggered neurite outgrowth of cells treated with COX inhibitor. Taken together, COX 1 appears to play an important role in dexamethasone-mediated neuronal differentiation.
Animals ; Anti-Inflammatory Agents/pharmacology ; Cell Differentiation/*drug effects ; Cyclooxygenase Inhibitors/pharmacology ; Dexamethasone/*pharmacology ; Dinoprostone/metabolism ; Enzyme Induction ; Hybrid Cells ; Indomethacin/pharmacology ; Isoenzymes/*biosynthesis ; Mice ; Prostaglandin-Endoperoxide Synthase/*biosynthesis ; Rats ; Tumor Cells, Cultured

OBJECTIVETo explore the effects of Triptolide (TP) on TNFalpha-induced cell proliferation and expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and their inducing products PGE2, NO in human rheumatoid arthritis synovial fibroblasts (RASF).

METHODSFibroblasts (RASF) were obtained from synovial tissue of patients with RA and were cultured in vitro. RASF were stimulated with TNFalpha(20 microg/L) in the presence or absence of TP(0 - 100 microg/L) for 20 h. The RASF proliferation was determined by (3)H-TdR incorporation, and the productions of PGE2 and NO in culture supernatants of RASF were detected with competitive ELISA and enzyme reduction of nitrate. Expressions of COX-2 and iNOS mRNA in RASF were analyzed by semi-quantitative RT-PCR. Expressions of COX-2 and iNOS protein were estimated by Western-blot method and cellular enzyme immunoassay in synovial fibroblasts. NF-kappaB activity in whole-cell extract of RASF was also measured by an ELISA-based method.

RESULTSTP (>20 microg/L) down-regulated markedly TNFalpha-induced COX-2 and iNOS mRNA and protein expression, and their inducing products PGE2 and NO of synovial fibroblasts. This effect was positively correlated with TP concentrations. NF-kappaB activity in TNFalpha-stimulated synovial cells was suppressed profoundly by TP treatment (IC(50) approximately 35microg/L). The activity of NF-kappaB was correlated with the levels of COX-2 and iNOS expression in TNFalpha-stimulated RASF. No change was observed in proliferation of synovial cells after treatment of TP.

CONCLUSIONTP could significantly down-regulate TNFalpha-induced COX-2, iNOS expression and production of PGE2, NO in human RASF, which is associated with the suppression of NF-kappaB activity.

Arthritis, Rheumatoid ; drug therapy ; metabolism ; Cyclooxygenase 2 ; Diterpenes ; pharmacology ; Epoxy Compounds ; Fibroblasts ; metabolism ; Gene Expression Regulation ; drug effects ; Humans ; Isoenzymes ; analysis ; genetics ; Membrane Proteins ; NF-kappa B ; metabolism ; Nitric Oxide Synthase ; analysis ; genetics ; Nitric Oxide Synthase Type II ; Phenanthrenes ; pharmacology ; Prostaglandin-Endoperoxide Synthases ; analysis ; genetics ; RNA, Messenger ; analysis ; Synovial Membrane ; cytology ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology