BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using immunohistochemical techniques. The COX-2 immunohistochemical staining score was assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each scoring system was based on a sum of the parameters of staining intensity and distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5 +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al. scoring systems. The percentage samples of high COX-2 expression score (4 to 5) in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3% vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX-2 expression scores based on the severity of hepatic fibrosis scored using Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/- 1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009), respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2 expression scores according to Ishak's staging was significantly higher in the advanced fibrosis group. COX-2 may play a role in the progression of hepatic fibrosis.
Adult ; Aged ; Cyclooxygenase 2/analysis/*physiology ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Progression ; Female ; Hepatitis, Chronic/enzymology ; Humans ; Immunohistochemistry ; Liver Cirrhosis/drug therapy/*enzymology ; Male ; Middle Aged

OBJECTIVETo study the relation between cyclooxygenase-2 (COX-2) protein expression and biologic behavior of ovarian carcinoma.

METHODSThe level of COX-2 protein expression was detected by Western Blot assay in 54 biopsy specimens from ovarian serous tumor patients and 10 normal ovarian samples.

RESULTSThe level of COX-2 protein expression and relative quantity in ovarian serous carcinoma (81.8%, 20.08 +/- 3.53) were statistically higher than those in the benign ovarian serous tumor (0, 15.04 +/- 0.12) and in the normal ovary (0, 15.33 +/- 0.60) (P < 0.05). The level of COX-2 protein expression and relative quantity in borderline ovarian serous tumor (90.0%, 20.61 +/- 3.03) were statistically higher than those in benign ovarian serous tumor and the normal ovary (P < 0.05). The level of COX-2 protein expression and relative quantity were not significantly different from ovarian serous carcinoma and borderline ovarian serous tumor (P > 0.05); as they were between the benign ovarian serous tumor and the normal ovary (P > 0.05). The level of COX-2 protein expression and relative quantity were not significantly different among different clinical stages (I + II and III + IV), different histological grades, with or without ascites or lymphatic metastasis either.

CONCLUSIONCOX-2 overexpression may be significantly related to the oncogenesis and development of ovarian serous carcinoma, which may be an early diagnostic parameter and, hence, an attractive target for chemopreventive strategy in the treatment of ovarian serous carcinoma.

Adult ; Aged ; Blotting, Western ; Cyclooxygenase 2 ; analysis ; genetics ; physiology ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms ; enzymology ; etiology

OBJECTIVEThis study examined the effects of curcumin on intestinal histopathological changes, cyclooxygenase-2 (COX-2) expression, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations in neonatal rats with necrotizing enterocolitis (NEC), in order to investigate the effects of curcumin against NEC.

METHODSForty neonatal rats were randomly divided into four groups (n=10 each): normal control, solvent control, NEC model, and curcumin intervention. The general situations of rats were observed for 3 consecutive days, and the rats were then sacrificed on the 4th day. Intestinal tissues were obtained for examining the histopathological changes, COX-2 expression, and TNF-alpha and IL-10 concentrations.

RESULTSCurcumin treatment ameliorated the general situations and histopathological signs in rats with NEC. TNF-alpha and IL-10 concentrations in the NEC model and the curcumin intervention groups increased significantly compared with those in the normal and solvent control groups (p<0.05). The concentration of TNF-alpha decreased (p<0.05), while the concentration of IL-10 increased significantly in the curcumin intervention group in comparison with the NEC model group (p<0.05). Immunohistochemistry results indicated that the positive expression of COX-2 in the curcumin intervention group was significantly lower than that in the NEC model group.

CONCLUSIONSCurcumin has protective effects against NEC in neonatal rats, possibly through inhibiting COX-2 expression, reducing TNF-alpha content, and increasing IL-10 content.

Animals ; Animals, Newborn ; Body Weight ; Curcumin ; therapeutic use ; Cyclooxygenase 2 ; analysis ; physiology ; Disease Models, Animal ; Enterocolitis, Necrotizing ; drug therapy ; pathology ; Female ; Interleukin-10 ; analysis ; Intestines ; pathology ; Male ; NF-kappa B ; physiology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo study the expression of cyclooxygenase-2 (COX-2) gene in breast cancer and its clinicopathologic characteristics.

METHODSWith beta-actin gene as reference, the COX-2 mRNA was monitored in 30 specimens of breast cancer tissue and adjacent normal breast tissue by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSThe COX-2 mRNA expression was significantly upregulated in most breast cancer tissues with range of 0.05 - 0.91 (median 0.56), which was rare in normal breast tissue with range of 0 - 0.09 (median 0). The difference of COX-2 mRNA expression between cancer and normal breast tissue was significant (rank sum test, P < 0.05). COX-2 overexpression in breast cancer was related to its lymph node metastasis (P < 0.05) but not to age, tumor size, pathologic grade or pathologic type (P > 0.05).

CONCLUSIONThe level of COX-2 mRNA expression is obviously higher in the breast cancer tissue than that in normal breast tissue. COX-2 overexpression may play a crucial role in the carcinogenesis, development of cancer and lymph node metastasis in breast cancer patients.

Adult ; Biomarkers, Tumor ; biosynthesis ; genetics ; Breast Neoplasms ; enzymology ; metabolism ; Cyclooxygenase 2 ; Female ; Gene Expression ; Humans ; Isoenzymes ; biosynthesis ; genetics ; physiology ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases ; biosynthesis ; genetics ; physiology ; RNA, Messenger ; biosynthesis ; RNA, Neoplasm ; analysis ; Reverse Transcriptase Polymerase Chain Reaction

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-activated transcription factor and plays an important role in growth, differentiation, and inflammation in different tissues. In this study, we investigated the effects of 15d-PGJ2, a high-affinity ligand of PPAR-gamma, on dedifferentiation and on inflammatory responses such as COX-2 expression and PGE2 production in rabbit articular chondrocytes with a focus on ERK-1/-2, p38 kinase, and PPAR-gamma activation. We report here that 15d-PGJ2 induced dedifferentiation and/or COX-2 expression and subsequent PGE2 production. 15d-PGJ2 treatment stimulated activation of ERK-1/-2, p38 kinase, and PPAR-gamma. Inhibition of ERK-1/-2 with PD98059 recovered 15d-PGJ2-induced dedifferentiation and enhanced PPAR-gamma activation, whereas inhibition of p38 kinase with SB203580 potentiated dedifferentiation and partially blocked PPAR-gamma activation. Inhibition of ERK-1/-2 and p38 kinase abolished 15d-PGJ2-induced COX-2 expression and subsequent PGE2 production. Our findings collectively suggest that ERK-1/-2 and p38 kinase oppositely regulate 15d-PGJ2-induced dedifferentiation through a PPAR-gamma-dependent mechanism, whereas COX-2 expression and PGE2 production is regulated by ERK-1/-2 through a PPAR-gamma-independent mechanism but not p38 kinase in articular chondrocytes. Additionally, these data suggest that targeted modulation of the PPAR-gamma and mitogen-activated protein kinase pathway may offer a novel approach for therapeutic inhibition of joint tissue degradation.
Animals ; Cartilage, Articular/*cytology ; Cell Differentiation/drug effects ; Chondrocytes/cytology/*drug effects/metabolism ; Cyclooxygenase 2/*analysis ; Dinoprostone/biosynthesis ; Mitogen-Activated Protein Kinase 1/*physiology ; Mitogen-Activated Protein Kinase 3/*physiology ; PPAR gamma/*physiology ; Prostaglandin D2/*analogs & derivatives/pharmacology ; Rabbits ; p38 Mitogen-Activated Protein Kinases/*physiology

Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary compounds are therefore potential chemopreventive agents. Thirty Sprague-Dawley rats (4 months old) were experimentally treated with procarcinogen dimethylhydrazine to induce colon cancer development. The rats were randomly assigned to three groups: a control group (CG), a group treated with dimethylhydrazine (DMH), and a group given DMH and inulin, a prebiotic (DMH+PRE). The effects of inulin on the activities of bacterial glycolytic enzymes, short-chain fatty acids, coliform and lactobacilli counts, cytokine levels, and cyclooxygenase-2 (COX-2) and transcription nuclear factor kappa beta (NFkappaB) immunoreactivity were measured. Inulin significantly decreased coliform counts (p < 0.01), increased lactobacilli counts (p < 0.001), and decreased the activity of beta-glucuronidase (p < 0.01). Butyric and propionic concentrations were decreased in the DMH group. Inulin increased its concentration that had been reduced by DMH. Inulin decreased the numbers of COX-2- and NFkappaB-positive cells in the tunica mucosae and tela submucosae of the colon. The expression of IL-2, TNFalpha, and IL-10 was also diminished. This 28-week study showed that dietary intake of inulin prevents preneoplastic changes and inflammation that promote colon cancer development.
Animals ; Bacterial Proteins/genetics/metabolism ; Colon/enzymology ; Colonic Neoplasms/chemically induced/*drug therapy/metabolism ; Colony Count, Microbial ; Cyclooxygenase 2/genetics/metabolism ; Cytokines/blood/genetics ; Diet ; Dietary Supplements/analysis ; Dimethylhydrazines/toxicity ; Enterobacteriaceae/drug effects/physiology ; Fatty Acids, Volatile/genetics/metabolism ; Female ; Gene Expression Regulation/drug effects ; Inulin/administration & dosage/*metabolism ; Lactobacillaceae/drug effects/physiology ; Male ; NF-kappa B/genetics/metabolism ; Prebiotics/*analysis ; Rats ; Rats, Sprague-Dawley