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Cyclooxygenase-2 Expression (cyclooxygenase-2 + expression)
Selected AbstractsCyclooxygenase-2 Expression and Prostaglandin E2 Production in Response to Acidic pH Through OGR1 in a Human Osteoblastic Cell Line,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2008Hideaki Tomura Abstract Acidosis has been shown to induce depletion of bone calcium from the body. This calcium release process is thought to be partially cell mediated. In an organ culture of bone, acidic pH has been shown to induce cyclooxygenase-2 (COX-2) induction and prostaglandin E2 (PGE2) production, resulting in stimulation of bone calcium release. However, the molecular mechanisms whereby osteoblasts sense acidic circumstances and thereby induce COX-2 induction and PGE2 production remain unknown. In this study, we used a human osteoblastic cell line (NHOst) to characterize cellular activities, including inositol phosphate production, intracellular Ca2+ concentration ([Ca2+]i), PGE2 production, and COX-2 mRNA and protein expression, in response to extracellular acidification. Small interfering RNA (siRNA) specific to the OGR1 receptor and specific inhibitors for intracellular signaling pathways were used to characterize acidification-induced cellular activities. We found that extracellular acidic pH induced a transient increase in [Ca2+]i and inositol phosphate production in the cells. Acidification also induced COX-2 induction, resulting in PGE2 production. These proton-induced actions were markedly inhibited by siRNA targeted for the OGR1 receptor and the inhibitors for Gq/11 protein, phospholipase C, and protein kinase C. We conclude that the OGR1/Gq/11/phospholipase C/protein kinase C pathway regulates osteoblastic COX-2 induction and subsequent PGE2 production in response to acidic circumstances. [source] Cyclooxygenase-2 Expression Induced by Photofrin Photodynamic Therapy Involves the p38 MAPK Pathway,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008Marian Luna Photodynamic therapy (PDT), using the porphyrin photosensitizer Photofrin (PH), is approved for the clinical treatment of solid tumors. In addition to the direct cytotoxic responses of PH,PDT-mediated oxidative stress, this procedure also induces expression of angiogenic and prosurvival molecules including cyclooxygenase-2 (COX-2). In vivo treatment efficacy is improved when PH-PDT is combined with inhibitors of COX-2. In the current study we evaluated the signaling pathways involved with PH,PDT-mediated COX-2 expression in a mouse fibrosarcoma cell line. COX-2 promoter reporter constructs with mutated transcription elements documented that the nuclear factor kappa B (NF,B) element, cyclic-AMP response element 2 (CRE-2), CCAAT/enhancer binding protein (C/EBP) element and activator binding protein-1 (AP-1) element were responsive to PH-PDT. Transcription factor binding assays demonstrated that nuclear protein binding to NF,B, CRE-2, c-fos and c-jun elements were elevated following PH-PDT. Kinase phosphorylation upstream of COX-2 expression was also examined following PH-PDT. Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and c-Jun were phosphorylated following PH-PDT but the SAPK/JNK inhibitor SP600125 failed to attenuate COX-2 expression. In contrast, p38 mitogen-activated protein kinase (MAPK), which activates CRE-2 binding, was phosphorylated following PH-PDT and inhibitors of p38 MAPK, SB203580 and SB202190, decreased PH,PDT-induced COX-2 expression at both the mRNA and protein levels. Extracellular signal-regulated kinase (ERK1/2) phosphorylation, which also increases CRE-2 binding activity, was initially high in untreated cells, decreased immediately following PH-PDT and then rapidly increased. MEK1/2 is immediately upstream of ERK1/2 and the MEK1 inhibitor PD98059 failed to attenuate COX-2 expression while the MEK1/2 inhibitor U0126 induced a slight decrease in COX-2 expression. The NF,B inhibitor SN50 failed to reduce COX-2 expression. These results demonstrate that multiple protein kinase cascades can be activated by oxidative stress and that the p38 MAPK signaling pathway and CRE-2 binding are involved in COX-2 expression following PH-PDT. [source] Cyclooxygenase-2 Expression in Murine and Human Nonmelanoma Skin Cancers: Implications for Therapeutic Approaches,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2002Kathy P. An ABSTRACT Inflammatory stimuli result in the production of cutaneous eicosanoids, which are known to contribute to the process of tumor promotion. Cyclooxygenase (COX), the rate-limiting enzyme for the production of prostaglandins (PG) from arachidonic acid, exists in at least two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and plays various physiological roles, whereas increased COX-2 expression is known to occur in several types of epithelial neoplasms. Enhanced PG synthesis is a potential contributing factor in UVB-induced nonmelanoma skin cancers (NMSC). Increased COX-2 staining occurs in murine skin neoplasms after chronic exposure to carcinogenic doses of UVB. In this study, immunohistochemical and Western blot analyses were employed to assess longitudinally COX-2 expression in a standard mouse UVB complete carcinogenesis protocol and in human basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). During UVB irradiation of mice, COX-2 expression consistently increased in the hyperplastic skin, the benign papillomas and the SCC. COX-2 expression was also increased in human actinic keratoses, SCC and BCC as well as in murine SCC and BCC. The pattern of COX-2 expression was quite variable, occurring in a patchy distribution in some lesions with staining confined mainly to suprabasal cell layers. In general, COX-2 expression progressively became more extensive in benign papillomas and well-differentiated murine SCC. The staining was predominantly cytoplasmic and perinuclear in some focal areas in tissue stroma around both murine and human tumors. Western blot analysis confirmed negative COX-2 expression in normal skin, whereas acute UVB exposure resulted in increased enzyme expression, which continued to increase in developing papillomas and SCC. Because of the evidence indicating a pathogenic role for eicosanoids in murine and human skin neoplasms, we performed studies to assess the anti-inflammatory and anticarcinogenic effects of green tea extracts, which are potent antioxidants. Acute exposure of the human skin to UVB (minimum erythema dose × 4) caused a transient enhancement of the COX-2 expression, which reverted to baseline within hours; however, in murine skin the expression persisted for several days. Pretreatment with the topically applied green tea extract (1 mg/cm2) largely abrogated the acute COX-2 response to UVB in mice or humans. In summary, enhanced COX-2 expression serves as a marker of epidermal UVB exposure for murine and human NMSC. These results suggest that COX-2 inhibitors could have potent anticarcinogenic effects in UVB-induced skin cancer. [source] Cyclooxygenase-2 expression correlates with phaeochromocytoma malignancy: evidence for a Bcl-2-dependent mechanismHISTOPATHOLOGY, Issue 6 2007I S Cadden Aims:, Phaeochromocytomas are rare but potentially life-threatening neuroendocrine tumours of the adrenal medulla or sympathetic nervous system ganglia. There are no histological features which reliably differentiate benign from malignant phaeochromocytomas. The aim of the study was to evaluate cyclooxygenase (COX)-2 and Bcl-2 as tissue-based biomarkers of phaeochromocytoma prognosis. Methods and results:, COX-2 and Bcl-2 expression were examined immunohistochemically in tissue from 41 sporadic phaeochromocytoma patients followed up for a minimum of 5 years after diagnosis. There was a statistically significant association between COX-2 histoscore (intensity × proportion) and the development of tumour recurrence or metastases (P = 0.006). A significant relationship was observed between coexpression of COX-2 and Bcl-2 in the primary tumour and the presence of recurrent disease (P = 0.034). A highly significant association was observed between (i) tumour-associated expression of these two oncoproteins (P = 0.001) and (ii) COX-2 histoscore and the presence of Bcl-2 expression (P = 0.002). COX regression analysis demonstrated no significant relationship between (i) the presence or absence of either COX-2 or Bcl-2 and patient survival or (ii) COX-2 histoscore and patient survival. Conclusions:, COX-2 and Bcl-2 may promote phaeochromocytoma malignancy, and these oncoproteins may be valuable surrogate markers of an aggressive tumour phenotype. [source] Cyclooxygenase-2 expression in dermatofibroma and dermatofibrosarcoma protuberansJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2008Neta Adler Background:, Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) occasionally resemble each other histologically but differ in histogenesis and biological behavior. This study sought to determine if these lesions can be differentiated by the quantity or quality of expression of cyclooxygenase-2 (COX-2), an enzyme associated with both reactive and neoplastic processes. Patients and methods:, Formalin-fixed and paraffin-embedded samples from 20 DFs and 20 DFSPs were stained immunohistochemically with antibodies directed against COX-2. Staining was evaluated semiquantitatively for percentage and intensity using a three-tiered system. DFs were graded and analyzed by cellularity. Findings within the tumors were compared with fibrocyte staining in adjacent tissue. The results were analyzed. Results:, Nineteen DFs (95%) and 15 DFSPs (75%) were immunopositive for COX-2; this difference was not statistically significant. Highly cellular DFs showed more widespread (p = 0.0039; r = 0.614) and more intense (p = 0.0586; r = 0.429) staining than less cellular DFs and more prominent staining in adjacent fibroblasts (p = 0.044; r = 0.608). Conclusions:, COX-2 immunostaining does not distinguish DFs from DFSPs. However, the enzyme is expressed more widely and more intensely in more cellular, possibly younger, DFs. The prominent expression of COX-2 in DFSP may have clinical implications for treatment with COX-2 inhibitors in tumors that are not amenable to surgery. [source] Effect of Helicobacter pylori infection on cyclooxygenase-2 expression in gastric antral mucosaJOURNAL OF DIGESTIVE DISEASES, Issue 2 2002Hong LU OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX-2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX-2 may contribute to gastrointestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX-2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori- infected patients, who also had chronic gastritis, both before and after anti- H. pylori treatment. The COX-2 protein was stained by using immunohistochemical methods and COX-2 expression was quantified as the percentage of epithelial cells expressing COX-2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase-2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase-2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX-2 expression in H. pylori -infected mucosa was compared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX-2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX-2 protein, suggesting that the enzyme is involved in H. pylori -related gastric pathology in humans. [source] Cyclooxygenase-2 expression and connection with tumor recurrence and histopathologic parameters in gastrointestinal stromal tumorsAPMIS, Issue 11 2009HÜSEYIN KEMAL TÜRKÖZ Tissue cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin synthesis and has been shown to have roles in carcinogenesis and tumor progression. Evaluation of COX-2 overexpression in malignancies has been performed mostly on tumors of epithelial origin, and little is known about its presence in mesenchymal tumors, especially gastrointestinal stromal tumors (GIST). COX-2 has been reported to be widely expressed in GIST and has been suggested as a potential diagnostic marker. We evaluated the overexpression and roles of COX-2 in tumorigenesis in GIST with regard to its relation to prognostic parameters and tumor recurrence. We studied the presence of COX-2 expression immunohistochemically and its relation to clinicopathologic prognostic variables in 41 cases of GIST. COX-2 was overexpressed in 21 (51%) of 41 tumors. The extent of overexpression was greater in tumors that recurred after surgical resection. COX-2 overexpression was also higher in tumors with coagulative necrosis, high mitotic index and an infiltrative pattern of growth. The observation of greater COX-2 expression levels in GIST with unfavorable histopathologic variables is contrary to previous reports and consistent with the reported roles of COX-2 in carcinogenesis of epithelial malignancies. [source] Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinomaAPMIS, Issue 1 2009MONA MOUSSA Cyclooxygenase-2 (COX-2) is a key inducible enzyme involved in the production of prostaglandins. It contributes to human carcinogenesis by various mechanisms. The aim of the current study was to elucidate the possible involvement of COX-2 in human bladder carcinoma by examining its expression on both urothelial and inflammatory cells in tissue biopsies and urine cytology samples of different urinary bladder lesions. A total of 65 patients were included in the study and were selected from cases admitted to Urology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt. They represented seven control cases with almost normal-looking bladder tissue; pure chronic cystitis (n=12); premalignant lesions (18) in the form of squamous metaplasia (n=8) or urothelial dysplasia (n=10) as well as transitional cell carcinoma (TCC) (n=18), and squamous cell carcinoma (SqCC) (n=10). Immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections and urine cytology samples was performed for all cases using COX-2 (H-62): sc-7951, a rabbit polyclonal antibody. The study revealed positive COX-2 expression on the urothelial and inflammatory cells of cystoscopic biopsies from all cases of pure chronic cystitis, squamous metaplasia and SqCC compared with 42.8% and 71.4% of normal controls, respectively. The score of urothelial COX-2 expression was sequentially up-regulated from normal to chronic cystitis (either pure or associated with premalignant changes) (p<0.05) to malignant changes (p<0.05). However, the inflammatory cellular expression was down-regulated with malignant transformation compared with chronic cystitis (p<0.05). In TCC, COX-2 was over-expressed on both urothelial and inflammatory cells in advanced tumors. Urine cytology samples were positive for COX-2 in a comparable manner to that observed in cystoscopic biopsies. Accordingly, the results of the current study have provided new information in two aspects: First, is the possibility of using the differential COX-2 expression on both inflammatory and urothelial cells as markers for premalignant or malignant transformation; second, besides cystoscopy, urine cytology was found to have a high sensitivity for COX-2 expression and hence proved to be valuable in malignancy as a non-invasive substitute for cystoscopy. [source] Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 casesBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004T. Nijsten Summary Background, Cyclooxygenase (COX)-2 expression and tumour-induced angiogenesis appear to be increased in squamous cell carcinoma (SCC) of the skin. In other cancers, COX-2 is a pro-angiogenic factor. The association between angiogenesis and COX-2 has not been studied in skin cancer. Objectives, To assess the onset of increased COX-2 expression and angiogenesis in the multistage carcinogenesis of SCC as well as the correlation between those two parameters. Patients/methods, We performed a retrospective paired immunohistochemical analysis of normal skin, actinic keratosis (AK), Bowen's disease (BD) and SCC among 35 individuals. Specimens were considered COX-2 immunopositive when 5% or more of the tumour cells showed clear evidence of immunostaining. To quantify active angiogenesis, we used a Ki-67,CD34 double-labelling immunohistochemical stain and calculated the fraction of proliferating endothelial cells. The Chalkley method was used to determine the microvessel density. To detect hypoxia, a carboanhydrase IX immunostain was used. Results, Compared with normal epidermis (0%), AK (31%), BD (22%) and SCC (40%) were significantly more likely to be COX-2 immunopositive (P < 0·01). The fraction of proliferating endothelial cells and the Chalkley scores paralleled multistage carcinogenesis (P < 0·05 between different stages). COX-2 immunopositivity was fairly correlated with hypoxia and higher proliferating endothelial cell fractions but not with Chalkley counts. Conclusions, Induction of COX-2 expression and angiogenesis are both early events in the development of SCC. In addition to ultraviolet light, hypoxia and COX-2 may be involved in skin tumour angiogenesis. [source] | ||||||||||