Expression of cyclooxygenase-1 and -2 and clinicopathologic features of colorectal cancer in northern Thailand.

Two isoforms of cyclooxygenase, COX-1 and COX-2, have been identified and shown to be involved in tumorigenesis. Although, overexpression of COX-2 in human cancers has been repeatedly reported, no data have hitherto been available for Thai patients. To cast light on the role(s) of COX enzymes in the development and progression of colorectal cancers and to determine the incidence of COX-2 overexpression, the expression levels of COX-1 and COX-2 proteins using Western blot analysis in tumor tissues and adjacent normal tissues obtained from 44 Thai patients with colorectal cancer. Compared with paired normal tissues, COX-2 was overexpressed in 13 of 44 colorectal tumor tissues (29.5%). Overall, COX-2 levels in colorectal tumor specimens were significantly correlated with histological differentiation, in particular in the tumors with poor differentiation (p<0.05). In addition, overexpression of COX-2 was found more frequently in colorectal tumors with lymphatic invasion, regional lymph node metastasis and larger size, although without statistical significance. In contrast to the relatively consistent alteration in COX-2 expression, the level of COX-1 expression was quite varied in tumor tissues. Forty-eight percent of colorectal tumors exhibited a decreased level of COX-1 in comparison to normal tissues and overexpressed in 23%. Thus both isoforms may both play roles in promoting tumorigenesis. However, there was no significant relationship between the alteration of COX-1 protein levels and any pathological features of tumors.

Expression and significance of cyclooxygenase 2 gene in lung cancer / 华中科技大学学报（医学）（英德文版）

To study the expression of cyclooxygenase 2 (COX-2) gene and its relationship with clinicopathological characteristics of lung cancer, expression of the COX-2 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in cancerous tissues and paired adjacent non-cancerous tissues from 56 patients and benign lesions from 12 patients. Our results showed that expression of COX-2 gene was detected in a significantly greater proportion of cancerous tissues (60.7%) than adjacent noncancerous tissues (10.7%, P0.05). The up-regulation of COX-2 gene in lung cancer tissues especially in adenocarcinoma suggested that COX-2 may play a role in the lung carcinogenesis and COX-2 gene may serve as a potential therapeutic target in lung cancer.

Dexamethasone differentiates NG108-15 cells through cyclooxygenase1 induction

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.

NF-kappaB Binding Activity and Cyclooxygenase-2 Expression in Persistent betaCCI(4)-Treated Rat Liver Injury

The involvement of NF-kappaB binding activity is known to be important in the mechanism of acute liver injury and in the induction of cyclooxygenase (COX-2). This study was performed to evaluate NF-kappaB binding activity and the expression of COX-2 in chronic liver injury induced by carbon tetrachloride (betaCCI(4)). Liver tissues from Sprague - Dawley rats were collected at 1, 3, 5, and 7th week after intraperitoneal injection of 0.1 mL of betaCCI(4)/100 g body weight twice a week. Reactive oxy-gen species (ROS) were measured in the postmitochondrial fraction by dichlorofluorescein formation with a fluorescent probe. An electrophoretic mobility shift assay was performed for NF-kappaB binding activity. Western blot was performed to measure the level of COX-1, COX-2, p65, p50, and I B proteins. ROS and NF-kappaB activity increased during the CCl4-induced chronic liver injury. The expression of nuclear p65 protein and p50 protein increased compared with that of the control, while the cytoplasmic I B protein decreased as the inflammation persisted. The expression of COX-2 in betaCCI(4)-treated rat liver increased compared with that of the control. It could be suggested that ROS produced by betaCCI(4) treatment increased NF-kappaB binding activity and thereby COX-2 expression, and these might be implicated in the progress of chronic liver damage.

Expression of cyclooxygenase-1 and -2 in rheumatoid arthritis synovium

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.

Effecto del clonixinato de lisina y la indometacina sobre la actividad de la lipooxigenasa y la ciclooxigenasa de colon aislado de pacientes con neoplasias / Effect of lysine clonixinate and indomethacin on the lipooxygenase and cycloogygenase activity of clon isolated from cancer patients

Las ulceraciones de la mucosa gástrica y colónica producida por los antiinflamatorios no esteroides (AINES) son producidas por la reducción de la síntesis de prostaglandinas (PGs) por inhibición de la ciclooxigenasa. Por otro lado se ha demosntrado que los productos de la 5-lipoxigenasa (5-LO) son agentes ulcerogénicos. En algunos casos el uso de AINES se acompaña de una mayor producción de productos de la 5-LO debido a un exceso de sustrato (ácido araquidónico) al estar bloqueada la ciclooxigenasa. Cuando ocurre esto último aumentan los efectos lesivos de los AINES ya que no sólo disminuyen las PGS citoprotectoras, sino que también aumentan los productos de la 5-LO. El objeto de este trabajo, fue estudiar en segmentos de colon aislado de pacientes con neoplasias el efecto del Clonixinato de lisina (CL) y de la indometacina (INDO) sobre la síntesis de PGs e hidroxiácidos (HETEs). Las concentraciones de CL (4 y 6 mug/ml) y de indo (0,035 y 0,035 y 0,35 mug/ml utilizadas, se corresponden con los valores plasmáticos alcanzados con dosis terapéuticos orales de ambas drogas. Se observó que el CL con ninguna de las dosis utilizadas modificó la producción basal de PGE(2). Por el contrario la INDO inhibió significativamente la síntese de PGE(2) con ambas dosis. Llamó la atención que el CL tanto a 4 mug/ml como 6 mug/ml produjo una profunda disminución en la producción de 5-HETE, efecto sólo observado con la concentración más alta de INDO. Este resultado indicaría una probable acción inhibitoria sobre la 5-LO, primeira enzima del camino metabólico del ácido araquidónico hacia formación de HETEs y Lts. Concluimos que el CL en dosis terapéuticas tiene un mecanismo de acción diferente al de los AINES clásicos. Los datos obtenidos en este estudo explicarían la baja incidencia de efectos gastrointestinales lesivos observados con CL.