Disease relevance of COX2

• The purpose of this study was to evaluate the effectiveness of inhibiting COX-2 with FK3311 for the minimization of ischemia-reperfusion injury and for the improvement of donor heart function following transplantation in a canine model [1].
• COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic fmolecular markers [2].
• The objective of this study was to investigate the effects of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and folic acid on the chemoprevention of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Wistar rats, and to evaluate the cell proliferation of gastric mucosa in different experimental groups [3].
• Inhibition of COX-2 by celecoxib in the canine groove model of osteoarthritis [4].
• Selective COX-2 inhibitors may provide a possible therapeutic option for diabetic gastroparesis [5].

High impact information on COX2

• To evaluate the role of COX-2-derived metabolites in the regulation of renal function, we infused a selective inhibitor (nimesulide) in anesthetized dogs with normal or low sodium intake [6].
• COX-2 inhibition reduced urinary prostaglandin E(2) excretion in both groups but did not modify plasma renin activity in dogs with low (8.1+/-1.1 ng angiotensin I. mL(-1). h(-1)) or normal (1.8+/-0.4 ng angiotensin I. mL(-1). h(-1)) sodium intake [6].
• New water-soluble sulfonylphosphoramidic acid derivatives of the COX-2 selective inhibitor cimicoxib. A novel approach to sulfonamide prodrugs [7].
• Role of COX-2-derived metabolites in regulation of the renal hemodynamic response to norepinephrine [8].
• Moreover, LPS-induced up-regulation of cPLA2 and COX-2 linked to PGE2 synthesis was inhibited by AACOCF3 (a selective cPLA2 inhibitor), implying the involvement of cPLA2 in these responses [9].

Chemical compound and disease context of COX2

• These data indicate that COX-2 may play a pathophysiologic role in keratitis and suggest potential therapeutic implications of prostaglandin modulation in inflammatory eye diseases [10].
• Effect of deracoxib, a new COX-2 inhibitor, on the prevention of lameness induced by chemical synovitis in dogs [11].

Biological context of COX2

• The mRNA for Cox1 and Cox2 were detected at all stages of diestrus [12].
• These data suggested that increased expression of Cox2 is associated with luteal growth and development and not luteal regression [12].
• Inhibition of canine COX2 (IC50, 0.102 microM) for the racemic mixture of carprofen (S and R stereoisomers) was primarily attributable to the S enantiomer (IC50, 0.0371 microM), which was approximately 200-fold more potent than the R enantiomer (IC50, 5.97 microM) [13].
• Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities [14].
• Furthermore, LPS-induced NF-kappaB activation correlated with the degradation of IkappaB-alpha, COX-2 expression, and PGE(2) synthesis, was inhibited by transfection with dominant negative mutants of NIK and IKK-alpha, but not by IKK-beta [15].

Anatomical context of COX2

• Immunohistochemistry localized expression of Cox2 in the cytoplasm of luteal cells [12].
• PROCEDURE: Constitutive COX1 was obtained from washed canine platelets, and COX2 was obtained from a canine macrophage-like cell line that was induced with endotoxin [13].
• Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels [16].
• Immunohistochemical staining revealed that COX-2 expression was reduced significantly in the myocardium of FK-treated dogs compared with controls [1].
• Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb [14].

Associations of COX2 with chemical compounds

• To test for possible paracrine/autocrine effects of locally produced PGF2alpha, luteal expression of the key rate-limiting enzymes in prostaglandin biosynthesis, i.e. cyclooxygenase 1 and 2 (Cox1 and Cox2), was examined in dogs during diestrus, including the periods of CL formation, as well as early and late CL regression [12].
• CLINICAL RELEVANCE: The selectivity of carprofen for canine COX2 may be an important factor for its use in dogs [13].
• Nimesulide had the next highest selectivity for COX2 (38-fold), and tolfenamic acid and meclofenamic acid had 15-fold selectivity for COX2 [13].
• A 5-lipoxygenase inhibitor (zileuton), a corticosteroid (dexamethasone) and a dual COX-2 selective/5-lipoxygenase inhibitor (RWJ 63556) had similar profiles in that they all inhibited cell infiltration and eicosanoid production in the fluid and also attenuated leukotriene B4 production in both the fluid and blood [17].
• Treatment of cells with either a COX-1-selective inhibitor, SC-560, or COX-2-selective inhibitors, SC-58125 or NS-398, inhibited basal and UTP-stimulated cAMP levels [18].

Regulatory relationships of COX2

• In conclusion, glucagon induces delayed gastric emptying partially via COX-2-derived prostaglandins [5].

Other interactions of COX2

• The other compounds tested did not have substantial selectivity for canine COX2 or were more selective for canine COX1 [13].
• However, COX-2-derived prostaglandins are not involved in glucagon-evoked gastric dysrhythemia [5].
• In conclusion, our results suggested that the PGE2 induced by COX-2 might play a role in mucin secretion from the gallbladder epithelium through the increment of cAMP [19].
• OBJECTIVE: To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively [20].
• The macrophages were positive for IL-1beta, TNF-alpha, i-NOS, and COX-2 [21].

Analytical, diagnostic and therapeutic context of COX2

• On the mRNA-level, expression of Cox1 and Cox2 was tested by qualitative and quantitative, Real Time (Taq Man) RT-PCR; on the protein level, expression of Cox2 was studied by immunohistochemistry [12].
• It has been reported that COX-2 plays an important role in ischemia-reperfusion injury and that COX-2 mRNA and protein expression were up-regulated during cardiac allograft rejection [1].
• BACKGROUND: Cyclooxygenase-2 (COX-2) mediates the late phase of ischemic preconditioning (IPC), but whether this enzyme modulates early IPC, anesthetic-induced preconditioning (APC), or other forms of pharmacologic preconditioning (PPC) is unknown [22].
• Effects of standard antiinflammatory agents (aspirin, indomethacin, dexamethasone, tenidap and zileuton) and newer cyclooxygenase-2 (COX-2) selective agents (nimesulide, nabumetone and SC-58125) were determined after oral administration [17].
• Cartilage specimens were stained for TUNEL reaction and immunostained using specific antibodies for caspase 3, COX-2, iNOS, and nitrotyrosine [23].

References