PURPOSE Emerging data continue to link carcinogenesis to inflammatory events involving the eicosanoid metabolic pathways. We therefore evaluated the effects of cyclooxygenase (COX)-2 inhibition on leukotriene (LT) B(4) synthesis in the lungs of active smokers, as part of a pilot lung cancer chemoprevention study with celecoxib (Celebrex), an oral COX-2 inhibitor. EXPERIMENTAL DESIGN Bronchoal...

PURPOSE Arachidonic acid metabolism via the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways modulates cell growth and apoptosis. Many studies have examined the effects of COX inhibitors on human colorectal cancer, but the role of 5-LOX in colonic cancer development has not been well studied. The purpose of this study was to evaluate the expression of 5-LOX in colonic polyps and cancer ...

In the field of gene expression analysis, DNA microarray technology is having a major impact on many different areas including toxicology. For instance, a number of studies have shown that transcription profiling can generate the information needed to assign a compound to a mode-of-action class. In this study, we investigated whether compounds inducing similar toxicological endpoints produce si...

OBJECTIVES Esculetin (6,7-dihydroxycoumarin) is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX) and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9). Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in...

OBJECTIVE To assess the utilization of leukotriene modifiers (LM) relative to national guidelines and to investigate possible emergency room utilization differences for LMs as monotherapy versus inhaled corticosteroid (ICS) monotherapy or combination ICS and LM therapy. METHODS The utilization of leukotriene modifiers (montelukast sodium, zafirlukast, and zileuton), concurrent inhaled steroid...

TRPM7 is a ubiquitous divalent-selective ion channel with its own kinase domain. Recent studies have shown that suppression of TRPM7 protein expression by RNA interference increases resistance to ischemia-induced neuronal cell death in vivo and in vitro, making the channel a potentially attractive pharmacological target for molecular intervention. Here, we report the identification of the 5-lip...

OBJECTIVE Myogenic vasoconstriction is mediated by vascular smooth muscle cells of resistance arteries sensing mechanical stretch. Angiotensin II AT1 receptors and in particular AT1BRs in murine vascular smooth muscle cells have been characterized as mechanosensors that cannot fully account for myogenic vasoconstriction observed. Therefore, we aimed at uncovering novel vascular mechanosensors b...

BACKGROUND Cysteinyl leukotrienes (CysLT) are a class of inflammatory mediators synthesized by eosinophils and mast cells through the breakdown of arachidonic acid. They are known to play a key role in the molecular pathophysiology of asthma and chronic rhinosinusitis (CRS), promoting bronchoconstriction, mucus production, edema, and chemotaxis of neutrophils and eosinophils. Indeed, upregulati...

We recently reported the synthesis and anti-inflammatory properties of a novel long chain polyunsaturated fatty acid (PUFA) with an oxygen atom in the beta-position, beta-oxa-21:3 n-3 (Z,Z,Z)-(octadeca-9,12,15-trienyloxy) acetic acid). Our data, from studies aimed at elucidating the mechanism of its action, show that pretreatment of human neutrophils with the beta-oxa-PUFA substantially depress...

Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), activates neutrophils to produce superoxide anion (O2-) by a mechanism that involves phospholipase C-dependent hydrolysis of membrane phosphoinositides; however, subsequent signal transduction mechanisms are unknown. We undertook this study to determine whether phospholipase A2-dependent release of arachidonic acid is involved in PCB-...