An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.
A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.
Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.
A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.
Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.
A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.
Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.
A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.
A group of compounds that contain the structure SO2NH2.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.
An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.
The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.
A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.
An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).
A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.
Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.
An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC
An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.
Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.
A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.
Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2.
A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).
A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.
A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.
The relationship between the dose of an administered drug and the response of the organism to the drug.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.
Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.
A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.
The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES. The receptor may also signal through the activation of PHOSPHATIDYLINOSITOL 3-KINASE.
A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GQ and the subsequently activates TYPE C PHOSPHOLIPASES. Additional evidence has shown that the receptor can act through a calcium-dependent signaling pathway.
Compounds that inhibit the action of prostaglandins.
The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.
The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.
A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.
Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).
A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.
An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)
Drugs used to cause dilation of the blood vessels.
A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)
Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.
A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)
A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI and subsequently inhibits ADENYLYL CYCLASES.
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
Drugs used to cause constriction of the blood vessels.
A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.
Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Substances that reduce or suppress INFLAMMATION.
The smallest divisions of the arteries located between the muscular arteries and the capillaries.
An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
(9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
A subcategory of phospholipases A2 that occur in the CYTOSOL.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Ulceration of the GASTRIC MUCOSA due to contact with GASTRIC JUICE. It is often associated with HELICOBACTER PYLORI infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).
The nonstriated involuntary muscle tissue of blood vessels.
Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins.
Arteries which arise from the abdominal aorta and distribute to most of the intestines.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.
FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.
The rate dynamics in chemical or physical systems.
An anti-inflammatory 9-fluoro-glucocorticoid.
Elements of limited time intervals, contributing to particular results or situations.
Established cell cultures that have the potential to propagate indefinitely.
A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)
Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.
An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in PLATELETS.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.
A competitive inhibitor of nitric oxide synthetase.
A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)
A cytosolic phospholipase A2 group that plays an important role in the release of free ARACHIDONIC ACID, which in turn is metabolized to PROSTAGLANDINS by the CYCLOOXYGENASE pathway and to LEUKOTRIENES by the 5-LIPOXYGENASE pathway.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
A potent vasodilator agent that increases peripheral blood flow.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities.
A class of cyclic prostaglandins that contain the 6,9-epoxy bond. Endogenous members of this family are biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.
A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21)
A series of prostaglandin-like compounds that are produced by the attack of free-radical species on unsaturated fatty acids, especially ARACHIDONIC ACID, of cellular MEMBRANES. Once cleaved from the lipid membrane by the action of phospholipases they can circulate into various bodily fluids and eventually be excreted. Although these compounds resemble enzymatically synthesized prostaglandins their stereoisometric arrangement is usually different than the "naturally occurring" compounds.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.
Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
20-carbon saturated monocarboxylic acids.
Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.
Paracrine substances produced by the VASCULAR ENDOTHELIUM with VASCULAR SMOOTH MUSCLE relaxation (VASODILATION) activities. Several factors have been identified, including NITRIC OXIDE and PROSTACYCLIN.
Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.
Tumors or cancer of the COLON.
A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.
A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.
Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.
The main trunk of the systemic arteries.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The circulation of the BLOOD through the MICROVASCULAR NETWORK.
A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.
The flow of BLOOD through or around an organ or region of the body.
A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.
The circulation of the BLOOD through the LUNGS.
The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.
A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)
An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
An essential amino acid that is physiologically active in the L-form.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
An antiseptic and disinfectant aromatic alcohol.
Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)

Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2. (1/6133)

The precise role of TGF-beta in colorectal carcinogenesis is not clear. The purpose of this study was to determine the phenotypic alterations caused by chronic exposure to TGF-beta in non-transformed intestinal epithelial (RIE-1) cells. Growth of RIE-1 cells was inhibited by >75% following TGF-beta1 treatment for 7 days, after which the cells resumed a normal growth despite the presence of TGF-beta1. These 'TGF-beta-resistant' cells (RIE-Tr) were continuously exposed to TGF-beta for >50 days. Unlike the parental RIE cells, RIE-Tr cells lost contact inhibition, formed foci in culture, grew in soft agarose. RIE-Tr cells demonstrated TGF-beta-dependent invasive potential in an in vitro assay and were resistant to Matrigel and Na-butyrate-induced apoptosis. The RIE-Tr cells were also tumorigenic in nude mice. The transformed phenotype of RIE-Tr cells was associated with a 95% decrease in the level of the type II TGF-beta receptor (TbetaRII) protein, a 40-fold increase in cyclooxygenase-2 (COX-2) protein, and 5.9-fold increase in the production of prostacyclin. Most RIE-Tr subclones that expressed low levels of TbetaRII and high levels of COX-2 were tumorigenic. Those subclones that express abundant TbetaRII and low levels of COX-2 were not tumorigenic in nude mice. A selective COX-2 inhibitor inhibited RIE-Tr cell growth in culture and tumor growth in nude mice. The reduced expression of TbetaRII, increased expression of COX-2, and the ability to form colonies in Matrigel were all reversible upon withdrawal of exogenous TGF-beta1 for the RIE-Tr cells.  (+info)

Down-regulation of oxytocin-induced cyclooxygenase-2 and prostaglandin F synthase expression by interferon-tau in bovine endometrial cells. (2/6133)

Oxytocin (OT) is responsible for the episodic release of luteolytic prostaglandin (PG) F2alpha from the uterus in ruminants. The attenuation of OT-stimulated uterine PGF2alpha secretion by interferon-tau (IFN-tau) is essential for prevention of luteolysis during pregnancy in cows. To better understand the mechanisms involved, the effect of recombinant bovine IFN-tau (rbIFN-tau) on OT-induced PG production and cyclooxygenase-2 (COX-2) and PGF synthase (PGFS) expression in cultured endometrial epithelial cells was investigated. Cells were obtained from cows at Days 1-3 of the estrous cycle and cultured to confluence in RPMI medium supplemented with 5% steroid-free fetal calf serum. The cells were then incubated in the presence or absence of either 100 ng/ml OT or OT+100 ng/ml rbIFN-tau for 3, 6, 12, and 24 h. OT significantly increased PGF2alpha and PGE2 secretion at all time points (p < 0.01), while rbIFN-tau inhibited the OT-induced PG production and reduced OT receptor binding in a time-dependent manner. OT increased the steady-state level of COX-2 mRNA, measured by Northern blot, which was maximal at 3 h (9-fold increase) and then decreased with time (p < 0.01). OT also caused an increase in COX-2 protein, which peaked at 12 h (11-fold increase), as measured by Western blot. Addition of rbIFN-tau suppressed the induction of COX-2 mRNA (89%, p < 0.01) and COX-2 protein (50%, p < 0.01) by OT. OT also increased PGFS mRNA, and this stimulation was attenuated by rbIFN-tau (p < 0.01). To ensure that the decrease in COX-2 was not solely due to down-regulation of the OT receptor, cells were stimulated with a phorbol ester (phorbol 12-myristate 13-acetate; PMA) in the presence and absence of rbIFN-tau. The results showed that rbIFN-tau also decreased PMA-stimulated PG production and COX-2 protein. It can be concluded that rbIFN-tau inhibition of OT-stimulated PG production is due to down-regulation of OT receptor, COX-2, and PGFS.  (+info)

Mechanisms of prostaglandin E2 release by intact cells expressing cyclooxygenase-2: evidence for a 'two-component' model. (3/6133)

Prostaglandin (PG) release in cells expressing constitutive cyclooxygenase-1 is known to be regulated by liberation of arachidonic acid by phospholipase A2 followed by metabolism by cyclooxygenase. However, the relative contribution of phospholipase A2 to the release of PGs in cells expressing cyclooxygenase-2 is not clear. We addressed this question by using radioimmunoassay to measure PGE2 release by human cells (A549) induced to express cyclooxygenase-2 (measured by Western blot analysis) by interleukin-1beta. Cells were either unstimulated or stimulated with agents known to activate phospholipase A2 (bradykinin, Des-Arg10-kallidin, or the calcium ionophore A23187) or treated with exogenous arachidonic acid. When cells were treated to express cyclooxygenase-2, the levels of PGE2 released over 15 min were undetectable; however, in the same cells stimulated with bradykinin, A23187, or arachidonic acid, large amounts of prostanoid were produced. Using selective inhibitors/antagonists, we found that the effects of bradykinin were mediated by B2 receptor activation and that prostanoid release was due to cyclooxygenase-2, and not cyclooxygenase-1, activity. In addition, we show that the release of PGE2 stimulated by either bradykinin, A23187, or arachidonic acid was inhibited by the phospholipase A2 inhibitor arachidonate trifluoromethyl ketone. Hence, we have demonstrated that PGE2 is released by two components: induction of cyclooxygenase-2 and supply of substrate, probably via activation of phospholipase A2. This is illustrated in A549 cells by a clear synergy between the cytokine interleukin-1beta and the kinin bradykinin.  (+info)

Inhibition of prostaglandin synthesis up-regulates cyclooxygenase-2 induced by lipopolysaccharide and peroxisomal proliferators. (4/6133)

Primary cultures of fetal hepatocytes expressed cyclooxygenase-2 (COX-2) upon stimulation with bacterial lipopolysaccharide (LPS) or peroxisomal proliferators. This enzyme was active and a good correlation between the mRNA levels, the amount of protein, and the synthesis of prostaglandin E2 was observed. However, when cells were incubated in the presence of indomethacin or the COX-2-specific inhibitor NS398, the amount of COX-2 protein increased 5-fold after activation with LPS and 2-fold after treatment with clofibrate. This up-regulation of COX-2 was not observed at the mRNA level. The mechanism of protein accumulation might involve either a direct stabilization of the enzyme by the inhibitors or the absence of prostaglandins involved in the regulation of its turnover. Among the prostaglandins assayed, only 15-deoxy-Prostaglandin J2 exerted a statistically significant decrease in the COX-2 levels in cells stimulated with LPS or LPS plus NS398. The accumulation of COX-2 in the presence of inhibitors was also observed in peritoneal macrophages treated under identical conditions. These results indicate that COX-2 protein accumulates after enzyme inhibition, and because removal of the inhibitors restored the enzyme activity, suppression of treatment with reversible COX-2 inhibitors may cause a transient overproduction of prostaglandins.  (+info)

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. (5/6133)

The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.  (+info)

Oxidative bioactivation of the lactol prodrug of a lactone cyclooxygenase-2 inhibitor. (6/6133)

The lactol derivative of a lactone cyclooxygenase-2 inhibitor (DFU) was evaluated in vivo and in vitro for its potential suitability as a prodrug. DFU-lactol was found to be 10 to 20 times more soluble than DFU in a variety of aqueous vehicles. After administration of DFU-lactol at 20 mg kg-1 p.o. in rats, a Cmax of 7.5 microM DFU was reached in the plasma. After oral administration, the ED50s of DFU-lactol in the carrageenan-induced paw edema and lipopolysaccharide-induced pyresis assays in rats are comparable with the ED50s observed when dosing with DFU. Incubations of DFU-lactol with rat and human hepatocytes demonstrated that the oxidation of DFU-lactol can be mediated by liver enzymes and that a competing pathway is direct glucuronidation of the DFU-lactol hydroxyl group. Assays with subcellular fractions from rat liver indicated that most of the oxidation of DFU-lactol occurs in the cytosolic fraction and requires NAD(P)+. Human liver cytosol can also support the oxidation of DFU-lactol to DFU when NAD(P)+ is added to the incubations. Fractionation of human liver cytosolic proteins showed that at least three enzymes are capable of efficiently effecting the oxidation of DFU-lactol to DFU. Incubations with commercially available dehydrogenases suggest that alcohol and hydroxysteroid dehydrogenases are involved in this oxidative process. These data together suggest that lactols may represent useful prodrugs for lactone-containing drugs.  (+info)

Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. (7/6133)

Activation of platelets results in shedding of membrane microparticles (MP) with potentially bioactive properties. Platelet MP modulate platelet, monocyte, and vascular endothelial cell function, both by direct effects of MP arachidonic acid (AA) and by its metabolism to bioactive prostanoids. We have previously reported that platelet MP induce expression of cyclooxygenase (COX)-2 and prostacyclin production in monocytes and endothelial cells. To elucidate further the molecular mechanisms that underlie MP-induced up-regulation of COX-2 expression, we investigated the response of a human monocytoid (U-937) cell line to platelet MP stimulation. In U-937 cells, MP-induced COX-2 expression and eicosanoid formation is prevented by pharmacological inhibitors of protein kinase C (PKC), PI 3-kinase, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, and p38 kinase. Treatment with the PI 3-kinase inhibitors wortmannin and LY294002 also blocked MP-induced p42/p44 MAPK, p38, and JNK1 phosphorylation. Conversely, platelet MP stimulation of U-937 cells results in direct activation of PKC, p42/p44 MAPK, p38 kinase, and c-Jun N-terminal kinase (JNK) as well as activation of the transcription factors c-Jun and Elk-1. However, MP failed to activate the cAMP response element. Activation of U-937 cells by MP induces translocation of classical (PKCbeta), novel (PKCdelta) and atypical (PKCzeta and PKClambda) isozymes of PKC from the cytosol to the membrane, with concomitant activation of downstream MAPK. While MP-induced activation of p42/p44 MAPK and p38 kinase is transient, a sustained activation of JNK1 was observed. Although PKC activation is required for MP-induced p42/p44 MAPK, activation of the stress kinases p38 and JNK1 was PKC-independent. The fatty acid fraction of the MP accounted for these effects, which were mimicked by MP AA. Rather than acting directly via nuclear receptors, MP AA activates COX-2-dependent prostaglandin production by a PKC/p42/p44 MAPK/p38 kinase-sensitive pathway in which PI 3-kinase plays a significant role. MP AA also stimulates transcriptional activation of COX-2 as well as c-Jun and Elk-1.  (+info)

Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors. (8/6133)

Evidence is accumulating which indicates that cyclooxygenase-2 (COX-2) is involved in the pathogenesis of colorectal cancer. We evaluated the expression of COX-2 in replication error-positive (RER) colon cancers, colon cancers metastatic to liver and azoxymethane (AOM)-induced rat colonic tumors. Immunohistochemistry showed that COX-2 was low to undetectable in normal human mucosa, but abundant in the RER adenocarcinomas we examined. COX-2 immunoreactivity in metastatic colon cancers was less abundant, but clearly detectable. In the colon of AOM-treated rats, COX-2 protein was not detectable in normal mucosa, but present in most of the epithelial cells comprising the tumors. The TGF-beta1 staining pattern in these human and rat tumors was similar to that observed for COX-2. The role of TGF-beta in RER adenocarcinomas is complex because of the increased mutation rate of TGF-beta type II receptors. Northern analysis showed abundant TGF-beta1 mRNA in AOM-induced tumors, but not in paired mucosa. TGF-beta1 induced the expression of COX-2 mRNA and protein in intestinal epithelial cells (IEC-6). Chronic TGF-beta1 treatment caused a TGF-beta-dependent overexpression of COX-2 in rat intestinal epithelial cells (RIE-1). TGF-beta1 may regulate COX-2 expression during the colonic adenoma to carcinoma sequence.  (+info)

Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase, is the key enzyme in prostaglandin biosynthesis, and acts both as a dioxygenase and as a peroxidase. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2, which differ in their regulation of expression and tissue distribution. This gene encodes the inducible isozyme. It is regulated by specific stimulatory events, suggesting that it is responsible for the prostanoid biosynthesis involved in inflammation and mitogenesis. [provided by RefSeq, Feb 2009 ...
TY - JOUR. T1 - Store-operated Ca2+ Entry Facilitates the Lipopolysaccharide-induced Cyclooxygenase-2 Expression in Gastric Cancer Cells. AU - Wong, Jhen Hong. AU - Ho, Kuo Hao. AU - Nam, Sean. AU - Hsu, Wen Li. AU - Lin, Chia Hsien. AU - Chang, Che Mai. AU - Wang, Jaw Yuan. AU - Chang, Wei Chiao. PY - 2017/12/1. Y1 - 2017/12/1. N2 - Helicobacter pylori has been identified as one of the major causes of chronic gastritis, gastric and duodenal ulcers, and gastric cancer. Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria, and H. pylori LPS might play an exclusively important role in activating inflammatory pathways in monocytes and macrophages. To study the role of LPS in the underlying mechanism of inflammatory responses, we established an in vitro model using the human AGS gastric cancer cell line. We found that LPS mediates inflammation through setting off a cascade of events: activation of the store-operated calcium (SOC) channel, initiation of ...
PTGS2 (COX-2) is unexpressed under normal conditions in most cells, but elevated levels are found during inflammation. PTGS1 (COX-1) is constitutively expressed in many tissues and is the predominant form in gastric mucosa and in the kidneys. Inhibition of PTGS1 (COX-1) reduces the basal production of cytoprotective PGE2 and PGI2 in the stomach, which may contribute to gastric ulceration. Since PTGS2 (COX-2) is generally expressed only in cells where prostaglandins are upregulated (e.g., during inflammation), drug-candidates that selectively inhibit PTGS2 (COX-2) were suspected to show fewer side-effects[25] but proved to substantially increase risk for cardiovascular events such as heart attack and stroke. Two different mechanisms may explain contradictory effects. Low-dose aspirin protects against heart attacks and strokes by blocking PTGS1 (COX-1) from forming a prostaglandin called thromboxane A2. It sticks platelets together and promotes clotting; inhibiting this helps prevent heart ...
The size of the PCR products from cyclooxygenase-1 and cyclooxygenase-2 are 524 and 583 base pairs, respectively. The specificity of the PCR reaction for cyclooxygenase-1 and cyclooxygenase-2 complementary deoxyribonucleic acid (cDNA) was confirmed by digestion of PCR products by sequence-specific restriction enzymes (cyclooxygenase-1: Sac I and Sma I; cyclooxygenase-2: Pst I and Nco I). For quantitation of cyclooxygenase-1 and cyclooxygenase-2 mRNA levels, the Escherichia coli plasmid pT2M containing specific internal standards for cyclooxygenase-1 and cyclooxygenase-2 was constructed by internal deletion of sequences: The truncated fragments (320 base pairs) from cyclooxygenase-1 and cyclooxygenase-2 PCR products were incorporated into the E. coli cloning plasmid pBSII SK(+)(Stratagene, La Jolla, CA) at the EcoR I and Kpn I restriction sites and multiplied as plasmids in an E. coli strain Dh5 alpha. Plasmid solutions were adjusted to 1 x 104molecules/micro liter after double digestion by ...
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain. Drugs, like Aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Non-steroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, exert their effects through inhibition of COX. The main COX inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs).. ...
We investigated the effects of Th2 cell-associated cytokines, IL-4, IL-10, and IL-13, on prostaglandin (PG) production by human peripheral blood monocytes (HPBM) in terms of four parameters: PGE2 synthesis; cyclooxygenase activity; protein; and mRNA of two cyclooxygenase isozymes (cyclooxygenase-1 and cyclooxygenase-2). LPS-stimulated PGE2 synthesis and cyclooxygenase activity were suppressed by IL-4, IL-10, or IL-13. Furthermore, the LPS-dependent increase of cyclooxygenase activity in HPBM was attributable to cyclooxygenase-2 because it was inhibited by NS-398 (a cyclooxygenase-2-specific inhibitor). Western and Northern blot analyses revealed that the LPS-induced increases in cyclooxygenase-2 protein and mRNA were attenuated by the addition of IL-4, IL-10, or IL-13. In contrast, cyclooxygenase-1 protein and mRNA were hardly detected in monocytes that were incubated with or without LPS in the presence or absence of IL-4, IL-10, and IL-13. These results suggest that the reduction of LPS-induced ...
PTGS2 is the inducible isozyme of prostaglandin-endoperoxide synthase, also known as cyclooxygenase. It has been linked to numerous conditions, especially involving inflammation or cancer. Also known as COX2. [PMID 17479405] Haplotypes A-1195G-765T8473 and A-1195C-765T8473 variants of COX-2 were associated with 1.3X increased risk of breast cancer in a Chinese population [PMID 16361272] Relative to individuals with a PTGS2 Ex10 +837 TT genotype, those carrying the C allele (TC or CC genotype) had a 1.8-fold risk of bile duct cancer in a Chinese population [PMID 12920574] In a group of Pima Indians, individuals with the variant PTGS2 rs20417 CC genotype had a 30% higher Type 2 diabetes prevalence compared with subjects with the GG genotype ...
Cystic fibrosis (CF) is one of the most common autosomal recessive diseases among Caucasians caused by a mutation in the CFTR gene. However, the clinical outcome of CF pulmonary disease varies remarkably even in patients with the same CFTR genotype. This has led to a search for genetic modifiers located outside the CFTR gene. The aim of this study was to evaluate the effect of functional variants in prostaglandin-endoperoxide synthase genes (COX1 and COX2) on the severity of lung disease in CF patients. To the best of our knowledge, it is the first time when analysis of COX1 and COX2 as potential CF modifiers is provided. The study included 94 CF patients homozygous for F508del mutation of CFTR. To compare their clinical condition, several parameters were recorded, e.g. a unique clinical score: disease severity status (DSS). To analyse the effect of non-CFTR genetic polymorphisms on the clinical course of CF patients, the whole coding region of COX1 and selected COX2 polymorphisms were analysed. ...
The cyclooxygenase (COX) isoforms COX-1 and COX-2 convert arachidonic acid to prostaglandin (PG) precursors and are a limiting step in PG production. Interleukin-1beta (IL-1beta) treatment of type II A549 cells increases PGE2 synthesis via transcription- and translation-dependent induction of COX-2. …
COX1 / Cyclooxygenase 1兔单克隆抗体[EPR5866](ab109025)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC, Flow Cyt, ICC/IF实验严格验证,被2篇文献引用并得到2个独立的用户反馈。
Cyclooxygenase is the key enzyme in the biosynthetic pathway of prostaglandins (PGs) and thromboxane from arachidonic acid. There are two isozymes of cyclooxygenase; constitutive cyclooxygenase-1 and...
Cyclooxygenase is an enzyme that produces signals that can lead to pain and inflammation. Medications that inhibit cyclooxygenase...
购买我们的人COX1 / Cyclooxygenase 1肽。ab22901可作为ab2338的封闭肽并经过Blocking实验验证。Abcam提供免费的实验方案,操作技巧及专业的支持。中国80%以上现货。
Rabbit polyclonal COX2 / Cyclooxygenase 2 antibody. Validated in WB, ICC/IF and tested in Mouse, Rat, Human. Cited in 63 publication(s). Independently reviewed in 5 review(s). Immunogen corresponding…
高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab62331 交差種: Ms,Hu 適用: WB,Flow Cyt,ICC/IF
ptgs2, cox-2, cox2, gripghs, hcox-2, pgg/hs, pghs-2, phs-2; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase); K11987 prostaglandin-endoperoxide synthase 2 [EC:] ...
Sirtuin 1 (Sirt1) is a NAD+-dependent deacetylase that exerts many of the pleiotropic effects of oxidative metabolism. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress. Here, we set out to investigate the role of Sirt1 in the kidney. Our initial analysis indicated that it was abundantly expressed in mouse renal medullary interstitial cells in vivo. Knocking down Sirt1 expression in primary mouse renal medullary interstitial cells substantially reduced cellular resistance to oxidative stress, while pharmacologic Sirt1 activation using either resveratrol or SRT2183 improved cell survival in response to oxidative stress. The unilateral ureteral obstruction (UUO) model of kidney injury induced markedly more renal apoptosis and fibrosis in Sirt1+/¨C mice than in wild-type controls, while pharmacologic Sirt1 activation substantially attenuated apoptosis and fibrosis in wild-type mice. Moreover, Sirt1 deficiency attenuated oxidative stress¨Cinduced COX2 ...
Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of two cyclooxygenases. Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid. This protein was purified more than 20 years ago and cloned in 1988. There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors. This gene encodes COX-1, which regulates angiogenesis in endothelial cells. COX-1 is also involved in cell signaling and maintaining tissue homeostasis. A splice variant of COX-1 termed COX-3 was identified in the CNS of dogs, but does not result in a functional protein in humans. ...
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prostacyclin, from arachidonic acid. A member of the animal-type heme peroxidase family, it is also known as prostaglandin G/H synthase. The specific reaction catalyzed is the conversion from arachidonic acid to Prostaglandin H2, via a short-living Prostaglandin G2 intermediate ...
Non-steroidal anti-inflammatory drugs (NSAIDs), which include over-the-counter pharmaceuticals such as ibuprofen, naproxen, and aspirin, rank among the most widely used pharmaceuticals worldwide. Their chief mechanism of action is inhibition of two forms of cyclo-oxygenase (COX), namely COX-1 and COX-2 (1). Also known as prostaglandin-endoperoxide synthase (PTGS), COX is responsible for the production of downstream mediators of pain and inflammation, such as thromboxane and prostaglandins. Due to their suppression of prostaglandins, which exert protective roles in the gastrointestinal tract, one of the most frequent adverse effects of NSAIDs is irritation of the gastric mucosa.. Thus, newer generation selective COX-2 drugs, known as the coxibs, were introduced in the 1990s to mitigate the risk of peptic ulceration that results from COX-1 suppression. By 2004, coxibs had dominated the prescription drug market for NSAIDs, with worldwide sales of approximately $10 billion (2). Their development was ...
Ibuprofen is a well-established non-steroidal anti-inflammatory drug, inhibiting the prostaglandin-endoperoxide synthase. One of the key features defining the ibuprofen structure is the doubly intermolecular O-H⋯O [[double bond, length as m-dash]] C hydrogen bond in cyclic dimers as know from carboxylic acids a...
Cyclooxygenase (COX) is a bifunctional enzyme exhibiting coupled peroxidase and dioxygenase activities.1,2 Human COX-1 and COX-2 are two structurally homologous hemoproteins responsible for the biosynthesis of prostaglandin H2 from arachidonic acid (AA).1-3 They have been found to play great roles in certain diseases, including cancer,4 and nervous system5 and apoptosis-related diseases.6 COX-1 is constitutively expressed in a variety of cells,7 whereas COX-2 is induced by various inflammatory and proliferative stimuli. COX enzymes are important drug targets for the non-steroidal anti-inflammatory drugs. Over the past decades, COX-2 inhibitors have widely been used as anti-inflammatory medicine, although they usually elicit potential cardiotoxic side effects. Hence, many efforts have been made in recent years to eliminate or reduce such kinds of adverse effects.6,8,9 Crystal structure studies10,11 reveal that COX-2 has a larger substrate binding pocket than COX-1 (Fig. S1†), providing the ...
Coincident with the FDA approval of refecoxib and celecoxib, FitzGerald et al reported that these drugs suppress the formation of prostacyclin (PGI2), leaving the production of thromboxane A2 (TXA2) unaltered.30 PGI2 is a key COX product in the endothelium that inhibits platelet aggregation, causes vasodilatation, and prevents proliferation of vascular smooth muscle cells.31 Evidence was also provided that PGI2 production in vivo was COX-2 dependent, possibly through COX-2 induction in endothelial cells by shear stress.31 In contrast to PGI2, the COX-1-derived prostanoid TXA2, causes platelet aggregation, vasoconstriction, and vascular proliferation.31 FitzGerald et al speculated that suppression of COX-2-dependent formation of PGI2 by the COX-2 inhibitors left TXA2 generation unopposed, promoting vasoconstriction, thrombosis, and atherogenesis.32 A number of publications began to surface suggesting that the COX-2 inhibitors might be associated with an increased risk of cardiovascular events. ...
The role of NSAIDs in the prevention of colorectal cancer is mediated through various mechanisms including the inhibition of COX-2 and the induction of apoptosis through COX-2 independent pathways (26). Previous studies from our laboratory suggested that ASA partially suppresses the MSI-H phenotype of human colon cancer cell lines through an apoptotic mechanism that appeared to be COX independent (22). In vitro ASA has been shown to arrest colon cancer cells at the G1/S checkpoint and induce apoptosis through activation of ATM, p21, and BAX (27). Among NSAIDS, ASA is still a preferred choice for chemoprevention in average-risk individuals. This is not only because of its shown chemopreventive efficacy but also because of its unique potential in cardiovascular protection (3, 4).. In this study, we investigated the chemopreventive potential of ASA and NO-ASA using a newly developed mouse model of LS/HNPCC. LS/HNPCC mice treated with ASA at 400 mg/kg had an increased median survival time compared ...
Cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) synthesis exacerbates occlusive and aneurysmal vascular disease by inducing macrophage proteinase and...
Sevigny M.B., Li C.F., Alas M., Hughes-Fulford M.. Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). COX-2 exists as 72 and 74kDa glycoforms, the latter resulting from an additional oligosaccharide chain at residue Asn(580). In this study, Asn(580) was mutated to determine the biological significance of this variable glycosylation. COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 protein and have five times greater COX-2 activity than cells expressing both glycoforms. Thus, COX-2 turnover appears to depend upon glycosylation of the 72kDa glycoform.. FEBS Lett. 580:6533-6536(2006) [PubMed] [Europe PMC] ...
It is generally accepted that ovarian cancer is associated with local elevation of gonadotropins (FSH and LH), with repeated ovulation and accompanying expression of inducible cyclooxygenase 2 (COX2)....
We investigated the mechanisms by which inhibitors of prostaglandin G/H synthase-2 (PGHS-2; known colloquially as COX-2) increase… Expand ...
Boster Bio Anti-COX2/Cyclooxygenase 2/PTGS2 Antibody Picoband™ catalog # A00084. Tested in WB applications. This antibody reacts with Human, Mouse, Rat. Supplied as 100μg/vial in Lyophilized form antibody.
Rabbit recombinant monoclonal COX2 / Cyclooxygenase 2 antibody [EPR18376-119] validated for WB, IP, Flow Cyt, ICC/IF and tested in Mouse. Immunogen…
So the problem has to do with the fact that sometimes our understanding of how the body does what it does is incomplete, and when we isolate a chemical or split a natural chemical down to only part of its molecule, it ends up turning off one bad function of the body but unwittingly turning off some beneficial functions, too. For instance, aspirin inhibits cyclooxygenase, the bodys natural chemical that normally mediates the synthesis of natural chemicals that enable platelets to activate and stick together and form a clot when blood vessel damage occurs so you dont bleed out... some people are inappropriately prone to clotting and need to tone that natural process down a bit, so they take aspirin. Well, unfortunately cyclooxygenase also mediates processes that cause your stomach to protect its lining against its own acid... so inhibiting cyclooxygenase will stop platelets of clot-prone people from clotting inappropriately, but at the same time it has the potential to also cause you to get a ...
Interleukin-1 (IL-1) induces hypophagia, which can be reduced by cyclooxygenase (COX) inhibitors. Earlier studies with COX knockout (COXko) mice suggested that COX2 was more important for hypophagia than COX1. However, behavioral responses occur long before COX2 is induced. Hypophagia was assessed in mice by measuring the intake of sweetened milk in a brief period. The intake was reduced within 30 min after intraperitoneal injection of IL-1β and was depressed for about 2 h. When milk intake was measured 30 to 40 min after IL-1β, COX1ko mice showed an attenuated response, whereas COX2ko mice responded more like wild-type animals. By contrast, 90 to 120 min after IL-1β COX1ko mice responded normally, whereas COX2ko mice showed only small responses. The COX2-selective inhibitor, celecoxib, failed to alter the response to IL-1β 30 min after administration, but low doses antagonized the effects of IL-1β at 90 to 120 min. The COX1-selective inhibitor, SC560, attenuated both the early and late ...
Celecoxibe hampered EMD-induced mitosis and proliferation, which, in association with EMD-increased COX-2 expression, indicates that COX-2 may be involved in the proliferative response of HPLF cells to EMD.
Drug Discovery, Drugs, Inflammation, Pain, Therapeutic, Community, Homo, Inhibition, Mechanics, Cyclooxygenase, Cyclooxygenase-1, Literature, Pathologies
Several studies suggest that cyclooxygenase-2 contributes to the delayed progression of ischemic brain damage. In this study we examined whether the highly selective cyclooxygenase-2 inhibitor DFU reduces neuronal damage when administered several hours after 5 min of transient forebrain ischemia in gerbils. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity and by histopathological evaluation of the extent of CA1 hippocampal pyramidal cell injury 7 days after ischemia. DFU treatment (10 mg/kg, p.o.) significantly reduced hippocampal neuronal damage even if the treatment is delayed until 12 h after ischemia. These results suggest that selective cyclooxygenase-2 inhibitors may be a valuable therapeutic strategy for ischemic brain injury. ...
Cholangiocyte cytokines stimulate inducible nitric oxide synthase (NOS2) to produce nitric oxide (NO), a known DNA mutagen linked to malignant transformation (5, 13). The generation of NO is also important for bile duct development because it induces Notch1 expression (14, 15). The four Notch genes identified in mammals (Notch 1-4) are expressed in a wide variety of cells and play a significant role in cellular differentiation. The activation of Notch by cell-to-cell interaction causes a transcriptional silencing effect that inhibits differentiation in some cells but not in others (16-18). While the Notch pathway is known to be associated with pancreatic carcinogenesis in rats and humans (19), this same pathway may also have a role in cholangiocarcinogenesis via NOS2.. Cyclooxygenase-2 (prostaglandin-endoperoxide synthase 2, PTGS2) is also implicated in the initiation of malignant cholangiocytes (20). PTGS2 is up-regulated in murine and rat models of biliary adenocarcinoma, while the antisense ...
Background Giardia lamblia trophozoites colonize in the upper small intestine resulting in diarrhea and various clinical manifestations, including abdominal pain, anorexia, and signs of malabsorption. A decrease in the level of trace elements might occur because of this absorption deficiency resulting from giardiasis. Experimentally, the excretory secretory product of G. lamblia trophozoites increased the level of reactive oxygen species in mice enterocytes. The levels of bilirubin, uric acid, and albumin are often used as major nonenzymatic oxidative biomarkers. Objective This study was designed to determine the effect of therapy by metronidazole (MTZ) and artemether (ART) on trophozoite and cyst forms in experimentally Giardia spp.-infected hamsters and to reveal the changes in iron (Fe), manganese (Mn), copper (Cu), and chromium (Cr) serum levels pretreatment and post-treatment. Another objective was to evaluate the impact of this therapy on serum levels of bilirubin, uric acid, and albumin ...
We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E2 (PGE2), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A2 enzymes (cPLA2 and sPLA2), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and − 2) in wild type and COX-1-/- mice. We found that brain PGE2 concentration was significantly increased, whereas thromboxane B2 (TXB2) concentration was decreased in COX-1-/- mice. There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-κB pathway, and also an increase in the upstream cPLA2 and sPLA2 enzymes. The mechanism of NF-κB activation in the ...
Thank you for sharing this Cancer Research article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...
Learn more about prostaglandin-e2. We enable science by offering product choice, services, process excellence and our people make it happen.
TY - JOUR. T1 - Increased expression of cyclooxygenase 2 frequently occurs in human lung cancers, specifically in adenocarcinomas.. AU - Kozaki, Kenichi. PY - 1998. Y1 - 1998. M3 - Article. VL - 58. SP - 3761. EP - 3764. JO - Cancer Research. JF - Cancer Research. IS - 17. ER - ...
This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation. Compounds of particular interest are defined by Formula I wherein A, Y, R1, R2, R3, R4 and R5 are as defined in the specification.
COX-1抑制劑篩選K548 | COX活性測定試劑盒 | COX-2抑制劑篩選試劑盒 | 環氧合酶2(COX-2)ELISA試劑盒 | PTGS2 / COX-2(人類)ELISA試劑 COX-1抑制劑篩選試劑盒 | 貨號K548 Cyclooxygenase-1 (COX-1) Inhibitor
Liu, X., Wong, P.T.-H., Lee, T.L. (2006). Cyclooxygenase-1 inhibition shortens the duration of diazepam-induced loss of righting reflex in mice. Anesthesia and Analgesia 102 (1) : 135-140. [email protected] Repository. ...
Ibuprofen has analgesic, anti-inflammatory and antipyretic action due to inhibition of biosynthesis of prostaglandins by inhibiting the enzyme cyclooxygenase.
Eicosanoids exert their cellular action through specific G-protein coupled receptors. Prostanoids are the products of cyclooxygenases action on C-20…
Rabbit Polyclonal Anti-COX-2 Antibody. Validated: WB, Simple Western, IHC, IHC-Fr, IHC-P. Tested Reactivity: Human, Mouse, Rat. 100% Guaranteed.
Reversible COX-1/COX-2 inhibition.. Topical.. No data.. Skin disorders.. Skin conditions, such as contact dermatitis. ... Reversible COX-1/COX-2 inhibition.. PO, IM, IV, rectal.. No data.. Pain.. As per diclofenac. ... Irreversibly inhibits COX-1 and COX-2; hence inhibiting prostaglandin synthesis.. PO, IM, IV, rectal. Bioavailability = 80-100 ... Reversible COX-1/COX-2 inhibitor.. Ophthalmologic.. N/A. Postoperative pain and inflammation.. Corneal ulceration. ...
Inhibitory COX-2[edytuj , edytuj kod]. Jak wspomniano wcześniej, w polipach myszy Lkb+/- i pacjentów z PJS stwierdzono ... 2, s. 1460-9, 1999. PMID: 9891079. *↑ a b c d e f g h i j k l m n Ylikorkala A, Rossi DJ, Korsisaari N, Luukko K, Alitalo K, ... Dane te zachęcają do dalszych badań nad skutecznością wybiórczych inhibitorów COX-2 u pacjentów z PJS, jednak w związku z ... Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome. „J ...
Cox, Caroline; Catherine Butcher (2006). Cox's book of modern saints and martyrs. Continuum. pp. 6-8. ISBN 9780826487889. ... This account has been reprinted in Cox's 2006 book and on Christian blogs, a photo purported to be of Roy exists online. " ... Retrieved 2 April 2011. Workers of Open Doors, a Christian organisation, claim to have interviewed a friend of Roy Pontoh who ... Retrieved 2 April 2011. van Klinken 2007, p. 179 Littik, Semmy. "The Battle of Waai and the Ambon Demo". Sala Foundation Waku ...
"Caitlyn Jenner and Laverne Cox's fierce first meeting". Zap2it. Retrieved July 21, 2015 ... Season 2 premiered on March 6, 2016.[18] Supporting cast[edit]. The show features a range of members from the transgender ... Season 2 (2016)[edit]. No.. overall. No. in. season. Title. Original air date. U.S. viewers. (millions). ... "I Am Cait' Episode 2 Recap: You Know Nothing, Caitlyn Jenner".. *^ Bibel, Sara (August 4, 2015). "Sunday Cable Ratings: 'Rick ...
ISBN 0-9578521-4-2 *^ a b c Azzouni F, Godoy A, Li Y, Mohler J, et al. (2012). "The 5 alpha-reductase isozyme family: a review ... 978-3-11-015793-2. .. *^ Mutschler, Ernst; Gerd Geisslinger; Heyo K. Kroemer; Monika Schäfer-Korting (2001). ... D2 receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, ... Finasteride (brand names Proscar, Propecia) inhibits the function of two of the isoenzymes (types 2 and 3) of 5α-reductase.[6][ ...
302 (2): 497-519. doi:10.1006/jmbi.2000.4075. PMID 10970748.. *. Bretscher LE, Abel RL, Raines RT (Apr 2000). "A ribonuclease A ...
medium (1-2 hrs.)[21] neuromuscular junction[21] *Reverse neuromuscular block (intravenously)[21] ... medium (2-3 hrs.)[21] neuromuscular junction[21] *Treat myasthenia gravis (orally)[21] ... Consumer Reports: 2. Archived (PDF) from the original on 5 September 2012. Retrieved 1 May 2013.. , which claims Alzheimer's ... To increase chances of lucid dreaming (by prolonging REM sleep)[2]. *To treat Alzheimer's disease, the Lewy body dementias and ...
Matveyenko AV, Dry S, Cox HI, et al. (July 2009). "Beneficial endocrine but adverse exocrine effects of sitagliptin in the ... October 2, 2015.. *^ "SatRx LLC Announces First Registration in Russia of SatRx (gosogliptin), an Innovative Drug for Treatment ... The mechanism of DPP-4 inhibitors is to increase incretin levels (GLP-1 and GIP),[2][3][4] which inhibit glucagon release, ... "DPP-4 Inhibitors for Type 2 Diabetes: Drug Safety Communication - May Cause Severe Joint Pain". FDA. 2015-08-28. Retrieved 1 ...
2. ). [. X. ]. [. X. ]. +. K. x. {\displaystyle K_{m1}-(K_{m1}-K_{m2}){\cfrac {\ce {[X]}}{[{\ce {X}}]+K_{x}}}}. Special cases[ ... 2. ). [. I. ]. [. I. ]. +. K. i. {\displaystyle V_{\max 1}-(V_{\max 1}-V_{\max 2}){\cfrac {\ce {[I]}}{[{\ce {I}}]+K_{i}}}}. ... 2. ). [. X. ]. [. X. ]. +. K. x. {\displaystyle V_{\max 1}-(V_{\max 1}-V_{\max 2}){\cfrac {\ce {[X]}}{[{\ce {X}}]+K_{x}}}}. ... 2 (1): 68-77. doi:10.1208/ps020108. PMC 2751003 . PMID 11741224.. *^ Loo JA, DeJohn DE, Du P, Stevenson TI, Ogorzalek Loo RR ( ...
37 (2): 151-159. doi:10.1007/BF01092051.. CS1 maint: Multiple names: authors list (link). ... doi:10.1007/s00535-006-1874-2. PMID 17048046.. CS1 maint: Multiple names: authors list (link). ... When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.[2] ...
Cox, Lisa; Watts, Jonathan (2 February 2019). "Australia's extreme heat is sign of things to come, scientists warn". The ... Cox, Lisa (24 February 2020). "'Unprecedented' globally: more than 20% of Australia's forests burnt in bushfires". The Guardian ... 16 (2). doi:10.5751/ES-04023-160212. ISSN 1708-3087.. *^ a b c Green, Donna; Billy, Jack; Tapim, Alo (1 May 2010). "Indigenous ... Retrieved 2 January 2020.. *^ a b Howden, S.M., and Jones, R.N. (2001) Costs and benefits of CO. 2 increase and climate change ...
Ian Cox; Marie A. Gaudard; Philip J. Ramsey; Mia L. Stephens; Leo Wright (21 December 2009). Visual Six Sigma: Making Data ... Version 2 was twice the size as the original, though it was still delivered on a floppy disk. It required 2 MB of memory and ... 32 (2): 174-175. doi:10.1021/ci00006a600. ISSN 1549-9596. John P. Sall, Northern Illinois University, archived from the ... doi:10.1198/jcgs.2011.204c. Kim, Ki (1992). "JMP, Version 2. Software for Statistical Visualization on the Apple Macintosh". ...
Cox. It features a foreword written by liberal Senator Edward Kennedy (D-MA). The Yarborough Branch of the Austin Public ... 57-71 Cox, Patrick. Ralph Yarborough: The People's Senator. Austin, Texas. University of Texas Press. 2002. Listen to this ... Retrieved 2 August 2012. Abernethy, Francis E.: Big Thicket from the Handbook of Texas Online. Retrieved August 24, 2012. Texas ... Retrieved 2 August 2012. YARBOROUGH, Ralph Webster 1903 - 1996 Obadele-Starks, Ernest M. B. (1994). "Ralph Yarborough of Texas ...
First, COX-1 catalyzes the addition of two free oxygens to form the 1,2-Dioxane bridge and a peroxide functional group to form ... Second, COX-2 reduces the peroxide functional group to a Secondary alcohol, forming Prostaglandin H2. Other peroxidases like ... Hla T, Neilson K (August 1992). "Human cyclooxygenase-2 cDNA". Proceedings of the National Academy of Sciences of the United ... It is synthesized from arachidonic acid in a reaction catalyzed by a cyclooxygenase enzyme. The conversion from Arachidonic ...
Cox, Harold (November 3, 2004). "Pennsylvania House of Representatives - 1973-1974" (PDF). Wilkes University Election ... Cox, Harold. "House Members G". Wilkes University Election Statistics Project. Wilkes University. v t e. ...
Cox, Michael, ed. (2004). The Concise Oxford Chronology of English Literature. Oxford University Press. ISBN 0-19-860634-6. ... p. 2. Trager, James (1979). The People's Chronology. New York: Holt, Rinehart and Winston. Bondanella, Peter; Bondanella, Julia ... August 2 - Girolamo Mercuriale, Italian physician and philologist (died 1606) November 1 - Étienne de La Boétie, French judge, ...
August 2005). "Cyclooxygenase-2-mediated DNA damage". The Journal of Biological Chemistry. 280 (31): 28337-46. doi:10.1074/jbc. ... As an example of the latter, 15-hydroperoxyicosatetraenocic acid, a natural product of cellular cyclooxygenases and ... for example through the activity of the cytochrome P450 system and other oxygenases such as cyclooxygenase. Such mutagens are ... 2-Acetylaminofluorene, originally used as a pesticide but may also be found in cooked meat, may cause cancer of the bladder, ...
ISBN 978-0-19-569651-6. Anthony Cox (2 April 2013). Empire, Industry and Class: The Imperial Nexus of Jute, 1840-1940. ...
Cox, Lisa (4 June 2019). "Adani jobs explained: why there are new questions over Carmichael mine". The Guardian. ISSN 0261-3077 ... Cox, Lisa (4 December 2018). "Court challenge launched over minister's 'flawed' decision on Adani water trigger". the Guardian ... "Abbott Tells Business: Forget Talk, Time to Act on Trade Pact and Adani". Cox, Lisa (7 September 2015). "'Quite simply ... Retrieved 2 August 2014. "Adani's new mini version of its mega mine still faces some big hurdles". 3 December 2018. "Mineral ...
COX-2 modified in activity by aspirin or atorvastatin or, alternatively, a microbial or possibly mammalian cytochrome P450 ... COX-2), and certain Cytochrome P450 monooxygenases. RvDs are poly-hydroxyl metabolites of DHA. To date, six RvDs, which vary in ... aspirin and atorvastatin change the activity of COX2 from a cyclooxygenase to an hydroxyperoxidase-forming enzyme. The ... 7 (2): a016311. doi:10.1101/cshperspect.a016311. PMC 4315926. PMID 25359497. Duvall, M. G.; Levy, B. D. (2015). "DHA- and EPA- ...
Cox, Jamieson (July 2, 2018). "Drake: Scorpion". Pitchfork. Archived from the original on July 2, 2018. Retrieved July 2, 2018 ... Purdom, Clayton (July 2, 2018). "Scorpion is a whole shitload of Drake". The A.V. Club. Retrieved November 22, 2020. Cush, Andy ... Jenkins, Craig (July 2, 2018). "Drake Fails to Grow on Scorpion". Vulture. Retrieved November 21, 2020. Ingham, Tim (June 30, ... 86318-2.CS1 maint: others in cite AV media (notes) (link) "Scorpion / Drake TIDAL". Tidal. Retrieved July 13, 2018. "Australian ...
When pretreated with aspirin, however, COX-1 is inactive while COX-2 attacks arachidonic acid to produce almost exclusively 15( ... 13E-eicosatetraenoic acid synthesis within the cyclooxygenase active site of murine COX-2. Why acetylated COX-1 does not ... Lee, S. H.; Rangiah, K; Williams, M. V.; Wehr, A. Y.; Dubois, R. N.; Blair, I. A. (2007). "Cyclooxygenase-2-mediated metabolism ... Lee, S. H.; Williams, M. V.; Dubois, R. N.; Blair, I. A. (2005). "Cyclooxygenase-2-mediated DNA damage". Journal of Biological ...
Cox, Lorin (December 2, 2018). "WATCH: Kyle Fuller baits Eli Manning for league-leading 6th interception". NBC Sports Chicago. ... Cox, Lorin (October 9, 2017). "Bears CB Marcus Cooper inactive vs. Vikings with back injury". Retrieved ... In week 2 against the Denver Broncos, Fuller made his first interception of the season off a pass from Joe Flacco that was ...
Cox, Susan (March 27, 1979). "Play about singing star Hank Williams excellent". The Lompoc Record (Lompoc, CA). Retrieved ... Retrieved March 2, 2020. Roland, Tom and Hieronymus, Clara (May 3, 1996). "Williams' Light Returns to Ryman in Highway". The ... Retrieved March 2, 2020. Myler, Randal; Harelik, Mark (2004). Hank Williams: Lost Highway : the Music and Legend of Hank ... Retrieved March 2, 2020. "2003 Obie Award Winners". Johnson, Zac. "Hank Williams: Lost Highway Original Cast ...
Cox. Collier, John Payne; Percy Society (1840). "The Reading Skirmish". Early English poetry, ballads, and popular literature ...
Cox, Harold. "House Members K". Wilkes University Election Statistics Project. Wilkes University. "Kenneth Kruszewski" ( ...
Eicher, p. 569; Cox, p. 11. Baumgartner, Richard A. Blue Lightning: Wilder's Mounted Infantry Brigade in the Battle of ... Cox, Steven. Chattanooga Was His Town: The Life of General John T. Wilder, presentation to the Chattanooga Area Historical ... ISBN 978-1-885033-35-2. Terrell, W.H.H. (1866). Report of the Adjutant General of the State of Indiana (Volume III ed.). ... ISBN 978-1-885033-35-2. Cozzens, p. 15; Korn, p. 21. Cozzens, Peter (1992). This Terrible Sound. ISBN 0-252-01703-X. Woodworth ...
Cox Enterprises. April 2, 2014. Retrieved October 11, 2020. Burns, Rebecca (February 3, 2014). "BeltLine's latest art addition ...
Simon Cox of BBC News said the word is "the latest buzzword for teenage drop-outs". He says "Neets are 20 times more likely to ... 8-9. Cox, Simon. "A 'Neet' solution" Archived 2006-03-16 at the Wayback Machine. BBC News. Accessed 24 August 2011. See also: ... Cox, Simon. "A 'Neet' solution" Archived 2006-03-16 at the Wayback Machine. BBC News. Accessed 24 August 2011. Smith, David. " ... 60 (2): 289-309. doi:10.1006/jvbe.2001.1868. S2CID 144116273. Archived from the original on 2021-02-09. Retrieved 2019-12-01. " ...
Cox, Harold. "Senate Members "G"". Wilkes University Election Statistics Project. Wilkes University. Natasha Lindstrom ( ... Cox, Harold (2004). "Pennsylvania Senate - 1967-1968" (PDF). Wilkes University Election Statistics Project. Wilkes University. ... Cultural Contributions of Americans with Roots in Slovakia,; accessed March 2, 2015. ...
Yi, John S.; Cox, Maureen A.; Zajac, Allan J. T-cell exhaustion: characteristics, causes and conversion. Immunology. 2010-04, ... T细胞耗竭的直接原因包括持续的抗原刺激、以及CD4细胞的缺失[42]。长时间的抗原暴露和高病毒负载可以加重T细胞耗竭的程度。2-4周的
Nelson, D. L.; Cox, M. M. (2000) Lehninger, Principles of Biochemistry. 3rd Ed. Worth Publishing: New York. ISBN 1-57259-153-6. ... R2CH(OH) + O → R2C=O + H2O. Typical strong oxidants (source of "O" in the above reaction) include potassium permanganate or a ... The most widely used member of this class of compounds is methyl vinyl ketone, CH3C(O)CH=CH2, which is useful in the Robinson ... The simplest class have the formula (CH2)nCO, where n varies from 2 for cyclopropanone to the teens. Larger derivatives exist. ...
David L. Nelson, Michael M. Cox (2005). Principles of Biochemistry (4th izd.). New York: W. H. Freeman. ISBN 0-7167-4339-6. ... Funkcija 2,3-bisfosfoglicerinske kiseline je otkrivena 1967.[4]. Reference[uredi - уреди , uredi izvor]. *↑ Li Q, Cheng T, Wang ... 2. 2. Fosfoglicerat kinaza. 3-Fosfoglicerat. Fosfoglicerat mutaza. 2-Fosfoglicerat. Fosfopiruvat hidrataza(Enolaza). ... 2,3-Bisfosfoglicerinska kiselina (2,3-Bisfosfoglicerat, 2,3-BPG, 2,3-difosfoglicerat, 2,3-DPG) je trougljenični izomer ...
Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6. ... 150-30-1 (DL) , 63-91-2 (L). Fenüülalaniin (lühend Phe või F)[2] on organismi- ja toiduvalkudes sisalduv aromaatne α-aminohape ... NH2)COOH. Fenüülalaniin kuulub asendamatute aminohapete hulka. Molekuli peetakse mittepolaarseks, sest selle kõrvalahelas on ...
Midshipman Phil Cox Vannais, and[16]. *Midshipman Frederick R. Zito.[16]. Post-graduation service obligations[edit]. ... 2 members of the House of Representatives appointed by the Speaker of the House of Representatives, at least 1 of whom shall be ... 5 individuals appointed by the President, at least 2 of which shall be graduates of the academy, at least 1 shall be a senior ... 2 Senators appointed by the Chairman of the Senate Committee on Commerce, Science, and Transportation; ...
Cox, C. Barry & Moore, Peter D. (1993): Biogeography. An ecological and evolutionary approach (5th ed.). Blackwell Scientific ... 24 (2): 453-463. doi:10.1671/2401.. [permanent dead link]. *^ a b Olivier Lambert; Giovanni Bianucci; Klaas Post; Christian de ... The Miocene ( /ˈmaɪəˌsiːn/[2][3]) is the first geological epoch of the Neogene Period and extends from about 23.03 to 5.333 ... doi:10.1666/0022-3360(2005)079[1120:csaasg];2.. *^ a b Guillame, Benjamin; Martinod, Joseph; Husson, Laurent; Roddaz, ...
Cox, A.J. (2002). "An experiment to measure Mie and Rayleigh total scattering cross sections". American Journal of Physics. 70 ... 2. ⁡. θ. 2. R. 2. (. 2. π. λ. ). 4. (. n. 2. −. 1. n. 2. +. 2. ). 2. (. d. 2. ). 6. {\displaystyle I=I_{0}{\frac {1+\cos ^{2}\ ... 2. π. 5. 3. d. 6. λ. 4. (. n. 2. −. 1. n. 2. +. 2. ). 2. {\displaystyle \sigma _{\text{s}}={\frac {2\pi ^{5}}{3}}{\frac {d^{6 ... 2. V. 2. σ. ϵ. 2. 2. λ. 4. R. 2. (. 1. +. cos. 2. ⁡. θ. ). {\displaystyle I=I_{0}{\frac {\pi ^{2}V^{2}\sigma _{\epsilon }^{2}}{ ...
Simpson NB, Cunliffe WJ (2004). "Disorders of the sebaceous glands". In Burns, Tony, Breathnach, Stephen, Cox, Neil, Griffiths ... 12 (2): e30-5. PMID 23377402.. *^ a b Danby FW (27 January 2015). Acne: Causes and Practical Management. John Wiley & Sons. pp ... 50 (Pt 2): 95-107. doi:10.1258/acb.2012.012159. PMID 23431485.. *^ a b c Katsambas AD, Dessinioti C (2010). "Hormonal therapy ... p. 2. ISBN 978-0071440196. .. *^ Hoeger PH, Irvine AD, Yan AC (2011). "Chapter 79: Acne". Harper's Textbook of Pediatric ...
Orange Is the New Black, season 3 (2015): Aduba, Birbiglia, Blake, Brooks, Cox, Cruz, Curtin, DeLaria, Fowler, Glenn, Golden, ... Cox, Cruz, Curtin, DeLaria, Fowler, Freeman, Gardner, Glenn, Golden, Guerrero, Harney, Jeudy, Lake, Lapkus, Leyva, Lyonne, ... Modern Family, season 1/season 2 (2010): Bowen, Burrell, Ferguson, Gould, Hyland, O'Neill, Rodriguez, Stonestreet, Vergara, ... Modern Family, season 2/season 3 (2011): Anderson-Emmons, Bowen, Burrell, Ferguson, Gould, Hyland, O'Neill, Rodriguez, ...
March 2004). "The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans". Pain. 108 ... 98 (2): 246-54. doi:10.1093/bja/ael344. PMID 17251214.. *^ Warncke T, Stubhaug A, Jørum E (August 1997). "Ketamine, an NMDA ...
Laverne Cox. *Lee Ae-ran. *Leopold I of Belgium. *Lil Pump. *List of active volcanoes ...
2 million[1]. White Hunter Black Heart is a 1990 American adventure drama film directed by and starring Clint Eastwood and ... The film was shot on location in Kariba, Zimbabwe and surrounds including at Lake Kariba, Victoria Falls and Hwange,[2] over ... White Hunter Black Heart's gross theatrical earnings reached just over $2 million, well below the film's $24 million budget.[1] ... The boat used in the film was constructed in England of glass fibre and shipped to Africa for filming.[2] It was electrically ...
Been JV, Nurmatov UB, Cox B, Nawrot TS, van Schayck CP, Sheikh A (May 2014). "Effect of smoke-free legislation on perinatal and ... 2: CD005992. doi:10.1002/14651858.CD005992.pub3. PMC 6486282. PMID 26842828.. *^ Shetty KD, DeLeire T, White C, Bhattacharya J ... 2 March 2007. Retrieved 4 January 2010.. *^ "Better regulation, Better Benefits: Getting the Balance Right. Case Studies" (PDF) ... 5 (2): 240-268.. *^ "Press Advisory - Statement of Councilmember Carol Schwartz at the 14 June 2005 Smoke-Free Hearing". 14 ...
Cox/flexion-distraction (a gentle, low-force adjusting procedure which mixes chiropractic with osteopathic principles and ... 14 (2): E14-18.. *^ a b c d e f g h i j k World Health Organization (2005). "WHO guidelines on basic training and safety in ... 11 (2): 77-94. doi:10.1177/1533210106292467.. *^ a b Parkman CA (2004). "Issues in credentialing CAM providers". Case Manager. ... 8 (2): e498. doi:10.7759/cureus.498. PMC 4794386 . PMID 27014532.. *^ Chung CL, Côté P, Stern P, L'espérance G (2014). "The ...
Tom A. Williams, Peter G. Foster, Tom M. W. Nye, Cymon J. Cox, T. Martin Embley. A congruent phylogenomic signal places ... 2,8-2,7 mld lat[7]. Podział systematyczny[edytuj , edytuj kod]. Podział naturalny jądrowców przysparza wiele problemów z powodu ... Szacunki dotyczące liczby gatunków w obrębie tej grupy wahają się pomiędzy 5 a 10 mln[1][2]. Według analiz przeprowadzonych ...
1920 (San Francisco): Cox/Roosevelt. *1924 (New York): J. Davis/C. Bryan ... Class 2). 1918, 1924, 1930, 1936 Succeeded by. Carl Edward Bailey Preceded by. Ollie M. James Permanent Chair of the Democratic ... U.S. Senator (Class 2) from Arkansas. 1913-1937 Served alongside: James Paul Clarke, William F. Kirby, Thaddeus H. Caraway, ... Arkansas U.S. Senatorial Election (Class 2) Results 1918 - 1936 Year. Democratic. PCT. Challenger. Party. Pct ...
Cox, Lisa (12 March 2019). "'Almost certain extinction': 1,200 species under severe threat across world". ... 978-2-914-935289. .. *^ a b c d e Pimm, S. L.; Jenkins, C. N.; Abell, R.; Brooks, T. M.; Gittleman, J. L.; Joppa, L. N.; Raven ... Retrieved 2 April 2016.. *^ a b Ruddiman, W.F. (2013). "The Anthropocene". Annual Review of Earth and Planetary Sciences. 41: ... 29 (2): 452-462. doi:10.1111/cobi.12380. PMID 25159086.. *^ Lawton, J. H.; May, R. M. (1995). "Extinction Rates". Journal of ...
Coordinates: 51°18′42″N 2°44′30″W / 51.31156°N 2.74170°W / 51.31156; -2.74170 ... 2] As a result of the Variscan mountain-building, the Mendip area now comprises at least four anticlinal fold structures, with ...
... haplotype (Also: AH8.1, COX,[1] Super B8, ancestral MHC 8.1[2] or 8.1 ancestral haplotype[3]) is a multigene ... 19 (2): 129-32. doi:10.1002/art.1780190201. PMID 1259797.. *^ Parks CG, Pandey JP, Dooley MA, et al. (June 2004). "Genetic ... 56 (2): 130-3. doi:10.1590/S0043-31442007000200005. PMID 17910142.. *^ Hirsch TJ, Enlow RW, Bias WB, Arnett FC (October 1981). ... 21 (2): 202-15. PMC 1538268. PMID 1081023.. *^ Pirskanen R (January 1976). "Genetic associations between myasthenia gravis and ...
Boris, A.; Scott, J. W.; DeMartino, L.; Cox, D. C. (1973). "ENDOCRINE PROFILE OF A NONSTEROIDAL ANTIANDROGEN N-(3,5-DIMETHYL-4- ... 90-. ISBN 978-1-4557-2758-2.. *^ a b c d e f g h i William Figg; Cindy H. Chau; Eric J. Small (14 September 2010). Drug ... 7 (2): 211-47. doi:10.2174/0929867003375371. PMID 10637363.. *^ a b c d Shen, Howard C.; Taplin, Mary-Ellen; Balk, Steven P. ( ... 165-. ISBN 978-1-4831-8711-2.. *^ a b c Ralph M. Trüeb; Won-Soo Lee (13 February 2014). Male Alopecia: Guide to Successful ...
a b Cox, T., & Tisserand, M. (2006). Editorial: Work & Stress comes of age: Twenty years of occupational health psychology. ... What is occupational health psychology [2] *^ a b Tetrick, L.E., & Quick, J.C. (2011). Overview of occupational health ... a b Schmitt, L. (2008). OHP interventions: Wellness programs (Part 2). Newsletter of the Society for Occupational Health ... Administrative Science Quarterly, 24(2), 285-307. *^ de Lange, A.H., Taris, T.W., Kompier, M.A., Houtman, I.L., & Bongers, P.M ...
Kosman, D.; Mizutani, C. M.; Lemons, D; Cox, W. G.; McGinnis, W; Bier, E (2004). "Multiplex Detection of RNA Expression in ... "Defining the sister rat mammary tumor cell lines HH-16 cl.2/1 and as an in vitro cell model for Erbb2". PLOS ONE. 7 ... Paraspeckles visualized by single-molecule FISH against NEAT1 (Quasar 570) in U-2 OS cells (DAPI). ... 2] FISH can also be used to detect and localize specific RNA targets (mRNA, lncRNA and miRNA) in cells, circulating tumor cells ...
Cyclooxygenase 2 inhibitors. *Dipeptidyl peptidase-4 inhibitors. *Direct thrombin inhibitors. *Direct Xa inhibitors ... 19 (2): 578-88. PMID 9880578.. *^ a b Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (May 1986). "Steroid hormone ... 300 (1): 2-8. doi:10.1124/jpet.300.1.2. PMID 11752090.. *^ Perrais D, Ropert N (Jan 1999). "Effect of zolpidem on miniature ... Fig 2. Schematic diagram of a GABAA receptor protein ((α1)2(β2)2(γ2)) which illustrates the five combined subunits that form ...
Cox, G. (2003). "Adverse effects of khat: a review". Advances in Psychiatric Treatment. 9 (6): 456-63. doi:10.1192/apt.9.6.456. ... Retrieved 2 April 2010.. *^ Powell, Betsy (20 April 2012). "Woman who brought khat to Canada wins appeal". The Star. Archived ... Retrieved 2 April 2010.. *^ "Qat niet verboden" (in Dutch). Archived from the original on 19 July 2011. Retrieved 2 ... The khat plant is known by a variety of names, such as qat and gat in Yemen, qaat and jaad in Somalia, and chat in Ethiopia.[2] ...
These include the works of Atisa and Tilopa.[2] Medieval Hindu philosophy featured the works of Chaitanya. ... In 1932-33 it was renamed as Bengal Technological Institute with the introduction of 3 years diploma course and a 2 year ...
61 (2): 189-206. doi:10.1353/csd.2020.0017.. *^ a b c d e Julie Kliegman (26 July 2018). "When You're An Asexual Assault ... Retrieved 2 December 2018.. *^ Morgan Lev Edward Holleb (2019). The A-Z of Gender and Sexuality: From Ace to Ze. Jessica ... Discrimination against asexual people, also known as acephobia[1][2][3] or aphobia,[4][5][6] encompasses a range of negative ... Retrieved 2 December 2018.. *^ "Anything but lacking". The McGill Daily. 21 November 2017. ...
Cox, Brian, 1968- (2009). Why does E=mc2 : (and why should we care?). Forshaw, J. R. (Jeffrey Robert), 1968-. Cambridge, MA: Da ...
Kenny Ray Cox. *William E. DePuy (1946). *Jacob L. Devers (1925). *Roger H.C. Donlon (1971) ... 2] In 1907 it changed its title to the School of the Line. The curriculum expanded throughout World War I, World War II, the ...
2. [. ES. ]. =. k. 2. K. i. [. S. ]. [. E. ]. 0. K. m. K. i. +. K. i. [. S. ]. +. K. m. [. I. ]. {\displaystyle V_{0}=k_{2}[{\ ... 2. [. E. ]. 0. [. S. ]. K. m. +. [. S. ]. +. K. m. [. I. ]. K. i. {\displaystyle V_{0}={\frac {k_{2}[{\ce {E}}]_{0}[{\ce {S ... 2. [. ES. ]. −. k. 3. [. E. ]. [. I. ]. +. k. −. 3. [. EI. ]. {\displaystyle {\frac {d[{\ce {E}}]}{dt}}=0=-k_{1}[{\ce {E}}][{\ ... 2. ). [. ES. ]. {\displaystyle k_{1}[{\ce {E}}][{\ce {S}}]=(k_{-1}+k_{2})[{\ce {ES}}]\,\!}. Dividing by k. 1. [. S. ]. {\ ...
Cox & Cox furnishings, is north of Frome in Berkley, Somerset off the A361. Fox Brothers make cloth in Wellington, and Relyon ( ... Actavis UK (former Cox Pharmaceuticals, part of Hoechst AG), off the A361 east of Barnstaple, make levothyroxine and other ... Retrieved 2 January 2016.. *^ "South West Region" (PDF). Regional profiles of higher education 2007. HEFCE. Archived (PDF) from ... Retrieved 2 December 2007.. *^ "Britannia in the Ravenna Cosmography". cyberhome of Keith Fitzpatrick-Matthews. Archived from ...
Coxs Bazar-2 is a constituency represented in the Jatiya Sangsad (National Parliament) of Bangladesh since 2014 by Asheq Ullah ... "Coxs Bazar-2". The Daily Star. Retrieved 31 December 2018. "Constituency Maps of Bangladesh" (PDF). Bangladesh Election ... Chittagong and Coxs Bazar. Asheq Ullah Rafiq was elected unopposed in the 2014 general election after opposition parties ...
... cyclooxygenase. Prostaglandins whose synthesis involves the cyclooxygenase-I enzyme, or COX-1, are responsible for maintenance ... Non-steroidal anti-inflammatory drugs (NSAIDs) are the competitive inhibitors of cyclooxygenase (COX), the enzyme which ... 170-fold more potent in inhibiting COX-1 than COX-2. Studies of meloxicam 7.5 mg per day for 23 days find a level of gastric ... Some COX-2 inhibitors are used in a single dose to treat pain after surgery. Etoricoxib appears as good as, if not better than ...
Prostaglandins whose synthesis involves the cyclooxygenase-I enzyme, or COX-1, are responsible for maintenance and protection ... 170-fold more potent in inhibiting COX-1 than COX-2.[32] Studies of meloxicam 7.5 mg per day for 23 days find a level of ... "COX-2 Inhibitors and Cancer". Fact Sheet. United States National Cancer Institute. Archived from the original on May 9, 2008.. ... COX-2 up-regulation has also been linked to the phosphorylation and activation of the E3 ubiquitin ligase HDM2, a protein that ...
... Laurel J. Mengle-Gaw and Benjamin D. Schwartz ... Laurel J. Mengle-Gaw and Benjamin D. Schwartz, "Cyclooxygenase-2 inhibitors: promise or peril?," Mediators of Inflammation, vol ...
A list of US medications equivalent to Cox-2 is available on the website. ... Cox-2 is a medicine available in a number of countries worldwide. ... Cox-2 may be available in the countries listed below.. Ingredient matches for Cox-2. Celecoxib. Celecoxib is reported as an ...
a) COX isozyme expression in epidermis from wt mice and the transgenic lines K5.COX-2/19+/− (19) and K5.COX-2/667+/− (667). (b ... Although COX-1 expression does not change in the course of tumor development, aberrant expression of COX-2 is also a consistent ... In contrast to the constitutively and ubiquitously expressed COX-1, COX-2 is not expressed in most tissues but becomes ... Nonsteroidal antiinflammatory drugs (NSAIDs) prevent prostaglandin (PG) biosynthesis through inhibition of cyclooxygenase (COX ...
However, the chief investigator is stressing that the study is not a reason for people to stop taking COX-2 inhibitors and that ... A new study in mice could help shed light on why COX-2 inhibitors might increase the risk of thrombotic events. ... COX-1, the form of cyclooxygenase found in platelets, makes TxA2, which causes blood vessels to constrict and platelets ... COX-2, by contrast, is expressed in blood vessels and is a major source of PGI2, which dilates blood vessels and prevents the ...
Mark Einstein, a Bronx, N.Y., specialist in gynecological cancer, said the Cox-2 drugs show promise for potential treatment of ... The agencys scientific experts said the Cox-2 medicines, used to alleviate the symptoms of rheumatoid arthritis, carry "an ... the European Medicines Agency issued a new warning that people who have had heart disease or a stroke should not take any Cox-2 ... that the military carries Cox-2 drugs into battle. They are needed, he said, because of concerns about excess bleeding that can ...
Cox 2 Inhibitor News and Research. RSS Cox-2 Inhibitors are nonsteroidal anti-inflammatory drugs used to relieve pain and ... The cyclooxygenase-2 enzyme is just such a protein, as the concentration of COX-2 is greater in cancer cells than in adjacent ... COX-2 inhibitor extends sunitinib activity in renal cell carcinoma The effectiveness of sunitinib for the treatment of renal ... COX-2 inhibitors are being studied in the prevention of colon polyps, and as anticancer drugs. Also called cyclo-oxygenase-2 ...
... Sevigny M.B., Li C.F., Alas M., Hughes-Fulford M. ... COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 ... Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid ... Thus, COX-2 turnover appears to depend upon glycosylation of the 72kDa glycoform. ...
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
Role of cyclooxygenase 2 in acute spinal cord injury.. Resnick DK1, Graham SH, Dixon CE, Marion DW. ... COX-2 was expressed in the normal adult rat spinal cord. COX-2 mRNA and protein production were increased following injury with ... Cyclooxygenase, or prostaglandin G/H synthase, is the rate-limiting step in the production of prostaglandins. A new isoform, ... Selective inhibition of COX-2 activity with SC58125 resulted in improved mean Basso, Beattie, and Bresnahan scores in animals ...
COX-2 expression in pseudomyxoma peritonei.. Gatalica Z1, Loggie B.. Author information. 1. Department of Pathology, Creighton ... COX-2 expression was studied using an immunohistochemical method in 75 patients with pseudomyxoma peritonei (PMP). Twenty-five ... In addition, COX-2 was detected in stromal, endothelial, inflammatory cells and reactive mesothelium. This preliminary ... COX-2 was expressed in neoplastic mucinous epithelium of 30 cases (40%): 20 in PMCA (40%), 10 in DPAM (40%). Weak COX-2 ...
Another COX-2 inhibitor has been shot down by the FDA. Having spent the last two months reviewing the safety of the COX-2- ... THE COX-2s: Oh well, back to the drawing board. What Doctors Dont Tell You ... COX-2 AGAIN: Sorry, we havent finished with you yet. What Doctors Dont Tell You ... COX-2 drugs:A Pandoras box of adverse effects. What Doctors Dont Tell You ...
Two isoforms for COX have been described, COX-1 and COX-2. We and others have shown that COX-2 levels are markedly increased in ... Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans ... Two COX isoforms have been characterized, COX-1 and COX-2. COX-1 is expressed in normal intestine, but its levels do not change ... COX,. cyclooxygenase;. NSAID,. nonsteroidal antiinflammatory drug;. MMP-2,. metalloproteinase-2;. MT MMP,. membrane-type ...
Here, the potential utility of selective COX-2 inhibitors in the prevention and treatment of cancer is considered. The ... mechanisms by which COX-2 levels increase in cancers, key data that indi … ... COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers. ... Cyclooxygenase 2: a molecular target for cancer prevention and treatment Trends Pharmacol Sci. 2003 Feb;24(2):96-102. doi: ...
Buy Castigata Dal Boss 2 by Samantha Cox (eBook) online at Lulu. Visit the Lulu Marketplace for product details, ratings, and ... ... 2) and (3) of the DMCA. Should a properly filed counter notification be filed, you will be notified and have 10 business days ...
Two large pivotal trials have been published, in which the efficacy and safety of the COX 2 inhibitors celecoxib and rofecoxib ... Efficacy and safety of COX 2 inhibitors New data are encouraging but the risk:benefit ratio remains unclear ... with more specific inhibitory effects on cyclo-oxygenase 2 (COX 2) pathways, promised equivalent efficacy with greater safety ... Efficacy and safety of COX 2 inhibitors. BMJ 2002; 325 doi: (Published 21 September ...
Cox Communications, the third-largest cable operator in the U.S., will eliminate about 460 positions, representing 2% of its ... Cox To Cut 2% Of Workforce Author:. By Todd Spangler. Updated:. Mar 29, 2018. Original:. Nov 4, 2008. ... Coxs wireless group will not be affected by the cutbacks, according to spokesman Todd Smith. Last week the Atlanta-based MSO ... Privately held Cox had gross revenue of $8.3 billion in 2007. The MSO has 6.2 million residential and commercial customers. ...
Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. COX-inhibitors ... In this study, we investigated the prognostic impact of expression of both COX-isoforms as well as the association of COX ... Diese wurden mittels immunhistochemischer Methoden auf beide COX-Isoenzyme untersucht. Eine erhöhte COX-2 Expression wurde in ... The expression of COX-1 and -2 was determined by immunohistochemistry retrospectivly in a cohort of 221 women. An elevated ...
These data demonstrate that COX-2 contributes to prostate cancer progression and suggest that it mediates this effect, in part ... Background: Cyclooxygenase (COX) -2, an inducible isoform of COX, has been observed to be expressed in prostate cancer. Several ... Cyclooxygenase-2 promotes prostate cancer progression Prostate. 2002 Nov 1;53(3):232-40. doi: 10.1002/pros.10152. ... Overexpression of COX-2 increased both proliferation in vitro and tumor growth rate in vivo. However, the pro-tumor effect was ...
... compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation. Compounds ... a. Preparation of recombinant COX baculoviruses. Recombinant COX-1 and COX-2 were prepared as described by Gierse et al, [J. ... Evaluation of COX-1 and COX-2 activity in vitro. The compounds of this invention exhibited inhibition in vitro of COX-2. The ... b. Assay for COX-1 and COX-2 and COX-2 activity ... to generate the baculovirus transfer vectors for COX-1 and COX- ...
COX-2) protein and the prognosis of pancreatic cancer. The following electronic... ... We conducted a meta-analysis of relevant cohort studies to investigate the relationships between cyclooxygenase-2 ( ... Cyclooxygenase in normal human tissues-is COX-1 really a constitutive isoform, and COX-2 an inducible isoform? J Cell Mol Med. ... shRNA-targeted cyclooxygenase (COX)-2 inhibits proliferation, reduces invasion and enhances chemosensitivity in laryngeal ...
COX 2 inhibitors, traditional NSAIDs, and the heart BMJ 2005; 330 :1342 doi:10.1136/bmj.330.7504.1342 ... COX 2 inhibitors, traditional NSAIDs, and the heart. BMJ 2005; 330 doi: (Published 09 ...
Cox-2 inhibitor definition at, a free online dictionary with pronunciation, synonyms and translation. Look it up ... cox-2 inhibitor in Medicine Expand. COX-2 inhibitor n. Any of a class of nonsteroidal anti-inflammatory drugs thought to have ...
COX-2 inhibitors are associated with increased risk of heart attack, heart failure and death from stroke. ... COX-2 inhibitors linked to increased risk of stroke death. Written by David McNamee on November 6, 2014 ... Last year, Medical News Today also reported on a study that suggested a possible "fix" for the side effects associated with COX ... The study shows that people who were current users of COX-2 inhibitors were 19% more likely to die after a stroke than people ...
Cyclooxygenase 2 antibody. Validated in WB, ICC/IF and tested in Mouse, Rat, Human. Cited in 63 publication(s). Independently ... Primary - Rabbit Anti-COX2 / Cyclooxygenase 2 antibody (ab52237) WB, ICC/IF Protein - Recombinant human COX2 / Cyclooxygenase 2 ... Anti-COX2 / Cyclooxygenase 2 antibody (ab52237) (Human mesothelioma whole cell lysate.). Secondary. Goat anti-rabbit HRP. ... Anti-COX2 / Cyclooxygenase 2 antibody (ab52237) at 1/1000 dilution + Human primary myometrial cells whole cell lysate at 20 µg ...
Cyclooxygenase 2 protein. Ab81696 is a full length protein produced in Nativesyntheticaly and has been validated in WB. Abcam… ... References for Natural Sheep COX2 / Cyclooxygenase 2 protein (ab81696). ab81696 has not yet been referenced specifically in any ... Natural Sheep COX2 / Cyclooxygenase 2 protein. See all COX2 / Cyclooxygenase 2 proteins and peptides. ...
COX-2 gene promoter haplotypes and prostate cancer risk.. Panguluri RC1, Long LO, Chen W, Wang S, Coulibaly A, Ukoli F, Jackson ... Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflammatory prostaglandins. COX ... Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and ... However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we ...
Two related isoforms of the cyclo-oxygenase (COX) enzyme have been described: COX-1 (PGHS-1) and COX-2 (PGHS-2). COX-1 is ... COX-2 inhibitors and gastroduodenal toxicity: Major clinical trials. Author. Mark Feldman, MD, MACP, AGAF, FACG. Mark Feldman, ... COX-2 inhibitors. Lancet 1999; 353:307.. *Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal ... Other COX-2 inhibitors are available in some countries. Parecoxib is a prodrug that is converted to valdecoxib. Etoricoxib and ...
  • Selective COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2 , an enzyme responsible for inflammation and pain . (
  • After several COX-2 inhibiting drugs were approved for marketing, data from clinical trials revealed that COX-2 inhibitors caused a significant increase in heart attacks and strokes, with some drugs in the class having worse risks than others. (
  • Many COX-2-specific inhibitors have been removed from the U.S. market. (
  • COX-2 inhibitors appear to work as well as nonselective NSAIDS. (
  • COX inhibitors have been shown to reduce the occurrence of cancers and pre-cancerous growths. (
  • [8] COX-2 inhibitors are currently being studied in breast cancer [9] and appear to be beneficial. (
  • COX-2 inhibitors have been found to be effective in suppressing inflammatory neurodegenerative pathways in mental illness, with beneficial results in trials for major depressive disorder as well as schizophrenia . (
  • Cyclooxygenase-2 inhibitors: promise or peril? (
  • Laurel J. Mengle-Gaw and Benjamin D. Schwartz, "Cyclooxygenase-2 inhibitors: promise or peril? (
  • Furthermore, newly developed COX-2-selective inhibitors strongly suppressed the development of epithelial cancers in animals ( 5-7 ) and significantly reduced the number of colorectal polyps in patients suffering from familial adenomatous polyposis coli ( 8 ). (
  • COX-2-selective inhibitors exhibited chemopreventive activity against chemically ( 6 ) and UV light-induced ( 11 , 12 ) skin carcinogenesis in mice. (
  • COX-2 inhibitors can prevent the hypoxic upregulation of a potent angiogenic factor, vascular endothelial growth factor. (
  • These results indicate that COX-2 inhibitors may, therefore, serve as effective chemopreventive and therapeutic agents in cancer of the prostate. (
  • Philadelphia, PA - A new study in mice could help shed light on why COX-2 inhibitors might increase the risk of thrombotic events. (
  • However, he stressed to heart wire , "a mouse study is not reason enough for people to stop taking COX-2 inhibitors," and that much more clinical work would be required to determine whether the murine data can be extrapolated into humans. (
  • A mouse study is not reason enough for people to stop taking COX-2 inhibitors. (
  • Concerns about the potential prothrombotic effects of COX-2 inhibitors first arose with rofecoxib (Vioxx® - Merck) in the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial, when the rate of MIs in patients taking rofecoxib was higher than in those taking the comparator NSAID naproxen . (
  • The move came as a new crop of COX-2 inhibitors hit the market, amidst growing concerns that any risk of thrombotic events may be a class effect. (
  • In an attempt to mimic in vivo in mice what happens when COX-2 inhibitors are administered to humans, Fitzgerald and his colleagues inflicted injury on the carotid artery with a catheter in animals bred to lack receptors for PGI 2 . (
  • Dr. Christopher Grubb told a joint meeting of Food and Drug Administration advisory committees studying the risks of a group of drugs known as Cox-2 inhibitors " including Vioxx, Celebrex and Bextra " that the military carries Cox-2 drugs into battle. (
  • Cox-2 Inhibitors are nonsteroidal anti-inflammatory drugs used to relieve pain and inflammation. (
  • COX-2 inhibitors are being studied in the prevention of colon polyps, and as anticancer drugs. (
  • Some COX-2 inhibitors are used in a single dose to treat pain after surgery. (
  • This preliminary information indicates a potential for the use of COX-2 inhibitors in patients with PMP. (
  • Rofecoxib is one of the new breed of anti-inflammatories known as COX-2 (cyclo-oxygenase-2) inhibitors that are supposed to be safer than NSAIDs such as aspirin. (
  • But NSAIDs quickly became COX-2 inhibitors associated with adverse gastrointestinal effects such as peptic. (
  • Here, the potential utility of selective COX-2 inhibitors in the prevention and treatment of cancer is considered. (
  • Selective COX-2 inhibitors appear to be sufficiently safe to permit large-scale clinical testing and numerous clinical trials are currently under way to determine whether selective inhibitors of COX-2 are effective in the prevention and treatment of cancer. (
  • Two large pivotal trials have been published, in which the efficacy and safety of the COX 2 inhibitors celecoxib and rofecoxib were compared with various traditional NSAIDs. (
  • COX-inhibitors (NSAIDs) showed a significant reduction of tumor incidence and tumor size in rodent models. (
  • Further studies on selective COX-2 inhibitors will investigate their role in treatment of patients with breast cancer. (
  • The drugs assessed in the study - COX-2 inhibitors - are a type of "selective" nonsteroidal anti-inflammatory drug ( NSAID ). (
  • Examples of COX-2 inhibitors include older drugs such as diclofenac, etodolac, nabumeton and meloxicam, and newer drugs like celecoxib and rofecoxib. (
  • The team looked at information on these patients' history of COX-2 inhibitor use, including when they were using these drugs and what type of COX-2 inhibitors they were taking. (
  • The study shows that people who were current users of COX-2 inhibitors were 19% more likely to die after a stroke than people who did not use COX-2 inhibitors. (
  • Earlier this year, scientists from the Perelman School of Medicine at the University of Pennsylvania, PA, published a report in the Proceedings of the National Academy of Sciences of research into a potential new class of drugs that could provide a safer alternative to COX-2 inhibitors . (
  • Last year, Medical News Today also reported on a study that suggested a possible "fix" for the side effects associated with COX-2 inhibitors. (
  • See 'COX-2 selective inhibitors: Adverse cardiovascular effects' . (
  • Other COX-2 inhibitors are available in some countries. (
  • See 'Overview of selective COX-2 inhibitors' . (
  • This topic review will summarize the major clinical trials that have focused on the gastroduodenal protective effects of the COX-2 inhibitors as compared to nonselective NSAIDs. (
  • An overview of COX-2 inhibitors is also available. (
  • Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E 2 , mainly via its prostaglandin E receptor 3 (EP 3 ), exacerbated neovascularization. (
  • EP 3 stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36. (
  • Hypertension and Cyclooxygenase-2 Inhibitors. (
  • Medications known as COX-2 inhibitors were developed to work as well as traditional NSAIDs but with fewer stomach problems. (
  • COX-2 Inhibitors - Where to From Here? (
  • From the date of first marketing, Medsafe (and other regulatory agencies around the world) have collected and analysed adverse reaction reports for rofecoxib and the other COX-2 inhibitors as part of standard post-marketing monitoring practice. (
  • In New Zealand, the Medicines Adverse Reactions Committee (MARC) had previously reviewed all significant data but found that the evidence for an association between any of the COX-2 inhibitors and increased cardiovascular events was inconclusive. (
  • The local pattern of use indicated that users of COX-2 inhibitors were older, had other co-morbidities and were often on multiple medicines that could have increased their risk of this type of event. (
  • Medsafe and MARC have also monitored and reviewed published literature on adverse events in general with the COX-2 inhibitors. (
  • Sponsors of other COX-2 inhibitors will also be asked for updated safety data, including details of any studies underway. (
  • Published data on cardiovascular events for all the COX-2 inhibitors, along with New Zealand case reports of adverse reactions and any other available unpublished data, will be reviewed by the MARC. (
  • What about the other COX-2 inhibitors? (
  • At this stage, there is insufficient information available to comment on the cardiovascular safety of the other COX-2 inhibitors (i.e. celecoxib, etoricoxib, meloxicam, parecoxib and valdecoxib). (
  • Medsafe will be asking the MARC to determine whether the risk of cardiovascular events is similar for the other COX-2 inhibitors, in comparison to rofecoxib. (
  • This requires consideration of both the adverse event profile of possible substitutes (such as NSAIDs or other COX-2 inhibitors) and patients' individual risk factors for gastrointestinal and cardiovascular harm. (
  • Prescribers can assist in monitoring the safety of all COX-2 inhibitors by reporting adverse events to the Centre for Adverse Reactions Monitoring (CARM) in Dunedin. (
  • The selective COX-2 inhibitors, celecoxib ( Celebrex ™) and rofecoxib (Vioxx™), may interact with warfarin causing an increase in the international normalised ratio (INR) and putting the patient at risk of a haemorrhagic event. (
  • The interaction between COX-2 inhibitors and warfarin has now been included in the list of adverse reactions of current concern in order to encourage reporting of these adverse events and to gather more data about them. (
  • This data initially popularized the use of selective COX-2 inhibitors. (
  • Cyclooxygenase 2 (COX-2) inhibitors have a lower incidence of GI bleeding as compared with other NSAIDs, although there is still a risk involved. (
  • Selective inhibitors of cyclooxygenase-2 have been suggested to spare gastrointestinal prostaglandin synthesis, and therefore lack the ulcerogenic effects associated with standard nonsteroidal antiinflammatory drugs. (
  • However, the effects of cyclooxygenase-2 inhibitors on inflamed gastrointestinal mucosa have not been examined. (
  • We examined cyclooxygenase-2 mRNA and protein expression before and after induction of colitis in the rat, the contribution of cyclooxygenase-2 to colonic prostaglandin synthesis during colitis and the effects of selective inhibitors of cyclooxygenase-2 on colonic injury in this model. (
  • Treatment with selective cyclooxygenase-2 inhibitors resulted in exacerbation of colitis, with perforation occurring when the compounds were administered for a week. (
  • COX-2 inhibitors are used in the treatment of arthritis and acute gout. (
  • COX-2-targeted delivery was unambiguously confirmed by blocking the COX-2 active site with high affinity inhibitors in both in vitro and in vivo mouse models. (
  • The study, published in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, suggests a potential role for COX-2 inhibitors in pancreatic cancer prevention among high-risk patients. (
  • With these results, I certainly wouldn't say everyone should be taking COX-2 inhibitors to protect against cancer," said Eibl. (
  • However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high risk populations. (
  • In the future, Dr. Eibl and others plan to study the long-term effects of nimesulide and additional COX-2 inhibitors on the onset and progression of pancreatic cancer. (
  • If you use painkillers such as ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors to treat inflammation, you may be at increased risk of irregular heart rhythm, or atrial fibrillation. (
  • Before now, no study had explored whether NSAIDs and COX-2 inhibitors could increase the risk of this disorder. (
  • Investigators looked at their use of six commonly used painkillers: non-aspirin NSAIDS (ibuprofen, naproxen) and both older (diclofenac, etodolac) and newer (celecoxib, rofecoxib) COX-2 inhibitors. (
  • Patients and controls were classified based on their use of NSAIDs and COX-2 inhibitors: no use, recent use, current use (those who got their first prescription within 60 days of their diagnosis), long-term use, and new use. (
  • The increased risk differed depending on the drugs used: there was about a 40 percent increased risk for those who used non-selective NSAIDs and 70 percent among those who used COX-2 inhibitors. (
  • They included older people and patients with chronic kidney disease or rheumatoid arthritis who started treatment with COX-2 inhibitors. (
  • Both non-selective NSAIDS and COX-2 inhibitors have been associated with a number of side effects (e.g., gastrointestinal problems) and serious long-term risks, including an increased chance of a stroke and heart attack. (
  • There is no evidence to back up claims that the new generation of anti-inflammatory drugs (COX-2 inhibitors) are less harmful to the stomach lining than many traditional anti-inflammatory drugs, concludes a study in this week s BMJ. (
  • Increased risks of adverse gastrointestinal events were associated with current use of COX-2 inhibitors and with conventional non-steroidal anti-inflammatory drugs. (
  • Evidence of enhanced gastrointestinal safety with any of the new cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs is lacking, say the authors. (
  • These results suggest that COX-2 inhibitors may not be as safe as originally thought, although a possible confounding effect cannot be ruled out, they conclude. (
  • During the past few years specific inhibitors of the COX-2 enzyme have emerged as important pharmacological tools for treatment of pain and arthritis. (
  • COX-2 specific inhibitors are thought to relieve pain and inflammation by targeting the COX-2 enzyme. (
  • Unlike ketorolac, which affects both COX-1 and COX-2, COX-2-specific inhibitors like parecoxib are less likely to cause GI ulceration or promote bleeding, while still effectively reducing pain and inflammation. (
  • Aims: The current study aims at evaluating the beneficial effects of statins and COX-2 receptor inhibitors on ALI elicited by blunt trauma to the chest. (
  • Methods: After approval by the institutional ethics and a scientific committee, and obtaining informed consent , patients admitted to the emergency department (ED) due to blunt trauma with a diagnosis of lung contusion will be enrolled in the study.The effects of statins and COX 2 inhibitors on ALI will be assessed by recording clinical parameters and measuring inflammatory mediators levels in the serum and in the bronchoalveolar space. (
  • Mukhtar and his colleagues have previously shown COX-2 inhibitors like celecoxib (known under the brand name Celebrex) suppress prostate cancer in animal models. (
  • COX-2 inhibitors also have been shown to cause adverse cardiovascular effects when administered at high doses over long durations. (
  • We believed that COX-2 inhibitors may still prove beneficial if used in combination with complementary agents," Mukhtar said. (
  • Our studies showed that the additive effect of green tea enables us to utilize the cancer-fighting abilities of COX-2 inhibitors, but at lower, safer doses. (
  • The novel benzopyran class of selective cyclooxygenase-2 inhibitors. (
  • In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. (
  • These findings, coupled with recent evidence demonstrating the benefits of COX-2 inhibitors in many cancer models, underscore the significance of aberrant COX-2 expression and suggest that pharmacologic inhibition of COX-2 and/or regulation of its expression may limit cancer progression. (
  • Therefore, they could modify individual risks for developing cancer and other diseases or the occurrence of side effects or sensitivity toward selective or nonselective COX inhibitors. (
  • Inhibition with selective or nonselective COX inhibitors was essentially the same for the two enzymes. (
  • Therefore, specific COX-2 inhibitors, like celecoxib and rofecoxib, were developed that have an equivalent effect on pain relief and inflammation than nonselective NSAIDs but have reduced occurrence of side effects ( Brooks and Day, 2000 ). (
  • Recent animal studies showed that selective COX-2 inhibitors seem to have antitumorigenic properties. (
  • Our data show that levels of COX-2 are increased in adenocarcinoma of the pancreas and raise the possibility that selective inhibitors of COX-2 may be useful in the prevention or treatment of this disease. (
  • The Food and Drug Administration on February 16-18, 2005 held an advisory committee meeting to discuss the cardiovascular risk posed by painkillers known as Cox-2 inhibitors, which include Celebrex, Bextra and Vioxx. (
  • The CSPI research uncovered affiliations between 10 of the scientists that served on the committee and the three manufacturers of Cox-2 inhibitors. (
  • 1 The approval by the Food and Drug Administration (FDA) of highly selective COX-2 inhibitors for the treatment of pain and rheumatoid arthritis (RA) raised the possibility that these agents could also be used in the treatment of neurological diseases including stroke. (
  • However, the occurrence of serious cardiovascular complications in patients receiving COX-2 inhibitors has led to the recent withdrawal from the market of a popular COX-2 inhibitor and has called for a re-evaluation of the therapeutic potential of these drugs. (
  • On the other hand, it has been hypothesized that the cardiovascular complications of COX-2 inhibitors derive from the fact that COX-2 inhibition attenuates endothelial PGI 2 production, leaving COX-1-dependent TXA 2 synthesis unopposed. (
  • both selective COX-2 inhibitors), are effective in preventing the development as well as reducing the size and decreasing the number of polyps in FAP patients (compared with matched controls). (
  • NSAIDs are inhibitors of the COX enzyme family, whose members regulate the conversion of arachidonic acid to prostaglandins ( 11 ). (
  • The benefit of cyclo-oxygenase-2 (COX-2) inhibitors in preventing serious gastrointestinal adverse events is likely overstated. (
  • COX-2 inhibitors are important drugs with analgesic and anti-inflammatory effects. (
  • COX-2 inhibitors are newly developed drugs for inflammation that selectively block the COX-2 enzyme. (
  • COX-2 selective inhibitors are a new class of nonsteroidal anti-inflammatory drugs, or NSAIDs that directly targets the COX-2 enzyme. (
  • Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. (
  • A 2006 review of 138 randomized trials and almost 150,000 participants revealed selective COX-2 inhibitors were associated with a moderately increased risk of vascular events, mainly due to a twofold-increased risk of myocardial infarction. (
  • PORTLAND, Oregon-Cyclooxygenase 2 (COX-2) inhibitors are attracting attention as potential anti-cancer drugs because of evidence of increased survival in patients with low levels of COX-2. (
  • Dr. Blanke said that COX-2 inhibitors enhance the efficacy of radiotherapy in mouse sarcomas. (
  • Early studies have also found that COX-2 inhibitors can increase the efficacy of cytotoxic drugs. (
  • Therefore, selective inhibitors of COX-2 may also block PGE 2 generation minimizing its colorectal-tumor-promoting effects. (
  • The induction of COX-2 by EGF was suppressed by inhibitors of tyrosine kinase activity, phosphatidylinositol 3-kinase, mitogen-activated protein kinase kinase, and p38 mitogen-activated protein kinase. (
  • The aim of the study reported here was to investigate the preventive effects and underlying potential molecular mechanisms of selective cyclooxygenase-2 (COX-2) inhibitors in a rodent model of postoperative intra-abdominal adhesions. (
  • Furthermore, using selective COX-2 inhibitors to prevent intra-abdominal adhesions did not adversely affect the weight, bowel motility, or healing of intestinal anastomoses in a rat model. (
  • Targeting delivery of COX-2 inhibitors to macrophages may conserve their efficacy while limiting cardiovascular risk. (
  • Extended dosing with COX-2 inhibitors in 3 placebo-controlled trials was associated with emergence of a detectable increase in cardiovascular events in patients initially selected to be at low risk of heart disease. (
  • However, experiments with inhibitors of COX-2 and conventional COX-2 knockout (KO) mice showed accelerated, delayed, or no effect on atherosclerosis. (
  • Cox-2 inhibitors are non-steroidal anti-inflammatory drugs (NSAIDs) which selectively inhibit cyclooxygenase-2. (
  • The development of the Cox-2 selective inhibitors was intended to provide drugs that would offer the same pain relieving and anti-inflammatory effects as the traditional NSAIDs without causing the gastric ulcers that have been associated with the older drugs. (
  • In early studies, the Cox-2 inhibitors appeared to be fulfilling their promise. (
  • However, a French review warned that certain selective Cox-2 inhibitors (i.e. celecoxib, rofecoxib) have not been tested for safety on patients with ulcers or cardiovascular or renal disease. (
  • Even so, there were evidences of concern about the potential risks of the Cox-2 inhibitors. (
  • Examination of the relative importance of COX enzymes in AIA can be partly assessed from studies using preferential COX-2 inhibitors. (
  • The identification of COX-2 has also led to the development and marketing of both relatively and highly selective COX-2 inhibitors for use as analgesics, antipyretics, and anti-inflammatory agents. (
  • Selective COX-2 inhibitors (COXIBs) have been shown to possess much improved GI tolerability and reduced GI related adverse events when compared with nonselective COX-1inhibitors. (
  • All COX inhibitors had shown this CV toxicity. (
  • The COX inhibitors associated CV toxicity has multiple manifestations, which include the induction of myocardial infarction (MI), edema, thrombosis, blood pressure destabilization and death. (
  • Patients at risk of CV disease or with a history of CV disease were the most significant determinants of CV events after receiving COX inhibitors. (
  • Additional comprehensive, long-term, prospective investigations comparing the CV and GI safety profile of marketed NSAIDs against each other and against selective inhibitors are needed to address the controversy of COX inhibitors. (
  • Such important findings led to the development and subsequent introduction of the selective COX-2 inhibitors celecoxib, valdecoxib and rofecoxib, which have considerably reduced GI ulcerogenicity potential when compared with the older, non-selective NSAIDs [5]. (
  • Background: Fracture-healing is impaired in mice lacking a functional cyclooxygenase-2 (COX-2) gene or in rats continuously treated with COX-2 inhibitors. (
  • Conventional non-steroidal anti-inflammatory drugs (NSAIDs) and newer specific cyclooxygenase-2 (cox-2) inhibitors are commonly used in muscular skeletal trauma and in relation to orthopedic surgery to reduce the inflammatory response and pain. (
  • Do COX-2 inhibitors offer reduced GI toxicity. (
  • Renal effects of cyclooxygenase inhibitors in volume-depleted dogs. (
  • This may imply that COX-2 inhibitors could be a means for chemoprevention in this syndrome. (
  • Is the Subject Area "COX-2 inhibitors" applicable to this article? (
  • On the eve of vital meetings of US Food and Drug Administration advisory panels on the safety of COX-2 inhibitors, a senior official at the agency dropped a bombshell by refusing to present new data on the cardiac risk of painkillers, saying he feels intimidated by his superiors in the FDA. (
  • Population rates of upper gastrointestinal (GI) hemorrhage have been observed to increase with the introduction and rapid uptake of selective cyclooxygenase-2 (COX-2) inhibitors. (
  • The introduction of selective cyclooxygenase-2 (COX-2) inhibitors, a group of NSAIDs, has resulted in a rapid increase in the number of people exposed to NSAIDs. (
  • Many patients who would otherwise not have used an NSAID are now using COX-2 inhibitors without a corresponding decrease in the use of more traditional nonselective NSAIDs. (
  • 1 , 2 Although COX-2 inhibitors have been found to be associated with a lower risk of significant adverse gastrointestinal events than have traditional nonselective NSAIDs at the level of the individual patient, 3 , 4 recent evidence suggests that the market expansion created by COX-2 inhibitors may increase rates of hospital admissions because of upper gastrointestinal (GI) bleeding at the population level. (
  • For example, COX-2 inhibitors were listed in the Ontario Drug Benefit (ODB) formulary in April 2000 as limited-use drugs, which means that prescribers must indicate that the recipient has failed a trial of at least 3 nonselective NSAIDs or has clinically significant GI disease. (
  • In contrast, COX-2 inhibitors are highly restricted in British Columbia and can be obtained only through a "special authority" process, which involves a written request and approval by the drug plan. (
  • These differences in the nature and timing of reimbursement for COX-2 inhibitors have contributed to vastly different rates of NSAID use at the population level. (
  • To explore this issue further, we conducted a population-based study to compare changes over time in the prevalence of NSAID use and rates of admission to hospital because of upper GI bleeding after the introduction of COX-2 inhibitors in the elderly populations of British Columbia and Ontario. (
  • The prevalence of NSAID use in each interval was determined by dividing the unique number of people dispensed any NSAID (either nonselective NSAIDs or COX-2 inhibitors) by the total number of people alive at the beginning of the interval. (
  • Basically, all COX inhibitors work by blocking or interferring with normal hormone and enzyme activity. (
  • PGHSs are targets for NSAIDs and PTGS2 (COX-2) specific inhibitors called coxibs. (
  • The inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of the selective COX-2 inhibitor celecoxib. (
  • We have demonstrated that treatment of human prostate-cancer cell lines with a selective COX-2 inhibitor induces apoptosis both in vitro and in vivo. (
  • The in vivo results also indicate that the COX-2 inhibitor decreases tumor microvessel density and angiogenesis. (
  • Also called cyclo-oxygenase-2 inhibitor. (
  • By combining a COX-2 inhibitor, similar to Celebrex, and an epoxide hydrolase (sEH) inhibitor, the drug controls angiogenesis (blood vessel formation), limiting a tumor's ability to grow and spread. (
  • The effectiveness of sunitinib for the treatment of renal cell carcinoma could be enhanced with the addition of a cyclooxygenase-2 inhibitor, study findings show. (
  • Finally, using the highly selective COX-2 inhibitor, 1-[(4-methylsufonyl)phenyl]-3-tri-fluro-methyl-5-[(4-flur o)phenyl]prazole (SC58125), the effect of COX-2 inhibition on functional outcome following a spinal cord injury was determined. (
  • Another COX-2 inhibitor has been shot down by the FDA. (
  • Increased invasiveness and prostaglandin production were reversed by treatment with sulindac sulfide, a known COX inhibitor. (
  • In a proof-of-principle clinical trial, treatment with the selective COX-2 inhibitor celecoxib reduced the number of colorectal polyps in patients with familial adenomatous polyposis. (
  • Apricoxib, a novel inhibitor of COX-2, markedly improves standard therapy response in molecularly defined models of pancreatic cancer. (
  • While newer versions of these COX-2 inhibitor drugs have been pulled off shelves, older ones are still frequently prescribed. (
  • Rofecoxib is a COX-2 inhibitor that was removed due to an increased risk of stroke and myocardial infarction with long-term use. (
  • Celecoxib is a type of medication known as a COX-2 inhibitor because of the way it works in the body. (
  • As a COX-2 inhibitor, celecoxib blocks an inflammation-promoting enzyme called COX-2. (
  • If a COX-2 inhibitor is considered necessary for a patient taking warfarin, the INR should be checked a few days after introduction of the COX-2 inhibitor and monitored closely for the first two weeks. (
  • If the INR increases, the dose of warfarin should be reduced or the COX-2 inhibitor withdrawn. (
  • If celecoxib or rofecoxib are considered necessary for a patient taking warfarin, the INR should be checked a few days after introduction of the COX-2 inhibitor and monitored closely for the first two weeks. (
  • If the INR increases, it may be possible to continue the selective COX-2 inhibitor by reducing the dose of warfarin. (
  • 2,3 Otherwise the COX-2 inhibitor should be discontinued to avoid a haemorrhagic event. (
  • The INR should be checked and restabilised following any dose reduction of warfarin or cessation of the COX-2 inhibitor. (
  • The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). (
  • 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfon-amide), the only FDA approved COX-2 inhibitor, has been used in the treatment of OA [ 13 , 14 ]. (
  • (21) have reported that celecoxib, a specific Cox-2 inhibitor suppressed both incidence and multiplicity of azoxymethane-induced colon cancer in rats by ∼93 and 97%, respectively. (
  • cox-2 inhibitor: see nonsteroidal anti-inflammatory drug . (
  • Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delays the progression of precancerous pancreatic lesions in mice, according to researchers at David Geffen School of Medicine at UCLA. (
  • While inflammation has been shown to be a factor in many forms of cancer, the researchers say this is the first study to demonstrate the effect of an anti-inflammatory COX-2 inhibitor on the development of pancreatic cancer. (
  • If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection. (
  • The Onion, a satiric Web site, has a pretty funny take on the whole COX-2 inhibitor thing . (
  • More particularly, the invention provides a combination therapy for the treatment of pain, inflammation or inflammation mediated disorders comprising the administration to a subject of a potassium ion channel modulator in combination with a cyclooxygenase-2 selective inhibitor. (
  • b) administering to the subject a combination comprising a cyclooxygenase-2 selective inhibitor or an isomer, a pharmaceutically acceptable salt, ester, or prodrug thereof and a potassium ion channel modulator or an isomer, a pharmaceutically acceptable salt, ester, or prodrug thereof. (
  • 2. The method of claim 1 wherein the cyclooxgenase-2 selective inhibitor has a selectivity ratio of COX-1 IC 50 to COX-2 IC 50 not less than about 50. (
  • Of 9407 cases, 45% had been prescribed a conventional non-steroidal anti-inflammatory drug (NSAID) in the previous three years and 10% had been prescribed a COX-2 inhibitor. (
  • Of 88,867 controls, 33% had been prescribed an NSAID and 6% had been prescribed a COX-2 inhibitor. (
  • ATLANTA-Parecoxib, the first injectable COX-2 inhibitor, demonstrated impressive analgesic efficacy in postsurgical patients, according to a study presented at the 19th Annual Scientific Meeting of the American Pain Society (APS). (
  • The new injectable cyclooxygenase (COX)-2 inhibitor may provide a new postoperative pain management option. (
  • The study will evaluate the effect on cells and clinical response to study medications: Epidermal Growth Factor Receptor (EGFR), Tyrosine Kinase Inhibitor Erlotinib (OSI-774, Tarceva™), and Cyclooxygenase-2 (COX-2) Inhibitor (Celecoxib). (
  • But now researchers have found that a component of green tea, combined with low doses of a COX-2 inhibitor, could slow the spread of human prostate cancer . (
  • In the March 1 issue of Clinical Cancer Research , researchers from University of Wisconsin-Madison demonstrate that low doses of the COX-2 inhibitor celecoxib, administered with a green tea polyphenol called pigallocatechin-3-gallate (EGCG), can slow the growth of human prostate cancer . (
  • Alone, both EGCG and NS-398, a COX-2 inhibitor similar to celecoxib, demonstrated the ability to slow cancer cell growth and limit the presence of known cancer-promoting proteins within the cell samples. (
  • Novartis also has a Cox-2 inhibitor in its pipeline. (
  • SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by ∼70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells. (
  • Treatment of mice with the nonspecific COX inhibitor indomethacin impaired the generation of cell-mediated immunity. (
  • This phenotype was due to inhibition of the inducible COX-2 enzyme, as treatment with the COX-2-selective inhibitor celecoxib similarly inhibited the development of immunity. (
  • COX-2 inhibitor no safer than naproxen and PPI. (
  • The researchers were able to achieve similar heart-stopping results in rat cardiac cells, whereas aspirin, another potent COX-2 inhibitor, had no effect, confirming that another mechanism is at work. (
  • In vitro studies of NSCLC cells treated with irinotecan (Camptosar), docetaxel (Taxotere), etoposide (VePesid), or cisplatin (Platinol), with or without the COX-2 inhibitor nimesulide showed that the COX-2 inhibitor alone induced apoptosis at low concentrations and was 'near-synergistic' for selected anticancer agents, according to Dr. Blanke. (
  • L-arginine (2 mM), a substrate for nitric oxide synthases (NOS), decreased COX-2 and PGE 2 levels, while N G -nitro-L-arginine methyl ester (L-NAME) (2 mM), a NOS inhibitor, had no influence on COX-2 and PGE 2 levels but limited tumor cell motility. (
  • NS398 (75 μM), a selective COX-2 inhibitor, had no significant influence on NO level but decreased motility of tumor cells. (
  • Data indicate that selective COX-2 inhibitor prevents in vivo intra-abdominal adhesion by inhibition of basic fibroblast growth factor and transforming growth factor-beta expression, but not through an antiangiogenic mechanism. (
  • There have been recent reviews of aspirin induced asthma (AIA), 1 2 the use of the COX-2 preferential inhibitor nimesulide in asthmatic patients intolerant to non-steroidal anti-inflammatory drugs (NSAIDs), 3 and of nimesulide in general. (
  • This sulphonanilide NSAID, which is effective in treating a wide spectrum of inflammatory and painful conditions, 7 was first marketed in 1985 and 10 years later it was found to be a preferential inhibitor of COX-2. (
  • Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity. (
  • The non-steroidal anti-inflammatory drug, sulindac and a specific COX-2 inhibitor, NS398, were shown to act similarly in LPS-activated RAW 264.7 cells. (
  • David Graham, associate director for science and medicine at the FDA's Office of Drug Safety, who has been critical of the handling of the withdrawal of Merck & Co's COX-2 inhibitor, Vioxx (rofecoxib) last year [[19/11/04a]], was due to present data from California's Medicaid programme which looked at more than 15,000 heart attack patients. (
  • Changes in COX-2 inhibitor use and upper GI bleeding rates in regions with relatively restrictive drug policies (e.g. (
  • However, with regard to this drug's promise for the therapy of advanced cancers, it is unclear whether the inhibition of COX-2 plays a dominant role, and this has become a controversial and intensely researched issue. (
  • However, when the ability of all these compounds to kill tumor cells in cell culture was investigated, it turned out that the antitumor potency did not at all depend on whether or not the respective compound could inhibit COX-2, showing that inhibition of COX-2 was not required for the anticancer effects. (
  • Nonsteroidal antiinflammatory drugs (NSAIDs) prevent prostaglandin (PG) biosynthesis through inhibition of cyclooxygenase (COX) activity and are used as antiinflammatory, analgesic, and fever-relieving drugs ( 1 ). (
  • As of 2012 results have been converging on the hypothesis that the adverse cardiovascular effects are most likely due to inhibition of COX-2 in blood vessels, which leads to a decrease in the production of prostacyclin in them. (
  • The objectives of this study are to determine the nature of COX-2 expression in normal and traumatized rat spinal cord, and to determine the effects of selective COX-2 inhibition on functional recovery following spinal cord injury. (
  • These data demonstrate that COX-2 mRNA and protein expression are induced by spinal cord injury, and that selective inhibition of COX-2 improves functional outcome following experimental spinal cord injury. (
  • To examine the role of COX-2 in intestinal epithelial tumorigenesis we have shown that constitutive COX-2 expression in nontransformed rat intestinal epithelial cells leads to inhibition of programmed cell death ( 21 ). (
  • These drugs have at least a 200- to 300-fold selectivity for inhibition of COX-2 over COX-1. (
  • Beneficial effects of NSAIDs on inflammation are mediated by COX-2 inhibition, whereas unwanted gastrointestinal effects are caused by primarily inhibition of COX-1 [ 12 ]. (
  • Inhibition of COX-1 may contribute to NSAID GI toxicity. (
  • It has been demonstrated that long-term nNOS inhibition generates hypertension in rats 8 and that nNOS activity is decreased in the nonclipped kidney of 2-kidney, 1-clip rats 9 and the kidneys of rats infused with angiotensin II long term. (
  • In rat kidneys, nonselective COX inhibition with meclofenamate and indomethacin blunted arterial pressure-mediated increases in papillary blood flow when RPP was elevated. (
  • 11 Nevertheless, in dog 12 and rat 13 kidney preparations, nonselective COX inhibition has consistently failed to alter the autoregulatory responses to changes in perfusion pressure. (
  • The mechanism of NSAID-induced polyp regression is not completely known, but it thought that it is at least in part due to inhibition of cyclooxygenase 2 (COX2) and the resultant decrease in prostaglandin synthesis although a non-COX mechanism may also contribute. (
  • Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2. (
  • Whereas many of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., gastrointestinal ulceration and bleeding, platelet dysfunctions) are caused by a suppression of COX-1 activity, inhibition of COX-2-derived prostanoids facilitates the anti-inflammatory, analgesic, and antipyretic effects of NSAIDs. (
  • Compositions comprising an effective amount of a curcuminoid species and an effective amount of a diterpene lactone species, a triterpene species or derivatives thereof that have a synergistic effect on specific inhibition of inducible COX-2 activity and have minimal effect on COX-1 activity are disclosed. (
  • Here we tested the hypothesis that acetaminophen blocks fever through inhibition of cyclooxygenase-2 (Cox-2), by monitoring lipopolysaccharide induced fever in mice with genetic manipulations of enzymes in the prostaglandin cascade. (
  • For example, the use of nonsteroidal anti-inflammatory drugs (NSAID) drastically reduces the overall number and size of adenomas in patients with FAP, as well as in experimental animal models, such as the Apc m in mice ( 9 ), by the pharmacologic inhibition of two enzymes involved in prostaglandin biosynthesis, cyclooxygenase (COX)-1 and COX-2. (
  • Inhibition or elevation of COX-2 has been shown to suppress or enhance excitatory glutamatergic neurotransmission and long-term potentiation (LTP). (
  • 2 COX-3, a splice variant of COX-1, is highly sensitive to inhibition by acetaminophen and is most abundant in heart and brain. (
  • 7-10 Inhibition of COX-2 attenuates ischemic injury after middle cerebral artery occlusion with a relatively wide therapeutic window (6 to 24 hours). (
  • Given this background, attempts to combine COX-2 inhibition with chemotherapy constitute a logical next step. (
  • The effects of COX-2 inhibition and radiation are synergistic, and treatment increases the actual cure rate. (
  • COX-2 overexpression is independently associated with disease-free survival, and COX-2 inhibition might be useful in preventing hematogenous metastasis,' he said. (
  • Selective COX-2 inhibition enhances mitomycin-C-induced apoptosis,' Dr. Blanke said. (
  • Clinical trials should incorporate COX-2 inhibition into treatment regimens,' he concluded. (
  • Selective inhibition of COX-2 and PGE 2 production and influencing NO synthesis in the tumor microenvironment may represent important goals for prevention or therapy of colon cancers. (
  • Assays were performed to elucidate the effect of COX-2 inhibition on hypoxia-induced fibroblast activity in vitro and on intra-abdominal adhesion formation in vivo. (
  • Inhibition of COX-2 attenuated the activating effect of hypoxia on normal peritoneal fibroblasts in vitro. (
  • Inhibition of COX-2 prevents postoperative intra-abdominal adhesions through suppression of inflammatory cytokines. (
  • Background- Placebo-controlled trials of nonsteroidal anti-inflammatory drugs selective for inhibition of cyclooxygenase-2 (COX-2) reveal an emergent cardiovascular hazard in patients selected for low risk of heart disease. (
  • 2 More controversial has been the potential impact of COX-2 inhibition on atherosclerosis. (
  • 8 Because this confusion may have reflected the failure to characterize the pharmacological specificity of enzyme inhibition and the diverse consequences of missing COX-2 during development, we induced global deletion of COX-2 postnatally. (
  • Prostaglandins in human lung are formed by various tissues and cells, including bronchial muscle, epithelium, and inflammatory cells, 1 2 so the inhibition of prostaglandin formation can have numerous effects. (
  • 6 Inhibition of PGE 2 synthesis seems to be particularly important in AIA for several reasons: PGE 2 can relax bronchial muscle, inhibit the formation or release of various bronchoconstrictor agents such as leukotrienes and histamine (levels of which are raised in patients with AIA), and PGE 2 administered as an aerosol inhibits aspirin induced bronchoconstriction. (
  • After the recognition that COX was the target of aspirin ( 3 ), the pharmaceutical industry developed a substantial number of nonsteroidal anti-inflammatory drugs (NSAID), whose mechanism of action involves competitive or noncompetitive inhibition of COX activity. (
  • It was initially postulated that the major gastrointestinal and renal side effects of the original NSAID, termed "nonselective" because of their inhibition of both COX-1 and COX-2, would be avoided by the development of COX-2 selective NSAID, because COX-1 was recognized to be abundantly expressed in gastric mucosa and in kidney. (
  • The efficacy and toxicity of NSAIDs is a consequence of the inhibition of the COX enzymes [2]. (
  • RESEARCH DESIGN AND METHODS- Renal function was assessed during clamped euglycemia and hyperglycemia on 2 consecutive days before and then again after 14 days of COX2 inhibition using 200 mg celecoxib once daily by mouth. (
  • RESULTS- Under euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR in the hyperfiltration group (150 ± 5 to 139 ± 5 ml/min per 1.73 m 2 ) but increased GFR in the normofiltration group (118 ± 5 to 138 ± 5 ml/min per 1.73 m 2 ). (
  • This effect was found to be due to inhibition of COX-2 enzyme activity by chamomile. (
  • Moreover, in animal studies NSAIDs interrupted the development of various epithelial tumors, and in man long-term intake of these drugs substantially reduced the risk for developing colorectal cancer ( 2 ). (
  • The COX-2 isozyme has been identified as a major target for the antitumor activities of NSAIDs ( 3 ). (
  • Having spent the last two months reviewing the safety of the COX-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), the US regulatory agency. (
  • Most NSAIDs currently in use inhibit both cyclooxygenase (COX)-1 and COX-2 at their recommended dosages ( 11 - 14 ). (
  • Versuche mit COX Inhibitoren (NSAIDs) zeigten im Tiermodell eine deutliche Reduktion von Inzidenz und Größe der Tumoren in einer dosisabhängigen Weise. (
  • Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. (
  • The anti-inflammatory effects of NSAIDs are mainly due to their ability to inhibit cyclooxygenase (COX), impairing production of prostaglandins, which are important mediators of both pain and the inflammatory response. (
  • At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions, may be decreased when compared to nonselective NSAIDs. (
  • NSAIDs suppress cyclooxygenase-2 (COX-2), which affects epithelial proliferation and apoptosis. (
  • Recently developed non-steroidal anti-inflammatory drugs (NSAIDS) are targeted to inhibit COX-2 and treat inflammation and arthritic pain. (
  • Polymorphisms in the COX-2 gene could alter enzyme expression, function, and/or the response to NSAIDs. (
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), like aspirin, which inhibit PG formation by inactivating COX ( Vane and Botting, 1987 ), are used for the treatment of a wide variety of diseases. (
  • Indeed, the accumulating clinical and experimental evidence now supports a potent antitumorigenic efficacy of inhibiting COX-2 with NSAIDs as a chemopreventive strategy for colon cancer (reviewed in refs. (
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. (
  • Because they selectively block the COX-2 enzymeâ€"the enzyme responsible for inflammation and painâ€"and not the COX-1 enzyme, these drugs are uniquely different from traditional NSAIDs. (
  • Dr. Blanke said that numerous studies have assessed the effects on the development of colorectal cancer of a wide variety of nonsteroidal anti-inflammatory drugs (NSAIDS), which inhibit COX-2, and acetaminophen. (
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) designed specifically to inhibit cyclooxygenase-2 (COX-2) relieve pain and inflammation but expose patients to a cardiovascular hazard comprising myocardial infarction and stroke, hypertension, heart failure, arrhythmogenesis, and sudden cardiac death. (
  • The traditional NSAIDs inhibit both cyclooxygenase 1 and 2 (Cox-1 and Cox-2). (
  • 4 5 This paper discusses the importance of inhibiting prostaglandin E 2 (PGE 2 ) synthesis in AIA, and the relative safety of NSAIDs that preferentially inhibit COX-2. (
  • Furthermore, NSAIDs may alter the synthesis of various prostaglandins differently in patients with AIA-for example, aspirin reduces the synthesis of PGE 2 but not of the bronchoconstrictors PGD 2 and PGF 2α . (
  • However, as with all NSAIDs, its COX-1/COX-2 ratio varies in different reports (from about 4.5 to 2500 in favour of COX-2). (
  • Traditional NSAIDs inhibit the constitutional cyclooxygenase-1 (COX-1) enzyme responsible for eicosanoids biosynthesis not only in joints, a beneficial effect, but also in the stomach, a detrimental effect. (
  • Selective NSAIDs were specifically designed to preferentially inhibit the cyclooxygenase-2 (COX-2), an inducible enzyme mediating the production of inflammatory eicosanoids in the joints but sparing the endogenous protective eicosanoids in the stomach. (
  • Cyclooxygenase-2 (COX-2) is the inducible isozyme of COX, a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. (
  • The cyclooxygenase-2 enzyme is just such a protein, as the concentration of COX-2 is greater in cancer cells than in adjacent normal tissues. (
  • The COX-2 enzyme was discovered in 1988 by Daniel Simmons, a Brigham Young University researcher. (
  • One property shared by all of these drugs is their ability to inhibit cyclooxygenase (COX), a key enzyme in the conversion of arachidonic acid to prostaglandins. (
  • The study found that the COX-2 enzyme is mostly found just in the brain, gut, kidney and thymus gland. (
  • Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflammatory prostaglandins. (
  • Two related isoforms of the cyclo-oxygenase (COX) enzyme have been described: COX-1 (PGHS-1) and COX-2 (PGHS-2). (
  • There are two isoforms of the COX enzyme: COX-1, found in most tissues and constitutively expressed in normal cells, and COX-2, which is not expressed in healthy tissue but is induced by various catabolic mediators, such as cytokines, growth factors, and mechanical stress [ 11 ]. (
  • Cyclooxygenase-2 (COX-2) enzyme is expressed in many malignant tumor types, even in very early stage pre-adenomas. (
  • COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. (
  • Expression of the inducible isoform of the cyclooxygenase gene (PGHS-2, COX-2) which codes for the enzyme that catalyzes formation of prostaglandins, was detected in 13/13 human breast tumors of high grade but not in samples of normal breast tissue. (
  • The enzyme cyclooxygenase (COX) catalyzes the first step of the synthesis of prostanoids. (
  • COX-1 is constitutively expressed as a "housekeeping" enzyme in most tissues. (
  • Cyclo-oxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins (PG), and evidence suggests that COX-2 plays an important role in the pathogenesis of acute lung injury (ALI). (
  • Previous research has linked the cyclooxygenase-2 enzyme, commonly known as COX-2, to many cancer types, including prostate cancer , said Mukhtar. (
  • The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in inflammatory states, and COX-2 overexpression plays a key role in carcinogenesis. (
  • The absence of functionally important polymorphisms in the COX-2 gene may suggest that there has been selective pressure against those single nucleotide polymorphisms because of the critical role of this enzyme in maintenance of homeostasis. (
  • Results from recent studies have established the presence of two distinct COX 3 enzymes, a constitutive enzyme (COX-1) and an inducible form (COX-2). (
  • Cyclooxygenase-2 (COX-2), a rate-limiting enzyme converting arachidonic acid to prostaglandins and a key player in neuroinflammation, has been implicated in the pathogenesis of neurodegenerative diseases such as multiple sclerosis, Parkinsons and Alzheimers diseases, and in traumatic brain injury- and ischemia-induced neuronal damage, and epileptogenesis. (
  • The rate-limiting enzyme for prostanoid synthesis cyclooxygenase-2 (COX-2) has been implicated in the basic mechanisms of several brain diseases, including stroke, multiple sclerosis and neurodegenerative diseases. (
  • Cyclooxygenase-2 (COX-2) is an enzyme that catalyses the formation of prostaglandins and therefore participates in the regulation of the consecutive stages of inflammatory processes. (
  • COX2 (Cyclooxygenase 2) is an inducible enzyme. (
  • More interestingly, this effect is independent of the COX-2 enzyme. (
  • Blocking the COX-2 enzyme stops the production of the chemical messengersâ€"or prostaglandinsâ€"that cause the pain and swelling of arthritis inflammation. (
  • We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E 2 (PGE 2 ), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. (
  • Postnatal global deletion of COX-2 accelerates atherogenesis in hyperlipidemic mice, a process delayed by selective enzyme deletion in macrophages. (
  • Conclusions- Although atherogenesis is accelerated in global COX-2 knockouts, consistent with evidence of risk transformation during chronic nonsteroidal anti-inflammatory drug administration, this masks the contrasting effects of enzyme depletion in macrophages versus vascular smooth muscle cells and endothelial cells. (
  • To regain balance, Source Naturals introduces HOLY BASIL, a legendary Ayurvedic herb that is making news for its ability to inhibit the inflammatory COX-2 enzyme, balance cortisol levels and normalize blood sugar. (
  • Cyclooxygenase (COX), the enzyme responsible for the initial rate-limiting metabolism of arachidonic acid to prostaglandin G2 and subsequently to prostaglandin H2, was first purified in ram seminal vesicles and was cloned in 1988 by DeWitt and Smith ( 1 ). (
  • This enzyme has been renamed cyclooxygenase-1 (COX-1) to indicate that it encodes the constitutive enzyme. (
  • However, by the early 1990s, experimental studies began to suggest that COX-1 might not be the enzyme responsible for increased prostanoid production in inflammatory states. (
  • Recent research has disclosed at least two types of COX enzymes exits: COX-1 is a constitutive enzyme responsible for housekeeping functions in organs such as the stomach, kidney, intestine and platelets, while COX-2 is an inducible enzyme exerting its action at inflammatory sites of the joints and muscles [3,4]. (
  • First step in prostaglandins synthesis originated from arachidonic acid is regulated by prostaglandin enzyme G/H sintetase, also called cyclooxygenase (COX) [10]. (
  • HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the PTGS2 gene. (
  • Each monomer of the enzyme has a peroxidase and a PTGS (COX) active site. (
  • Abstract -This study was designed to examine the contribution of cyclooxygenase-2 (COX-2) in the afferent arteriolar autoregulatory responses to increases in perfusion pressure and its relationship with neuronal nitric oxide synthase (nNOS). (
  • Cyclooxygenase, or prostaglandin G/H synthase, is the rate-limiting step in the production of prostaglandins. (
  • Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. (
  • Cyclooxygenase type 1 is constitutively expressed and accounts for synthesis of prostaglandins in the normal gastrointestinal tract. (
  • The prostaglandins produced during colitis were largely derived from cyclooxygenase-2. (
  • Prostaglandins and thromboxane are formed by the enzymatic oxidation of arachidonic acid catalyzed by the cyclooxygenases, COX 1 and COX-2. (
  • Cyclooxygenases are key enzymes in the conversion of free arachidonic acid to prostaglandins. (
  • Hence, these observations implicate the contribution of COX-2 and its metabolites, prostaglandins, in colon cancer development ( 11 , 12 ). (
  • COX-1 and COX-2 are key enzymes in the biosynthetic pathway by which arachidonic acid is first converted into an intermediate prostaglandin, PG-G2, and then metabolized to at least five structurally related prostaglandins, including prostaglandin E 2 (PGE 2 ), PGD 2 , PGF 2α , PGI 2 , and thromboxane A 2 by specific prostaglandin synthases ( 13 ). (
  • Recent evidence shows that endogenous cannabinoids are substrates for COX-2 and can be oxygenated by COX-2 to form new classes of prostaglandins (prostaglandin glycerol esters and prostaglandin ethanolamides). (
  • These discoveries suggest that the contributions of COX-2 to neurotransmission and brain malfunction result not only from its conversion of arachidonic acid to classic prostaglandins but also from its oxidative metabolism of endocannabinoids to novel prostaglandins. (
  • COX are essential enzymes which catalyze the conversion of arachidonic acid (AA) to prostaglandins (PGs). (
  • 1 These effects are attributable to suppression of COX-2-derived cardioprotective prostaglandins, particularly prostacyclin (prostaglandin I 2 [PGI 2 ]) in the vasculature and in cardiomyocytes. (
  • The cyclooxygenases are required for the creation of prostaglandins. (
  • Generally, in various tissues and organs such as the gastrointestinal mucosa and kidney, COX-1 produces prostaglandins that have physiological protective roles, whereas COX-2 induced at sites of inflammation forms prostaglandins that contribute to the disease. (
  • Prostaglandins play myriad roles as local mediators of inflammation and as modulators of physiologic functions, such as maintenance of gastric mucosal integrity and modulation of renal microvascular hemodynamics, renin release, and tubular salt and water reabsorption ( 2 ). (
  • The PTGS (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins in two steps. (
  • A new isoform, cyclooxygenase-2 (COX-2), has been cloned that is induced during inflammation in leukocytes and by synaptic activity in neurons. (
  • This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation. (
  • It had been proposed that the ideal NSAID would inhibit the inducible COX-2 isoform (thereby decreasing inflammation) without having any effect on the constitutive COX-l isoform (thereby minimizing gastric toxicity) [ 1 ]. (
  • Cyclooxygenase (COX)-2 is also an immediate-early gene product of inflammation. (
  • COX-2 is induced by cytokines, mitogens, and endotoxins, accounting for elevated prostaglandin production during inflammation. (
  • These agents inhibit COX-2, thus suppress production of prostaglandin E2 at inflammation sites. (
  • Cyclooxygenase-2 is expressed at sites of inflammation. (
  • These studies demonstrate that suppression of cyclooxygenase-2 can result in exacerbation of inflammation-associated colonic injury. (
  • COX-2 appears to play an emerging role in inflammation and carcinogenesis. (
  • Thus, COX-2 represents the best target for therapeutic intervention in several disease states that involve chronic inflammation, including cancer ( 14 ). (
  • However, while Cox-2 is associated with inflammation and pain , Cox-1 maintains the integrity of the gastric mucosa, mediates normal platelet function, and regulates renal blood flow. (
  • This second COX isoform has subsequently been renamed cyclooxygenase-2 (COX-2), and a vast amount of research has identified it to be an inducible and glucocorticoid-sensitive gene that is highly expressed in many tissues in response to inflammation. (
  • In addition to its central role in inflammation, aberrantly upregulated COX-2 expression is increasingly implicated in the pathogenesis of a number of epithelial cell carcinomas, including colon, esophagus, breast, and skin, and in Alzheimer's disease and possibly other neurologic conditions ( 12 , 13 , 14 ). (
  • Inducible cyclooxygenase (COX-2) has been implicated in the process of inflammation and carcinogenesis. (
  • However, COX-2 is constitutively overexpressed in various preneoplasias and epithelial tumors, suggesting that this isoform plays a role in cancer development ( 2-4 ). (
  • Das Ziel der vorliegenden Arbeit war, das Expressionsmuster der induzierbaren Isoform COX-2 und der konstitutiven Isoform COX-1 im Mammakarzinom zu untersuchen. (
  • Zidar N, Odar K, Glavac D, Jerse M, Zupanc T, Stajer D. Cyclooxygenase in normal human tissues-is COX-1 really a constitutive isoform, and COX-2 an inducible isoform? (
  • The inducible isoform of cyclooxygenase, COX-2, is an immediate-early response gene not expressed constitutively in most cells. (
  • A third isoform of COX (COX-3) has also been described but is not shown here. (
  • Cox-2 is the predominant isoform contributing to high levels of PGE 2 found in chronic inflammatory conditions ( 9 ). (
  • These results led Needleman and co-workers ( 7 ) to postulate the existence of a second, inflammatory-mediated COX isoform. (
  • Targeting selectivity for COX-2 reduces the risk of peptic ulceration , and is the main feature of celecoxib , rofecoxib and other members of this drug class. (
  • 1,2 Less is known about the interaction with rofecoxib. (
  • Compares the gastrointestinal adverse effects of celecoxib and rofecoxib cyclooxygenase-2 (COX-2) isoenzymes with traditional nonsteroidal anti-inflammatory drugs. (
  • Synthetic peptide corresponding to Human COX2/ Cyclooxygenase 2. (
  • This is a cross-sectional, controlled study designed to investigate the association of single nucleotide polymorphisms (SNPs) in the cyclooxygenase-2 (COX2) gene, also called prostaglandin endoperoxidase synthase 2 (PTGS2), on T-cell differentiation and function. (
  • Simple Western: COX-2 Antibody [NB100-689] - Simple Western lane view shows a specific band for COX2 in 1.0 mg/ml of Rat Brain at an antibody concentration of 1:100. (
  • OBJECTIVE- Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes. (
  • COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 protein and have five times greater COX-2 activity than cells expressing both glycoforms. (
  • COX-2 protein expression was examined by immunohistochemistry and Western analysis. (
  • COX-2 mRNA and protein production were increased following injury with increases in COX-2 mRNA production detectable at 2 h following injury. (
  • Increased levels of COX-2 protein were detectable for at least 48 h following traumatic spinal cord injury. (
  • We have reported that COX-2 mRNA and protein levels are elevated in colonic tumors that develop in rodents following carcinogen treatment ( 19 ) and in intestinal adenomas taken from Min mice ( 20 ). (
  • Caco-2 cells normally express barely detectable levels of the COX-2 protein, even following growth stimulation. (
  • We conducted a meta-analysis of relevant cohort studies to investigate the relationships between cyclooxygenase-2 (COX-2) protein and the prognosis of pancreatic cancer. (
  • Thus, COX-2 protein may be a useful biomarker for pancreatic cancer. (
  • Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBP alpha) and NF-kappa B binding sites. (
  • Cox 2 is a cellular protein that had been related to onset and development of cancer. (
  • Cyclooxygenase-2 mRNA expression increased three to sixfold during the period 24 h to 1 wk after induction of colitis, with marked increases in cyclooxygenase-2 protein expression in the lamina propria and muscularis of the colon during colitis. (
  • Cyclooxygenase-1 expression (mRNA and protein) was not affected by the induction of colitis. (
  • Protein expression of COX-1 and COX-2 in the kidney cortex, renal microvessels and glomeruli was studied. (
  • increased COX-2 protein expression was observed in the kidney cortex and microvessels of the Obese Zucker rats at 10-12 and 20-21 weeks of age. (
  • RNA binding studies, performed to identify ARE-binding regulatory factors, demonstrated binding of the translational repressor protein TIA-1 to COX-2 mRNA. (
  • The significance of TIA-1-mediated regulation of COX-2 expression was observed in TIA-1 null fibroblasts that produced significantly more COX-2 protein than wild-type fibroblasts. (
  • We previously identified an AU-rich element (ARE) within the 3′ untranslated region (3′UTR) of COX-2 mRNA that confers posttranscriptional regulation by controlling both mRNA decay and protein translation ( 4 , 5 ). (
  • The ability of this cis-acting mRNA element to regulate COX-2 protein levels and associated prostaglandin synthesis was observed in cells maintaining low to undetectable COX-2 levels ( 4 ). (
  • In contrast, AUF1/hnRNP D protein binding of the COX-2 ARE is proposed to regulate rapid mRNA decay similar to other ARE-containing transcripts ( 7 ). (
  • Thus, the relative abundance of these functionally distinct ARE-binding proteins can determine the fate of COX-2 transcript levels and impact COX-2 protein levels. (
  • We have identified the apoptosis-associated protein TIA-1 as a regulator of COX-2 expression at the posttranscriptional level. (
  • Through its ability to bind the COX-2 ARE, this RNA-binding protein acts as a translational silencer of COX-2 expression but does not affect mRNA stability. (
  • More importantly, deficiencies in TIA-1 mRNA binding are observed in colon cancer cells overexpressing COX-2 protein through increased polysome association with COX-2 mRNA. (
  • These findings suggest that misregulated association of the TIA-1 RNA-binding protein with COX-2 mRNA contributes to enhanced expression and perhaps the overall neoplastic potential of cancer cells. (
  • A COX-2 molecular model was used to locate the coding region polymorphisms relative to functional sites in the protein, and the COX-2 V511A polymorphism was very near to the active site. (
  • This variant protein was expressed, and function was evaluated, but no difference was detected in metabolism of the COX-2 substrates, arachidonic acid, linoleic acid, and 2-arachidonyl glycerol, compared with the wild type. (
  • Recent findings suggest that the prostaglandin E 2 , the proinflammatory product of elevated cyclooxygenase-2 activity in colon cancer, stimulates cancer cell growth through a G protein-dependent signaling pathway coupling the prostaglandin EP2 receptor to β-catenin control. (
  • In particular, the loss of a functional APC protein is one of the earliest events occurring in sporadic colon cancer, suggesting that APC may act as a gatekeeper of the colonic epithelium ( 2 ). (
  • The latter is a large scaffold protein that binds APC and β-catenin, which inhibits the β-catenin pathway by forming a molecular complex with glycogen synthase kinase-3β (GSK-3β), a kinase that phosphorylates β-catenin and targets it for degradation by the proteosome ( 2 , 7 ). (
  • COX-2 protein was present in 9 of 10 cases of adenocarcinoma of the pancreas but was undetectable in nontumorous pancreatic tissue. (
  • In cultured human pancreatic cancer cells, levels of COX-2 mRNA and protein were induced by treatment with tumor-promoting phorbol esters. (
  • These events are mainly mediated via PGE2, the predominant reaction product of COX-2, and the PGE2 subtype 2 receptor (EP2)-protein kinase A pathway. (
  • The actions of these COX-2 metabolites are likely mediated by mitogen-activated protein kinase (MAPK) and inositol 1,4,5-trisphosphate (IP3) signal transduction pathways. (
  • The present study did not confirm a direct relationship between the expressions of COX‑2 and MUC1, or between the expression of either protein and the clinicopathological features of patients, including survival. (
  • All together, our data suggest that biallelic MYH patients might benefit from NSAID treatment, because in these patients COX-2 is overexpressed in the whole colorectal mucosa, a finding possibly related to the interplay between COX-2 and APC protein being the APC gene a common target of mutations in MYH patients. (
  • Clinicopathologic studies have showed that COX-2 protein is weakly expressed in the normal mucosa of FAP patients ( 12 ) and overexpressed in 50% of adenoma and 80% to 90% of carcinoma in both sporadic and FAP patients ( 11 ), suggesting relationships between functionally based immunophenotypic findings and trial-based clinical evidence. (
  • The mechanism of NF-κB activation in the COX-1 -/- mice involved the up-regulation of protein expression of the p50 and p65 subunits of NF-κB, as well as the increased protein levels of phosphorylated IκBα and of phosphorylated IKKα/β. (
  • Treatment with EGF markedly induced COX-2 protein, COX-2 mRNA, and stimulated COX-2 promoter activity. (
  • In cultured cells and tissue, COX activity increased rapidly in response to mitogens and cytokines ( 4 , 5 , 6 ), although COX-1 mRNA and immunoreactive protein were not altered. (
  • In addition, chamomile caused reduction in LPS-induced COX-2 mRNA and protein expression, without affecting COX-1 expression. (
  • COX-2 protein, normally not expressed in the colon, was present and increased in polyp epithelium. (
  • Both the cyclooxygenase and the peroxidase active sites are located in the catalytic domain, which accounts for approximately 80% of the protein. (
  • The rats were treated with different doses of celecoxib (a COX-2-selective nonsteroidal anti-inflammatory drug) or were treated for different periods before or after fracture with celecoxib. (
  • Conclusions: COX-2-selective nonsteroidal anti-inflammatory drug therapy during the early stages of fracture repair significantly reduced fracture callus mechanical properties at later stages of healing and increased the proportion of nonunions in this animal model. (
  • Objective: The objective of this study was to investigate the renal effects of celecoxib, a cyclooxygenase-2 (COX-2) specific nonsteroidal anti-inflammatory drug (NSAID). (
  • [12] Moreover, a recent study with various malignant tumor cells showed that celecoxib could inhibit the growth of these cells, even though some of these cancer cells didn't even contain COX-2. (
  • Thus, COX-2 overexpression, which leads to high levels of epidermal prostaglandin E 2 , prostaglandin F 2α , and 15-deoxy Δ12,14 -PGJ 2 , is insufficient for tumor induction but transforms epidermis into an "autopromoted" state, i.e., dramatically sensitizes the tissue for genotoxic carcinogens. (
  • Although COX-1 expression does not change in the course of tumor development, aberrant expression of COX-2 is also a consistent feature of nonmelanoma skin cancer in man and mice. (
  • Data from gene knockout ( 13 , 14 ) and transgenic mice ( 15 , 16 ) provide support for the hypothesis that there is a causal relationship between COX-2 overexpression and tumor development. (
  • This multistage model allows the analysis of the carcinogenic process in terms of distinct stages, i.e., initiation by application of a subcarcinogenic dose of a carcinogen such as 7,12-dimethylbenz[ a ]anthracene (DMBA), promotion by repeated applications of a tumor promoter such as phorbol 12-myristate 13-acetate (PMA), and malignant progression, which may occur spontaneously or after administration of additional carcinogen ( 2 ). (
  • As shown here, overexpression of COX-2 targeted to basal keratinocytes contributes to skin-tumor promotion and progression by establishing an autopromoted skin phenotype, i.e., the initiating dose of DMBA is sufficient to induce skin carcinogenesis in COX-2 transgenic mice. (
  • An elevated expression of COX-2 as the inducible form of the cyclooxygenases was detected in 36% of tumors and was significantly associated with several clinicopathological parameters, for example positive nodal status, poor differentiation and larger tumor size. (
  • In contrast, an increased expression of COX-1 was detected in 45% of breast carcinomas and was associated with smaller tumor size and negative nodal status. (
  • Gonadotropins induce tumor cell migration and invasion by increasing cyclooxygenases expression and prostaglandin E(2) production in human ovarian cancer cells. (
  • COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. (
  • Because inflammatory mechanisms influence vitreal neovascularization and cyclooxygenase (COX)-2 promotes tumor angiogenesis, we investigated the role of COX-2 in ischemic proliferative retinopathy. (
  • 10 It has also been shown that prostanoids, notably prostaglandin E 2 (PGE 2 ), stabilize the hypoxia-inducible factor 11 and stimulate expression of basic regulators of angiogenesis, including vascular endothelial growth factor (VEGF) in tumor endothelium, 8 resulting in endothelial cell proliferation. (
  • In all types of OA, mechanical stress and overuse result in stimulation of proinflammatory cytokines like TNF- α (tumor necrosis factor) and matrix metalloproteinases (MMPs) [ 2 - 4 ]. (
  • Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. (
  • In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. (
  • The fluorescent compound has adequate physicochemical properties to penetrate freely into living cells and allow direct imaging of COX-2 in four different mouse models: (a) liver metastasis model, (b) xenograft model, (c) C57BL/6 lung tumor model, and (d) min mouse intestinal polyp model. (
  • It is noteworthy that in an in vivo mouse xenograft model, indomethacin blocked 92.6% (Ã'±1.5%) of the COX-2 expressing tumor uptake of the lead compound. (
  • COX-2 also appears to play a role in tumor biology. (
  • The development of colon cancer results from the sequential accumulation of activating mutations in oncogenes, such as ras , and inactivating mutations, truncations, or deletions in the coding sequence of several tumor suppressor genes, including p53 and adenomatous polyposis coli ( APC ), together with aberrant activity of molecules controlling genomic stability ( 2 ). (
  • Whereas COX-1 is expressed at relatively constant levels in numerous tissues, the expression of COX-2 is normally low or absent in most cells and tissues but rapidly up-regulated by proinflammatory cytokines and tumor promoters ( 14 ). (
  • Tumor cells of MYH -associated polyposis (MAP) therefore contain an excess of somatic G:C → T:A transversions, mainly in the APC gene ( 2 , 6 ). (
  • COX-2 expression has also been implicated in tumor angiogenesis. (
  • Dr. Blanke said that COX-2 is expressed in human colorectal cancer neovasculature, including liver metastases, and that expression in the neovasculature is actually greater than in the tumor cells. (
  • COX-2 is also thought to play a role in survival of tumor cells after radiation therapy. (
  • In this study, we aimed to investigate the associations between COX-2, PGE 2 and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. (
  • COX-2, PGE 2 and NO levels depended on the tumor grade of the cells, being the highest in Duke's stage III colon carcinoma. (
  • Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE 2 amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. (
  • 4) The expression of COX-2 was significantly correlated with Helicobacter pylori infection, clinical stage, depth of invasion and tumor size (P (
  • Conclusions: Expressions of CD97, NF-κB and COX-2 were correlated with tumor invasion and metastasis in gastric MALT lymphoma. (
  • COX-2 is usually absent in majority of normal tissues, but can be induced in response to tumor promoters, carcinogens, citocines and growth factors. (
  • Thus, the literature shows increasing evidence that overexpression of the COX-2 plays an important role in tumor growth and spread of tumors by interfering with different biological processes such as cell proliferation, cellular adhesion, immune surveillance, apoptosis, and angiogenesis. (
  • Our results indicate a direct link between COX-2 and activation of matrix degrading metalloproteinase enzymes. (
  • COX enzymes metabolize arachidonic acid, forming prostaglandin H2, which is subsequently metabolized by prostaglandin E synthase into prostaglandin E2 (PGE2) [ 9 , 10 ]. (
  • Cyclooxygenases (COX)-1 and -2 are the key enzymes in the conversion of arachidonic acid to prostaglandin (PG) H 2 , the precursor of a diverse family of bioactive lipid mediators including PGs, thromboxane, and prostacyclin ( Hamberg and Samuelsson, 1973 ). (
  • Cyclooxygenase (Cox) enzymes catalyze a bisoxygenase reaction in which arachidonic acid is converted to PGH 2 , the common precursor to all prostanoids, including PGE 2 , PGD 2 , PGF 2α , PGI 2 , and thromboxane. (
  • Researchers were surprised at the results because Drosophila do not have COX-2 enzymes. (
  • To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A 2 enzymes (cPLA 2 and sPLA 2 ), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and − 2) in wild type and COX-1 -/- mice. (
  • There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-κB pathway, and also an increase in the upstream cPLA 2 and sPLA 2 enzymes. (
  • Additionally, COX-1 deficiency can affect the expression of reciprocal and coupled enzymes, COX-2, Ca 2+ -dependent PLA 2 , and terminal mPGES-2, to overcome defects in brain AA cascade. (
  • Since PGE 2 and other prostanoids are formed by both constitutive COX-1 and induced COX-2, the effect on the lung may partly reflect the relative activities of each NSAID on the enzymes. (
  • Our own investigations were on COX-1 and COX-2 sheep pure enzymes, and human gastric mucosa (constitutive COX-1) and leucocytes (induced COX-2). (
  • Expression of recombinant enzymes and determination of the crystal structure of COX-2 have provided insights into the observed physiologic and pharmacologic similarities to and differences from COX-1 ( 10 , 11 ). (
  • The tertiary and quaternary structures of PTGS1 (COX-1) and PTGS2 (COX-2) enzymes are almost identical. (
  • PTGS1 (COX-1) and PTGS2 (COX-2) are bifunctional enzymes that carry out two consecutive chemical reactions in spatially distinct but mechanistically coupled active sites. (
  • One NSAID that selectively inhibits COX-2, celecoxib, is currently approved by the US Food and Drug Administration (FDA). (
  • Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). (
  • Overall, our data suggest that COX-1 and COX-2 play a distinct role in brain PG biosynthesis, with basal PGE 2 production being metabolically coupled with COX-2 and TXB 2 production being preferentially linked to COX-1. (
  • Methods and Results- In the present study, selective depletion of COX-2 in vascular smooth muscle cells and endothelial cells depressed biosynthesis of prostaglandin I 2 and prostaglandin E 2 , elevated blood pressure, and accelerated atherogenesis in Ldlr knockout mice. (
  • Deletion of COX-2 in vascular smooth muscle cells and endothelial cells coincided with an increase in COX-2 expression in lesional macrophages and increased biosynthesis of thromboxane. (
  • In contrast to the constitutively and ubiquitously expressed COX-1, COX-2 is not expressed in most tissues but becomes transiently induced in response to growth factors, proinflammatory cytokines, mechanical tissue damage, and UV light ( 1 , 3 ). (
  • The Caco-2 cells, which constitutively expressed COX-2, acquired increased invasiveness compared with the parental Caco-2 cells or the vector transfected control cells. (
  • We found that the Caco-2 cells, programmed to constitutively expressed COX-2, acquired increased invasiveness compared with the parental Caco-2 cells or the vector transfected control cells. (
  • 2 COX-2 is expressed constitutively in some organs, such as brain, but is markedly upregulated by a wide variety of stimuli, most notably inflammatory mediators. (
  • COX-2 is constitutively expressed in only a few cells but is rapidly upregulated in response to any kind of insult,' Dr. Blanke said. (
  • Mitomycin-C (Mutamycin) induces COX-2 in MKN-74 gastric cancer cells, and this induction causes cellular resistance to apoptosis. (
  • To delineate COX-2 functions for carcinogenesis, we have used the initiation-promotion model ( 2 ) for the induction of skin tumors in wild-type (wt) NMRI mice and COX-2 transgenic mouse lines. (
  • COX-2 is expressed at high levels in intestinal tumors in humans and rodents. (
  • 7 COX-2 exerts an angiogenic effects in tumors 8,9 and in corneal neovascularization. (
  • Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. (
  • Therefore, to clarify additionally the prognostic role of Cox-2 in colorectal carcinoma and to evaluate the possible contribution of isoenzyme Cox-1, we immunohistochemically determined the expression of both proteins in a series of patients with primary tumors, who were treated at our institution. (
  • Studies of breast, colon, and pancreatic cancers have led researchers to believe COX-2 plays a key role in the development and growth of tumors. (
  • COX-2 expression is increased in many tumors, including 76% of colorectal cancers [CRC]. (
  • Furthermore, the expression of COX-2 might shed some light over the physiopathology and clinical behavior of tumors of the head and neck, including benign odontogenic neoplasms of the jaws with an aggressive behavior, such as keratocystic odontogenic tumors (KCOT). (
  • Patients with high COX-2-expressed tumors had shorter overall survival, but it was not statistically significant. (
  • PTGS2 (COX-2), converts arachidonic acid (AA) to prostaglandin endoperoxide H2. (
  • First, hydrogen is abstracted from carbon 13 of arachidonic acid, and then two molecules of oxygen are added by the PTGS2 (COX-2), giving PGG2. (
  • PTGS2 (COX-2) exists as a homodimer, each monomer with a molecular mass of about 70 kDa. (
  • It has been found that human PTGS2 (COX-2) functions as a conformational heterodimer having a catalytic monomer (E-cat) and an allosteric monomer (E-allo). (
  • Reporting their findings in Science , Fitzgerald, together with first author Dr Yan Cheng (University of Pennsylvania) and colleagues, explain how they wanted to clarify the interplay of the two products of the cyclooxygenases - thromboxane (TxA 2 ) and prostacyclin (PGI 2 ) - in the cardiovascular system. (
  • thromboxane B 2 . (
  • We found that brain PGE 2 concentration was significantly increased, whereas thromboxane B2 (TXB 2 ) concentration was decreased in COX-1 -/- mice. (
  • Expression of cyclooxygenase-2 in ovarian serous carcinoma: correlation with angiogenesis, nm23 expression and survival. (
  • OBJECTIVE: To evaluate the expression of cyclooxygenase (COX)-2 in ovarian serous carcinomas (OSC) and its correlation with microvessel density (MVD), nm23 expression, clinicopathologic prognostic factors and survival. (
  • In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). (
  • A large body of evidence suggests that cyclooxygenase-2 (COX-2) is important in gastrointestinal cancer. (
  • The mouse COX-2 gene was cloned by UCLA scientist Harvey Herschman, a finding published in 1991. (
  • COX-2 gene promoter haplotypes and prostate cancer risk. (
  • However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. (
  • Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. (
  • Our findings disclose an important role for this immediate-early gene product in proliferative retinopathy mediated (at least in part) by PGE 2 mostly via prostaglandin E receptor 3 (EP 3 ) through a previously undescribed action involving thrombospondin-1 (TSP-1) and CD36. (
  • The COX-2 gene may help decide the balance of cell types that the body makes as part of the immune system. (
  • To study how the COX-2 gene works in the body s immune system. (
  • We sequenced the COX-2 gene of 72 individuals and identified rare polymorphisms in the promoter and the coding region. (
  • MYH is a base excision repair gene which removes adenines mispaired with 8-oxo-7,8-hydroxy-2′-deoxyguanosine (a particularly stable product of oxidative DNA damage) preventing somatic G:C → T:A transversion mutations ( 5 ). (
  • COX-1 is a housekeeping gene with essentially constant levels of expression. (
  • Shortly after the Needleman hypothesis was formulated, Xie and co-workers ( 8 ) detected the presence of a second avian COX mRNA species, and Kujubu and co-workers ( 9 ) identified a phorbol ester-activated immediate early murine gene (TIS10) that possesses similar COX activity but shares only approximately 66% homology in amino acid sequence. (
  • Genetic and pharmacological evidence suggests that overexpression of cyclooxygenase-2 (COX-2) is critical for epithelial carcinogenesis and provides a major target for cancer chemoprevention by nonsteroidal antiinflammatory drugs. (
  • Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. (
  • Several lines of evidence demonstrate that unregulated COX-2 expression occurs at multiple stages in colon carcinogenesis and is important in the promotion of tumorigenesis ( 1 , 2 ). (
  • Multiple lines of evidence suggest that COX-2 is important in carcinogenesis. (
  • In addition to the genetic evidence implicating COX-2 in carcinogenesis, there are supporting pharmacological data. (
  • These findings highlight the role of COX-2 and Ki-67 in carcinogenesis, but do not confirm the relationship between COX-2 expression and increased cell proliferation in dogs. (
  • COX-2 may play a role in carcinogenesis, but this pathway is not responsible for cellular proliferation in actinic keratosis and cutaneous SCC in dogs. (
  • Upregulation of COX-2 expression has been demonstrated in several neoplasms in dogs, as well as its role in carcinogenesis [14]. (
  • However, tight molecular regulation allows for rapid COX-2 expression and increased prostaglandin synthesis when necessary. (
  • COX-2 activity is primarily responsible for PG synthesis in the central nervous system and inflammatory cells. (
  • Two Cox isoforms are known: a "constitutive" type (Cox-1) that supports prostanoid synthesis for tissue homeostasis and an inducible form (Cox-2) that is expressed in response to cytokines, growth factors, and some infectious agents ( 8 ). (
  • 5,6 In rodents as in humans, cerebral ischemia upregulates COX-2 expression in neurons, glia, vascular cells, and in inflammatory cells invading the ischemic brain. (
  • Moreover, COX-2 has been prominent in actinic keratosis, SCC and Bowen's disease in humans. (
  • In humans it is one of two cyclooxygenases. (
  • Cyclooxygenase2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers. (
  • We found that mice heterozygous for Cox-2, but not for microsomal prostaglandin E synthase-1 (mPGES-1), displayed attenuated fever, indicating a rate limiting role of Cox-2. (
  • These studies demonstrate that constitutive expression of COX-2 can lead to phenotypic changes that alter the metastatic potential of colorectal cancer cells. (
  • We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. (
  • Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients. (
  • In colorectal cancer (CRC), pathological factors that correlate with negative prognosis include, among others, overexpression of cyclooxygenase‑2 (COX‑2) and abundant expression of mucin 1 (MUC1). (
  • In 2018, colorectal cancer (CRC) was the cause of 881,000 deaths ( 2 ). (
  • COX-2 expression is also associated with risk of colorectal cancer recurrence. (
  • Transgenic mouse lines with keratin 5 promoter-driven COX-2 overexpression in basal epidermal cells exhibit a preneoplastic skin phenotype. (
  • Recently, we have shown that the keratin 5 (K5) promoter-driven overexpression of COX-2 in basal cells of interfollicular epidermis and the pilosebaceous unit led to a preneoplastic skin phenotype in 4 of 4 high-expression mouse lines ( 15 ). (
  • COX‑2 overexpression may therefore be associated with MUC1 overexpression. (
  • In CRCs overexpression of COX-2 has been shown to correlate with poor survival and metastasis ( 6 ). (
  • The overexpression of COX-2 and the overexpression of MUC1 might be related and this relationship has already been studied in pancreatic cancer ( 11 ). (
  • In addition, MUC1 has been proposed as an alternative target for blocking COX-2 overexpression ( 11 ). (
  • COX-2 overexpression is significantly associated with metastasis, and transfection of COX-2 into human Caco-2 cells greatly increases their metastatic potential. (
  • Dr. Blanke said that COX-2 overexpression is significantly correlated with metastases, and particularly with hematogenous metastasis in patients with resected large bowel malignancies. (
  • Nevertheless, the tumorigenic mechanisms of COX-2 overexpression still remain poorly understood and may include mechanisms that may act at different stages of the disease. (
  • 6 Prostanoids are synthesized principally via activities of COX-1 and COX-2. (
  • However, although COX-2 was initially regarded as a source of pathological prostanoids only, recent studies have indicated that this isoenzyme mediates a variety of physiological responses within the organism. (
  • 3 The COX reaction product PGH 2 is converted into 5 different prostanoids by a corresponding number of isomerases ( Figure ), the distribution of which is cell and organ specific. (
  • 2 Thus, PGH 2 can give rise to different prostanoids depending on the isomerases available to metabolize it. (
  • Arachidonic acid is metabolized by COX-1 and COX-2 into PGH 2 , which is metabolized further by distinct isomerases into 5 prostanoids. (
  • Because of the cellular and subcellular compartmentation of COX isoforms and isomerases, the prostanoids linked to the enzymatic activity of COX-1 or COX-2 vary from cell type to cell type. (
  • Both nitric oxide (NO) and cyclooxygenase (COX) metabolites are recognized as paracrine factors of renal microvascular function. (
  • 2 3 Because the TGF mechanism contributes to afferent arteriolar autoregulation, 4 5 6 nNOS also exerts a counteracting modulatory influence on the afferent arteriolar autoregulatory responses to changes in renal perfusion pressure (RPP). (
  • 15 In addition, we recently demonstrated that renal vasodilator responses to NO are partially mediated by the production of vasodilatory metabolites, which is caused by the increased activity of COX-2. (
  • COX-2 regulation and its association with renal damage are not known in the Obese Zucker rat. (
  • Furthermore, glucocorticoid administration was shown to decrease COX activity in peritoneal macrophages after lipopolysaccharides ( 7 ) but not to affect constitutive renal medullary COX activity. (
  • Identification of the pattern of distribution of COX-2 in the kidney has also begun to resolve previous conundrums concerning renal prostanoid physiology. (
  • Alterations in renal hemodynamic function are prevalent in diabetes ( 1 , 2 ) and include increased intraglomerular capillary pressure and hyperfiltration ( 3 - 5 ). (
  • COX-1 modulates physiologic responses such as regulation of renal and vascular homeostasis [13]. (
  • Two isoforms of COX have been characterized, COX-1 and COX-2. (
  • In this study, we investigated the prognostic impact of expression of both COX-isoforms as well as the association of COX expression and other clinicopathological parameters in primary breast cancer. (
  • In the early 1990s, COX was demonstrated to exist as two distinct isoforms. (
  • 2 Three isoforms of COX have been described. (
  • 7,11 In addition, ischemic injury is attenuated in COX-2-deficient mice and is exacerbated in transgenic mice overexpressing COX-2. (
  • At therapeutic doses, they do not affect COX-1, which helps regulate normal cell function in the stomach and blood. (
  • In this article, we briefly review the role of COX-2 in ischemic brain injury and re-examine the validity of the COX-2 pathway as a therapeutic target for ischemic stroke. (
  • Immunohistochemistry-Paraffin: COX-2 Antibody [NB100-689] - Formalin fixed paraffin embedded colon carcinoma stained with COX-2 antibody (NB100-689). (
  • These findings reveal that acetaminophen, similar to aspirin and other non-steroidal anti-inflammatory drugs, is antipyretic by inhibiting cyclooxygenase-2, and not by inhibiting mPGES-1 or signaling cascades downstream of prostaglandin E 2 . (
  • The widespread use of nonsteroidal anti-inflammatory drugs and Cox-2-selective inhibitory drugs may therefore reduce vaccine efficacy, especially when vaccines are poorly immunogenic or the target population is poorly responsive to immunization. (
  • Nonsteroidal anti-inflammatory drugs inhibit COX-2 function and in so doing can impair fracture-healing. (
  • Similarly, mice that overexpressed receptors for TxA 2 also produced these exaggerated effects. (
  • This is because knockout PGI 2 mice do not naturally develop thrombosis, he explained, but "if you induce thrombosis in these animals by other means, the lack of this receptor renders them more susceptible to thrombosis. (
  • In the murine model, C57BL/6 mice at postnatal day (P) 7 were exposed, with their mothers, for 5 days to hyperoxic conditions (75% O 2 ), inducing vaso-obliteration of the central retinal vasculature. (
  • Their analyses revealed that the nimesulide diet greatly reduced the number of late-stage PanINs in KrasG12D (10 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on nimesulide diet versus 40 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on normal diet). (
  • However, when the same dose of acetaminophen was given to Cox-2 heterozygous mice, the febrile response to lipopolysaccharide was strongly attenuated, resulting in an almost normalized temperature curve, whereas no difference was seen between wild-type and heterozygous mPGES-1 mice. (
  • Cox-2-deficient mice produce 70% less IgG, 50% fewer Ab-secreting cells, and 10-fold less neutralizing Ab to HPV 16 VLP vaccination compared with wild-type mice. (
  • The reduction in Ab production by Cox-2 −/− mice was partially due to a decrease in class switching. (
  • Genetic approaches using Cox-2-deficient (Cox-2 −/− ) mice have contributed to a clearer understanding of the physiological and pathological roles of Cox-2 ( 10 , 11 , 12 , 13 ). (
  • Cyclooxygenase-2 expression in skeletal muscle of knockout mice suffering Duchenne muscular dystrophy. (
  • The purpose of the present study was to investigate the role of cyclooxygenase-2 (COX-2) expression in fibrotic lesion in mdx mice. (
  • 3 - 5 Consistent with this observation, deletion of the PGI 2 receptor fosters initiation and early development of atherogenesis in hyperlipidemic mice, 6 , 7 offering a potential mechanism for risk transformation during chronic drug exposure. (
  • In recent years, several additional intracellular components (besides COX-2) were discovered that appear to be important for mediating the anticancer effects of celecoxib in the absence of COX-2. (
  • 1 - 3 The introduction of new anti-inflammatory agents, with more specific inhibitory effects on cyclo-oxygenase 2 (COX 2) pathways, promised equivalent efficacy with greater safety and tolerability. (
  • To test this hypothesis, afferent arteriolar autoregulatory responses to increases in RPP were assessed under conditions of normal and inhibited COX-2 activity with the blood-perfused juxtamedullary nephron technique combined with videomicroscopy. (
  • Tobacco smoke increases the levels of Cox 2. (
  • We recently reported that activated human B lymphocytes express Cox-2 following polyclonal stimulation ( 14 ). (
  • shRNA-targeted cyclooxygenase (COX)-2 inhibits proliferation, reduces invasion and enhances chemosensitivity in laryngeal carcinoma cells. (
  • Primarily inhibits COX-2. (
  • The expression of COX-1 and -2 was determined by immunohistochemistry retrospectivly in a cohort of 221 women. (
  • Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in pancreatic tissue. (
  • Here we evaluated, by immunohistochemistry and mRNA analysis, the COX-2 expression in adenomas, synchronous adenocarcinomas, and healthy mucosa (surrounding the malignant lesion or at the resection margin) in patients with no evidence of germ line APC mutations but carrying germ line MYH mutations. (
  • COX-2 expression was assessed by immunohistochemistry. (
  • Immunohistochemistry revealed COX-2 in malignant epithelial cells. (
  • The expression of COX-2 in postoperative intra-abdominal adhesions and normal peritoneal tissue was examined by immunohistochemistry and Western blot analysis. (
  • Immunohistochemistry was performed on sections using antibodies for BMPR1A and COX-2. (
  • METHODS: Specimens from 44 patients with OSC were evaluated by immunohistochemistry for COX-2 and nm23 expression. (
  • [14] Some of these analogs retained COX-2 inhibitory activity, whereas many others didn't. (
  • 1. A composition comprising an effective amount of curcumin and an effective amount of andrographolide, wherein the ratio of curcumin and andrographolide is from 1:10 to 10:1, said composition having at least 5 times less inhibitory activity on cyclooxygenase-1 (COX-1) than on cyclooxygenase-2 (COX-2). (
  • The data of this study show a prognostic role of COX-2 expression. (
  • Although we could not confirm the prognostic significance of Cox-2 expression in the present cohort of OSC patients, the p value for overall survival was just slightly greater than alpha, and this result can be referred as almost significant. (
  • Further studies involving a larger number of patients are needed to clarify the prognostic significance of COX-2 expression in ovarian carcinomas. (
  • COX-2 is expressed in the epithelial cells of high-grade prostatic intraepithelial neoplasia and cancer. (
  • Immunohistochemical analysis showed that COX-2 was expressed in malignant epithelial cells. (
  • Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) is an important target for preventing epithelial malignancies. (
  • Human colon cancer cells (Caco-2) were permanently transfected with a COX-2 expression vector or the identical vector lacking the COX-2 insert. (
  • The aim of the present study was to investigate the effect of constitutive COX-2 expression in human colon cancer cells on the invasive potential of these cells. (
  • Colon cancer cells demonstrated to overexpress COX-2 through increased polysome association with COX-2 mRNA also showed defective TIA-1 binding both in vitro and in vivo. (
  • In contrast, COX-2 expression is found in only 8% of normal colon tissue specimens. (
  • Cyclooxygenases (COX), prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. (
  • The optimal immobilization process was as follows: about 0.02 g of aminated silica gel microspheres was activated by 0.25% GA solution for 6 h and mixed with 5 U of free recombinant COX-2 solution. (

No images available that match "cyclooxygenase 2"