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Results for “Cyclooxygenase 2 Inhibitors”

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At least 19 recordsLinked to original sources

PubMed2002

Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors.

OBJECTIVE: Selective cyclooxygenase 2 (COX-2) inhibitors are now being used as antiinflammatory agents that cause fewer gastrointestinal complications, compared with other antiinflammatory drugs, in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether selective COX-2 inhibitors could induce apoptosis of RA synovial fibroblasts (RASFs). METHODS: RASFs were exposed to selective COX-2 inhibitors, i.e., celecoxib, etodolac, meloxicam, nimesulide, N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide, and rofecoxib, under various conditions. Cell proliferation and cell viability were assessed by incorporation of 5-bromo-2'-deoxyuridine and by the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, respectively. Apoptosis was detected by identifying DNA fragmentation. Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) was measured by the luciferase reporter gene assay with a PPAR response element-driven luciferase reporter plasmid and a PPARgamma expression plasmid. RESULTS: Celecoxib strongly inhibited the proliferation of RASFs, whereas other selective COX-2 inhibitors had little or no effect. In addition, celecoxib reduced the viability of RASFs by induction of apoptosis, in a concentration-dependent manner. This action was abolished by addition of caspase inhibitors. Interleukin-1beta had a weak enhancing effect on celecoxib-induced apoptosis in RASFs. In contrast, other selective COX-2 inhibitors at concentrations up to 100 microM did not induce apoptosis of RASFs. Indomethacin, a nonselective COX inhibitor, activated PPARgamma transcription, while celecoxib did not. CONCLUSION: Celecoxib suppressed the proliferation of RASFs by COX-2-independent and PPARgamma-independent induction of apoptosis. Although the mechanism involved remains unclear, celecoxib may have not only antiinflammatory activity, but also a disease-modifying effect on rheumatoid synovial proliferation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Inhibition of the expression of alpha-smooth muscle actin in human hepatic stellate cell line, LI90, by a selective cyclooxygenase 2 inhibitor, NS-398.

Cyclooxygenase 2 (COX-2) has been thought to be associated with liver fibrosis whereas it is well known that hepatic stellate cells (HSC) play a central role in the pathogenesis of liver fibrosis. There is little evidence of how COX-2 regulates the activation of human HSC or the mechanism involved. In this study, we investigated the effect of a COX-2 inhibitor, NS-398, on a line of human HSC, LI90. Our findings demonstrated that alpha-smooth muscle actin (alpha-SMA) protein expression was inhibited in a dose-dependent manner by treatment with NS-398. Proliferation cell nuclear antigen (PCNA) expression and cell growth were partially down-regulated. The generation of PGE2, IL-8, IL-6, and hyaluronan in the cultured medium was also inhibited. In conclusion, our findings imply that a selective COX-2 inhibitor might be a potential drug for the chemoprevention and treatment of liver fibrosis by inhibiting the activation of HSC.

Actins↗

PubMed2005

Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via a Bcl-2 independent pathway.

NS-398, a selective inhibitor of cyclooxygenase 2 (COX-2), has been reported to inhibit growth and induce apoptosis in several cancer cell lines that overexpress COX-2. However it has not been extensively studied in multiple myeloma (MM). Here, we studied the effects of COX-2 inhibitors on MM cell lines and primary myeloma patient cells. We investigated the effects of NS-398 on proliferation and apoptosis in three myeloma cell lines (PCM6, U266 and RPMI8226) and isolated CD138-positive cells from MM patients. Furthermore, the combined effects of NS-398 plus dexamethasone (Dex) or thalidomide (Thal) were investigated. All myeloma cell lines express COX-2. NS-398 inhibited growth and induced apoptosis in PCM6, RPMI8226 and CD138-positive MM cells in a time- and dose-dependent manner. At low concentrations (10 microM), NS-398 primarily induced growth arrest without affecting cell viability, but at higher concentrations (over 25 microM), apoptosis was induced. During the process of apoptosis, the number of Fas-positive cells increased. Downstream signals of Fas, such as caspase 8, 3 and 9, were also activated. On the other hand, protein levels of the Bcl-2 family did not change, although mitochondrial transmembrane potential ((Delta)(psi)m) was decreased. Combined incubation with Dex or Thal enhanced NS-398-induced growth inhibition and apoptosis in RPMI8226 cells. The combined effect of Dex was more potent than that of Thal. Our findings suggests that COX-2 plays an important role in regulation of apoptosis in myeloma cells, and COX-2 inhibitors might serve as an effective tool for future chemoprevention and/or treatment of myeloma.

Apoptosis↗

PubMed2003

Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial.

CONTEXT: Controlling postoperative pain after knee replacement while reducing opioid-induced adverse effects and improving outcomes remains an important challenge. OBJECTIVE: To assess the effect of combined preoperative and postoperative administration of a selective inhibitor of cyclooxygenase 2 on opioid consumption and outcomes after total knee arthroplasty (TKA). DESIGN, SETTING, AND PATIENTS: Randomized, placebo-controlled, double-blind trial conducted June 2001 through September 2002, enrolling 70 patients aged 40 to 77 years and undergoing TKA at a university hospital in the United States. INTERVENTIONS: Patients were randomly assigned to receive 50 mg of oral rofecoxib at 24 hours and at 1 to 2 hours before TKA, 50 mg daily for 5 days postoperatively, and 25 mg daily for another 8 days, or matching placebo at the same times. MAIN OUTCOME MEASURES: Postoperative outcomes including postsurgical analgesic consumption and pain scores achieved, nausea and vomiting, joint range of motion, sleep disturbance, patient satisfaction with analgesia, and hematologic and coagulation parameters. RESULTS: Total epidural analgesic consumption and in-hospital opioid consumption were less in the group receiving rofecoxib compared with the group receiving placebo (P<.05). Median pain score (visual analog scale [VAS], 0-10) achieved for the knee was lower in the rofecoxib group compared with the placebo group during hospital stay (2.2 [interquartile range [IQR], 1.4-3.2] vs 3.5 [IQR, 2.7-4.3], P<.001) and 1 week after discharge (2.6 [IQR, 1.4-3.5] vs 3.7 [IQR, 2.9-4.7], P =.03). There was less postoperative vomiting in the rofecoxib group (6%) compared with the placebo group (26%) (P =.047), as well as a decrease in sleep disturbance compared with the placebo group on the night of surgery (P =.006) and on the first (P =.047) and second (P<.001) days postoperatively. Knee flexion was increased in the rofecoxib group compared with the placebo group at discharge (active flexion: mean [SD], 84.2 degrees [11.1 degrees ] vs 73.2 degrees [13.6 degrees ], P =.03; passive flexion: 90.5 degrees [6.8 degrees ] vs 81.8 degrees [13.4 degrees ], P =.05) and at 1 month postoperatively (109.3 degrees [8.5 degrees ] vs 100.8 degrees [11.8 degrees ], P =.01), with shorter time in physical therapy to achieve effective joint range of motion. The rofecoxib group was more satisfied with analgesia and anesthesia at discharge compared with the placebo group (median satisfaction score, 4.3 [IQR, 3.0-4.7] vs 3.3 [IQR, 2.3-4.3], respectively; P =.03), and the differences persisted at 2-week and at 1-month follow-up. There was no intergroup difference in surgical blood loss (P>.05 for both intraoperative and postoperative blood loss). CONCLUSION: Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia that reduces opioid consumption, pain, vomiting, and sleep disturbance, with improved knee range of motion after TKA.

Adult↗

PubMed1998

The effects of cyclooxygenase 2 inhibitors on cartilage erosion and bone loss in a model of Mycobacterium tuberculosis-induced monoarticular arthritis in the rat.

Selective cyclooxygenase 2 (COX 2) inhibitors NS-398 and nimesulide were investigated for their effects on patellar cartilage and bone content in a model of Mycobacterium tuberculosis (M.tb)-induced monoarticular arthritis in the rat. The protective/destructive properties of these nonsteroidal antiinflammatory drugs (NSAIDs) were compared with piroxicam, known to accelerate cartilage breakdown and reduce bone erosion in this model in comparison to untreated arthritic controls. Male CFHB Wistar rats were injected intraarticularly with heat killed M.tb into the left stifle joint, resulting in loss of patellar cartilage glycosaminoglycans (GAG), bone erosion and inflammation. The right stifle joint received saline. Animals were dosed daily, p.o., with NS-398 (1, 10 mg/kg), nimesulide (0.5, 5 mg/kg) or piroxicam (10 mg/kg). Four days after M.tb injection, patellar GAG content, bone weight and joint swelling were measured in drug-treated animals and untreated arthritic controls. Changes in the left joint were compared to the right. The expression and distribution of COX 2 protein was determined by immunocytochemistry in synovial tissue from arthritic controls over the time course. Focal accumulations of inflammatory cells were positively immunolabelled for COX 2 in the synovium from the left stifle joint of untreated arthritic animals, 6 h after injection of M.tb. Labeling of inflammatory cell infiltrates increased and was widespread in the synovium at 24 h. By day 4 fibroblasts were positively labelled for COX 2 in addition to polymorphonuclear and mononuclear leukocytes. Piroxicam and nimesulide at the higher dose significantly exacerbated M.tb-induced cartilage GAG loss while NS-398 was without effect. Both COX 2 inhibitors did not alter M.tb-induced patellar bone loss. In contrast, piroxicam significantly reduced bone loss. All COX inhibitors significantly reduced joint swelling. In conclusion, the selective inhibition of COX 2 may result in the amelioration of synovitis with a lowered risk of NSAID-induced cartilage damage in rheumatic disease.

Animals↗

PubMed2000

Thrombosis in patients with connective tissue diseases treated with specific cyclooxygenase 2 inhibitors. A report of four cases.

Specific inhibitors of cyclooxygenase 2 (COX-2) have been approved for the treatment of osteoarthritis and rheumatoid arthritis. Unlike nonsteroidal anti-inflammatory drugs, specific COX-2 inhibitors do not inhibit platelet activation. However, these agents significantly reduce systemic production of prostacyclin. As a result, theoretical concerns have been raised that specific COX-2 inhibitors could shift the hemostatic balance toward a prothrombotic state. Patients with connective tissue diseases (CTD), who may be predisposed to vasculopathy and thrombosis, often have arthritis or pain syndromes requiring treatment with antiinflammatory agents. Herein we describe 4 patients with CTD who developed ischemic complications after receiving celecoxib. All patients had a history of Raynaud's phenomenon, as well as elevated anticardiolipin antibodies, lupus anticoagulant, or a history compatible with antiphospholipid syndrome. It was possible to measure a urinary metabolite of thromboxane A2 in 2 of the patients as an indicator of in vivo platelet activation, and this was markedly elevated in both. In addition, the patients had evidence of ongoing inflammation as indicated by elevated erythrocyte sedimentation rate, hypocomplementemia, and/or elevated levels of anti-DNA antibodies. The findings in these 4 patients suggest that COX-2 inhibitor-treated patients with diseases that predispose to thrombosis should be monitored carefully for this complication.

Adult↗

PubMedDate not supplied

Effects of intravenous administration of FR122047 (a selective cyclooxygenase 1 inhibitor) and FR188582 (a selective cyclooxygenase 2 inhibitor) on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits.

PURPOSE: Two isoforms of cyclooxygenase (COX-1 and COX-2) exist. To determine in vivo effects of the intravenous administration of FR122047 (a selective COX-1 inhibitor), FR188582 (a selective COX-2 inhibitor), diclofenac sodium or dexamethasone phosphate disodium on prostaglandin-E2 (PGE2)-induced aqueous flare elevation and mRNA levels for COX-1 and COX-2 in pigmented rabbits. METHODS: To produce aqueous flare elevation in rabbits, PGE2, 25 microg/ml, was applied to the cornea with the use of a glass cylinder. FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium was intravenously injected before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. The mRNA levels for COX-1 and COX-2 in the iris-ciliary body were determined by real-time polymerase chain reaction. RESULTS: FR122047, FR188582 and diclofenac sodium (15 micromol/kg each) injected intravenously 30 min before PGE2 application inhibited 29 +/- 5, 40 +/- 12 and 50 +/- 9% of aqueous flare elevation, respectively. Simultaneous injection of FR122047 (15 micromol/kg) and FR188582 (15 micromol/kg) 30 min before PGE2 application inhibited 61 +/- 8% of flare elevation. Dexamethasone phosphate disodium (15 micromol/kg) injected intravenously 300 min before PGE2 application inhibited 68 +/- 8% of aqueous flare elevation. Less than 3-fold changes in mRNA levels for COX-1 and COX-2 in the iris-ciliary body were noted after PGE2, FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium treatment. CONCLUSION: It is possible that enzyme activities of both COX-1 and COX-2 may be involved in the mechanism of PGE2-induced aqueous flare elevation in pigmented rabbits.

Animals↗

PubMed2001

[Selective cyclooxygenase 2 inhibitors (COX-2)].

Cyclooxygenase is key enzyme in the prostaglandin synthesis. It exists in two isoforms, which have distinct functions in the organism. Cyclooxygenase-2 (COX-2) participates in the pathophysiology of inflammation. Differences in the molecular structure of cyclooxygenases allowed to develop drug that selectively inhibit that isoform. Recently, selective inhibitors of COX-2 were introduced into therapy, providing new opportunities to the treatment of inflammation.

Celecoxib↗

PubMed2002

Nimesulide, a preferential cyclooxygenase 2 inhibitor, suppresses peroxisome proliferator-activated receptor induction of cyclooxygenase 2 gene expression in human synovial fibroblasts: evidence for receptor antagonism.

OBJECTIVE: To characterize the inhibitory effects of therapeutic concentrations of the nonsteroidal antiinflammatory drug nimesulide (NIM) on peroxisome proliferator-activated receptor (PPAR)-induced cyclooxygenase 2 (COX-2) gene expression in human synovial fibroblasts (HSFs) from patients with osteoarthritis (OA) and to define the intracellular mechanisms mediating the response. METHODS: PPARalpha and PPARgamma messenger RNA (mRNA) expression and protein synthesis in OA HSFs were measured by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay, respectively. Experiments investigating endogenous and overexpressed PPARalpha and PPARgamma activation of COX-2 mRNA and protein were conducted by incubating nontransfected and transfected cells with increasing concentrations of cognate ligands WY-14,643 (alpha agonist), ciglitasone (gamma agonist), and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) in the absence or presence of NIM and NS-398 (1 microM). COX-2 mRNA and protein were measured by Northern and Western blotting procedures, respectively. Receptor activation studies were evaluated by cotransfecting pSG5-Gal 4 DNA binding domain (DBD)-PPARalpha ligand binding domain (LBD) or pSG5-Gal 4 DBD-PPARgamma LBD chimeric constructs with a 5x Gal 4 enhancer site tk-tataa-luciferase reporter under ligand stimulation in the presence or absence of increasing concentrations of NIM. Gene transactivation analyses were conducted by treating cells overexpressing cytomegalovirus (CMV)-PPARalpha or CMV-PPARgamma expression constructs with either a PPAR response element (PPRE)-luciferase construct containing 3 DR1 acyl-coenzyme A (acyl-CoA) oxidase gene response elements or human COX-2 promoter constructs with WY-14,643, ciglitasone, and 15d-PGJ(2) in the presence or absence of increasing concentrations of NIM. RESULTS: Human synovial cells expressed functional PPAR isoforms, PPARalpha and PPARgamma. Neither receptor agonists nor antagonists modulated the intracellular protein levels of PPAR. PPARalpha and, especially, PPARgamma mediated the induction of COX-2 gene expression by receptor agonists. Stimulation of COX-2 mRNA expression and protein synthesis by 15d-PGJ(2) appeared to occur through a receptor-independent process. NIM inhibited PPAR agonist stimulation of COX-2 expression and synthesis in a dose-dependent manner in both nontransfected cells and cells overexpressing both receptor isoforms. NIM potently abrogated basal and ligand-stimulated PPRE(3X) DR1 acyl-CoA oxidase-driven luciferase activity and also human PPRE-containing COX-2 promoter activity. CONCLUSION: PPAR-mediated induction of COX-2 expression and synthesis in human OA synovial fibroblasts is inhibited by therapeutic concentrations of NIM through the functional antagonism of ligand-dependent receptor activation, with the resultant suppression of PPAR-dependent transactivation of target genes (e.g., COX-2).

Cells, Cultured↗

PubMed2006

Meloxicam, a cyclooxygenase 2 inhibitor, supports hematopoietic recovery in gamma-irradiated mice.

Meloxicam, a selective inhibitor of cyclooxygenase 2, a nonsteroidal anti-inflammatory drug with an improved side-effects profile in terms of gastrointestinal toxicity, has been found to stimulate hematopoiesis in whole-body gamma-irradiated mice. A distinct corroboration of this positive action of meloxicam is an enhancement of the recovery of hematopoietic progenitor cells committed to granulocyte-macrophage and erythroid development, which has been demonstrated in sublethally irradiated animals treated with meloxicam at a dose of 20 mg/kg administered intraperitoneally either singly 1 h before irradiation or repeatedly after radiation exposure. The results suggest that meloxicam can be added to the list of biological response modifiers that can be used in the treatment of hematopoietic damage induced by ionizing radiation.

Animals↗

PubMed2005

Tolerance of nonsteroidal anti-inflammatory drug-sensitive patients to the highly specific cyclooxygenase 2 inhibitors rofecoxib and valdecoxib.

BACKGROUND: Selective inhibitors of cyclooxygenase 2 (COX-2) are generally tolerated by patients sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-1. Valdecoxib is a new sulfonamide-containing COX-2-specific inhibitor indicated for the treatment of acute pain, osteoarthritis, and rheumatoid arthritis. OBJECTIVE: To compare the clinical tolerance to rofecoxib and valdecoxib in patients who previously developed urticaria and angioedema while taking classic NSAIDs. METHODS: Patients with challenge-proven NSAID cutaneous sensitivity were submitted to single-blinded controlled oral challenges with rofecoxib, 50 mg, and valdecoxib, 40 mg. RESULTS: Twenty-eight patients (19 females and 9 males; mean +/- SD age, 28.6 +/- 15.0 years; age range, 10-61 years) participated in this study. Twenty-two (85%) of 26 patients who underwent skin tests were atopic, as demonstrated by a clinical history of rhinitis and/or asthma plus positive immediate-type skin hypersensitivity test results. A previous exclusive cutaneous reaction pattern (urticaria and/or angioedema) had occurred in 10 patients (36%), whereas a mixed pattern of skin and respiratory symptoms had occurred in 18 patients (64%). Twenty patients (71%) were multiple reactors, and 8 patients (28%) were single reactors. In this current study, 2 patients (7%) taking rofecoxib experienced angioedema, and 1 patient (4%) taking valdecoxib experienced urticaria. CONCLUSIONS: Rofecoxib and valdecoxib can be safely used by most NSAID-sensitive patients with cutaneous reactions. Our findings suggest that isolated cross-reactions may occur in these patients, and for this reason, controlled oral provocation may be prudent when prescribing valdecoxib or rofecoxib for patients who have previously had urticaria or angioedema triggered by NSAIDs.

Adolescent↗

PubMed2002

Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer.

Cyclooxygenase 2 (HER-2) (Cox-2), an inducible form of Cox, is overexpressed in HER-2/neu-positive human breast cancers. The aim of this study was to determine whether celecoxib, a selective Cox-2 inhibitor, protected against HER-2/neu-induced experimental breast cancer. Cox-2 protein was detected in breast carcinomas from mouse mammary tumor virus (MMTV)/neu mice. Treatment with celecoxib (500 ppm) significantly reduced the incidence of mammary tumors in MMTV/neu mice (P = 0.003) and caused about a 50% reduction in mammary prostaglandin E2 (PGE2) levels. Because mammary glands from MMTV/neu mice expressed all four PGE2 receptor subtypes, we speculate that signaling through PGE2 receptors is important for mammary tumorigenesis. These results strengthen the rationale for developing clinical trials to determine whether selective Cox-2 inhibitors possess anticancer properties in humans at risk for breast cancer.

Animals↗

PubMed2003

Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery.

OBJECTIVE: Inhibition of cyclooxygenase 2 provides analgesia in ambulatory patients. We prospectively evaluated the safety and efficacy of a newly introduced cyclooxygenase 2 inhibitor in patients undergoing coronary artery bypass grafting surgery through a median sternotomy in a randomized clinical trial. METHODS: A total of 462 patients with New York Heart Association classes I to III who were less than 77 years of age and were from 58 institutions in the United States, Canada, Germany, and the United Kingdom participated in this multicenter, phase III, placebo-controlled, double-blind, randomized, parallel-group trial. Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or standard care (control) groups, respectively. Intravenous study drug (40 mg) was administered within 30 minutes after extubation and every 12 hours for a minimum of 3 days. Subsequently, oral treatment at a dose of 40 mg every 12 hours was initiated and administered for a combined total of 14 days. Patient-controlled analgesia with morphine, oral opioids, or acetaminophen was available as required. Assessment of the analgesic efficacy of the study drug was primarily based on morphine and morphine equivalent use. Additional efficacy evaluations included daily pain intensity, patient and physician global evaluation of study medication, and pain effect on quality of life. Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period. RESULTS: Patients in the parecoxib/valdecoxib group received significantly less morphine or morphine equivalents than patients in the control group during the 0- to 24-hour (P =.009), 24- to 48-hour (P =.017), 72- to 96-hour (P =.002), 96- to 120-hour (P =.004), and 120- to 144-hour (P =.037) periods. Both patients (P <.001) and physicians (P <.001) evaluated the study medication as significantly better than control therapy. The modified Brief Pain Inventory questionnaire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested (eg, current pain, worst pain, and mood) beginning on day 4 and continuing for at least 4 days. Although there were no differences between the groups in overall adverse events, serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients (19.0%, 59/311 patients) than in control patients (9.9%, 15/151 patients; P =.015). Regarding individual serious adverse events, a greater incidence in sternal wound infection was found in the parecoxib/valdecoxib patients (10 [3.2%]) versus control patients (0 [0%]) (P =.035). The incidences of other individual serious adverse events, including cerebrovascular complications, myocardial infarction, and renal dysfunction, were proportionally greater but not significantly different between the groups. CONCLUSIONS: In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.

Administration, Oral↗

PubMed2004

[Cyclooxygenase 2 inhibitors and lung carcinoma].

Cyclooxygenase-2 (Cox2) may play a crucial role in lung carcinogenesis. In fact, overexpression of Cox2 is common in non-small cell lung cancer (NSCLC) and seems to be associated with tumor progression, invasion and metastasis. In experimental animal models Cox2 has been shown to be involved in tumor angiogenesis, suggesting that Cox2 is a potential target for NSCLC therapy. Several in vivo studies have already shown that Cox2 specific inhibitors (celecoxib, rofecoxib) have anti-tumor activity and clinical trials using Cox2 inhibitors are currently ongoing in patients with NSCLC.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

[Cyclooxygenase 2 inhibitors and lung carcinoma].

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

[Cyclooxygenase 2 inhibitors and colorectal cancer].

Cyclooxygenase-2 (Cox2) is an inductible isoenzyme of cyclooxygenase undetectable in normal colonic mucosa and overexpressed in 80% colonic tumor. Several works in vitro and in vivo showed that Cox2 plays a key role in the multistep process of colorectal tumorigenesis such apoptosis inhibition of cellular proliferation and angiogenesis induction. So that Cox2 represent a potential molecular target in colorectal management and specific Cox2 inhibitors may be useful as chemopreventive as well as therapeutic agent in humans. In animals study Cox2 inhibitors was shown to be effective and in humans Cox2 inhibitors are approved by the Food and Drug Administration as an adjunct to endoscopic surveillance and surgery in patients with Familial Adenomatous Polyposis (FAP). The purpose of this article is to review the relationship between Cox2/Cox2 inhibitors and differents signaling pathways of colorectal carcinogenesis and to precise their possible molecular mechanisms of action. This work although review clinicals data of their efficacy as chemopreventive agent as well as therapeutic in the differents group at risk for colorectal cancer.

Adenomatous Polyposis Coli↗

PubMed2004

[Cyclooxygenase 2 inhibitors and colorectal cancer].

Cyclooxygenase-2 (Cox2) is an inductible isoenzyme of cyclooxygenase undetectable in normal colonic mucosa and overexpressed in 80% colonic tumor. Several works in vitro and in vivo showed that Cox2 plays a key role in the multistep process of colorectal tumorigenesis such apoptosis inhibition of cellular proliferation and angiogenesis induction. So that Cox2 represent a potential molecular target in colorectal management and specific Cox2 inhibitors may be useful as chemopreventive as well as therapeutic agent in humans. In animals study Cox2 inhibitors was shown to be effective and in humans Cox2 inhibitors are approved by the Food and Drug Administration as an adjunct to endoscopic surveillance and surgery in patients with Familial Adenomatous Polyposis (FAP). The purpose of this article is to review the relationship between Cox2\Cox2 inhibitors and differents signaling pathways of colorectal carcinogenesis and to precise their possible molecular mechanisms of action. This work although review clinicals data of their efficacy as chemopreventive agent as well as therapeutic in the differents group at risk for colorectal cancer.

Adenomatous Polyposis Coli↗

PubMed2005

Selective cyclooxygenase 2 inhibitor induces indefinite survival of fully allogeneic cardiac grafts and generates CD4+ regulatory cells.

BACKGROUND: Selective inhibition of cyclooxygenase 2 has been reported to have not only anti-inflammatory effects but also effects on the immune response. We investigated ability of a cyclooxygenase 2 inhibitor to inhibit alloimmune response in a murine cardiac transplantation model. METHODS: CBA (H2(k)) mice underwent transplantation of C57BL/10 (H2(b)) hearts. On the day of transplantation, the recipients received either no treatment or single administration of aspirin (a cyclooxygenase 1 and 2 inhibitor) or the selective cyclooxygenase 2 inhibitor NS-398. Naive CBA mice (secondary recipients) underwent adoptive transfer of splenocytes from treated mice with long-surviving grafts (primary recipients) to determine whether regulatory cells developed after NS-398 treatment. Histologic, cell-proliferation, and cytokine studies were also performed. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time, 8 days). The majority of recipients given aspirin rejected their grafts within 20 days (median survival time, 11 days). In mice given NS-398, the majority of the grafts survived indefinitely (median survival time, >100 days). Secondary CBA recipients given CD4+ splenocytes from primary CBA recipients treated with NS-398 also had indefinite survival of C57BL/10 hearts (median survival time, >60 days). Graft acceptance and proliferative hyporesponsiveness were also confirmed by the histologic and cell-proliferation studies, respectively. Production of interleukin 4 and 10 from splenocytes of the recipients treated with NS-398 were significantly higher than that from untreated recipients. CONCLUSIONS: In our model administration of cyclooxygenase 2 inhibitor induced indefinite survival of fully mismatched cardiac grafts and generated CD4+ regulatory cells. Cyclooxygenase 2 inhibitor could warrant consideration for use as an immunomodulating agent in clinical transplantation.

Animals↗