23 results on '"Cyclooxygenase Inhibitors"'
Search Results
2. NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study.
- Author
-
Reese, Justin T., Coleman, Ben, Chan, Lauren, Blau, Hannah, Callahan, Tiffany J., Cappelletti, Luca, Fontana, Tommaso, Bradwell, Katie R., Harris, Nomi L., Casiraghi, Elena, Valentini, Giorgio, Karlebach, Guy, Deer, Rachel, McMurry, Julie A., Haendel, Melissa A., Chute, Christopher G., Pfaff, Emily, Moffitt, Richard, Spratt, Heidi, and Singh, Jasvinder A.
- Subjects
- *
NONSTEROIDAL anti-inflammatory agents , *COVID-19 , *COVID-19 pandemic , *COHORT analysis , *EXTRACORPOREAL membrane oxygenation - Abstract
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. Methods: A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. Results: Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53–0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47–0.56), invasive ventilation (OR: 0.59 95% CI: 0.55–0.64), AKI (OR: 0.67 95% CI: 0.63–0.72), or ECMO (OR: 0.51 95% CI: 0.36–0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. Conclusions: Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq.
- Author
-
Maeda, Shingo, Tomiyasu, Hirotaka, Tsuboi, Masaya, Inoue, Akiko, Ishihara, Genki, Uchikai, Takao, Chambers, James K., Uchida, Kazuyuki, Yonezawa, Tomohiro, and Matsuki, Naoaki
- Subjects
- *
BLADDER cancer prevention , *RNA sequencing , *GENE expression , *PROSTAGLANDIN receptors , *CYCLOOXYGENASE inhibitors - Abstract
Background: Invasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC.Methods: Total RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks.Results: Differential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property.Conclusions: Our data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
4. Acetylsalicylic acid supplementation improves protein utilization efficiency while vitamin E supplementation reduces markers of the inflammatory response in weaned pigs challenged with enterotoxigenic E. coli.
- Author
-
Jae Cheol Kim, Mullan, Bruce P., Black, John L., Hewitt, Robert J. E., van Barneveld, Robert J., and Pluske, John R.
- Subjects
- *
ASPIRIN , *CYCLOOXYGENASE inhibitors , *MESSENGER RNA , *FACTORIAL experiment designs , *LABORATORY swine - Abstract
Background: This experiment was conducted to test the hypothesis that vitamin E (Vit E) and acetylsalicylic acid (ASA), a cyclooxygenase-2 (COX-2) inhibitor, will additively reduce the production of the immunosuppressive molecule prostaglandin E2 (PGE2) and hence reduce inflammatory responses in weaner pigs experimentally infected with an enterotoxigenic strain of E. coli. Methods: The experiment was conducted in a research facility with 192 individually-housed male weaner pigs (Landrace × Large White) weighing 6.6 ± 0.04 kg (mean ± SEM). The pigs were experimentally infected with an enterotoxigenic strain of E. coli and were allocated to a 2 × 3 factorial design with the respective factors being without and with 125 ppm ASA and three levels of Vit E supplementation (50, 100 or 200 IU/kg diet, dl-α-tocopheryl acetate). Results: Acetylsalicylic acid supplementation improved average daily gain (P < 0.05) and tended to improve feed:gain ratio (P < 0.10) during the first 14 d after weaning. Acetylsalicylic acid supplementation also improved (P < 0.001) amino acid utilization efficiency (as assessed by plasma urea level) and tended to decrease (P < 0.10) PGE2 production in the liver without affecting small intestinal histology and tight junction protein mRNA expression in the jejunal epithelium. Vitamin E supplementation greater than 100 IU/kg diet sustained both the plasma Vit E concentration (P < 0.001) and plasma haptoglobin content (P < 0.001) after weaning. However, there was no additive effects of the combined supplementation of ASA and Vit E on performance, intestinal barrier function and inflammatory responses of weaned pigs. Conclusions: Although ASA and vitamin E improved amino acid utilization efficiency and reduced acute inflammatory responses, ASA and vitamin E did not additively reduce production of PGE2 and inflammatory responses in weaner pigs experimentally infected with an enterotoxigenic strain of E. coli. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
5. Cyclooxygeanse-2 promotes metastasis in osteosarcoma.
- Author
-
Liyan Qu and Bing Liu
- Subjects
- *
CYCLOOXYGENASE 2 , *OSTEOSARCOMA , *CYCLOOXYGENASE inhibitors , *METASTASIS , *NEOPLASTIC cell transformation , *CARCINOGENESIS , *APOPTOSIS - Abstract
Cyclooxygenase-2 (COX-2), an inducible form of the enzyme that catalyzes the first step in the synthesis of prostanoids, is associated with carcinogenesis, which is suspected to promote angiogenesis and tissue invasion of tumors and resistance to apoptosis. COX-2 is also involved in metastasis and poor prognosis of cancer. Osteosarcoma with COX-2 positivity is from 67 to 92 %. COX-2-positive rate in metastatic lesions was greater than that of biopsy and/or resected samples of the primary site in osteosarcoma. And, what role does COX-2 play in osteosarcoma metastasis? Genetic studies support a cause-effect connection between COX-2 and tumorigenesis. COX-2 expression had a poor prognosis with regard to metastasis, and patients with increased COX-2 expression in lung metastases died of the disease. COX-2 expression has also been established as a marker in human osteosarcoma, and COX-2 inhibition has been suggested as a possible way of improving therapeutic outcome. In addition, COX-inhibitors inhibit the tumor initiation, matrix metalloproteinases (MMPs), cell differentiation and T cell proliferation and suppression of the antitumor activity of natural killer cells and macrophages, angiogenic mechanism. Therefore, we can exert the COX-inhibitors to potentialize the effects of chemotherapeutic agents, and reverse the metastasis in osteosarcoma to facilitate the patient who may benefit from addition of COX-inhibitors to standard cytotoxic therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
6. The prognostic value of arachidonic acid metabolism in breast cancer by integrated bioinformatics.
- Author
-
Li W, Guo X, Chen C, and Li J
- Subjects
- Arachidonic Acid, CD8-Positive T-Lymphocytes pathology, Computational Biology, Cyclooxygenase Inhibitors, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Prognosis, Tumor Microenvironment genetics, Breast Neoplasms genetics, Breast Neoplasms pathology
- Abstract
Background: As the second cause of cancer death in women, breast cancer has become a worldwide priority. Previous studies based on tumour cell lines demonstrated that arachidonic acid (AA) and its metabolites promote cancer development. However, recent studies based on the tumour microenvironment revealed the antitumour effect of AA metabolism. Therefore, it is essential to reevaluate and elucidate the effect of AA metabolism on breast cancer., Methods: Raw data were obtained from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) databases. The AA metabolic score of each sample, enrichment of differentially expressed genes (DEGs) and immune infiltration were analysed by bioinformatics. Cox regression and least absolute shrinkage and selection operator regression were performed to establish an AA metabolism prognostic signature. An AA metabolism related nomogram for predicting the survival probability of patients was built., Result: AA metabolism was related to good prognosis in the TCGA-BRCA and METABRIC cohort. DEGs enrichment suggested that the upregulated DEGs of the high AA metabolism group were significantly enriched in immune-related pathways. The high AA metabolism group was infiltrated with more CD8
+ T cells and activated NK cells. An AA metabolic signature (SPINK8, KLRB1, APOD and PIGR) was constructed for breast cancer prognosis., Conclusion: The study indicated that a high level of AA metabolism may be a biomarker for good prognosis in breast cancer, providing a possible explanation for the discouraging effect of cyclooxygenase inhibitors in cancer therapy. Moreover, a novel AA metabolic prognostic signature was constructed in the study, providing a novel strategy for breast cancer., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
7. Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor growth in mice.
- Author
-
Tsz Yan Wong, Fengjuan Li, Shu-mei Lin, Chan, Franky L., Shiuan Chen, and Leung, Lai K.
- Subjects
- *
BREAST cancer treatment , *CELECOXIB , *CYCLOOXYGENASE inhibitors , *MICRORNA , *CELL cycle regulation , *THERAPEUTICS - Abstract
Background: Breast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Previous studies have demonstrated that use of cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk. Methods: In the present study, we employed an established mouse model for postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2 inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or aspirin at 200 ppm by oral administration with androstenedione injection. Results: Our results showed that both COX inhibitors could suppress the cancer xenograft growth without changing the plasma estrogen level. Protein expression of ERα, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor samples, whereas only Bcl-xL expression was suppressed in those treated with aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated in samples treated with celecoxib. Further studies in culture cells verified that the increase in miR-222 expression might contribute to ERα downregulation but not the growth deterrence of cells. Conclusion: Overall, this study suggested that both celecoxib and aspirin could prevent breast cancer growth by regulating proteins in the cell cycle and apoptosis without blocking estrogen synthesis. Besides, celecoxib might affect miR expression in an undesirable fashion. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
8. PPARα ligand, AVE8134, and cyclooxygenase inhibitor therapy synergistically suppress lung cancer growth and metastasis
- Author
-
Meiyan Dai, Huihui Li, Lujin Wu, Wei Wang, Dao Wen Wang, and Chen Chen
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Cancer Research ,Lung Neoplasms ,Angiogenesis ,Indomethacin ,Drug Evaluation, Preclinical ,Benzoates ,11-HETE ,Metastasis ,Mice ,0302 clinical medicine ,Cell Movement ,Neoplasm Metastasis ,Oxazoles ,Mice, Knockout ,biology ,Neovascularization, Pathologic ,Chemistry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,EETs ,Lung cancer ,medicine.drug ,Research Article ,Antineoplastic Agents ,lcsh:RC254-282 ,AVE8134 ,03 medical and health sciences ,In vivo ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Cyclooxygenase Inhibitors ,PPAR alpha ,Cytochrome P450 Family 2 ,Protein kinase B ,Cell Proliferation ,Bezafibrate ,PPARα agonist ,medicine.disease ,Xenograft Model Antitumor Assays ,Mice, Inbred C57BL ,030104 developmental biology ,Pyrimidines ,Eicosanoid ,biology.protein ,Cancer research ,Eicosanoids ,Cyclooxygenase - Abstract
BackgroundLung cancer (LC) is one of the leading causes of death worldwide, which highlights the urgent need for better therapies. Peroxisome proliferator-activated nuclear receptor alpha (PPARα), known as a key nuclear transcription factor involved in glucose and lipid metabolism, has been also implicated in endothelial proliferation and angiogenesis. However, the effects and potential mechanisms of the novel PPARα ligand, AVE8134, on LC growth and progression remain unclear.MethodsA subcutaneous tumour was established in mice by injecting TC-1 lung tumour cells (~ 1 × 106cells) into their shaved left flank. These mice were treated with three different PPARα ligands: AVE8134 (0.025% in drinking water), Wyeth-14,643 (0.025%), or Bezafibrate (0.3%). Tumour sizes and metastasis between treated and untreated mice were then compared by morphology and histology, and the metabolites of arachidonic acid (AA) were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Inhibition of either Cyp2c44 expression by genetic disruption or cyclooxygenase (COX) activity by indomethacin was used to test the mechanisms by which AVE8134 affects tumour growth.ResultsThe pharmacodynamics effects of AVE8134, Wyeth-14,643, and Bezafibrate on lipids control were similar. However, their effects on tumour suppression were different. Eicosanoid profile analysis showed that all PPARα ligands reduced the production of AA-derived epoxyeicosatrienoic acids (EETs) and increased the hydroxyl product, 11-hydroxyeicosatetraenoic acids (11-HETE). Moreover, increased 11-HETE promoted endothelial proliferation, angiogenesis, and subsequent tumour deterioration in a dose-dependent manner possibly via activating the AKT/extracellular signal-regulated kinase (ERK) pathway. The increased 11-HETE partly neutralized the benefits provided by the Cyp2c44-EETs system inhibited by PPARα ligands in tumour-bearing mice. AVE8134 treatment worsened the tumour phenotype in Cyp2c44 knockout mice, indicating that AVE8134 has contradictory effects on tumour growth. The COX inhibitor indomethacin strengthened the inhibitory actions of AVE8134 on tumour growth and metastasis by inhibiting the 11-HETE production in vivo and in vitro.ConclusionIn this study, we found that the degrees of inhibition on LC growth and metastasis by PPARα ligands depended on their bidirectional regulation on EETs and 11-HETE. Considering their safety and efficacy, the novel PPARα ligand, AVE8134, is a potentially ideal anti-angiogenesis drug for cancer treatment when jointly applied with the COX inhibitor indomethacin.
- Published
- 2019
9. Flurbiprofen, a Cyclooxygenase Inhibitor, Protects Mice from Hepatic Ischemia/Reperfusion Injury by Inhibiting GSK-3β Signaling and Mitochondrial Permeability Transition.
- Author
-
Hailong Fu, Huan Chen, Chengcai Wang, Haitao Xu, Fang Liu, Meng Guo, Quanxing Wang, and Xueyin Shi
- Subjects
- *
FLURBIPROFEN , *CYCLOOXYGENASES , *CYCLOOXYGENASE inhibitors , *REPERFUSION , *REPERFUSION injury - Abstract
Flurbiprofen acts as a nonselective inhibitor for cyclooxygenases (COX-1 and COX-2), but its impact on hepatic ischemia/ reperfusion (I/R) injury remains unclear. Mice were randomized into sham, I/R and flurbiprofen (Flurb) groups. The hepatic artery and portal vein to the left and median liver lobes were occluded for 90 min and unclamped for reperfusion to establish a model of segmental (70%) warm hepatic ischemia. Pretreatment of animals with flurbiprofen prior to I/R insult significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and prevented hepatocytes from I/R-induced apoptosis/necrosis. Moreover, flurbiprofen dramatically inhibited mitochondrial permeability transition (MPT) pore opening, and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that flurbiprofen markedly inhibited glycogen synthase kinase (GSK)-3β activity and increased phosphorylation of GSK-3β at Ser9, which, consequently, could modulate the adenine nucleotide translocase (ANT)-cyclophilin D (CyP-D) complex and the susceptibility to MPT induction. Therefore, administration of flurbiprofen prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through inhibition of MPT and inactivation of GSK-3β, and provides experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings in addition to its conventional use for pain relief. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
10. Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infants.
- Subjects
PATENT ductus arteriosus ,LUNG diseases ,LOW birth weight ,CYCLOOXYGENASE inhibitors ,CYCLOOXYGENASES ,THERAPEUTICS - Abstract
The article offers information on optimal treatment regimen for managing a persistent patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. It states that 71.4 percent of those who survived, received 1-3 courses of cyclooxygenase inhibitor(COI) treatment for a symptomatic PDA. A total of 40 percent failed COI treatment and underwent PDA ligation. The failure of a repeat course of COI to close a PDA is a risk factor for developing chronic lung disease CLD in ELBW infants.
- Published
- 2012
- Full Text
- View/download PDF
11. AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity
- Author
-
Soraya Wilke Saliba, Ariel R. Marcotegui, Ellen Fortwängler, Johannes Ditrich, Juan Carlos Perazzo, Eduardo Muñoz, Antônio Carlos Pinheiro de Oliveira, and Bernd L. Fiebich
- Subjects
Inflammation ,Research ,AM404 ,Anti-Inflammatory Agents ,Arachidonic Acids ,lcsh:RC346-429 ,Rats ,Cyclooxygenase ,Mice, Inbred C57BL ,Rats, Sprague-Dawley ,Mice ,Cyclooxygenase 2 ,Cyclooxygenase 1 ,Prostaglandins ,Animals ,Cyclooxygenase Inhibitors ,lipids (amino acids, peptides, and proteins) ,Microglia ,lcsh:Neurology. Diseases of the nervous system ,Cells, Cultured ,Acetaminophen - Abstract
Background N-arachidonoylphenolamine (AM404), a paracetamol metabolite, is a potent agonist of the transient receptor potential vanilloid type 1 (TRPV1) and low-affinity ligand of the cannabinoid receptor type 1 (CB1). There is evidence that AM404 exerts its pharmacological effects in immune cells. However, the effect of AM404 on the production of inflammatory mediators of the arachidonic acid pathway in activated microglia is still not fully elucidated. Method In the present study, we investigated the effects of AM404 on the eicosanoid production induced by lipopolysaccharide (LPS) in organotypic hippocampal slices culture (OHSC) and primary microglia cultures using Western blot, immunohistochemistry, and ELISA. Results Our results show that AM404 inhibited LPS-mediated prostaglandin E2 (PGE2) production in OHSC, and LPS-stimulated PGE2 release was totally abolished in OHSC if microglial cells were removed. In primary microglia cultures, AM404 led to a significant dose-dependent decrease in the release of PGE2, independent of TRPV1 or CB1 receptors. Moreover, AM404 also inhibited the production of PGD2 and the formation of reactive oxygen species (8-iso-PGF2 alpha) with a reversible reduction of COX-1- and COX-2 activity. Also, it slightly decreased the levels of LPS-induced COX-2 protein, although no effect was observed on LPS-induced mPGES-1 protein synthesis. Conclusions This study provides new significant insights about the potential anti-inflammatory role of AM404 and new mechanisms of action of paracetamol on the modulation of prostaglandin production by activated microglia. Electronic supplementary material The online version of this article (10.1186/s12974-017-1014-3) contains supplementary material, which is available to authorized users.
- Published
- 2017
12. PPARα ligand, AVE8134, and cyclooxygenase inhibitor therapy synergistically suppress lung cancer growth and metastasis.
- Author
-
Wu, Lujin, Wang, Wei, Dai, Meiyan, Li, Huihui, Chen, Chen, and Wang, Daowen
- Subjects
- *
NUCLEAR receptors (Biochemistry) , *ARACHIDONIC acid , *LUNG cancer , *TUMOR growth , *LIQUID chromatography-mass spectrometry , *CYCLOOXYGENASE inhibitors , *METASTASIS - Abstract
Background: Lung cancer (LC) is one of the leading causes of death worldwide, which highlights the urgent need for better therapies. Peroxisome proliferator-activated nuclear receptor alpha (PPARα), known as a key nuclear transcription factor involved in glucose and lipid metabolism, has been also implicated in endothelial proliferation and angiogenesis. However, the effects and potential mechanisms of the novel PPARα ligand, AVE8134, on LC growth and progression remain unclear.Methods: A subcutaneous tumour was established in mice by injecting TC-1 lung tumour cells (~ 1 × 106 cells) into their shaved left flank. These mice were treated with three different PPARα ligands: AVE8134 (0.025% in drinking water), Wyeth-14,643 (0.025%), or Bezafibrate (0.3%). Tumour sizes and metastasis between treated and untreated mice were then compared by morphology and histology, and the metabolites of arachidonic acid (AA) were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Inhibition of either Cyp2c44 expression by genetic disruption or cyclooxygenase (COX) activity by indomethacin was used to test the mechanisms by which AVE8134 affects tumour growth.Results: The pharmacodynamics effects of AVE8134, Wyeth-14,643, and Bezafibrate on lipids control were similar. However, their effects on tumour suppression were different. Eicosanoid profile analysis showed that all PPARα ligands reduced the production of AA-derived epoxyeicosatrienoic acids (EETs) and increased the hydroxyl product, 11-hydroxyeicosatetraenoic acids (11-HETE). Moreover, increased 11-HETE promoted endothelial proliferation, angiogenesis, and subsequent tumour deterioration in a dose-dependent manner possibly via activating the AKT/extracellular signal-regulated kinase (ERK) pathway. The increased 11-HETE partly neutralized the benefits provided by the Cyp2c44-EETs system inhibited by PPARα ligands in tumour-bearing mice. AVE8134 treatment worsened the tumour phenotype in Cyp2c44 knockout mice, indicating that AVE8134 has contradictory effects on tumour growth. The COX inhibitor indomethacin strengthened the inhibitory actions of AVE8134 on tumour growth and metastasis by inhibiting the 11-HETE production in vivo and in vitro.Conclusion: In this study, we found that the degrees of inhibition on LC growth and metastasis by PPARα ligands depended on their bidirectional regulation on EETs and 11-HETE. Considering their safety and efficacy, the novel PPARα ligand, AVE8134, is a potentially ideal anti-angiogenesis drug for cancer treatment when jointly applied with the COX inhibitor indomethacin. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
13. Low-dose aspirin and survival from lung cancer: a population-based cohort study
- Author
-
McMenamin, Una C., Cardwell, Chris C., Hughes, Carmel M., and Murray, Liam M.
- Subjects
Adult ,Aged, 80 and over ,Male ,Cancer Research ,Lung Neoplasms ,Aspirin ,Low-dose aspirin ,Pharmacoepidemiology ,Antineoplastic Agents ,Lung cancer survival ,Middle Aged ,United Kingdom ,Cohort Studies ,SDG 3 - Good Health and Well-being ,Oncology ,Case-Control Studies ,Genetics ,Humans ,CPRD ,Cyclooxygenase Inhibitors ,Female ,Research Article ,Aged - Abstract
BackgroundPreclinical evidence suggests that aspirin may inhibit lung cancer progression. In a large cohort of lung cancer patients, we investigated whether low-dose aspirin use was associated with a reduction in the risk of lung cancer-specific mortality.MethodsWe identified lung cancer patients from English cancer registries diagnosed between 1998 to 2009 from the National Cancer Data Repository. Medication usage was obtained from linkages to the UK Clinical Practice Research Datalink and lung cancer-specific deaths were identified from Office of National Statistics mortality data. Hazard ratios (HR) and 95 % confidence intervals (CI) for the association between low-dose aspirin use (before and after diagnosis) and risk of lung cancer-specific mortality were calculated using Cox regression models.ResultsA total of 14,735 lung cancer patients were identified during the study period. In analysis of 3,635 lung cancer patients, there was no suggestion of an association between low-dose aspirin use after diagnosis and cancer-specific mortality (adjusted HR = 0.96, 95 % CI: 0.85, 1.09). Similarly, no association was evident for low-dose aspirin use before diagnosis and cancer-specific mortality (adjusted HR = 1.00, 95 % CI: 0.95, 1.05). Associations were comparable by duration of use and for all-cause mortality.ConclusionOverall, we found little evidence of a protective association between low-dose aspirin use and cancer-specific mortality in a large population-based lung cancer cohort.
- Published
- 2015
14. Celecoxib analogues disrupt Akt signaling, which is commonly activated in primary breast tumours
- Author
-
Michael Pollak, Cathy Lee, Jiuxiang Zhu, David G. Huntsman, Sandra E. Dunn, C. Blake Gilks, Erika Yorida, Jill E. Kucab, Joanne T. Emerman, Maggie C.U. Cheang, and Ching Shih Chen
- Subjects
Programmed cell death ,Cell Survival ,Morpholines ,Breast Neoplasms ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,GSK-3 ,Cell Line, Tumor ,medicine ,Humans ,Cyclooxygenase Inhibitors ,Phosphorylation ,Enzyme Inhibitors ,skin and connective tissue diseases ,Protein kinase B ,030304 developmental biology ,Phosphoinositide-3 Kinase Inhibitors ,Medicine(all) ,Sirolimus ,Sulfonamides ,0303 health sciences ,Antibiotics, Antineoplastic ,Kinase ,Anti-Inflammatory Agents, Non-Steroidal ,Gene Amplification ,medicine.disease ,3. Good health ,Gene Expression Regulation, Neoplastic ,Celecoxib ,Chromones ,Apoptosis ,030220 oncology & carcinogenesis ,Commentary ,Cancer research ,Pyrazoles ,Female ,Signal transduction ,Proto-Oncogene Proteins c-akt ,medicine.drug ,Research Article ,Signal Transduction - Abstract
Introduction Phosphorylated Akt (P-Akt) is an attractive molecular target because it contributes to the development of breast cancer and confers resistance to conventional therapies. Akt also serves as a signalling intermediate for receptors such as human epidermal growth factor receptor (HER)-2, which is overexpressed in 30% of breast cancers; therefore, inhibitors to this pathway are being sought. New celecoxib analogues reportedly inhibit P-Akt in prostate cancer cells. We therefore examined the potential of these compounds in the treatment of breast cancer. The analogues were characterized in MDA-MB-453 cells because they overexpress HER-2 and have very high levels of P-Akt. Methods To evaluate the effect of the celecoxib analogues, immunoblotting was used to identify changes in the phosphorylation of Akt and its downstream substrates glycogen synthase kinase (GSK) and 4E binding protein (4EBP-1). In vitro kinase assays were then used to assess the effect of the drugs on Akt activity. Cell death was evaluated by poly(ADP-ribose) polymerase cleavage, nucleosomal fragmentation and MTS assays. Finally, tumour tissue microarrays were screened for P-Akt and HER-2 expression. Results OSU-03012 and OSU-O3013 inhibited P-Akt and its downstream signalling through 4EBP-1 and GSK at concentrations well below that of celecoxib. Disruption of P-Akt was followed by induction of apoptosis and more than 90% cell death. We also noted that the cytotoxicity of the celecoxib analogues was not significantly affected by serum. In contrast, the presence of 5% serum protected cells from celecoxib induced death. Thus, the structural modification of the celecoxib analogues increased P-Akt inhibition and enhanced the bioavailability of the drugs in vitro. To assess how many patients may potentially benefit from such drugs we screened tumour tissue microarrays. P-Akt was highly activated in 58% (225/390) of cases, whereas it was only similarly expressed in 35% (9/26) of normal breast tissues. Furthermore, HER-2 positive tumours expressed high levels of P-Akt (P < 0.01), supporting in vitro signal transduction. Conclusion We determined that Celecoxib analogues are potent inhibitors of P-Akt signalling and kill breast cancer cells that overexpress HER-2. We also defined an association between HER-2 and P-Akt in primary breast tissues, suggesting that these inhibitors may benefit patients in need of new treatment options.
- Published
- 2005
15. Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors.
- Author
-
Beeghly-Fadiel, Alicia, Wilson, Andrew J., Keene, Spencer, El Ramahi, Meral, Xu, Shu, Marnett, Lawrence J., Fadare, Oluwole, Crispens, Marta A., and Khabele, Dineo
- Subjects
- *
CYCLOOXYGENASES regulation , *CYCLOOXYGENASE inhibitors , *OVARIAN tumors , *MESSENGER RNA , *HEALTH outcome assessment , *CANCER chemotherapy , *DIAGNOSIS , *TUMOR treatment - Abstract
Background: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, low grade endometrioid and low grade serous) and type II (high grade serous and high grade endometrioid) ovarian tumors. Methods: We developed and validated a new COX-1 antibody, and conducted immunohistochemical (IHC) staining for COX-1 and COX-2 on a tissue microarray (TMA) of 190 primary ovarian tumors. In addition to standard IHC scoring and H-scores to combine the percentage of positive cells and staining intensity, we also measured COX-1 and COX-2 mRNA expression by QPCR. High expression was defined as greater than or equal to median values. Clinical characteristics and disease outcomes were ascertained from medical records. Associations with disease-free survival (DFS) and overall survival (OS) were quantified by hazard ratios (HRs) and confidence intervals (CIs) from proportional hazards regression. Results: Type I tumors had high COX-2 expression, while type II tumors had high COX-1 expression. In multivariable adjusted regression models, higher COX-1 mRNA expression was associated with shorter DFS (HR: 6.37, 95% CI: 1.84–22.01) and OS (HR: 2.26, 95% CI: 1.04–4.91), while higher H-scores for COX-2 expression were associated with shorter DFS (HR: 1.92, 95% CI: 1.06–3.49). Stratified analysis indicated that COX-2 was significantly associated with DFS among cases with Type II tumors (HR: 1.93, 95% CI: 1.06–3.53). Conclusions: These findings suggest that ovarian tumor type contributes to differences in COX expression levels and associations with survival. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
16. COX-2: Where are we in 2003? - Specific cyclooxygenase-2 inhibitors and aspirin-exacerbated respiratory disease
- Author
-
Crofford, Leslie J
- Subjects
cyclooxygenase inhibitors ,Aspirin ,Cyclooxygenase 2 Inhibitors ,Anti-Inflammatory Agents, Non-Steroidal ,Membrane Proteins ,asthma ,Isoenzymes ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Meeting Abstract ,Commentary ,non-steroidal anti-inflammatory drugs ,Humans ,Oral Presentation ,Drug Interactions - Abstract
The use of analgesic anti-inflammatory agents in patients with asthma is clinically challenging because of the prevalence (10-20%) of aspirin hypersensitivity. Aspirin-exacerbated respiratory disease (AERD), or aspirin-induced asthma, is characterized by asthma and rhinitis triggered by the ingestion of aspirin and non-steroidal anti-inflammatory drugs. AERD is associated with upper and lower respiratory-tract mucosal inflammation, progressive sinusitis, nasal polyposis, and asthma regardless of whether patients avoid triggering drugs. The mechanism underlying the propensity of aspirin and non-steroidal anti-inflammatory drugs to cause this reaction is thought to involve inhibition of the synthesis of protective prostaglandins (PGs), resulting in an increase in the synthesis of cysteinyl leukotrienes by eosinophils and mast cells. Clinical data suggest that protective PGs are derived from cyclooxygenase (COX)-1 because studies have now confirmed that drugs specifically inhibiting COX-2 are not cross-reactive with aspirin in patients with AERD.
- Published
- 2002
17. Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink
- Author
-
Janine A. Cooper, Christopher Cardwell, Des G. Powe, Carmel Hughes, and Liam J. Murray
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Biomedical Research ,Time Factors ,Breast Neoplasms ,Drug Prescriptions ,Cohort Studies ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,Epidemiology of cancer ,Outcome Assessment, Health Care ,Medicine ,Humans ,Cyclooxygenase Inhibitors ,Survival rate ,Aged ,Medicine(all) ,Gynecology ,Aged, 80 and over ,Aspirin ,Dose-Response Relationship, Drug ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,United Kingdom ,Cancer registry ,Survival Rate ,Logistic Models ,Oncology ,Case-Control Studies ,Nested case-control study ,Cohort ,Female ,business ,medicine.drug ,Research Article ,Follow-Up Studies - Abstract
INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.
- Published
- 2014
18. Modulation of CXCR3 ligand secretion by prostaglandin E2 and cyclooxygenase inhibitors in human breast cancer
- Author
-
Marion Kiechle, Stefanie Avril, Holger Bronger, U Schwarz-Boeger, Claudia Cerny, S Kraeft, Manfred Schmitt, and Alexandra Stöckel
- Subjects
Cell Survival ,Indomethacin ,Breast Neoplasms ,CXCR3 ,Chemokine CXCL9 ,Dinoprostone ,Interferon-gamma ,Breast cancer ,Cell Line, Tumor ,medicine ,Tumor Microenvironment ,Humans ,Cyclooxygenase Inhibitors ,skin and connective tissue diseases ,Medicine(all) ,Tumor microenvironment ,Sulfonamides ,biology ,Aspirin ,Tumor-infiltrating lymphocytes ,Chemistry ,Tumor Necrosis Factor-alpha ,Cancer ,medicine.disease ,Chemokine CXCL10 ,stomatognathic diseases ,Celecoxib ,Cyclooxygenase 2 ,Cancer cell ,Cancer research ,biology.protein ,Cyclooxygenase 1 ,Pyrazoles ,Tumor necrosis factor alpha ,Female ,Cyclooxygenase ,Research Article - Abstract
Introduction In murine breast cancer models, the two interferon-gamma (IFN-γ) inducible chemokines and CXC-chemokine receptor 3 (CXCR3) receptor ligands, monokine induced by γ-interferon (CXCL9) and interferon-γ-inducible protein-10 (CXCL10) impair tumor growth and metastasis formation through recruitment of natural killer (NK) cells and tumor-suppressive T lymphocytes. In human breast cancer, CXCL9 mRNA overexpression correlates with the number of tumor infiltrating lymphocytes and predicts response to different chemotherapeutic regimens. Raising the intratumoral CXCR3 ligand concentration is therefore a possible way to enhance immune intervention in breast cancer. Little is known, however, about expression levels and regulation of these chemokines in human breast cancer. Since the inhibition of cyclooxygenases (COX) has been shown to reduce tumor growth and incidence of metastases in a lymphocytic and IFN-γ dependent manner, we argued that COX isoenzymes are a pharmacologic target to increase intratumoral CXCR3 ligand concentration in human breast cancer. Methods CXCL9 was visualized in breast cancer specimens by immunohistochemistry, expression levels of CXCL9 and cyclooxygenases were determined by ELISA and western blotting, respectively. For regulation studies, Michigan Cancer Foundation-7 (MCF-7) and M.D. Anderson - Metastatic Breast 231 (MDA-MB 231) breast cancer cells were stimulated with IFN-γ with or without prostaglandin E2 (PGE2) or COX inhibitors (indomethacin, acetylsalicylic acid (ASA), celecoxib). CXCR3 ligand release from cells was measured by ELISA. Results Within the tumor microenvironment, cancer cells are the major source of CXCL9. PGE2 impairs IFN-γ mediated CXCL9 and CXCL10 release from MCF-7 and MDA-MB 231 cells, and inhibition of endogenous cyclooxygenases by indomethacin or ASA correspondingly increases this secretion. Otherwise, high concentrations of the Cyclooxygenase-2 (COX-2) specific antagonist celecoxib have opposite effects and impair CXCL9 and CXCL10 release. In human breast cancer tissue specimens there is an inverse correlation between COX-2 overexpression and CXCL9 concentration, suggesting that the observed in vitro effects are of importance in vivo as well. Conclusions Suppressing endogenous PGE2 synthesis by cyclooxygenase inhibition increases CXCL9 and CXCL10 release from breast cancer cells and is therefore a pharmacologic candidate to enhance intratumoral immune infiltration. Yet, to this end the unselective COX inhibitors ASA and indomethacin seem preferable to celecoxib that at higher concentrations reduces CXCR3 ligand release most probably due to COX independent mechanisms.
- Published
- 2012
19. Kinin B1 receptors contributes to acute pain following minor surgery in humans
- Author
-
Jaime S. Brahim, Albert Adam, Janet S. Rowan, May Hamza, Gilberto N. Carmona, Xiaomin Wang, and Raymond A. Dionne
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Receptor, Bradykinin B2 ,TRPV1 ,Bradykinin ,Down-Regulation ,TRPV Cation Channels ,Inflammation ,Receptor, Bradykinin B1 ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Young Adult ,Downregulation and upregulation ,Internal medicine ,lcsh:Pathology ,medicine ,Humans ,Cyclooxygenase Inhibitors ,RNA, Messenger ,Receptor ,Regulation of gene expression ,Pain, Postoperative ,business.industry ,Research ,Kinin ,Up-Regulation ,Anesthesiology and Pain Medicine ,Endocrinology ,chemistry ,Gene Expression Regulation ,Hyperalgesia ,Acute Disease ,Molecular Medicine ,Female ,medicine.symptom ,business ,Ketorolac ,lcsh:RB1-214 - Abstract
Background:Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1and B2receptors. It is generally accepted that the B2receptor is constitutively expressed, whereas the B1receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.Results:Tissue injury resulted in a significant up-regulation in the gene expression of B1and B2receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1and B2receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1and B2receptors were correlated. Following tissue injury, B1ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1receptor but not B2receptor.Conclusions:These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B1receptors may contribute to acute inflammatory pain through TRPV1 activation.
- Published
- 2010
20. Effect of cyclooxygenase inhibition on cholesterol efflux proteins and atheromatous foam cell transformation in THP-1 human macrophages: a possible mechanism for increased cardiovascular risk
- Author
-
Chan, Edwin SL, Zhang, Hongwei, Fernandez, Patricia, Edelman, Sari D, Pillinger, Michael H, Ragolia, Louis, Palaia, Thomas, Carsons, Steven, and Reiss, Allison B
- Subjects
Macrophages ,Membrane Proteins ,Membrane Transport Proteins ,Proteins ,Monocytes ,Cholesterol ,Cardiovascular Diseases ,Cyclooxygenase 2 ,Risk Factors ,Cell Line, Tumor ,Cyclooxygenase 1 ,Humans ,lipids (amino acids, peptides, and proteins) ,ATP-Binding Cassette Transporters ,Cyclooxygenase Inhibitors ,Research Article ,ATP Binding Cassette Transporter 1 ,Foam Cells - Abstract
Both selective cyclooxygenase (COX)-2 inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) have been beneficial pharmacological agents for many patients suffering from arthritis pain and inflammation. However, selective COX-2 inhibitors and traditional NSAIDs are both associated with heightened risk of myocardial infarction. Possible pro-atherogenic mechanisms of these inhibitors have been suggested, including an imbalance in prostanoid production leaving the pro-aggregatory prostaglandins unopposed, but the precise mechanisms involved have not been elucidated. We explored the possibility that downregulation of proteins involved in reverse cholesterol transport away from atheromatous plaques contributes to increased atherogenesis associated with COX inhibition. The reverse cholesterol transport proteins cholesterol 27-hydroxylase and ATP-binding cassette transporter A1 (ABCA1) export cholesterol from macrophages. When mechanisms to process lipid load are inadequate, uncontrolled cholesterol deposition in macrophages transforms them into foam cells, a key element of atheromatous plaques. We showed that in cultured THP-1 human monocytes/macrophages, inhibition of COX-1, COX-2, or both reduced expression of 27-hydroxylase and ABCA1 message (real-time reverse transcription-polymerase chain reaction) and protein (immunoblot). The selective COX-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS398) significantly reduced 27-hydroxylase and ABCA1 message (to 62.4% +/- 2.2% and 71.1% +/- 3.9% of control, respectively). Incubation with prostaglandin (PG) E2 or PGD2 reversed reductions in both of these cholesterol transport proteins induced by NS398. Cholesterol-loaded THP-1 macrophages showed significantly increased foam cell transformation in the presence of NS398 versus control (42.7% +/- 6.6% versus 20.1% +/- 3.4%, p = 0.04) as determined by oil red O staining. Pharmacological inhibition of COX in monocytes is involved in downregulation of two proteins that mediate cholesterol efflux: cholesterol 27-hydroxylase and ABCA1. Because these proteins are anti-atherogenic, their downregulation may contribute to increased incidence of cardiac events in patients treated with COX inhibitors. Reversal of inhibitory effects on 27-hydroxylase and ABCA1 expression by PGD2 and PGE2 suggests involvement of their respective signaling pathways. NS398-treated THP-1 macrophages show greater vulnerability to form foam cells. Increased cardiovascular risk with COX inhibition may be ascribed at least in part to altered cholesterol metabolism.
- Published
- 2007
21. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. [ISRCTN36233495]
- Author
-
Jerome S. Tobis, Sibylle Reinsch, Fred K. Hoehler, Phillip W Harvey, and Wadie Najm
- Subjects
musculoskeletal diseases ,Adult ,Male ,medicine.medical_specialty ,Alternative medicine ,S-Adenosylmethionine ,lcsh:Diseases of the musculoskeletal system ,S-adenosyl methonine ,Osteoarthritis ,Severity of Illness Index ,law.invention ,Rheumatology ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Cyclooxygenase Inhibitors ,Prospective Studies ,Prospective cohort study ,Pain Measurement ,Analgesics ,Sulfonamides ,Arthitis ,Cross-Over Studies ,business.industry ,Recovery of Function ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Crossover study ,Affect ,Treatment Outcome ,Celecoxib ,Joint pain ,Physical therapy ,joint pain ,Pyrazoles ,Female ,Onset of action ,lcsh:RC925-935 ,medicine.symptom ,business ,medicine.drug ,Research Article - Abstract
Background S-Adenosylmethionine (SAMe) is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating SAMe in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of SAMe to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee. Methods A randomized double-blind cross-over study, comparing SAMe (1200 mg) with celecoxib (Celebrex 200 mg) for 16 weeks to reduce pain associated with OA of the knee. Sixty-one adults diagnosed with OA of the knee were enrolled and 56 completed the study. Subjects were tested for pain, functional health, mood status, isometric joint function tests, and side effects. Results On the first month of Phase 1, celecoxib showed significantly more reduction in pain than SAMe (p = 0.024). By the second month of Phase 1, there was no significant difference between both groups (p < 0.01). The duration of treatment and the interaction of duration with type of treatment were statistically significant (ps ≤ 0.029). On most functional health measures both groups showed a notable improvement from baseline, however no significant difference between SAMe and celecoxib was observed. Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment. Conclusion SAMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. Longer studies are needed to evaluate the long-term effectiveness of SAMe and the optimal dose to be used.
- Published
- 2004
22. Antiphospholipid antibodies and thrombosis: pathogenesis of antiphospholipid syndrome
- Author
-
Koike, T
- Subjects
rheumatoid arthritis ,Aspirin ,Cyclooxygenase 2 Inhibitors ,celecoxib ,Arthritis ,Membrane Proteins ,COX-2 selective inhibitors ,rofecoxib ,Isoenzymes ,osteoarthritis ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Meeting Abstract ,Commentary ,Oral Presentation ,Humans ,Cyclooxygenase Inhibitors ,Drug Therapy, Combination ,Digestive System - Abstract
Cyclooxygenase (COX)-2 selective inhibitors have been shown to have comparable efficacy to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Large outcome studies have shown that patients with OA and RA not taking low-dose aspirin have fewer symptomatic and complicated upper GI events when treated with COX-2 selective inhibitors than with nonselective NSAIDs. When used in recommended dosages, there is no convincing evidence that patients treated with COX-2 selective inhibitors have an increased incidence of cardiovascular thrombotic events, including non-fatal myocardial infarction, than patients treated with either placebo or nonselective NSAIDs other than naproxen. Co-therapy with low-dose aspirin is recommended in patients with OA and RA at increased risk for cardiovascular events; the need for gastroprotective therapy in such patients is controversial.
- Published
- 2003
23. Anti-Ro/SSA antibodies in rheumatoid arthritis (RA)
- Author
-
Franceschini, F, Cavazzana, I, Malacarne, F, Airo, P, Cattaneo, R, Del Papa, N, Radice, A, SINICO, RENATO ALBERTO, Franceschini, F, Cavazzana, I, Malacarne, F, Airo, P, Cattaneo, R, Del Papa, N, Radice, A, and Sinico, R
- Subjects
cardiovascular risk ,Clinical Trials as Topic ,Cyclooxygenase 2 Inhibitors ,cyclooxygenase-2 inhibitors ,prothrombotic effects ,Membrane Proteins ,Rheumatoid arthritis, anti-SSA ,Thrombosis ,prostaglandins ,Isoenzymes ,Mice ,Dogs ,Cardiovascular Diseases ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Risk Factors ,Meeting Abstract ,Commentary ,Oral Presentation ,Animals ,Humans ,Cyclooxygenase Inhibitors ,Rabbits - Abstract
Selective cyclooxygenase-2 (COX-2) inhibitors were developed to reduce the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents. However, COX-2 inhibitors decrease prostacyclin production and may disrupt the normal homeostatic balance, leading to a prothrombotic state and offsetting the potential gastrointestinal benefits. Available clinical data and basic biological studies raise significant concern about the potential prothrombotic effect of this class of drugs. Two recent studies with a newer, more selective COX-2 inhibitor have added to the already existing concern about the cardiovascular safety of these agents. The widespread use of these agents mandates prospective, randomized evaluation of the cardiovascular safety of COX-2 inhibitors.
- Published
- 2003
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.