4,922 research outputs found
JS-K, but not JS-43-126, decreases the invasiveness of breast cancer cells across Matrigel
No full textMDA-MB-231, F10, and MCF-7/COX-2 cells were added into Matrigel-coated transwell inserts and incubated with JS-K or JS-43-126 for 72 hours. Cells that invaded through the pores onto the lower side of the filter were fixed, stained, and photographed. The number of invaded cells for each filter was counted in five fields. The invasiveness of the cells is expressed as the mean number of cells that invaded to the lower side of the filter. Columns indicate the mean of triplicate wells ± standard deviation. *Significant decrease in the number of invaded cells relative to untreated cells, < 0.05. MDA-MB-231, F10, and MCF-7/COX-2 cells were plated on Matrigel-coated wells and incubated with JS-K. After 72 hours, cell proliferation was determined by Celltiter 96AQnonradioactive cell proliferation assay. Columns indicate the mean of pentaplicate wells ± standard deviation. MDA-MB-231 and F10 cells were added into type I collagen-coated transwell inserts and incubated with JS-K for 72 hours. Cells that invaded through the pores onto the lower side of the filter were fixed, stained, and photographed.<p><b>Copyright information:</b></p><p>Taken from "TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells"</p><p>http://breast-cancer-research.com/content/10/3/R44</p><p>Breast Cancer Research : BCR 2008;10(3):R44-R44.</p><p>Published online 12 May 2008</p><p>PMCID:PMC2481491.</p><p></p
JS-K, but not JS-43-126, increases nitric oxide production in breast cancer cells
No full textConditioned medium supernatant was collected from MDA-MB-231, F10, and MCF-7/COX-2 cells treated in the absence or presence of JS-K or JS-43-126 for 72 hours. Total nitric oxide (NO) was determined by quantifying nitrite, the stable end product of NO oxidation, spectrophotometrically using a colorimetric nonenzymatic nitric oxide assay kit. Nitrite values were normalized for total cell counts and expressed as picomoles per 10cells. Columns indicate the mean of triplicate wells ± standard deviation. *Significant increase in NO levels relative to untreated cells, < 0.05.<p><b>Copyright information:</b></p><p>Taken from "TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells"</p><p>http://breast-cancer-research.com/content/10/3/R44</p><p>Breast Cancer Research : BCR 2008;10(3):R44-R44.</p><p>Published online 12 May 2008</p><p>PMCID:PMC2481491.</p><p></p
Selective COX-2 inhibitors and risk of myocardial infarction
No full textSelective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel
JS-K increases TIMP-2 production to suppress breast cancer invasion through Matrigel
No full textExpression of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs) in the conditioned medium supernatant obtained from untreated and JS-K-treated cells was qualitatively screened using a human MMP array kit. TIMP-2 levels in the conditioned medium supernatant obtained from untreated and JS-K-treated cells were determined using a commercial ELISA kit. Columns indicate the mean of triplicate wells ± standard deviation. *Significant increase in the TIMP-2 levels relative to untreated cells, < 0.05. MDA-MB-231, F10, and MCF-7/COX-2 cells were treated with JS-K (1 μM) in the presence or absence of a TIMP-2 neutralizing antibody (2.5 μg/ml) for 72 hours in a Matrigel invasion assay. The number of invaded cells was counted. Columns indicate the mean of triplicate wells ± standard deviation. *Significant decrease in the number of invaded cells relative to untreated cells, < 0.05. Increase relative to JS-K-treated cells, < 0.05.<p><b>Copyright information:</b></p><p>Taken from "TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells"</p><p>http://breast-cancer-research.com/content/10/3/R44</p><p>Breast Cancer Research : BCR 2008;10(3):R44-R44.</p><p>Published online 12 May 2008</p><p>PMCID:PMC2481491.</p><p></p
Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Die Hemmung der Cyclooxygenase (COX) durch Acetylsalicylsäure (ASS) verstärkt die Antitumorwirkung von JS-K bei Glioblastomen in vitro
No full textGlioblastome sind hochmaligne undifferenzierte Tumore, die sich durch eine aggressive Infiltration auszeichnen. Die Prognose des GBM hat sich trotz interdisziplinärer Therapieansätze nicht signifikant verbessert, da Glioblastome eine hohe Chemo- sowie Radioresistenz aufweisen. Aufgrund verschiedener Charakteristika wird das Glioblastom von der World Health Organisation (WHO) als Grad IV Tumor eingeordnet. Da das mittlere Überleben von 14,6 Monaten sehr gering ist und die Fortschritte bezüglich der Überlebenschancen sich nicht verbessert haben, sollte ein stärkerer Fokus auf die Erforschung dieser Erkrankung und deren alternativen Therapiemöglichkeiten gelegt werden. Diese Arbeit setzte sich intensiv mit dem Stickstoffmonoxid-Donor JS-K auseinander, der einen zytotoxischen sowie proliferationshemmenden Effekt auf die GBM-Zelllinien aufweist. Die Validierung eines RNA-Micro-Arrays identifizierte mehrere Gene, die durch eine JS-K-Behandlung hochreguliert wurden und einen Einfluss auf die Proliferation oder auf Resistenzmechanismen haben. Die RT-PCR Analyse konnte eine konzentrations- und zeitabhängige Hochregulation des Gens cox-2 durch die Behandlung mit JS-K feststellen. Auch wurde ein konzentrationsabhängiger Anstieg der Aktivität des Enzyms Cyclooxygenase in Folge einer JS-K-Behandlung detektiert. Im Viabilitätsassay zeigte eine Kombination von JS-K und Acetylsalicylsäure (ASS), einem COX-Hemmer, einen signifikanten synergistischen Effekt im Vergleich zur jeweiligen Monotherapie. Um den Einfluss von JS-K und ASS auf verschiedene Zelltodmechanismen zu analysieren, wurde per Western Blot Analyse das Proteinlevel der gespaltenen Caspase 3, p-Akt sowie in der Durchflusszytometrie der Anteil der apoptotischen als auch nekrotischen Zellpopulationen gemessen. Es konnte keine Apoptose, aber ein aktivierter Akt-Signalweg nachgewiesen werden. In der FACS-Analyse wurde ein konzentrationsabhängiger Anstieg der nekrotischen Zellen nach Behandlung detektiert. Ein signifikanter Unterschied zwischen Mono- und Kombinationstherapie konnte nachgewiesen werden. Da der Calciumhaushalt bei verschiedenen Zelltodmechanismen eine Rolle spielt, wurde die intrazelluläre Calciumkonzentration nach einer Behandlung mit JS-K sowie in der Kombination mit ASS untersucht. Die intrazelluläre Calciumkonzentration war dosisabhängig durch JS-K erhöht, und es war wiederum ein signifikanter synergistischer Unterschied zwischen der Mono- und Kombinationstherapie aufzeigbar. Um den Synergismus auf molekularer Ebene zu analysieren, wurde die Regulation der Gene atf3, egr1 und egr2 nach Behandlung mit JS-K und Aspirin untersucht. Nach einer Monotherapie konnte eine konzentrationsabhängige Hochregulation festgestellt werden, die darüber hinaus durch die Kombinationstherapie synergistisch verstärkt wurde. Diese drei Gene spielen eine wichtige Rolle in der Tumorgenese. Trotz Aktivierung von antiapoptotischen Mechanismen induzieren JS-K und ASS eine starke synergistische Antitumor-Aktivität in Form von nekrotischem Zelltod sowie einem reduzierten Energiemetabolismus in GBM-Zellen. Die Kombination von JS-K und ASS führt zu einer Wirkverstärkung der NO-basierten Tumortherapie mit einem gut etablierten Medikament in Glioblastom-Zellen
Chosen logistics processes in Škoda JS
No full textThis master thesis deals with the purchase and sale process in Škoda JS company. The aim of this work is to assess whether the setting of the purchase and sale process is met by the company also within a real business case, in compliance with set controls, and whether the degree of perfect delivery is sufficient. In the introduction, the author specifies the basic terms: logistics, logistic chain, customer benefits, information systems in logistics, buying and selling. The following chapter introduces Škoda JS company, including the sphere of its entrepreneurial activity. This chapter also deals with the nuclear power industry. In the crucial chapter, the author describes the process of purchase and sale in Škoda JS company and compares it with a real business case. In conclusion, the author evaluates discrepancies and suggests recommendations to avoid them
Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury
No full textYing An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA; 4Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USAAbstract: In a previous study, we found that intracerebral administration of excitotoxin (RS)-(tetrazole-5yl) glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox). In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2) in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection.Keywords: neural injury, prostaglandins, neutrophil, conditional COX-2 deletion, PGI
Regression calibration for Cox regression under heteroscedastic measurement error - Determining risk factors of cardiovascular diseases from error-prone nutritional replication data
No full textFor instance nutritional data are often subject to severe measurement error, and an adequate adjustment of the estimators is indispensable to avoid deceptive conclusions. This paper discusses and extends the method of regression calibration to correct for measurement error in Cox regression. Special attention is paid to the modelling of quadratic predictors, the role of heteroscedastic measurement error, and the efficient use of replicated measurements of the surrogates. The method is used to analyze data from the German part of the MONICA cohort study on cardiovascular diseases. The results corroborate the importance of taking into account measurement error carefully
A Cox Regression Analysis of Covariates for Asthma Hospital Readmissions
No full textBackground. Asthma hospital admissions and readmissions are unacceptably high, thus, a method to identify those at greatest risk could be helpful. Methods. An observational retrospective study using a Cox regression to determine the relationship between the time interval between admissions and possible covariates of a readmission. The covariates were age, sex, ethnicity, smoking habit, history of allergy or eczema/hay fever, age of onset, Townsend index (TI), Jarman score (JS), and drugs on discharge. Those with p < 0.2, together with interacting covariates, from the preliminary analysis were eligible for the multivariate Cox regression analysis. Results. Of the 523 patients admitted between 1994 and 1998 because of their asthma, complete data were available for 440. Of these, 112 were readmitted. Eligible covariates for the multivariate Cox regression analysis were sex, allergy status, history of eczema/hay fever, the JS and TI together with interactions between JS and TI, JS and allergy, and allergy with eczema/hay fever. There were 278 subjects (71 with a readmission) with complete data for these eligible covariates. The multivariate analysis revealed that female sex (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.42, 4.92), high JS (OR = 2.03, 95% CI 1.13-3.65), and history of allergy (OR= 1.88, 95% CI 1.06-3.32) formed the final model as significant predictors of readmission. Conclusion. Females with a history of allergy that were registered at a practice with a high workload (JS) had a higher risk of readmission. The analysis method used highlights how those at risk of readmission can be identified so that they can be targeted post discharge.link_to_subscribed_fulltex
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