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Sample records for juanita zink cox

  1. Koper, zink en cadmium in voeding

    NARCIS (Netherlands)

    Smolders, E.A.A.

    2003-01-01

    In een tabel is aangegeven hoeveel koper, zink en cadmium een rantsoen gemiddeld moet bevatten om de behoefte van melkvee te dekken. Daarbij is uitgegaan van een gemiddelde benutting. De vraag is of er bij een tekort aangevuld moet worden en of er bij een teveel weggelaten moet worden.

  2. The John Zink Hamworthy combustion handbook

    CERN Document Server

    Baukal, Charles E

    2013-01-01

    Despite the length of time it has been around, its importance, and vast amounts of research, combustion is still far from being completely understood. Issues regarding the environment, cost, and fuel consumption add further complexity, particularly in the process and power generation industries. Dedicated to advancing the art and science of industrial combustion, The John Zink Hamworthy Combustion Handbook, Second Edition: Volume 3 - Applications offers comprehensive, up-to-date coverage of equipment used in the process and power generation industries. Under the leadership of Charles E. Baukal

  3. Geology of the Juanita Arch quadrangle, Mesa county, Colorado

    Science.gov (United States)

    Shoemaker, Eugene M.

    1954-01-01

    The Juanita Arch quadrangle is one of eighteen 7 1/2-minute quadrangles covering the principal carnotite-producing area of southwestern Colorado. The geology of these quadrangles was mapped by the U.S. Geological Survey for the Atomic Energy Commission as part of a comprehensive study of carnotite deposits. The rocks exposed in the eighteen quadrangles consist of crystalline rocks of pre-Cambrian age and sedimentary rocks that range in age from late Paleozoic to Quaternary. Over much of the area the sedimentary rocks are flat lying, but in places the rocks are disrupted by high-angle faults and northwest-trending folds. Conspicuous among the folds are large anticlines having cores of intrusive salt and gypsum. Most of the carnotite deposits are confined to the Salt Wash sandstone member of the Jurassic Morrison formation. Within this sandstone, most of the deposits are spottily distributed through an arcuate zone known as the "Uravan Mineral Belt". Individual deposits range in size from irregular masses containing only a few tons of ore ro large, tabular masses containing many thousands of tons. The ore consists largely of sandstone selectively impregnated and in part replaced by uranium and vanadium minerals. Most of the deposits appear to be related to certain sedimentary structures in sandstone of favorable construction.

  4. The John Zink Hamworthy combustion handbook, v.1 fundamentals

    CERN Document Server

    Baukal, Charles E

    2012-01-01

    Despite the length of time it has been around, its importance, and vast amounts of research, combustion is still far from being completely understood. Environmental, cost, and fuel consumption issues add further complexity, particularly in the process and power generation industries. Dedicated to advancing the art and science of industrial combustion, The John Zink Hamworthy Combustion Handbook, Second Edition: Volume One - Fundamentals gives you a strong understanding of the basic concepts and theory. Under the leadership of Charles E. Baukal, Jr., top combustion engineers and technologists f

  5. Toxische effecten van zink op de worm Eisenia andrei; resultaten proefveldexperimenten Amsterdam 1995 en 1996

    NARCIS (Netherlands)

    Bakker J; Posthuma L; Baerselman R; ECO/EEB

    1997-01-01

    De toxische effecten van zink voor de compostworm Eisenia andrei werden bestudeerd in twee proefveldexperimenten, om de veldrelevantie van laboratorium-toxiciteitsgegevens te onderzoeken indien blootstellingscondities op natuurlijke wijze fluctueren. Coconproductie werd hierbij gebruikt als subleth

  6. Untersuchungen zur Eliminierung und Resorption von Zink aus Säugerspermatozoen während der Nebenhodenpassage

    OpenAIRE

    Baldauf, Christina

    2003-01-01

    Während der Spermatogenese wird das Element Zink an die Sulfhydrylreste der Cysteine in den Mantelfaserproteinen der Spermienflagellen gebunden. So kann in den noch unreifen Mantelfasern die ungerichtete Ausbildung von Disulfidbrücken verhindert werden. Im Zuge der Spermatozoenreifung während der Nebenhodenpassage wird dieses Zink androgenabhängig zu einem hohen Prozentsatz wieder eliminiert. Die nun gerichtete Ausbildung von Disulfidbrücken ermöglicht die Versteifung der Mantelfasern. Diese ...

  7. An Explicit Construction of a sequence of codes attaining the Tsfasman-Vladut-Zink Bound:The first steps

    DEFF Research Database (Denmark)

    Høholdt, Tom; Voss, Cornelia

    1997-01-01

    We present a sequence of codes attaining the Tsfasman-Vladut-Zink bound. The construction is based on the tower of Artin-Schreier extensions described by Garcia and Stichtenoth (1995). We also determine the dual codes. The first steps of the constructions are explicitly given as generator matrices...

  8. Het gehalte aan cadmium, lood, koper, mangaan en zink in sla, spinazie en andijvie uit de kas en van de volle grond

    NARCIS (Netherlands)

    Ellen G; Tolsma K; van Loon JW

    1988-01-01

    In totaal 41 monster sla, 38 spinazie en 41 andijvie, 50% van de volle grond en 50% uit de kas, zijn geanalyseerd op gehalten aan cadmium, lood, koper, mangaan en zink. De gemiddelde gehalten, in mg/kg vers produkt waren: cadmium in sla 0,012, in spinazie 0,027 en in andijvie 0,024 ; lood in sla

  9. Het gehalte aan cadmium, lood, koper, mangaan en zink in sla, spinazie en andijvie uit de kas en van de volle grond

    NARCIS (Netherlands)

    Ellen G; Tolsma K; van Loon JW

    1988-01-01

    In totaal 41 monster sla, 38 spinazie en 41 andijvie, 50% van de volle grond en 50% uit de kas, zijn geanalyseerd op gehalten aan cadmium, lood, koper, mangaan en zink. De gemiddelde gehalten, in mg/kg vers produkt waren: cadmium in sla 0,012, in spinazie 0,027 en in andijvie 0,024 ; lood in sla 0

  10. Pengaruh Temperatur, Massa Zink, Substrat Dan Waktu Tahan Terhadap Struktur Dan Morfologi Zno Hasil Sintesis Dengan Metode Chemical Vapour Transport (CVT

    Directory of Open Access Journals (Sweden)

    Arisela Distyawan

    2013-09-01

    Full Text Available Normal 0 false false false MicrosoftInternetExplorer4 Material Zink Oksida (ZnO telah berhasil disintesis menggunakan metode Chemical Vapour Transport dengan bahan dasar prekursor berupa serbuk Zn yang dipanaskan hingga mencapai temperatur uap dalam furnace horisontal. Adapun variasi yang diberikan dalam penelitian adalah berupa temperatur pemanasan (850, 900, dan 950oC, massa prekursor Zn (0,15, 0,25, dan 0,35g, lama waktu sputtering substrat (90 dan 180 detik, dan waktu tahan khusus untuk mengetahui initial growth ZnO (10, 20, 30, 40, 50, dan 60 menit. Pembentukan Zink Oksida (ZnO dikonfirmasi melalui data X-RD, dimana telah terbentuk material ZnO dengan struktur hexagonal wurtzite. Berdarsarkan data XRD juga diketahui ukuran kristal pada sampel sputtering 90 detik mengalami penurunan bersamaan penambahan massa Zn. Dari hasil pengamatan SEM didapatkan bahwa morfologi permukaan lapisan tipis ZnO terdiri dari berbagai macam bentuk berupa nanoparticle, nanowires, nanorods, dan nanotetrapod. Lapisan Zno paling tebal sebesar ±350 nm pada sampel 950oC-0,15g sputter 90 detik. Semakin tinggi temperatur operasi berdampak peningkatan ukuran partikel. Pengujian FTIR turut menguatkan terbentuknya lapisan tipis di permukaan substrat Alumina. Hal ini didasarkan terjadinya penyerapan vibrasi yang membentuk lekukan pada kisaran area 509 cm-1 dari masing-masing sampel.

  11. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    Probabilistic properties of Cox processes of relevance for statistical modelling and inference are studied. Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment propertie...

  12. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    2005-01-01

    Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment properties and point process operations such as thinning, displacements, and super positioning. We also discuss how t...

  13. COX-2 Inhibitors and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    2014-01-01

    Full Text Available The evidence that cyclooxygenase-2 (COX-2 is upregulated and plays an important role in carcinogenesis of gastric cancer has triggered the topic of COX-2 inhibitors as chemopreventive agents for gastric cancer. Studies find that COX-2 inhibitors are associated not only with chemoprophylactic effects, but also with chemotherapeutic potentials in gastric cancer. Both COX-dependent and COX-independent pathways have a role in the anticancer efficiency of COX-2 inhibitors. However, enthusiasm is thwarted by the potential toxicity, that is, gastrointestinal toxicity of nonselective COX-2 inhibitors and cardiovascular risk of selective COX-2 inhibitors. Therefore, more studies are needed to develop new targeted antitumor agents (such as prostaglandin E receptor antagonist and to define fundamental questions such as optimal treatment regimens, integration of cotherapy, and careful selection of candidates.

  14. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-01-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models...

  15. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introducea general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive...

  16. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models...

  17. Sorption reactions in groundwater: various aspects to modelling the transport behaviour of zinc; Sorptionsreaktionen im Grundwasser: Unterschiedliche Aspekte bei der Modellierung des Transportverhaltens von Zink

    Energy Technology Data Exchange (ETDEWEB)

    Hadeler, A.

    1999-08-01

    The dispersal of trace substance in groundwater may be limited by dissolution and precipitation and, of particular interest in this paper, by sorption and desorption processes. These surface-active processes, which have a decisive influence on groundwater quality, depend on the concomitant geochemical conditions prevailing in the water, the constituents of the aquifer and on the surface properties of the solids. Taking the geochemical conditions prevailing naturally in brown coal mining areas as a point of departure this study was aimed at examining the influence of acidification processes on the transport behaviour inorganic pollutants for the example of zinc. For this purpose oxic column trials were carried out on sandy aquifer material. The data were supplemented by a detailed characterisation of the solid surfaces and modelled on the basis of a transport-reaction model as well as mechanistically with due regard to surface complexing. [German] Die Ausbreitung von Spurenstoffen im Grundwasser wird ausser durch Loesungs- und Faellungsprozesse vor allem durch Sorptions- bzw. Desorptionsvorgaenge limitiert. Diese fuer die Grundwasserqualitaet entscheidenden oberflaechenaktiven Prozesse sind von den variablen geochemischen Randbedingungen im Wasser, vom Stoffbestand des Aquifers und von den Oberflaecheneigenschaften der Feststoffe abhaengig. In Anlehnung an die natuerlichen im Bereich von Braunkohle-Abbaugebieten herrschenden geochemischen Bedingungen wurde der Einfluss von Versauerungsprozessen auf das Transportverhalten von anorganischen Schadstoffen, am Beispiel von Zink, auf der Basis von oxischen Saeulenversuchen an sandigem Aquifermaterial untersucht. Die Daten wurden durch eine detaillierte Charakterisierung der Feststoff-Oberflaechen ergaenzt und sowohl mit Hilfe eines Transport-Reaktionsmodells als auch mechanistisch unter Einbeziehung der Oberflaechenkomplexierung modelliert. (orig.)

  18. Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

    Directory of Open Access Journals (Sweden)

    Richard Dela Cruz

    2016-06-01

    Full Text Available Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.

  19. COX-1 and COX-2 expression in feline oral squamous cell carcinoma.

    Science.gov (United States)

    Hayes, A; Scase, T; Miller, J; Murphy, S; Sparkes, A; Adams, V

    2006-01-01

    This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.

  20. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney

    OpenAIRE

    Wei Qi; Smith, Francine G.; Megan L. Lewis; Wade, Andrew W

    2012-01-01

    This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role...

  1. Digestive disease and COX - 1, COX - 2%COX-1和COX-2抑制剂与胃肠道疾病

    Institute of Scientific and Technical Information of China (English)

    李文晰; 梅冬艳; 段芳龄

    2001-01-01

    @@ COX(cvclo-oxygenase)有两种异构体:COX-1和COX-2,阿斯匹林和其它NSAIDs既有消炎镇痛作用也有较多的副作用,主要是由于其抑制COX的非选择性,因而较少副作用的选择性COX抑制剂(抑制COX异构体COX-2)在近几年越来越受到人们重视,这些药物有meloxicam、nimesulin、celecoxib、etodolac、尼美舒利(nimesulide)等.

  2. Postimperiale Diskurse und literarische Mobilitätsforschung. Thomas Grob, Boris Previšić, Andrea Zink (Hgg.): Erzählte Mobilität im östlichen Europa. (Post-)Imperiale Räume zwischen Erfahrung und Imagination. Tübingen: Francke Verlag 2014 (= Kultur - Herrschaft - Diifferenz 18), 308 S.

    OpenAIRE

    Car, Milka

    2015-01-01

    Rezension zu: Thomas Grob, Boris Previšić, Andrea Zink (Hgg.): Erzählte Mobilität im östlichen Europa. (Post-)Imperiale Räume zwischen Erfahrung und Imagination. Tübingen: Francke Verlag 2014 (= Kultur - Herrschaft - Diifferenz 18), 308 S. (review)

  3. COX-1 and COX-2 expression in canine cutaneous, oral and ocular melanocytic tumours.

    Science.gov (United States)

    Pires, I; Garcia, A; Prada, J; Queiroga, F L

    2010-01-01

    In order to evaluate the potential value of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of canine malignant melanoma, expression of cyclooxygenase (COX)-1 and COX-2 was determined in 20 cutaneous, nine oral and two ocular malignant melanomas, and in nine cutaneous melanocytomas. Almost all tumours expressed COX-1, but COX-2 expression was restricted to the malignant tumours being found in 11 of the 20 cutaneous malignant melanomas, all oral malignant melanomas and in one of two ocular malignant melanomas. COX-1 expression did not differ significantly between benign and malignant skin lesions, but COX-2 expression was significantly greater in cutaneous malignant melanoma compared with melanocytoma (P=0.047). COX-2 labelling was particularly intense in the more highly malignant oral tumours. The results of the study suggest that NSAIDs, particularly COX-2 inhibitors, may be useful in the treatment of canine malignant melanoma.

  4. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus

    This paper reviews useful results related to Palm distributions of spatial point processes and provides a new result regarding the characterization of Palm distributions for the class of log Gaussian Cox processes. This result is used to study functional summary statistics for a log Gaussian Cox...

  5. Cyclooxygenase (COX Inhibitors and the Newborn Kidney

    Directory of Open Access Journals (Sweden)

    Wei Qi

    2012-10-01

    Full Text Available This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2 plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.

  6. An Exponential Bound for Cox Regression☆

    Science.gov (United States)

    Kosorok, M. R.

    2012-01-01

    We present an asymptotic exponential bound for the deviation of the survival function estimator of the Cox model. We show that the bound holds even when the proportional hazards assumption does not hold. PMID:23565013

  7. An Exponential Bound for Cox Regression.

    Science.gov (United States)

    Goldberg, Y; Kosorok, M R

    2012-07-01

    We present an asymptotic exponential bound for the deviation of the survival function estimator of the Cox model. We show that the bound holds even when the proportional hazards assumption does not hold.

  8. Is COX-2 a perpetrator or a protector? Selective COX-2 inhibitors remain controversial

    Institute of Scientific and Technical Information of China (English)

    Cheng LUO; Ming-liang HE; Lars BOHLIN

    2005-01-01

    Aim: COX-2(cyclooxygenase-2) has sparked a surge in pharmaceutical interest since its discovery at the beginning of the 1990s. Several COX-2 selective inhibitors that avoid gastrointestinal side effects have been successfully launched into the market in recent years. The first selective COX-2 inhibitor, celecoxib, entered the market in December 1999. However, there are a few organs that physiologically and functionally express COX-2, particularly the glomeruli of the kidney and the cortex of the brain. Inhibition of COX-2 expression in these organs possibly causes heart attack and stroke in long-term COX-2 inhibitor users. Recently, a USA Food and Drug Agency (FDA) advisory panel re-evaluated COX-2 inhibitors and unanimously concluded that the entire class of COX-2 inhibitors increase the risk of cardiovascular problems. Thus the use of COX-2 inhibitors is still controversial, and there is a challenge for not only pharmacologists, but also the pharmaceutical industry, to develop improved painkilling and anti-inflammatory drugs. This may involve exploring a new generation of COX-2 inhibitors with different inhibitory mechanisms through computer-aided design, screening different sources of inhibitors with lower Selectivity, or seeking completely new targets.Synthetic COX-2 inhibitors have high selectivity and the advantage of irreversible inhibition, whereas naturally derived COX-2 inhibitors have lower selectivity and fewer side effects, with the medical effects in general not being as striking as those achieved using synthetic inhibitors. This review discusses the mechanism of COX-2 inhibitor therapy and a possible new way of exploration in the development of anti-inflammatory, analgetic, and antipyretic drugs.

  9. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  10. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

    Directory of Open Access Journals (Sweden)

    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  11. The Mitochondrial Genome of Conus textile, coxI-coxII Intergenic Sequences and Conoidean Evolution

    OpenAIRE

    2007-01-01

    The cone snails belong to the superfamily Conoidea, comprising ∼10,000 venomous marine gastropods. We determined the complete mitochondrial DNA sequence of Conus textile. The gene order is identical in Conus textile, Lophiotoma cerithiformis (another Conoidean gastropod), and the neogastropod Ilyanassa obsoleta, (not in the superfamily Conoidea). However, the intergenic interval between the coxI/coxII genes, was much longer in C. textile (165 bp) than in any other previously analyzed gastropo...

  12. Randomized controlled trials of COX-2 inhibitors

    DEFF Research Database (Denmark)

    Stefansdottir, Gudrun; De Bruin, Marie L; Knol, Mirjam J

    2011-01-01

    BACKGROUND: Naproxen, ibuprofen and diclofenac are frequently used as comparators in randomized controlled trials (RCTs) on the safety and efficacy of cyclooxygenase (COX)-2 inhibitors. Different comparator doses may influence the results of RCTs. It has been hypothesized that RCTs of COX-2...... 1995 and 2009 in which celecoxib or rofecoxib were compared with naproxen, ibuprofen or diclofenac. All articles labelled as RCTs mentioning rofecoxib or celecoxib and one or more of the comparator drugs in the title and/or abstract were included. We extracted information on doses of both non...... dose trends in the case of rofecoxib. CONCLUSIONS: Although the dose trends over time differed for RCTs comparing rofecoxib and celecoxib with diclofenac, ibuprofen or naproxen, the results of our study do not support the hypothesis that dose trends influenced the decision to continue marketing...

  13. Acute upregulation of COX-2 by renal artery stenosis

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin...... causal relationship between the changes of COX-2 and of renin expression, clipped rats were treated with the COX-2 blocker celecoxib (40 mg. kg(-1). day(-1)). This treatment, however, did not change renin mRNA either in the clipped or in the contralateral intact kidney. Our findings indicate that renal...... artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin...

  14. Acute upregulation of COX-2 by renal artery stenosis

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin...... activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all...... artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin...

  15. Differentials of Cox rings: Jaczewski's theorem revisited

    CERN Document Server

    Kedzierski, Oskar

    2011-01-01

    A generalized Euler sequence over a complete normal variety X is the unique "identity" extension of the trivial bundle H^1(X,\\Omega_X) \\otimes O_X by the sheaf of differentials \\Omega_X. We prove that, if X is a smooth Mori Dream Space and the bundle arising from the Euler sequence splits into a direct sum of line bundles, then X is a toric variety. The proof of this characterization of toric varieties depends on a somewhat more general result which, in the case of a Mori Dream Space, identifies the module of sections of the twisted sheaf coming from the Euler extension with the module of differentials of the Cox ring of the variety in question.

  16. HER2 and COX2 expression in human prostate cancer.

    Science.gov (United States)

    Edwards, J; Mukherjee, R; Munro, A F; Wells, A C; Almushatat, A; Bartlett, J M S

    2004-01-01

    COX2 and HER2 expression are associated with a poor prognosis in prostate cancer and HER2 has been linked to COX2 expression in colorectal cancer. The association between COX2 and HER2 expression was investigated in 117 patients with prostate cancer (89) or Benign prostatic hyperplasia (BPH) (28). Tissue was analysed for HER2 amplification by fluorescent in situ hybridisation, and HER2 and COX2 protein expression by immunohistochemistry (IHC). All tumours analysed expressed COX2 at a significantly higher level than BPH tissue (P=0.041). Only low levels of HER2 gene amplification (8%, 7/89) and HER2 protein expression (12%, 11/89) were observed. HER2 protein expression was rarely observed and did not correlate with HER2 amplification or COX2 expression. Although HER2 does not drive COX2 expression in prostate cancer, this study identified high levels of COX2 expressed in locally advanced prostate cancer, suggesting COX2 could be a potential therapeutic target. COX2 inhibitors are currently being used in clinical trials for the treatment of other tumour types.

  17. Binding Energy Calculation of Patchouli Alcohol Isomer Cyclooxygenase Complexes Suggested as COX-1/COX-2 Selective Inhibitor

    Directory of Open Access Journals (Sweden)

    Sentot Joko Raharjo

    2014-01-01

    Full Text Available To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX, the three-dimensional (3D structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117 was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2.

  18. COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.

    Science.gov (United States)

    Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael

    2009-12-15

    The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.

  19. COX2 genetic variation, NSAIDs, and advanced prostate cancer risk

    OpenAIRE

    Cheng, I.; Liu, X.; Plummer, S J; Krumroy, L M; Casey, G; Witte, J S

    2007-01-01

    Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate canc...

  20. Cox-2 inhibitors and the risk of cardiovascular thrombotic events.

    LENUS (Irish Health Repository)

    Khan, M

    2012-04-01

    In 1971, Vane showed that the analgesic action of traditional NSAIDs relies on inhibition of the cyclo-oxygenase (COX) enzyme, which in turn results in reduced synthesis of proalgesic prostaglandins. Two decades later COX was shown to exist as two distinct isoforms. The constitutive isoform COX-1, supports the beneficial homeostatic functions whereas the inducible isoform, COX-2 becomes up regulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis. Despite the benefits of NSAIDs for acute and chronic pain one of the most clinically significant and well characterized adverse effect is on GI mucosa. The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. The COX-2 selective (COX-1 sparing) inhibitors are associated with reduced GI mucosal damage as demonstrated in several trials. In light of the overwhelming and sometimes contradictory information for patients and physicians regarding the safety of COX-2 agents this article will summarize the available evidence regarding cardiovascular (CV) safety data and contemporary recommendations for prescribing of COX-2-selective NSAIDs.

  1. Transport Properties of the Tunnel Junctions Al1-xCox/{Al1-xCox-oxide}/Al

    Institute of Scientific and Technical Information of China (English)

    X.F.Han; J. Murai; H.Kubota; Y.Ando; Q.Y.Wang; N.Tezuka; T.Miyazaki

    2000-01-01

    The oxides of Al1-xCox (x=0,0.25,0.5,0.75, and 1.0) alloys were chosen as barrier materials in this work. The tunnel junction consists of the bottom electrode Al1-xCox and the top electrode Al with an insulating layer { Al1-xCox-oxide} which was formed by natural oxidation in a baking-box at 333K. The oxidation time for forming an Al1-xCox-oxide layer on the surface of the bottom Al1-xCox layers were optimized.The resistance of Al1-xCox/{ Al1-xCox-oxide}/Al tunnel junctions varied between 101 and 106 Ω measured at 1 my and 4.2 K. The effective barrier height and width of insulating layers Al1-xCox-oxide ( x=0.25, 0.5, and 0.75 )varied between 0.6 and 2.7 eV and between 1.3 and 2.1 nm. It is shown that the thin oxide layer of Al1-xCox alloys can be chosen as barrier materials.

  2. The heme a synthase Cox15 associates with cytochrome c oxidase assembly intermediates during Cox1 maturation.

    Science.gov (United States)

    Bareth, Bettina; Dennerlein, Sven; Mick, David U; Nikolov, Miroslav; Urlaub, Henning; Rehling, Peter

    2013-10-01

    Cox1, the core subunit of the cytochrome c oxidase, receives two heme a cofactors during assembly of the 13-subunit enzyme complex. However, at which step of the assembly process and how heme is inserted into Cox1 have remained an enigma. Shy1, the yeast SURF1 homolog, has been implicated in heme transfer to Cox1, whereas the heme a synthase, Cox15, catalyzes the final step of heme a synthesis. Here we performed a comprehensive analysis of cytochrome c oxidase assembly intermediates containing Shy1. Our analyses suggest that Cox15 displays a role in cytochrome c oxidase assembly, which is independent of its functions as the heme a synthase. Cox15 forms protein complexes with Shy1 and also associates with Cox1-containing complexes independently of Shy1 function. These findings indicate that Shy1 does not serve as a mobile heme carrier between the heme a synthase and maturing Cox1 but rather cooperates with Cox15 for heme transfer and insertion in early assembly intermediates of cytochrome c oxidase.

  3. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were

  4. On spatio-temporal Lévy based Cox processes

    DEFF Research Database (Denmark)

    Prokesova, Michaela; Hellmund, Gunnar; Jensen, Eva Bjørn Vedel

    2006-01-01

    The paper discusses a new class of models for spatio-temporal Cox point processes. In these models, the driving field is defined by means of an integral of a weight function with respect to a Lévy basis. The relations to other Cox process models studied previously are discussed and formulas for t...

  5. Extensions and Applications of the Cox-Aalen Survival Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2003-01-01

    Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects......Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects...

  6. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were as

  7. Radiolabeled COX-2 Inhibitors for Non-Invasive Visualization of COX-2 Expression and Activity — A Critical Update

    Directory of Open Access Journals (Sweden)

    Torsten Kniess

    2013-05-01

    Full Text Available Cyclooxygenase-2 (COX-2 is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs for use in cancer treatment is in the focus of the medicinal chemistry research field. For this purpose, a set of methods is available to determine COX-2 expression and activity in vitro and ex vivo but it is still a problem to functionally characterize COX-2 in vivo. This review focusses on imaging agents targeting COX-2 which have been developed for positron emission tomography (PET and single photon emission computed tomography (SPECT since 2005. The literature reveals that different radiochemical methods are available to synthesize COXIBs radiolabeled with fluorine-18, carbon-11, and isotopes of radioiodine. Unfortunately, most of the compounds tested did not show sufficient stability in vivo due to de[18F]fluorination or de[11C]methylation or they failed to bind specifically in the target region. So, suitable stability in vivo, matching lipophilicity for the target compartment and both high affinity and selectivity for COX-2 were identified as prominent criteria for radiotracer development. Up to now, it is not clear what approach and which model is the most suited to evaluate COX-2 targeting imaging agents in vivo. However, for proof of principle it has been shown that some radiolabeled compounds can bind specifically in COX-2 overexpressing tissue which gives hope for future work in this field.

  8. Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells.

    Science.gov (United States)

    Hussain, Tajamul; Gupta, Sanjay; Adhami, Vaqar M; Mukhtar, Hasan

    2005-02-10

    Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic conditions, including cancer. One practical inference of this finding is that sustained inhibition of COX-2 could serve as a promising target for prevention or therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells. Therefore, there is a need to define novel, nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX-2 but not COX-1 inhibitory activity. Recent studies on green tea and its major polyphenolic constituent (-)epigallocatechin-3-gallate (EGCG) have established its remarkable cancer preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma cells. Based on our study, it is tempting to suggest that a combination of EGCG with chemotherapeutic drugs could be an improved strategy for prevention and treatment of prostate cancer.

  9. A Comparative Study of Cox Regression vs. Log-Logistic ...

    African Journals Online (AJOL)

    Journal of Medical and Biomedical Sciences ... using non-parametric Cox model and parametric Log-logistic model, factors influencing survival of ... colorectal cancer referred to Taleghani Medical and Training Center of Tehran between 2001 ...

  10. COX-2 and p53 in human sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Cyr, Diane; Luce, Danièle

    2008-01-01

    the exposures and p53 accumulation were found; however, the p53 accumulation pattern (p = 0.062 for wood dust exposure) resembled that of COX-2 expression. In summary, our findings show increased COX-2 expression in SNC adenocarcinoma with wood dust exposure, suggesting a role for inflammatory components......The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2......; 41 for p53). Occupational histories and smoking habits were available for majority of the cases. Most of the adenocarcinoma cases with exposure history data had been exposed to wood dust at work in the past (88%, 14/16). For smokers, 63% (12/19) presented with SSC, whereas 64% (7/11) of nonsmokers...

  11. Convergence of posteriors for discretized log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    2004-01-01

    In Markov chain Monte Carlo posterior computation for log Gaussian Cox processes (LGCPs) a discretization of the continuously indexed Gaussian field is required. It is demonstrated that approximate posterior expectations computed from discretized LGCPs converge to the exact posterior expectations...

  12. Comparison of Cox and Gray's survival models in severe sepsis

    DEFF Research Database (Denmark)

    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate.......Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  13. Simultaneous confidence bands for Cox regression from semiparametric random censorship.

    Science.gov (United States)

    Mondal, Shoubhik; Subramanian, Sundarraman

    2016-01-01

    Cox regression is combined with semiparametric random censorship models to construct simultaneous confidence bands (SCBs) for subject-specific survival curves. Simulation results are presented to compare the performance of the proposed SCBs with the SCBs that are based only on standard Cox. The new SCBs provide correct empirical coverage and are more informative. The proposed SCBs are illustrated with two real examples. An extension to handle missing censoring indicators is also outlined.

  14. COX2 genetic variation, NSAIDs, and advanced prostate cancer risk.

    Science.gov (United States)

    Cheng, I; Liu, X; Plummer, S J; Krumroy, L M; Casey, G; Witte, J S

    2007-08-20

    Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate cancer. Nine single-nucleotide polymorphisms (SNPs) in COX2 were genotyped among 1012 men in our case-control study of advanced prostate cancer. Gene-environment interactions between COX2 polymorphisms and NSAID use were also evaluated. Information on NSAID use was obtained by questionnaire. Three SNPs demonstrated nominally statistically significant associations with prostate cancer risk, with the most compelling polymorphism (rs2745557) associated with a lower risk of disease (odds ratio (OR) GC vs GG=0.64; 95% confidence interval (CI): 0.49-0.84; P=0.002). We estimated through permutation analysis that a similarly strong result would occur by chance 2.7% of the time. Nonsteroidal anti-inflammatory drug use was associated with a lower risk of disease in comparison to no use (OR=0.67; 95% CI: 0.52-0.87). No significant statistical interaction between NSAID use and rs2745557 was observed (P=0.12). Our findings suggest that variation in COX2 is associated with prostate cancer risk.

  15. Allan V. Cox: AGU President 1978”1980

    Science.gov (United States)

    Richman, Barbara T.

    When Allan V. Cox was presented AGU's John Adam Fleming Medal in 1969, John Verhoogen described Cox's work as “characterized by painstaking care, proper attention to and use of statistics, and great insight.” Those same thoughts were echoed on February 3, 1987, during the memorial service for Cox, who died in a bicycling accident on January 27. The Stanford Memorial Church was crowded with colleagues, students, and friends.The Fleming Medal was presented to Cox in recognition of his studies on the fluctuation of the geomagnetic field. These studies helped to confirm theories of continental drift and seafloor spreading. The medal is awarded annually by AGU for original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, and related sciences. In addition to the Fleming Medal, Cox received the Antarctic Service Medal in 1970, the Vetlesen Prize in 1971, and the Arthur L. Day Prize of the National Academy of Sciences in 1984. He was a Fellow of AGU and a member of the National Academy of Sciences.

  16. Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase.

    Science.gov (United States)

    Bourens, Myriam; Boulet, Aren; Leary, Scot C; Barrientos, Antoni

    2014-06-01

    Cytochrome c oxidase (CIV) deficiency is one of the most common respiratory chain defects in patients presenting with mitochondrial encephalocardiomyopathies. CIV biogenesis is complicated by the dual genetic origin of its structural subunits, and assembly of a functional holoenzyme complex requires a large number of nucleus-encoded assembly factors. In general, the functions of these assembly factors remain poorly understood, and mechanistic investigations of human CIV biogenesis have been limited by the availability of model cell lines. Here, we have used small interference RNA and transcription activator-like effector nucleases (TALENs) technology to create knockdown and knockout human cell lines, respectively, to study the function of the CIV assembly factor COX20 (FAM36A). These cell lines exhibit a severe, isolated CIV deficiency due to instability of COX2, a mitochondrion-encoded CIV subunit. Mitochondria lacking COX20 accumulate CIV subassemblies containing COX1 and COX4, similar to those detected in fibroblasts from patients carrying mutations in the COX2 copper chaperones SCO1 and SCO2. These results imply that in the absence of COX20, COX2 is inefficiently incorporated into early CIV subassemblies. Immunoprecipitation assays using a stable COX20 knockout cell line expressing functional COX20-FLAG allowed us to identify an interaction between COX20 and newly synthesized COX2. Additionally, we show that SCO1 and SCO2 act on COX20-bound COX2. We propose that COX20 acts as a chaperone in the early steps of COX2 maturation, stabilizing the newly synthesized protein and presenting COX2 to its metallochaperone module, which in turn facilitates the incorporation of mature COX2 into the CIV assembly line.

  17. Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease Avaliação da imunoexpressão de COX-1, COX-2 e p53 na doença de Crohn

    Directory of Open Access Journals (Sweden)

    Mônica Romero

    2008-12-01

    Full Text Available BACKGROUND: Crohn's disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2 in Crohn's disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2. AIMS: To investigate the immunoexpression of cyclooxygenase 1 (COX-1, COX-2 and p53 in Crohn's ileocolitis and to correlated this expression with clinical and histopathological parameters. METHODS: Forty-five cases of Crohn's disease, 16 cases of actinic colitis (diseased-control group and 11 cases without a history of intestinal disease (normal control group were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method. RESULTS: Sixty percent of the Crohn's disease patients were women and 40% were men, with 75.5% whites and 25.5% non-whites. The disease involved the terminal ileum in 44.5% of cases, ileum in 33.3%, colon in 20% and duodenum-ileum in 2.2%. A significant association was observed between COX-2 immunoreactivity and age RACIONAL: A doença de Crohn, junto com a colite ulcerativa idiopática ou inespecífica constituem a doença inflamatória intestinal. A imunoexpressão de ciclooxigenase 2 (COX-2 na doença de Crohn acentua-se com a progressão da doença, enquanto que a presença do tipo selvagem de p53 suprime a transcrição de COX-2. OBJETIVOS: Investigar a imunoexpressão de ciclooxigenase 1 (COX-1, COX-2 e p53 na doença de Crohn e correlacionar os achados com parâmetros clínico-histopatológicos. MÉTODOS: Foram estudados 45 casos de doença de Crohn (grupo teste, 16 casos de colite actínica (grupo controle-doente e 11 casos sem história de doença intestinal (grupo controle normal. A avaliação histopatológica foi feita

  18. Post-translational regulation of COX2 activity by FYN in prostate cancer cells.

    Science.gov (United States)

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-06-30

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.

  19. Seizure following the Use of the COX-2 Inhibitor Etoricoxib

    Science.gov (United States)

    Arnao, Valentina; Riolo, Marianna; Fierro, Brigida

    2017-01-01

    We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors. PMID:28210513

  20. COX-1 inhibitory effect of medicinal plants of Ghana

    DEFF Research Database (Denmark)

    Larsen, Birgitte HV; Soelberg, Jens; Jäger, Anna

    2015-01-01

    Plants used to treat inflammatory ailments, pain, fever and infections in Ghana, were tested for COX-1 inhibitory activity. Ethanolic extracts of 17 species were tested in a COX-1 assay. The extracts of Gardenia ternifolia, Thonningia sanguinea, Triumfetta rhomboidea, and the root of Zanthoxylum...... zanthoxyloides showed an inhibitory effect over 90% in the final concentration 0.1 μg/μL. The HPLC profiles indicated that the extracts of the four active species did not contain tannins. The observed in vitro activities support the use of some of the plant species in the traditional medicine system in Ghana....

  1. Multifocal fixed drug eruption with COX-2 inhibitor-celecoxib

    Directory of Open Access Journals (Sweden)

    Shikha Chugh

    2013-01-01

    Full Text Available Cyclooxygenase-2 (COX-2 inhibitors are rapidly becoming the first choice nonsteroidal anti-inflammatory drugs (NSAIDs for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE with celecoxib which has not yet been reported in Indian settings.

  2. Multifocal Fixed Drug Eruption with COX-2 Inhibitor-Celecoxib

    Science.gov (United States)

    Chugh, Shikha; Sarkar, Rashmi; Garg, Vijay K; Singh, Avninder; Keisham, Chitralekha

    2013-01-01

    Cyclooxygenase-2 (COX-2) inhibitors are rapidly becoming the first choice nonsteroidal anti-inflammatory drugs (NSAIDs) for various rheumatological and other painful conditions. However, they might not be as safe or free of side effects as they are considered to be. These COX-2inhibitors may cause a variety of dermatological and systemic side effects of which we should be aware to avoid their indiscriminate use. We hereby report a case of multifocal fixed drug eruption (FDE) with celecoxib which has not yet been reported in Indian settings. PMID:23716804

  3. Post-translational regulation of COX2 activity by FYN in prostate cancer cells

    OpenAIRE

    Alexanian, Anna; Miller, Bradley; Chesnik, Marla; Mirza, Shama; Sorokin, Andrey

    2014-01-01

    While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates h...

  4. Prescriber adoption of newly approved selective COX-2 inhibitors

    NARCIS (Netherlands)

    Layton, Deborah; Souverein, Patrick C.; Heerdink, Eibert R.; Shakir, Saad A. W.; Egberts, A. G. C.

    2008-01-01

    Introduction There is no consistent definition of prescribers who adopt new drug treatments early. This study examines if COX-2 inhibitors (coxibs) were prescribed by subsets of practitioners and describes GP adoption patterns of coxibs and existing NSAIDs over time. Methods A population-based drug

  5. A time inhomogeneous Cox-Ingersoll-Ross diffusion with jumps

    CERN Document Server

    Hoepfner, Reinhard

    2009-01-01

    We consider a time inhomogeneous Cox-Ingersoll-Ross diffusion with positive jumps. We exploit a branching property to prove existence of a unique strong solution under a restrictive condition on the jump measure. We give Laplace transforms for the transition probabilities, with an interpretation in terms of limits of mixtures over Gamma laws.

  6. Role of COX-2 in microcirculatory disturbance in experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Wen-Wei Yan; Zong-Guang Zhou; You-Dai Chen; Hong-Kai Gao

    2004-01-01

    AIM: To elucidate the role of COX-2 in the development of capillary leakage in rats with acute interstitial pancreatitis.METHODS: Rats with acute interstitial pancreatitis were induced by caerulein subcutaneous injection. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of COX-2 in pancreatic tissues, spectrophotometry was used to assay the parameters of acute pancreatitis such as the serum amylase and plasma myeloperoxidase, and determination of capillary permeability in the pancreas by quantifying the permeability index (PI) assisted response of pancreatic microvascular via intravital fluorescence microscope video image analysis system.RESULTS: A significant increase of COX-2 expression,elevation of serum amylase, and plasma myeloperoxidase were detected in rats with acute edematous pancreatitis compared with control rats. The changes of pancreatic microvascular after caerulein injection were as following: (a) the decrease of pancreatic capillary blood flow (4th h,0.56±0.09 nL/min, P<0.05; 8 th h, 0.34±0.10 nL/min, P<0.001);(b) reduction of functional capillary density (4 th h, 381±9 cm-1,P>0.05; 8th h, 277±13 cm-1 P<0.001); (c) irregular and intermittent capillary perfusion was observed at the 8th h and these vessels were also prone to permeation.CONCLUSION: COX-2 plays an important role in mediating capillary permeability in pancreatitis, thereby contributing to capillary leakage.

  7. Intravenous glutamine enhances COX-2 activity giving cardioprotection.

    LENUS (Irish Health Repository)

    McGuinness, Jonathan

    2009-03-01

    Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

  8. Resistance of prostate cancer cell lines to COX-2 inhibitor treatment.

    Science.gov (United States)

    Wagner, Matthew; Loos, James; Weksler, Nicole; Gantner, Marin; Corless, Christopher L; Barry, John M; Beer, Tomasz M; Garzotto, Mark

    2005-07-08

    Targeting of cyclooxygenase-2 (COX-2) for cancer chemoprevention is well supported for several tumor types, most notably colon cancer. In contrast, the data for its role in prostate cancer carcinogenesis are correlative only. Thus, we compared the COX-2 expression, activity, and effects of inhibition in prostate cancer cells on COX-2-dependent colon cancer cells. COX-2 levels in benign and malignant human prostate tissue were determined by immunohistochemistry. Compared to colon cancer cells, prostate cancer cells expressed lower levels of COX-2, produced less PGE2, and were resistant to selective COX-2 inhibition. Examination of benign prostatic epithelium from prostatectomy samples demonstrated rare foci of COX-2. Whereas, human prostate cancer sections were uniformly negative for COX-2. In conclusion, these studies indicate the lack of a putative role for COX-2 in prostate cancer development. Direct evidence for the involvement of COX-2 in prostate cancer carcinogenesis is desperately needed.

  9. COX-2 gene promoter haplotypes and prostate cancer risk.

    Science.gov (United States)

    Panguluri, Ramesh C K; Long, Layron O; Chen, Weidong; Wang, Songping; Coulibaly, Aoua; Ukoli, Flora; Jackson, Aaron; Weinrich, Sally; Ahaghotu, Chiledum; Isaacs, William; Kittles, Rick A

    2004-06-01

    Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflammatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBP alpha) and NF-kappa B binding sites. A case-control study of the four SNPs in African American (n = 288), Bini Nigerian (n = 264) and European American (n = 184) prostate cancer cases and age-matched controls revealed that SNP -297G was associated with a decreased risk for prostate cancer [odds ratio (OR) = 0.49; CI = 0.2-0.9; P = 0.01]. The effect on risk was observed in both African Americans (OR = 0.51; CI = 0.2-0.9; P = 0.01) and European Americans (OR = 0.33; CI = 0.1-0.9; P = 0.02). In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR = 2.72; CI = 1.3-5.8; P = 0.007 and OR = 3.67; CI = 1.4-9.9; P = 0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR = 0.4; CI = 0.1-0.9; P = 0.02) and European Americans (OR = 0.2; CI = 0.1-0.9; P = 0.03). These data

  10. In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

    Science.gov (United States)

    Dewi, Lestari

    2016-01-01

    Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main stages, the docking between COX-1 and COX-2 with Fucoidan, alginate and aspirin (for comparison) and the analysis of the amount of interactions formed and the residues directly involved in the process of interaction. Results: Our results showed that both Fucoidan and alginate had an excellent potential as inhibitors of COX-1 and COX-2. Fucoidan had a better potential as an inhibitor of COX than alginate. COX inhibition was expected to provide a more favorable effect on inflammation-related pathological conditions. Conclusion: The active compounds Fucoidan and alginate derived from Sargassum sp. were suspected to possess a good potential as inhibitors of COX-1 and COX-2. PMID:27594740

  11. Multivariate Product-Shot-noise Cox Point Process Models

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Mateu, Jorge

    We introduce a new multivariate product-shot-noise Cox process which is useful for model- ing multi-species spatial point patterns with clustering intra-specific interactions and neutral, negative or positive inter-specific interactions. The auto and cross pair correlation functions of the proces...... can be obtained in closed analytical forms and approximate simulation of the process is straightforward. We use the proposed process to model interactions within and among five tree species in the Barro Colorado Island plot.......We introduce a new multivariate product-shot-noise Cox process which is useful for model- ing multi-species spatial point patterns with clustering intra-specific interactions and neutral, negative or positive inter-specific interactions. The auto and cross pair correlation functions of the process...

  12. Jackknifed random weighting for Cox proportional hazards model

    Institute of Scientific and Technical Information of China (English)

    LI Xiao; WU YaoHua; TU DongSheng

    2012-01-01

    The Cox proportional hazards model is the most used statistical model in the analysis of survival time data.Recently,a random weighting method was proposed to approximate the distribution of the maximum partial likelihood estimate for the regression coefficient in the Cox model.This method was shown not as sensitive to heavy censoring as the bootstrap method in simulation studies but it may not be second-order accurate as was shown for the bootstrap approximation.In this paper,we propose an alternative random weighting method based on one-step linear jackknife pseudo values and prove the second accuracy of the proposed method.Monte Carlo simulations are also performed to evaluate the proposed method for fixed sample sizes.

  13. Prostanoids in tumor angiogenesis: therapeutic intervention beyond COX-2.

    Science.gov (United States)

    Salvado, M Dolores; Alfranca, Arántzazu; Haeggström, Jesper Z; Redondo, Juan Miguel

    2012-04-01

    Prostanoids regulate angiogenesis in carcinoma and chronic inflammatory disease progression. Although prostanoid biosynthetic enzymes and signaling have been extensively analyzed in inflammation, little is known about how prostanoids mediate tumor-induced angiogenesis. Targeted cyclooxygenase (COX)-2 inhibition in tumor, stromal and endothelial cells is an attractive antiangiogenic strategy; however, the associated cardiovascular side effects have led to the development of a new generation of nonsteroidal anti-inflammatory drugs (NSAIDs) acting downstream of COX. These agents target terminal prostanoid synthases and prostanoid receptors, which may also include several peroxisome proliferator-activated receptors (PPARs). Here, we discuss the role of prostanoids as modulators of tumor angiogenesis and how prostanoid metabolism reflects complex cell-cell crosstalk that determines tumor growth. Finally, we discuss the potential of new NSAIDs for the treatment of angiogenesis-dependent tumor development.

  14. Targeting Estrogen-Induced COX-2 Activity in Lymphangioleiomyomatosis (LAM)

    Science.gov (United States)

    2014-12-01

    rapamycin treatment. However both Torin 1 treatment and Rictor knockdown, led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin... rapamycin complex 1 (mTORC1), a master regulator of cell growth, protein translation, and metabolism. In LAM patients the mTORC1 inhibitor Rapamycin ...published PLOS One 2014. “ Rapamycin -insensitive up-regulation of adipocyte phospholipase A2 in tuberous sclerosis complex and

  15. Some functional limit theorems for compound Cox processes

    Science.gov (United States)

    Korolev, Victor Yu.; Chertok, A. V.; Korchagin, A. Yu.; Kossova, E. V.; Zeifman, Alexander I.

    2016-06-01

    An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

  16. Positively skewed data: revisiting the box-cox power transformation.

    OpenAIRE

    2015-01-01

    Although the normal probability distribution is the cornerstone of applying statistical methodology; data do not always meet the necessary normal distribution assumptions. In these cases, researchers often transform non-normal data to a distribution that is approximately normal. Power transformations constitute a family of transformations, which include logarithmic and fractional exponent transforms. The Box-Cox method offers a simple method for choosing the most appropriate power transformat...

  17. COX-2 Inhibitors for Cancer Treatment in Dogs

    Directory of Open Access Journals (Sweden)

    Andrigo Barboza De Nardi*, Talita Mariana Morata Raposo1, Rafael Ricardo Huppes1, Carlos Roberto Daleck2 and Renée Laufer Amorim3

    2011-10-01

    Full Text Available Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2 whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

  18. [New studies of COX-inhibitors, yet issues remain].

    Science.gov (United States)

    Wollheim, Frank A

    2003-09-18

    Advantages and risks related to the use of selective COX-2 inhibitors when treating arthritis are currently being scrutinized by authorities and public. The discussion tends towards exaggerated claims for or against their usefulness. The issue of cardiovascular safety is still not finally settled. In an experimental study using patients with severe coronary disease, administration of celecoxib resulted in improved endothelial function together with reduced CRP levels. Gastrointestinal tolerance was studied in patients who had recently recovered from peptic ulcer bleeding. In this group of high risk patients, celecoxib was as safe as combined therapy using omeprazol and diclofenac when given for 6 months. However, both COX inhibitors caused hypertension and adverse renal effects. The second generation of selective inhibitors is being launched. Etoricoxib--related to rofecoxib--was shown to be as potent as indomethacin in the treatment of acute gout, but it caused fewer adverse reactions. In general, however, any advantage of second generation as compared to first generation COX-2 inhibitors remains to be proven. The Swedish Council on Technology Assessment in Health Care, in its "SBU Alert", has published an appraisal of celecoxib and rofecoxib, in which the need for further long-term safety studies is emphasized.

  19. Survival analysis of cervical cancer using stratified Cox regression

    Science.gov (United States)

    Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

  20. Perbandingan efektivitas kombinasi zink-probiotik dengan zink tunggal dalam mengurangi keparahan diare akut

    OpenAIRE

    Hatta, Muhammad

    2011-01-01

    Bacground The incidence of diarrhea in Indonesia has declined in the last five years, but the mortality rate in under five years old is still high, appropriate and comprehensive management is essential. Many studies described the management of diarrhea, especially zinc and probiotics. It is not yet known whether a combination of both is better than single zinc in reducing the severity of acute diarrhea. Objective To compare the efficacy of zinc-probiotic combination with zinc in reducing...

  1. Effect of isolated fractions of Harpagophytum procumbens D.C. (devil's claw) on COX-1, COX-2 activity and nitric oxide production on whole-blood assay.

    Science.gov (United States)

    Anauate, Maria Cecilia; Torres, Luce Maria; de Mello, Suzana Beatriz Veríssimo

    2010-09-01

    The present study evaluates the effect of isolated fractions of Harpagophytum procumbens (devil's claw) on cyclooxygenase (COX-1 and COX-2) activities and NO production using a whole blood assay. The activity of COX-1 was quantified as platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin E(2) production in LPS-stimulated whole blood. Total NO(2) (-)/NO(3) (-) concentration was determined by Griess reaction in LPS stimulated blood. Assays were performed by incubation of isolated fractions obtained by flash chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing different amounts of harpagoside with blood from healthy donors. Indomethacin and etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows that fraction containing the highest concentration of harpagoside inhibited indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and greatly inhibited NO production (66%). In contrast the fraction including iridoid pool increased COX-2 and did not alter NO and COX-1 activities. The fraction containing cinnamic acid was able to reduce only NO production (67%). Our results demonstrated that the harpagoside fraction is the main responsible for the effect of devils claw on these enzyme activities. However, other components from devil's claw crude extract could antagonize or increase the synthesis of inflammatory mediators.

  2. Expression of gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors.

    Science.gov (United States)

    Lipari, L; Mauro, A; Gallina, S; Tortorici, S; Buscemi, M; Tete, S; Gerbino, A

    2012-01-01

    Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. The aim of this study is to analyse the expression and possible interactions between gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors. We investigated the expression of gelatinases and cyclooxigenases in control salivary gland, Pleomorphic adenoma and Warthin's tumor through immunohistochemistry and Reverse Transcription - Polymerase Chain Reaction (PCR). We identified the expression of both classes of enzyme in normal samples and in the two types of pathological samples without any quantitative differences. From the present data no significant differences emerge in the expression of these enzymes among the different pathologies examined. Nevertheless, due to the small number of samples included in this study, general statements regarding correlation between the degree of severity of the tumoral pathology and the quantitative expression of these potential tumoral markers can not be made.

  3. Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Edwin Roger Parra

    2013-12-01

    Full Text Available OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc and idiopathic pulmonary fibrosis (IPF patients, correlating that expression with patient survival.METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP in SSc patients and usual interstitial pneumonia (UIP in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP, and low COX-1 expression in alveolar septa.CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.

  4. The Arabidopsis COX11 Homolog is Essential for Cytochrome c Oxidase Activity.

    Science.gov (United States)

    Radin, Ivan; Mansilla, Natanael; Rödel, Gerhard; Steinebrunner, Iris

    2015-01-01

    Members of the ubiquitous COX11 (cytochrome c oxidase 11) protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410). Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD) or overexpression (OE) affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type), still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems, or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was altered, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as an essential COX complex assembly factor.

  5. In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2

    Directory of Open Access Journals (Sweden)

    Nunung Yuniarti

    2012-03-01

    Full Text Available Curcumin has been widely reported as an anti-inflammatory agent isolated from the plant Curcuma longa L. (turmeric. This anti-inflammatory activity was associated with the ability of this compound to inhibit the activity of both cyclooxygenase-1 (COX-1 and cyclooxygenase-2 (COX-2 in arachidonic acid metabolism. Dual COX-1 and COX-2 inhibitors are preferred to be employed in the therapy of chronic inflammatory diseases compared to selective inhibitors, since it was reported that the use of selective inhibitors led to severe adverse side effect. In the present study, in vitro and in silico assays on curcumin and its analogues as dual inhibitors for both COX-1 and COX-2 were performed. The results provide theoretical contribution in understanding the ligand-protein interactions at the molecular level to develop new curcumin analogues which possess better anti-inflammatory activity as well as to avoid unsolicited side effects.

  6. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression.

    Directory of Open Access Journals (Sweden)

    Nicholas S Kirkby

    Full Text Available There are two schools of thought regarding the cyclooxygenase (COX isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibody-based techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system.

  7. In Silico Analysis of the Potential of the Active Compounds Fucoidan and Alginate Derived from Sargassum Sp. as Inhibitors of COX-1 and COX-2

    OpenAIRE

    Dewi, Lestari

    2016-01-01

    Introduction: The enzyme cyclooxygenase (COX) is an enzyme that catalyzes the formation of one of the mediators of inflammation, the prostaglandins. Inhibition of COX allegedly can improve inflammation-induced pathological conditions. Aim: The purpose of the present study was to evaluate the potential of Sargassum sp. components, Fucoidan and alginate, as COX inhibitors. Material and methods: The study was conducted by means of a computational (in silico) method. It was performed in two main ...

  8. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

  9. Synthesis and biological evaluation of 3-amino-2-pyrones as selective cyclooxygenase-1 (COX-1) inhibitors

    Institute of Scientific and Technical Information of China (English)

    Xue-Ping Chu; Qing-Fa Zhou; Shen Zhao; Fei-Fei Ge; Mian Fu; Jia-Peng Chen; Tao Lu

    2013-01-01

    A group of 3-amino-2-pyrones were synthesized and their biological activities were evaluated for inhibiting cyclooxygenase (COX) activity.This study has led to the identification of COX-1-selective inhibitors.Among the tested compounds,the compound 5j exhibited the most potent COX-1 inhibitory activity (IC50 =19.32 μg/mL) and COX-1 selectivity index (SI =41.98).

  10. Extended cox regression model: The choice of timefunction

    Science.gov (United States)

    Isik, Hatice; Tutkun, Nihal Ata; Karasoy, Durdu

    2017-07-01

    Cox regression model (CRM), which takes into account the effect of censored observations, is one the most applicative and usedmodels in survival analysis to evaluate the effects of covariates. Proportional hazard (PH), requires a constant hazard ratio over time, is the assumptionofCRM. Using extended CRM provides the test of including a time dependent covariate to assess the PH assumption or an alternative model in case of nonproportional hazards. In this study, the different types of real data sets are used to choose the time function and the differences between time functions are analyzed and discussed.

  11. Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

    NARCIS (Netherlands)

    Bijnsdorp, Irene; Berg, van den Jaap; Kuipers, Gitta; Wedekind, Laurine; Slotman, Ben; Rijn, van Johannes; Lafleur, M.; Sminia, Peter

    2007-01-01

    The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 in

  12. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

    DEFF Research Database (Denmark)

    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

    2011-01-01

    It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP...

  13. Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate

    DEFF Research Database (Denmark)

    Nielsen, Marianne; Bazan, Nicolas G; Diemer, Nils H;

    2002-01-01

    and immunohistochemistry. An up-regulation of COX-2, c-fos, and c-jun, but not COX-1, was observed around the lesion as well as in the neocortex 4 hr after the injection. Hippocampal up-regulation of COX-2 was seen in dentate gyrus 8 hr after injection. When glutamate was injected, up-regulation of the early...

  14. COX-2 in Cancer: Gordian knot or Achilles heel?

    Directory of Open Access Journals (Sweden)

    Ioannis eStasinopoulos

    2013-03-01

    Full Text Available The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of, or themselves are results of, changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis. These molecular and phenotypic changes approach the complexities of a ‘Gordian Knot’. We review evidence from our studies and from literature suggesting that COX-2 biology presents a nodal point in cancer biology and an ‘Achilles heel’ of COX-2-dependent tumors.

  15. 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.

    Directory of Open Access Journals (Sweden)

    Paul C Armstrong

    Full Text Available BACKGROUND: Clinical use of selective inhibitors of cyclooxygenase (COX-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI(2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. METHODOLOGY/PRINCIPAL FINDINGS: A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control diclofenac (1 mg.kg(-1, i.v. and parecoxib (0.5 mg.kg(-1, i.v. on thrombus formation induced by collagen or the thromboxane (TX A(2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. CONCLUSIONS/SIGNIFICANCE: Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA(2, but not that induced by U46619, which is independent of platelet TXA(2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis.

  16. Statistical Inference in Cox-Ingersoll-Ross Model%Cox-Ingersoll-Ross模型的统计推断

    Institute of Scientific and Technical Information of China (English)

    陈萍; 杨孝平

    2005-01-01

    本文研究了Cox-Ingersoll-Ross模型的统计推断问题.给出了CIR过程的平稳均值m与平稳方差v的矩估计,并利用m和v给出了CIR过程中尺度参数α与波动率β之间的关系,讨论了参数α的条件矩估计和渐近极大似然估计.并通过数值模拟对条件矩估计,渐近极大似然估计这两种方法作了比较.

  17. Niacin and biosynthesis of PGD₂ by platelet COX-1 in mice and humans

    DEFF Research Database (Denmark)

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela

    2012-01-01

    The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1-dependent formation of PGD₂ and PGE₂ followed by COX-2-dependent production of PGE₂. Consistent with this, niacin......-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD₂ receptor DP1. NSAID-mediated suppression of COX-2-derived PGI₂ has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD₂. Here, we show that PGD₂ biosynthesis is augmented....... Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased...

  18. Cox26 is a novel stoichiometric subunit of the yeast cytochrome c oxidase.

    Science.gov (United States)

    Levchenko, Maria; Wuttke, Jan-Moritz; Römpler, Katharina; Schmidt, Bernhard; Neifer, Klaus; Juris, Lisa; Wissel, Mirjam; Rehling, Peter; Deckers, Markus

    2016-07-01

    The cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain. The complex accepts electrons from cytochrome c and passes them onto molecular oxygen. This process contributes to energy capture in the form of a membrane potential across the inner membrane. The enzyme complex assembles in a stepwise process from the three mitochondria-encoded core subunits Cox1, Cox2 and Cox3, which associate with nuclear-encoded subunits and cofactors. In the yeast Saccharomyces cerevisiae, the cytochrome c oxidase associates with the bc1-complex into supercomplexes, allowing efficient energy transduction. Here we report on Cox26 as a protein found in respiratory chain supercomplexes containing cytochrome c oxidase. Our analyses reveal Cox26 as a novel stoichiometric structural subunit of the cytochrome c oxidase. A loss of Cox26 affects cytochrome c oxidase activity and respirasome organization.

  19. Cyclooxygenases (COX-1 and COX-2) for tissue engineering of articular cartilage--from a developmental model to first results of tissue and scaffold expression.

    Science.gov (United States)

    Brochhausen, Christoph; Zehbe, Rolf; Gross, Ulrich; Libera, Jeanette; Schubert, Helmut; Nüsing, Rolf M; Klaus, Günter; Kirkpatrick, C James

    2008-01-01

    Tissue engineering of articular cartilage remains an ongoing challenge. Since tissue regeneration recapitulates ontogenetic processes the growth plate can be regarded as an innovative model to target suitable signalling molecules and growth factors for the tissue engineering of cartilage. In the present study we analysed the expression of cyclooxygenases (COX) in a short-term chondrocyte culture in gelatin-based scaffolds and in articular cartilage of rats and compared it with that in the growth plate. Our results demonstrate the strong cellular expression of COX-1 but only a focal weak expression of COX-2 in the seeded scaffolds. Articular cartilage of rats expresses homogeneously COX-1 and COX-2 with the exception of the apical cell layer. Our findings indicate a functional role of COX in the metabolism of articular chondrocytes. The expression of COX in articular cartilage and in the seeded scaffolds opens interesting perspectives to improve the proliferation and differentiation of chondrocytes in scaffold materials by addition of specific receptor ligands of the COX system.

  20. Hepatic ischemia and reperfusion injury in the absence of myeloid cell-derived COX-2 in mice.

    Directory of Open Access Journals (Sweden)

    Sergio Duarte

    Full Text Available Cyclooxygenase-2 (COX-2 is a mediator of hepatic ischemia and reperfusion injury (IRI. While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2-M/-M to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2-M/-M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2-M/-M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2-M/-M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2-M/-M and WT mice. COX-2-M/-M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9 expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2-M/-M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype.

  1. COX-2 inhibitors: a CLASS act or Just VIGORously promoted.

    Science.gov (United States)

    Malhotra, Samir; Shafiq, N; Pandhi, P

    2004-03-23

    Abstract Selective cyclo-oxygenase (COX)-2 inhibitors were developed with the hope of producing lesser gastrointestinal (GI) side effects as compared with the conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Soon after their introduction into the market, the sales of celecoxib and rofecoxib went up considerably. Most of this was attributed to the results of the Celecoxib Long-term Arthritis Safety Study (CLASS) and Vioxx Gastrointestinal Outcome Research (VIGOR) trials. However, several discrepancies were noted in the presentation of the actual trial results submitted to the US Food and Drug Administration (FDA) and those used for the purpose of publication in scientific journals. These issues were discussed subsequently by the way of scientific communications. Moreover, with increasing use of these agents, evidence of their adverse effects is coming to light. The present review aims at discussing the above issues, with emphasis on the results of the CLASS and VIGOR trials.

  2. Gaussian estimation for discretely observed Cox-Ingersoll-Ross model

    Science.gov (United States)

    Wei, Chao; Shu, Huisheng; Liu, Yurong

    2016-07-01

    This paper is concerned with the parameter estimation problem for Cox-Ingersoll-Ross model based on discrete observation. First, a new discretized process is built based on the Euler-Maruyama scheme. Then, the parameter estimators are obtained by employing the maximum likelihood method and the explicit expressions of the error of estimation are given. Subsequently, the consistency property of all parameter estimators are proved by applying the law of large numbers for martingales, Holder's inequality, B-D-G inequality and Cauchy-Schwarz inequality. Finally, a numerical simulation example for estimators and the absolute error between estimators and true values is presented to demonstrate the effectiveness of the estimation approach used in this paper.

  3. Random weighting method for Cox's proportional hazards model

    Institute of Scientific and Technical Information of China (English)

    CUI WenQuan; LI Kai; YANG YaNing; WU YueHua

    2008-01-01

    Variance of parameter estimate in Cox's proportional hazards model is based on asymptotic variance.When sample size is small,variance can be estimated by bootstrap method.However,if censoring rate in a survival data set is high,bootstrap method may fail to work properly.This is because bootstrap samples may be even more heavily censored due to repeated sampling of the censored observations.This paper proposes a random weighting method for variance estimation and confidence interval estimation for proportional hazards model.This method,unlike the bootstrap method,does not lead to more severe censoring than the original sample does.Its large sample properties are studied and the consistency and asymptotic normality are proved under mild conditions.Simulation studies show that the random weighting method is not as sensitive to heavy censoring as bootstrap method is and can produce good variance estimates or confidence intervals.

  4. Inverse probability weighted Cox regression for doubly truncated data.

    Science.gov (United States)

    Mandel, Micha; de Uña-Álvarez, Jacobo; Simon, David K; Betensky, Rebecca A

    2017-09-08

    Doubly truncated data arise when event times are observed only if they fall within subject-specific, possibly random, intervals. While non-parametric methods for survivor function estimation using doubly truncated data have been intensively studied, only a few methods for fitting regression models have been suggested, and only for a limited number of covariates. In this article, we present a method to fit the Cox regression model to doubly truncated data with multiple discrete and continuous covariates, and describe how to implement it using existing software. The approach is used to study the association between candidate single nucleotide polymorphisms and age of onset of Parkinson's disease. © 2017, The International Biometric Society.

  5. Regularization for Cox's Proportional Hazards Model With NP-Dimensionality

    CERN Document Server

    Bradic, Jelena; Jiang, Jiancheng

    2010-01-01

    High throughput genetic sequencing arrays with thousands of measurements per sample and a great amount of related censored clinical data have increased demanding need for better measurement specific model selection. In this paper we establish strong oracle properties of non-concave penalized methods for {\\it non-polynomial} (NP) dimensional data with censoring in the framework of Cox's proportional hazards model. A class of folded-concave penalties are employed and both LASSO and SCAD are discussed specifically. We unveil the question under which dimensionality and correlation restrictions can an oracle estimator be constructed and grasped. It is demonstrated that non-concave penalties lead to significant reduction of the "irrepresentable condition" needed for LASSO model selection consistency. The large deviation result for martingales, bearing interests of its own, is developed for characterizing the strong oracle property. Moreover, the non-concave regularized estimator, is shown to achieve asymptotically ...

  6. Box-Cox Mixed Logit Model for Travel Behavior Analysis

    Science.gov (United States)

    Orro, Alfonso; Novales, Margarita; Benitez, Francisco G.

    2010-09-01

    To represent the behavior of travelers when they are deciding how they are going to get to their destination, discrete choice models, based on the random utility theory, have become one of the most widely used tools. The field in which these models were developed was halfway between econometrics and transport engineering, although the latter now constitutes one of their principal areas of application. In the transport field, they have mainly been applied to mode choice, but also to the selection of destination, route, and other important decisions such as the vehicle ownership. In usual practice, the most frequently employed discrete choice models implement a fixed coefficient utility function that is linear in the parameters. The principal aim of this paper is to present the viability of specifying utility functions with random coefficients that are nonlinear in the parameters, in applications of discrete choice models to transport. Nonlinear specifications in the parameters were present in discrete choice theory at its outset, although they have seldom been used in practice until recently. The specification of random coefficients, however, began with the probit and the hedonic models in the 1970s, and, after a period of apparent little practical interest, has burgeoned into a field of intense activity in recent years with the new generation of mixed logit models. In this communication, we present a Box-Cox mixed logit model, original of the authors. It includes the estimation of the Box-Cox exponents in addition to the parameters of the random coefficients distribution. Probability of choose an alternative is an integral that will be calculated by simulation. The estimation of the model is carried out by maximizing the simulated log-likelihood of a sample of observed individual choices between alternatives. The differences between the predictions yielded by models that are inconsistent with real behavior have been studied with simulation experiments.

  7. Prognostic relevance of cyclooxygenase-2 (COX-2) expression in Chinese patients with prostate cancer.

    Science.gov (United States)

    Bin, Wu; He, Wang; Feng, Zhang; Xiangdong, Lu; Yong, Chen; Lele, Kou; Hongbin, Zhang; Honglin, Guo

    2011-02-01

    Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression and metastasis. The present study was designed to investigate the clinicopathological and prognostic significance of COX-2 in Chinese patients with prostate cancer. Firstly, RT-PCR and Western blot assays were performed to detect the expression of COX-2 mRNA and protein in prostate cancer cell lines and 20 tissue samples (tumor or corresponding non-tumor). Next, immunohistochemistry was performed to detect the expression of COX-2 protein in 88 prostate cancer tissue samples. Finally, the correlation between COX-2 expression and clinicopathological factors and patient survival was evaluated. We found that the expression levels of COX-2 mRNA and protein showed significant difference among four prostate cancer cell lines. Moreover, the levels of COX-2 mRNA and protein were significantly higher in prostate cancer tissues than in corresponding non-tumor tissues. COX-2 staining was positive in the cytoplasm of prostate cancer cells. High-COX-2 expression was correlated with the Gleason score (P=0.009), tumor stage (P=0.012), and lymph-node status (P=0.036). Furthermore, patients with high-COX-2 expression showed lower disease-free (P=0.014) and overall survival (P=0.047) rates than those with low-COX-2 expression. Univariate and multivariate analyses suggested that the status of COX-2 protein expression was an independent prognostic indicator for patients' survival. Taken together, higher COX-2 protein expression might provide an independent prognostic marker for Chinese patients with prostate cancer who have undergone surgery.

  8. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    Science.gov (United States)

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

  9. Lineage-specific fragmentation and nuclear relocation of the mitochondrial cox2 gene in chlorophycean green algae (Chlorophyta).

    Science.gov (United States)

    Rodríguez-Salinas, Elizabeth; Riveros-Rosas, Héctor; Li, Zhongkui; Fucíková, Karolina; Brand, Jerry J; Lewis, Louise A; González-Halphen, Diego

    2012-07-01

    In most eukaryotes the subunit 2 of cytochrome c oxidase (COX2) is encoded in intact mitochondrial genes. Some green algae, however, exhibit split cox2 genes (cox2a and cox2b) encoding two polypeptides (COX2A and COX2B) that form a heterodimeric COX2 subunit. Here, we analyzed the distribution of intact and split cox2 gene sequences in 39 phylogenetically diverse green algae in phylum Chlorophyta obtained from databases (28 sequences from 22 taxa) and from new cox2 data generated in this work (23 sequences from 18 taxa). Our results support previous observations based on a smaller number of taxa, indicating that algae in classes Prasinophyceae, Ulvophyceae, and Trebouxiophyceae contain orthodox, intact mitochondrial cox2 genes. In contrast, all of the algae in Chlorophyceae that we examined exhibited split cox2 genes, and could be separated into two groups: one that has a mitochondrion-localized cox2a gene and a nucleus-localized cox2b gene ("Scenedesmus-like"), and another that has both cox2a and cox2b genes in the nucleus ("Chlamydomonas-like"). The location of the split cox2a and cox2b genes was inferred using five different criteria: differences in amino acid sequences, codon usage (mitochondrial vs. nuclear), codon preference (third position frequencies), presence of nucleotide sequences encoding mitochondrial targeting sequences and presence of spliceosomal introns. Distinct green algae could be grouped according to the form of cox2 gene they contain: intact or fragmented, mitochondrion- or nucleus-localized, and intron-containing or intron-less. We present a model describing the events that led to mitochondrial cox2 gene fragmentation and the independent and sequential migration of cox2a and cox2b genes to the nucleus in chlorophycean green algae. We also suggest that the distribution of the different forms of the cox2 gene provides important insights into the phylogenetic relationships among major groups of Chlorophyceae.

  10. Cox-Ingersoll-Ross模型的统计推断%Statistical Inference of Cox-Ingersoll-Ross Model

    Institute of Scientific and Technical Information of China (English)

    舒丽玲; 周占功

    2006-01-01

    该文在离散样本观察下,研究了Cox-Ingersoll-Ross模型的统计推问题,给出了CIR过程的平稳均值m与平稳方差ν的矩估计,并用-m和-ν给出了CIR过程中尺度参数α与β波动率之间的关系,基于CIR过程的平方变差,得到参数β的平方变差估计和参数α的估计.通过数值模拟的方法对平方变差估计与条件矩估计([9])方法作了比较,并选择1997-2006年的R007数据对这两种方法进行了实证分析.

  11. Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX-2 adn iNOS inhibitors for treatment in Malaysia.

    Science.gov (United States)

    Hong, Seok Kwan; Gul, Yunus A; Ithnin, Hairuszah; Talib, Arni; Seow, Heng Fong

    2004-01-01

    Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

  12. COX-2: A Pivotal Enzyme in Mucosal Protection and Resolution of Inflammation

    Directory of Open Access Journals (Sweden)

    John L. Wallace

    2006-01-01

    Full Text Available The discovery of a second form of cyclooxygenase, COX-2, led to a burst of research aimed at the development of nonsteroidal anti-inflammatory drugs that would not damage the gastrointestinal tract. In the years since, this promise has only been partially fulfilled. Selective COX-2 inhibitors cause less gastric damage than conventional, nonselective COX inhibitors, but their use is still associated with significant gastrointestinal injury, and with toxicity in the renal and cardiovascular systems. COX-2 is now recognized as a source of mediators that produce many beneficial and detrimental effects in the digestive system. In this review, the roles of COX-2 in mucosal defense and injury are discussed. Furthermore, contributions of COX-2–derived products to the long-term consequences of intestinal inflammation, including cancer, are reviewed.

  13. Regulation of COX-2 expression by miR-146a in lung cancer cells.

    Science.gov (United States)

    Cornett, Ashley L; Lutz, Carol S

    2014-09-01

    Prostaglandins are a class of molecules that mediate cellular inflammatory responses and control cell growth. The oxidative conversion of arachidonic acid to prostaglandin H2 is carried out by two isozymes of cyclooxygenase, COX-1 and COX-2. COX-1 is constitutively expressed, while COX-2 can be transiently induced by external stimuli, such as pro-inflammatory cytokines. Interestingly, COX-2 is overexpressed in numerous cancers, including lung cancer. MicroRNAs (miRNAs) are small RNA molecules that function to regulate gene expression. Previous studies have implicated an important role for miRNAs in human cancer. We demonstrate here that miR-146a expression levels are significantly lower in lung cancer cells as compared with normal lung cells. Conversely, lung cancer cells have higher levels of COX-2 protein and mRNA expression. Introduction of miR-146a can specifically ablate COX-2 protein and the biological activity of COX-2 as measured by prostaglandin production. The regulation of COX-2 by miR-146a is mediated through a single miRNA-binding site present in the 3' UTR. Therefore, we propose that decreased miR-146a expression contributes to the up-regulation and overexpression of COX-2 in lung cancer cells. Since potential miRNA-mediated regulation is a functional consequence of alternative polyadenylation site choice, understanding the molecular mechanisms that regulate COX-2 mRNA alternative polyadenylation and miRNA targeting will give us key insights into how COX-2 expression is involved in the development of a metastatic condition.

  14. Population death sequences and Cox processes driven by interacting Feller diffusions

    CERN Document Server

    Wei Gang; Feng Jian Feng

    2002-01-01

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

  15. Use of cox-2 inhibitors in patients with retinal venous occlusive disease.

    Science.gov (United States)

    Recchia, Franco M; Chen, Eric; Li, Chun; Maguluri, Srilakshmi

    2008-01-01

    To determine the prevalence of prior or current usage of COX-2 inhibitors among patients with retinal venous occlusion (RVO). Records of all patients with RVO and control patients matched by age and gender without the diagnosis of RVO seen in a retina referral practice between May 1999 and October 2004 were reviewed. Prevalence of COX-2 inhibitor usage was compared. Multivariable analysis was used to assess the independent correlation of COX-2 inhibitor usage with RVO. A total of 111 consecutive patients with RVO and 316 controls without RVO were identified. There was no significant difference in race or presence of hypertension between cases and controls. Ten of the RVO patients (9%) had a history of using COX-2 inhibitors. Of these 10 patients, one had a central RVO, one had a hemi-central RVO, and eight had a branch RVO. Thirty-nine of the 321 controls (12%) had a history of COX-2 inhibitor use. The prevalence of COX-2 inhibitor usage among RVO patients was not significantly different from that of controls (9% versus 12%; P = 0.37). In a multivariable analysis adjusting for effects of age, gender, hypertension, diabetes, and cardiovascular disease, the association of COX-2 inhibitor usage and RVO was still not significant (P = 0.48). A few patients with RVO had prior or concurrent use of COX-2 inhibitors. The prevalence of COX-2 inhibitor usage does not appear to be significantly higher in patients with RVO.

  16. Structural insight into DNA binding and oligomerization of the multifunctional Cox protein of bacteriophage P2.

    Science.gov (United States)

    Berntsson, Ronnie P-A; Odegrip, Richard; Sehlén, Wilhelmina; Skaar, Karin; Svensson, Linda M; Massad, Tariq; Högbom, Martin; Haggård-Ljungquist, Elisabeth; Stenmark, Pål

    2014-02-01

    The Cox protein from bacteriophage P2 is a small multifunctional DNA-binding protein. It is involved in site-specific recombination leading to P2 prophage excision and functions as a transcriptional repressor of the P2 Pc promoter. Furthermore, it transcriptionally activates the unrelated, defective prophage P4 that depends on phage P2 late gene products for lytic growth. In this article, we have investigated the structural determinants to understand how P2 Cox performs these different functions. We have solved the structure of P2 Cox to 2.4 Å resolution. Interestingly, P2 Cox crystallized in a continuous oligomeric spiral with its DNA-binding helix and wing positioned outwards. The extended C-terminal part of P2 Cox is largely responsible for the oligomerization in the structure. The spacing between the repeating DNA-binding elements along the helical P2 Cox filament is consistent with DNA binding along the filament. Functional analyses of alanine mutants in P2 Cox argue for the importance of key residues for protein function. We here present the first structure from the Cox protein family and, together with previous biochemical observations, propose that P2 Cox achieves its various functions by specific binding of DNA while wrapping the DNA around its helical oligomer.

  17. Evaluating COX-2-765 G →C Genetic Polymorphism in Migraineurs

    Directory of Open Access Journals (Sweden)

    E Mozaffari

    2015-08-01

    Results: The study results revealed that the frequency of the COX-2-765CC and COX-2-765CG genotypes in migraine cases were significantly higher than those of controls. Conclusion: The study findings demonstrated that COX-2-765G→C polymorphism can increase the risk of migraine susceptibility. However, further studies are necessitated to be conducted on larger samples in different nations in other parts of the world in order to assess the role of COX-2 gene variants in the migraine development.

  18. COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

    Science.gov (United States)

    Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard

    2013-01-01

    The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.

  19. Cox7a2 mediates steroidogenesis in TM3 mouse Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Liang Chen; Zhong-Cheng Xin; Xin Li; Long Tian; Yi-Ming Yuan; Gang Liu; Xue-Jun Jiang; Ying-Lu Guo

    2006-01-01

    Aim: To investigate the regulatory function of Cox7a2 on steroidogenesis and the mechanism involved in TM3 mouse Leydig cells. Methods: The cDNA of Cox7a2 was cloned from TM3 mouse Leydig cells. It was subcloned to pDsRedExpress-N1 and transfected back into TM3 mouse Leydig cells for Cox7a2 overexpression by transient gene transfection.Steroidogenesis affected by overexpressed Cox7a2 was studied by ELISA. To elicit the mechanism of this effect,expression of steroidogenic acute regulatory (StAR) protein and reactive oxygen species (ROS) were examined by Western blot and fluorometer, respectively. Results: The cDNA of Cox7a2 (249 bp) was cloned from Leydig cells and confirmed by DNA sequencing. After constructed pDsRed-Express-Nl-Cox7a2 was transfected back into TM3 mouse Leydig cells, Cox7a2 inhibited not only luteinizing hormone (LH)-induced secretion of testosterone but also the expression of StAR protein. At the same time, Cox7a2 increased the activity of ROS in TM3 mouse Leydig cells. Conclusion:Cox7a2 inhibited LH-induced StAR protein expression, and consequent testosterone production, at least in part, by increasing ROS activity in TM3 mouse Leydig cells.

  20. Expression and significance of COX-2 and VEGF in osteosarcoma%骨肉瘤组织中COX-2、VEGF的表达及意义

    Institute of Scientific and Technical Information of China (English)

    马隽; 陈晓明; 钟艳平; 黎丹戎; 肖增明

    2011-01-01

    目的 观察骨肉瘤组织中环氧化酶2(COX-2)、血管内皮生长因子(VEGF)的表达情况,并探讨其意义.方法 对骨肉瘤患者45例行截肢术或瘤段切除假体置换术.术中分别切取骨肉瘤组织及对应癌旁(肿瘤组织边缘外5.0 cm处)组织标本.采用免疫组化SP法检测骨肉瘤组织及其癌旁组织中的COX-2、VEGF;以CD34为标记,计算微血管密度(MVD).结果 COX-2和VEGF阳性表达率及MVD在骨肉瘤组织中分别为80.0%、75.6%和(43.6±11.4)条/HP,均高于癌旁组织的22.2%、17.8%和(13.5±7.3)条/HP,且三者与骨肉瘤的外科分期有关(P均<0.05).COX-2与VEGF的表达呈正相关,COX-2和VEGF的表达均与MVD呈正相关(r分别为0.75、0.58和0.75,P均<0.05).COX-2和VEGF同时阳性表达时,MVD显著增高(P<0.05).结论 COX-2和VEGF在骨肉瘤组织中呈高表达,且与骨肉瘤外科分期呈正相关.二者共同参与了骨肉瘤的发生、发展,其机制可能是促进骨肉瘤组织中血管生成.%Objective To investigate the expression of cyclooxygenase 2 (COX-2) and vascular endothelial growth factor (VEGF) in osteosarcoma and explore the significance.Methods 45 patients with osteosarcoma were treated with amputation or prosthesis replacement.Osteosarcoma and corresponding adjacent ( > 5.0 cm at the outer edge of the tumor tissue) tissue samples were obtained during operation.The expression of COX-2, VEGF and MVD marked by CD34 of osteosarcoma and their adjacent tissues were detected by immuno histochemistry.Results The positive rates of COX-2, VEGF and MVD in osteosarcoma tissues were 80.0%, 75.6% and (43.6 ± 11.4) stripe/HP, respectively, which were higher than those in adjacent tissues(P all <0.05).In patients with osteosarcoma, the expression of COX-2, VEGF and MVD were associated with Enneking stage( P all <0.05).There was a positive relationship between the expression of COX-2 and VEGF,the expression of COX-2 and VEGF were positively correlated with MVD

  1. 沉默COX-2抑制A549细胞的恶性增殖%COX-2 silencing inhibits cell proliferation in A549 cell

    Institute of Scientific and Technical Information of China (English)

    Weiying Li; Wentao Yue; Lina Zhang; Xiaoting Zhao; Li Ma; Xuehui Yang; Chunyan Zhang; Yue Wang; Meng Gu

    2011-01-01

    Objective: The aim of this study was to explore the effects on malignant proliferation of A549 cell by silencing cyclooxygenase (COX)-2. Methods: In the present study, we constructed three siRNA vectors producing small interference RNA. The siRNA vectors and the vacant vectors were transfected into A549 cell with lipofectamine respectively and the transfected cell strains were constructed. The change of COX-2 expression levels was examined by Western blot and RT-PCR. The effects on the proliferation of lung cancer cells were studied by cell growth curve, clonogenic assay and xenograft assays. Results: The siRNA expression vectors produced marked effects in A549 cell but the inhibited effects were different. The effect of psi-10 was best and the mRNA and protein levels of COX-2 reduced 61.2% and 56.2% respectively in A549-si10 cell in contrast to the control.The growth of A549 cell slowed and the colony formation rate reduced after silencing COX-2. In xenograft assays, the growth speeds of tumor became slow and the numbers of tumor reduced after silencing COX-2. Conclusion: The si10 target of COX-2 has the best silencing effect in A549 cell and the best inhibition effect on malignant proliferation of A549 cell in vivo and in vitro.

  2. Prognostic Significance and Clinicopathological Associations of COX-2 SNP in Patients with Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peter P. Grimminger

    2009-01-01

    Full Text Available Background. To further improve the screening, diagnosis, and therapy of patients with nonsmall cell lung cancer (NSCLC additional diagnostic tools are urgently needed. Gene expression of Cyclooxygenase-2 (COX-2 has been linked to prognosis in patients with NSCLC. The role of the COX-2 926G>C Single Nucleotide Polymorphism (SNP in patients with NSCLC remains unclear. The aim of this study was to investigate the potential of the COX-2 926G>C SNP as a molecular marker in this disease. Methods. COX-2 926G>C SNP was analyzed in surgically resected tumor tissue of 85 patients with NSCLC using a PCR-based RFLP technique. Results. The COX-2 926G>C SNP genotypes were detected with the following frequencies: GG n=62 (73%, GC n=20 (23%, CC n=3 (4%. There were no associations between COX-2 SNP genotype and histology, grading or gender detectable. COX-2 SNP was significantly associated with tumor stage (P=.032 and lymph node status (P=.016, Chi-square test. With a median followup of 85.9 months, the median survival was 59.7 months. There were no associations seen between the COX-2 SNP genotype and patients prognosis. Conclusions. The COX-2 926G>C SNP is detectable at a high frequency in patients with NSCLC. The COX-2 926G>C SNP genotype is not a prognostic molecular marker in this disease. However, patients with the GC or CC genotype seem more susceptible to lymph node metastases and higher tumor stage than patients with the GG genotype. The results suggest COX-2 926G>C SNP as a molecular marker for lymph node involvement in this disease.

  3. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1.

    Science.gov (United States)

    Islam, Abul B M M K; Dave, Mandar; Amin, Sonia; Jensen, Roderick V; Amin, Ashok R

    2016-04-01

    The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2(-/-) or COX-1(-/-) mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2(-/-)>COX-1(-/-)>WT+IL-1β. COX-1(-/-) or COX-2(-/-) cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive "anti-inflammatory, proinflammatory, and redox-activated" signature in the protein-protein interactome map was observed in COX-2(-/-) cells. The augmented COX-1 mRNA (in COX-2(-/-) cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2(-/-) cells generated an "eicosanoid storm". The genomic characteristics of COX-2(-/-) is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1(-/-) and COX-2(-/-) cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  4. Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1

    Directory of Open Access Journals (Sweden)

    Abul B.M.M.K. Islam

    2016-04-01

    Full Text Available The constitutively-expressed cyclooxygenase 1 (COX-1 and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA to prostaglandins (PGs. However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT mice and COX-2-/- or COX-1-/- mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-/- > COX-1-/- > WT + IL-1β. COX-1-/- or COX-2-/- cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory, proinflammatory, and redox-activated” signature in the protein–protein interactome map was observed in COX-2-/- cells. The augmented COX-1 mRNA (in COX-2-/- cells was associated with the upregulation of mRNAs for glutathione S-transferase (GST, superoxide dismutase (SOD, NAD(PH dehydrogenase quinone 1 (NQO1, aryl hydrocarbon receptor (AhR, peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4, PGF1α, thromboxane B2 (TXB2, and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an “eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  5. Imaging of cyclooxygenase-2 (COX-2) expression : Potential use in diagnosis and drug evaluation

    NARCIS (Netherlands)

    de Vries, E. F. J.

    2006-01-01

    Cyclooxygenase is an enzyme that catalyzes the first two steps in the biosynthesis of prostanoids. The constitutively expressed isoform COX-1 is regarded as a housekeeping enzyme that is responsible for the normal production of prostanoids. The inducible isoform COX-2, on the other hand, is transien

  6. Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

    Institute of Scientific and Technical Information of China (English)

    BaocunSun; ShiwuZhang; XiulanZhao; YanxueLiu; ChunshengNi; DanfangZhang; HongQi; ZhiyongLiu; XishanHao

    2004-01-01

    OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

  7. COX-2 and TGF-β expression in proliferative disorders of canine prostate

    OpenAIRE

    Marcela M.P. Rodrigues; Di Santis, Giovana W.; De Moura, Veridiana M.B.D.; Amorim, Renée Laufer [UNESP

    2010-01-01

    COX-2 and TGF-β expression was determined in order to correlate non-neoplastic lesions, preneoplastic lesions and carcinoma in the prostate of dogs. The results show that neoplastic and preneoplastic lesions express more COX-2 and TGF-β when compared to carcinomas, which suggests these proteins may cooperate in the process of prostate tumorigenesis.

  8. Protective effect of NSAIDs on cancer and influence of COX-2 C-765G genotype

    NARCIS (Netherlands)

    C. Siemes (Claire); L.E. Visser (Loes); J.W.W. Coebergh (Jan Willem); A. Hofman (Albert); A.G. Uitterlinden (André); B.H.Ch. Stricker (Bruno)

    2008-01-01

    textabstractPurpose: Inhibition of COX-2 enzymes is a frequently suggested mechanism for the beneficial effects of NSAIDs on carcinogenesis. The aim of this study was to explore the role of cumulative NSAID use on four common non-skin related cancers and modification by COX-2 G-765C genotype. Patien

  9. Predicting and Modelling of Survival Data when Cox's Regression Model does not hold

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects...

  10. Comparing treatment effects after adjustment with multivariable Cox proportional hazards regression and propensity score methods

    NARCIS (Netherlands)

    Martens, Edwin P|info:eu-repo/dai/nl/088859010; de Boer, Anthonius|info:eu-repo/dai/nl/075097346; Pestman, Wiebe R; Belitser, Svetlana V; Stricker, Bruno H Ch; Klungel, Olaf H|info:eu-repo/dai/nl/181447649

    PURPOSE: To compare adjusted effects of drug treatment for hypertension on the risk of stroke from propensity score (PS) methods with a multivariable Cox proportional hazards (Cox PH) regression in an observational study with censored data. METHODS: From two prospective population-based cohort

  11. Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

    Science.gov (United States)

    Gao, Shui-Ping; Sun, He-Fen; Jiang, Hong-Lin; Li, Liang-Dong; Hu, Xin; Xu, Xiao-En; Jin, Wei

    2015-12-22

    COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

  12. Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.

    Science.gov (United States)

    Indrieri, Alessia; van Rahden, Vanessa Alexandra; Tiranti, Valeria; Morleo, Manuela; Iaconis, Daniela; Tammaro, Roberta; D'Amato, Ilaria; Conte, Ivan; Maystadt, Isabelle; Demuth, Stephanie; Zvulunov, Alex; Kutsche, Kerstin; Zeviani, Massimo; Franco, Brunella

    2012-11-02

    Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.

  13. Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells.

    Science.gov (United States)

    Oğuz, Nurgül; Kırça, Mustafa; Çetin, Arzu; Yeşilkaya, Akın

    2017-10-01

    Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

  14. Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Ermelinda Vernieri

    2013-01-01

    Full Text Available Cyclooxygenase (COX is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic development and offer a new perspective for a further use of COX-2 inhibitors. The present study extends the evaluation of the COX activity to all 203 possible natural tripeptide sequences following a rational approach consisting in molecular modeling, synthesis, and biological tests. Based on data obtained from virtual screening, only those peptides with better profile of affinity have been selected and classified into two groups called S and E. Our results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of the new selective COX-2 inhibitors drugs.

  15. Cox-2 expression in ovarian malignancies: a review of the clinical aspects.

    Science.gov (United States)

    Menczer, Joseph

    2009-10-01

    COX-2 is an inducible enzyme expressed only in response to stimuli such as mitogens, cytokines, growth factors or hormones, and is pro-inflammatory. It plays an important role in tumorigenesis. The purpose of the present report is to review the clinical aspects of COX-2 expression in ovarian malignancies. A PubMed (http://www.pubmed.gov/) search of investigations published from July 2001 until August 2008 and containing the term COX-2 in combination with ovarian malignancies was conducted. The clinical aspects of the relevant investigations were reviewed. COX-2 is expressed in ovarian tumors of low malignant potential (LMP), in epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC) and apparently plays a role in their carcinogenesis. Its expression seems to be correlated with VEGF that serves as a predictor of poor prognosis in some non-gynecologic malignancies. COX-2 expression is higher in EOC than in LMPs. The results with regard to the association between COX-2 expression and prognostic factors, response to treatment and outcome in ovarian malignancies are inconsistent. Clinical studies dealing with the effect of COX-2 inhibitors on outcome are scarce. The use of COX-2 expression in gynecological malignancies in clinical practice remains to be elucidated.

  16. Nucleobindin co-localizes and associates with cyclooxygenase (COX-2 in human neutrophils.

    Directory of Open Access Journals (Sweden)

    Patrick Leclerc

    Full Text Available The inducible cyclooxygenase isoform (COX-2 is associated with inflammation, tumorigenesis, as well as with physiological events. Despite efforts deployed in order to understand the biology of this multi-faceted enzyme, much remains to be understood. Nucleobindin (Nuc, a ubiquitous Ca(2+-binding protein, possesses a putative COX-binding domain. In this study, we investigated its expression and subcellular localization in human neutrophils, its affinity for COX-2 as well as its possible impact on PGE(2 biosynthesis. Complementary subcellular localization approaches including nitrogen cavitation coupled to Percoll fractionation, immunofluorescence, confocal and electron microscopy collectively placed Nuc, COX-2, and all of the main enzymes involved in prostanoid synthesis, in the Golgi apparatus and endoplasmic reticulum of human neutrophils. Immunoprecipitation experiments indicated a high affinity between Nuc and COX-2. Addition of human recombinant (hr Nuc to purified hrCOX-2 dose-dependently caused an increase in PGE(2 biosynthesis in response to arachidonic acid. Co-incubation of Nuc with COX-2-expressing neutrophil lysates also increased their capacity to produce PGE(2. Moreover, neutrophil transfection with hrNuc specifically enhanced PGE(2 biosynthesis. Together, these results identify a COX-2-associated protein which may have an impact in prostanoid biosynthesis.

  17. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

    Science.gov (United States)

    Hugo, Honor J; Saunders, C; Ramsay, R G; Thompson, E W

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

  18. Glutathione selectively modulates the binding of platinum drugs to human copper chaperone Cox17.

    Science.gov (United States)

    Zhao, Linhong; Wang, Zhen; Wu, Han; Xi, Zhaoyong; Liu, Yangzhong

    2015-12-01

    The copper chaperone Cox17 (cytochrome c oxidase copper chaperone) has been shown to facilitate the delivery of cisplatin to mitochondria, which contributes to the overall cytotoxicity of the drug [Zhao et al. (2014) Chem. Commun. 50: , 2667-2669]. Kinetic data indicate that Cox17 has reactivity similar to glutathione (GSH), the most abundant thiol-rich molecule in the cytoplasm. In the present study, we found that GSH significantly modulates the reaction of platinum complexes with Cox17. GSH enhances the reactivity of three anti-cancer drugs (cisplatin, carboplatin and oxaliplatin) to Cox17, but suppresses the reaction of transplatin. Surprisingly, the pre-formed cisplatin-GSH adducts are highly reactive to Cox17; over 90% platinum transfers from GSH to Cox17. On the other hand, transplatin-GSH adducts are inert to Cox17. These different effects are consistent with the drug activity of these platinum complexes. In addition, GSH attenuates the protein aggregation of Cox17 induced by platination. These results indicate that the platinum-protein interactions could be substantially influenced by the cellular environment.

  19. Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer.

    Science.gov (United States)

    Foersch, Sebastian; Neufert, Clemens; Neurath, Markus F; Waldner, Maximilian J

    2013-01-01

    Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC) development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC.

  20. Endomicroscopic Imaging of COX-2 Activity in Murine Sporadic and Colitis-Associated Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Sebastian Foersch

    2013-01-01

    Full Text Available Although several studies propose a chemopreventive effect of aspirin for colorectal cancer (CRC development, the general use of aspirin cannot be recommended due to its adverse side effects. As the protective effect of aspirin has been associated with an increased expression of COX-2, molecular imaging of COX-2, for instance, during confocal endomicroscopy could enable the identification of patients who would possibly benefit from aspirin treatment. In this pilot trial, we used a COX-2-specific fluorescent probe for detection of colitis-associated and sporadic CRC in mice using confocal microscopy. Following the injection of the COX-2 probe into tumor-bearing APCmin mice or mice exposed to the AOM + DSS model of colitis-associated cancer, the tumor-specific upregulation of COX-2 could be validated with in vivo fluorescence imaging. Subsequent confocal imaging of tumor tissue showed an increased number of COX-2 expressing cells when compared to the normal mucosa of healthy controls. COX-2-expression was detectable with subcellular resolution in tumor cells and infiltrating stroma cells. These findings pose a proof of concept and suggest the use of CLE for the detection of COX-2 expression during colorectal cancer surveillance endoscopy. This could improve early detection and stratification of chemoprevention in patients with CRC.

  1. Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance.

    Science.gov (United States)

    Queiroga, Felisbina Luisa; Perez-Alenza, Maria Dolores; Silvan, Gema; Peña, Laura; Lopes, Carlos; Illera, Juan Carlos

    2005-01-01

    Cyclo-oxygenase (Cox-2) plays an important role in mammary carcinogenesis, nevertheless, its role in canine mammary tumors, and particularly in inflammatory mammary carcinoma (IMC), is unknown. Tumor Cox-2 levels were analyzed by enzyme immunoassay, in post-surgical tumor homogenates of 129 mammary tumors (62 dysplasias and benign tumors, 57 malignant non-IMC and 10 IMC) from 57 female dogs. The highest Cox-2 values were detected in the IMC group. In non-IMC malignant tumors, high values of Cox-2 were related to skin ulceration (p IMC cases could indicate a special role of Cox-2 in the inflammatory phenotype and open the possibility of additional new therapeutic approaches in this special type of mammary cancer in humans and dogs.

  2. Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach.

    Science.gov (United States)

    Shahraki, Hadi Raeisi; Salehi, Alireza; Zare, Najaf

    2015-01-01

    We used to LASSO-Cox method for determining prognostic factors of male breast cancer survival and showed the superiority of this method compared to Cox proportional hazard model in low sample size setting. In order to identify and estimate exactly the relative hazard of the most important factors effective for the survival duration of male breast cancer, the LASSO-Cox method has been used. Our data includes the information of male breast cancer patients in Fars province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox models were fitted for 20 classified variables. To reduce the impact of missing data, the multiple imputation method was used 20 times through the Markov chain Mont Carlo method and the results were combined with Rubin's rules. In 50 patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10 year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led to eliminating 8 low effect variables and also decreased the standard error by 2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox proportional hazard method was calculated as 22.39. The19 years follow of male breast cancer patients show that the age, having a history of alcohol use, nipple discharge, laterality, histological grade and duration of symptoms were the most important variables that have played an effective role in the patient's survival. In such situations, estimating the coefficients by LASSO-Cox method will be more efficient than the Cox's proportional hazard method.

  3. Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

    Science.gov (United States)

    Fernandes, Carla; Palmeira, Andreia; Ramos, Inês I.; Carneiro, Carlos; Afonso, Carlos; Tiritan, Maria Elizabeth; Cidade, Honorina; Pinto, Paula C.A.G.; Saraiva, M. Lúcia M.F.S.; Reis, Salette; Pinto, Madalena M.M.

    2017-01-01

    Searching of new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties, particularly those with anti-inflammatory activity, has remained an area of interest of our group. Herein, we describe in silico studies and in vitro inhibitory assays of cyclooxygenases (COX-1 and COX-2) for different enantiomeric pairs of CDXs. The evaluation of the inhibitory activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs; known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx—Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(−)-enantiomer of the nonsteroidal anti-inflammatory drug ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer, protein binding affinity for CDXs was also evaluated by spectrofluorimetry as well as in in silico. For some CDXs enantioselectivity was observed. PMID:28561772

  4. Flavocoxid Inhibits Phospholipase A2, Peroxidase Moieties of the Cyclooxygenases (COX, and 5-Lipoxygenase, Modifies COX-2 Gene Expression, and Acts as an Antioxidant

    Directory of Open Access Journals (Sweden)

    Bruce P. Burnett

    2011-01-01

    Full Text Available The multiple mechanisms of action for flavocoxid relating to arachidonic acid (AA formation and metabolism were studied in vitro. Flavocoxid titrated into rat peritoneal macrophage cultures inhibited cellular phospholipase A2 (PLA2 (IC50 = 60 μg/mL. In in vitro enzyme assays, flavocoxid showed little anti-cyclooxygenase (CO activity on COX-1/-2 enzymes, but inhibited the COX-1 (IC50 = 12.3 and COX-2 (IC50 = 11.3 μg/mL peroxidase (PO moieties as well as 5-lipoxygenase (5-LOX (IC50 = 110 μg/mL. No detectable 5-LOX inhibition was found for multiple traditional and COX-2 selective NSAIDs. Flavocoxid also exhibited strong and varied antioxidant capacities in vitro and decreased nitrite levels (IC50 = 38 μg/mL in rat peritoneal macrophages. Finally, in contrast to celecoxib and ibuprofen, which upregulated the cox-2 gene, flavocoxid strongly decreased expression. This work suggests that clinically favourable effects of flavocoxid for management of osteoarthritis (OA are achieved by simultaneous modification of multiple molecular pathways relating to AA metabolism, oxidative induction of inflammation, and neutralization of reactive oxygen species (ROS.

  5. Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

    Science.gov (United States)

    McCarty, Mark F

    2012-01-01

    A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth

  6. Demethoxycurcumin Preserves Renovascular Function by Downregulating COX-2 Expression in Hypertension

    Science.gov (United States)

    2016-01-01

    Hypertension-associated endothelial dysfunction is largely due to the exaggerated vasoconstrictor generation by cyclooxygenase-2 (COX-2). COX-2 is induced under inflammatory condition. Demethoxycurcumin (DMC) is a major component of Curcuma longa L, which possesses anti-inflammatory action. This study aimed to examine whether DMC protects endothelial function in hypertension by modulating COX-2. Changes in isometric tension showed that in vivo and ex vivo treatment with DMC rescued the attenuated endothelium-dependent relaxations (EDRs) and elevated endothelium-dependent contractions (EDCs) in the renal arteries of SHR, which were also corrected by acute usage of the COX-2 inhibitor celecoxib. The restoration of renovascular activity by DMC was accompanied by the normalization of COX-2 expression. The enhanced COX-2 expression observed in the renal arteries of hypertensive patients was suppressed by incubation of excised arteries with DMC for 12 hrs. In the renal arteries of Wistar-Kyoto rats (WKY), DMC prevented the endothelial dysfunction caused by angiotensin II. The reduction in the generation of nitric oxide (NO) and expression of eNOS phosphorylation (Ser1177) in human umbilical vein endothelial cells caused by angiotensin II (Ang II) were restored by DMC or celecoxib. Our findings suggest that DMC may decrease COX-2 expression and improve endothelial function in hypertension. PMID:28105253

  7. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  8. Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kreipke, Christian W; Thomas, David M; Van Shura, Kerry E; Lyman, Megan; McDonough, John H; Kuhn, Donald M

    2010-12-01

    Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4h to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity.

  9. A cyclooxygenase (COX) inhibitory biflavonoid from the seeds of Semecarpus anacardium.

    Science.gov (United States)

    Selvam, C; Jachak, Sanjay M

    2004-12-01

    Semecarpus anacardium Linn., Anacardiaceae, is being most commonly used in India for the treatment of rheumatoid arthritis and other inflammatory disorders. Bioactivity guided fractionation of ethyl acetate extract led to the isolation of major active principle, tetrahydroamentoflavone (THA), a biflavonoid. The in vitro cyclooxygenase (COX-1) catalyzed prostaglandin biosynthesis assay of THA gave an IC(50) value of 29.5 microM (COX-1) and 40.5% inhibition at 100 microg/mL (COX-2). The in vivo carrageenan induced paw edema assay resulted in dose dependent anti-inflammatory effect of THA and the activity was comparable to that of ibuprofen, one of the well known NSAIDs.

  10. The Distribution of the Interval between Events of a Cox Process with Shot Noise Intensity

    Directory of Open Access Journals (Sweden)

    Angelos Dassios

    2008-01-01

    Full Text Available Applying piecewise deterministic Markov processes theory, the probability generating function of a Cox process, incorporating with shot noise process as the claim intensity, is obtained. We also derive the Laplace transform of the distribution of the shot noise process at claim jump times, using stationary assumption of the shot noise process at any times. Based on this Laplace transform and from the probability generating function of a Cox process with shot noise intensity, we obtain the distribution of the interval of a Cox process with shot noise intensity for insurance claims and its moments, that is, mean and variance.

  11. Recollections on the early days of the Marcé Society for Perinatal Mental Health from Professor John Cox.

    Science.gov (United States)

    Cox, John L; Wisner, Katherine L

    2016-02-01

    Dr. Katherine Wisner interviewed Dr. John Cox, a founding member of the Marcé Society. Dr. Cox discussed the beginnings of the Marcé Society, his views about the current Society, and his vision for the future.

  12. Expression of COX-2 and p53 in juvenile polyposis coli and its correlation with adenomatous changes

    Directory of Open Access Journals (Sweden)

    Shatavisha Das Gupta

    2016-01-01

    Conclusion: We observed significantly higher COX-2 expression in JPC. Establishment of the role of COX-2 in JPC will help us formulate chemopreventive therapies as an adjunct to its surgical management.

  13. Enforced Expression of miR-101 Inhibits Prostate Cancer Cell Growth by Modulating the COX-2 Pathway In Vivo

    OpenAIRE

    Hao, Yubin; Gu, Xinbin; Zhao, Yuan; Greene, Stephen; Sha, Wei; Smoot, Duane T.; Califano, Joseph; Wu, T.-C.; Pang, Xiaowu

    2011-01-01

    It is commonly agreed that there is an association of chronic inflammation with tumorigenesis. COX-2, a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth; thus, overexpression of COX-2 is often found in tumor tissues. Therefore, a better understanding of the regulatory mechanism(s) of COX-2 could lead to novel targeted cancer therapies. In this study, we investigated the mechanism of microRNA-101 (miR-101)-regulated COX-2 expression and the therape...

  14. Cyclooxygenases in human and mouse skin and cultured human keratinocytes: association of COX-2 expression with human keratinocyte differentiation

    Science.gov (United States)

    Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.

    1996-01-01

    Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.

  15. Forecasts of non-Gaussian parameter spaces using Box-Cox transformations

    CERN Document Server

    Joachimi, B

    2011-01-01

    Forecasts of statistical constraints on model parameters using the Fisher matrix abound in many fields of astrophysics. The Fisher matrix formalism involves the assumption of Gaussianity in parameter space and hence fails to predict complex features of posterior probability distributions. Combining the standard Fisher matrix with Box-Cox transformations, we propose a novel method that accurately predicts arbitrary posterior shapes. The Box-Cox transformations are applied to parameter space to render it approximately multivariate Gaussian, performing the Fisher matrix calculation on the transformed parameters. We demonstrate that, after the Box-Cox parameters have been determined from an initial likelihood evaluation, the method correctly predicts changes in the posterior when varying various parameters of the experimental setup and the data analysis, with marginally higher computational cost than a standard Fisher matrix calculation. We apply the Box-Cox-Fisher formalism to forecast cosmological parameter con...

  16. COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1.

    Science.gov (United States)

    Ban-Ishihara, Reiko; Tomohiro-Takamiya, Shiho; Tani, Motohiro; Baudier, Jacques; Ishihara, Naotada; Kuge, Osamu

    2015-10-07

    Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX)-assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56-repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology.

  17. a study of the slope of cox proportional hazard and weibull models

    African Journals Online (AJOL)

    Adejumo & Ahmadu

    the values of the unknown parameters. These include the ... semi parametric cox proportional hazard model when the parametric ... simulated and the real life data approach. ... greatest risk progression of TB infection to active disease. People.

  18. Neoplasms escape selective COX-2 inhibition in an animal model of breast cancer.

    LENUS (Irish Health Repository)

    Barry, M

    2009-06-01

    Cyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.

  19. Study of gastrointestinal toxicity of selective COX-2 inhibitors in comparison with conventional NSAIDs

    Directory of Open Access Journals (Sweden)

    Hima Bindu K.

    2016-12-01

    Conclusions: In our short-term study, selective COX-2 inhibitors did not show any advantage over non-selective NSAIDs regarding their gastrointestinal toxicity. [Int J Res Med Sci 2016; 4(12.000: 5180-5184

  20. Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor.

    Science.gov (United States)

    Hasegawa, Kiyoshi; Ishikawa, Kunimi; Kawai, Satoshi; Torii, Yutaka; Kawamura, Kyoko; Kato, Rina; Tsukada, Kazuhiko; Udagawa, Yasuhiro

    2013-12-01

    Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the resistance of cancer cells to chemotherapeutic drugs by affecting multidrug resistance 1 (MDR1) expression. In the present study, we investigated the association between COX-2 and MDR1 expression in endometrial cancers and evaluated the effects of the COX-2 inhibitor, etodolac, in combination with paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36 endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was established from OMC-2 cells. Paclitaxel (1 µg/ml) with or without etodolac (10 µg/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression levels were examined. The concentration of prostaglandin E2 (PGE2) in the supernatant of each cell line was examined by enzyme-linked immunosorbent assay. The function of MDR1 was determined by intracellular accumulation of rhodamine 123 using flow cytometry, and the concentration of intracellular paclitaxel was determined by high-performance liquid chromatography. We found a positive relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA levels were significantly upregulated by paclitaxel treatment and downregulated by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was also significantly upregulated by paclitaxel treatment and tended to be downregulated by co-administration with etodolac. Moreover, co-administration of paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123 efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2 cells and was increased in response to paclitaxel

  1. An observational study of the discrediting of COX-2 NSAIDs in Australia: Vioxx or class effect?

    Directory of Open Access Journals (Sweden)

    Parkinson Lynne

    2011-11-01

    Full Text Available Abstract Background When a medicine such as rofecoxib (Vioxx is withdrawn, or a whole class of medicines discredited such as the selective COX-2 inhibitors (COX-2s, follow-up of impacts at consumer level can be difficult and costly. The Australian Longitudinal Study on Women's Health provides a rare opportunity to examine individual consumer medicine use following a major discrediting event, the withdrawal of rofecoxib and issuing of safety warnings on the COX-2 class of medicines. The overall objective of this paper was to examine the impact of this discrediting event on dispensing of the COX-2 class of medicines, by describing medicine switching behaviours of older Australian women using rofecoxib in September 2004; the uptake of other COX-2s; and the characteristics of women who continued using a COX-2. Methods Participants were concessional beneficiary status women from the Older cohort (born 1921-26 of the Australian Longitudinal Study on Women's Health who consented to linkage to Pharmaceutical Benefits Scheme data, with at least one rofecoxib prescription dispensed in the 12 months before rofecoxib withdrawal. A prescription was defined as one dispensing occasion. Women were grouped by rofecoxib pattern of use: continuous (nine or more prescriptions dispensed in the 12 months prior to rofecoxib withdrawal or non-continuous (eight or less prescriptions dispensed in the 12 months prior to rofecoxib withdrawal users. Incidence rate per 100,000 person days and incidence risk ratio described uptake of alternate medicines, following rofecoxib withdrawal. Kaplan-Meier curves described differences in uptake patterns by medicine and pattern of rofecoxib use. Patterns of use of COX-2s in the next 100 days after first COX-2 uptake were described. Results Medicine switches and pattern of medicines uptake differed significantly depending upon whether a woman was a continuous or non-continuous rofecoxib user prior to rofecoxib discrediting. Continuous

  2. Variations from Zn1-xCoxO Magnetic Semiconductor to Co-ZnCoO Granular Composite

    Institute of Scientific and Technical Information of China (English)

    CHEN Yan-Xue; YAN Shi-Shen; LIU Guo-Lei; MEI Liang-Mo; REN Miao-Juan

    2007-01-01

    @@ We investigate the variations from as-deposited Zn1-xCoxO magnetic semiconductors to the post-annealed CoZnCoO granular composite. The as-deposited Zn1-xCoxO magnetic semiconductor deposited under thermal nonequilibrium conditions is composed of Zn1-xCoxO nanograins of high Co concentration.

  3. Ester Prodrugs of Ketoprofen: Synthesis, In Vitro Stability, In Vivo Biological Evaluation and In Silico Comparative Docking Studies Against COX-1 and COX-2.

    Science.gov (United States)

    Ahmed, Musa; Azam, Faizul; Gbaj, Abdul; Zetrini, Abdulmottaleb E; Abodlal, Amna Salem; Rghigh, Abir; Elmahdi, Eman; Hamza, Amel; Salama, Mabruk; Bensaber, Salah M

    2016-01-01

    Prompted by the ineptness of the currently used non-steroidal antiinflammatory drugs (NSAIDs) to control gastric mucosal and renal adverse reactions, several ester prodrugs of ketoprofen were synthesized and characterized by IR, 1H NMR and mass spectral data. Physicochemical properties such as aqueous solubility, octanol-water partition coefficient log P, chemical stability and enzymatic hydrolysis of the synthesized molecules have been studied to assess their potential as prodrugs. The obtained results confirmed that all ester prodrugs are chemically stable, possess increased lipophilicity compared to their parent compounds and converted to the active drugs in vivo. All of the tested ester prodrugs exhibited marked anti-inflammatory activity ranging from 91.8% to 113.3% in comparison with the parent drug, ketoprofen. A mutual prodrug obtained from two antiinflammatory molecules, ketoprofen and salicylic acid has been noted to potentiate the activity making it most active molecule of the series. The ulcerogenic index of the ester prodrugs was significantly lower than the parent drug, ketoprofen. Comparative docking studies against X-ray crystal structures of COX-1 and COX-2 further provided understanding of their interaction with the cyclooxygenases that will facilitate design of better inhibitors (or prodrugs) with sufficient specificity for COX-2 against COX-1. The study offers an innovative strategy for finding a molecule with safer therapeutic profile for longterm treatment of inflammatory diseases.

  4. Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension.

    Science.gov (United States)

    Avendaño, M S; Martínez-Revelles, S; Aguado, A; Simões, M R; González-Amor, M; Palacios, R; Guillem-Llobat, P; Vassallo, D V; Vila, L; García-Puig, J; Beltrán, L M; Alonso, M J; Cachofeiro, M V; Salaices, M; Briones, A M

    2016-05-01

    Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg · kg(-1) · day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg · kg(-1) · day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg · kg(-1) · day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-α expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage. © 2016 The British Pharmacological Society.

  5. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  6. Hypermethylation of the COX-2 gene is a potential prognostic marker for cervical cancer.

    Science.gov (United States)

    Jo, Hoenil; Kang, Sokbom; Kim, Jae W; Kang, Gyeong H; Park, Noh H; Song, Yong S; Park, Sang Y; Kang, Soon B; Lee, Hyo P

    2007-06-01

    The aim of the present study was to evaluate the DNA hypermethylation profiles of 14 genes known to be associated with tumor behavior and their clinical significance in cervical cancer. The clinical features of 82 patients with stage IB cervical cancer were analyzed in terms of DNA hypermethylation of 14 genes (hMLH1, p16, COX-2, CDH1, APC, DAPK, MGMT, p14, RASSF1A, RUNX3, TIMP3, FHIT, THBS1, and HLTF). Of 14 genes investigated, only hypermethylation of COX-2 showed significant association with poor disease-free survival (P = 0.001). To further investigate an alteration in COX-2 expression by DNA hypermethylation, immunohistochemistry for COX-2 protein was performed in the cervical cancer tissues. We found no significant association between hypermethylation and expression patterns of the COX-2 gene. The present results suggest that DNA hypermethylation of the COX-2 gene may be a potential prognostic marker in early stage cervical cancer, the underlying mechanism of which is independent of gene silencing.

  7. Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation.

    Science.gov (United States)

    Hermanson, Daniel J; Hartley, Nolan D; Gamble-George, Joyonna; Brown, Naoko; Shonesy, Brian C; Kingsley, Phillip J; Colbran, Roger J; Reese, Jeffrey; Marnett, Lawrence J; Patel, Sachin

    2013-09-01

    Augmentation of endogenous cannabinoid (eCB) signaling represents an emerging approach to the treatment of affective disorders. Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid to form prostaglandins, but also inactivates eCBs in vitro. However, the viability of COX-2 as a therapeutic target for in vivo eCB augmentation has not been explored. Using medicinal chemistry and in vivo analytical and behavioral pharmacological approaches, we found that COX-2 is important for the regulation of eCB levels in vivo. We used a pharmacological strategy involving substrate-selective inhibition of COX-2 to augment eCB signaling without affecting related non-eCB lipids or prostaglandin synthesis. Behaviorally, substrate-selective inhibition of COX-2 reduced anxiety-like behaviors in mice via increased eCB signaling. Our data suggest a key role for COX-2 in the regulation of eCB signaling and indicate that substrate-selective pharmacology represents a viable approach for eCB augmentation with broad therapeutic potential.

  8. Antiinflammatory and antinociceptive activities of gossypin and procumbentin--cyclooxygenase-2 (COX-2) inhibition studies.

    Science.gov (United States)

    Mada, Sripal Reddy; Metukuri, Mallikarjuna Reddy; Burugula, Laxminarayana; Reddanna, Pallu; Krishna, Devarakonda Rama

    2009-06-01

    In the present study the antiinflammatory and antinociceptive activities of a few selected flavonoids were investigated. Procumbentin, gossypin, chrysin and methylhespiridin were studied for antiinflammatory and antinociceptive activities using in vitro enzymatic assays and in animal models utilizing acetic acid-induced writhing in mice and hind paw edema in rats. In vitro studies were performed using TMPD (NNN'N'-tetramethyl-p-phenylene diamine) and oxygraphic methods for COX-1 (cyclooxygenase-1), COX-2, 5-LOX (5-lipoxygenase) and 15-LOX. Gossypin and procumbentin showed COX-2 inhibitory activity and exhibited IC(50) (COX-2/COX-1) ratios of 0.14 and 0.11, respectively. None of the flavonoids tested in this study showed LOX inhibitory activity. Four groups were studied for each test compound following intraperitoneal (i.p.) administration of doses of 10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin-induced rat hind paw edema model and antinociceptive activity by acetic acid-induced writhing. Procumbentin and gossypin showed antinociceptive activity at the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30, 100 mg/kg. Procumbentin and gossypin exhibited COX-2 inhibitory activity when tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and gossypin showed antiinflammatory, activities.

  9. Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition.

    Science.gov (United States)

    Qiu, Han-Yue; Wang, Peng-Fei; Li, Zhen; Ma, Jun-Ting; Wang, Xiao-Ming; Yang, Yong-Hua; Zhu, Hai-Liang

    2016-02-01

    COX-2 has long been exploited in the treatment of inflammation and relief of pain; however, research increasingly suggests COX-2 inhibitors might possess potential benefits to thwart tumour processes. In the present study, we designed a series of novel COX-2 inhibitors based on analysis of known inhibitors combined with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Derivative 4d was identified as a potent COX-2 enzyme inhibitor and exerted an anticancer effect through COX-2 inhibition. Further investigation confirmed that 4d could induce A549 cell apoptosis and arrest the cell cycle at the G2/M phase. Moreover, treatment with 4d reduced A549 cell adhesive ability and COX-2 expression. The morphological variation of treated cells was also visualized by confocal microscopy. Overall, the biological profile of 4d suggests that this compound may be developed as a potential anticancer agent.

  10. Expression of COX-2 and bcl-2 in oral lichen planus lesions and lichenoid reactions

    Science.gov (United States)

    Arreaza, Alven J; Rivera, Helen; Correnti, María

    2014-01-01

    Oral lichen planus and lichenoid reactions are autoimmune type inflammatory conditions of the oral mucosa with similar clinical and histological characteristics. Recent data suggest that oral lichenoid reactions (OLR) present a greater percentage of malignant transformation than oral lichen planus (OLP). Objective To compare the expression of bcl-2 and COX-2 in OLP and OLR. Methods The study population consisted of 65 cases; 34 cases diagnosed as OLR and 31 as OLP. A retrospective study was done, and bcl-2 and COX-2 expression was semiquantitatively analysed. Results Fifty-three per cent (18/34) of the ORL samples tested positive for COX-2, whereas in the OLP group, 81% of the samples (25/31) immunostained positive for COX-2. The Fisher’s exact test for the expression of COX-2 revealed that there are significant differences between the two groups, P = 0.035. With respect to the expression of the bcl-2 protein, 76% (26/34) of the samples were positive in OLR, while 97% (30/31) were positive in the group with OLP. The Fisher’s exact test for the expression of bcl-2 revealed that there are significant statistical differences between the two groups, P = 0.028. Conclusions The expression of bcl-2 and COX-2 was more commonly expressed in OLP when compared with OLR. PMID:24834112

  11. Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production.

    Science.gov (United States)

    Alfajaro, Mia Madel; Choi, Jong-Soon; Kim, Deok-Song; Seo, Ja-Young; Kim, Ji-Yun; Park, Jun-Gyu; Soliman, Mahmoud; Baek, Yeong-Bin; Cho, Eun-Hyo; Kwon, Joseph; Kwon, Hyung-Jun; Park, Su-Jin; Lee, Woo Song; Kang, Mun-Il; Hosmillo, Myra; Goodfellow, Ian; Cho, Kyoung-Oh

    2017-02-01

    Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E2 (PGE2) pathway. Targeting

  12. The expression of COX-2 in VEGF-treated endothelial cells is mediated through protein tyrosine kinase

    Directory of Open Access Journals (Sweden)

    Pravit Akarasereenont

    2002-01-01

    Full Text Available Cyclooxygenase (COX, existing as the COX-1 and COX-2 isoforms, converts arachidonic acid to prostaglandin H2, which is then further metabolized to various prostaglandins. Vascular endothelial growth factor (VEGF has been shown to play important roles in inflammation and is upregulated by the prostaglandin E series through COX-2 in several cell types. Here, we have investigated the effects of VEGF on the COX isoform expressed in human umbilical vein endothelial cells (HUVEC. The signalling mechanism of the COX isoform expressed in endothelial cells activated with VEGF will be also investigated using the tyrosine kinase inhibitor, genistein, and protein kinase C inhibitor, staurosporine. The activity of COX2 was assessed by measuring the production of 6-keto-prostaglandin F1α in the presence of exogenous arachidonic acids (10 μM, 10 min by enzyme immunoassay. The expression of COX isoform protein was detected by immunoblot using specific antibodies. Untreated HUVEC contained no COX-2 protein. In HUVEC treated with VEGF (0.01-50 ng/ml, COX-2 protein, but not COX-1, and COX activity were increased in a dose-dependent manner. Interestingly, the increased COX-2 protein and activity in response to VEGF (10 ng/ml was inhibited by the tyrosine kinase inhibitor, genistein (0.05-5 μg/ml, but not by the protein kinase C inhibitor, staurosporine (0.1-10 ng/ml. Thus, the induction of COX-2 by VEGF in endothelial cells was mediated through protein tyrosine kinase, and the uses of specific COX-2 inhibitors in these conditions, in which VEGF was involved, might have a role.

  13. NS-398, Ibuprofen and COX-2 RNAi produce significantly different gene expression profiles in prostate cancer cells

    OpenAIRE

    John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Falduto, Michael T.; Magnuson, Scott R.; Coleman, C. Norman

    2009-01-01

    Cyclooxygenase-2 (COX-2) plays a significant role in tumor development and progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit potent anticancer effects in vitro and in vivo by COX-2 dependent and independent mechanisms. In this study, we used microarray analysis to identify the change of expression profile regulated by a COX-2 specific NSAID NS-398 (0.01 and 0.1mM), a non-specific NSAID ibuprofen (0.1 and 1.5mM) and RNA interference-mediated COX-2 inhibition (COX-2 RNAi) in PC...

  14. COX-2-dependent PGE2 acts as a growth factor in mycosis fungoides (MF)

    DEFF Research Database (Denmark)

    Kopp, Katharina Luise Maria; Kauczok, C. S.; Lauenborg, Britt Thyssing

    2010-01-01

    production of PGE(2) in malignant T cells in vitro. These cells express prostaglandin receptors EP3 and EP4 and the receptor antagonist as well as small interfering RNA (siRNA) directed against COX-2, and specific COX-2 inhibitors strongly reduce their spontaneous proliferation. In conclusion, our data...... in prostaglandin synthesis. Aberrant COX-2 expression and prostaglandin E(2) (PGE(2)) production have been implicated in tumorigenesis. In this study we show that COX-2 is ectopically expressed in malignant T-cell lines from patients with cutaneous T-cell lymphoma (CTCL) as well as in situ in lymphocytic cells...... in 21 out of 22 patients suffering from mycosis fungoides (MF) in plaque or tumor stage. COX-2 is not expressed in lymphocytes of 11 patients with patch-stage MF, whereas sporadic COX-2 staining of stromal cells is observed in the majority of patients. COX-2 expression correlates with a constitutive...

  15. The synthesis of isotopic fluorine and iodine-labeled COX-II inhibitor and in vitro validation

    Energy Technology Data Exchange (ETDEWEB)

    An, Gwang Gil; Lee, Tae Sub; Lee, Kyo Chul; Moon, Byung Seok; Choi, Chang Woon; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    In these day, NASIDs (non-steroidal antiinflammatory drugs) such as aspirin, diclofenac and ibuprofen are the most common medications used to reduce pain and inflammation. However, they act by inhibiting both COX-I and COX-II which can cause serious gastrointestinal side effects such as ulcers, stomach perforations and bleeds. COX-I produces prostaglandins believed to be responsible for the protection of the stomach lining. However, COX-II produces prostaglandins believed to be responsible for pain and inflammation. Recently, the most widely studied selective COX-II inhibitor such as celecoxib and rofecoxib' one work by inhibiting the effect of COX-II on pain and inflammation without inhibiting COX-I which protects gastrointestinal lining.

  16. Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish.

    Science.gov (United States)

    Teraoka, Hiroki; Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi; Peterson, Richard E; Stegeman, John J; Kitazawa, Takio; Hiraga, Takeo; Kubota, Akira

    2014-09-01

    The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration-response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac edema formation following TCDD exposure in developing zebrafish.

  17. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  18. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2 inhibitors

    Directory of Open Access Journals (Sweden)

    Alshafie Galal A

    2006-01-01

    Full Text Available Abstract Background Epidemiologic and laboratory investigations suggest that nonsteroidal anti-inflammatory drugs (NSAIDs have chemopreventive effects against breast cancer due to their activity against cyclooxygenase-2 (COX-2, the rate-limiting enzyme of the prostaglandin cascade. Methods We conducted a case control study of breast cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 323 incident breast cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003–2004 and compared with 649 cancer free controls matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and breast cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR and 95% confidence intervals. Results Results showed significant risk reductions for selective COX-2 inhibitors as a group (OR = 0.29, 95% CI = 0.14–0.59, regular aspirin (OR = 0.49, 95% CI = 0.26–0.94, and ibuprofen or naproxen (0.36, 95% CI = 0.18–0.72. Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg produced no significant change in the risk of breast cancer. Conclusion Selective COX-2 inhibitors (celecoxib and rofecoxib were only recently approved for use in 1999, and rofecoxib (Vioxx was withdrawn from the marketplace in 2004. Nevertheless, even in the short window of exposure to these compounds, the selective COX-2 inhibitors produced a significant (71% reduction in the risk of breast cancer, underscoring their strong potential for breast cancer chemoprevention.

  19. Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

    Science.gov (United States)

    de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; Duarte, Gloria Pinto; Xavier, Fabiano Elias

    2017-09-01

    This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA2, PGE2 and PGF2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA2, PGE2 and PGF2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA2, PGE2 and PGF2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Different role of COX-2 and angiogenesis in canine inflammatory and non-inflammatory mammary cancer.

    Science.gov (United States)

    Clemente, Mónica; Sánchez-Archidona, Ana Rodríguez; Sardón, David; Díez, Lucía; Martín-Ruiz, Asunción; Caceres, Sara; Sassi, Francesco; Dolores Pérez-Alenza, M; Illera, Juan C; Dunner, Susana; Peña, Laura

    2013-08-01

    Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and fatal types of mammary cancer, and both have a very poor prognosis and low survival rate. Human IBC is characterised by exacerbated angiogenesis, lymphangiogenesis, and lymphangiotropism. Lymphangiotropism is also characteristic of IMC, but microvascular density (MVD) and lymphangiogenesis have not been previously studied in canine IMC. In this study immunohistochemical expression of several angiogenesis-related factors (cyclooxygenase [COX]-2, vascular endothelial growth factors A and D [VEGF-A, VEGF-D], and vascular endothelial growth factor receptor 3 [VEGFR-3]), MVD, lymphatic proliferation index (LPI), and Ki-67 tumour proliferation index (PI) were studied in 21 canine IMC samples, 20 canine high-grade malignant non-IMC mammary tumours (MMTs), and four normal mammary gland samples (NMGs). All mammary neoplasms were histologically categorised as grade III. COX-2 values were also analysed by RT-PCR in seven IMCs, six MMTs and four NMGs. The expressions of COX-2, VEGF-A, and VEGF-D were significantly higher in IMC, MVD and LPI tumours, but not PI. In MMTs, COX-2 immunoexpression was significantly associated with VEGF-A, while in IMCs COX-2 was associated with VEGF-D (lymphangiogenic factor), its receptor VEGFR-3, and LPI. These results suggested that lymphangiogenic pathway stimulation isa specific role of COX-2 in IMC angiogenesis, which justifies the use of COX-2-based targeted palliative therapies in dogs. The exacerbated angiogenesis and lymphangiogenesis and the increased expression of angiogenesis-related factors further support canine IMC as a natural model for the study of human IBC.

  1. New Element no. 112 prepared from Zink and Lead

    DEFF Research Database (Denmark)

    Berg, Rolf W.

    1996-01-01

    The preparation of element no. 112 in the Periodic Table of the Elements has been reviewed in a popular scientific magazine.......The preparation of element no. 112 in the Periodic Table of the Elements has been reviewed in a popular scientific magazine....

  2. COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tie-Jun Li; Jun Cui

    2013-01-01

    Objective:To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM (P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP (P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM (P<0.01). The COX-2 expression was associated with clinical stage (P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis (P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions:The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.

  3. COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation.

    Science.gov (United States)

    Majumder, Mousumi; Landman, Erin; Liu, Ling; Hess, David; Lala, Peeyush K

    2015-06-01

    MicroRNAs (miRs) are small regulatory molecules emerging as potential biomarkers in cancer. Previously, it was shown that COX-2 expression promotes breast cancer progression via multiple mechanisms, including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 overexpression also upregulated microRNA-526b (miR-526b), in association with aggressive phenotype. Here, the functional roles of miR-526b in breast cancer and the mechanistic role of EP4 signaling in miR-526b upregulation were examined. A positive correlation was noted between miR-526b and COX-2 mRNA expression in COX-2 disparate breast cancer cell lines. Stable overexpression of miR-526b in poorly metastatic MCF7 and SKBR3 cell lines resulted in increased cellular migration, invasion, EMT phenotype and enhanced tumorsphere formation in vitro, and lung colony formation in vivo in immunodeficient mice. Conversely, knockdown of miR-526b in aggressive MCF7-COX-2 and SKBR3-COX-2 cells reduced oncogenic functions and reversed the EMT phenotype, in vitro. Furthermore, it was determined that miR-526b expression is dependent on EP4 receptor activity and downstream PI3K-AKT and cyclic AMP (cAMP) signaling pathways. PI3K-AKT inhibitors blocked EP4 agonist-mediated miR-526b upregulation and tumorsphere formation in MCF7 and SKBR3 cells. NF-κB inhibitor abrogates EP agonist-stimulated miRNA expression in MCF7 and T47D cells, indicating that the NF-κB pathway is also involved in miR-526b regulation. In addition, inhibition of COX-2, EP4, PI3K, and PKA in COX-2-overexpressing cells downregulated miR-526b and its functions in vitro. Finally, miR-526b expression was significantly higher in cancerous than in noncancerous breast tissues and associated with reduced patient survival. In conclusion, miR-526b promotes breast cancer progression, SLC-phenotype through EP4-mediated signaling, and correlates with breast cancer patient survival. This study presents novel

  4. Analysis of the cytochrome c oxidase subunit II (COX2) gene in giant panda, Ailuropoda melanoleuca.

    Science.gov (United States)

    Ling, S S; Zhu, Y; Lan, D; Li, D S; Pang, H Z; Wang, Y; Li, D Y; Wei, R P; Zhang, H M; Wang, C D; Hu, Y D

    2017-01-23

    The giant panda, Ailuropoda melanoleuca (Ursidae), has a unique bamboo-based diet; however, this low-energy intake has been sufficient to maintain the metabolic processes of this species since the fourth ice age. As mitochondria are the main sites for energy metabolism in animals, the protein-coding genes involved in mitochondrial respiratory chains, particularly cytochrome c oxidase subunit II (COX2), which is the rate-limiting enzyme in electron transfer, could play an important role in giant panda metabolism. Therefore, the present study aimed to isolate, sequence, and analyze the COX2 DNA from individuals kept at the Giant Panda Protection and Research Center, China, and compare these sequences with those of the other Ursidae family members. Multiple sequence alignment showed that the COX2 gene had three point mutations that defined three haplotypes, with 60% of the sequences corresponding to haplotype I. The neutrality tests revealed that the COX2 gene was conserved throughout evolution, and the maximum likelihood phylogenetic analysis, using homologous sequences from other Ursidae species, showed clustering of the COX2 sequences of giant pandas, suggesting that this gene evolved differently in them.

  5. Bond and CDS Pricing via the Stochastic Recovery Black-Cox Model

    Directory of Open Access Journals (Sweden)

    Albert Cohen

    2017-04-01

    Full Text Available Building on recent work incorporating recovery risk into structural models by Cohen & Costanzino (2015, we consider the Black-Cox model with an added recovery risk driver. The recovery risk driver arises naturally in the context of imperfect information implicit in the structural framework. This leads to a two-factor structural model we call the Stochastic Recovery Black-Cox model, whereby the asset risk driver At defines the default trigger and the recovery risk driver Rt defines the amount recovered in the event of default. We then price zero-coupon bonds and credit default swaps under the Stochastic Recovery Black-Cox model. Finally, we compare our results with the classic Black-Cox model, give explicit expressions for the recovery risk premium in the Stochastic Recovery Black-Cox model, and detail how the introduction of separate but correlated risk drivers leads to a decoupling of the default and recovery risk premiums in the credit spread. We conclude this work by computing the effect of adding coupons that are paid continuously until default, and price perpetual (consol bonds in our two-factor firm value model, extending calculations in the seminal paper by Leland (1994.

  6. Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1.

    Science.gov (United States)

    Bareth, Bettina; Nikolov, Miroslav; Lorenzi, Isotta; Hildenbeutel, Markus; Mick, David U; Helbig, Christin; Urlaub, Henning; Ott, Martin; Rehling, Peter; Dennerlein, Sven

    2016-05-15

    The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and specialized chaperone-like assembly factors, are formed. In addition, cofactors such as heme and copper have to be inserted into the nascent complex. To regulate the assembly process, the availability of Cox1 is under control of a regulatory feedback cycle in which translation of COX1 mRNA is stalled when assembly intermediates of Cox1 accumulate through inactivation of the translational activator Mss51. Here we isolate a cytochrome c oxidase assembly intermediate in preparatory scale from coa1Δ mutant cells, using Mss51 as bait. We demonstrate that at this stage of assembly, the complex has not yet incorporated the heme a cofactors. Using quantitative mass spectrometry, we define the protein composition of the assembly intermediate and unexpectedly identify the putative methyltransferase Oms1 as a constituent. Our analyses show that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly synthesized Cox1.

  7. The Characterization And Role of Zinc Binding in Yeast Cox4

    Energy Technology Data Exchange (ETDEWEB)

    Coyne, H.J., III; Ciofi-Baffoni, S.; Banci, L.; Bertini, I.; Zhang, L.; George, G.N.; Winge, D.R.; /Utah U. /Florence U. /Saskatchewan U.

    2007-07-09

    Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only cofactor-containing subunit that is not directly part of the catalytic core of the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown to be distinct from the bovine ortholog, as it results from the x-ray structure of the entire cytochrome c oxidase in having a single histidyl residue and three conserved cysteines residues in the coordination sphere. Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to lead to cytochrome oxidase assembly. Limited function exists in His-119 mutants when overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability of the complex. The solution structure of yeast Cox4 elucidated by multidimensional NMR reveals a C-terminal globular domain consisting of two {beta} sheets analogous to the bovine ortholog except the loop containing the coordinating His in the yeast protein and the fourth Cys in the bovine protein are in different positions in the two structures. The conformation of this loop is dictated by the different sequence position of the fourth coordinating zinc ligand. The Zn(II) ion is buried within the domain, consistent with its role in structural stability. Potential functions of this matrix-facing subunit are discussed.

  8. The flavouring phytochemical 2-pentanone reduces prostaglandin production and COX-2 expression in colon cancer cells.

    Science.gov (United States)

    Pettersson, Jenny; Karlsson, Pernilla Christina; Göransson, Ulf; Rafter, Joseph James; Bohlin, Lars

    2008-03-01

    Many phytochemicals found in the diet may prevent colon carcinogenesis by affecting biochemical processes in the colonic mucosa. Inflammation and subsequent elevation of the enzyme cyclooxygenase-2 (COX-2) are two such factors involved in the development of colon cancer, and inhibition of these processes could be important targets for chemoprevention. We have previously shown COX-2 inhibitory activity locally in the colon; e.g. in human fecal water from a group of vegetarians. In this study we focus on 2-pentanone, a frequently occurring compound in common foods such as banana and carrot. The aim was to study the inhibitory effects on prostaglandin production and COX-2 protein expression in tumour necrosis factor-alpha stimulated colon cancer cells (HT29) by radioimmunoassay and Western blotting. 2-Pentanone inhibited both prostaglandin production and COX-2 protein expression in human colon cancer cells. A concentration of 400 mumol/l 2-pentanone inhibited the prostaglandin production by 56.9+/-12.9% which is in the same range as the reference compound NS398 (59.8+/-7.6%). The two highest concentrations of 2-pentanone were further analyzed by Western blot, and 400 micromol/l and 200 micromol/l 2-pentanone resulted in a 53.3+/-9.6% and +/-27.1% reduction of the COX-2 protein levels respectively. Further studies on flavouring compounds, for example 2-pentanone, as colon cancer chemopreventives would be very valuable, and such results may contribute to future dietary recommendations.

  9. Leptin induces CREB-dependent aromatase activation through COX-2 expression in breast cancer cells.

    Science.gov (United States)

    Kim, Hyung Gyun; Jin, Sun Woo; Kim, Yong An; Khanal, Tilak; Lee, Gi Ho; Kim, Se Jong; Rhee, Sang Dal; Chung, Young Chul; Hwang, Young Jung; Jeong, Tae Cheon; Jeong, Hye Gwang

    2017-08-01

    Leptin plays a key role in the control of adipocyte formation, as well as in the associated regulation of energy intake and expenditure. The goal of this study was to determine if leptin-induced aromatase enhances estrogen production and induces tumor cell growth stimulation. To this end, breast cancer cells were incubated with leptin in the absence or presence of inhibitor pretreatment, and changes in aromatase and cyclooxygenase-2 (COX-2) expression were evaluated at the mRNA and protein levels. Transient transfection assays were performed to examine the aromatase and COX-2 gene promoter activities and immunoblot analysis was used to examine protein expression. Leptin induced aromatase expression, estradiol production, and promoter activity in breast cancer cells. Protein levels of phospho-STAT3, PKA, Akt, ERK, and JNK were increased by leptin. Leptin also significantly increased cAMP levels, cAMP response element (CRE) activation, and CREB phosphorylation. In addition, leptin induced COX-2 expression, promoter activity, and increased the production of prostaglandin E2. Finally, a COX-2 inhibitor and aromatase inhibitor suppressed leptin-induced cell proliferation in MCF-7 breast cancer cells. Together, our data show that leptin increased aromatase expression in breast cancer cells, which was correlated with COX-2 upregulation, mediated through CRE activation and cooperation among multiple signaling pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus

    2010-01-01

    significant interactions between genotypes and alcohol intake, smoking and NSAID use in relation to risk of ACS. Among males, there was interaction between COX-2 T8473C and alcohol in relation to total cholesterol, non-HDL cholesterol and LDL levels (p for interaction: 0.003, 0.007 and 0.01, respectively......Background: The use of specific COX-2 inhibitors in cancer prevention has been associated with higher risk of acute coronary syndrome (ACS) and myocardial infarction. The aim of this study was to investigate if the polymorphisms COX2 T8473C (rs5275), and COX2 A-1195G (rs689466), which modify...... the enzyme levels of COX-2, were associated with risk of ACS and if alcohol intake, smoking, and use of NSAID would modify the associations. We also wanted to investigate associations with blood lipid levels. Methods: A case–cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested...

  11. A comparison between the use of Cox regression and the use of partial least squares-Cox regression to predict the survival of kidney-transplant patients

    Science.gov (United States)

    Solimun

    2017-05-01

    The aim of this research is to model survival data from kidney-transplant patients using the partial least squares (PLS)-Cox regression, which can both meet and not meet the no-multicollinearity assumption. The secondary data were obtained from research entitled "Factors affecting the survival of kidney-transplant patients". The research subjects comprised 250 patients. The predictor variables consisted of: age (X1), sex (X2); two categories, prior hemodialysis duration (X3), diabetes (X4); two categories, prior transplantation number (X5), number of blood transfusions (X6), discrepancy score (X7), use of antilymphocyte globulin(ALG) (X8); two categories, while the response variable was patient survival time (in months). Partial least squares regression is a model that connects the predictor variables X and the response variable y and it initially aims to determine the relationship between them. Results of the above analyses suggest that the survival of kidney transplant recipients ranged from 0 to 55 months, with 62% of the patients surviving until they received treatment that lasted for 55 months. The PLS-Cox regression analysis results revealed that patients' age and the use of ALG significantly affected the survival time of patients. The factor of patients' age (X1) in the PLS-Cox regression model merely affected the failure probability by 1.201. This indicates that the probability of dying for elderly patients with a kidney transplant is 1.152 times higher than that for younger patients.

  12. Increased COX2 in the trigeminal nucleus caudalis is involved in orofacial pain induced by experimental tooth movement.

    Science.gov (United States)

    Gao, Yuan; Duan, Yin-Zhong

    2010-03-01

    Pain is among the major problems during orthodontic treatment. Recent studies have shown that central Cyclooxygenase2 (COX2) pathway was involved in several pain models. The present study investigated whether inducible COX2 within the trigeminal nucleus caudalis (Vc) contributed to experimental tooth movement pain in freely moving rats. Elastic rubber bands were inserted between the first and second maxillary molars bilaterally to establish tooth movement model. The directed mouth wiping behavior was used to evaluate the pain during tooth movement. COX2 distribution in Vc was studied by immunohistochemistry and the changes of COX2 expression were detected by Western blot at different time point after rubber band insertion. Our results showed that tooth movement significantly increased COX2 expression in Vc and the time spent on mouth wiping, reaching a maximum at 1 day and then decreasing gradually. Furthermore, the rhythm change of COX2 expression in Vc and the mouth wiping behavior were much correlative with each other. All of the COX2-immunoreactive structures in Vc exhibited NeuN-immunopositive staining and most of these COX2-immunoreactive neurons were Fos-immunopositive. Importantly, the mouth wiping behavior could be attenuated by intracisternal injection of NS-398 (a selective COX2 inhibitor) but not by periodontal administration of NS-398. All these results suggested that increased COX2 in Vc was involved in tooth movement pain and thus may be a central target for orthodontic pain treatment.

  13. In vitro import and assembly of the nucleus-encoded mitochondrial subunit III of cytochrome c oxidase (Cox3).

    Science.gov (United States)

    Vázquez-Acevedo, Miriam; Rubalcava-Gracia, Diana; González-Halphen, Diego

    2014-11-01

    The cox3 gene, encoding subunit III of cytochrome c oxidase (Cox3) is in mitochondrial genomes except in chlorophycean algae, where it is localized in the nucleus. Therefore, algae like Chlamydomonas reinhardtii, Polytomella sp. and Volvox carteri, synthesize the Cox3 polypeptide in the cytosol, import it into mitochondria, and integrate it into the cytochrome c oxidase complex. In this work, we followed the in vitro internalization of the Cox3 precursor by isolated, import-competent mitochondria of Polytomella sp. In this colorless alga, the precursor Cox3 protein is synthesized with a long, cleavable, N-terminal mitochondrial targeting sequence (MTS) of 98 residues. In an import time course, a transient Cox3 intermediate was identified, suggesting that the long MTS is processed more than once. The first processing step is sensitive to the metalo-protease inhibitor 1,10-ortophenantroline, suggesting that it is probably carried out by the matrix-located Mitochondrial Processing Protease. Cox3 is readily imported through an energy-dependent import pathway and integrated into the inner mitochondrial membrane, becoming resistant to carbonate extraction. Furthermore, the imported Cox3 protein was assembled into cytochrome c oxidase, as judged by the presence of a labeled band co-migrating with complex IV in Blue Native Electrophoresis. A model for the biogenesis of Cox3 in chlorophycean algae is proposed. This is the first time that the in vitro mitochondrial import of a cytosol-synthesized Cox3 subunit is described.

  14. Characterization of the Cytochrome C Oxidase Assembly Factor Cox19 of 'Saccharomyces Cerevisiae'

    Energy Technology Data Exchange (ETDEWEB)

    Rigby, K.; Zhang, L.; Cobine, P.A.; George, G.N.; Winge, D.R.; /Utah U. /Saskatchewan U.

    2007-07-12

    Cox19 is an important accessory protein in the assembly of cytochrome c oxidase in yeast. The protein is functional when tethered to the mitochondrial inner membrane, suggesting its functional role within the intermembrane space. Cox19 resembles Cox17 in having a twin CX{sub 9}C sequence motif that adopts a helical hairpin in Cox17. The function of Cox17 appears to be a Cu(I) donor protein in the assembly of the copper centers in cytochrome c oxidase. Cox19 also resembles Cox17 in its ability to coordinate Cu(I). Recombinant Cox19 binds 1 mol eq of Cu(I) per monomer and exists as a dimeric protein. Cox19 isolated from the mitochondrial intermembrane space contains variable quantities of copper, suggesting that Cu(I) binding may be a transient property. Cysteinyl residues important for Cu(I) binding are also shown to be important for the in vivo function of Cox19. Thus, a correlation exists in the ability to bind Cu(I) and in vivo function.

  15. The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study.

    Science.gov (United States)

    Huang, Jian; Zhang, Di; Xie, Fuqiang; Lin, Degui

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.

  16. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Energy Technology Data Exchange (ETDEWEB)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  17. Effect of nimesulide-a preferential COX-2 inhibitor on arterial blood pressure, compared to ketoprofen.

    Science.gov (United States)

    Saran, Tomasz; Sodolski, Wojciech; Sodolska, Katarzyna; Danilkiewicz, Wit Cezary; Schabowski, Janusz

    2004-01-01

    Clinical and experimental studies have shown that renal and cardiovascular effects of most selective COX-2 inhibitors (rofecoxib, celecoxib) are similar to other traditional NSAIDs (dual COX inhibitors). In these study the effect of nimesulide--preferential COX-2 inhibitor, administration on 24-hour blood pressure profile was investigated in 40 adult individuals on antihypertensive therapy with pain states caused by osteoartritis. Nimesulide was administered orally, twice a day at the conventional dose of 0.1 g for five days. In the next (or previous) 5 days the same patients were administered with ketoprofen at the dose of 0.05 g three times a day. On the last day of the NSAID administration period, 24-hour blood pressure monitoring was performed. Our results indicate no difference between nimesulide and ketoprofen effects on mean blood pressure values during antihypertensive therapy.

  18. The respiratory chain supercomplex organization is independent of COX7a2l isoforms.

    Science.gov (United States)

    Mourier, Arnaud; Matic, Stanka; Ruzzenente, Benedetta; Larsson, Nils-Göran; Milenkovic, Dusanka

    2014-12-01

    The organization of individual respiratory chain complexes into supercomplexes or respirasomes has attracted great interest because of the implications for cellular energy conversion. Recently, it was reported that commonly used mouse strains harbor a short COX7a2l (SCAFI) gene isoform that supposedly precludes the formation of complex IV-containing supercomplexes. This claim potentially has serious implications for numerous mouse studies addressing important topics in metabolism, including adaptation to space flights. Using several complementary experimental approaches, we show that mice with the short COX7a2l isoform have normal biogenesis and steady-state levels of complex IV-containing supercomplexes and consequently have normal respiratory chain function. Furthermore, we use a mouse knockout of Lrpprc and show that loss of complex IV compromises respirasome formation. We conclude that the presence of the short COX7a2l isoform in the commonly used C57BL/6 mouse strains does not prevent their use in metabolism research.

  19. Electrochemical performance of compounds Ho6Fe23-xCox (x=0,1,3)

    Institute of Scientific and Technical Information of China (English)

    HE Wei; ZHAO Yunhong; HUANG Jinli; ZHANG Yongzhi; ZENG Lingmin

    2011-01-01

    Alloys with composition of Ho6Fe23-xCox(x=0, 1, 3) were prepared and e xamined by X-ray diffraction technique and automatic battery testing instrument. The compounds Ho6Fe23-xCox(x=0, 1, 3) crystallized in cubic Th6Mn23-type structure with space group Fm(-3)m (No. 225). The electrochemical properties of these alloys such as discharge capacity, cycling performance and high rate dischargeability were investigated by battery testing instruments in alkaline electrolyte. Substitution of small amounts of Co for Fe in Ho6Fe23-xCox improved the activation, discharge capacity and the high rate dischargeability. The alloy with x=3 (Ho6Fe20Co3) had better discharge capacity, HRD and plateau pressure at discharge current density of 150 mA/g.

  20. Dietary glycerol for quail: association between productive performance and COX III mRNA expression.

    Science.gov (United States)

    Silva, S C C; Gasparino, E; Batista, E; Tanamati, F; Vesco, A P D; Lala, B; de Oliveira, D P

    2016-05-25

    This study was carry out to evaluate mRNA expression of mitochondrial cytochrome c oxidase III in the Pectoralis superficialis muscle of 28-day-old quails fed diets containing 0, 8, and 12% glycerol. Total RNA was extracted (N = 10) and cDNA was amplified using specifics primers for qRT-PCR. Feed efficiency and feed intake were evaluated. COX III mRNA expression in breast muscle was higher in the group fed with 12% glycerol (0.863 AU); no differences were observed in the expression of this gene between the muscle of animals fed diets without glycerol (0.357 AU) and 8% glycerol (0.415 AU). Quails that showed greater COX III mRNA expression also showed the lowest feed efficiency. These results show that there is a difference in COX III mRNA expression in breast muscle of 28-day-old quail fed diets different concentrations of glycerol.

  1. Timosaponin AIII inhibits melanoma cell migration by suppressing COX-2 and in vivo tumor metastasis.

    Science.gov (United States)

    Kim, Ki Mo; Im, A-Rang; Kim, Seung Hyung; Hyun, Jin Won; Chae, Sungwook

    2016-02-01

    Melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. We examined the effects of timosaponin AIII, a compound isolated from Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and the molecular mechanisms underlying these effects using B16-F10 and WM-115 melanoma cells lines. Overexpression of COX-2, its metabolite prostaglandin E2 (PGE2), and PGE2 receptors (EP2 and EP4) promoted cell migration in vitro. Exposure to timosaponin AIII resulted in concentration-dependent inhibition of cell migration, which was associated with reduced levels of COX-2, PGE2, and PGE2 receptors. Transient transfection of COX-2 siRNA also inhibited cell migration. Exposure to 12-O-tetradecanoylphorbal-13-acetate enhanced cell migration, whereas timosaponin AIII inhibited 12-O-tetradecanoylphorbal-13-acetate-induced cell migration and reduced basal levels of EP2 and EP4. Moreover, timosaponin AIII inhibited activation of nuclear factor-kappa B (NF-κB), an upstream regulator of COX-2 in B16-F10 cells. Consistent with our in vitro findings, in vivo studies showed that timosaponin AIII treatment significantly reduced the total number of metastatic nodules in the mouse lung and improved histological alterations in B16-F10-injected C57BL/6 mice. In addition, C57BL/6 mice treated with timosaponin AIII showed reduced expression of COX-2 and NF-κB in the lung. Together, these results indicate that timosaponin AIII has the capacity to inhibit melanoma cell migration, an essential step in the process of metastasis, by inhibiting expression of COX-2, NF-κB, PGE2, and PGE2 receptors.

  2. RELATIONSHIP AMONG COX-2 PROTEIN EXPRESSION, PGs LEVELS AND BIOLOGIC BEHAVIOR IN OVARIAN CARCINOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    王敏; 王欣彦; 唐丽霞; 高岩

    2004-01-01

    Objective: To study the relationship among cyclooxygenase-2 (COX-2) protein expression, prostaglandins levels and biologic behavior in ovarian carcinoma tissues. Methods: The expression of COX-2 protein, levels of prostaglandin (PG)E2, 6-keto-PGF1( and thromboxane (TX)B2 in 54 biopsy specimens from patients with ovarian serous tumors which included three groups: 33 samples of ovarian serous carcinoma; 10 samples of borderline ovarian serous tumors and 11 samples of benign ovarian serous tumors and 10 samples of normal ovarian tissues were detected by Western blot analysis and radioimmunoassay to investigate their clinical significance. Results: The expression of COX-2 protein (82%, 27/33) and its relative content (20.08±3.53) in ovarian serous carcinoma tissues were statistically higher than those in benign ovarian serous tumor tissues and normal ovary tissues i.e., 0 and (15.04(0.12), 0 and (15.33(0.60) (P0.05). The levels of PGE2, 6-keto-PGF1( and TXB2 showed no significant differences in ovarian carcinoma tissues with different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymph metastasis. COX-2 expression was correlated with the levels of PGE2, 6-KETO-PGF1( and TXB2 (P<0.01). Conclusion: Our data suggest that COX-2 overexpression leads to increased PGE2, 6-KETA-PGF1( and TXB2 biosynthesis, which may be mechanisms underlying the contribution of COX-2 to the development of ovarian serous carcinoma. BGF2, 6-keto-PGF1( and TXB2 may be helpful parameters of diagnosis and differentiate diagnosis in ovarian serous carcinoma.

  3. The first characterization of free radicals formed from cellular COX-catalyzed peroxidation.

    Science.gov (United States)

    Gu, Yan; Xu, Yi; Law, Benedict; Qian, Steven Y

    2013-04-01

    Through free radical-mediated peroxidation, cyclooxygenase (COX) can metabolize dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) to form well-known bioactive metabolites, namely, the 1-series of prostaglandins (PGs1) and the 2-series of prostaglandins (PGs2), respectively. Unlike PGs2, which are generally viewed as proinflammatory and procarcinogenic PGs, PGs1 may possess anti-inflammatory and anti-cancer activity. Previous studies using ovine COX along with spin trapping and the LC/ESR/MS technique have shown that certain exclusive free radicals are generated from different free radical reactions in DGLA and AA peroxidation. However, it has been unclear whether the differences were associated with the contrasting bioactivity of DGLA vs AA. The aim of this study was to refine the LC/MS and spin trapping technique to make it possible for the association between free radicals and cancer cell growth to be directly tested. Using a colon cancer cell line, HCA-7 colony 29, and LC/MS along with a solid-phase extraction, we were able to characterize the reduced forms of radical adducts (hydroxylamines) as the free radicals generated from cellular COX-catalyzed peroxidation. For the first time, free radicals formed in the COX-catalyzed peroxidation of AA vs DGLA and their association with cancer cell growth were assessed (cell proliferation via MTS and cell cycle distribution via propidium iodide staining) in the same experimental setting. The exclusive free radicals formed from the COX-catalyzed peroxidation of AA and DGLA were shown to be correlated with the cell growth response. Our results indicate that free radicals generated from the distinct radical reactions in COX-catalyzed peroxidation may represent the novel metabolites of AA and DGLA that correspond to their contrasting bioactivity.

  4. The polyacetylene falcarindiol with COX-1 activity isolated from Aegopodium podagraria L.

    Science.gov (United States)

    Prior, Rikke M; Lundgaard, Nanna H; Light, Marnie E; Stafford, Gary I; van Staden, Johannes; Jäger, Anna K

    2007-08-15

    Extracts of Aegopodium podagraria L. were screened in vitro for cyclooxygenase-1 (COX-1) inhibitory activity. The isolation of the active compound falcarindiol was achieved by bioassay-guided fractionation. The identification of the active compound was confirmed by (1)H NMR and (13)C NMR. The IC(50)-value of falcarindiol was 0.3 microM in the COX-1 assay. A quantitative determination of the seasonal variation in the content of falcarindiol in different plant parts was carried out by HPLC analysis. The flowers from Aegopodium podagraria collected in June 2006 had the highest concentration of falcarindiol (88 mg/g plant material).

  5. A comparison of the newer COX-2 drugs and older nonnarcotic oral analgesics.

    Science.gov (United States)

    Sunshine, A

    2000-09-01

    The newer COX-2 drugs are safer analgesics than the older NSAIDs. At the usual dose used in osteoarthritis, they have less analgesic effect than the older NSAIDs. The non-narcotic analgesics such as acetaminophen, salicylate, NSAIDs, and the newer COX-2 drugs seem to have distinctly different mechanisms of action. In limited clinical trials, some of these drugs in combination give additive analgesia. Consideration should be given to using these drugs in combination, after suitable clinical trials, to enhance the efficacy of this category of analgesics.

  6. Cox report and the US-China arms control technical exchange program

    Energy Technology Data Exchange (ETDEWEB)

    Di Capua, M S

    1999-09-01

    The ACE program furthered the national security interests of the US by promoting technical approaches to the implementation and verification of arms control treaties that the international community embraces. The Cox Committee report suggests that uncontrolled interactions were taking place between US and Chinese nuclear weapons scientists in the course of the ACE program. On the contrary, elaborate controls were in place at the very beginning and remained in place to control the interactions and protect US national security information. The ACE program payoff to national security was just beginning and its suspension, resulting from the Cox reports allegations, is a setback to US-China progress on arms control.

  7. Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.

    Science.gov (United States)

    Kong, Shengchun; Nan, Bin

    2014-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses.

  8. Non-asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso

    CERN Document Server

    Kong, Shengchun

    2012-01-01

    We consider the finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz. We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulty caused by the lack of iid and Lipschitz property.

  9. Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells

    Directory of Open Access Journals (Sweden)

    Yu Danny CW

    2008-07-01

    Full Text Available Abstract Background Cyclooxygenase (COX-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC. We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF and interleukin-8 (IL-8 in lung cancer cells. Methods The levels of IL-8, VEGF and prostaglandin E2 (PGE2 were measured by ELISA. Expression of COX-1 and COX-2 was determined by Western blotting. Inhibition or knockdown of COX-2 was achieved by treating NSCLC cells with specific COX-2 inhibitor NS-398 or COX-2 siRNA, respectively. Results We found that NSCLC cell lines produced more IL-8 than VEGF (p 2 was significantly higher in NSCLC cell lines than SCLC cell lines (p 2 production. VEGF was significantly reduced following the treatment of NS-398 in A549 (by 31% and MOR/P (by 47% cells lines which expressing strong COX-2, but not in H460 cell line which expressing very low COX-2. However, IL-8 was not reduced in these cell lines. To confirm these results, we knocked down COX-2 expression with COX-2 siRNA in these cell lines. VEGF was significantly decreased in A549 (by 24% and in MOR/P (by 53%, but not in H460 whereas IL-8 was not affected in any cell line. Conclusion We conclude that NSCLC cells produce much higher levels of IL-8 than SCLC cells whereas both NSCLC and SCLC cells produce similar levels of VEGF. COX-2 is only expressed in NSCLC cells, but not in SCLC cells. VEGF is produced in both NSCLC and SCLC cells regardless of COX-2 expression. However, VEGF production is, at least partly, COX-2 dependent in NSCLC cells expressing COX-2. In contrast, IL-8 production is COX-2 independent in both NSCLC and SCLC cells. We speculate that combined targeting of COX-2 and IL-8 may be useful in the treatment of patients with NSCLC and targeting VEGF may be useful in the treatment of patients with SCLC.

  10. Efek ekstrak daun singkong (Manihot utilissima terhadap ekspresi COX-2 pada monosit yang dipapar LPS E.coli (The effect of Manihot utilissima extracts on COX-2 expression of monocytes induced by LPS E. coli

    Directory of Open Access Journals (Sweden)

    Zahara Meilawaty

    2013-12-01

    Full Text Available Background: Periodontal disease is a common and widespread disease in the community. Gram negative bacteria have a role inperiodontitis. These bacteria secrete a variety of products such as endotoxin lipopolysaccharide (LPS, which causes the occurrenceof inflammation or infection. The body defense responses are neutrophils and mononuclear cells (monocytes and macrophages. Inresponse to defense mechanism, the body will be expressed enzyme cyclooxygenase (COX which functions convert arachidonic acidto prostaglandins. Cassava leaf cells known to play a role in reducing inflammation, but the mechanism for inhibiting COX-2, is notknown. Purpose: The study was aimed to determine the effect of cassava leaf extract (Manihot utilissima on expression of enzyme COX-2 in monocytes which were exposed by LPS E. coli. Methods: This study was in vitro experimental studies with the design of posttestonly control group design. The sample was the cassava leaves extract (Manihot utilissima at concentration of 12.5 % and 25 %. Theexpression of COX-2 was determined by immunocytochemistry method. Isolated monocytes were incubated in cassava leaf extract, andthen exposed to LPS, after washing imunostaning procedure was performed using a monoclonal antibody (MAb anti-human COX-2.The research data was the number of monocytes that express COX-2. Results: Expression of COX-2 in the group cassava leaf extractwas higher than the group that induced by LPS E. coli only. Conclusion: Cassava leaf extract did not inhibit the expression of COX-2in monocytes which were exposed by LPS E. coli.Latar belakang: Penyakit periodontal merupakan penyakit umum dan tersebar luas di masyarakat. Bakteri yang banyak berperanpada periodontitis adalah Gram negatif. Bakteri ini mengeluarkan berbagai produk antara lain endotoksin lipopolisakarida (LPS yangmenyebabkan inflamasi atau infeksi. Respon pertahanan tubuh pertama adalah netrofil dan sel mononuklear (monosit dan makrofag.Pada respon

  11. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

    Science.gov (United States)

    Baertling, Fabian; Al-Murshedi, Fathiya; Sánchez-Caballero, Laura; Al-Senaidi, Khalfan; Joshi, Niranjan P; Venselaar, Hanka; van den Brand, Mariël Am; Nijtmans, Leo Gj; Rodenburg, Richard Jt

    2017-03-01

    COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts.

  12. COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.

    Science.gov (United States)

    Botti, Gerardo; Fratangelo, Federica; Cerrone, Margherita; Liguori, Giuseppina; Cantile, Monica; Anniciello, Anna Maria; Scala, Stefania; D'Alterio, Crescenzo; Trimarco, Chiara; Ianaro, Angela; Cirino, Giuseppe; Caracò, Corrado; Colombino, Maria; Palmieri, Giuseppe; Pepe, Stefano; Ascierto, Paolo Antonio; Sabbatino, Francesco; Scognamiglio, Giosuè

    2017-02-23

    The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAF(V600E) A375 and NRAS(Q61R) SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. BRAF(V600E/V600K) and NRAS(Q61R/Q61L) were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions (P = 0.002). COX-2 expression significantly correlated with PD-L1 expression in both primary (P = 0.001) and not matched metastatic (P = 0.048) lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAF(V600E) A375 and NRAS(Q61R) SK-MEL-2 melanoma cell lines. COX-2 expression

  13. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Goodman Julie E

    2010-11-01

    Full Text Available Abstract Background Inducible cyclooxgenase-2 (COX-2 is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Methods Tumor COX-2, HER2 and estrogen receptor α (ER expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. Results COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR = 2.72; 95% confidence interval (CI, 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52. However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9. Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Conclusions Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.

  14. Effects of Ge Gen Decoction on PGE2 Content and COX Activity in the Degenarated Cervical Intervertebral Discs of Rats

    Institute of Scientific and Technical Information of China (English)

    Zhou Jun; Fang Suping; Huo Hairu; Qi Yun; Guo Shuying; Jiang Tingliang; Shi Qi; Wang Youjing

    2005-01-01

    After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay.The results indicated that the PGF2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.

  15. The potential role of COX-2 in cancer stem cell-mediated canine mammary tumor initiation: an immunohistochemical study

    OpenAIRE

    Huang, Jian; Zhang, Di; Xie, Fuqiang; LIN, Degui

    2015-01-01

    Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding tran...

  16. Ekspresi COX-2 setelah pemberian ekstrak etanolik kulit manggis (Garcinia mangostana Linn pada tikus wistar (COX-2 expression after mangosteen rind (Garcinia mangostana Linn etanolic extract administration in wistar rats

    Directory of Open Access Journals (Sweden)

    Rendra Chriestedy Prasetya

    2013-12-01

    Full Text Available Background: Cyclooxygenase is an enzyme for prostaglandins (PGs synthesis from arachidonic acid. Cyclooxygenase have been characterized and named as COX-1 and COX-2. COX-1 is responsible for constitutive PGs production under physiological condition and maintains normal function. On the other hand, while COX-2 expression is inducible by cytokines and endotoxin. Periodontitis is a chronic inflammatory disease caused by anaerobic bacteria especially gram negative bacteria. The periodontitis occurrence is followed by increased of COX-2 expression. Mangosteen rind (Garcinia mangostana Linn contains gamma mangostin which inhibits the synthesis of PGE2 through inhibition of COX-2 expression. Purpose: This research was aimed to study COX-2 expression in experimental-induced periodontitis in wistar rats after mangosteen rind etanolic extract administration. Methods: Forty eight male wistar rats were induced periodontitis by putting silk ligature subgingivally around the cervical of the anterior lower teeth for 7 days. After the ligation was taken out, the rats were divided into 4 groups, and treated orally with mangosteen rind extract 60 mg/kg BB, 30 mg/kg BB, ibuprofen and saline respectively. The rats were sacrificed on the 1st, 3rd, 4th, 7th day after the treatment. The rats’ anterior lower jaws were processed for paraffin embedded tissue, cut serially and stained with immunohistochemistry. COX-2 expression were observed and counted under the microscope (400x. The data were analyzed using kruskall wallis test. Results: Kruskal wallis test showed a significant difference COX-2 expression among group indicating that mangosteen rind etanolic extract affected COX-2 expression. Conclusion: Mangosteen rind etanolic extract reduced COX-2 expression in periodontitis rats.Latar belakang: Siklooksigenase adalah enzim yang mensintesis prostaglandin (PG dari asam arakhidonat. Siklooksigenase dibagi menjadi 2 yaitu COX-1 dan COX-2. COX-1 bertanggung jawab pada

  17. Interaction of apoptotic cells with macrophages upregulates COX-2/PGE2 and HGF expression via a positive feedback loop.

    Science.gov (United States)

    Byun, Ji Yeon; Youn, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Woo, So-Yeon; Kang, Jihee Lee

    2014-01-01

    Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.

  18. Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE2 and HGF Expression via a Positive Feedback Loop

    Directory of Open Access Journals (Sweden)

    Ji Yeon Byun

    2014-01-01

    Full Text Available Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2/prostaglandin E2 (PGE2 and hepatocyte growth factor (HGF play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition.

  19. COX-2 Induces Breast Cancer Stem Cells via EP4/PI3K/AKT/NOTCH/WNT Axis.

    Science.gov (United States)

    Majumder, Mousumi; Xin, Xiping; Liu, Ling; Tutunea-Fatan, Elena; Rodriguez-Torres, Mauricio; Vincent, Krista; Postovit, Lynne-Marie; Hess, David; Lala, Peeyush K

    2016-09-01

    Cancer stem-like cells (SLC) resist conventional therapies, necessitating searches for SLC-specific targets. We established that cyclo-oxygenase(COX)-2 expression promotes human breast cancer progression by activation of the prostaglandin(PG)E-2 receptor EP4. Present study revealed that COX-2 induces SLCs by EP4-mediated NOTCH/WNT signaling. Ectopic COX-2 over-expression in MCF-7 and SKBR-3 cell lines resulted in: increased migration/invasion/proliferation, epithelial-mesenchymal transition (EMT), elevated SLCs (spheroid formation), increased ALDH activity and colocalization of COX-2 and SLC markers (ALDH1A, CD44, β-Catenin, NANOG, OCT3/4, SOX-2) in spheroids. These changes were reversed with COX-2-inhibitor or EP4-antagonist (EP4A), indicating dependence on COX-2/EP4 activities. COX-2 over-expression or EP4-agonist treatments of COX-2-low cells caused up-regulation of NOTCH/WNT genes, blocked with PI3K/AKT inhibitors. NOTCH/WNT inhibitors also blocked COX-2/EP4 induced SLC induction. Microarray analysis showed up-regulation of numerous SLC-regulatory and EMT-associated genes. MCF-7-COX-2 cells showed increased mammary tumorigenicity and spontaneous multiorgan metastases in NOD/SCID/IL-2Rγ-null mice for successive generations with limiting cell inocula. These tumors showed up-regulation of VEGF-A/C/D, Vimentin and phospho-AKT, down-regulation of E-Cadherin and enrichment of SLC marker positive and spheroid forming cells. MCF-7-COX-2 cells also showed increased lung colonization in NOD/SCID/GUSB-null mice, an effect reversed with EP4-knockdown or EP4A treatment of the MCF-7-COX-2 cells. COX-2/EP4/ALDH1A mRNA expression in human breast cancer tissues were highly correlated with one other, more marked in progressive stage of disease. In situ immunostaining of human breast tumor tissues revealed co-localization of SLC markers with COX-2, supporting COX-2 inducing SLCs. High COX-2/EP4 mRNA expression was linked with reduced survival. Thus, EP4 represents a novel SLC

  20. Phil Cox Takes on APPA Presidency with Energy, Experience, and Commitment.

    Science.gov (United States)

    Thaler-Carter, Ruth E.

    2002-01-01

    Describes the background, experience, and goals of Philip L. Cox, the new president of APPA, the Association of Higher Education Facilities Officers, who currently serves as director of facilities management for Cornell University in Ithaca, New York. Explores his vision for APPA. (EV)

  1. Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products.

    Science.gov (United States)

    Chandrasekaran, C V; Deepak, H B; Thiyagarajan, P; Kathiresan, S; Sangli, Gopal Krishna; Deepak, M; Agarwal, Amit

    2011-02-15

    Glycyrrhiza glabra and its phytoconstituents have been known to possess widespread pharmacological properties as an anti-inflammatory, anti-viral, antitumour and hepatoprotective drug. In this study, we examined the inhibitory potential of extract of G. glabra (GutGard™) root and its phytoconstituents (glabridin, glycyrrhizin, and isoliquiritigenin) on both cyclooxygenase (COX) and lipoxygenase (LOX) products in order to understand the mechanism of its anti-inflammatory action. Inhibitory effect of GutGard™ and its phytoconstituents on lipopolysaccharide (LPS) induced prostaglandin E(2) (PGE(2)), calcimycin (A23187) induced thromboxane (TXB(2)), and leukotriene (LTB(4)) release was studied using murine macrophages (J774A.1) and human neutrophil (HL-60) cells. Results revealed that, G. glabra and glabridin significantly inhibited PGE(2), TXB(2) (COX) and LTB(4) (LOX), while, isoliquiritigenin exerted inhibitory effect only against COX products but failed to suppress LOX product. However, glycyrrhizin at the tested concentrations failed to exhibit inhibitory effect on both COX and LOX products. Here, we report for the first time that G. glabra (almost devoid of glycyrrhizin) exhibits anti-inflammatory property likely through the inhibition of PGE(2), TXB(2) and LTB(4) in mammalian cell assay system, which could be influenced in part by glabridin and isoliquiritigenin.

  2. A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Mortensen, John Pløen; Bisgaard, Claus;

    2008-01-01

    BACKGROUND AND AIM: The aim of this study was to investigate the possible effect of a COX-2 inhibitor in addition to chemoradiation of locally advanced rectal cancer. MATERIALS AND METHODS: The study included 35 patients with rectal adenocarcinoma. All patients had a tumor localised....

  3. Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Huimin, E-mail: huiminchen.jq@gmail.com [Department of Geratology, Liaoning Jinqiu Hospital, Shenyang 110015 (China); Ma, Feng [Institute of Immunology, Zhejiang University of Medicine, Hangzhou 310058 (China); Hu, Xiaona; Jin, Ting; Xiong, Chuhui [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China); Teng, Xiaochun, E-mail: tengxiaochun@126.com [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)

    2013-10-11

    Highlights: •Downregulation of RXRα in senescent macrophage. •RXRα suppresses NF-κB activity and COX2 expression. •Increased PGE2 production due to downregulation of RXRα. -- Abstract: Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXRα, a nuclear receptor that can suppress NF-κB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXRα agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXRα antagonist HX531 in young mice increases COX2, TNF-α, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-κB activity and PGE2 production in senescent macrophages, but also provides RXRα as a potential therapeutic target for treating the age-related diseases.

  4. Cyclooxygenase 1 (COX1 expression in Type 2 diabetes mellitus: A preliminary study from north India

    Directory of Open Access Journals (Sweden)

    Sushma Verma

    2016-01-01

    Conclusion: Although COX1 is known to be a “housekeeping” gene, our study showed that its expression can be correlated with the disease condition and be used as a marker. However, further studies are required in more number of samples from other ethnic populations to confirm the findings.

  5. Analysis of multi-species point patterns using multivariate log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus; Guan, Yongtao; Jalilian, Abdollah;

    Multivariate log Gaussian Cox processes are flexible models for multivariate point patterns. However, they have so far only been applied in bivariate cases. In this paper we move beyond the bivariate case in order to model multi-species point patterns of tree locations. In particular we address...

  6. Prognostic significance of COX-2 and β-catenin in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Amani Kazem

    2014-09-01

    Conclusion: Both β-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

  7. Isoorientin, a Selective Inhibitor of Cyclooxygenase-2 (COX-2) from the Tubers of Pueraria tuberosa.

    Science.gov (United States)

    Sumalatha, Manne; Munikishore, Rachakunta; Rammohan, Aluru; Gunasekar, Duvvuru; Kumar, Kotha Anil; Reddy, Kakularam Kumar; Azad, Rajaram; Reddanna, Pallu; Bodo, Bernard

    2015-10-01

    Bioassay-guided fraction of the methanol extract of the roots of Pueraria tuberose DC yielded puerarin, an isoflavone C-glycoside (PT-1), isoorientin, a flavone C-glycoside (PT-2) and mangiferin, a xanthone C-glycoside (PT-3). The extracts and the isolated compounds were screened for potent anti-inflammatory components inhibiting the cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX), the target enzymes of inflammation, by employing spectroscopic/polorographic methods. Among these, isoorientin was found to be a potent inhibitor of COX-2with an IC50 value of 39 μM. Docking studies were carried out to understand the interactions of isorientin (PT-2) with COX-2.The structures of the isolates were determined by mass spectrometry and 2D-NMR techniques including HSQC, HMBC, NOESY and 1H-1H COSY experiments. Although isoorientin and mangiferin have been reported from several plant sources, this is the first report of their isolation from a Pueraria species.

  8. Systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov (Hemiptera: Pseudococcidae)

    Science.gov (United States)

    A systematic revision of the mealybug genus Delottococcus Cox & Ben-Dov is presented. Nine species are treated, including D. millari which is described as new. The 8 previously described species are: Delottococcus aberiae (De Lotto), D. confusus (De Lotto), D. elisabethae (Brain), D. euphorbiae (E...

  9. Measures to assess the prognostic ability of the stratified Cox proportional hazards model

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures w...

  10. Magnetic and transport properties of Fe1-xCoxSb2

    Science.gov (United States)

    Hu, Rongwei; Petrovic, Cedomir; Mitrovic, Vesna

    2006-03-01

    Anisotropic magnetic and electronic transport measurements were carried out on large single crystals of Fe1-xCoxSb2, grown by self flux method, in the temperature range 1.8-350K for 0Pnnm structure of FeSb2 to monoclinic P21/c structure of CoSb2. Large magnetoresistance and anisotropy in electronic transport were observed.

  11. High-Dimensional Cox Regression Analysis in Genetic Studies with Censored Survival Outcomes

    Directory of Open Access Journals (Sweden)

    Jinfeng Xu

    2012-01-01

    Full Text Available With the advancement of high-throughput technologies, nowadays high-dimensional genomic and proteomic data are easy to obtain and have become ever increasingly important in unveiling the complex etiology of many diseases. While relating a large number of factors to a survival outcome through the Cox relative risk model, various techniques have been proposed in the literature. We review some recently developed methods for such analysis. For high-dimensional variable selection in the Cox model with parametric relative risk, we consider the univariate shrinkage method (US using the lasso penalty and the penalized partial likelihood method using the folded penalties (PPL. The penalization methods are not restricted to the finite-dimensional case. For the high-dimensional (p→∞, p≪n or ultrahigh-dimensional case (n→∞, n≪p, both the sure independence screening (SIS method and the extended Bayesian information criterion (EBIC can be further incorporated into the penalization methods for variable selection. We also consider the penalization method for the Cox model with semiparametric relative risk, and the modified partial least squares method for the Cox model. The comparison of different methods is discussed and numerical examples are provided for the illustration. Finally, areas of further research are presented.

  12. Survival prediction based on compound covariate under Cox proportional hazard models.

    Directory of Open Access Journals (Sweden)

    Takeshi Emura

    Full Text Available Survival prediction from a large number of covariates is a current focus of statistical and medical research. In this paper, we study a methodology known as the compound covariate prediction performed under univariate Cox proportional hazard models. We demonstrate via simulations and real data analysis that the compound covariate method generally competes well with ridge regression and Lasso methods, both already well-studied methods for predicting survival outcomes with a large number of covariates. Furthermore, we develop a refinement of the compound covariate method by incorporating likelihood information from multivariate Cox models. The new proposal is an adaptive method that borrows information contained in both the univariate and multivariate Cox regression estimators. We show that the new proposal has a theoretical justification from a statistical large sample theory and is naturally interpreted as a shrinkage-type estimator, a popular class of estimators in statistical literature. Two datasets, the primary biliary cirrhosis of the liver data and the non-small-cell lung cancer data, are used for illustration. The proposed method is implemented in R package "compound.Cox" available in CRAN at http://cran.r-project.org/.

  13. Ruin Probabilities and Aggregrate Claims Distributions for Shot Noise Cox Processes

    DEFF Research Database (Denmark)

    Albrecher, H.; Asmussen, Søren

    We consider a risk process Rt where the claim arrival process is a superposition of a homogeneous Poisson process and a Cox process with a Poisson shot noise intensity process, capturing the effect of sudden increases of the claim intensity due to external events. The distribution of the aggregate...

  14. [Effect of COX-2 inhibitor celecoxib on proliferation, apoptosis of HL-60 cells and its mechanism].

    Science.gov (United States)

    Xie, Xia; Li, Jie; Wang, Rui-Cang; Geng, Rui-Li; Wang, Su-Yun; Wang, Chao; Zhao, Xiao-Yun; Hao, Hong-Ling

    2014-06-01

    This study was aimed to investigate the effect of COX-2 inhibitor celecoxib on proliferation, apoptosis of human acute myeloid leukemia cell line HL-60 and its mechanism. HL-60 cells were cultured with different concentrations of celecoxib for 24 h. Cell proliferation was analyzed by CCK-8 assay, cell apoptosis and cell cycle distribution were detected by flow cytometry. Cyclin D1, cyclin E1 and COX-2 mRNA expressions were determined by RT-PCR. The results showed that after the HL-60 cells were treated with different concentrations of celecoxib for 24 h, the cell growth was significantly inhibited in a dose-dependent manner(r = 0.955), IC50 was 63.037 µmol/L of celecoxib. Celecoxib could effectively induce apoptosis in HL-60 cells also in dose-dependent manner(r = 0.988), blocked the HL-60 cells in the G0/G1 phase. The expression of cyclin D1, cyclin E1 and COX-2 mRNA were downregulated. It is concluded that celecoxib can inhibit the proliferation of HL-60 cells in dose-dependent manner, celecoxib causes cell G0/G1 arrest and induces cell apoptosis possibly through down-regulation of the cyclin D1 and cyclin E1 expression, and down-regulation of COX-2 expression respectively.

  15. Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation

    Institute of Scientific and Technical Information of China (English)

    Ananya Chatterjee; Sirshendu Chatterjee; Smita Das; Arpita Saha; Subrata Chattopadhyay; Sandip K. Bandyopadhyay

    2012-01-01

    The mechanism of indomethacin-induced gastric ulcer healing by ellagic acid (EA) in experimental mice model is described in our study.Ulcer index (UI) and myeloperoxidase (MPO) activity of the stomach tissues showed maximum ulceration on the third day after indomethacin (18 mg/kg,single dose) administration.Preliminary observation of UI and MPO activity suggests that EA possesses ulcer-healing activity.Other anti-ulcer parameters such as the levels of prostaglandin E2,cyclooxygenase (COX) 1 and 2 enzymes,anti-inflammatory cytokines [interleukin (IL)-4 and -5J,pro-angiogenic factors,e.g.vascular endothelial growth factor,hepatocyte growth factor (HGF),and endothelial growth factor (EGF) were down-regulated by indomethacin.EA (7 mg/kg/day) treatment for 3 days shifted the indomethacin-induced pro-inflammatory biochemical parameters to the healing side.These activities were correlated with the ability of EA to alter the COX-2-dependent healing pathways.The ulcer-healing activity of EA was,however,compromised by pre-administration of the specific COX-2 inhibitor,celecoxib,and NS-398.Taken together,these results suggested that the EA treatment accelerates ulcer healing by inducing IL-4,EGF/HGF levds and enhances COX-2 expression.

  16. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  17. Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor.

    Science.gov (United States)

    Rathore, Ankita; Rahman, Mujeeb Ur; Siddiqui, Anees Ahamad; Ali, Abuzer; Shaharyar, Mohammad

    2014-12-01

    New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2-(2-((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide as 1-((5-substituted alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-ylthio)methyl)-1H-benzimidazoles (5a-r) with the aim to acquire selective cyclooxygenase (COX-2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX-1 and COX-2 inhibitory potency and the results showed that they had good-to-remarkable activity with an IC50 range of 11.6-56.1 µM. The most active compounds were further screened for their in vivo anti-inflammatory activity by using the carrageenan-induced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX-2 inhibition with an IC50 value of 8.2 µM and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO-31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX-2 inhibitors.

  18. COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease.

    Science.gov (United States)

    Oliveira-Filho, Jamary; Ornellas, Ana C P; Zhang, Cathy R; Oliveira, Luciana M B; Araújo-Santos, Théo; Borges, Valeria M; Ventura, Laís M G B; Reis, Francisco J F B; Aras, Roque; Fernandes, André M; Rosand, Jonathan; Greenberg, Steven M; Furie, Karen L; Rost, Natalia S

    2015-08-01

    To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P = 5 × 10(-6)) and decreased PGE2 levels (P = 4 × 10(-5)); similarly, Chagas was associated with stroke (P = 4 × 10(-3)) and decreased PGE2 levels (P = 7 × 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P = .037), but not among cardioembolic stroke patients. Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. The David Y. Graham lecture: use of nonsteroidal antiinflammatory drugs in a COX-2 restricted environment.

    Science.gov (United States)

    Chan, Francis K L

    2008-01-01

    Recent evidence suggests that both cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs, with the possible exception of naproxen, increase cardiovascular (CV) hazard. Clinicians should assess not only patients' GI risk but also their CV risk before prescribing these drugs. Patients with low CV risk can be managed according to their GI risk-low-risk patients (without risk factors) receive nonselective NSAIDs, medium risk patients (1-2 risk factors) receive COX-2 inhibitors or nonselective NSAIDs plus a proton pump inhibitor (PPI) or misoprostol, whereas high-risk patients (multiple risk factors, previous ulcer complications, or concomitant anticoagulants) receive a COX-2 inhibitor plus a PPI or misoprostol. Among patients with high CV risk (e.g., prior cardiothrombotic events) who require NSAIDs, naproxen is preferred. These patients should receive a prophylactic PPI or misoprostol because the risk of ulcer bleeding is substantially increased with concomitant use of naproxen and low-dose aspirin. Substitution of clopidogrel for aspirin is not recommended in patients at risk for upper GI bleeding who require antiplatelet therapy. Patients with high GI and high CV risk should avoid NSAIDs and COX-2 inhibitors. If antiinflammatory analgesics are required, the choice of therapy depends on the relative importance of GI and CV risks of individual patients. Combination of naproxen, low-dose aspirin, and a PPI or misoprostol is recommended if CV risk is the major concern (e.g., recent myocardial infarction). In contrast, combination of low-dose COX-2 inhibitor, low-dose aspirin, and a PPI or misoprostol is preferred if GI risk outweighs CV risk (e.g., recent ulcer bleeding and stable CV disease).

  20. IL-1β stimulates COX-2 dependent PGE₂ synthesis and CGRP release in rat trigeminal ganglia cells.

    Directory of Open Access Journals (Sweden)

    Lars Neeb

    Full Text Available OBJECTIVE: Pro-inflammatory cytokines like Interleukin-1 beta (IL-1β have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified. METHODS AND RESULTS: 1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE(2 release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib and a non-selective COX-inhibitor (indomethacin. 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE(2 and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect. CONCLUSION: We identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE(2 (by COX-2 in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2

  1. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-{alpha}-treated A549 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Lixin; Zhang, Shuang; Jiang, Zhenzhou; Huang, Xin; Wang, Tao; Huang, Xiao; Li, Han [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Triptolide inhibited COX-2 expression and the half-life of COX-2 mRNA is decreased. Black-Right-Pointing-Pointer The HuR protein shuttling from nucleus to cytoplasm is inhibited by triptolide. Black-Right-Pointing-Pointer Triptolide inhibited 3 Prime -UTR fluorescence reporter gene activity. Black-Right-Pointing-Pointer COX-2 mRNA binding to HuR is decreased by triptolide in pull-down experiments. -- Abstract: Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non-small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-{alpha}-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3 Prime -untranslated region (3 Prime -UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer.

  2. Pulmonary and Cardiorenal Cyclooxygenase-1 (COX-1, -2 (COX-2, and Microsomal Prostaglandin E Synthase-1 (mPGES-1 and -2 (mPGES-2 Expression in a Hypertension Model

    Directory of Open Access Journals (Sweden)

    Zaher A. Radi

    2007-01-01

    Our work suggests that in hypertensive mice, there are (a significant microanatomic variations in the pulmonary, renal, and cardiac distribution and cellular localization of COX-1, COX-2, mPGES-1, and mPGES-2, and (b no differences in expression between genders.

  3. Genomic,Lipidomic,and Metabolomic Analysis ®CrossMark of Cyclooxygenase-null Cells:Eicosanoid Storm, Cross Talk, and Compensation by COX-1

    Institute of Scientific and Technical Information of China (English)

    Abul BMMK Islam; Mandar Dave; Sonia Amin; oderick V Jensen; Ashok R Amin

    2016-01-01

    The constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2"^' or COX-1'^" mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-" > COX-1"^' > WT + IL-lp. COX-l /_ or COX-2'^" cells shared about 50% of the induced transcripts with WT cells treated with IL-lp, respectively. An interactive 4"anti-inflammatory, proinflammatory, and redox-activated” signature in the protein—protein interactome map was observed in COX-2'^' cells. The augmented COX-1 mRNA (in COX-2cells) was associated with the upregulation of mRNAs for glutathione 5-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQOl),aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1a, thromboxane B2 (TXB2), and PGF2a. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an ‘‘eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1b induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels.

  4. A comparative immunohistochemical analysis of COX-2, p53, and Ki-67 expression in keratocystic odontogenic tumors

    NARCIS (Netherlands)

    Mendes, R.A.; Carvalho, J.F.C.; van der Waal, I.

    2011-01-01

    Objective. The aim of the present study was to investigate the association between the expression of cyclooxygenase-2 (COX-2) in keratocystic odontogenic tumors (KCOT) and more commonly used markers, such as p53 and Ki-67. Study design. Expression of cyclooxygenase-2 (COX-2) in 20 biopsy specimens o

  5. Deep RNA sequencing reveals the smallest known mitochondrial micro exon in animals: The placozoan cox1 single base pair exon.

    Science.gov (United States)

    Osigus, Hans-Jürgen; Eitel, Michael; Schierwater, Bernd

    2017-01-01

    The phylum Placozoa holds a key position for our understanding of the evolution of mitochondrial genomes in Metazoa. Placozoans possess large mitochondrial genomes which harbor several remarkable characteristics such as a fragmented cox1 gene and trans-splicing cox1 introns. A previous study also suggested the existence of cox1 mRNA editing in Trichoplax adhaerens, yet the only formally described species in the phylum Placozoa. We have analyzed RNA-seq data of the undescribed sister species, Placozoa sp. H2 ("Panama" clone), with special focus on the mitochondrial mRNA. While we did not find support for a previously postulated cox1 mRNA editing mechanism, we surprisingly found two independent transcripts representing intermediate cox1 mRNA splicing stages. Both transcripts consist of partial cox1 exon as well as overlapping intron fragments. The data suggest that the cox1 gene harbors a single base pair (cytosine) micro exon. Furthermore, conserved group I intron structures flank this unique micro exon also in other placozoans. We discuss the evolutionary origin of this micro exon in the context of a self-splicing intron gain in the cox1 gene of the last common ancestor of extant placozoans.

  6. Effects of the estrous cycle, pregnancy and interferon tau on expression of cyclooxygenase two (COX-2 in ovine endometrium

    Directory of Open Access Journals (Sweden)

    Bazer Fuller W

    2003-08-01

    Full Text Available Abstract In sheep, the uterus produces luteolytic pulses of prostaglandin F2α (PGF on Days 15 to 16 of estrous cycle to regress the corpus luteum (CL. These PGF pulses are produced by the endometrial lumenal epithelium (LE and superficial ductal glandular epithelium (sGE in response to binding of pituitary and/or luteal oxytocin to oxytocin receptors (OTR and liberation of arachidonic acid, the precursor of PGF. Cyclooxygenase-one (COX-1 and COX-2 are rate-limiting enzymes in PGF synthesis, and COX-2 is the major form expressed in ovine endometrium. During pregnancy recognition, interferon tau (IFNτ, produced by the conceptus trophectoderm, acts in a paracrine manner to suppress development of the endometrial epithelial luteolytic mechanism by inhibiting transcription of estrogen receptor α (ERα (directly and OTR (indirectly genes. Conflicting studies indicate that IFNτ increases, decreases or has no effect on COX-2 expression in bovine and ovine endometrial cells. In Study One, COX-2 mRNA and protein were detected solely in endometrial LE and sGE of both cyclic and pregnant ewes. During the estrous cycle, COX-2 expression increased from Days 10 to 12 and then decreased to Day 16. During early pregnancy, COX-2 expression increased from Days 10 to 12 and remained higher than in cyclic ewes. In Study Two, intrauterine infusion of recombinant ovine IFNτ in cyclic ewes from Days 11 to 16 post-estrus did not affect COX-2 expression in the endometrial epithelium. These results clearly indicate that IFNτ has no effect on expression of the COX-2 gene in the ovine endometrium. Therefore, antiluteolytic effects of IFNτ are to inhibit ERα and OTR gene transcription, thereby preventing endometrial production of luteolytic pulses of PGF. Indeed, expression of COX-2 in the endometrial epithelia as well as conceptus is likely to have a beneficial regulatory role in implantation and development of the conceptus.

  7. The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Weng

    Full Text Available OBJECTIVE: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643 from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity via a meta-analysis. METHODS AND RESULTS: In total, there were 4 (353/595, 6 (344/698, 10 (588/878 and 7 (209/676 articles (patients/controls qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2. The risk estimate was expressed as odds ratio (OR and 95% confidence interval (95% CI. Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005 and rs1126643 (2.37; 1.44-3.89; 0.001 with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03. Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034 and averaged platelet numbers (P = 0.012 between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. CONCLUSION: Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

  8. Potential of a COX-2 inhibitor in lowering chemotherapy-induced neutropenia%Potential of a COX-2 inhibitor in lowering chemotherapy induced neutropenia

    Institute of Scientific and Technical Information of China (English)

    Louis Wing-Cheong Chow; Adrian Yun-San Yip; Eleanor Yuen-Yuen Ong; Chi-Kei Lam; Masakazu Toi

    2010-01-01

    Objective This study was initially designed to evaluate the effect of celecoxib on the regimen of 5 fluorouracil, epirubicin, and cyclophosphamide (FEC) combination, followed by docetaxel (T) in neoadjuvant setting. An unplanned preliminary review on safety was conducted after a halt of the study due to the concerned potential cardiovascular risk of using COX 2 inhibitors.Methods We studied 23 consecutive cases of operable breast cancer having received four cycles of FEC(500 mg/m2, 100 mg/m2, 500 mg/m2) followed by four cycles of T(100 mg/m2) with concurrent celecoxib (400 mg twice daily) (group A) or same chemotherapy regimen but without concurrent celecoxib (group B). These combined chemotherapies were administered every 3 weeks. The Chi square test or Fisher's exact test were used to assess the difference in incidence of limiting hematological toxicites between groups. Results 23 patients (group A: n=12; group B, n=11) received a total of 183 out of 184 planned treatment cycles; one (4%, 1/23) of them omitted the fourth cycle of FEC owing to repeated incidences of febrile neutropenia. Received dose intensity (RDI) for FEC in group A (90%±11%) was higher than that in group B (80%±8%) while RDI for T was similar between group A (93%±8%) and group B (96%±9%). Of the first 91 treatment cycles of FEC, limiting hematological toxicity, severe neutropenia including febrile neutropenia, was significantly different between group A and B [(10.4%, 5/48) vs.( 32.6%, 14/43), P=0.009]. Other toxicities commonly observed in chemotherapy receiving patients were manageable. Conclusions Neoadjuvant use of FEC followed by T with concurrent celecoxib appeared to be safe for treatment of operable invasive breast cancer. The observed lower incidence of chemotherapy induced neutropenia is possibly contributed by the administration of COX inhibitor. We believe that further investigation might provide more evidence on the use of COX 2 inhibitors in breast cancer.

  9. The measurement of radon working levels at a mineral separation pilot plant in Cox's Bazar, Bangladesh.

    Science.gov (United States)

    Hamid Khan, M A; Chowdhury, M S

    2003-10-01

    Beach Sand Exploitation Centre at Cox's Bazar, Bangladesh, produces commercial grade concentrations of magnetite, ilmenite, zircon, etc., from the high-grade accumulations available along the beach and foredune of Cox's Bazar. Solid state nuclear track detectors (CR-39 foils) were used to determine indoor radon concentration of radioactive mineral sands and the technologically enhanced radiation level inside the pilot plant of the Centre. It is found that the concentrations at processed mineral stock areas are high, and the maximum concentration was found to be 2,103 +/- 331 Bq m(-3) (0.23 +/- 0.03 WL). The indoor concentration of radon and its decay products in the raw sand stock area and at other locations was in the range of 116 +/- 27 Bq m(-3) (0.03 +/- 0.003 WL) to 2,042 +/- 233 Bq m(-3) (0.22 +/- 0.03 WL).

  10. INHOMOGENEITY IN SPATIAL COX POINT PROCESSES – LOCATION DEPENDENT THINNING IS NOT THE ONLY OPTION

    Directory of Open Access Journals (Sweden)

    Michaela Prokešová

    2010-11-01

    Full Text Available In the literature on point processes the by far most popular option for introducing inhomogeneity into a point process model is the location dependent thinning (resulting in a second-order intensity-reweighted stationary point process. This produces a very tractable model and there are several fast estimation procedures available. Nevertheless, this model dilutes the interaction (or the geometrical structure of the original homogeneous model in a special way. When concerning the Markov point processes several alternative inhomogeneous models were suggested and investigated in the literature. But it is not so for the Cox point processes, the canonical models for clustered point patterns. In the contribution we discuss several other options how to define inhomogeneous Cox point process models that result in point patterns with different types of geometric structure. We further investigate the possible parameter estimation procedures for such models.

  11. Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation

    DEFF Research Database (Denmark)

    Yang, Ye; Christensen, Ole Fredslund; Sorensen, Daniel

    2011-01-01

    of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box–Cox transformations. Litter size data in rabbits and pigs that had previously been analysed...... in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box–Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis...... in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected...

  12. Maximum Likelihood Inference for the Cox Regression Model with Applications to Missing Covariates.

    Science.gov (United States)

    Chen, Ming-Hui; Ibrahim, Joseph G; Shao, Qi-Man

    2009-10-01

    In this paper, we carry out an in-depth theoretical investigation for existence of maximum likelihood estimates for the Cox model (Cox, 1972, 1975) both in the full data setting as well as in the presence of missing covariate data. The main motivation for this work arises from missing data problems, where models can easily become difficult to estimate with certain missing data configurations or large missing data fractions. We establish necessary and sufficient conditions for existence of the maximum partial likelihood estimate (MPLE) for completely observed data (i.e., no missing data) settings as well as sufficient conditions for existence of the maximum likelihood estimate (MLE) for survival data with missing covariates via a profile likelihood method. Several theorems are given to establish these conditions. A real dataset from a cancer clinical trial is presented to further illustrate the proposed methodology.

  13. Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin.

    Science.gov (United States)

    Stegbauer, Johannes; Coffman, Thomas M

    2015-11-02

    The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet induces expression of cyclooxygenase-2 (COX-2) in macrophages, resulting in enhanced levels of prostaglandin E2 (PGE2), autocrine activation of the macrophage E-prostanoid 4 (EP4) receptor, and subsequent triggering of parallel pathways in the kidney and in skin that help dispose of excess sodium. The authors found that blockade or genetic elimination of the COX-2/PGE2/EP4 receptor pathway in hematopoietic cells causes salt-sensitive hypertension in mice. These studies illuminate an unexpected central role for the macrophage in coordinating homeostatic responses to dietary salt intake and suggest a complex pathophysiology for hypertension associated with NSAID use.

  14. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

    2015-12-01

    The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer's disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM.

  15. Aerobic oxidation of hydroxymethylfurfural and furfural by using heterogeneous Cox Oy -N@C catalysts.

    Science.gov (United States)

    Deng, Jin; Song, Hai-Jie; Cui, Min-Shu; Du, Yi-Ping; Fu, Yao

    2014-12-01

    2,5-Furandicarboxylic acid (FDCA) is considered to be a promising replacement for terephthalic acid since they share similar structures and properties. In contrast to FDCA, 2,5-furandicarboxylic acid methyl (FDCAM) has properties that allow it to be easily purified. In this work, we reported an oxidative esterification of 5-hydroxymethylfurfural (HMF) and furfural to prepare corresponding esters over Cox Oy -N@C catalysts using O2 as benign oxidant. High yield and selectivity of FDCAM and methyl 2-furoate were obtained under optimized conditions. Factors which influenced the product distribution were examined thoroughly. The Cox Oy -N@C catalysts were recycled five times and no significant loss of activity was detected. Characterization of the catalysts could explain such phenomena. Using XPS and TGA, we made a thorough investigation of the effects of ligand and pyrolysis temperature on catalyst activity.

  16. DWCox: A density-weighted Cox model for outlier-robust prediction of prostate cancer survival

    OpenAIRE

    Jinfeng Xiao; Sheng Wang; Jingbo Shang; Henry Lin; Doris Xin; Xiang Ren; Jiawei Han; Jian Peng

    2016-01-01

    Reliable predictions on the risk and survival time of prostate cancer patients based on their clinical records can help guide their treatment and provide hints about the disease mechanism. The Cox regression is currently a commonly accepted approach for such tasks in clinical applications. More complex methods, like ensemble approaches, have the potential of reaching better prediction accuracy at the cost of increased training difficulty and worse result interpretability. Better performance o...

  17. Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors

    OpenAIRE

    Harris, Randall; Beebe,; Alshafie,

    2012-01-01

    Randall E Harris,1 Joanne Beebe,1 Galal A Alshafie21College of Medicine and College of Public Health, 2College of Pharmacy, The Ohio State University, Columbus, Ohio, USAAbstract: We conducted a series of epidemiologic studies to evaluate the chemopreventive effects of aspirin, ibuprofen, and selective cyxlooxygenase-2 (COX-2) inhibitors (coxibs) against cancers of the breast, colon, prostate, and lung. Composite results across all four cancer sites revealed that regular intake of 325 mg aspi...

  18. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.

    Science.gov (United States)

    Willenberg, Ina; Meschede, Anna K; Gueler, Faikah; Jang, Mi-Sun; Shushakova, Nelli; Schebb, Nils Helge

    2015-01-01

    Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX-2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX-2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX-2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.

  19. Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin

    OpenAIRE

    Stegbauer, Johannes; Coffman, Thomas M.

    2015-01-01

    The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet induces expression of cyclooxygenase-2 (COX-2) in macrophages, resulting in enhanced levels of prostaglandin E2 (PGE2), autocrine activation of the macrophage E-prostanoid 4 (EP4) receptor, and subsequent triggering of parallel pathways in the...

  20. On Model Specification and Selection of the Cox Proportional Hazards Model*

    OpenAIRE

    Lin, Chen-Yen; Halabi, Susan

    2013-01-01

    Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox’s model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing tradi...

  1. COxSwAIN: Compressive Sensing for Advanced Imaging and Navigation

    Science.gov (United States)

    Kurwitz, Richard; Pulley, Marina; LaFerney, Nathan; Munoz, Carlos

    2015-01-01

    The COxSwAIN project focuses on building an image and video compression scheme that can be implemented in a small or low-power satellite. To do this, we used Compressive Sensing, where the compression is performed by matrix multiplications on the satellite and reconstructed on the ground. Our paper explains our methodology and demonstrates the results of the scheme, being able to achieve high quality image compression that is robust to noise and corruption.

  2. A Bayes Formula for Nonlinear Filtering with Gaussian and Cox Noise

    Directory of Open Access Journals (Sweden)

    Vidyadhar Mandrekar

    2011-01-01

    Full Text Available A Bayes-type formula is derived for the nonlinear filter where the observation contains both general Gaussian noise as well as Cox noise whose jump intensity depends on the signal. This formula extends the well-known Kallianpur-Striebel formula in the classical non-linear filter setting. We also discuss Zakai-type equations for both the unnormalized conditional distribution as well as unnormalized conditional density in case the signal is a Markovian jump diffusion.

  3. Optical properties of BaFe2-xCoxAs2

    NARCIS (Netherlands)

    van Heumen, E.; Huang, Y.; de Jong, S.; Kuzmenko, A.B.; Golden, M.S.; van der Marel, D.

    2010-01-01

    We present detailed temperature-dependent optical data on BaFe2-xCoxAs2 (BCFA), with x = 0.14, between 4 meV and 6.5 eV. We analyze our spectra to determine the main optical parameters and show that in this material the interband conductivity already starts at energies as low as 10 meV. We determine

  4. COX2 and NOS3 gene polymorphisms in women with gestational diabetes.

    Science.gov (United States)

    Tarnowski, Maciej; Tkacz, Marta; Dziedziejko, Violetta; Safranow, Krzysztof; Pawlik, Andrzej

    2017-08-01

    Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnancy. Low-grade inflammation plays an important role in the pathogenesis of this disorder. The present study aimed to examine the association between COX2 (rs6681231) and NOS3 (rs1799983 and rs2070744) gene polymorphisms and GDM. The study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks of gestation. We observed an increased frequency of COX2 rs6681231 CC and GC genotype carriers among women with GDM (CC + GC versus GG, odds ratio = 1.55, 95% confidence interval = 1.01-2.36, p = 0.043; C versus G, odds ratio = 1.59, 95% confidence interval = 1.10-2.30, p = 0.013). There were no statistically significant differences in the distribution of NOS3 rs1799983 and rs2070744 between GDM and healthy women. Moreover, among women treated with insulin, we observed an increased frequency of COX2 rs6681231 CC and NOS3 rs1799983 TT genotype carriers. The results of the present study suggest that the CC genotype of the COX2 rs6681231 polymorphism is associated with an increased risk of GDM and the need for insulin therapy, whereas the TT genotype of the NOS3 rs1799983 polymorphism may be associated with the need for insulin therapy in women with GDM. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Epigenetic change in e-cardherin and COX-2 to predict chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-11-01

    Full Text Available Abstract Background DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2 in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis. Methods Total DNA was extracted from the blood samples of 108 systemically healthy non-periodontitis subjects, and the gingival tissues and blood samples of 110 chronic periodontitis patient as well as neoplastic tissues of 106 breast cancer patients. Methylation-specific PCR for E-Cadherin and COX-2 was performed on these samples and the PCR products were analyzed on 2% agarose gel. Results Hypermethylation of E-Cadherin and COX-2 was observed in 38% and 35% of the breast cancer samples, respectively. In chronic periodontitis patients the detection rate was 25% and 19% respectively, and none was found in the systemically healthy non-periodontitis control subjects. The hypermethylation status was shown to be correlated among the three groups with statistical significance (p Conclusions This set of data shows that the epigenetic change in E-Cadherin and Cyclooxygenase-2 is associated with chronic periodontitis. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to the effects of cancer. Chronic periodontitis to some extent might be associated with DNA hypermethylation which is related to cancer risk factors.

  6. Simultaneous abrogation of NOS-2 and COX-2 activities is lethal in partially hepatectomised mice.

    Science.gov (United States)

    Zeini, Miriam; Hortelano, Sonsoles; Través, Paqui G; Martín-Sanz, Paloma; Boscá, Lisardo

    2004-06-01

    We have investigated the role of the nitric oxide (NO) and prostaglandins (PGs), respectively, synthesized by nitric oxide synthase 2 (NOS-2) and cyclooxygenase-2 (COX-2), in the outcome of liver regeneration after partial hepatectomy (PH). Liver mass recovery and molecular parameters related to cell proliferation and apoptotic death have been determined. NOS-2 and COX-2 are normally both expressed in the remnant liver after PH, and inhibition of either one delays regeneration. We found, however, that simultaneous suppression of the activities of NOS-2 (by gene knockout) and COX-2 (by pharmacological inhibition) resulted in animal death between 24 and 72 h after PH. Analysis of liver mass recovery and molecular parameters related to cell proliferation and apoptotic death revealed increased liver-cell apoptosis and an insufficient proliferative response. Broad-specificity caspase inhibitors, such as z-Val-Ala-Asp.fmk (z-VAD), or administration of NO-donors, rescued animals from death, revealing a critical apoptotic bias at this stage of proliferation. These findings demonstrate that simultaneous signaling by NO and prostaglandins plays an important role in the mechanism of liver regeneration after PH by protecting the remnant tissue from apoptotic death.

  7. [Tubulointerstitial nephritis associated with treatment with selective Cox-2 inhibitors, celecoxib and rofecoxib].

    Science.gov (United States)

    Ortiz, M; Mon, C; Fernández, M J; Sánchez, R; Mampaso, F; Alvarez Ude, F

    2005-01-01

    The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs (NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relation to the NSAIDS is the production of a very similar analgesic effect, but with fewer gastrointestinal side effects. However, their effects on renal function are little known as yet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitors as anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renal biopsy, associated with administration of the two Cox-2 inhibitors currently available on the market, celecoxib and rofecoxib. In both cases, we were talking about elderly women, with deterioration of the general condition and acute renal failure. In the former case, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly "variegated" in its histologic expression. In the second case, was associated with strong indications of chronicity. Treatment with steroid was initiated in both patients and improvement of renal function was observed.

  8. Synthesis and evaluation of benzimidazole derivatives as selective COX-2 inhibitors.

    Science.gov (United States)

    Rathore, Ankita; Mujeeb-Ur-Rahman; Siddiqui, Anees A; Ali, Abuzer; Yar, Mohammad Shahar

    2015-01-01

    A new series of 1-{(5-substituted-alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl}-2-(piperidin-1-ylmethyl)-1Hbenzimidazoles (5a-5r) was synthesized and screened for their inhibitory activity against COX (1 and 2). In vivo antiinflammatory activity of potent compounds was done by carrageenan-induced rat paw edema model. In vitro anticancer activity of synthesized compounds was also performed at the National Cancer Institute (NCI) against NCI 60 cell lines panel. Out of the 18 compounds screened, 5h, 5i, 5j and 5l were found to be potent COX-2 inhibitors in the range of IC50 0.06-0.81 μM. In vivo anti-inflammatory screening results revealed that the compounds 5h and 5j manifested profound percent protection of 72.8 and 75.0%, respectively. Compound 5f exhibited moderate cytotoxicity with 58.79% growth inhibition against SNB-75 (CNS Cancer) cell lines and moderate activity against COX-2 (IC50 = 8.0 μM).

  9. COX-2 Inhibition Reduces Brucella Bacterial Burden in Draining Lymph Nodes

    Science.gov (United States)

    Gagnaire, Aurélie; Gorvel, Laurent; Papadopoulos, Alexia; Von Bargen, Kristine; Mège, Jean-Louis; Gorvel, Jean-Pierre

    2016-01-01

    Brucella is a Gram-negative facultative intracellular bacterium responsible for a chronic disease known as brucellosis, the most widespread re-emerging zoonosis worldwide. Establishment of a Th1-mediated immune response characterized by the production of IL-12 and IFNγ is essential to control the disease. Leukotrienes derived from arachidonic acid (AA) metabolism are known to negatively regulate a protective Th1 immune response against bacterial infections. Here, using genomics approaches we demonstrate that Brucella abortus strongly stimulates the prostaglandin (PG) pathway in dendritic cells (DC). We also show an induction of AA production by infected cells. This correlates with the expression of Ptgs2, a gene encoding the downstream cyclooxygenase-2 (COX-2) enzyme in infected DC. By comparing different infection routes (oral, intradermal, intranasal and conjunctival), we identified the intradermal inoculation route as the more potent in inducing Ptgs2 expression but also in inducing a local inflammatory response in the draining cervical lymph nodes (CLN). NS-398, a specific inhibitor of COX-2 enzymatic activity decreased B. melitensis burden in the CLN after intradermal infection. This effect was accompanied by a decrease of Il10 and a concomitant increase of Ifng expression. Altogether, these results suggest that Brucella has evolved to take advantage of the PG pathway in the harsh environment of the CLN in order to persist and subvert immune responses. This work also proposes that novel strategies to control brucellosis may include the use of COX-2 inhibitors. PMID:28018318

  10. Melatonin, a novel selective ATF-6 inhibitor, induces human hepatoma cell apoptosis through COX-2 downregulation

    Science.gov (United States)

    Bu, Li-Jia; Yu, Han-Qing; Fan, Lu-Lu; Li, Xiao-Qiu; Wang, Fang; Liu, Jia-Tao; Zhong, Fei; Zhang, Cong-Jun; Wei, Wei; Wang, Hua; Sun, Guo-Ping

    2017-01-01

    AIM To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin. METHODS Hepatoma cells, HepG2, were cultured in vitro. Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes’ expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis. RESULTS In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed. CONCLUSION These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis. PMID:28246472

  11. Influence of COX-2 and OXTR polymorphisms on treatment outcome in treatment resistant depression.

    Science.gov (United States)

    Mendlewicz, Julien; Crisafulli, Concetta; Calati, Raffaella; Kocabas, Neslihan Aygun; Massat, Isabelle; Linotte, Sylvie; Kasper, Siegfried; Fink, Martin; Sidoti, Antonina; Scantamburlo, Gabrielle; Ansseau, Marc; Antonijevic, Irina; Forray, Carlos; Snyder, Lenore; Bollen, Joseph; Montgomery, Stuart; Zohar, Joseph; Souery, Daniel; Serretti, Alessandro

    2012-05-10

    Inflammatory pathways play a crucial role in the pathomechanisms of antidepressant efficacy. The aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within cyclooxygenase-2 (COX-2, rs5275 and rs20417) and oxytocin receptor (OXTR, rs53576 and rs2254298) genes was associated with antidepressant treatment resistance, response or remission. Three hundred seventy-two patients were recruited in the context of a multicenter resistant depression study. They were genotyped for COX-2 and OXTR SNPs. Treatment resistance (according to two different definitions), response and remission were recorded. We did not observe any association between the genotypes or alleles of the selected SNPs within COX-2 and OXTR genes and treatment resistance, response and remission in the whole sample. Our results are consistent with those of some studies but not with those of other ones. Indeed, several factors could be involved in the discrepancy observed across studies. They include sample size, environmental factors, differences in ethnicity, different study designs, and different definitions of treatment resistance.

  12. Accounting for covariate measurement error in a Cox model analysis of recurrence of depression.

    Science.gov (United States)

    Liu, K; Mazumdar, S; Stone, R A; Dew, M A; Houck, P R; Reynolds, C F

    2001-01-01

    When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.

  13. Influence of Electroacupuncture on COX Activity of Hippocampal Mitochondria in Senescence- accelerated Mouse Prone 8 Mice

    Institute of Scientific and Technical Information of China (English)

    Peng Jing; Zeng Fang; He Yu-heng; Tang Yong; Yin Hai-yan; Yu Shu-guang

    2014-01-01

    Objective: To observe the effect of electroacupuncture (EA) on cytochrome c oxidase (COX)activity of hippocampal mitochondria in senescence-accelerated mouse prone 8 (SAMP8) mice, and to explore the EA mechanism on Alzheimer disease (AD) in improving energy metabolic disorder. Methods: Twelve SAMP8 mice were randomly divided into a model group and an EA group, with six in each group. Six senescence-accelerated mouse resistance 1 (SAMR1) mice were prepared as blank group. Mice in the EA group received EA on Baihui (GV 20) and Yongquan (KI 1), once a day for 7 d as a course, altogether 3 courses with one day intervalbetween two courses. Mice in the model group and the blank group were manipulated and fixed as those in the EA group. After interventions, Morris water maze was employed to test spatial learning and memory ability to evaluate EA effect; spectrophotometry was used to detect the activity of hippocampal mitochondria COX. Results: Compared with the blank group, mean escape latenciesof the EA group and model group were prolonged significantly in Morris water maze tests (P Conclusion: It’s plausible that EA improves AD learning and memory ability by increasing mitochondria COX activity, protecting the structure and function, and improving energy metabolism.

  14. Synthesis and Characterization of LiCoxMn2-xO4 Cathode Materials

    Institute of Scientific and Technical Information of China (English)

    YAO Yaochun; DAI Yongnian; YANG Bin; MA Wenhui; Takayuki Watanabe

    2007-01-01

    LiCoxMn2-xO4 cathode materials for lithium ion batteries were synthesized by mechanical activation-solid state reaction at 750℃ for 24 h in air atmosphere, and their crystal structure, morphology, element composition and electrochemical performance were characterized with XRD, SEM, ICP-AES and charge-discharge test. The experimental results show that all samples have a single spinel structure, well formed crystal shape and uniformly particle size distribution. The lattice parameters of LiCoxMa2-xO4 decrease and the average oxidation states of manganese ions increase with an increase in Co content. Compared with pure LiMn2O4, the LiCoxMn2-xO4(x=0.03-0.12) samples show a lower special capacity, but their cycling life are improved. The capacity loss of LiCo0.09Mn1.91O4 and LiCo0.12Mn1.88O4 is only 0.95% ,respectively, after the 20th cycle. The improvement of the cycle performance is attributed to the substitution of Co at the Mn sites in the spinel structure, which suppresses the Jahn-Teller distortion and improves the structural stability.

  15. Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach.

    Science.gov (United States)

    Amić, Ana; Marković, Zoran; Marković, Jasmina M Dimitrić; Jeremić, Svetlana; Lučić, Bono; Amić, Dragan

    2016-12-01

    Free radical scavenging and inhibitory potency against cyclooxygenase-2 (COX-2) by two abundant colon metabolites of polyphenols, i.e., 3-hydroxyphenylacetic acid (3-HPAA) and 4-hydroxyphenylpropionic acid (4-HPPA) were theoretically studied. Different free radical scavenging mechanisms are investigated in water and pentyl ethanoate as a solvent. By considering electronic properties of scavenged free radicals, hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms are found to be thermodynamically probable and competitive processes in both media. The Gibbs free energy change for reaction of inactivation of free radicals indicates 3-HPAA and 4-HPPA as potent scavengers. Their reactivity toward free radicals was predicted to decrease as follows: hydroxyl>alkoxyls>phenoxyl≈peroxyls>superoxide. Shown free radical scavenging potency of 3-HPAA and 4-HPPA along with their high μM concentration produced by microbial colon degradation of polyphenols could enable at least in situ inactivation of free radicals. Docking analysis with structural forms of 3-HPAA and 4-HPPA indicates dianionic ligands as potent inhibitors of COX-2, an inducible enzyme involved in colon carcinogenesis. Obtained results suggest that suppressing levels of free radicals and COX-2 could be achieved by 3-HPAA and 4-HPPA indicating that these compounds may contribute to reduced risk of colon cancer development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Melatonin, a novel selective ATF-6 inhibitor, induces human hepatoma cell apoptosis through COX-2 downregulation.

    Science.gov (United States)

    Bu, Li-Jia; Yu, Han-Qing; Fan, Lu-Lu; Li, Xiao-Qiu; Wang, Fang; Liu, Jia-Tao; Zhong, Fei; Zhang, Cong-Jun; Wei, Wei; Wang, Hua; Sun, Guo-Ping

    2017-02-14

    To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin. Hepatoma cells, HepG2, were cultured in vitro. Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes' expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis. In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed. These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis.

  17. Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events

    Institute of Scientific and Technical Information of China (English)

    Francisco M Ojeda; Christian Muller; Daniela Bornigen; David-Alexandre Tregouet; Arne Schillert; Matthias Heinig; Tanja Zeller; Renate B Schnabel

    2016-01-01

    Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i) full model using all available predictors and estimated by standard tech-niques, (ii) backward elimination (BE), (iii) ridge regression, (iv) least absolute shrinkage and selec-tion operator (lasso), and (v) elastic net. Based on a prospective cohort of patients with manifest coronary artery disease (CAD), we performed a simulation study to compare the predictive accu-racy, calibration, and discrimination of these approaches. Candidate predictors for incident cardio-vascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a compara-ble performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.

  18. Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events

    Directory of Open Access Journals (Sweden)

    Francisco M. Ojeda

    2016-08-01

    Full Text Available Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i full model using all available predictors and estimated by standard techniques, (ii backward elimination (BE, (iii ridge regression, (iv least absolute shrinkage and selection operator (lasso, and (v elastic net. Based on a prospective cohort of patients with manifest coronary artery disease (CAD, we performed a simulation study to compare the predictive accuracy, calibration, and discrimination of these approaches. Candidate predictors for incident cardiovascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparable performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.

  19. Differential effect of DDT, DDE, and DDD on COX-2 expression in the human trophoblast derived HTR-8/SVneo cells.

    Science.gov (United States)

    Dominguez-Lopez, Pablo; Diaz-Cueto, Laura; Olivares, Aleida; Ulloa-Aguirre, Alfredo; Arechavaleta-Velasco, Fabian

    2012-11-01

    The purpose of this study was to investigate the effect of 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) isomers on COX-2 expression in a human trophoblast-derived cell line. Cultured HTR-8/SVneo trophoblast cells were exposed to DDT isomers and its metabolites for 24 h, and COX-2 mRNA and protein expression were assessed by RT-PCR, Western blotting, and ELISA. Prostaglandin E₂ production was also measured by ELISA. Both COX-2 mRNA and protein were detected under control (unexposed) conditions in the HTR-8/SVneo cell line. COX-2 protein expression and prostaglandin E₂ production but not COX-2 mRNA levels increased only after DDE and DDD isomers exposure. It is concluded that DDE and DDD exposure induce the expression of COX-2 protein, leading to increased prostaglandin E2 production. Interestingly, the regulation of COX-2 by these organochlorines pesticides appears to be at the translational level.

  20. Monitoring of Fasciola Species Contamination in Water Dropwort by cox1 Mitochondrial and ITS-2 rDNA Sequencing Analysis.

    Science.gov (United States)

    Choi, In-Wook; Kim, Hwang-Yong; Quan, Juan-Hua; Ryu, Jae-Gee; Sun, Rubing; Lee, Young-Ha

    2015-10-01

    Fascioliasis, a food-borne trematode zoonosis, is a disease primarily in cattle and sheep and occasionally in humans. Water dropwort (Oenanthe javanica), an aquatic perennial herb, is a common second intermediate host of Fasciola, and the fresh stems and leaves are widely used as a seasoning in the Korean diet. However, no information regarding Fasciola species contamination in water dropwort is available. Here, we collected 500 samples of water dropwort in 3 areas in Korea during February and March 2015, and the water dropwort contamination of Fasciola species was monitored by DNA sequencing analysis of the Fasciola hepatica and Fasciola gigantica specific mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear ribosomal internal transcribed spacer 2 (ITS-2). Among the 500 samples assessed, the presence of F. hepatica cox1 and 1TS-2 markers were detected in 2 samples, and F. hepatica contamination was confirmed by sequencing analysis. The nucleotide sequences of cox1 PCR products from the 2 F. hepatica-contaminated samples were 96.5% identical to the F. hepatica cox1 sequences in GenBank, whereas F. gigantica cox1 sequences were 46.8% similar with the sequence detected from the cox1 positive samples. However, F. gigantica cox1 and ITS-2 markers were not detected by PCR in the 500 samples of water dropwort. Collectively, in this survey of the water dropwort contamination with Fasciola species, very low prevalence of F. hepatica contamination was detected in the samples.

  1. RNA editing in gymnosperms and its impact on the evolution of the mitochondrial coxI gene.

    Science.gov (United States)

    Lu, M Z; Szmidt, A E; Wang, X R

    1998-05-01

    Sequence analysis of the mitochondrial coxI gene in eight gymnosperm species revealed a high rate of nonsynonymous nucleotide substitutions with a strong (98%) predominance of C-T substitutions. Further analysis of the corresponding coxI cDNA sequences showed that all the non-synonymous C-T changes in the coxI genomic DNA sequences were eliminated by RNA editing resulting in nearly identical mRNA (amino acid) sequences among the species. Pronounced variation in the number and location of edited sites was found among species. Most species had a relatively large number of edited sites (from 25 to 34). However, no RNA editing of the coxI sequence was found in Gingko biloba or Larix sibirica. The sequence composition of the investigated coxI fragment suggests that the coxI gene in G. biloba and L. sibirica originated from edited mitochondrial coxI transcripts by reverse transcription followed by insertion into the nuclear genome or back into the mitochondrial genome. Our results also demonstrate that where there are a large number of edited sites, RNA editing can accelerate the divergence of nucleotide sequences among species.

  2. DNA Damage Drives an Activin A-Dependent Induction of COX-2 in Premalignant Cells and Lesions

    Science.gov (United States)

    Fordyce, Colleen; Fessenden, Tim; Pickering, Curtis; Jung, Jason; Singla, Veena; Berman, Hal; Tlsty, Thea

    2010-01-01

    COX-2 catalyzes the rate-limiting step in the synthesis of prostaglandins. Its overexpression induces numerous tumor-promoting phenotypes and is associated with cancer metastasis and poor clinical outcome. Although COX-2 inhibitors are promising chemotherapeutic and chemopreventative agents for cancer, the risk of significant cardiovascular and gastrointestinal complications currently outweighs their potential benefits. Systemic complications of COX-2 inhibition could be avoided by specifically decreasing COX-2 expression in epithelial cells. To that end, we have investigated the signal transduction pathway regulating COX-2 expression in response to DNA damage in breast epithelial cells. In variant human mammary epithelial cells that have silenced p16 (vHMEC), double strand DNA damage or telomere malfunction results in a p53-and activin A-dependent induction of COX-2 and continued proliferation. In contrast, telomere malfunction in HMEC with an intact p16/Rb pathway induces cell cycle arrest. Importantly, in ductal carcinoma in situ (DCIS) lesions, high COX-2 expression is associated with high γH2AX, TRF2, activin A and telomere malfunction. These data demonstrate that DNA damage and telomere malfunction can have both cell autonomous and cell non-autonomous consequences and provides a novel mechanism for the propagation of tumorigenesis. PMID:20028875

  3. Expression of COX-2 in Different Subtypes of Gastric Intestinal Metaplasia and Gastric Carcinoma by T-issue Microarray

    Institute of Scientific and Technical Information of China (English)

    LIUGuisheng; GONGJun; CHENGPeng; DAIFei; ZHANGJun; CHANGYing

    2005-01-01

    Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis.Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM loci in CAG, IM loci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively,significantly higher than in diffuse-type gastric cancer (16.67~)(P<0.05, 0.005 and 0.005, respectively),and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM loci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type I and type Ⅲ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type I to type UI IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.

  4. Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma

    Institute of Scientific and Technical Information of China (English)

    Hong-Ling Li; Bing-Zhong Sun; Fu-Cheng Ma

    2004-01-01

    AIM:To assess the expression of cyclooxygenase-2 (COX-2),nitric oxide synthase (iNOS), p53 and Ki-67 in gastric mucosaassociated lymphoid tissue (MALT) lymphoma and clarify the relationship between COX-2 expression and iNOS or p53 expression in these patients.METHODS: The expressions of COX-2, iNOS, p53 and Ki-67 were detected in 32 gastric MALT lymphoma specimens and 10 adjacent mucosal specimens by immunohistochemical Envision method.RESULTS: COX-2 and iNOS expressions were significantly higher in gastric MALT lymphoma tissues than those in adjacent normal tissues. The expression of COX-2 was observed in 22 of 32 cases of MALT lymphoma tissues(68.8%). A positive cytoplasmic immunoreactivity for iNOS was detected in 17 of 31 cases (53.1%). COX-2 expression in gastric MALT lymphoma tissues was positively correlated with iNOS expression (r=0.448, P=0.010) and cell proliferative activity analyzed by Ki-67 labeling index (r=0.410, P=0.020).The expression of COX-2 protein did not correlate with age,sex, stage of disease, lymph node metastasis or differentiation.The accumulation of p53 nuclear phosphoprotein was detected in 19(59.4%) of tumors. p53 protein was expressed in 11 of 23 assessed LG tumors and in 8 of 9 assessed HG tumors.The difference of p53 positivity was found statistically significant between LG and HG cases (P=0.0302). The p53 accumulation correlated with advanced clinical stage (stage Ⅲ+Ⅳ vs stage Ⅰ+Ⅱ, P=-0.017). There was a significant positive correlation between COX-2 expression and p53 accumulation status (r=0.403, P=0.022). The mean PI of Ki-67 in each grade group were 36.0±7.73% in HG and 27.4±9.21% in LG. High-proliferation rate correlated with HG tumors (r=0.419, P=0.017). The correlation coefficient showed a significant positive correlation between PI and COX-2 expression in MALT lymphoma patients (r=0.410,P=0.020).CONCLUSION: COX-2 expresses in the majority of gastric MALT lymphoma tissues and correlates with cellular

  5. 丙酮醛诱导细胞凋亡相关基因COX-VA的生物信息学分析%Bioinformatics Analysis for Cell Apoptosis Induced by Methylglyoxal Related Gene COX-VA

    Institute of Scientific and Technical Information of China (English)

    曾军英; 刘学伟; 张杰; 汤少勋; 谭支良

    2008-01-01

    在用基因芯片技术检测丙酮醛诱导人牙周膜成纤维细胞凋亡的基因表达研究中,发现一个未知基因表现为显著下调,其名称是COX-VA,并推测该基因与细胞凋亡密切相关.因此利用生物信息学方法对COX-VA基因及其蛋白产物进行各种分析,发现COX-VA基因与细胞色素C氧化酶具有较高的相似性.COX-VA在细胞中低表达与丙酮醛造成线粒体DNA损伤所引发的细胞凋亡相关.

  6. Efeito dos extratos de Harpagohytum procumbens (garra-do-diabo) e suas frações na atividade da COX-1 e COX-2 e na produção de NO em sangue total

    OpenAIRE

    Maria Cecilia Cattai Anauate

    2008-01-01

    OBJETIVO: O presente estudo avaliou o efeito dos extratos de H. procumbens e suas frações na atividade da COX-1 e COX-2 e produção de NO em ensaio de sangue total de voluntários sadios e pacientes com OA. MÉTODOS: A atividade da COX-1 foi determinada através da produção de TxB2 por plaquetas e da COX-2 pela produção de PGE2 por monócitos estimulados por LPS. A produção de NO2 -/NO3 - foi determinada por reação de Griess. Os ensaios in vitro foram realizados por incubação do extrato do extrato...

  7. GROWTH FACTORS AND COX2 IN WOUND HEALING: AN EXPERIMENTAL STUDY WITH EHRLICH TUMORS.

    Science.gov (United States)

    Salgado, Flávio L L; Artigiani-Neto, Ricardo; Lopes-Filho, Gaspar de Jesus

    2016-01-01

    Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlich's neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and

  8. 鼻内翻性乳头状瘤组织中COX-2的表达及临床意义%Expression and Significance of COX-2 in Nasal Inverted Papilloma

    Institute of Scientific and Technical Information of China (English)

    范西惠; 韩佳利; 阎艾慧; 李明彦; 赵明俊

    2012-01-01

    目的 探讨COX-2蛋白在鼻内翻性乳头状瘤(NIP)组织中的表达及在该病恶变中的临床意义.方法 采用免疫组织化学SABC法检测72例NIP组织中COX-2蛋白的表达水平,利用图像分析技术测量阳性细胞的平均光密度值(AOD),并取10例下鼻甲组织做对照.结果 NIP组织中AOD高于正常鼻黏膜,差异有统计学意义(P<0.05);NIP组织中COX-2的表达与患者的年龄、性别无关(P>0.05),与吸烟、Krouse分期有关(P<0.05).结论 COX-2与NIP的发生及其恶变有一定相关性,抑制COX-2活性及戒烟对预防NIP的发生及恶变有一定的临床价值.%Objective To detect the expression of COX-2 protein in nasal inverted papilloma (NIP) and investigate their clinicopathologi-cal significances in occurrence and aggravation of this disease. Methods 10 cases of inferior turbinate tissues (IT) ,60 cases of NIP without malignant transformation, 12 cases of NIP with malignant transformation were examined for COX-2 expression by Immunohistochemistry. Results Hie expression of COX-2 in NIP with malignant transformation was significantly higher than that of NIP without malignant transformation and in IT (P 0.05).Besides, the expression of COX-2 protein had no correlation with age and gender(P> 0.05),but a correlation with smoking was detected(P< 0.05). Conclusion The abnormal expression of COX-2 protein might play an important role in occurrence and aggravation of NIP,it would be valuable of inhibition the COX-2 activity and smoking cessation for prevention and aggravation of NIP.

  9. COX-2、CCR7表达与乳腺癌临床病理参数的关系%Correlation between the expressions of COX-2, CCR7 and clinicopathologic parameters in breast cancer

    Institute of Scientific and Technical Information of China (English)

    余术宜; 李建哲; 吉午阳; 周志群; 庞琼; 陈玉祥

    2011-01-01

    目的 探讨环氧合酶2(cyclooxygenase 2,COX-2)、C-C家族趋化因子受体7(C-C chemokinereceptor 7,CCR7)表达与乳腺癌临床病理学参数的关系,并分析COX-2、CCR7表达的相关性.方法 用免疫组织化学检测乳腺癌组织80例、乳腺癌癌旁组织15例中COX-2、CCR7的表达,分析其表达与临床病理学参数的关系,对COX-2、CCR7的表达进行相关性分析.结果 在乳腺癌组织,COX-2、CCR7均高表达,表达率分别为42.5%和38.8%,两者表达有相关性(P<0.05).COX-2、CCR7高表达均与肿瘤的病理分化、肿瘤大小、淋巴转移、TNM分期相关(p<0.05),与组织学分型、患者年龄无关.结论 COX-2、CCR7在乳腺癌组织高表达,两者表达有相关性,且与乳腺癌临床病理学参数有关.提示临床上联合检测COX-2和CCR7对乳腺癌转移的预测可能会有所帮助.

  10. Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells

    Science.gov (United States)

    Brancaccio, Mariarita; Coretti, Lorena; Florio, Ermanno; Pezone, Antonio; Calabrò, Viola; Falco, Geppino; Keller, Simona; Lembo, Francesca; Avvedimento, Vittorio Enrico; Chiariotti, Lorenzo

    2016-01-01

    Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene. PMID:27253528

  11. Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2016-01-01

    BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began...... on the date of breast cancer primary surgery and continued until the first of recurrence, death, emigration, or 1 January 2013. We used Cox regression models to compute hazard ratios (HR) and corresponding 95% confidence intervals (95% CI) associating prescriptions with recurrence, adjusting for confounders...

  12. The inhibition of Typhonium flagelliforme Lodd. Blume leaf extract on COX-2 expression of Wi Dr colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Agustina Setiawati; Handika Immanuel; Mery Tri Utami

    2016-01-01

    Objective: To determine the inhibition activity of Typhonium flagelliforme Lodd. Blume(T. flagelliforme) leaf extract on cyclooxygenase 2(COX-2) expression of colon cancer cells.Methods: T. flagelliforme leaf extract was prepared to macerate in ethyl acetate. In vitro anticancer activity was assayed by MTT method on Wi Dr colon cancer cells. This study applied apoptosis induction assay to investigate the mechanism of cell death using double staining method. COX-2 expression was stained by immunocytochemistry.Results: T. flagelliforme showed anticancer activity and induced apoptosis on Wi Dr cells through inhibition of COX-2 expression with IC5070 mg/m L.Conclusions: This study showed that T. flagelliforme is a promising chemopreventive agent for colon cancer through COX-2 inhibition.

  13. A semi-analytical method to estimate the slip length of spreading cap-shaped droplets using Cox theory

    CERN Document Server

    Wörner, Martin; Alla, Hocine; Yue, Pengtao

    2016-01-01

    The Cox-Voinov law on dynamic spreading relates the difference between the cubic values of the apparent contact angle (theta) and the equilibrium contact angle to the instantaneous contact line speed (U). Comparing spreading results with this law requires accurate data of theta and U during the entire process. We consider the case when gravitational forces are negligible and transform the general Cox law in a relationship for the temporal evolution of the spreading radius. For cap-shaped droplets, this enables a comparison of experimental or computational results with Cox theory without the need for instantaneous data of theta and U. The fitting of Cox theory against measured or computed base-radius-over-time curves allows estimating the effective slip length. This is useful for establishing relationships between slip length and parameters in numerical methods for moving contact lines. The procedure is illustrated by numerical simulations for partially wetting droplets employing the coupled level-set volume-o...

  14. Differential expression of biphenyl synthase gene family members in fire-blight-infected apple 'Holsteiner Cox'.

    Science.gov (United States)

    Chizzali, Cornelia; Gaid, Mariam M; Belkheir, Asma K; Hänsch, Robert; Richter, Klaus; Flachowsky, Henryk; Peil, Andreas; Hanke, Magda-Viola; Liu, Benye; Beerhues, Ludger

    2012-02-01

    Fire blight, caused by the bacterium Erwinia amylovora, is a devastating disease of apple (Malus × domestica). The phytoalexins of apple are biphenyls and dibenzofurans, whose carbon skeleton is formed by biphenyl synthase (BIS), a type III polyketide synthase. In the recently published genome sequence of apple 'Golden Delicious', nine BIS genes and four BIS gene fragments were detected. The nine genes fall into four subfamilies, referred to as MdBIS1 to MdBIS4. In a phylogenetic tree, the BIS amino acid sequences from apple and Sorbus aucuparia formed an individual cluster within the clade of the functionally diverse type III polyketide synthases. cDNAs encoding MdBIS1 to MdBIS4 were cloned from fire-blight-infected shoots of apple 'Holsteiner Cox,' heterologously expressed in Escherichia coli, and functionally analyzed. Benzoyl-coenzyme A and salicoyl-coenzyme A were the preferred starter substrates. In response to inoculation with E. amylovora, the BIS3 gene was expressed in stems of cv Holsteiner Cox, with highest transcript levels in the transition zone between necrotic and healthy tissues. The transition zone was the accumulation site of biphenyl and dibenzofuran phytoalexins. Leaves contained transcripts for BIS2 but failed to form immunodetectable amounts of BIS protein. In cell cultures of apple 'Cox Orange,' expression of the BIS1 to BIS3 genes was observed after the addition of an autoclaved E. amylovora suspension. Using immunofluorescence localization under a confocal laser-scanning microscope, the BIS3 protein in the transition zone of stems was detected in the parenchyma of the bark. Dot-shaped immunofluorescence was confined to the junctions between neighboring cortical parenchyma cells.

  15. A Benchmark and Comparative Study of Video-Based Face Recognition on COX Face Database.

    Science.gov (United States)

    Huang, Zhiwu; Shan, Shiguang; Wang, Ruiping; Zhang, Haihong; Lao, Shihong; Kuerban, Alifu; Chen, Xilin

    2015-12-01

    Face recognition with still face images has been widely studied, while the research on video-based face recognition is inadequate relatively, especially in terms of benchmark datasets and comparisons. Real-world video-based face recognition applications require techniques for three distinct scenarios: 1) Videoto-Still (V2S); 2) Still-to-Video (S2V); and 3) Video-to-Video (V2V), respectively, taking video or still image as query or target. To the best of our knowledge, few datasets and evaluation protocols have benchmarked for all the three scenarios. In order to facilitate the study of this specific topic, this paper contributes a benchmarking and comparative study based on a newly collected still/video face database, named COX(1) Face DB. Specifically, we make three contributions. First, we collect and release a largescale still/video face database to simulate video surveillance with three different video-based face recognition scenarios (i.e., V2S, S2V, and V2V). Second, for benchmarking the three scenarios designed on our database, we review and experimentally compare a number of existing set-based methods. Third, we further propose a novel Point-to-Set Correlation Learning (PSCL) method, and experimentally show that it can be used as a promising baseline method for V2S/S2V face recognition on COX Face DB. Extensive experimental results clearly demonstrate that video-based face recognition needs more efforts, and our COX Face DB is a good benchmark database for evaluation.

  16. The tariff for fire and theft car insurance: analysis with a Cox model

    Directory of Open Access Journals (Sweden)

    Bruno Scarpa

    2013-05-01

    Full Text Available In this paper we analyze the problem of identification of a tariff for a Fire & Theft Car policy for Insurance Companies. Usually companies obtain this tariff by empirical estimate of the pure rate by evaluating the impact of some personalization variables. In this paper we propose the usage of a semi-parametric Cox model, where the response variable is not the waiting time until an event, but the degree of damage because of theft or fire of a car. The proposed model allows to easily tackle typical problems in data available to the companies, like the presence of franchises, which are treated as censored data.

  17. CoxC nanorod magnets: Highly magnetocrystalline anisotropy with lower Curie temperature for potential applications

    Energy Technology Data Exchange (ETDEWEB)

    El-Gendy, AA; Almugaiteeb, T; Carpenter, EE

    2013-12-01

    Magnetic CoxC nanorods with larger magnetocrystalline anisotropy of 5 x 10(5) J/m(3) as well as larger coercivity and lower Curie temperature are introduced. The particles have an average diameter of 8 nm and shows three different magnetic behaviors. The sample shows ferromagnetism up to 400 K, superparamagnetism at temperature > 400 K and

  18. Design and synthesis of a biotinylated probe of COX-2 inhibitor nimesulide analog JCC76.

    Science.gov (United States)

    Zhong, Bo; Lama, Rati; Smith, Kerri M; Xu, Yan; Su, Bin

    2011-09-15

    JCC76 is a derivative of cyclooxygenase-2(COX-2) selective inhibitor nimesulide and exhibits potent anti-breast cancer activity. It selectively induces apoptosis of Her2 positive breast cancer cells. However, the specific molecular targets of JCC76 still remain unclear, which significantly withdraw the further drug development of JCC76. To identify the molecular targets of JCC76, a six carbon linker and biotin conjugated JCC76 probe was designed and synthesized. The anti-proliferation activity of the probe and its analogs was evaluated.

  19. Role of COX-2 in the regulation of the metastatic potential of human breast tumor cells

    Directory of Open Access Journals (Sweden)

    M. A. Taipov

    2014-01-01

    Full Text Available The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105, and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

  20. PyCox: Computing with (finite) Coxeter groups and Iwahori-Hecke algebras

    CERN Document Server

    Geck, Meinolf

    2012-01-01

    We introduce the computer algebra package {\\sf PyCox}, written entirely in the {\\sf Python} language. It implements a set of algorithms - in a spirit similar to the older {\\sf CHEVIE} system - for working with Coxeter groups and Hecke algebras. This includes a new variation of the traditional algorithm for computing Kazhdan-Lusztig cells and $W$-graphs, which works efficiently for all groups of rank $\\leq 8$ (except $E_8$). Our experiments suggest a re-definition of Lusztig's "special" representations which, conjecturally, should also apply to the unequal parameter case.

  1. Fluorescence imaging of dendritic spines of Golgi-Cox-stained neurons using brightening background

    Science.gov (United States)

    Ai, Min; Xiong, Hanqing; Yang, Tao; Shang, Zhenhua; Chen, Muqing; Liu, Xiuli; Zeng, Shaoqun

    2015-01-01

    We report a novel fluorescence imaging approach to imaging nonfluorescence-labeled biological tissue samples. The method was demonstrated by imaging neurons in Golgi-Cox-stained and epoxy-resin-embedded samples through the excitation of the background fluorescence of the specimens. The dark neurons stood out clearly against background fluorescence in the images, enabling the tracing of a single dendritic spine using both confocal and wide-field fluorescence microscopy. The results suggest that the reported fluorescence imaging method would provide an effective alternative solution to image nonfluorescence-labeled samples, and it allows tracing the dendritic spine structure of neurons.

  2. Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury

    DEFF Research Database (Denmark)

    Stubbe, Jane; Madsen, Kirsten; Nielsen, Finn T

    2007-01-01

    at postnatal day 10. Adrenalectomized rats were divided into no steroid substitution (ADX), corticosterone replacement (ADX-C), and corticosterone and DOCA substitution (ADX-CD) groups that received subcutaneous pellets with steroids. Without replacement, pups failed to thrive and exhibited impaired urinary...... deprivation, parecoxib attenuated weight loss and the increase in plasma Na+ concentration and osmolality. It is concluded that mineralocorticoid is required for normal postnatal development of the renal medulla. COX-2 contributes to impaired urine-concentrating ability, NaCl loss, and extracellular volume...

  3. Anisotropy in the magnetic and transport properties of Fe1-xCoxSb2

    Science.gov (United States)

    Hu, Rongwei; Mitrović, V. F.; Petrovic, C.

    2006-11-01

    Anisotropic magnetic and electronic transport measurements were carried out on large single crystals of Fe1-xCoxSb2 (0⩽x⩽1) . The semiconducting state of FeSb2 evolves into metallic and weakly ferromagnetic by substitution of Fe with Co for xPnnm structure of FeSb2 to monoclinic P21/c structure of CoSb2 , where semiconducting and diamagnetic ground state is restored again. Large magnetoresistance and anisotropy in electronic transport were observed.

  4. Maximum likelihood estimation for Cox's regression model under nested case-control sampling

    DEFF Research Database (Denmark)

    Scheike, Thomas; Juul, Anders

    2004-01-01

    Nested case-control sampling is designed to reduce the costs of large cohort studies. It is important to estimate the parameters of interest as efficiently as possible. We present a new maximum likelihood estimator (MLE) for nested case-control sampling in the context of Cox's proportional hazards...... model. The MLE is computed by the EM-algorithm, which is easy to implement in the proportional hazards setting. Standard errors are estimated by a numerical profile likelihood approach based on EM aided differentiation. The work was motivated by a nested case-control study that hypothesized that insulin...

  5. The role of anti-LeY antibody in the downregulation of MAPKs/COX-2 pathway in gastric cancer.

    Science.gov (United States)

    Aziz, Faisal; Qiu, Yan

    2014-04-01

    Monoclonal antibody-based treatments of cancer which serve as magic 'bullets' have been established as one of the most successful therapeutic strategies. A variety of antigens has been investigated as targets for the mAb therapy of gastric cancer, including the carbohydrate type 2 blood group antigen. Lewis Y (LeY) is overexpressed on tumor cells surface either as glycoproteins or glycolipids. LeY is difucosylated oligosaccharide with the chemical structure [Fucα1,2Galβ1→4(Fucα1,3)GlcNAcβ1→R], which is catalyzed by fucosyltransferases, such as FUT1 (α1,2) and FUT4 (α1,3). The role of LeY antigen in cancer treatment and prevention has been extensively studied. Moreover, the cyclooxygenase- 2 (COX-2) is an early event protein, highly expressed in H. pylori-related gastric cancer. COX-2 may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. The COX-2 is upregulated in a variety of cancers, including gastric cancer. However, its inhibition may prevent or reverse gastric carcinogenesis. H. pylori mediated alteration of COX-2 through MAPKs pathway is one of the mechanisms that is implicated in gastric cancer. We have found COX-2 and LeY to be correlative sources of specific gastric biomarkers in gastric cancer, which is upregulated in the gastric cancer through MAPKs pathway. In addition, the anti-LeY antibody significantly downregulated the COX-2 expression through MAPKs pathway, helpful to the treatment of gastric cancer. In this review, we summarize the therapeutic effect of anti-LeY antibody, including the crucial role of COX-2 and LeY antigen in gastric cancer and discuss the COX-2 inhibition by anti-LeY antibody through MAPKs pathway.

  6. Cyclooxygenase-2 (COX-2) Polymorphisms and Risk of Inflammatory Bowel Disease in a Scottish and Danish Case–Control Study

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Nimmo, Elaine; Krarup, Henrik B.;

    2011-01-01

    Background: Inflammatory bowel diseases (IBDs) are a result of interactions between luminal pathogens and the intestinal immune response. Cyclooxygenase-2 (COX-2) plays a key role in the regulation of the inflammatory response upon stimulation by luminal pathogens via Toll-like receptors. Methods...... among never-smokers, suggesting that low activity of COX-2 may predispose to UC. Our results suggest that inclusion of smoking status may be essential for the evaluation of the role of genetic predisposition to IBD....

  7. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

    Directory of Open Access Journals (Sweden)

    Ülker KARAGECE YALÇIN

    2012-05-01

    Full Text Available Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostaining by p53 and COX-2 was performed on sections of the paraffin blocks.Results: p53 expression was observed in 98% of basal cell carcinoma, 88.9% of squamous cell carcinoma and all actinic keratosis cases. p53 expression was also noted in non-dysplastic appearing epithelium in actinic keratosis cases. COX-2 expression was seen in 90, 100 and 88.9% of the basal cell carcinoma, squamous cell carcinoma and actinic keratosis groups, respectively. Skin appendages, inflammatory cells and vascular structures were also stained by COX-2 besides tumor tissue. COX-2 expression increased by the p53 expression increase in basal cell carcinoma and squamous cell carcinoma. p53 and COX-2 expressions were not related in terms of tumor type in the BCC and were not related in terms of differentiation in SCC.Conclusion: The existence of p53 expression in actinic keratosis cases has supported the idea that p53 plays a role in the early steps of carcinogenesis in skin cancers. The fact that the expression of COX-2 increases in line with the increase of p53 expression in basal cell carcinoma and squamous cell carcinoma cases indicates that COX-2 expression may be affected by p53

  8. Cox-Ingersoll-Ross债券定价模型的推广%An Extention of the Cox-Ingersoll-Ross Bond-pricing Model

    Institute of Scientific and Technical Information of China (English)

    郭君默; 李时银; 潘素娟

    2009-01-01

    债券一直被认为是一种风险较低,收益稳定的投资对象.债券融资是直接融资的一种重要方式.债券定价的高低直接影响到发行人的融资成本和投资人的获利空间.随着我国债券市场的发展,如何对其进行定价是当前金融市场研究的核心内容.Cox-Ingersoll-Ross债券定价模型假定即期利率服从扩散过程,利率长期均值为常数.基于此模型对其进行推广,假设利率的长期均值θ遵循一个离散跳跃过程,跳跃的次数与幅度由中央银行根据物价指数确定,建立一个新的模型,运用引理和资本资产定价模型给出到期日价值为1的零息票债券的定价公式.

  9. Quantitative assessment of the association of COX-2 (Cyclooxygenase-2 immunoexpression with prognosis in human osteosarcoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhe Wang

    Full Text Available BACKGROUND: Numerous studies examining the relationship between Cyclooxygenase-2 (COX-2 immunoexpression and clinical outcome in osteosarcoma patients have yielded inconclusive results. METHODS: We accordingly conducted a meta-analysis of 9 studies (442 patients that evaluated the correlation between COX-2 immunoexpression and clinical prognosis (death. Pooled odds ratios (OR and risk ratios (RR with 95% confidence intervals (95% CI were calculated using the random-effects or fixed-effects model. RESULTS: Meta-analysis showed no significant association between COX-2 positivity and age, gender, tumor location, histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression was associated with overall survival rate (RR=2.12; 95% CI: 1.10-3.74; P=0.009 and disease-free survival rate (RR=1.63; 95% CI: 1.17-2.28; P=0.004 at 2 years. Sensitivity analysis performed by omitting low quality studies showed that the pooled results were stable. CONCLUSIONS: COX-2 positivity was associated with a lower 2-year overall survival rate and disease-free survival rate. COX-2 expression change is an independent prognostic factor in patients with osteosarcoma.

  10. Analysis of the cytochrome c oxidase subunit 1 (COX1) gene reveals the unique evolution of the giant panda.

    Science.gov (United States)

    Hu, Yao-Dong; Pang, Hui-Zhong; Li, De-Sheng; Ling, Shan-Shan; Lan, Dan; Wang, Ye; Zhu, Yun; Li, Di-Yan; Wei, Rong-Ping; Zhang, He-Min; Wang, Cheng-Dong

    2016-11-05

    As the rate-limiting enzyme of the mitochondrial respiratory chain, cytochrome c oxidase (COX) plays a crucial role in biological metabolism. "Living fossil" giant panda (Ailuropoda melanoleuca) is well-known for its special bamboo diet. In an effort to explore functional variation of COX1 in the energy metabolism behind giant panda's low-energy bamboo diet, we looked at genetic variation of COX1 gene in giant panda, and tested for its selection effect. In 1545 base pairs of the gene from 15 samples, 9 positions were variable and 1 mutation leaded to an amino acid sequence change. COX1 gene produces six haplotypes, nucleotide (pi), haplotype diversity (Hd). In addition, the average number of nucleotide differences (k) is 0.001629±0.001036, 0.8083±0.0694 and 2.517, respectively. Also, dN/dS ratio is significantly below 1. These results indicated that giant panda had a low population genetic diversity, and an obvious purifying selection of the COX1 gene which reduces synthesis of ATP determines giant panda's low-energy bamboo diet. Phylogenetic trees based on the COX1 gene were constructed to demonstrate that giant panda is the sister group of other Ursidae. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway.

    Science.gov (United States)

    Qin, Ge; Xu, Fei; Qin, Tao; Zheng, Qiufan; Shi, Dingbo; Xia, Wen; Tian, Yun; Tang, Yanlai; Wang, Jingshu; Xiao, Xiangshen; Deng, Wuguo; Wang, Shusen

    2015-12-08

    Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial-mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells.

  12. Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine

    Directory of Open Access Journals (Sweden)

    Rita Ghosh

    2007-11-01

    Full Text Available We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP model. Our data also indicate that the antiproliferative effects of NexrutineR are mediated in part by Akt and Cyclic AMP response element binding protein (CREB. Cyclooxygenase (Cox-2, a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2 and suppresses apoptosis. Treatment of LNCaP cells with NexrutineR reduced tumor necrosis factor α-induced enzymatic as well as promoter activities of Cox-2. NexrutineR also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating NexrutineR response. Immunohistochemical analysis of human prostate tumors show increased expression of CREB and DNA binding activity in high-grade tumors (three-fold higher in human prostate tumors compared to normal prostate; P = .01. We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like NexrutineR, demonstrating a prospective for development of NexrutineR for prostate cancer management.

  13. Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies.

    Science.gov (United States)

    Pacheu-Grau, David; Bareth, Bettina; Dudek, Jan; Juris, Lisa; Vögtle, F-Nora; Wissel, Mirjam; Leary, Scot C; Dennerlein, Sven; Rehling, Peter; Deckers, Markus

    2015-06-02

    Three mitochondria-encoded subunits form the catalytic core of cytochrome c oxidase, the terminal enzyme of the respiratory chain. COX1 and COX2 contain heme and copper redox centers, which are integrated during assembly of the enzyme. Defects in this process lead to an enzyme deficiency and manifest as mitochondrial disorders in humans. Here we demonstrate that COA6 is specifically required for COX2 biogenesis. Absence of COA6 leads to fast turnover of newly synthesized COX2 and a concomitant reduction in cytochrome c oxidase levels. COA6 interacts transiently with the copper-containing catalytic domain of newly synthesized COX2. Interestingly, similar to the copper metallochaperone SCO2, loss of COA6 causes cardiomyopathy in humans. We show that COA6 and SCO2 interact and that corresponding pathogenic mutations in each protein affect complex formation. Our analyses define COA6 as a constituent of the mitochondrial copper relay system, linking defects in COX2 metallation to cardiac cytochrome c oxidase deficiency.

  14. Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

    Institute of Scientific and Technical Information of China (English)

    Derya Gumurdulu; Seyda Erdogan; Fazilet Kayaselcuk; Gulsah Seydaoglu; Cem K Parsak; Orhan Demircan; Ilhan Tuncer

    2007-01-01

    AIM: To investigate the expression of Cyclooxygenase-2(COX-2), proliferating cell nuclear antigen (PCNA), Ki-67and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters.METHODS: Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34,SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2,PCNA, Ki-67 and p53.RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI,tumor grade and tumor size.CONCLUSION: COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.

  15. Prognostic significance of cyclooxygenase-2 (COX-2 expression in patients with surgically resectable adenocarcinoma of the oesophagus

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    Cree Ian A

    2006-05-01

    Full Text Available Abstract Background COX-2 expression in tumour cells has been associated with poor prognosis in gastrointestinal and non-gastrointestinal cancers. The aim of our study was to test the hypothesis that higher levels of COX-2 expression are prognostically related to poor clinico-pathologic features in adenocarcinoma of the oesophagus. Methods We reviewed the records of 100 consecutive patients undergoing resection for adenocarcinoma of the oesophagus to collect data on T-stage, N-stage, tumour recurrence and survival. T & N-stage was further confirmed by histological examination. COX-2 protein expression was assessed by immunohistochemistry in all patients and COX-2 m-RNA expression was measured by quantitative RT-PCR in a small group of patients. Results Higher levels of COX-2 expression were associated with higher T stage (p = 0.008, higher N stage (p = 0.049, increased risk of tumour recurrence (p = 0.01 and poor survival (p = 200 was associated with a median survival of 10 months compared to 26 months with a score of Conclusion Higher levels of COX-2 expression are associated with poor clinico-pathologic features and poor survival in patients with oesophageal adenocarcinoma.

  16. The Distinction of Taenia asiatica from Taenia saginata by PCR of Mitochondrial cox1 Gene Fragment%用cox1基因片段的PCR鉴别亚洲带绦虫和牛带绦虫

    Institute of Scientific and Technical Information of China (English)

    陈峥宏; 郎书源; 吴晓娟; 包怀恩

    2009-01-01

    目的:用cox1基因片段的PCR技术对亚洲带绦虫和牛带绦虫的快速鉴别.方法: 用亚洲带绦虫和牛带绦虫线粒体cox1基因片段的特异性引物以及带绦虫cox1基因片段的通用引物,对贵州省都匀地区和从江地区的带绦虫虫卵和节片DNA进行常规PCR扩增,扩增产物经琼脂糖凝胶电泳检测和核酸序列测定,并用NCBI Blast 对扩增产物的核酸序列与NCBI 数据库中带绦虫的cox1基因进行比对.结果: 5株都匀带绦虫DNA样品经亚洲带绦虫cox1基因片段的特异性引物PCR,均扩增出约260 bp的产物,PCR产物的核酸序列与NCBI 数据库中亚洲带绦虫线粒体cox1基因片段的同源性为100%;2株从江带绦虫的DNA 样品用亚洲带绦虫特异性引物和牛带绦虫特异性引物的PCR均未见扩增产物,而通用引物PCR则扩增出约1 000 bp的产物,核酸序列与NCBI 数据库中牛带绦虫线粒体cox1基因片段的同源性为99%,在牛带绦虫特异性引物的结合位点存在一个碱基差异.结论: 常规PCR扩增特异性的cox1基因片段可快速鉴定亚洲带绦虫;从江牛带绦虫株的cox1基因特异性片段部分存在变异,导致与特异性引物结合能力的差异,可采用cox1基因通用引物PCR结合测序进行鉴定.

  17. BOX-COX transformation and random regression models for fecal egg count data

    Directory of Open Access Journals (Sweden)

    Marcos Vinicius Silva

    2012-01-01

    Full Text Available Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants fecal egg count (FEC is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used to achieve normality before analysis. However, the transformed data are often not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6,375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (covariance components. We also proposed using random regression models (RRM for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4 adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated.

  18. Effect of COX-2 inhibitor after TNBS-induced colitis in Wistar rats.

    Science.gov (United States)

    Paiotti, Ana Paula Ribeiro; Miszputen, Sender Jankiel; Oshima, Celina Tizuko Fujiyama; de Oliveira Costa, Henrique; Ribeiro, Daniel Araki; Franco, Marcello

    2009-08-01

    Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Some studies suggest that antiinflammatory drugs are a promising alternative for treatment of the disease. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. Wistar rats (n = 25) were randomized into four groups, as follows: Group (1) Sham group: sham induced-colitis rats; Group (2) TNBS group: nontreated induced-colitis rats; Group (3) Lumiracoxib control group; and Group (4) Lumiracoxib-treated induced-colitis rats. Our results showed that rats from groups 2 and 4 presented similar histopathological damage and macroscopic injury in the distal colon as depicted by significant statistically differences (P TNBS-induced experimental colitis. Thus, the use of COX-2 inhibitors for treating IBD should be considered with caution and warrants further experimental investigation to elucidate their applicability.

  19. Modified Box-Cox transform for modulating the dynamic range of flow cytometry data.

    Science.gov (United States)

    Dvorak, J A; Banks, S M

    1989-11-01

    We describe an algorithm, Vout = Integer ([2(12)-1/2(12 lambda)-1] V lambda in-1) + 1; lambda greater than 0 based upon Box-Cox transformations as an alternative to nonlinear electronic amplifiers to expand or compress high- or low-amplitude flow cytometer-derived signals. If the indexing parameter lambda less than 1, input channels in the high-amplitude input range are compressed in the output range as occurs when an electronic logarithmic amplifier is used. However, if lambda greater than 1, input channels in the low-amplitude input range are compressed in the output range as occurs when an electronic power amplifier is used. Our modified Box-Cox transform can be implemented either during data collection or off-line for the transformation of previously collected raw data. The transform is the equivalent of an infinite class of nonlinear amplifiers. As the transform is implemented in software, it does not suffer from many of the disadvantages of nonlinear electronic amplifiers.

  20. PPARγ pathway activation results in apoptosis and COX-2 inhibition in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    Ming-Yi Li; Hua Deng; Jia-Ming Zhao; Dong Dai; Xiao-Yu Tan

    2003-01-01

    AIM: To investigate whether troglitazone (TGZ), theperoxisome proliferator-activated receptor (PPAR) gammaligand, can induce apoptosis and inhibit cell proliferation inhuman liver cancer cell line HepG2 and to explore themolecular mechanisms. METHODS: [3-(4,5)-dimethyithiazol-2-yl]-2,5-diphenyltetrazolium bromide (NTT), [3H] Thymidine incorporation,Hochest33258 staining, DNA ladder, enzyme-linkedimmunosorbent assay (ELISA), RT-PCR, Northern and Western blotting analyses were employed to investigate the effect of TGZ on HepG2 cells and related molecular mechanisms.RESULTS: TGZ was found to inhibit the growth of HepG2cells and to induce apoptosis. During the process, the expression of COX-2 mRNA and protein and Bcl-2 protein was down-regulated, while that of Bax and Bak proteins was up-regulated, and the activity of caspase-3 was elevated.Furthermore, the level of PGE2 was decreased transiently after 12 h of treatment with 30 gM troglitazone. CONCLUSION: TGZ inhibits cell proliferation and induces apoptosis in HepG2 cells, which may be associated with the activation of caspase-3-like proteases, down-regulation of the expression of COX-2 mRNA and protein, Bcl-2 protein,the elevation of PGE2 levels, and up-regulation of the expressions of Bax and Bak proteins.

  1. COX inhibitors Indomethacin and Sulindac derivatives as antiproliferative agents: synthesis, biological evaluation, and mechanism investigation.

    Science.gov (United States)

    Chennamaneni, Snigdha; Zhong, Bo; Lama, Rati; Su, Bin

    2012-10-01

    Cyclooxygenase (COX) inhibitors Indomethacin and its structural analogs Sulindac exhibit cell growth inhibition and apoptosis inducing activities in various cancer cell lines via COX independent mechanisms. In this study, the molecular structures of Indomethacin and Sulindac were used as starting scaffolds to design novel analogs and their effects on the proliferation of human cancer cells were evaluated. Compared to Indomethacin and Sulindac inhibiting cancer cell proliferation with IC(50)s of more than 1 mM, the derivatives displayed significantly increased activities. Especially, one of the Indomethacin analogs inhibited the growth of a series of cancer cell lines with IC(50)s around 0.5 μM-3 μM. Mechanistic investigation revealed that the new analog was in fact a tubulin inhibitor, although the parental compound Indomethacin did not show any tubulin inhibitory activity. Tubulin polymerization assay indicated this compound inhibited tubulin assembly at high concentrations, but promoted this process at low concentrations which is a very unique mechanism. The binding mode of this compound in tubulin was predicted using the molecular docking simulation.

  2. Role of Cox-2 in Vascular Inflammation: An Experimental Model of Metabolic Syndrome

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    Nicolás F. Renna

    2013-01-01

    Full Text Available The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n=8 each: control (W; W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR: WKY rats receiving 10% (w/v fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR: SHR receiving 10% (w/v fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases, VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

  3. [Clinical research XXII. From clinical judgment to Cox proportional hazards model].

    Science.gov (United States)

    Pérez-Rodríguez, Marcela; Rivas-Ruiz, Rodolfo; Palacios-Cruz, Lino; Talavera, Juan O

    2014-01-01

    Survival analyses are commonly used to determine the time of an event (for example, death). However, they can be used also for other clinical outcomes on the condition that these are dichotomous, for example healing time. These analyses only consider the relationship of one variable. However, Cox proportional hazards model is a multivariate analysis of the survival analysis, in which other potentially confounding covariates of the effect of the main maneuver studied, such as age, gender or disease stage, are taken into account. This analysis can include both quantitative and qualitative variables in the model. The measure of association used is called hazard ratio (HR) or relative risk ratio, which is not the same as the relative risk or odds ratio (OR). The difference is that the HR refers to the possibility that one of the groups develops the event before it is compared with the other group. The proportional hazards multivariate model of Cox is the most widely used in medicine when the phenomenon is studied in two dimensions: time and event.

  4. CoxFe1-x oxide coatings on metallic interconnects for solid oxide fuel cells

    Science.gov (United States)

    Shen, Fengyu; Lu, Kathy

    2016-10-01

    In order to improve the performance of Cr-containing steel as an interconnect material for solid oxide fuel cells, CoFe alloy coatings with Co:Fe ratios of 9:1, 8:2, 7:3, 6:4, and 5:5 are deposited by electrodeposition and then oxidized to CoxFe1-x oxide coatings with a thickness of ∼6 μm as protective layers on the interconnect. The area specific resistance of the coated interconnect increases with the Fe content. Higher Co content oxide coatings are more effective in limiting the growth of the chromia scale while all coatings are effective in inhibiting Cr diffusion and evaporation. With the Co0.8Fe0.2 oxide coated interconnect, the electrochemical performance of the Sm0.5Sr0.5Co0.2Fe0.8O3 cathode is improved. Only 1.54 atomic percentage of Cr is detected on the surface of the Sm0.5Sr0.5Co0.2Fe0.8O3 cathode while no Cr is detected 0.66 μm or more into the cathode. CoxFe1-x oxide coatings are promising candidates for solid oxide fuel cell interconnects with the advantage of using existing cathode species for compatibility and performance enhancement.

  5. A Metabolomic Approach to Target Compounds from the Asteraceae Family for Dual COX and LOX Inhibition

    Directory of Open Access Journals (Sweden)

    Daniela A. Chagas-Paula

    2015-07-01

    Full Text Available The application of metabolomics in phytochemical analysis is an innovative strategy for targeting active compounds from a complex plant extract. Species of the Asteraceae family are well-known to exhibit potent anti-inflammatory (AI activity. Dual inhibition of the enzymes COX-1 and 5-LOX is essential for the treatment of several inflammatory diseases, but there is not much investigation reported in the literature for natural products. In this study, 57 leaf extracts (EtOH-H2O 7:3, v/v from different genera and species of the Asteraceae family were tested against COX-1 and 5-LOX while HPLC-ESI-HRMS analysis of the extracts indicated high diversity in their chemical compositions. Using O2PLS-DA (R2 > 0.92; VIP > 1 and positive Y-correlation values, dual inhibition potential of low-abundance metabolites was determined. The O2PLS-DA results exhibited good validation values (cross-validation = Q2 > 0.7 and external validation = P2 > 0.6 with 0% of false positive predictions. The metabolomic approach determined biomarkers for the required biological activity and detected active compounds in the extracts displaying unique mechanisms of action. In addition, the PCA data also gave insights on the chemotaxonomy of the family Asteraceae across its diverse range of genera and tribes.

  6. Effect of composition and annealing on electrodeposited CoxPt1-X nanowires

    Science.gov (United States)

    Khatri, Manvendra Singh; Agarwal, Shivani; Hsu, Jen-Hwa; Chien, Chia-Hua; Chen, Cheng-Lung; Chen, Yang-Yuan

    2016-05-01

    Highly ordered CoxPt1-x (x ≤ 0.82) magnetic nanowire arrays of 60 nm diameter have been fabricated successfully by electrodeposition process into the pores of anodic aluminum oxide (AAO) templates. Electrodeposition process has been used as it is one of the simplest and most inexpensive, easily controlled method for the synthesis of nanowires.It was found that deposition potential is a key factor to control the composition and thus the magnetic properties of the nanowires. The as-deposited CoxPt1-x nanowires were characterized by XRD to have fcc structure with preferred orientation of (111) or (001) along the nanowire. Co-rich nanowires exhibit ferromagnetic behavior in contrast to near superparamagnetic response of the Pt-rich nanowires. Upon annealing the effects of crystallization cause the decrease of anisotropy along the wire axis for Co82Pt18 nanowires due to the increase of magnetocrystalline anisotropy perpendicular to the wire axis. In the next phase of our work segmented CoPtP/Pt multilayers nanowires will be deposited within the AAO template. Such multilayers nanowires are expected to have the high anisotropy due to the formation of ordered Co-Pt alloy phase at the interface.

  7. QSAR analysis of furanone derivatives as potential COX-2 inhibitors: kNN MFA approach

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    Ruchi Bhatiya

    2014-12-01

    Full Text Available A series of thirty-two furanone derivatives with their cyclooxygenase-2 inhibitory activity were subjected to quantitative structural–activity relationship analysis to derive a correlation between biological activity as a dependent variable and various descriptors as independent variables by using V-LIFE MDS3.5 software. The significant 2D QSAR model showed correlation coefficient (r2 = 0.840, standard error of estimation (SEE = 0.195, and a cross-validated squared correlation coefficient (q2 = 0.773. The descriptors involved in the building of 2D QSAR model are retention index for six membered rings, total number of oxygen connected with two single bonds, polar surface area excluding P and S plays a significant role in COX-2 inhibition. 3D-QSAR performed via Step Wise K Nearest Neighbor Molecular Field Analysis [(SW kNN MFA] with partial least-square (PLS technique showed high predictive ability (r2 = 0.7622, q2 = 0.7031 and standard error = 0.3660 explaining the majority of the variance in the data with two principle components. The results of the present study may be useful in the design of more potent furanone derivatives as COX-2 inhibitors.

  8. History dependence of the magnetic properties of single-crystal Fe1 -xCoxSi

    Science.gov (United States)

    Bauer, A.; Garst, M.; Pfleiderer, C.

    2016-06-01

    We report the magnetization, ac susceptibility, and specific heat of optically float-zoned single crystals of Fe1 -xCoxSi , 0.20 ≤x ≤0.50 . We determine the magnetic phase diagrams for all major crystallographic directions and cooling histories. After zero-field cooling, the phase diagrams resemble that of the archetypal stoichiometric cubic chiral magnet MnSi. Besides the helical and conical state, we observe a pocket of skyrmion lattice phase just below the helimagnetic ordering temperature. At the phase boundaries between these states evidence for slow dynamics is observed. When the sample is cooled in small magnetic fields, the phase pocket of skyrmion lattice may persist metastably down to the lowest temperatures. Taken together with the large variation in the transition temperatures, transition fields, and helix wavelength as a function of the composition, this hysteresis identifies Fe1 -xCoxSi as an ideal material for future experiments exploring, for instance, the topological unwinding of the skyrmion lattice.

  9. Four cases of Taenia saginata infection with an analysis of COX1 gene.

    Science.gov (United States)

    Cho, Jaeeun; Jung, Bong-Kwang; Lim, Hyemi; Kim, Min-Jae; Yooyen, Thanapon; Lee, Dongmin; Eom, Keeseon S; Shin, Eun-Hee; Chai, Jong-Yil

    2014-02-01

    Human taeniases had been not uncommon in the Republic of Korea (=Korea) until the 1980s. The prevalence decreased and a national survey in 2004 revealed no Taenia egg positive cases. However, a subsequent national survey in 2012 showed 0.04% (10 cases) prevalence of Taenia spp. eggs suggesting its resurgence in Korea. We recently encountered 4 cases of Taenia saginata infection who had symptoms of taeniasis that included discharge of proglottids. We obtained several proglottids from each case. Because the morphological features of T. saginata are almost indistinguishable from those of Taenia asiatica, molecular analyses using the PCR-RFLP and DNA sequencing of the cytochrome c oxidase subunit 1 (cox1) were performed to identify the species. The PCR-RFLP patterns of all of the 4 specimens were consistent with T. saginata, and the cox1 gene sequence showed 99.8-100% identity with that of T. saginata reported previously from Korea, Japan, China, and Cambodia. All of the 4 patients had the history of travel abroad but its relation with contracting taeniasis was unclear. Our findings may suggest resurgence of T. saginata infection among people in Korea.

  10. Aqueous Rechargeable Alkaline CoxNi2-xS2/TiO2 Battery.

    Science.gov (United States)

    Liu, Jilei; Wang, Jin; Ku, Zhiliang; Wang, Huanhuan; Chen, Shi; Zhang, Lili; Lin, Jianyi; Shen, Ze Xiang

    2016-01-26

    An electrochemical energy storage system with high energy density, stringent safety, and reliability is highly desirable for next-generation energy storage devices. Here an aqueous rechargeable alkaline CoxNi2-xS2 // TiO2 battery system is designed by integrating two reversible electrode processes associated with OH(-) insertion/extraction in the cathode part and Li ion insertion/extraction in the anode part, respectively. The prototype CoxNi2-xS2 // TiO2 battery is able to deliver high energy/power densities of 83.7 Wh/kg at 609 W/kg (based on the total mass of active materials) and good cycling stabilities (capacity retention 75.2% after 1000 charge/discharge cycles). A maximum volumetric energy density of 21 Wh/l (based on the whole packaged cell) has been achieved, which is comparable to that of a thin-film battery and better than that of typical commercial supercapacitors, benefiting from the unique battery and hierarchical electrode design. This hybrid system would enrich the existing aqueous rechargeable LIB chemistry and be a promising battery technology for large-scale energy storage.

  11. Higher aluminum concentration in Alzheimer's disease after Box-Cox data transformation.

    Science.gov (United States)

    Rusina, Robert; Matěj, Radoslav; Kašparová, Lucie; Kukal, Jaromír; Urban, Pavel

    2011-11-01

    Evidence regarding the role of mercury and aluminum in the pathogenesis of Alzheimer's disease (AD) remains controversial. The aims of our project were to investigate the content of the selected metals in brain tissue samples and the use of a specific mathematical transform to eliminate the disadvantage of a strong positive skew in the original data distribution. In this study, we used atomic absorption spectrophotometry to determine mercury and aluminum concentrations in the hippocampus and associative visual cortex of 29 neuropathologically confirmed AD and 27 age-matched controls. The Box-Cox data transformation was used for statistical evaluation. AD brains had higher mean aluminum concentrations in the hippocampus than controls (0.357 vs. 0.090 μg/g; P = 0.039) after data transformation. Results for mercury were not significant. Original data regarding microelement concentrations are heavily skewed and do not pass the normality test in general. A Box-Cox transformation can eliminate this disadvantage and allow parametric testing.

  12. Antibacterial and COX-1 Inhibitory Effect of Medicinal Plants from the Pamir Mountains, Afghanistan

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    Anne S. Jeppesen

    2012-10-01

    Full Text Available Plants used to treat inflammatory ailments, pain, fever and infections in the Pamir Mountains in northeastern Afghanistan, were tested for antibacterial and COX-1 inhibitory activity. Water and ethanol extracts of 20 species were tested for antibacterial activity against two gram positive and two gram negative bacteria. The ethanol extract of Arnebia guttata inhibited Staphylococcus aureus with a MIC of 6 µg/mL. Water and ethanol extracts of Ephedra intermedia and the ethanol extracts of Lagochilus cabulicus and Peganum harmala inhibited Staphylococcus aureus at 0.5 mg/mL, and the P. harmala extract further inhibited the growth of Bacillus subtilis and E. coli, also with MICs of 0.5 mg/mL. Ethanol extracts of Artemisia persica (IC50: 0.5 µg/mL, Dragocephalum paulsenii (IC50: 0.5 µg/mL, Ephedra intermedia (IC50: 3.8 µg/mL, Hyoscyamus pusillus, Nepeta parmiriensis (IC50: 0.7 µg/mL and Rumex patientia subsp. pamiricus (IC50: 3.5 µg/mL exhibited COX-1 inhibitory activity. The observed in vitro activities support the use of some of the plant species in the traditional medicine systems of the Pamir Mountains.

  13. Effects of COX inhibition on experimental pain and hyperalgesia during and after remifentanil infusion in humans.

    Science.gov (United States)

    Lenz, Harald; Raeder, Johan; Draegni, Tomas; Heyerdahl, Fridtjof; Schmelz, Martin; Stubhaug, Audun

    2011-06-01

    Opioids may enhance pain sensitivity resulting in opioid-induced hyperalgesia (OIH). Activation of spinal cyclooxygenase may play a role in the development of OIH. The aim of this study was to demonstrate remifentanil-induced postinfusion hyperalgesia in an electrical pain and a cold pain model, and to investigate whether COX-2 (parecoxib) or COX-1 (ketorolac) inhibition could prevent hyperalgesia after remifentanil infusion. Sixteen healthy males were enrolled in this randomized, double-blind, placebo-controlled crossover study. Each subject went through 4 sessions: control, remifentanil, parecoxib+remifentanil, and ketorolac+remifentanil. Transcutaneous electrical stimulation induced acute pain and areas of pinprick hyperalgesia. The areas of pinprick hyperalgesia were assessed before, during, and after a 30-minute infusion of either remifentanil or saline. The cold-pressor test (CPT) was performed before, at the end of, and 1 hour after the infusions. The subjects received a bolus of either saline, 40 mg parecoxib, or 30 mg ketorolac intravenously after the first CPT. The areas of pinprick hyperalgesia and CPT pain after the end of remifentanil infusion increased significantly compared to control (P pain and cold-pressor pain. Both parecoxib and ketorolac prevented hyperalgesia in the electrical model, parecoxib to a larger extent.

  14. In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.

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    Ian M Packham

    Full Text Available We sought to determine a role for platelets in in vivo angiogenesis, quantified by changes in the capillary to fibre ratio (C:F of mouse skeletal muscle, utilising two distinct forms of capillary growth to identify differential effects. Capillary sprouting was induced by muscle overload, and longitudinal splitting by chronic hyperaemia. Platelet depletion was achieved by anti-GPIbα antibody treatment. Sprouting induced a significant increase in C:F (1.42±0.02 vs. contralateral 1.29±0.02, P<0.001 that was abolished by platelet depletion, while the significant C:F increase caused by splitting (1.40±0.03 vs. control 1.28±0.03, P<0.01 was unaffected. Granulocyte/monocyte depletion showed this response was not immune-regulated. VEGF overexpression failed to rescue angiogenesis following platelet depletion, suggesting the mechanism is not simply reliant on growth factor release. Sprouting occurred normally following antibody-induced GPVI shedding, suggesting platelet activation via collagen is not involved. BrdU pulse-labelling showed no change in the proliferative potential of cells associated with capillaries after platelet depletion. Inhibition of platelet activation by acetylsalicylic acid abolished sprouting, but not splitting angiogenesis, paralleling the response to platelet depletion. We conclude that platelets differentially regulate mechanisms of angiogenesis in vivo, likely via COX signalling. Since endothelial proliferation is not impaired, we propose a link between COX1 and induction of endothelial migration.

  15. 25-Hydroxycholesterol exerts both a cox-2-dependent transient proliferative effect and cox-2-independent cytotoxic effect on bovine endothelial cells in a time- and cell-type-dependent manner

    Directory of Open Access Journals (Sweden)

    Cantarutti Alyssa

    2010-11-01

    Full Text Available Abstract Background 25-hydroxycholesterol (25-OHC is a product of oxidation of dietary cholesterol present in human plasma. 25-OHC and other oxidized forms of cholesterol are implicated in modulating inflammatory responses involved in development of atherosclerosis and colon carcinogenesis. Methods Primary lymphatic, venous and arterial endothelial cells isolated from bovine mesentery (bmLEC, bmVEC, bmAEC were treated with 25-OHC and tested for several different cellular parameters. Results We found 25-OHC to be a potent inducer of cyclooxygenase-2 (Cox-2, prostaglandin G-H synthase-2 expression in bovine mesenteric lymphatic, venous, and arterial endothelial cells. The induction of Cox-2 expression in endothelial cells by 25-OHC led to an initial increase in cellular proliferation that was inhibited by the Cox-2 selective inhibitor celecoxib (Celebrex. Prolonged exposure to 25-OHC was cytotoxic. Furthermore, endothelial cells induced to express Cox-2 by 25-OHC were more sensitive to the effects of the Cox-2 selective inhibitor celecoxib (Celebrex. These results suggest that some effects of 25-OHC on cells may be dependent on Cox-2 enzymatic activity. Conclusions Cox-2 dependent elevating effects of 25-OHC on endothelial cell proliferation was transient. Prolonged exposure to 25-OHC caused cell death and enhanced celecoxib-induced cell death in a cell-type dependent manner. The lack of uniform response by the three endothelial cell types examined suggests that our model system of primary cultures of bmLECs, bmVECs, and bmAECs may aid the evaluation of celecoxib in inhibiting proliferation of different types of tumour-associated endothelial cells.

  16. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

    OpenAIRE

    Inoue Takeshi; Anai Satoshi; Onishi Sayuri; Miyake Makito; Tanaka Nobumichi; Hirayama Akihide; Fujimoto Kiyohide; Hirao Yoshihiko

    2013-01-01

    Abstract Background COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. Methods LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1...

  17. Polymorphism of the Mitochondrial cox1 Gene of Eustrongylides Spp. from Monopterus Albus%黄鳝胃瘤线虫线粒体 cox1基因的多态性研究

    Institute of Scientific and Technical Information of China (English)

    黄汉成; 王芝英; 林洁; 马光旭; 朱宏宏; 周荣琼

    2016-01-01

    The study was carried out to examine the genetic variations of the mitochondrial Cytochrome C oxidase subunit 1 gene (cox1 ) among Eustrongylides spp. isolates of Monopterus albus in Western Chongqing area ,and to investigate the phylogenetic relationship among other nematodes as well .Molecular cloning was performed to obtain the partial cox1 sequence of each E. spp. sample ,and the homology anal‐ysis of these sequences were conducted .The results showed the same length of cox1 sequences (441 bp. ) of 6 E. spp. isolates with similarity of 97.5% - 100% .Phylogenetic analysis of these sequences showed that all E. spp. isolates were grouped into a single clade .There was significant discrepancy between inter‐specific sequence and intra‐specific sequence in terms of cox1 sequence ,suggesting cox1 gene could be used as genetic marker for the specific identification .The result of this study provides scientific basis and theo‐retical reference on the molecular level and epidemiology survey of parasitic Eustrongylides .%为了解渝西地区黄鳝胃瘤线虫分离株线粒体细胞色素 C 氧化酶第 I 亚基(cox1)的遗传变异情况及与其他科线虫的种群遗传关系,本研究对该地区黄鳝胃瘤线虫 cox1部分序列进行了克隆测序和进化分析.结果表明渝西地区6株胃瘤线虫分离株的 cox1序列长度一致,均为441 bp ;各分离株之间的相似性为97.5%~100%.种系发育树表明,6个胃瘤线虫分离株均位于同一分枝.由于胃瘤线虫 cox1序列种内相对保守,种间差异较大,故可作为种间遗传变异研究的标记.本研究结果为胃瘤线虫的分类鉴定以及进一步的分子流行病学调查和群体遗传研究奠定了基础.

  18. Cox2 and β-Catenin/T-cell Factor Signaling Intestinalize Human Esophageal Keratinocytes When Cultured under Organotypic Conditions

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    Jianping Kong

    2011-09-01

    Full Text Available The incidence of esophageal adenocarcinoma (EAC is rising in the United States. An important risk factor for EAC is the presence of Barrett esophagus (BE. BE is the replacement of normal squamous esophageal epithelium with a specialized columnar epithelium in response to chronic acid and bile reflux. However, the emergence of BE from squamous keratinocytes has not yet been demonstrated. Our research has focused on this. Wnt and cyclooxygenase 2 (Cox2 are two pathways whose activation has been associated with BE and progression to EAC, but their role has not been tested experimentally. To explore their contribution, we engineered a human esophageal keratinocyte cell line to express either a dominant-active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional culture environment, Cox2 expression increases cell proliferation and migration, but neither transgene induces known BE markers. In contrast, when these cells were placed into three-dimensional organotypic culture conditions, we observed more profound effects. CatCLef-expressing cells were more proliferative, developed a thicker epithelium, and upregulated Notch signaling and several BE markers including NHE2. Cox2 expression also increased cell proliferation and induced a thicker epithelium. More importantly, we observed cysts form within the epithelium, filled with intestinal mucins including Muc5B and Muc17. This suggests that Cox2 expression in a three-dimensional culture environment induces a lineage of mucin-secreting cells and supports an important causal role for Cox2 in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional organotypic culture conditions.

  19. Diminished neurogenic femoral artery vasoconstrictor response in a Zucker obese rat model: differential regulation of NOS and COX derivatives.

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    Ana Cristina Martínez

    Full Text Available OBJECTIVE: Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR by examining cross-talk between endothelial and neural factors. METHODS AND RESULTS: Arterial preparations from lean (LZR and OZR were subjected to electrical field stimulation (EFS on basal tone. Nitric oxide synthase (NOS and cyclooxygenase (COX isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS and inducible NOS (iNOS were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa or voltage-dependent (KV K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. CONCLUSIONS: Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation.

  20. FABRICATION OF GdCoxOy NANOTUBE ARRAYS IN ANODIC ALUMINIUM OXIDE TEMPLATES AND MAGNETIC BEHAVIOUR%模板法制备GdCoxOy纳米管阵列及磁性能

    Institute of Scientific and Technical Information of China (English)

    庞菲; 刘桂林; 昌杰; 袁孝友

    2010-01-01

    在草酸溶液中以二次阳极氧化法制备了阳极氧化铝(anodic aluminium oxide,AAO)模板;采用减压抽滤法,在AAO模板的纳米孔中使Gd(NO3)3·6H2O,CoSO4·7H2O溶液与NaOH溶液反应并经高温分解,制各出GdCoxOy纳米管.通过扫描电镜、透射电镜、选区电子衍射、X射线衍射和能量色散谱表征了GdCoxOy纳米管形貌、结构、元素组成和含量:用振动样品磁强计测量了纳米管的磁性能.结果表明:制备的GdCoxOy纳米管为非晶态结构;Gd,Co和O元素的摩尔比为14.86:4.78:80.36;其质量比为59.88:7.18:32.94.室温下GdCoxOy,纳米管有明显的磁各向异性,易磁化方向平行于GdCoxOy纳米管阵列的方向.

  1. Transcription factor Ets-1 inhibits glucose-stimulated insulin secretion of pancreatic β-cells partly through up-regulation of COX-2 gene expression.

    Science.gov (United States)

    Zhang, Xiong-Fei; Zhu, Yi; Liang, Wen-Biao; Zhang, Jing-Jing

    2014-08-01

    Increased cyclooxygenase-2 (COX-2) expression is associated with pancreatic β-cell dysfunction. We previously demonstrated that the transcription factor Ets-1 significantly up-regulated COX-2 gene promoter activity. In this report, we used the pancreatic β-cell line INS-1 and isolated rat islets to investigate whether Ets-1 could induce β-cell dysfunction through up-regulating COX-2 gene expression. We investigated the effects of ETS-1 overexpression and the effects of ETS-1 RNA interference on endogenous COX-2 expression in INS-1 cells. We used site-directed mutagenesis and a dual luciferase reporter assay to study putative Ets-1 binding sites in the COX-2 promoter. The effect of ETS-1 1 overexpression on the insulin secretion function of INS-1 cells and rat islets and the potential reversal of these effects by a COX-2 inhibitor were determined in a glucose-stimulated insulin secretion (GSIS) assay. ETS-1 overexpression significantly induces endogenous COX-2 expression, but ETS-1 RNA interference has no effect on basal COX-2 expression in INS-1 cells. Ets-1 protein significantly increases COX-2 promoter activity through the binding site located in the -195/-186 region of the COX-2 promoter. ETS-1 overexpression significantly inhibited the GSIS function of INS-1 cells and islet cells and COX-2 inhibitor treatment partly reversed this effect. These findings indicated that ETS-1 overexpression induces β-cell dysfunction partly through up-regulation of COX-2 gene expression. Moreover, Ets-1, the transcriptional regulator of COX-2 expression, may be a potential target for the prevention of β-cell dysfunction mediated by COX-2.

  2. Streamlining DNA barcoding protocols: automated DNA extraction and a new cox1 primer in arachnid systematics.

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    Nina Vidergar

    Full Text Available BACKGROUND: DNA barcoding is a popular tool in taxonomic and phylogenetic studies, but for most animal lineages protocols for obtaining the barcoding sequences--mitochondrial cytochrome C oxidase subunit I (cox1 AKA CO1--are not standardized. Our aim was to explore an optimal strategy for arachnids, focusing on the species-richest lineage, spiders by (1 improving an automated DNA extraction protocol, (2 testing the performance of commonly used primer combinations, and (3 developing a new cox1 primer suitable for more efficient alignment and phylogenetic analyses. METHODOLOGY: We used exemplars of 15 species from all major spider clades, processed a range of spider tissues of varying size and quality, optimized genomic DNA extraction using the MagMAX Express magnetic particle processor-an automated high throughput DNA extraction system-and tested cox1 amplification protocols emphasizing the standard barcoding region using ten routinely employed primer pairs. RESULTS: The best results were obtained with the commonly used Folmer primers (LCO1490/HCO2198 that capture the standard barcode region, and with the C1-J-2183/C1-N-2776 primer pair that amplifies its extension. However, C1-J-2183 is designed too close to HCO2198 for well-interpreted, continuous sequence data, and in practice the resulting sequences from the two primer pairs rarely overlap. We therefore designed a new forward primer C1-J-2123 60 base pairs upstream of the C1-J-2183 binding site. The success rate of this new primer (93% matched that of C1-J-2183. CONCLUSIONS: The use of C1-J-2123 allows full, indel-free overlap of sequences obtained with the standard Folmer primers and with C1-J-2123 primer pair. Our preliminary tests suggest that in addition to spiders, C1-J-2123 will also perform in other arachnids and several other invertebrates. We provide optimal PCR protocols for these primer sets, and recommend using them for systematic efforts beyond DNA barcoding.

  3. The influence of COX - 2 inhibitor on the expression of HPV18 - E6 and COX - 2 in Hela cells%环氧化酶2抑制剂对宫颈癌 Hela 细胞中 HPV18- E6和 COX -2表达的影响

    Institute of Scientific and Technical Information of China (English)

    吴丽; 陶光实; 陈亦乐; 唐真姿; 杨俊

    2016-01-01

    Objective:To explore the influence of COX - 2 inhibitor Celecoxib on the expression of HPV18 - E6 and COX - 2 in Hela cells and its viability and apoptosis. Methods:Human uterine cervix cancer Hela cells were treated with different concentrations of Celecoxib. The expression of HPV18 - E6 and COX - 2 were detected by im-munocytochemical SP method and reverse transcription - polymerase chain reaction. Cell survival viability was tested by using the MTT assay. The change of cell apoptosis was detected by flow cytometry and its morphology was observed under microscope after Hoechst staining. Results:The expression of HPV18 - E6 and COX - 2 protein was inhibited by COX - 2 inhibitor,with time/ dose - dependent manner and they were positively related in Hela cells. The growth was inhibited and the apoptosis of Hela cells was induced by COX - 2 inhibitor. Conclusion:COX - 2 inhibitor can lower HPV18 - E6 and COX - 2 expression at the same time inhibit Hela cells viability and enhance its apoptosis.%目的:探讨环氧化酶2抑制剂 Celecoxib 对宫颈癌细胞 Hela 中 HPV18- E6、COX -2表达及其细胞增殖和凋亡的影响。方法:用不同浓度 Celecoxib 处理 Hela 细胞株后,免疫细胞化学 SP 法检测 HPV18- E6和COX -2蛋白的表达变化。RT - PCR 检测 HPV18- E6及 COX -2 mRNA 表达的改变。MTT 法检测其对细胞增殖的影响。流式细胞仪测定细胞凋亡情况。Hoechst33258染色观察细胞的形态学变化。结果:Celecoxib 作用 Hela 细胞后 HPV18- E6和 COX -2基因 mRNA 及蛋白表达量明显低于对照组,且随着药物浓度增加表达呈梯度下降。各组之间差异具有显著性(P <0.05),且两者之间具有显著相关性(P <0.01)。Celecoxib 抑制Hela 细胞增殖,作用呈量-效关系(P <0.05)。流式细胞仪显示各实验组凋亡率随浓度升高而增加,与对照组之间有显著差异(P <0.05)。Hoechst33258荧光染色显示经20μmol/ L 药物作用 Hela

  4. Involvement of COX2–thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Teraoka, Hiroki, E-mail: hteraoka@rakuno.ac.jp [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Okuno, Yuki; Nijoukubo, Daisuke; Yamakoshi, Ayumi [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Peterson, Richard E. [School of Pharmacy, University of Wisconsin, Madison, WI (United States); Stegeman, John J. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States); Kitazawa, Takio; Hiraga, Takeo [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Kubota, Akira [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA (United States)

    2014-09-15

    Highlights: • We establish a new indicator of pericardial edema in developing zebrafish (precardiac edema). • Property of precardiac edema by TCDD is similar to that for conventional pericardial edema. • COX2b (but not COX2a)–thromboxane pathway is involved in precardiac edema by TCDD. - Abstract: The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in fish larvae. However, knowledge of the mechanism of TCDD-induced edema after heterodimerization of aryl hydrocarbon receptor type 2 (AHR2) and AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac edema. A concentration–response curve for precardiac edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial edema at 3 dpf. Precardiac edema caused by TCDD was reduced by morpholino knockdown of AHR2 and ARNT1, as well as by an antioxidant (ascorbic acid). A selective inhibitor of cyclooxygenase type 2 (COX2), NS398, also markedly inhibited TCDD-induced precardiac edema. A thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished TCDD-induced precardiac edema and this effect was canceled by U46619, a TP agonist, which was not influential in the action of TCDD by itself. Knockdown of COX2b and thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced TCDD-induced precardiac edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by TCDD. The edema by TCDD was also inhibited by knockdown of c-mpl, a thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b

  5. Antiinflamatórios não esteróides inibidores da ciclooxigenase-2 (COX-2: aspectos atuais

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    Kummer Carmen Luize

    2002-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Devido à alta incidência de efeitos colaterais relacionados aos antiinflamatórios não hormonais (AINES, a descoberta de duas isoformas da enzima ciclooxigenase, classificadas como: COX-1 ou constitutiva e COX-2 ou indutiva, formulou o paradigma que as propriedades antiinflamatórias dos AINES seriam mediadas através da inibição da enzima COX-2; já os efeitos colaterais, do bloqueio da COX-1. Entretanto, a isoforma COX-2 tem sido detectada constitutivamente em tecidos normais, levantando a dúvida sobre o quão realmente são seguros os inibidores específicos desta enzima. O objetivo desta revisão é relatar as mais recentes evidências clínicas e experimentais envolvendo a COX-2 e os compostos inibidores desta isoforma. CONTEÚDO: São exibidos os novos conceitos sobre as diferenças estruturais entre COX-1 e COX-2, a existência destas isoformas nos diversos tecidos, os resultados de experimentos em animais e humanos, além da observação clínica dos compostos inibidores específicos COX-2 (coxibs. Algumas prováveis novas indicações de antiinflamatórios não esteróides, principalmente coxibs, na demência de Alzheimer e em neoplasias são exemplificadas. CONCLUSÕES: Os coxibs representam importante avanço farmacológico no tratamento antiinflamatório, reduzindo a incidência de lesões gastrointestinais e apresentando possível indicação na prevenção de neoplasias e doenças neurológicas. No entanto, tais compostos apresentam efeitos colaterais indistinguíveis dos AINES convencionais e são drogas de alto custo. Como toda medicação de recente lançamento no arsenal médico, maiores avaliações são necessárias para o estabelecimento da real segurança destes compostos.

  6. COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

    Directory of Open Access Journals (Sweden)

    Petasis Nicos A

    2008-05-01

    Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

  7. Increases in COX II mRNA in the rat spinal cord induced by cauda equina traction.

    Science.gov (United States)

    Hirabayashi, Kiyoko; Komagata, Masashi; Yamada, Jinzo; Isshiki, Atsushi; Watanabe, Yasuo

    2006-05-01

    This article investigated the time response of COX II induction by traction of the cauda equina assessed by a quantified RT-PCR method. Under deep GOI anesthesia, male Wistar rats were fixed in the prone position and a laminectomy of the dorsal part of the first and second sacral vertebrae was performed. Following, COX II-mRNA levels in the cervical, thoracic, lumbar, sacral, and caudal segments were measured at 2, 4, 6, and 24 h after traction by a quantified RT-PCR method. After cauda equina traction, significant levels of COX II mRNA were detected in all segments of the spinal cord examined. Maximum levels in each segment were determined 4 h after traction of the cauda equina. Particularly in the sacrocaudal segments significantly higher levels of COX II mRNA were measured 24 h after traction. These results indicate that significant induction of spinal COX II mRNA was caused by cauda equina traction and that such induction plays a regulatory role in the nociceptive pain pathway.

  8. Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis.

    Science.gov (United States)

    Lu, Xiao-Yuan; Wang, Zhong-Chang; Ren, Shen-Zhen; Shen, Fa-Qian; Man, Ruo-Jun; Zhu, Hai-Liang

    2016-08-01

    Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2 promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhibition and anticancer. Among them, compound 7t showed most powerful selective inhibitory and antiproliferative activity (IC50=0.09μM for COX-2, IC50=48.20μM for COX-1, IC50=0.36μM against HeLa cells), comparable to the control positive compound Celecoxib (0.31μM, 43.37μM, 7.79μM). Cancer cell apoptosis assay were performed and results indicated that compound 7t effectively fuels HeLa cells apoptosis in a dose and time-dependent manner. Moreover, 7t could significantly suppress cancer cell adhesion, migration and invasion which were essential process of cancer metastasis. Docking simulations results was further indicated that compound 7t could bind well to the COX-2 active site and guided a reasonable design of selective COX-2 inhibitor with anticancer activities in future.

  9. Effects of β-glucosidase hydrolyzed products of harpagide and harpagoside on cyclooxygenase-2 (COX-2) in vitro.

    Science.gov (United States)

    Zhang, Liuqiang; Feng, Li; Jia, Qi; Xu, Jinwen; Wang, Rui; Wang, Zhengtao; Wu, Yingchun; Li, Yiming

    2011-08-15

    Harpagide (1) and harpagoside (2) are two iridoid glycosides existing in many medicinal plants. Although they are believed to be the main bioactive compounds related to the anti-inflammatory efficacy of these plants, the mechanisms of their anti-inflammatory activities remain unclear. The results of our present study showed that 1 and 2 had no effects on inhibitions of cyclooxygenase (COX)-1/2 enzyme activity, tumor necrosis factor-α (TNF-α) release, and nitric oxide (NO) production in vitro. However, the hydrolyzed products of 1 and 2 with β-glucosidase treatment showed a significant inhibitory effect on COX-2 activity at 2.5-100 μM in a concentration-dependent manner. Our further study revealed that the hydrolyzed 2 product was structurally the same as the hydrolyzed 1 product (H-harpagide (3)). The structure of 3 was 2-(formylmethyl)-2,3,5-trihydroxy-5-methylcyclopentane carbaldehyde, with a backbone similar to prostaglandins and COX-2 inhibitors such as celecoxib. All of them have a pentatomic ring with two adjacent side chains. The result of molecular modeling and docking study showed that 3 could bind to the COX-2 active domain well through hydrophobic and hydrogen-bonding interactions, whereas 1 and 2 could not, implying that the hydrolysis of the glycosidic bond of 1 and 2 is a pre-requisite step for their COX-2 inhibitory activity.

  10. Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy.

    Science.gov (United States)

    Hallmann, Kerstin; Kudin, Alexei P; Zsurka, Gábor; Kornblum, Cornelia; Reimann, Jens; Stüve, Burkhard; Waltz, Stephan; Hattingen, Elke; Thiele, Holger; Nürnberg, Peter; Rüb, Cornelia; Voos, Wolfgang; Kopatz, Jens; Neumann, Harald; Kunz, Wolfram S

    2016-02-01

    Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient's fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease.

  11. MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly.

    Science.gov (United States)

    Dennerlein, Sven; Oeljeklaus, Silke; Jans, Daniel; Hellwig, Christin; Bareth, Bettina; Jakobs, Stefan; Deckers, Markus; Warscheid, Bettina; Rehling, Peter

    2015-09-08

    Cytochrome c oxidase, the terminal enzyme of the respiratory chain, is assembled from mitochondria- and nuclear-encoded subunits. The MITRAC complex represents the central assembly intermediate during this process as it receives imported subunits and regulates mitochondrial translation of COX1 mRNA. The molecular processes that promote and regulate the progression of assembly downstream of MITRAC are still unknown. Here, we identify MITRAC7 as a constituent of a late form of MITRAC and as a COX1-specific chaperone. MITRAC7 is required for cytochrome c oxidase biogenesis. Surprisingly, loss of MITRAC7 or an increase in its amount causes selective cytochrome c oxidase deficiency in human cells. We demonstrate that increased MITRAC7 levels stabilize and trap COX1 in MITRAC, blocking progression in the assembly process. In contrast, MITRAC7 deficiency leads to turnover of newly synthesized COX1. Accordingly, MITRAC7 affects the biogenesis pathway by stabilizing newly synthesized COX1 in assembly intermediates, concomitantly preventing turnover.

  12. COX-2 induces lytic reactivation of EBV through PGE2 by modulating the EP receptor signaling pathway.

    Science.gov (United States)

    Gandhi, Jaya; Gaur, Nivedita; Khera, Lohit; Kaul, Rajeev; Robertson, Erle S

    2015-10-01

    Inflammation is one of the predisposing factors known to be associated with Epstein Barr Virus (EBV) mediated tumorigenesis. However it is not well understood whether inflammation in itself plays a role in regulating the life cycle of this infectious agent. COX-2, a key mediator of the inflammatory processes is frequently over-expressed in EBV positive cancer cells. In various tumors, PGE2 is the principle COX-2 regulated downstream product which exerts its effects on cellular processes through the EP1-4 receptors. In this study, we further elucidated how upregulated COX-2 levels can modulate the events in EBV life cycle related to latency-lytic reactivation. Our data suggest a role for upregulated COX-2 on modulation of EBV latency through its downstream effector PGE2. This study demonstrates a role for increased COX-2 levels in modulation of EBV latency. This is important for understanding the pathogenesis of EBV-associated cancers in people with chronic inflammatory conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Korean Red Ginseng water extract inhibits COX-2 expression by suppressing p38 in acrolein-treated human endothelial cells

    Directory of Open Access Journals (Sweden)

    Seung Eun Lee

    2014-01-01

    Full Text Available Cigarette smoke is considered a major risk factor for vascular diseases. There are many toxic compounds in cigarette smoke, including acrolein and other α,β-unsaturated aldehydes, which are regarded as mediators of inflammation and vascular dysfunction. Furthermore, recent studies have revealed that acrolein, an α,β-unsaturated aldehyde in cigarette smoke, induces inflammatory mediator expression, which is known to be related to vascular diseases. In this study, we investigated whether Korean Red Ginseng (KRG water extract suppressed acrolein-induced cyclooxygenase (COX-2 expression in human umbilical vein endothelial cells (HUVECs. Acrolein-induced COX-2 expression was accompanied by increased levels of phosphorylated p38 in HUVECs and KRG inhibited COX-2 expression in HUVECs. These results suggest that KRG suppresses acrolein-induced COX-2 expression via inhibition of the p38 mitogen-activated protein kinase signaling pathway. In addition, KRG exhibited an inhibitory effect on acrolein-induced apoptosis, as demonstrated by annexin V–propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. Consistent with these results, KRG may exert a vasculoprotective effect through inhibition of COX-2 expression in acrolein-stimulated human endothelial cells.

  14. Physical exercise regulates p53 activity targeting SCO2 and increases mitochondrial COX biogenesis in cardiac muscle with age.

    Directory of Open Access Journals (Sweden)

    Zhengtang Qi

    Full Text Available The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-μ (PFTμ, sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2, p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTμ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle.

  15. Prolactin (PRL) induction of cyclooxygenase 2 (COX2) expression and prostaglandin (PG) production in hamster Leydig cells.

    Science.gov (United States)

    Matzkin, María Eugenia; Ambao, Verónica; Carino, Mónica Herminia; Rossi, Soledad Paola; González, Lorena; Turyn, Daniel; Campo, Stella; Calandra, Ricardo Saúl; Frungieri, Mónica Beatriz

    2012-01-02

    Serum prolactin (PRL) variations play a crucial role in the photoperiodic-induced testicular regression-recrudescence transition in hamsters. We have previously shown that cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins (PGs), is expressed mostly in Leydig cells of reproductively active hamsters with considerable circulating and pituitary levels of PRL. In this study, we describe a stimulatory effect of PRL on COX2/PGs in hamster Leydig cells, which is mediated by IL-1β and prevented by P38-MAPK and JAK2 inhibitors. Furthermore, by preparative isoelectric focusing (IEF), we isolated PRL charge analogues from pituitaries of active [isoelectric points (pI): 5.16, 4.61, and 4.34] and regressed (pI: 5.44) hamsters. More acidic PRL charge analogues strongly induced COX2 expression, while less acidic ones had no effect. Our studies suggest that PRL induces COX2/PGs in hamster Leydig cells through IL-1β and activation of P38-MAPK and JAK2. PRL microheterogeneity detected in active/inactive hamsters may be responsible for the photoperiodic variations of COX2 expression in Leydig cells.

  16. Synergistic COX2 Induction by IFNγ and TNFα Self-Limits Type-1 Immunity in the Human Tumor Microenvironment.

    Science.gov (United States)

    Wong, Jeffrey L; Obermajer, Nataša; Odunsi, Kunle; Edwards, Robert P; Kalinski, Pawel

    2016-04-01

    Maintenance of CTL-, Th1-, and NK cell-mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators of type-1 immune effector cells, IFNγ and TNFα, synergize in the induction of cyclooxygenase 2 (COX2), the key enzyme in prostaglandin (PG)E2 synthesis, and the subsequent hyperactivation of myeloid-derived suppressor cells (MDSC) within the tumor microenvironment (TME) of ovarian cancer patients. MDSC hyperactivation by type-1 immunity and the resultant overexpression of indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS/NOS2), IL10, and additional COX2 result in strong feedback suppression of type-1 immune responses. This paradoxical immune suppression driven by type-1 immune cell activation was found to depend on the synergistic action of IFNγ and TNFα, and could not be reproduced by either of these factors alone. Importantly, from a therapeutic standpoint, these negative feedback limiting type-1 responses could be eliminated by COX2 blockade, allowing amplification of type-1 immunity in the ovarian cancer TME. Our data demonstrate a new mechanism underlying the self-limiting nature of type-1 immunity in the human TME, driven by the synergistic induction of COX2 by IFNγ and TNFα, and provide a rationale for targeting the COX2-PGE2 axis to enhance the effectiveness of cancer immunotherapies.

  17. COX-2和VEGF-C基因在乳腺良恶性病变中的表达研究%Expression of COX-2 and VEGF-C mRNA in benign and malignant breast diseases

    Institute of Scientific and Technical Information of China (English)

    肖锋; 顾春燕; 姚建国; 陈咏梅; 李民

    2011-01-01

    Objective To investigate the expression of COX-2 and VEGF-C mRNA in benign and malignant breast diseases and their association with breast tumorigenesis. Methods Tissue specimens were collected from 8 cases of accessory breasts, 15 cases of adenosis, 16 cases of fibroadenoma, 11 cases of ductal carcinoma in situ (DCIS) and 40 cases of invasive ductal carcinoma (IDC). Real-time PCR was used to detect the expression of COX-2 and VEGF-C mRNA. Results The accessory breasts were all negative for COX-2 mRNA expression, and weakly expressed VEGF-C. The expression of COX-2 and VEGF-C mRNA were increased significantly in adenosis and fibroadenoma tissues (P<0.05). In DCIS and IDC the expressions of COX-2 and VEGF-C mRNA were higher than those in adenosis and fibroadenoma (P < 0. 05). In IDC the expressions of COX-2 and VEGF-C mRNA were correlated with the histological grades. In DCIS and IDC, there was a strong positive correlation between COX-2 and VEGF-C mRNA expression (r = 0.82, P=0.002;r = 0. 89,P= 0.000, respectively). Conclusion The expressions of COX-2 and VEGF-C genes are increased in both benign and malignant breast diseases, and the expression levels in malignant breast diseases are higher than those in benign diseases. These results suggest that they might be important factors in the breast tumorigenesis, especially in breast carcinogenesis and tumor development.%目的 研究COX-2和VEGF-C mRNA在乳腺良恶性病变中的表达情况,探讨两者在乳腺肿瘤发生过程中的相互关系.方法 运用Real-time PCR方法对90例乳腺良恶性病变组织中COX-2和VEGF-C mRNA的表达进行检测.结果 8例副乳腺组织中,COX-2和VEGF-C mRNA不表达或低表达,15例腺病和16例纤维腺瘤中两者表达明显增加(P<0.05),11例DCIS中,两者均高表达,高于腺病和纤维腺瘤(P<0.05),40例IDC中,两者同样高表达,并且肿瘤级别越高,表达水平越高.在DCIS和IDC中,两者表达存在正相关关系(分别r=0.82,P=0.002;r=0

  18. COX-2 mRNA expression at different stages of osteoarthritis synoviocytes%不同分期骨关节炎滑膜细胞中COX-2 mRNA表达的差异

    Institute of Scientific and Technical Information of China (English)

    曾明珠; 段戡; 袁长深; 梅其杰; 秦凯

    2014-01-01

    BACKGROUND:COX-2 gene actual y exists in the joint fibroblast-like synoviocytes, it affects osteoarthritis occurrence and development. Understanding the differences of COX-2 gene expression levels at different stages of osteoarthritis synoviocytes has important theoretical significance for the occurrence and development of osteoarthritis, as wel as the role of synoviocytes in this process. OBJECTIVE:To analyze the difference of COX-2 mRNA at different stages of osteoarthritis fibroblast-like synoviocytes. METHODS:Synovial membrane from 44 osteoarthritis patients and 12 normal cases were selected. Primary cells were cultured to passage 4 fibroblast-like synoviocytes for the use in the experiment. COX-2 mRNA expression in osteoarthritis fibroblast-like synoviocytes and normal fibroblast-like synoviocytes was detected using real-time fluorescence quantitative RT-PCR. The relative quantitative analysis was performed using 2-ΔΔCt method. RESULTS AND CONCLUSION:Expression of COX-2 mRNA in osteoarthritis fibroblast-like synoviocytes was significantly higher than that in normal fibroblast-like synoviocytes (P0.05). COX-2 mRNA might be important biological marker for the inflammation in osteoarthritis, and mainly plays a role in early osteoarthritis stage.%背景:COX-2基因实际存在于关节成纤维样滑膜细胞里,影响骨关节炎症的发生、发展。阐明不同分期骨关节炎滑膜细胞中COX-2基因表达量的差异对进一步深入了解骨关节炎的发生与发展,以及滑膜细胞在这一过程中的作用,具有重要的理论意义。  目的:分析COX-2 mRNA在不同分期骨关节炎成纤维样滑膜细胞中表达的差异。  方法:收集膝骨关节炎病变滑膜44例及正常滑膜12例,经原代细胞培养生长至4代的成纤维样滑膜细胞用于实验,应用实时荧光定量RT-PCR检测骨关节炎和正常成纤维样滑膜细胞中COX-2 mRNA的表达情况,最后使用2-ΔΔCt方法进行相对

  19. Expected Power-Utility Maximization Under Incomplete Information and with Cox-Process Observations

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Kazufumi, E-mail: m_fuji@kvj.biglobe.ne.jp [Bank of Tokyo-Mitsubishi UFJ, Ltd., Corporate Risk Management Division (Japan); Nagai, Hideo, E-mail: nagai@sigmath.es.osaka-u.ac.jp [Osaka University, Division of Mathematical Science for Social Systems, Graduate School of Engineering Science (Japan); Runggaldier, Wolfgang J., E-mail: runggal@math.unipd.it [Universita di Padova, Dipartimento di Matematica Pura ed Applicata (Italy)

    2013-02-15

    We consider the problem of maximization of expected terminal power utility (risk sensitive criterion). The underlying market model is a regime-switching diffusion model where the regime is determined by an unobservable factor process forming a finite state Markov process. The main novelty is due to the fact that prices are observed and the portfolio is rebalanced only at random times corresponding to a Cox process where the intensity is driven by the unobserved Markovian factor process as well. This leads to a more realistic modeling for many practical situations, like in markets with liquidity restrictions; on the other hand it considerably complicates the problem to the point that traditional methodologies cannot be directly applied. The approach presented here is specific to the power-utility. For log-utilities a different approach is presented in Fujimoto et al. (Preprint, 2012).

  20. Magnetocaloric Effect of Alloys Gd(Al1-xCox)2

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The magnetocaloric effect in alloys Gd(Al1-xCox)2 with x=0, 0.05, and 0.10 were investigated using X-ray diffraction (XRD) and magnetization measurements.It was found that three alloys crystallized in a single phase with MgCu2-type structure.The lattice parameter and Curie temperature decreased with increasing Co content, whereas the magnetic-entropy change increased.With a magnetic-field change of 2 T, the maximum of the magnetic-entropy change reached 4.6 J·kg-1·K-1 near Curie temperature at approximately 95 K in the alloy GdAl1.8Co0.2, which appeared to be an alternative candidate for active magnetic refrigerants working in the temperature range centered at 100 K.

  1. Cox process representation and inference for stochastic reaction-diffusion processes

    Science.gov (United States)

    Schnoerr, David; Grima, Ramon; Sanguinetti, Guido

    2016-05-01

    Complex behaviour in many systems arises from the stochastic interactions of spatially distributed particles or agents. Stochastic reaction-diffusion processes are widely used to model such behaviour in disciplines ranging from biology to the social sciences, yet they are notoriously difficult to simulate and calibrate to observational data. Here we use ideas from statistical physics and machine learning to provide a solution to the inverse problem of learning a stochastic reaction-diffusion process from data. Our solution relies on a non-trivial connection between stochastic reaction-diffusion processes and spatio-temporal Cox processes, a well-studied class of models from computational statistics. This connection leads to an efficient and flexible algorithm for parameter inference and model selection. Our approach shows excellent accuracy on numeric and real data examples from systems biology and epidemiology. Our work provides both insights into spatio-temporal stochastic systems, and a practical solution to a long-standing problem in computational modelling.

  2. Penalized variable selection procedure for Cox models with semiparametric relative risk

    CERN Document Server

    Du, Pang; Liang, Hua; 10.1214/09-AOS780

    2010-01-01

    We study the Cox models with semiparametric relative risk, which can be partially linear with one nonparametric component, or multiple additive or nonadditive nonparametric components. A penalized partial likelihood procedure is proposed to simultaneously estimate the parameters and select variables for both the parametric and the nonparametric parts. Two penalties are applied sequentially. The first penalty, governing the smoothness of the multivariate nonlinear covariate effect function, provides a smoothing spline ANOVA framework that is exploited to derive an empirical model selection tool for the nonparametric part. The second penalty, either the smoothly-clipped-absolute-deviation (SCAD) penalty or the adaptive LASSO penalty, achieves variable selection in the parametric part. We show that the resulting estimator of the parametric part possesses the oracle property, and that the estimator of the nonparametric part achieves the optimal rate of convergence. The proposed procedures are shown to work well i...

  3. A risk-adjusted CUSUM in continuous time based on the Cox model.

    Science.gov (United States)

    Biswas, Pinaki; Kalbfleisch, John D

    2008-07-30

    In clinical practice, it is often important to monitor the outcomes associated with participating facilities. In organ transplantation, for example, it is important to monitor and assess the outcomes of the transplants performed at the participating centers and send a signal if a significant upward trend in the failure rates is detected. In manufacturing and process control contexts, the cumulative summation (CUSUM) technique has been used as a sequential monitoring scheme for some time. More recently, the CUSUM has also been suggested for use in medical contexts. In this article, we outline a risk-adjusted CUSUM procedure based on the Cox model for a failure time outcome. Theoretical approximations to the average run length are obtained for this new proposal and for some discrete time procedures suggested in the literature. The proposed scheme and approximations are evaluated in simulations and illustrated on transplant facility data from the Scientific Registry of Transplant Recipients.

  4. Conformational Characterization of Ipomotaosides and Their Recognition by COX-1 and 2

    Directory of Open Access Journals (Sweden)

    Pablo R. Arantes

    2014-04-01

    Full Text Available The aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be difficult due to their high flexibility. In this context, the current work presents a conformational characterization of ipomotaosides A–D in aqueous and nonaqueous solvents. The employed protocol includes metadynamics evaluation and unrestrained molecular dynamics simulations (MD. The obtained data provided structural models for the ipomotaosides in good agreement with previous ROESY distances measured in pyridine. Accordingly, the most abundant conformation of ipomotaoside A in solution was employed in flexible docking studies, providing a structural basis for the compound’s inhibition of COX enzymes. The so-obtained complex supports resin glycosides’ role as original scaffolds for future studies, aiming at structural optimization and development of potential new anti-inflammatory agents.

  5. Ruin Probabilities in Cox Risk Models with Two Dependent Classes of Business

    Institute of Scientific and Technical Information of China (English)

    Jun Yi GUO; Kam C. YUEN; Ming ZHOU

    2007-01-01

    In this paper we consider risk processes with two classes of business in which the two claim-number processes are dependent Cox processes. We first assume that the two claim-number processes have a two-dimensional Markovian intensity. Under this assumption, we not only study the sum of the two individual risk processes but also investigate the two-dimensional risk process formed by considering the two individual processes separately. For each of the two risk processes we derive an expression for the ruin probability, and then construct an upper bound for the ruin probability.We next assume that the intensity of the two claim-number processes follows a Markov chain. In this case, we examine the ruin probability of the sum of the two individual risk processes. Specifically, a differential system for the ruin probability is derived and numerical results are obtained for exponential claim sizes.

  6. MEDV-13 for QSAR Studies on the COX-2 Inhibition by In domethacin Amides and Esters

    Institute of Scientific and Technical Information of China (English)

    LIU,Shu-Shen (刘树深); YIN,Chun-Sheng(印春生); SHI,Yun-Yu(施蕴渝); CAI,Shao-Xi(蔡绍皙); LI,Zhi-Liang(李志良)

    2001-01-01

    A molecular electronegativity distance vector based on 13 atomic types (MEDV-13), is a descriptor for predicting the biological activities of molecules based on the quantitative structure-activity relationship (QSAR). The MEDV-13 with 91 descriptors is employed to describe the structures of a series of selective cydooxygenase-2 (COX-2) inhibitors inchuding 16 indomethacin and its amide and ester derivatives (ImAE). A principal component regression (PCR) is used to derive a QSAR model relating the biological activities expressed by pIC50 values to the MEDV-13. With the number of principal components of 6, the correlation coeffcient (R) and the root mean square error (RMS) are 0.9245 and 0.1682 in modeling stage, and 0.8417 and 0.2389 in leave-one-out prediction step, respectively.

  7. Effect of atomic order on the electrical resistivity of CoxFe100-x alloys

    Science.gov (United States)

    Freitas, P. P.; Berger, L.

    1988-04-01

    We measured the electrical resistivity at 4.2 K of a series of CoxFe100-x alloys in the ordered and disordered state. For 30dTQ has a strong negative anomaly at To. At high temperatures and in equilibrium, ρ(T) decreases upon ordering and dρ/dT has a positive anomaly at To. This crossover from a gap-dominated to a relaxation-time-dominated critical behavior is induced by increasing the measuring temperature T, therefore exciting electrons across the energy gap. From the dependence of ρ(TQ,T) on T we estimate the gap width to be around 45 meV. For x=50 at.% Co both ρ(TQ,4.2 K) and ρ(T) decrease upon ordering. Here the gapless behavior of the resistivity is due to the particular topology of the Fermi surface.

  8. Cox regression with missing covariate data using a modified partial likelihood method

    DEFF Research Database (Denmark)

    Martinussen, Torben; Holst, Klaus K.; Scheike, Thomas H.

    2016-01-01

    us to calculate estimators without having to assume anything about the distribution of the covariates. We show that the proposed estimator is consistent and asymptotically normal, and derive a consistent estimator of the variance-covariance matrix that does not involve any choice of a perturbation......Missing covariate values is a common problem in survival analysis. In this paper we propose a novel method for the Cox regression model that is close to maximum likelihood but avoids the use of the EM-algorithm. It exploits that the observed hazard function is multiplicative in the baseline hazard...... function with the idea being to profile out this function before carrying out the estimation of the parameter of interest. In this step one uses a Breslow type estimator to estimate the cumulative baseline hazard function. We focus on the situation where the observed covariates are categorical which allows...

  9. A transcriptome analysis by lasso penalized Cox regression for pancreatic cancer survival.

    Science.gov (United States)

    Wu, Tong Tong; Gong, Haijun; Clarke, Edmund M

    2011-12-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the United States with five-year survival rates less than 5% due to rare detection in early stages. Identification of genes that are directly correlated to pancreatic cancer survival is crucial for pancreatic cancer diagnostics and treatment. However, no existing GWAS or transcriptome studies are available for addressing this problem. We apply lasso penalized Cox regression to a transcriptome study to identify genes that are directly related to pancreatic cancer survival. This method is capable of handling the right censoring effect of survival times and the ultrahigh dimensionality of genetic data. A cyclic coordinate descent algorithm is employed to rapidly select the most relevant genes and eliminate the irrelevant ones. Twelve genes have been identified and verified to be directly correlated to pancreatic cancer survival time and can be used for the prediction of future patient's survival.

  10. New Inference Procedures for Semiparametric Varying-Coefficient Partially Linear Cox Models

    Directory of Open Access Journals (Sweden)

    Yunbei Ma

    2014-01-01

    Full Text Available In biomedical research, one major objective is to identify risk factors and study their risk impacts, as this identification can help clinicians to both properly make a decision and increase efficiency of treatments and resource allocation. A two-step penalized-based procedure is proposed to select linear regression coefficients for linear components and to identify significant nonparametric varying-coefficient functions for semiparametric varying-coefficient partially linear Cox models. It is shown that the penalized-based resulting estimators of the linear regression coefficients are asymptotically normal and have oracle properties, and the resulting estimators of the varying-coefficient functions have optimal convergence rates. A simulation study and an empirical example are presented for illustration.

  11. CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma.

    Science.gov (United States)

    Rodríguez-Arámbula, Adriana; Torres-Álvarez, Bertha; Cortés-García, Diego; Fuentes-Ahumada, Cornelia; Castanedo-Cázares, Juan Pablo

    2015-10-01

    The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1β, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.

  12. Acacia ferruginea inhibits inflammation by regulating inflammatory iNOS and COX-2.

    Science.gov (United States)

    Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2016-01-01

    Inflammation is a local defensive reaction of a host to cellular injury or infection. Prolonged inflammation can contribute to pathogenesis of many disorders. Identification of naturally occurring phytoconstituents that can suppress inflammatory mediators can lead to the discovery of anti-inflammatory therapeutics. Acacia ferruginea is used traditionally to treat numerous ailments including hemorrhage, irritable bowel syndrome and leprosy. The present study evaluated the anti-inflammatory activity of A. ferruginea extract against acute (carrageenan) and chronic (formaldehyde) inflammation in Balb/c mice. Pre-treatment with A. ferruginea extract (10 mg/kg BW) for 5 consecutive days via intraperitonial (IP) administration significantly inhibited subsequent induction of paw edema in both models; the effects were comparable to that of the standard drug indomethacin. The results also showed the A. ferruginea extract significantly inhibited nitric oxide (NO) synthesis and iNOS expression (as measured in serum), diminished inflammation in - and neutrophil infiltration to - the paw tissues and led to a reduction in the number of COX-2(+) immunoreative cells (as evidenced by histologic and immunohistochemical analyses) in the paws relative to those in paws of mice that received the irritants only. Further, in vitro studies showed the extract could significantly scavenge free radicals generated as in DPPH and NO radical generating assays. Taken together, the results showed that A. ferruginea extract imparted potent anti-oxidant and -inflammatory effects, in part by maintaining oxidative homeostasis, inhibiting NO synthesis and suppressing iNOS and COX-2 expression and so could potentially be exploited as a potential plant-based medication against inflammatory disorders.

  13. A computer simulation of progesterone and Cox2 inhibitor treatment for preterm labor.

    Directory of Open Access Journals (Sweden)

    Ozlem Equils

    Full Text Available BACKGROUND: Sufficient information from in vitro and in vivo studies has become available to permit computer modeling of the processes that occur in the myometrium during labor. This development allows the in silico investigation of pathological mechanisms and the trialing of potential treatments. METHODS/RESULTS: Based on the human literature, we developed a computer model of the immune-endocrine environment of the myometrial cell. The interactions between molecules are represented by differential equations. The model is designed to simulate the estrogen and progesterone receptor changes during pregnancy and particularly the changes in the progesterone receptor (PR isoforms A and B that are thought to mediate functional progesterone withdrawal in the human at labor. Parturition is represented by an increase in the PRA to PRB ratio to levels seen in women in labor. Infection is shown by inducing inflammation in the system by increasing phospho-IkB kinase concentration (IKK levels; which lead to increased NF-kappaB activation, causing an increase in the PRA/PRB ratio. We examined the effects of progesterone or cyclo-oxygenase 2 (Cox2 inhibitor treatments on the PRA/PRB ratio in silico. The model predicted that high doses of progesterone and Cox2 inhibition would be effective in preventing an NF-kappaB-induced PRA/PRB ratio increase to the levels found during labor. CONCLUSIONS: Our data illustrate the use of dynamic biological computer simulations to test the effectiveness of therapeutic interventions. This may allow the early rejection of ineffective therapies prior to expensive field trials.

  14. c060: Extended Inference with Lasso and Elastic-Net Regularized Cox and Generalized Linear Models

    Directory of Open Access Journals (Sweden)

    Martin Sill

    2014-12-01

    Full Text Available We have developed the R package c060 with the aim of improving R software func- tionality for high-dimensional risk prediction modeling, e.g., for prognostic modeling of survival data using high-throughput genomic data. Penalized regression models provide a statistically appealing way of building risk prediction models from high-dimensional data. The popular CRAN package glmnet implements an efficient algorithm for fitting penalized Cox and generalized linear models. However, in practical applications the data analysis will typically not stop at the point where the model has been fitted. One is for example often interested in the stability of selected features and in assessing the prediction performance of a model and we provide functions to deal with both of these tasks. Our R functions are computationally efficient and offer the possibility of speeding up computing time through parallel computing. Another feature which can drastically reduce computing time is an efficient interval-search algorithm, which we have implemented for selecting the optimal parameter combination for elastic net penalties. These functions have been useful in our daily work at the Biostatistics department (C060 of the German Cancer Research Center where prognostic modeling of patient survival data is of particular interest. Although we focus on a survival data application of penalized Cox models in this article, the functions in our R package are in general applicable to all types of regression models implemented in the glmnet package, with the exception of prediction error curves, which are specific to time-to-event data.

  15. Electron doping evolution of the magnetic excitations in NaFe1 -xCoxAs

    Science.gov (United States)

    Carr, Scott V.; Zhang, Chenglin; Song, Yu; Tan, Guotai; Li, Yu; Abernathy, D. L.; Stone, M. B.; Granroth, G. E.; Perring, T. G.; Dai, Pengcheng

    2016-06-01

    We use time-of-flight (TOF) inelastic-neutron-scattering (INS) spectroscopy to investigate the doping dependence of magnetic excitations across the phase diagram of NaFe1 -xCoxAs with x =0 , 0.0175, 0.0215, 0.05, and 0.11 . The effect of electron doping by partially substituting Fe by Co is to form resonances that couple with superconductivity, broaden, and suppress low-energy (E ≤80 meV) spin excitations compared with spin waves in undoped NaFeAs. However, high-energy (E >80 meV) spin excitations are weakly Co-doping-dependent. Integration of the local spin dynamic susceptibility χ''(ω ) of NaFe1 -xCoxAs reveals a total fluctuating moment of 3.6 μB2/Fe and a small but systematic reduction with electron doping. The presence of a large spin gap in Co-overdoped nonsuperconducting NaFe0.89Co0.11As suggests that Fermi surface nesting is responsible for low-energy spin excitations. These results parallel the Ni-doping evolution of spin excitations in BaFe2 -xNixAs2 in spite of the differences in crystal structures and Fermi surface evolution in these two families of iron pnictides, thus confirming the notion that low-energy spin excitations coupling with itinerant electrons are important for superconductivity, while weakly doping-dependent high-energy spin excitations result from localized moments.

  16. A simulation study of finite-sample properties of marginal structural Cox proportional hazards models.

    Science.gov (United States)

    Westreich, Daniel; Cole, Stephen R; Schisterman, Enrique F; Platt, Robert W

    2012-08-30

    Motivated by a previously published study of HIV treatment, we simulated data subject to time-varying confounding affected by prior treatment to examine some finite-sample properties of marginal structural Cox proportional hazards models. We compared (a) unadjusted, (b) regression-adjusted, (c) unstabilized, and (d) stabilized marginal structural (inverse probability-of-treatment [IPT] weighted) model estimators of effect in terms of bias, standard error, root mean squared error (MSE), and 95% confidence limit coverage over a range of research scenarios, including relatively small sample sizes and 10 study assessments. In the base-case scenario resembling the motivating example, where the true hazard ratio was 0.5, both IPT-weighted analyses were unbiased, whereas crude and adjusted analyses showed substantial bias towards and across the null. Stabilized IPT-weighted analyses remained unbiased across a range of scenarios, including relatively small sample size; however, the standard error was generally smaller in crude and adjusted models. In many cases, unstabilized weighted analysis showed a substantial increase in standard error compared with other approaches. Root MSE was smallest in the IPT-weighted analyses for the base-case scenario. In situations where time-varying confounding affected by prior treatment was absent, IPT-weighted analyses were less precise and therefore had greater root MSE compared with adjusted analyses. The 95% confidence limit coverage was close to nominal for all stabilized IPT-weighted but poor in crude, adjusted, and unstabilized IPT-weighted analysis. Under realistic scenarios, marginal structural Cox proportional hazards models performed according to expectations based on large-sample theory and provided accurate estimates of the hazard ratio.

  17. The Application of CPA to Calculations of the Mean Magnetic Moment in the Gd1-xNi, Gd1-xFe, Gd1xCox, and Y1-xCox Intermetallic Compounds

    DEFF Research Database (Denmark)

    Szpunar, B.; Kozarzewski, B.

    1977-01-01

    with a narrow d-band is considered. The magnetic moment of the alloy at zero temperature is calculated within the molecular field and Hartree-Fock approximations. Disorder is treated in the coherent potential approximation. Results are in good agreement with the experimental data obtained for the crystalline......Calculations are made of the mean magnetic moment per atom of the transition metal and the rare-earth metal in the intermetallic compounds, Gd1-x,Nix, Gd1-x Fex, Gd1-x Cox, and Y1-x Cox. A simple model of the disordered alloy consisting of spins localized on the rare-earth atoms and interacting...

  18. Dynamic Expression of HIF -1α and COX -2 in Perihematoma after Intracerebral Hemorrhage in Rats%大鼠脑出血灶周HIF-1α和COX-2的动态变化

    Institute of Scientific and Technical Information of China (English)

    李婷婷; 牛小媛

    2012-01-01

    目的 观察大鼠脑出血后血肿灶周脑组织中HIF -1α、COX -2蛋白的动态表达,探讨二者与脑水肿的关系,以及HIF -1α和COX -2蛋白的表达在血肿灶周脑组织损伤中的作用机制.方法 SD大鼠35只,随机分为假手术组、脑出血6h、1、3、7、14、21天组,每组5只.采用自体血体内注射法建立脑出血动物模型,用免疫组化法检测脑出血后血肿灶周脑组织中HIF -1α和COX -2蛋白的动态表达,并用干/湿比重法测定脑含水量.结果 脑出血后6h HIF - 1α、COX -2蛋白的表达和脑水含量明显升高,3~7天达到高峰,第14天明显降低,COX -2及脑水含量在21天基本降至正常.HIF - 1α在21天仍有较高水平的表达.造模后6h,脑出血组与假手术组相比,HIF -1 α及COX -2蛋白的表达和脑水含量明显增高,其差异有统计学意义(P<0.05).脑出血组的各时间点间比较,其差异均有统计学意义(P<0.05).HIF - 1α蛋白的表达与脑水含量呈正相关(r =0.636,P<0.01);COX -2蛋白的表达与脑水含量呈正相关(r=0.927,P<0.01).结论 大鼠脑出血后血肿灶周HIF -1α、COX -2蛋白的表达呈一定的变化规律.随着脑出血时间的延长HIF -1α蛋白、COX -2蛋白的表达程度和脑组织水肿程度呈正相关.%Objective To investigate the dynamic changes of HIF-lot and COX-2 protein in perihematoma after Intracerebral hemorrhage in rats, to analysis their correlation with the time of ICH and brain edema, and try to explore the mechanism of action of the expression HIF-lα and COX-2 protein on the brain tissue injury. Methods Thirty-five healthy SD rats were randomly divided into sham operation group (n=5) and ICH model groups (n =30). Rats were sacrificed at 6h,1days,3days,7days, 14days and 21 days after operation, respectively. The expressions of HIF-1α and COX-2 were investigated using immunohistochemistry, Brain water content was measured by the wet/dry specific gravity method. Results HIF-1

  19. Expression of COX during early embryonic development in zebrafish%COX基因在斑马鱼胚胎早期发育过程中的表达

    Institute of Scientific and Technical Information of China (English)

    韩勇军; 吴新荣

    2010-01-01

    目的 克隆斑马鱼COX-1、COX-2a基因,研究其在斑马鱼胚胎早期发育中的表达情况.方法 提取24 h斑马鱼胚胎的总RNA,制备DIG标记的COX-1、COX-2a RNA反义探针,整胚原位杂交研究COX-1、COX-2a在斑马鱼胚胎早期发育过程中的表达.结果 COX-1在囊胚期和原肠胚期为弥散性表达,18 h集中表达在后部躯干,到24 h,COX-1在输尿管和远端脊索处有表达,24~36 h,头部表达量高,48 h COX-1的表达弱.COX-2a在原肠胚期前不表达,在10.8 h开始表达,位于前端神经外胚层,在26 h,COX-2a在前脑、小脑和后脑有特异性表达.结论 明确了COX-1、COX-2a基因在斑马鱼胚胎发育过程中的表达模式,为研究该基因功能提供了一定的理论基础.

  20. Effect of Co element on microstructure and mechanical properties of FeCoxNiCuAl alloys

    Institute of Scientific and Technical Information of China (English)

    Yanxin ZHUANG; Wenjie LIU; Pengfei XING; Fei WANG; Jicheng HE

    2012-01-01

    FeCoxNiCuAl (x values in molar ratio,x=0.2,0.5,1,1.5,2 and 3) alloys were prepared using a suck-casting method.The effect of Co element on phase constituents,microstructure and mechanical properties of the FeCoxNiCuAl alloys was investigated using X-ray diffraction,scanning electron microscopy,optical microscopy and compressive tests.It was found that the Co addition has a significant influence on the structure and properties of the FeCoxNiCuAl alloys.The alloys have typical dendrite microstructure,and are composed of a simple fcc structure and bcc structure.The addition of Co promotes the formation of fcc phase in the alloys,retards the compressive strength and hardness of the alloys,and enhances the plasticity of the alloys.

  1. Crystalline NiCo2S4 nanotube array coated with amorphous NiCoxSy for supercapacitor electrodes.

    Science.gov (United States)

    Ding, Rui; Zhang, Mingyi; Yao, Yunhe; Gao, Hong

    2016-04-01

    Hierarchical NiCo2S4@NiCoxSy core/shell nanoarrays grown on carbon cloth were successfully synthesized via a two-step hydrothermal route and following an electrodeposition process. Compared with bare NiCo2S4, the electrochemical performance of NiCo2S4@NiCoxSy nanoarrays have been apparently improved, which shows areal capacitance as high as 3.9F/cm(2) at a constant current density of 1mA/cm(2). And the composite material exhibits excellent rate capability that a high areal capacitance of 2.9F/cm(2) is still retaining as the current density increase to 50mA/cm(2). The superior electrochemical performance can be attributed to the reasonably designed core/shell hierarchical structure of NiCo2S4@NiCoxSy nanoarrays, which would be promising for high-performance supercapacitor materials.

  2. The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

    Directory of Open Access Journals (Sweden)

    Takahiro Tsutsumimoto

    2014-11-01

    Full Text Available Neuroblastoma (NB, which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2. In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB.

  3. Association between COX-2 A1195G polymorphism with migraine in patients with consanguineous marriage of parents

    Directory of Open Access Journals (Sweden)

    Elahe Mozaffari

    2016-09-01

    Full Text Available Background: Migraine is a common debilitating headache with current head pain attacks which associated with temporal changes of head blood vessels diameter and  has been classified into two main categories, migraine with aura (MA and migraine without aura (MO by the International criteria for Headache Society (IHS. This study was performed with the aim of studying the association of COX-2-1195A →G gene polymorphism, risk of migraine susceptibility and  it’s relation with parent marriage type in two control and case groups. Materials and Methods: Genomic DNA of blood samples was purified from 100 migraine cases and 100 controls in this study. By using the appropriative COX-2-1195A→G (rs89466 primer and Pvu II restriction enzyme in PCR- RFLP manner the expected region of subject’s COX-2 gene was amplified and digested. Results: After analysising the data with SPSS twentieth version software, it was observed that frequency of COX-2-1195 GG and COX-2-1195 AG genotypes carriers in patients were higher than in the controls (9 percent and 41 percent in migraine cases, 5 percent and 24 percent in controls respectively; (P>0.010, also it was specificated that frequences of mentioned genotypes has been significantly higher in patients with relative parent than in control group (8.1 percent and 48.6 percent in cases with relative parent, 5 percent and 24 percent in controls respectively; (P>0.011. Conclusion: Regarding high frequency of polymorph allele (G in between patients with consanguineous parents, it can be resulted that consanguineous marriage increase the risk of this allele incidence and migraine outbreak. So, further studies with larger sample groups are needed on different nations of other regions to achieve better results about genetic of migraine, especially COX-2 gene.

  4. Comparison of Cox Model and K-Nearest Neighbor to Estimation of Survival in Kidney Transplant Patients

    Directory of Open Access Journals (Sweden)

    J. Faradmal

    2016-01-01

    Full Text Available Introduction & Objective: Cox model is a common method to estimate survival and validity of the results is dependent on the proportional hazards assumption. K- Nearest neighbor is a nonparametric method for survival probability in heterogeneous communities. The purpose of this study was to compare the performance of k- nearest neighbor method (K-NN with Cox model. Materials & Methods: This retrospective cohort study was conducted in Hamadan Province, on 475 patients who had undergone kidney transplantation from 1994 to 2011. Data were extracted from patients’ medical records using a checklist. The duration of the time between kidney transplantation and rejection was considered as the surviv­al time. Cox model and k- nearest neighbor method were used for Data modeling. The prediction error Brier score was used to compare the performance models. Results: Out of 475 transplantations, 55 episodes of rejection occurred. 5, 10 and 15 year survival rates of transplantation were 91.70 %, 84.90% and 74.50%, respectively. The number of neighborhood optimized using cross validation method was 45. Cumulative Brier score of k-NN algorithm for t=5, 10 and 15 years were 0.003, 0.006 and 0.007, respectively. Cumulative Brier of score Cox model for t=5, 10 and 15 years were 0.036, 0.058 and 0.058, respectively. Prediction error of k-NN algorithm for t=5, 10 and 15 years was less than Cox model that shows that the k-NN method outperforms. Conclusions: The results of this study show that the predictions of KNN has higher accuracy than the Cox model when sample sizes and the number of predictor variables are high. Sci J Hamadan Univ Med Sci . 2016; 22 (4 :300-308

  5. Inhibition of PKC-Induced COX-2 and IL-8 Expression in Human Breast Cancer Cells by Glucosamine.

    Science.gov (United States)

    Chou, Wan-Yu; Chuang, Kun-Han; Sun, David; Lee, Yu-Hsiu; Kao, Pu-Hong; Lin, Yen-Yu; Wang, Hsei-Wei; Wu, Yuh-Lin

    2015-09-01

    Breast cancer is a common cancer leading to many deaths among females. Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two highly expressed inflammatory mediators to be induced by the protein kinase C (PKC) signaling via various inflammatory stimuli and both contribute significantly to cancer metastasis/progression. Glucosamine has been shown to act as an anti-inflammation molecule. The aim of this study was to clarify the role and acting mechanism of glucosamine during the PKC-regulation of COX-2/IL-8 expression and the associated impact on breast cancer. In MCF-7 breast cancer cells, glucosamine effectively suppresses the PKC induction of COX-2 and IL-8 promoter activity, mRNA and protein levels, as well as the production of prostaglandin E(2) (PGE(2)) and IL-8. Glucosamine is able to promote COX-2 protein degradation in a calpain-dependent manner and IL-8 protein degradation in calpain-dependent and proteasome-dependent manners. The MAPK and NF-κB pathways are involved in PKC-induced COX-2 expression, but only the NF-κB pathway is involved in PKC-induced IL-8 expression. Glucosamine attenuates PKC-mediated IκBα phosphorylation, nuclear NF-κB translocation, and NF-κB reporter activation. Both PGE(2) and IL-8 promote cell proliferation and IL-8 induces cell migration; thus, glucosamine appears to suppress PKC-induced cell proliferation and migration. Furthermore, glucosamine significantly inhibits the growth of breast cancer xenografts and this is accompanied by a reduction in COX-2 and IL-8 expression. In conclusion, glucosamine seems to attenuate the inflammatory response in vitro and in vivo and this occurs, at least in part by targeting to the NF-κB signaling pathway, resulting in an inhibition of breast cancer cell growth.

  6. Low-level laser therapy in IL-1β, COX-2, and PGE2 modulation in partially injured Achilles tendon.

    Science.gov (United States)

    de Jesus, Julio Fernandes; Spadacci-Morena, Diva Denelle; dos Anjos Rabelo, Nayra Deise; Pinfildi, Carlos Eduardo; Fukuda, Thiago Yukio; Plapler, Helio

    2015-01-01

    This study evaluated IL-1β, COX-2, and PGE2 modulation in partially injured Achilles tendons treated with low-level laser therapy (LLLT). Sixty-five male Wistar rats were used. Sixty were submitted to a direct injury on Achilles tendon and then distributed into six groups: LASER 1 (a single LLLT application), LASER 3 (three LLLT applications), and LASER 7 (seven LLLT applications) and Sham 1, 3, and 7 (the same injury but LLLT applications were simulated). The five remaining animals were allocated at control group (no procedure performed). LLLT (780 nm) was applied with 70 mW of mean power and 17.5 J/cm(2) of fluency for 10 s, once a day. The tendons were surgically removed and assessed immunohistochemically for IL-1β, COX-2, and PGE2. In comparisons with control (IL-1β: 100.5 ± 92.5 / COX-2: 180.1 ± 97.1 / PGE2: 187.8 ± 128.8) IL-1β exhibited (mean ± SD) near-normal level (p > 0.05) at LASER 3 (142.0 ± 162.4). COX-2 and PGE2 exhibited near-normal levels (p > 0.05) at LASER 3 (COX-2: 176.9 ± 75.4 / PGE2: 297.2 ± 259.6) and LASER 7 (COX-2: 259.2 ± 190.4 / PGE2: 587.1 ± 409.7). LLLT decreased Achilles tendon's inflammatory process.

  7. Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2 pathway.

    Science.gov (United States)

    Zhou, Ru; Xu, Qingbin; Xu, Yehua; Xiong, Aiqin; Wang, Yang; Ma, Ping

    2016-12-01

    Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2 pathway. Copyright © 2016. Published by Elsevier Masson SAS.

  8. Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2 inhibitors

    Directory of Open Access Journals (Sweden)

    Alshafie Galal A

    2008-08-01

    Full Text Available Abstract Background Epidemiologic and laboratory investigations suggest that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs have chemopreventive effects against colon cancer perhaps due at least in part to their activity against cyclooxygenase-2 (COX-2, the rate-limiting enzyme of the prostaglandin cascade. Methods We conducted a case control study of colon cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 326 incident colon cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003–2004 and compared with 652 controls with no history of cancer and matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and colon cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR and 95% confidence intervals. Results Results showed significant risk reductions for selective COX-2 inhibitors (OR = 0.31, 95% CI = 0.16–0.57, regular aspirin (OR = 0.33, 95% CI = 0.20–0.56, and ibuprofen or naproxen (0.28, 95% CI = 0.15–0.54. Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg produced no significant change in the risk of colon cancer. Conclusion These results suggest that both non-selective and selective COX-2 inhibitors produce significant reductions in the risk of colon cancer, underscoring their strong potential for colon cancer chemoprevention.

  9. Experiments to Determine Whether Recursive Partitioning (CART) or an Artificial Neural Network Overcomes Theoretical Limitations of Cox Proportional Hazards Regression

    Science.gov (United States)

    Kattan, Michael W.; Hess, Kenneth R.; Kattan, Michael W.

    1998-01-01

    New computationally intensive tools for medical survival analyses include recursive partitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P less than 0.05) with a C improvement of 0.1 (95% Cl, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P less than 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

  10. JTE-522, a selective COX-2 inhibitor, inhibits growth of pulmonary metastases of colorectal cancer in rats

    Directory of Open Access Journals (Sweden)

    Enomoto Masayuki

    2005-03-01

    Full Text Available Abstract Background Epidemiological studies have shown that individuals who regularly consume NSAIDs have lower rates of mortality associated with colorectal cancer. Because COX-2 inhibitors prevent tumor growth through some mechanisms, we assessed the effect of JTE-522, a selective COX-2 inhibitor, on pulmonary metastases of colon cancer in a rat model. Methods A suspension of 5 × 106 RCN-9 (rat colon cancer cells was injected into the tail vein of 24 anesthetized male F344/DuCrj rats. Oral JTE-522 (0, 3, 10, or 30 mg/kg/day was administered from the day before RCN-9 injection until the end of the study. Twenty-four days later, the lungs were removed from sacrificed rats and weighed. Pulmonary metastatic tumors were microscopically evaluated in the largest cross sections. We also performed immunohistochemical staining for both COX-2 and VEGF. Results JTE-522 dose-dependently decreased lung weight (p = 0.001 and the size of pulmonary metastatic tumors (p = 0.0002. However, the differences in the number of metastatic tumors among 4 groups were insignificant. Significant adverse effects of JTE-522 were undetectable. Immunohistochemical staining showed high levels of both COX-2 and VEGF in pulmonary metastatic tumors. Conclusion JTE-522 dose-dependently decreased the size, but not the number of pulmonary metastases. COX-2 inhibitors might block metastatic tumor growth, but not actual metastasis. Selective COX-2 inhibitors might be useful as therapeutic agents that inhibit the growth of metastatic tumors, as well as the tumorigenesis of colorectal cancer.

  11. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

    Directory of Open Access Journals (Sweden)

    Mingzhu Zhuang

    Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma.

  12. Protective Role of Cyclooxygenase (COX)-2 in Experimental Lung Injury: Evidence of a Lipoxin A(4)-Mediated Effect.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia\\/reperfusion (I\\/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I\\/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I\\/R group); (3) I\\/R and SC236, a selective COX-2 inhibitor; (4) I\\/R and aspirin; and (5) I\\/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet\\/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I\\/R significantly increased tissue MPO, the wet\\/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I\\/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I\\/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

  13. Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil

    DEFF Research Database (Denmark)

    Harsløf, Laurine B. S.; Damsgaard, Camilla T.; Hellgren, Lars I.;

    2014-01-01

    in humans. We explored possible effect modification by FADS, PPARG2, and COX2 genotypes to support potential effects of n-3 LCPUFA on metabolic markers in infants. Danish infants (133) were randomly allocated to daily supplementation with a teaspoon (~5 mL/day) of fish oil (FO) or sunflower oil (SO) from 9...... to 18 months of age. Before and after the intervention, we assessed BP, erythrocyte n-3 LCPUFA, plasma lipid profile, insulin, and glucose in addition to functional single nucleotide polymorphisms in FADS, PPARG2, and COX2. At 18 months, plasma TAG was lower in the FO compared with SO group (p = 0...

  14. OPN、COX-2在骨肉瘤组织中的表达及临床意义%Expression and clinical significance of OPN and COX-2 in osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    Youqiao Liao; Feng Li; Xiaogang Hu

    2007-01-01

    Objective: To detect the expression of osteopontin (OPN) in benign and malignant bone tumors and investigate the prognostic influence of OPN expression on the outcome of osteosarcoma patients. Methods: Fifty-seven osteosarcomas and 11 osteoblastomas as well as 5 bone specimens with remodeling sites were immunohistochemically analyzed for expression of OPN and cyclooxygenase-2 (COX-2). Results: OPN was not detected in osteoblasts of remodeling sites. Osteoblastoma osteoblasts as well as osteoclastlike giant cells and osteosarcoma mononuclear cells showed variable staining. In osteosarcomas OPN and COX-2 expression correlated with each other (r = 0.390, P = 0.003, Spearman's test). Although osteosarcoma patients with high COX-2 expression showed a trend towards shorter overall survival (P = 0.0841, log-rank test),OPN expression had no influence on patients overall or on disease-free survival. Conclusion: Our data indicated that expression of this protein might be unregulated in bone neoplasia. Although OPN expression correlates with COX-2 expression in osteosarcomas, OPN expression does not provide predictive information about the outcome of osteosarcoma patients.

  15. The Double Cox Risk Model of Reinsurance with Portfolio and Excess of Loss%带投资组合和超额赔款的再保险双 Cox 风险模型

    Institute of Scientific and Technical Information of China (English)

    牛银菊; 罗永丽; 夏亚峰

    2014-01-01

    For the insurance company policy arrival process and claims process are Cox process,considering the in-surance company investment combination and reinsurance to evade bankruptcy,the classical risk model is general-ized and a double Cox risk model of reinsurance with portfolio and excess of loss is established. Using the knowledge of martingale theory,the upper bounds of ruin probability,Lundberg exponent and the ultimate ruin probability of this model are studied.%对于保单到达过程与索赔过程均为 Cox 过程的情况,考虑到保险公司为了规避风险进行投资组合和再保险,将经典风险模型推广,建立了一类再保险双 Cox 风险模型,运用鞅论方法得到了此模型 Lund-berg 指数上界和破产概率的上界,并给出了最终破产概率的解析表达式。

  16. Changes of three COX isoforms expression after formalin induced inflammatory pain in brain and analgesic effects of different COX inhibitors%福尔马林所致炎性痛后脑内三种COX亚型的变化及不同选择性COX抑制剂的镇痛效应比较

    Institute of Scientific and Technical Information of China (English)

    路志红; 熊晓云; 孟静茹; 刘振国; 王志鹏; 梅其炳

    2005-01-01

    目的:比较炎性痛后三种环氧合酶(cyclooxygenase,COX)亚型的表达变化,以及选择性COX抑制剂不同应用方式对炎性痛的镇痛效应.方法:小鼠足底注射福尔马林诱导炎性痛.用放射免疫分析及RT-PCR分别评估脑COX-1、COX-2及COX-3在福尔马林注射前、注射后1、12 h、1、3、7、14、30、60 d的变化.在镇痛效应的比较中,动物被分成5组:对照组、SC组、NS组、IN组及NS+SC组.前4组分别灌胃生理盐水、SC-560、NS-398和indomethacin.NS+SC组在前一个月接受NS-398,后一个月接受SC-560.测定各组动物在福尔马林注射前、注射后1、12 h、1、3、7、14、30、60 d的热痛阈.结果:COX-2的表达在炎性痛后12 h到3 d升高显著,而COX-1的表达在2周到2月升高显著.在整个观察时限内COX-3的表达无明显变化.与其他组相比,NS+SC组动物的热痛阈在整个炎性痛过程中均明显提高.结论:炎性痛后早期COX-2升高而晚期COX-1升高.COX-3变化不明显.COX-1抑制剂和COX-2抑制剂的结合使用比单纯使用其中一种能取得更好的镇痛效果.%AIM: To compare the expression of three cyclooxygenase (COX) isoforms in the process of inflammatory pain and evaluate the analgesic effects of different protocols about usage of COX inhibitors on inflammatory pain. METHODS: Formalin was injected subplantarly to mice to induce inflammatory pain. The expression of COX-1, COX-2 and COX-3 was evaluated by radioimmunoassay and RT-PCR, respectively. For the analgesic effect assay, animals were divided into 5 groups including control, SC, NS, IN and NS + SC group. The former 4 spectively. In the NS + SC group, animals received NS398 during the first 1 month and SC-560 during the second month in the NS + SC group. RESULTS: The expression of COX-1 was higher at the late phase while that of COX-2 was higher at the early phase of inflammatory pain. The expression of COX-3 did not significantly change in the process of inflammatory pain

  17. Relationship and significance of the expression of COX-2 and IL-8 in breast cancer%乳腺癌组织中COX-2与IL-8表达的相关性及临床意义

    Institute of Scientific and Technical Information of China (English)

    陈守华; 张丽丽; 顾禾; 付荣湛

    2008-01-01

    目的:探讨乳腺癌组织中环氧化酶-2(COX-2)和白细胞介素-8(IL-8)表达的相关性及临床意义.方法:采用免疫组织化学法对60例乳腺癌患者病理组织中的COX-2和IL-8进行检测,并与31例乳腺良性疾病对照,分析其相关性,以及二者与肿瘤大小、浸润程度、TNM分期、淋巴结转移及雌激素受体(estrogen receptor,ER)和孕激素受体(progesteronreceptor,PR)表达等生物学行为的关系.结果:乳腺癌组织中COX-2和IL-8阳性表达率分别为66.7%、60.0%均显著高于对照组(P=0.000 6、P=0.000 2),且二者表达存在明显正相关(r=0.433,P0.05).结论:COX-2和IL-8在乳腺癌组织中过度表达且呈正相关,提示乳腺癌组织中COX-2和IL-8存在相互调控机制,共同促进肿瘤的发生和发展.

  18. COX-2抑制剂对膀胱癌细胞株裸鼠成瘤的影响%Inhibitive effect of COX-2 on human bladder cancer cell xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    张军卫; 靳风烁; 龚晋迁; 彭东涛; 王刚; 程伟; 潘永军

    2013-01-01

    目的 探讨COX-2抑制剂对膀胱癌T24细胞株裸鼠成瘤性的影响.方法 BALB/c裸鼠27只分为3组,每只皮下接种膀胱癌T24细胞5×106活细胞数建立移植瘤动物模型.COX-2抑制剂药物干预组(吲哚美辛、塞来昔布)采用喂饲途径,吲哚美辛3 mg/kg,塞来昔布10 mg/kg;对照组给予生理盐水溶液药物的投给.30 d后处死裸鼠,取瘤块称重,测量肿瘤体积,行免疫组化、半定量RT-PCR、Wester Blot检测移植瘤COX-2表达.结果 对照组细胞接种裸鼠后第5天可见肿瘤长出,第7天各组均有肿瘤长出,第30天后用药组移植瘤生长较对照组明显减慢.免疫组化染色、RT-PCR、Western-blot结果均显示对照组COX-2表达明显,而药物干预组均少量表达.结论 选择性与非选择性COX-2抑制剂在实验中表现出良好的抗肿瘤特性.

  19. A duplicated coxI gene is associated with cytoplasmic male sterility in an alloplasmic Brassica juncea line derived from somatic hybridization with Diplotaxis catholica

    Indian Academy of Sciences (India)

    Aruna Pathania; Rajesh Kumar; V. Dinesh Kumar; Ashutosh; K. K. Dwivedi; P. B. Kirti; P. Prakash; V. L. Chopra; S. R. Bhat

    2007-08-01

    A cytoplasmic male sterile (CMS) line of Brassica juncea was derived by repeated backcrossing of the somatic hybrid (Diplotaxis catholica + B. juncea) to B. juncea. The new CMS line is comparable to euplasmic lines for almost all characters, except for flowers which bear slender, needle-like anthers with aborted pollen. Detailed Southern analysis revealed two copies of coxI gene in the CMS line. One copy, coxI-1 is similar to the coxI gene of B. juncea, whereas the second copy, coxI-2 is present in a novel rearranged region. Northern analysis with eight mitochondrial gene probes showed altered transcript pattern only for the coxI gene. Two transcripts of 2.0 and 2.4 kb, respectively, were detected in the CMS line. The novel 2.4 kb transcript was present in floral bud tissue but absent in the leaf tissue. In plants where male sterility broke down under high temperature during the later part of the growing season, the 2.4 kb coxI transcript was absent, which suggested its association with the CMS. The two coxI genes from the CMS line showed two amino acid changes in the coding region. The novel coxI gene showed unique repeats in the 5′ region suggesting recombination of mitochondrial genomes of the two species. The possible role of the duplicated coxI gene in causing male sterility is discussed.

  20. A recombination point is conserved in the mitochondrial genome of higher plant species and located downstream from the cox2 pseudogene in Solanum tuberosum L.

    Directory of Open Access Journals (Sweden)

    Susely F.S. Tada

    2006-01-01

    Full Text Available The potato (Solanum tuberosum L. mitochondrial cox3/sdh4/pseudo-cox2 gene cluster has previously been identified by heterologous hybridization using a Marchantia polymorpha sdh4 probe. In our present study we used Southern blotting using sdh4 and cox2 probes to show that the sdh4 and cox2 genes are clustered in the mitochondria of potato, soybean and pea. Northern blotting revealed cotranscription of sdh4 and cox2 in potato but not in cauliflower, indicating that these genes are not clustered in cauliflower. A putative recombination point was detected downstream of the cox2 pseudogene (pseudo-cox2 in potato mitochondrial DNA (mtDNA. This sequence corresponds to a 32 bp sequence which appears to be well-conserved and is adjacent to the terminals of some mitochondrial genes in Citrullus lanatus, Beta vulgaris and Arabidopsis thaliana and is probably involved in the genic rearrangements. It is possible the potato mtDNA pseudo-cox2 gene was generated by recombination during evolution in the same way as that of several other mitochondrial genes and remains as an inactive partial copy of the functional cox2 which was also detected in potato mtDNA.

  1. Phase equilibria and microstructure in Sr4Fe6-xCoxO13 0 <= x <= 4 mixed conductors

    DEFF Research Database (Denmark)

    Fossdal, A.; Sagdahl, L.T.; Einarsrud, M.A.;

    2001-01-01

    The densification, microstructure and phase evolution of Sr4Fe6-xCoxO13 (0 less than or equal to x less than or equal to 4) materials have been investigated by powder X-ray diffraction, electron microscopy and thermal analysis. Powders were prepared by the solid state reaction method or by the ED...

  2. Evolution of magnetic states in frustrated diamond lattice antiferromagnetic Co(Al1-xCox)(2)O-4 spinels

    DEFF Research Database (Denmark)

    Zaharko, O.; Cervellino, A.; Tsurkan, V.

    2010-01-01

    Using neutron powder diffraction and Monte Carlo simulations we show that a spin-liquid regime emerges at all compositions in the diamond-lattice antiferromagnets Co(Al1−xCox)2O4. This spin-liquid regime induced by frustration due to the second-neighbor exchange coupling J2 is gradually superseded...

  3. A novel COX-independent mechanism of sulindac sulfide involves cleavage of epithelial cell adhesion molecule protein.

    Science.gov (United States)

    Liggett, Jason L; Min, Kyung-Won; Smolensky, Dmitriy; Baek, Seung Joon

    2014-08-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the counter to treat headaches and inflammation as well as clinically to prevent cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX-independent activity which is not fully understood. In this study, we report a novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM) protein. EpCAM is a type I transmembrane glycoprotein that has been implemented as an over-expressed oncogene in many cancers including colon, breast, pancreas, and prostate. We found EpCAM to be down-regulated by SS in a manner that is independent of COX activity, transcription regulation, de novo protein synthesis, and proteasomal degradation pathway. Our findings clearly demonstrate that SS drives cleavage of the extracellular portion of EpCAM near the N-terminus. This SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply mutating arginine residues at positions 80 and 81 to alanine of EpCAM. Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect anti-tumorigenesis at the post-translational level.

  4. The Gastrointestinal and Cardiovascular Safety of COX-2 selective inhibitors in general practice: the contribution of Prescription-Event Monitoring

    NARCIS (Netherlands)

    Layton, D.

    2007-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for many conditions, especially in the elderly. Whilst effective, they also have side-effects, most commonly on the stomach. Advances in the understanding of how NSAIDs work in the body led to newer NSAIDs (COX-2 selective inhibitors whi

  5. Isolation of linoleic and alpha-linolenic acids as COX-1 and -2 inhibitors in rose hip

    DEFF Research Database (Denmark)

    Jäger, Anna; Petersen, K N; Thomasen, G.

    2008-01-01

    Rose hip has previously shown clinical efficacy in the treatment of osteoarthritis, and organic solvent extracts of rose hip have showed inhibition of cyclooxygenase-1 and -2. A petroleum ether extract of rose hip was fractioned by VLC on silica; on a C-18 column and by HPLC. Each step was COX-1/...

  6. Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers.

    NARCIS (Netherlands)

    Hougee, S.; Faber, J.; Sanders, A.; Jong, R.B. de; Berg, W.B. van den; Garssen, J.; Hoijer, M.A.; Smit, H.F.

    2005-01-01

    In this study, an extract of Pterocarpus marsupium Roxb. containing pterostilbene has been evaluated for its PGE2-inhibitory activity in LPS-stimulated PBMC. In addition, the COX-1/2 selective inhibitory activity of P. marsupium (PM) extract was investigated. Biological activity, as well as safety

  7. Helicobacter pylori outer membrane vesicles inhibit human T cell responses via induction of monocyte COX-2 expression.

    Science.gov (United States)

    Hock, Barry D; McKenzie, Judith L; Keenan, Jacqueline I

    2017-06-01

    The modulation of T cell responses by Helicobacter pylori is thought to potentiate both H. pylori persistence and development of gastric pathologies including cancer. Release of outer membrane vesicles (OMV) by H. pylori provides a potential vehicle for modulation of the immune system. Although OMV are thought to have T cell suppressive activity, this has not yet been demonstrated. Their suppressive activity was investigated in this study using the responses of peripheral blood mononuclear cells (PBMC) to T cell stimuli as a readout. We demonstrate that addition of OMV to PBMC significantly inhibits subsequent T cell proliferation in a cyclo-oxygenase-2 (COX-2)-dependent manner. Addition of OMV did not significantly modulate PBMC apoptosis, but induced strong expression of COX-2 by the monocytes present and significantly increased levels of PGE2 and IL-10. These effects were independent of vacuolating cytotoxin expression. Together, these findings demonstrate that OMV can suppress human T cell responses and that the predominant mechanism is not through a direct effect on the T cells but results from the induction of COX-2 expression in monocytes. This increased COX-2 activity may modulate not only H. pylori-directed immune responses but also wider immune responses. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Structured Spatio-temporal shot-noise Cox point process models, with a view to modelling forest fires

    DEFF Research Database (Denmark)

    Møller, Jesper; Diaz-Avalos, Carlos

    2010-01-01

    Spatio-temporal Cox point process models with a multiplicative structure for the driving random intensity, incorporating covariate information into temporal and spatial components, and with a residual term modelled by a shot-noise process, are considered. Such models are flexible and tractable...

  9. Structured spatio-temporal shot-noise Cox point process models, with a view to modelling forest fires

    DEFF Research Database (Denmark)

    Møller, Jesper; Diaz-Avalos, Carlos

    Spatio-temporal Cox point process models with a multiplicative structure for the driving random intensity, incorporating covariate information into temporal and spatial components, and with a residual term modelled by a shot-noise process, are considered. Such models are flexible and tractable...

  10. Reduced Risk of Human Lung Cancer by Selective Cyclooxygenase 2 (Cox-2 Blockade: Results of a Case Control Study

    Directory of Open Access Journals (Sweden)

    Randall E. Harris, Joanne Beebe-Donk, Galal A. Alshafie

    2007-01-01

    Full Text Available We conducted a case control study of selective cyclooxygenase-2 (COX-2 blocking agents and lung cancer. A total of 492 newly diagnosed lung cancer cases were ascertained during January 1, 2002 to September 30, 2004, at The Ohio State University Medical Center, Columbus, Ohio. All cases were confirmed by examination of the pathology report. Healthy population controls without cancer were ascertained during the same time period. Controls were frequency matched at a rate of 2:1 to the cases by age, gender, and county of residence. We collected information on type, frequency, and duration of use of selective COX-2 inhibitors (primarily celecoxib or rofecoxib and nonselective NSAIDs such as ibuprofen and aspirin. Estimates of odds ratios (OR were obtained with adjustment for cigarette smoking, age and other potential confounders using logistic regression analysis. Odds Ratios for selective COX-2 inhibitors were adjusted for past use of other NSAIDs. Use of any selective COX-2 inhibitor for more than one year produced a significant (60% reduction in the risk of lung cancer (OR=0.40, 95% CI=0.19-0.81. Observed risk reductions were consistent for men (OR=0.26, 95% CI=0.10-0.62 and women (OR=0.52, 95% CI=0.24-1.13 and for individual COX-2 inhibitors (OR=0.28, 95% CI=-0.12-0.67, for celecoxib and OR=0.55, 95% CI=0.19-1.56, for rofecoxib. Intake of ibuprofen or aspirin also produced significant risk reductions (OR=0.40, 95% CI=0.23-0.73 and OR=0.53, 95% CI=0.34-0.82, respectively, whereas acetaminophen, an analgesic with negligible COX-2 activity, had no effect on the risk (OR=1.36, 95% CI=0.53-3.37. This investigation demonstrates for the first time that selective COX-2 blocking agents have strong potential for the chemoprevention of human lung cancer.

  11. Synthesis, anti-inflammatory, analgesic, COX1/2-inhibitory activity, and molecular docking studies of hybrid pyrazole analogues

    Directory of Open Access Journals (Sweden)

    Alam MJ

    2016-10-01

    Full Text Available Md Jahangir Alam,1 Ozair Alam,1 Suroor Ahmad Khan,1 Mohd Javed Naim,1 Mohammad Islamuddin,2 Girdhar Singh Deora3 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 2Parasite Immunology Laboratory, Department of Biotechnology, Faculty of Science, Jamia Hamdard, New Delhi, 3Institute of Life Sciences, University of Hyderabad, Hyderabad, India Abstract: This article reports on the design, synthesis, and pharmacological activity of a new series of hybrid pyrazole analogues: 5a–5u. Among the series 5a–5u, the compounds 5u and 5s exhibited potent anti-inflammatory activity of 80.63% and 78.09% and inhibition of 80.87% and 76.56% compared with the standard drug ibuprofen, which showed 81.32% and 79.23% inhibition after 3 and 4 hours, respectively. On the basis of in vivo studies, 12 compounds were selected for assessment of their in vitro inhibitory action against COX1/2 and TNFα. The compounds 5u and 5s showed high COX2-inhibitory activity, with half-maximal inhibitory concentrations of 1.79 and 2.51 µM and selectivity index values of 72.73 and 65.75, respectively, comparable to celecoxib (selectivity index =78.06. These selected compounds were also tested for TNFα, cytotoxicity, and ulcerogenicity. Docking studies were also carried out to determine possible interactions of the potent compounds (5u and 5s, which also showed high docking scores of -12.907 and -12.24 compared to celecoxib, with a -9.924 docking score. These selective COX2 inhibitors were docked into the active site of COX2, and showed the same orientation and binding mode to that of celecoxib (selective COX2 inhibitor. Docking studies also showed that the SO2NH2 of 5u and 5s is inserted deep inside the selective pocket of the COX2-active site and formed a hydrogen-bond interaction with His90, Arg513, Phe518, Ser353, Gln192, and Ile517, which was further validated by superimposed docked pose with celecoxib. Keywords: anti-inflammatory activity, analgesic activity

  12. Quantum Criticality and Superconductivity in SmFe1-xCoxAsO

    Science.gov (United States)

    Kaneko, H.; Yun, Y.; Shumsun, N.; Savinkov, A.; Suzuki, H.; Li, Y. K.; Tao, Q.; Cao, G. H.; Xu, Z. A.

    2012-12-01

    One of the iron pnictide superconductors, SmFe1-xCoxAsO shows a domelike TC curve against Co concentration x. The parent compound SmFeAsO shows the crystal structure transition and antiferromagnetic spin density wave (SDW) ordering. With increasing x, the structural transition temperature TD and SDW ordering temperature TN decrease and reach 0 K at the critical concentration xC. It is not so clear that the critical concentrations for TD and for TN coincident to each other or not. In our present report, we investigated the structural transition by the low temperature x-ray diffraction and the SDW ordering and the superconducting transition by measuring the magnetization using the SQUID magnetometer, MPMS We determined the phase diagram of TD, TN and the superconductive transition temperature TC against the Co concentration x near the xC precisely. We found that the maximum of TC in domelike shape locates near the xC, suggesting the QCP.

  13. QSAR Studies on the COX-2 Inhibition by 3,4-Diarylcycloxazolones Based on MEDV Descriptor

    Institute of Scientific and Technical Information of China (English)

    刘树深; 崔世海; 尹大强; 施蕴渝; 王连生

    2003-01-01

    Selective inhibition of cyclooxygenase-2 (COX-2) might avoid the side effects of current available nonsteroidal antiinflammatory drugs while retaining their therapeutic efficacy. A novel variable selection and modeling method based on prediction is developed to construct the quantitative structure-activity relationships (QSAR) between the molecular electronegativity distance vector (MEDV) based on 13 atomic types and the biological activities of a set of selective cyclooxygenase-2 inhibitory molecules, 3,4-diarylcycloxazolones (DAA) plus indomethacin,naproxen, and celecoxib. Using multiple linear regression, a 5-variable linear model is developed with the calibrated correlation coefficient of 0.9271 and root mean square error of 0.17 in modeling stage and the validated correlation coefficient of 0.9030 and root mean square error of 0.20 in leave-one-out validation step, respectively. To further test the predictive ability of the model, 20 DAA compounds are picked up to construct a training set which is used to build a QSAR model and then the model is employed to predict the biological activities of the balance compounds. The predicted correlation coefficient and root mean square error are 0.9332 and 0.19, respectively.

  14. Prospective performance evaluation of selected common virtual screening tools. Case study: Cyclooxygenase (COX) 1 and 2.

    Science.gov (United States)

    Kaserer, Teresa; Temml, Veronika; Kutil, Zsofia; Vanek, Tomas; Landa, Premysl; Schuster, Daniela

    2015-01-01

    Computational methods can be applied in drug development for the identification of novel lead candidates, but also for the prediction of pharmacokinetic properties and potential adverse effects, thereby aiding to prioritize and identify the most promising compounds. In principle, several techniques are available for this purpose, however, which one is the most suitable for a specific research objective still requires further investigation. Within this study, the performance of several programs, representing common virtual screening methods, was compared in a prospective manner. First, we selected top-ranked virtual screening hits from the three methods pharmacophore modeling, shape-based modeling, and docking. For comparison, these hits were then additionally predicted by external pharmacophore- and 2D similarity-based bioactivity profiling tools. Subsequently, the biological activities of the selected hits were assessed in vitro, which allowed for evaluating and comparing the prospective performance of the applied tools. Although all methods performed well, considerable differences were observed concerning hit rates, true positive and true negative hits, and hitlist composition. Our results suggest that a rational selection of the applied method represents a powerful strategy to maximize the success of a research project, tightly linked to its aims. We employed cyclooxygenase as application example, however, the focus of this study lied on highlighting the differences in the virtual screening tool performances and not in the identification of novel COX-inhibitors.

  15. Cooperative nucleation modes in polycrystalline CoxPd1-x nanowires

    Science.gov (United States)

    Viqueira, M. S.; Pozo-López, G.; Urreta, S. E.; Condó, A. M.; Cornejo, D. R.; Fabietti, L. M.

    2015-05-01

    Polycrystalline CoxPd1-x (x = 1, 0.60, 0.45, 0.23, and 0.11) cylindrical nanowires (ø = 18-35 nm, about 1 μm length) are produced by AC electrodeposition into hexagonally ordered alumina pores. Single-phase nanowires of an fcc Co-Pd solid solution, with randomly oriented equiaxed grains (7-12 nm) are obtained; in all the cases, the grain size is smaller than the wire diameter. The coercive field and the reduced remanence of Co-rich nanowire arrays are hardly sensitive to temperature within the range varying from 4 K to 300 K. On the other hand, in Pd-rich nanowires both magnitudes are smaller and they largely increase when cooling below 100 K. This behavior also depends on the mean grain size. These facts are systematized considering two main aspects: the non-trivial temperature and composition dependence of the crystalline anisotropy and the saturation magnetostriction in Co-Pd alloys; and a random anisotropy effect, which defines a nucleation localization length that may involve more than a single grain, and thus promotes more cooperative nucleation modes.

  16. FGFR1-induced epithelial to mesenchymal transition through MAPK/PLCγ/COX-2-mediated mechanisms.

    Directory of Open Access Journals (Sweden)

    Darren C Tomlinson

    Full Text Available Tumour invasion and metastasis is the most common cause of death from cancer. For epithelial cells to invade surrounding tissues and metastasise, an epithelial-mesenchymal transition (EMT is required. We have demonstrated that FGFR1 expression is increased in bladder cancer and that activation of FGFR1 induces an EMT in urothelial carcinoma (UC cell lines. Here, we created an in vitro FGFR1-inducible model of EMT, and used this model to identify regulators of urothelial EMT. FGFR1 activation promoted EMT over a period of 72 hours. Initially a rapid increase in actin stress fibres occurred, followed by an increase in cell size, altered morphology and increased migration and invasion. By using site-directed mutagenesis and small molecule inhibitors we demonstrated that combined activation of the mitogen activated protein kinase (MAPK and phospholipase C gamma (PLCγ pathways regulated this EMT. Actin stress fibre formation was regulated by PLCγ activation, and was also important for the increase in cell size, migration and altered morphology. MAPK activation regulated migration and E-cadherin expression, indicating that combined activation of PLCγ and MAPK is required for a full EMT. We used expression microarrays to assess changes in gene expression downstream of these signalling cascades. COX-2 was transcriptionally upregulated by FGFR1 and caused increased intracellular prostaglandin E(2 levels, which promoted migration. In conclusion, we have demonstrated that FGFR1 activation in UC cells lines promotes EMT via coordinated activation of multiple signalling pathways and by promoting activation of prostaglandin synthesis.

  17. Microvascular COX-2/mPGES-1/EP-4 axis in human abdominal aortic aneurysm.

    Science.gov (United States)

    Camacho, Mercedes; Dilmé, Jaume; Solà-Villà, David; Rodríguez, Cristina; Bellmunt, Sergi; Siguero, Laura; Alcolea, Sonia; Romero, José-María; Escudero, José-Román; Martínez-González, José; Vila, Luis

    2013-12-01

    We investigated the prostaglandin (PG)E2 pathway in human abdominal aortic aneurysm (AAA) and its relationship with hypervascularization. We analyzed samples from patients undergoing AAA repair in comparison with those from healthy multiorgan donors. Patients were stratified according to maximum aortic diameter: low diameter (LD) (PGE2 metabolites were higher in AAA than in controls (plasma-controls, 19.9 ± 2.2; plasma-AAA, 38.8 ± 5.5 pg/ml; secretion-normal aorta, 16.5 ± 6.4; secretion-AAA, 72.9 ± 6.4 pg/mg; mean ± SEM). E-prostanoid receptor (EP)-2 and EP-4 were overexpressed in AAA, EP-4 being the only EP substantially expressed and colocalized with mPGES-1 in the microvasculature. Additionally, EP-4 mediated PGE2-induced angiogenesis in vitro. We provide new data concerning mPGES-1 expression in human AAA. Our findings suggest the potential relevance of the COX-2/mPGES-1/EP-4 axis in the AAA-associated hypervascularization.

  18. Cox-Maze III procedure with valvular surgery in an autopneumonectomized patient

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    Wi Jin

    2012-11-01

    Full Text Available Abstract Destructive pulmonary inflammation can leave patients with only a single functional lung, resulting in anatomical and physiological changes that may interfere with subsequent cardiac surgeries. Such patients are vulnerable to perioperative cardiopulmonary complications. Herein, we report the first case, to our knowledge, of an autopneumonectomized patient who successfully underwent a modified Cox-Maze III procedure combined with valvular repairs. The three major findings in this case can be summarized as follows: (1 a median sternotomy with peripheral cannulations, such as femoral cannulations, can provide an optimal exposure and prevent the obstruction of vision that may occur as a result of multiple cannulations through a median sternotomy; (2 a modified septal incision combined with biatrial incisions facilitate adequate exposure of the mitral valve; and (3 the aggressive use of intraoperative ultrafiltration may be helpful for the perioperative managements as decreasing pulmonary water contents, thereby avoiding the pulmonary edema associated with secretion of inflammatory cytokines during a cardiopulmonary bypass. We also provide several suggestions for achieving similar satisfactory surgical outcomes in patients with a comparable condition.

  19. Kondo effect and quantum critical point in Mn(1-x)CoxSi

    Science.gov (United States)

    Teyssier, J.; Viennois, R.; Guritanu, V.; Giannini, E.; van der Marel, D.

    2010-01-01

    We report magnetic, transport and neutron diffraction studies of the solid solution Mn1-xCoxSi. For the Mn rich compounds, a sharp decrease of the Curie temperature is observed upon cobalt doping and neutron elastic scattering shows that the helimagnetic order of MnSi persists up to x = 0.06 with a shortening of the helix period. For higher Co concentrations (0.06 Weiss temperature changes sign and the system enters an antiferromagnetic state upon cooling (TN=9K for x = 0.50). In this doping range, the antiferromagnetic coupling leads to a Kondo effect marked by a minimum in the resistivity. This scenario is supported by the scaling of the magnetoresistance with a TK approx 6.5 K, close to the change in curvature of the resistivity and in agreement with the Weiss temperature from magnetic susceptibility. The sign change of the Weiss temperature and the transition from a helimagnetic to an antiferromagnetic ground state, with increasing the Co doping, point toward the existence of a quantum critical point at the composition Mn0.94Co0.06Si.

  20. Cox4i2, Ifit2, and Prdm11 Mutant Mice

    DEFF Research Database (Denmark)

    Horsch, Marion; Aguilar-Pimentel, Juan Antonio; Bönisch, Clemens

    2015-01-01

    and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared...... to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression...... in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition...

  1. Evidence of new species of Haematoloechus (Platyhelminthes: Digenea) using partial cox1 sequences.

    Science.gov (United States)

    León-Règagnon, Virginia

    2010-12-01

    Haematoloechus, digeneans parasites of amphibians, is a species-rich genus with more than 50 species around the globe. Establishing an accurate taxonomy for this group has been difficult due to high intraspecific variability. Nuclear DNA sequences have given independent information about species validity and phylogeny of the group. In this paper, I test the performance of partial sequences of the mitochondrial cytochrome c oxidase subunit I (cox1) gene in the differentiation of recognized species of the genus and in the detection of potential new taxa. Samples from 13 nominal species were sequenced, plus four samples that could not be assigned to any described species based on morphology. Parsimony analysis of the amplified 360 bp fragment resulted in six most parsimonious trees showing the same grouping of samples, differing in the samples' arrangement within those groups. All 13 species were recovered on the trees, and five potential new species are shown. Additional sampling and sequencing is necessary to support this hypothesis, but with this preliminary information the search for diagnostic characters that allow the description of the new taxa is less difficult.

  2. Perpendicular magnetic anisotropy in Fe2Cr1 - xCoxSi Heusler alloy

    Science.gov (United States)

    Wang, Yu-Pu; Qiu, Jin-Jun; Lu, Hui; Ji, Rong; Han, Gu-Chang; Teo, Kie-Leong

    2014-12-01

    Perpendicular magnetic anisotropy (PMA) was achieved in annealed Fe2Cr1 - xCoxSi (FCCS) Heusler alloys with different Co compositions x. The Co composition is varied to tune the Fermi level in order to achieve both higher spin polarization and better thermal stability. The PMA is thermally stable up to 400 oC for FCCS with x = 0, 0.3, 0.5 and 350 oC for FCCS with x = 0.7, 0.9, 1. The thickness of FCCS films with PMA ranges from 0.6 to 1.2 nm. The annealing temperature and FCCS thickness are found to greatly affect the PMA. The magnetic anisotropy energy density KU is 2.8  ×  106 erg cm-3 for 0.8 nm Fe2CrSi, and decreases as the Co composition x increases, suggesting that the PMA induced at the FCCS/MgO interface is dominated by the contribution of Fe atoms. There is a trade-off between high spin polarization and strong PMA by adjusting the Co composition.

  3. Nonidentical twins: Comparison of frequentist and Bayesian lasso for Cox models.

    Science.gov (United States)

    Zucknick, Manuela; Saadati, Maral; Benner, Axel

    2015-11-01

    One important task in translational cancer research is the search for new prognostic biomarkers to improve survival prognosis for patients. The use of high-throughput technologies allows simultaneous measurement of genome-wide gene expression or other genomic data for all patients in a clinical trial. Penalized likelihood methods such as lasso regression can be applied to such high-dimensional data, where the number of (genomic) covariables is usually much larger than the sample size. There is a connection between the lasso and the Bayesian regression model with independent Laplace priors on the regression parameters, and understanding this connection has been useful for understanding the properties of lasso estimates in linear models (e.g. Park and Casella, 2008). In this paper, we study the lasso in the frequentist and Bayesian frameworks in the context of Cox models. For the Bayesian lasso we extend the approach by Lee et al. (2011). In particular, we impose the lasso penalty only on the genome features, but not on relevant clinical covariates, to allow the mandatory inclusion of important established factors. We investigate the models in high- and low-dimensional simulation settings and in an application to chronic lymphocytic leukemia.

  4. A Modified Adaptive Lasso for Identifying Interactions in the Cox Model with the Heredity Constraint.

    Science.gov (United States)

    Wang, Lu; Shen, Jincheng; Thall, Peter F

    2014-10-01

    In many biomedical studies, identifying effects of covariate interactions on survival is a major goal. Important examples are treatment-subgroup interactions in clinical trials, and gene-gene or gene-environment interactions in genomic studies. A common problem when implementing a variable selection algorithm in such settings is the requirement that the model must satisfy the strong heredity constraint, wherein an interaction may be included in the model only if the interaction's component variables are included as main effects. We propose a modified Lasso method for the Cox regression model that adaptively selects important single covariates and pairwise interactions while enforcing the strong heredity constraint. The proposed method is based on a modified log partial likelihood including two adaptively weighted penalties, one for main effects and one for interactions. A two-dimensional tuning parameter for the penalties is determined by generalized cross-validation. Asymptotic properties are established, including consistency and rate of convergence, and it is shown that the proposed selection procedure has oracle properties, given proper choice of regularization parameters. Simulations illustrate that the proposed method performs reliably across a range of different scenarios.

  5. Effect of growth retardants, cytokinins and auxins on the multiplication and rooting in vitro of Alstroemeria x hybrida "Juanita"

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    Małgorzata Podwyszyńska

    2013-12-01

    Full Text Available Rhizome cultures of "Jiianita" Polish cultivar of Alstroemeria x hybrida were used to enhance an effectiveness of micropropagation method of new cultivars and selections. The effect of cytokinins (BAP. kinetin and 2iP, auxins (IAA, IBAand NAA, growth retardants (paclobutrazol and flurprimidol alone or in combination were studied in relation to rhizome branching. aerial shoot production and rooting of rhizome. The greatest number of aerial shoots as well as the shortest shoots were observed at the highest BAP concentration (6 mg l-1. However, the rhizonies had the poorest rooting ability. BAP at low concentrations combined with kinetin or 2iP also strongly stimulated aerial shoot formation and rhizome branching. Unfortunately. those shoots were of poor qualily. Application of BAP at low concentration with paclobutrazol (0,1-0,5 mg l-1 or flurprimidol (0,01- 1 mg l-1 in presence of 1 mg l-1 NAA resulted in high number of aerial shoots (5-6, reduction of their length and higher rooting ability of the rhizomes. Gr(wth retardants applied with NAA strongly stimulated formation of the roots but suppressed their elongation. Abbreviations: BAP - 6=benzylaminopurine; kinetin - 6-furfurylaminopurine; 2iP - 6-‌γ,γ-dime-thylallylamino]purine; IAA-indole-3-acetic acid; IBA-indole-3-butyric acid; NAA- naphthaleneacetic acid; paclobutrazol (ICI PP-333 - (2-RS,3-RS-1-(4-chlorophenyl-4-4-dimethyl-2(1,2,3-triazol-1-yl-pentan-3-ol flurprimidol (Dowelanco - α-(1-niethylethy 1-α-[4-trifluro-niethoxyphenyl]-5-pyridinemethanol.

  6. -765 G>C POLYMORPHISM OF THE COX-2 GENE AND GASTRIC CANCER RISK IN BRAZILIAN POPULATION

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    Vanessa Maria de Lima Pazine CAMPANHOLO

    2014-04-01

    Full Text Available Context Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. Objectives To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. Methods One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. Results G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033. A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90. Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. Conclusions The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.

  7. Prognostic implications of tumor volume response and COX-2 expression change during radiotherapy in cervical cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Jae Myoung; Park, Won; Huh, Seung Jae; Cho, Eun Yoon; Choi, Yoon La; Bae, Duk Soo; Kim, Byoung Gie [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-12-15

    The relationship between treatment outcomes, alteration of the expression of biological markers, and tumor volume response during radiotherapy (RT) in patients with uterine cervical cancer was analyzed. Twenty patients with cervical squamous cell carcinoma received definitive RT with (n = 17) or without (n = 3) concurrent chemotherapy. Tumor volumes were measured by three serial magnetic resonance imaging scans at pre-, mid-, and post-RT. Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining for cyclooxygenase (COX)-2 and epidermal growth factor receptor was performed. The median follow-up duration was 60 months. The median tumor volume response at mid-RT (V2R) was 0.396 (range, 0.136 to 0.983). At mid-RT, an interval increase in the distribution of immunoreactivity for COX-2 was observed in 8 patients, and 6 of them showed poor mid-RT tumor volume response (V2R {>=} 0.4). Four (20%) patients experienced disease progression after 10 to 12 months (median, 11 months). All 4 patients had poor mid-RT tumor volume response (p = 0.0867) and 3 of them had an interval increase in COX-2 expression. Overall survival (OS) and progression-free survival (PFS) decreased in patients with V2R {>=} 0.4 (p 0.0291 for both). An interval increase in COX-2 expression at mid-RT was also associated with a decreased survival (p = 0.1878 and 0.1845 for OS and PFS, respectively). Poor tumor volume response and an interval increase in COX-2 expression at mid-RT decreased survival outcomes in patients with uterine cervical cancer.

  8. Immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenoma and non-neoplastic mucosa

    Science.gov (United States)

    Nogueira, Renan Brito; Pires, Andréa Rodrigues Cordovil; Soares, Thélia Maria Santos; Rodrigues, Simone Rabello de Souza; Campos, Mariane Antonieta Menino; Toloi, Giovanna Canato; Waisberg, Jaques

    2013-01-01

    ABSTRACT Objective: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. Methods: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. Results: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. Conclusion: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa. PMID:24488384

  9. Limited efficacy of COX-2 inhibitors on nerve growth factor and metalloproteinases expressions in human synovial fibroblasts.

    Science.gov (United States)

    Yorifuji, Makiko; Sawaji, Yasunobu; Endo, Kenji; Kosaka, Taiichi; Yamamoto, Kengo

    2016-05-01

    Nerve growth factor (NGF) is associated with arthritic pain and metalloproteinases are implicated in collagen and aggrecan degradation. Although selective COX-2 inhibitors are recommended for the treatment of arthritic diseases, their effects on NGF and metalloproteinases remain unclear. This study investigated the regulations of NGF and metalloproteinases by selective COX-2 inhibitors in isolated human synovial cells. The isolated human synovial cells were stimulated with IL-1β in the presence of selective COX-2 inhibitors (NS-398 or celecoxib) with or without exogenous PGE2 or its receptor (EP1-4) agonists. The expressions of NGF, MMP-1, -3, -13, ADAMTS-4, and -5 were quantified by real-time PCR and their proteins were determined by Western blotting. The amount of PGE2 released was measured by enzyme-linked immunosorbent assay (ELISA). The IL-1β inductions of NGF and MMP-1 and MMP-13 were augmented by the COX-2 inhibitors, whereas the inductions of ADAMTS-4 and ADAMTS-5 were inhibited. These actions were reversed by supplementing PGE2 or the EP4 agonist exogenously. Our comprehensive analysis revealed that COX-2 inhibitors may be beneficial for suppressing aggrecan degradation and for reducing inflammatory pain by inhibiting PGE2 release, although they may have limited efficacy in suppressing collagen degradation and nerve growth. This study suggests the feedback roles of PGE2 in the negative regulation of NGF and MMP-1 and MMP-13 and the positive regulation of ADAMTS-4 and ADAMTS-5. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  10. The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients.

    Science.gov (United States)

    Morel, Agnieszka; Miller, Elzbieta; Bijak, Michal; Saluk, Joanna

    2016-09-01

    Platelet activation is increasingly postulated as a possible component of the pathogenesis of multiple sclerosis (MS), especially due to the increased risk of cardiovascular events in MS. Arachidonic acid cascade metabolized by cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our study was to investigate the COX-dependent arachidonic acid metabolic pathway in blood platelets from secondary progressive multiple sclerosis (SP MS) patients. The blood samples were obtained from 50 patients (man n = 22; female n = 28), suffering from SP MS, diagnosed according to the revised McDonald criteria. Platelet aggregation was measured in platelet-rich plasma after arachidonic acid stimulation. The level of COX activity and thromboxane B2 concentration were determined by ELISA method. Lipid peroxidation was assessed by measuring the level of malondialdehyde. The results were compared with a control group of healthy volunteers. We found that blood platelets obtained from SP MS patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger (about 14 %) relative to control. We also observed a significantly increased activity of COX (about 40 %) and synthesis of thromboxane B2 (about 113 %). The generation of malondialdehyde as a marker of lipid peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase-dependent arachidonic acid metabolism is significantly increased in blood platelets of patients with SP MS. Future clinical studies are required to recommend the use of low-dose aspirin, and possibly other COX inhibitors in the prevention of cardiovascular risk in MS.

  11. Artesunate Induces Apoptosis of Bladder Cancer Cells by miR-16 Regulation of COX-2 Expression

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    Wei Zuo

    2014-08-01

    Full Text Available Bladder cancer is the most common malignant tumor of the urinary tract and remains one of the major causes of cancer death worldwide. In this study, we investigated the effect and mechanism of Artesunate (ART, a traditional Chinese medicine, on inducing apoptosis of human bladder cancer cells. In vivo antitumor activity was investigated in bladder cancer in rat by subcutaneous injection of different concentration of ART. The effect of ART on growth inhibition and apoptosis of bladder cancer cells was evaluated using dimethylthiazoly-2,5-diphenyltetrazolium bromide (MTT assay and flow cytometry analysis, respectively. Cyclooxygenase-2 (COX-2 and miR-16 expression levels were determined with real-time PCR. The concentrations of prostaglandin E2 (PGE2 in the supernatants of bladder cancer cells were measured with an ELISA kit. The miR-16 inhibitor or mimic were transfected into cells to up- or down-regulate miR-16 expression. ART efficiently inhibited orthotopic tumor growth in the bladder cancer rat, which is accompanied with an increase of miR-16 expression and a decrease of COX-2 expression. In vitro, ART could induce cytotoxicity and apoptosis in bladder cancer cells, but presented a much lighter toxicity effect against normal human urothelial cells. ART significantly increased miR-16 expression and decreased the expression of COX-2 and the production of PGE2. More importantly, down-regulation of miR-16 expression could reverse the effect of ART on apoptosis and COX-2 expression in bladder cells. Moreover, exogenous PGE2 could inhibit apoptosis of bladder cancer cells treated with ART. In conclusion, ART can elicit an anti-tumor effect against bladder cancer by up-regulation of miR-16 expression, which resulted in the decrease of COX-2 expression and PGE2 production. Hence, ART might be an effective drug for the treatment of bladder cancer.

  12. COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ

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    Wiley Elizabeth L

    2008-01-01

    Full Text Available Abstract Background In women with duct carcinoma in-situ (DCIS receiving breast conservation therapy (BCT, in-breast recurrences are seen in approximately 10%, but cannot be accurately predicted using clinical and histological criteria. We performed a case-control study to identify protein markers of local recurrence risk in DCIS. Methods Women treated for DCIS with BCT, who later developed in-breast recurrence (cases were matched by age and year of treatment to women who remained free of recurrence (controls. Results A total of 69 women were included in the study, 31 cases and 38 controls. Immunohistochemical evaluation of DCIS tissue arrays was performed for estrogen receptor, progesterone receptor, HER-2/neu, cyclin D1, p53, p21, cycloxygenase-2 (COX-2 and peroxisome proliferator activated receptor γ (PPARγ. Two markers were significantly different between cases and controls on univariate analysis: strong COX-2 expression was associated with increased risk of recurrence, with 67% vs. 24% positivity in cases and controls p = 0.006; and nuclear expression of PPARγ was associated with protection from recurrence with 4% vs. 27% positivity in cases and controls, p = 0.024. In a multivariate model which included size, grade, COX-2 and PPARγ positivity, we found COX-2 positivity to be a strong independent risk factor for recurrence (OR 7.90, 95% CI 1.72–36.23., whereas size and grade were of borderline significance. PPARγ expression continued to demonstrate a protective trend, (OR 0.14, 95% CI 0.06–1.84. Conclusion Our findings suggest that COX-2 and PPARγ should be investigated further as biologic markers to predict DCIS recurrence, particularly since they are also potential therapeutic targets.

  13. Expression of COX-2 and VEGF in benign prostatic hyperplasia combined with prostatitis%合并前列腺炎的前列腺增生组织中COX-2、VEGF的表达

    Institute of Scientific and Technical Information of China (English)

    关胜; 曹林升

    2010-01-01

    Objectives To study the expressions of Vascular endothelial growth factor ( VEGF) and cyclooxygenase-2 in benign prostatic hyperplasia combined with Prostatitis,analyze their correlation and to investigate the effect and molecular mechanism of prostatitis on BPH.Methods 60 specimens were obtained from patients undergoing transurethral prostatic resection(TURP).The paraffin section of the specimens were stained with hematoxylin and eosin,and observed under light microscope to examine the inflammation pathological changes.Depending on whether the benign prostatic hyperplasia combined with prostatitis,those specimens were divided into group of simple benign prostatic hyperplasia ( A group) and group of benign prostatic hyperplasia combined with prostatitis ( B group),using inununohistochemistry and Real-time fluorescence quantitative PCR ( RT-PCR) to detect the expressions of COX-2 and VEGF in prostate tissues.Results (1) immunohistochemical staining: COX-2 and VEGF expressed in the A group and B group,but in the B group of tissues were significantly higher than A group of tissues( p <0.05); COX-2 and VEGF expression in the B group of organizations had a positive correlation ( R = 0.92,p <0.05) (2) COX-2 mRNA in the A group,the relative ratio; 0.141 ± 0.019,in the B group,the relative ratio: 0.161 ± 0.013;VEGF mRNA in the A group relative ratio: 0.2S4 ± 0.015,in the B group,the relative ratio; 0.341 ± 0.012,The expressions of COX-2mRNA and VEGF mRNA in the B group were significantly higher than the expressions of A group ( p <0.05) .Conclusions The inflammatory factor COX-2 and proliferative factor VEGF in the tissues of benign prostatic hyperplasia combined with prostatitis are significantly increased and the expression levels of both positive correlation,COX-2 by the way of up-regulating VEGF expression may be involved in the development process of benign prostatic hyperplasia.%目的 研究环氧化酶-2(COX-2)、血管内皮生长冈子(VEGF)在合并前列

  14. A STUDY OF COX-2 INHIBITOR CELECOXIB AND CHEMORADIATION IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

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    Kuppa Prakash

    2016-08-01

    Full Text Available AIMS AND OBJECTIVES To evaluate efficacy of concurrent oral Cox-2 Inhibitor (celecoxib and chemoradiation in locoregional control, distant control, disease free survival and/or overall survival in patients with locally advanced cervical cancer. To determine treatment related toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, intravenous cisplatin and concurrent pelvic radiation therapy. MATERIALS AND METHODS Study was done for a period of 2 years in a tertiary care cancer hospital which caters to the cancer patients. Advanced squamous, adenocarcinoma or adenosquamous carcinoma of uterine cervix, Patients with age <70 years, ECOG performance status 0-2, Normal haematological investigations, Normal renal function test, Normal liver function test, No disease outside of pelvis. RESULTS This prospective study consisted 30 patients, 15 patients on either arm. Overall pooled mean age for both study and comparison group was 50.3 years with a probability value P=0.91 for age. 14 patients (93.33% in both the arms had a performance status of ECOG 0 or 1 and 1 patient in both arms had ECOG PS-2. Stage distribution of the patients in study arm was 3 in IB2, 2 in IIA, 5 in IIB, 4 in III and 1 in stage IVA. In control arm, out of the 15 patients 2 are in IB2, 2 in IIA, 5 in IIB, 5 in III and 1 in stage IVA. The mean probability value was P=0.65 for stage distribution. 15 patients in arm-A (study arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr after pelvic RT on an average of 1 week along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22 and Cox-2 inhibitor oral celecoxib 400 mg twice daily (800 mg/d starting from day 1 to throughout the duration of the chemoradiation. 15 patients in arm-B (Control arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr on an average of 1 week after pelvic RT along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22

  15. Role of bile acids, prostaglandins and COX inhibitors in chronic esophagitis in a mouse model

    Institute of Scientific and Technical Information of China (English)

    C Poplawski; D Sosnowski; A Szaflarska-Poplawska; J Sarosiek; R McCallum; Z Bartuzi

    2006-01-01

    AIM: To develop a new experimental model of esophagitis that serves a complementary tool to clinical investigation in an insight into the mechanism of the damage to the esophagus mucosa by aggressive factors, and role of COX inhibitors in this process.METHODS: The study was conducted in 56 male mice.Animals were divided into seven groups: (1) perfused with HCl, (2) perfused with HCl and physiologic concentration of pepsin (HCl/P), (3) perfused with similar HCl/P solution enriched with conjugated bile acids (glycho- and tauro-sodium salts) designated esophageal infusion catheter under the general anesthesia, (4) perfused as in group 2 treated with indometacin, (5) perfused as in group 2 treated with NS-398, (6) perfused as in group 3 treated with indometacin, and (7) perfused as in group 3 treated with NS-398.The esophagus was divided into 3 parts: upper, middle and lower. The PGE2 concentration was measured in all parts of esophagus using RIA method. Esophagus of sacrificed animals was macroscopically evaluated using a low power dissecting microscope (20x). Specimeris, representing the most frequently seen changes were fixed,stained with H&E and assessed microscopically using the damage score, and inflammatory score.RESULTS: The macroscopic changes were significantly severer in HCl/P than those in HCl animals (77%) and in HCl/P/BA group (43%). In HCl/P NS-398 group we noticed significantly less changes than those in not treated group (42%) and in analogical group treated with indometacine (45%). In HCl/P/BA INDO group we observed significantly severer changes than that in not treated group (52%). We noticed less changes in HCl/P NS-398 than that in group with indometacine (46%). In HCl/P/BA NS-398 group we had less changes than that in indometacin group (34%). The microscopic changes observed in HCl/P/BA INDO group were severer than that in not treated group (48%). Esophagitis index in HCl group was significantly lower than in HCl/P and also HCl/P/BA group (32% and

  16. A single center's experience with pacemaker implantation after the Cox maze procedure for atrial fibrillation.

    Science.gov (United States)

    Ad, Niv; Holmes, Sari D; Ali, Rabia; Pritchard, Graciela; Lamont, Deborah

    2017-07-01

    The Cox maze procedure (CM) is safe and effective for all atrial fibrillation (AF) types. A recent randomized trial found alarming rates of pacemaker implantation (PMI) during hospitalization after CM. The purpose of this study was to assess the rate of PMI and its impact on outcomes after CM. Incidence of PMI was captured for all CM patients (2005-2015; N = 739). Data were collected prospectively. Multivariable logistic regression was conducted to determine risk factors for PMI. Propensity score matching was conducted between concomitant CM patients and patients without surgical ablation since 2011. Fifty-two patients (7.0%) had in-hospital PMI after CM. Most common primary indication for PMI was sick sinus syndrome (67%), followed by complete heart block (23%) and sinus bradycardia (10%). The only risk factor for in-hospital PMI was type of procedure (P = .020). Patients with multiple valve procedures were at greatest risk (P = .004-.035). STS-defined perioperative outcomes were similar for patients with and without in-hospital PMI. Sinus rhythm off antiarrhythmic drugs were similar by PMI. After propensity score matching (n = 180 per group), in-hospital PMI was similar in CM patients and those without surgical ablation (5% vs 4%, P = .609). This study demonstrated lower incidence of PMI after CM procedures than recently reported. When indicated, PMI was not associated with increased short- or long-term morbidity or inferior freedom from atrial arrhythmia. Efforts to increase surgeon training with the CM procedure and postoperative management awareness are warranted to improve rhythm outcome and minimize adverse events and PMI. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  17. Generating survival times to simulate Cox proportional hazards models with time-varying covariates.

    Science.gov (United States)

    Austin, Peter C

    2012-12-20

    Simulations and Monte Carlo methods serve an important role in modern statistical research. They allow for an examination of the performance of statistical procedures in settings in which analytic and mathematical derivations may not be feasible. A key element in any statistical simulation is the existence of an appropriate data-generating process: one must be able to simulate data from a specified statistical model. We describe data-generating processes for the Cox proportional hazards model with time-varying covariates when event times follow an exponential, Weibull, or Gompertz distribution. We consider three types of time-varying covariates: first, a dichotomous time-varying covariate that can change at most once from untreated to treated (e.g., organ transplant); second, a continuous time-varying covariate such as cumulative exposure at a constant dose to radiation or to a pharmaceutical agent used for a chronic condition; third, a dichotomous time-varying covariate with a subject being able to move repeatedly between treatment states (e.g., current compliance or use of a medication). In each setting, we derive closed-form expressions that allow one to simulate survival times so that survival times are related to a vector of fixed or time-invariant covariates and to a single time-varying covariate. We illustrate the utility of our closed-form expressions for simulating event times by using Monte Carlo simulations to estimate the statistical power to detect as statistically significant the effect of different types of binary time-varying covariates. This is compared with the statistical power to detect as statistically significant a binary time-invariant covariate.

  18. miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor.

    Science.gov (United States)

    Li, Huanan; Zhou, Jiawei; Wei, Xiajie; Chen, Ran; Geng, Junnan; Zheng, Rong; Chai, Jin; Li, Fenge; Jiang, Siwen

    2016-06-14

    Labor is initiated as a result of hormonal changes that are induced by the activation of the inflammatory response and a series of biochemical events. The amnion, which is the primary source of prostaglandin E2 (PGE2), plays an important role in the process of labor. In the present study, we uncovered a pathway in which c-fos, cyclooxygenase-2 (COX2) and miR-144 function as hormonal modulators in the amnions of pregnant mice and humans. miR-144 down-regulated the synthesis of PGE2 during pregnancy by directly and indirectly inhibiting COX2 expression and by directly inhibiting the expression of c-fos, a transcriptional activator of COX2 and miR-144. Estrogen (E2) activated c-fos, thus promoting the expression of miR-144 and COX2 during labor. However, the increase in COX2 resulted in the partial inhibition of COX2 expression by miR-144, thereby slightly reducing the secretion of PGE2. These observations suggest that miR-144 inhibits PGE2 secretion by section to prevent the initiation of premature labor. Up-regulated expression of miR-144, c-fos and COX2 was also observed both in preterm mice and in mice undergoing normal labor. In summary, miR-144, c-fos and COX2 play important roles in regulating PGE2 secretion in the amnion during pregnancy and labor.

  19. Detection of EGFR and COX-2 Expression by Immunohistochemical Method on a Tissue Microarray Section in Lung Cancer and Biological Significance

    Directory of Open Access Journals (Sweden)

    Xinyun WANG

    2010-02-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2, which can regulate growth, invasion and metastasis of tumor through relevant signaling pathway, have been detected in a variety of solid tumors. The aim of this study is to investigate the biological significance of EGFR and COX-2 expression in lung cancer and the relationship between them. Methods The expression of EGFR and COX-2 was detected in 89 primary lung cancer tissues, 12 premaliganant lesions, 12 lymph node metastases, and 10 normal lung tissues as the control by immunohistochemical method on a tissue microarray section. Results EGFR protein was detectable in 59.6%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively; COX-2 protein was detectable in 52.8%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively, which were significantly higher than those of the control (P 0.05. COX-2 expression was related to gross type (P < 0.05. A highly positive correlation was observed between EGFR and COX-2 expression (P < 0.01. Conclusion Overexpression of EGFR and COX-2 may play an important role in the tumorgenesis, progression and malignancy of lung cancer. Detection of EGFR and COX-2 expression might be helpful to diagnosis and prognosis of lung cancer.

  20. 75 FR 3217 - J&T Hydro Company; H. Dean Brooks and W. Bruce Cox; Notice of Application for Transfer of License...

    Science.gov (United States)

    2010-01-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission J&T Hydro Company; H. Dean Brooks and W. Bruce Cox; Notice of Application... 30, 2009, J&T Hydro Company (transferor) and W. Dean Brooks, and H. Bruce Cox (transferees) filed...

  1. The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging.

    Science.gov (United States)

    Luo, Cheng; Urgard, Egon; Vooder, Tõnu; Metspalu, Andres

    2011-08-01

    Oxidative stress and inflammation are constant features of many chronic diseases and complications, and have been linked to carcinogenesis. Cyclooxygenase 2 (COX-2), a rate-limiting enzyme for the synthesis of prostaglandins, plays important roles in physiology and pathology, but has been a source of controversy within the scientific and clinical community. However, recent work has shown that nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against oxidative stress. Furthermore, COX-2-dependent electrophile oxo-derivative (EFOX) molecules have been shown to act as anti-inflammatory mediators via activation of the Nrf2-dependent antioxidant response element (ARE). These studies have provided more insight into COX-2-mediated events. The function of all tissues, especially epithelial and endothelial tissues, declines with age, leading to the production of reactive oxygen species (ROS). COX-2 expression increases with aging in most tissues, due in part to ROS, chemical reactions, physical shearing, and dietary molecules. Here we discuss new findings related to COX-2 inflammatory and anti-inflammatory responses. Taken together, we hypothesize that COX-2 levels increase during the aging process because increasing levels of ROSs necessitate the involvement of COX-2-dependent EFOXs for anti-inflammation and Nrf2/ARE signaling for antioxidation. We also propose that COX-2 may act as an intrinsic biological aging clock due to its role in balancing inflammatory and anti-inflammatory responses.

  2. A density functional theory study of the electronic structures and magnetic properties of Fe(1-x)Cox alloy nanowires encapsulated in (10,0) carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    Xie You; Zhang Jian-Min

    2011-01-01

    Under the generalized gradient approximation,the electronic structures and magnetic properties of Fe(1-x)Coxalloy nanowires encapsulated inside zigzag (10,0) carbon nanotubes (CNTs) are investigated systematically using firstprinciple density functional theory calculations.For the fully relaxed Fe(1-x)Cox/CNT structures,all the C atoms relax outwards,and thus the diameters of the CNTs are slightly increased.Formation energy analysis shows that the combining processes of all Fe(1-x)Cox/CNT systems are exothermic,and therefore the Fe(1-x)Cox alloy nanowirescan be encapsulated into semiconducting zigzag (10,0) CNTs and form stable hybrid structures.The charges are transferred from the Fe(1-x)Cox nanowires to the more electronegative CNTs,and the Fe-C/Co-C bonds formed have polar covalent bond characteristics.Both the spin polarization and total magnetic moment of the Fe(1-x)Cox/CNT system are smaller than those of the corresponding freestanding Fe(1-x)Cox nanowire,and the magnetic moment of the Fe(1-x)Cox/CNT system decreases monotonously with increasing Co concentration,but the Fe(1-x)Cox/CNT systems still have a large magnetic moment,implying that they can be utilized in high-density magnetic recording devices.

  3. Resíduos generalizados de Cox-Snell na avaliação do ajuste de modelos Cox-Snell generalized residuals in the evaluation of model fitting

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Souza da Silva

    2004-10-01

    Full Text Available Vários tipos de resíduos têm sido propostos para modelos de sobrevivência, sendo os mais adequados resultado dos resíduos generalizados de Cox e Snell (1968. O objetivo com este trabalho é avaliar a adequacidade de modelos por meio de gráficos de diagnósticos gerados a partir dos resíduos generalizados de Cox-Snell. Para ilustrar a teoria, foram feitas três aplicações. A primeira aplicação visou a ilustrar a lógica existente entre a plotagem dos resíduos ordenados de três distribuições, normal (0,1, logística (0,1 e valor extremo (0,1 versus as estatísticas de ordem esperadas desses resíduos de acordo com as distribuições assumidas. Para a segunda aplicação, foram utilizados dados de tempo de vida de isolantes, obtidos em Nelson (1990. A partir da verificação por meio dos gráficos de diagnósticos utilizando-se os resíduos generalizados de Cox-Snell, encontrou-se que o modelo apropriado para o tempo de vida dos isolantes era o log-normal. Para a terceira aplicação, foram analisados dados censurados referentes ao tempo de vida de pacientes, obtidos em Collett (1994. Avaliou-se a adequacidade de vários modelos por meio dos resíduos de Cox-Snell adaptados para dados de sobrevivência. Pelos resultados constatou-se que o modelo Weibull foi o mais adequado.Several kinds of residuals have been proposed for survival models, the most suitable for this purpose are Cox and Snell (1968 generalized residuals. The objective of this work was to evaluate the adequacy of models by graphical diagnostics using Cox-Snell generalized residuals. To illustrate the theory three applications were considered. The first application sought to illustrate the heuristics by plotting ordered residuals from three distributions: normal (0,1, logistics (0,1 and extreme value (0,1, versus the expected order statistics of these residuals in consonance with the assumed distributions. The second application consisted of lifetime data of electric

  4. COX-2-derived prostanoids and oxidative stress additionally reduce endothelium-mediated relaxation in old type 2 diabetic rats.

    Directory of Open Access Journals (Sweden)

    Emilie Vessières

    Full Text Available Endothelial dysfunction in resistance arteries alters end organ perfusion in type 2 diabetes. Superoxides and cyclooxygenase-2 (COX-2 derivatives have been shown separately to alter endothelium-mediated relaxation in aging and diabetes but their role in the alteration of vascular tone in old diabetic subjects is not clear, especially in resistance arteries. Consequently, we investigated the role of superoxide and COX-2-derivatives on endothelium-dependent relaxation in 3 and 12 month-old Zucker diabetic fatty (ZDF and lean (LZ rats. Mesenteric resistance arteries were isolated and vascular tone was investigated using wire-myography. Endothelium (acetylcholine-dependent relaxation was lower in ZDF than in LZ rats (60 versus 84% maximal relaxation in young rats and 41 versus 69% in old rats. Blocking NO production with L-NAME was less efficient in old than in young rats. L-NAME had no effect in old ZDF rats although eNOS expression level in old ZDF rats was similar to that in old LZ rats. Superoxide level and NADPH-oxidase subunits (p67phox and gp91phox expression level were greater in ZDF than in LZ rats and were further increased by aging in ZDF rats. In young ZDF rats reducing superoxide level with tempol restored acetylcholine-dependent relaxation to the level of LZ rats. In old ZDF rats tempol improved acetylcholine-dependent relaxation without increasing it to the level of LZ rats. COX-2 (immunolabelling and Western-blot was present in arteries of ZDF rats and absent in LZ rats. In old ZDF rats arterial COX-2 level was higher than in young ZDF rats. COX-2 blockade with NS398 restored in part acetylcholine-dependent relaxation in arteries of old ZDF rats and the combination of tempol and NS398 fully restored relaxation in control (LZ rats level. Accordingly, superoxide production and COX-2 derivatives together reduced endothelium-dependent relaxation in old ZDF rats whereas superoxides alone attenuated relaxation in young ZDF or old LZ rats.

  5. Relationship between NOC/oFQ, dynorphin, and COX-2 activation in impaired NMDA cerebrovasodilation after brain injury.

    Science.gov (United States)

    Kulkarni, Miriam; Armstead, William M

    2002-08-01

    Previous studies have observed that the recently described endogenous opioid, nociceptin/orphanin FQ (NOC/oFQ), contributes to impairment of N-methyl-D-aspartate (NMDA)-induced cerebrovasodilation following fluid percussion brain injury (FPI) via a cyclooxygenase (COX)-dependent generation of superoxide anion (O(2)(-)). This study was designed to investigate the relationship between NOC/oFQ, another opioid, dynorphin, and activation of the COX-2 isoform of the enzyme in such impaired dilation to NMDA after FPI in piglets equipped with a closed cranial window. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O(-)(2) generation. Under non-brain injury conditions, NOC/oFQ (10(-10) M), the CSF concentration observed after FPI, increased CSF dynorphin, while the NOC/oFQ antagonist [F/G] NOC/oFQ (1-13) NH(2) attenuated the stimulated release of dynorphin following FPI (34 +/- 3 and 97 +/- 6 vs. 36 +/- 3 and 68 +/- 8 pg/mol for CSF dynorphin before and after FPI in untreated and NOC/oFQ antagonist-pretreated animals). FPI increased SOD-inhibitable NBT reduction, but pretreatment with norbinaltorphimine, a dynorphin antagonist, or NS398, a COX-2 inhibitor, blunted such reduction (1 +/- 1 vs. 19 +/- 3 vs. 4 +/- 1 vs. 4 +/- 1 pmol/mm(2) for control, FPI, FPI-norbinaltorphimine and FPI-NS398, respectively). Under non-brain injury conditions, dynorphin, in a concentration observed in CSF after FPI, also increased SOD-inhibitable NBT reduction, which was blunted by NS398. NMDA-induced pial artery dilation was reversed to vasoconstriction following FPI, but pretreatment with norbinaltorphimine or NS398 partially protected such responses (9 +/- 1 and 16 +/- 1, control; - 8 +/- 1 and - 13 +/- 2, FPI; 6 +/- 1 and 12 +/- 1% FPI-norbinaltorphimine for NMDA 10(-8), 10(-6) M, respectively). These data show that NOC/oFQ modulates the CSF release of dynorphin after FPI. These data also show that dynorphin contributes to O(2

  6. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

    Directory of Open Access Journals (Sweden)

    Inoue Takeshi

    2013-01-01

    Full Text Available Abstract Background COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. Methods LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT. Results LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (p Conclusions These in vitro and in vivo findings suggest that conventional COX inhibitor, diclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer.

  7. Efeito dos anti-inflamatórios não-esteroidais convencionais e seletivos para COX-2 sobre o reparo ósseo Effect of conventional and COX-2 selective non-steroidal antiinflammatory drugs on bone healing

    Directory of Open Access Journals (Sweden)

    Teresa Lúcia Lamano-Carvalho

    2007-01-01

    Full Text Available Na presente revisão de literatura foram relacionados trabalhos experimentais e clínicos dos últimos 15 anos referentes aos efeitos dos antiinflamatórios não-esteroidais (AINEs convencionais e seletivos para COX-2 sobre a formação óssea reparacional. A maioria dos trabalhos mostra que os AINEs convencionais podem atrasar o reparo de fratura de ossos longos e a fusão espinhal, em animais, e interferir negativamente com a taxa de fusão espinhal, em humanos. Apesar da importância comprovada da prostaglandina E2, sintetizada por osteoblastos sob estímulo da enzima ciclooxigenase-2 (COX-2, no controle da formação óssea, os resultados experimentais acerca dos prováveis efeitos inibitórios dos AINEs seletivos sobre o reparo ósseo além de raros são ainda controversos e não há comprovação de que eles interferem com a neoformação óssea reparacional em humanos.In the present literature review, experimental and clinical studies of the last 15 years concerning the effects of conventional and COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs on bone healing were reported. Most of the data pertaining to conventional NSAIDs have shown to cause delayed fracture healing and impairment of spinal fusion in animal studies, as well as a negative interference on spinal fusion rate in human beings. In spite of the established importance of prostaglandin E2, synthesized by osteoblasts under COX-2 stimulation, in controlling bone formation, the results regarding the potential inhibitory effects of selective NSAIDs on experimental bone healing are still controversial and there is no clinical data to confirm that they interfere negatively with repairing bone formation.

  8. The involvement of the CD40-CD40L pathway in activated platelet-induced changes in HUVEC COX-2 and PPARα expression.

    Science.gov (United States)

    Wu, Yan-qing; Chen, Xiao-shu; Chai, Jun-bing

    2012-06-01

    We aim to determine the extent of the CD40-CD40L pathway involvement in activated platelet-induced changes in human umbilical endothelial cells (HUVECs). Activated platelets were co-incubated with HUVECs in the presence or absence of CD40LmAb. HUVECs were also directly stimulated with rhCD40L. HUVEC endothelial cyclooxygenase 2 (COX-2) and peroxisome proliferator-activated receptor alpha (PPARα) expression was then assessed. To estimate COX-2 activity, PGE2 concentration was determined. PPARα activity was assessed using a nuclear factor activity kit. Co-incubation with activated platelets increased HUVEC COX-2 and PPARα mRNA expression (P HUVEC COX-2 mRNA and protein (P HUVEC COX-2 expression and activity partly through the CD40-CD40L pathway.

  9. Cyclooxygenase 2 (COX2 and Peroxisome Proliferator-Activated Receptor Gamma (PPARG Are Stage-Dependent Prognostic Markers of Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Stefanie Meyer

    2010-01-01

    TMA-1 contained normal and tumor tissues (n=3448 from 47 organs including skin neoplasms (n=323; TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.

  10. Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Arendt Thomas

    2005-11-01

    Full Text Available Abstract Neuronal expression of cyclooxygenase-2 (COX-2 and cell cycle proteins is suggested to contribute to neurodegeneration during Alzheimer's disease (AD. The stimulus that induces COX-2 and cell cycle protein expression in AD is still elusive. Activated glia cells are shown to secrete substances that can induce expression of COX-2 and cell cycle proteins in vitro. Using post mortem brain tissue we have investigated whether activation of microglia and astrocytes in AD brain can be correlated with the expression of COX-2 and phosphorylated retinoblastoma protein (ppRb. The highest levels of neuronal COX-2 and ppRb immunoreactivity are observed in the first stages of AD pathology (Braak 0–II, Braak A. No significant difference in COX-2 or ppRb neuronal immunoreactivity is observed between Braak stage 0 and later Braak stages for neurofibrillary changes or amyloid plaques. The mean number of COX-2 or ppRb immunoreactive neurons is significantly decreased in Braak stage C compared to Braak stage A for amyloid deposits. Immunoreactivity for glial markers KP1, CR3/43 and GFAP appears in the later Braak stages and is significantly increased in Braak stage V-VI compared to Braak stage 0 for neurofibrillary changes. In addition, a significant negative correlation is observed between the presence of KP1, CR3/43 and GFAP immunoreactivity and the presence of neuronal immunoreactivity for COX-2 and ppRb. These data show that maximal COX-2 and ppRb immunoreactivity in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia. In contrast to in vitro studies, post mortem data do not support a causal relation between the activation of microglia and astrocytes and the expression of neuronal COX-2 and ppRb in the pathological cascade of AD.

  11. Insights from the docking analysis of biologically active compounds from plant Litsea Genus as potential COX-2 inhibitors.

    Science.gov (United States)

    Gogoi, Dhrubajyoti; Bezbaruah, Rajib Lochan; Bordoloi, Manabjyoti; Sarmah, Rajeev; Bora, Tarun Chandra

    2012-01-01

    Litsea spp of Laural family are traditionally used as herbal medicine for treating inflammation including gastroenterologia, oedema and rheumatic arthritis. Therefore, it is of interest to investigate and understand the molecular principles for such actions. Here, we have illustrated the binding of thirteen Litsea derived biologically active compounds against the inflammation associated target COX (cyclo-oxygenase) -2 enzymes. We compared the binding information of these compounds with a selected number of already known COX-2 inhibitors. The comparison reflected that some of these compounds such as linderol, catechin, 6'-hydroxy-2',3',4' - trimethoxy-chalcone and litseaone have better or equivalent binding features compared to already known inhibitory compounds namely celecoxib, acetylsalicylic acid, rofecoxib. Therefore, all these small compounds reported from plant Litsea spp were found to possess potential medicinal values with anti-inflammatory properties.

  12. In-Silico search of Tailored Cox-2 Inhibitors: Screening of Quinazolinone derivatives via molecular modeling Tools

    Directory of Open Access Journals (Sweden)

    Samad Abdul

    2014-06-01

    Full Text Available Novel Quinazoline derivatives were designed through in silico studies including Molecular properties prediction, Toxicity risk prediction and by Molecular Docking approaches. The hypothetically designed molecules were studied for Lipinski rule of 5 properties. The successful molecules were subjected to toxicity risk prediction by Osiris property calculator.The docking methodology applied in the study was first validated by redocking the celecoxib in cox-2 domain with the co-crystallized one. Cox-2 protein was explored for the residues imperative for activity by analyzing the binding pattern of celecoxib and selected compounds of quinazolinone derivatives in the active domain. All the selected molecules passed Lipinski rule of five successfully and they were safe. The docking results explored that compound IQ1, IQ2, IQ5, IQ8 and IQ12 have binding affinity -9.3, which indicated that these compounds may prove successful anti-inflammatory oral candidates.

  13. Superconductivity and magnetic properties in SmFe1-xCoxAsO (x=0 to 1)

    Science.gov (United States)

    Qi, Yanpeng; Wang, Lei; Gao, Zhaoshun; Wang, Dongliang; Zhang, Xianping; Yao, Chao; Wang, Chunlei; Wang, Chengduo; Ma, Yanwei

    2011-10-01

    In this paper the effects of replacing Fe with Co in SmFe1-xCoxAsO (x=0 to 1) are reported. X-ray diffraction patterns indicate that all the samples have formed the ZrCuSiAs-type structure with a space group P4/nmm and a full solid solution forms between SmFeAsO and SmCoAsO. It is found that the antiferromagnetic spin-density-wave (SDW) order in the parent compounds is rapidly suppressed by Co-doping, and superconductivity emerges as 0.05 SmFeAsO-SmCoAsO system. The systemic study in the SmFe1-xCoxAsO system would add more ingredients to the underlying physics of this material.

  14. Role of COX-1 in the process of neuropathic pain and its mechanism Zhi-hong LU, Qi - bing MEI

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    AIM In neuropathic pain the peripheral or central nervous systems are malfunctioning and become the cause of the pain. Unlike other pain styles, most neuropathic pain responds poorly to opioid analgesics. The mainstay of treatment is predominantly the tricyclic antidepressants, the anticonvulsants and the systemic local anesthetics of which the long- term use could lead to great side effects. Recently, proin-flammatory cytokines, such as IL-6, TNF-α, etc, have been proved to be involved in the process of neuropathic pain, indicating the cross - talking between neuropathic pain and inflammation. As an important member in inflammatory process, COX is expected to play a part in the process of neuropathic pain.In this study, we observed the change of COX-1 after neuropathic pain and further investigated thechange it caused in the brain. METHODS Spared nerve injury (SNI) is used to induce neuropathic painin mice.

  15. A COX-2 inhibitor reduces muscle soreness, but does not influence recovery and adaptation after eccentric exercise

    DEFF Research Database (Denmark)

    Paulsen, G; Egner, I M; Drange, M

    2010-01-01

    The aim of this study was to investigate the effect of a cyclooxygenase (COX)-2 inhibitor on the recovery of muscle function, inflammation, regeneration after, and adaptation to, unaccustomed eccentric exercise. Thirty-three young males and females participated in a double-blind, placebo...... by celecoxib. In summary, celecoxib, a COX-2 inhibitor, did not detectably affect recovery of muscle function or markers of inflammation and regeneration after unaccustomed eccentric exercise, nor did the drug influence the repeated-bout effect. However, it alleviated muscle soreness.......-controlled experiment. Seventy unilateral, voluntary, maximal eccentric actions with the elbow flexors were performed twice (bouts 1 and 2) with the same arm, separated by 3 weeks. The test group participants were administered 400 mg/day of celecoxib for 9 days after bout 1. After both bouts 1 and 2, concentric...

  16. Insights from the docking analysis of biologically active compounds from plant Litsea Genus as potential COX-2 inhibitors

    Science.gov (United States)

    Gogoi, Dhrubajyoti; Bezbaruah, Rajib Lochan; Bordoloi, Manabjyoti; Sarmah, Rajeev; Bora, Tarun Chandra

    2012-01-01

    Litsea spp of Laural family are traditionally used as herbal medicine for treating inflammation including gastroenterologia, oedema and rheumatic arthritis. Therefore, it is of interest to investigate and understand the molecular principles for such actions. Here, we have illustrated the binding of thirteen Litsea derived biologically active compounds against the inflammation associated target COX (cyclo-oxygenase) -2 enzymes. We compared the binding information of these compounds with a selected number of already known COX-2 inhibitors. The comparison reflected that some of these compounds such as linderol, catechin, 6'-hydroxy-2',3',4' - trimethoxy-chalcone and litseaone have better or equivalent binding features compared to already known inhibitory compounds namely celecoxib, acetylsalicylic acid, rofecoxib. Therefore, all these small compounds reported from plant Litsea spp were found to possess potential medicinal values with anti-inflammatory properties. PMID:23139590

  17. Preparation and conductivity of nanocrystalline rare earth mixed oxides SmFe1-xCoxO3-δ

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Nanocrystalline rare earth mixed oxides SmFe1 xCoxO3-δ were prepared by sol-gel method at 1 073 K for 2h calcination and characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM). The results show that SmFe1-xCoxO3-δ has the structure ofperovskite type. The conductivity of the materials increases with the temperature rising and the maximum conductivity at 1 073 K is 2.6 S/cm with the best mole ratio of Fe3+ to Co3+ being 1: 4. This kind of oxide is a conductive ceramic material by means of conduction of electron and oxygen anion.

  18. PGE2 receptor EP2 mediates the antagonistic effect of COX-2 on TGF-beta signaling during mammary tumorigenesis.

    Science.gov (United States)

    Tian, Maozhen; Schiemann, William P

    2010-04-01

    The molecular mechanisms that enable cyclooxygenase-2 (COX-2) and its mediator prostaglandin E2 (PGE2) to inhibit transforming growth factor-beta (TGF-beta) signaling during mammary tumorigenesis remain unknown. We show here that TGF-beta selectively stimulated the expression of the PGE2 receptor EP2, which increased normal and malignant mammary epithelial cell (MEC) invasion, anchorage-independent growth, and resistance to TGF-beta-induced cytostasis. Mechanistically, elevated EP2 expression in normal MECs inhibited the coupling of TGF-beta to Smad2/3 activation and plasminogen activator inhibitor-1 (PAI1) expression, while EP2 deficiency in these same MECs augmented Smad2/3 activation and PAI expression stimulated by TGF-beta. Along these lines, engineering malignant MECs to lack EP2 expression prevented their growth in soft agar, restored their cytostatic response to TGF-beta, decreased their invasiveness in response to TGF-beta, and potentiated their activation of Smad2/3 and expression of PAI stimulated by TGF-beta. More important, we show that COX-2 or EP2 deficiency both significantly decreased the growth, angiogenesis, and pulmonary metastasis of mammary tumors produced in mice. Collectively, this investigation establishes EP2 as a potent mediator of the anti-TGF-beta activities elicited by COX-2/PGE2 in normal and malignant MECs. Our findings also suggest that pharmacological targeting of EP2 receptors may provide new inroads to antagonize the oncogenic activities of TGF-beta during mammary tumorigenesis.-Tian, M., Schiemann, W. P. PGE2 receptor EP2 mediates the antagonistic effect of COX-2 on TGF-beta signaling during mammary tumorigenesis.

  19. PGE2 receptor EP2 mediates the antagonistic effect of COX-2 on TGF-β signaling during mammary tumorigenesis

    Science.gov (United States)

    Tian, Maozhen; Schiemann, William P.

    2010-01-01

    The molecular mechanisms that enable cyclooxygenase-2 (COX-2) and its mediator prostaglandin E2 (PGE2) to inhibit transforming growth factor-β (TGF-β) signaling during mammary tumorigenesis remain unknown. We show here that TGF-β selectively stimulated the expression of the PGE2 receptor EP2, which increased normal and malignant mammary epithelial cell (MEC) invasion, anchorage-independent growth, and resistance to TGF-β-induced cytostasis. Mechanistically, elevated EP2 expression in normal MECs inhibited the coupling of TGF-β to Smad2/3 activation and plasminogen activator inhibitor-1 (PAI1) expression, while EP2 deficiency in these same MECs augmented Smad2/3 activation and PAI expression stimulated by TGF-β. Along these lines, engineering malignant MECs to lack EP2 expression prevented their growth in soft agar, restored their cytostatic response to TGF-β, decreased their invasiveness in response to TGF-β, and potentiated their activation of Smad2/3 and expression of PAI stimulated by TGF-β. More important, we show that COX-2 or EP2 deficiency both significantly decreased the growth, angiogenesis, and pulmonary metastasis of mammary tumors produced in mice. Collectively, this investigation establishes EP2 as a potent mediator of the anti-TGF-β activities elicited by COX-2/PGE2 in normal and malignant MECs. Our findings also suggest that pharmacological targeting of EP2 receptors may provide new inroads to antagonize the oncogenic activities of TGF-β during mammary tumorigenesis.—Tian, M., Schiemann, W. P. PGE2 receptor EP2 mediates the antagonistic effect of COX-2 on TGF-β signaling during mammary tumorigenesis. PMID:19897661

  20. CoxC encased in carbon nanotubes: an efficient oxygen reduction catalyst under both acidic and alkaline conditions.

    Science.gov (United States)

    Chen, Lisong; Cui, Xiangzhi; Wang, Qingsong; Zhang, Xiaohua; Wan, Gang; Cui, Fangming; Wei, Chenyang; Shi, Jianlin

    2015-12-21

    The design of a non-precious metal oxygen reduction reaction (ORR) catalyst of high activity and long durability in acidic electrolyte is of great importance for the development and commercialization of low-temperature fuel cells, which remains a great challenge to date. Here, we demonstrate a facile, scalable protocol for the controlled synthesis of CoxC encapsulated in carbon nanotubes as a novel kind of efficient electrochemical oxygen reduction reaction (ORR) catalyst. The synthesized CoxC/carbon nanotube features a high BET surface area, large pore volume and high graphitic content, which greatly favors enhanced ORR properties. The resultant composite electro-catalyst shows high ORR activity which is comparable with that of 20 wt% Pt/C in 0.1 M KOH electrolyte. More importantly, it also exhibits a high ORR activity in 0.1 M HClO4 with a near-complete 4e pathway. More attractively, compared to the most investigated FexC, CoxC as the proposed main catalytically active center shows much enhanced activity in acidic electrolyte, which will pave the way towards the rational design of an advanced electro-catalyst for an efficient ORR process especially under acidic conditions. Moreover, a fuel cell using the synthesized CoxC/carbon nanotube as a cathode catalyst showed a large open-circuit potential, high output power density and long durability, which make it a promising alternative to Pt/C as a non-precious metal ORR catalyst in proton exchange membrane fuel cells.

  1. Regulation of Cox-2 by Cyclic AMP Response Element Binding Protein in Prostate Cancer: Potential Role for Nexrutine

    OpenAIRE

    Rita Ghosh; Gretchen E. Garcia; Katherine Crosby; Hiroyasu Inoue; Thompson, Ian M.; Troyer, Dean A.; Kumar, Addanki P.

    2007-01-01

    We recently showed that NexrutineR, a Phellodendron amurense bark extract, suppresses proliferation of prostate cancer cell lines and tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Our data also indicate that the antiproliferative effects of NexrutineR are mediated in part by Akt and Cyclic AMP response element binding protein (CREB). Cyclooxygenase (Cox-2), a pro-inflammatory mediator, is a CREB target that induces prostaglandin E2 (PGE2) and suppresses a...

  2. TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells

    Science.gov (United States)

    Lin, Ang; Wang, Guan; Zhao, Huajun; Zhang, Yuyi; Han, Qiuju; Zhang, Cai; Tian, Zhigang; Zhang, Jian

    2016-01-01

    ABSTRACT Toll-like receptors (TLRs) can be expressed by tumor cells, and each TLR exhibits different biological functions. Evidences showed the activation of some certain TLRs could promote tumor progression. One of which TLR4 has been found to promote hepatocellular carcinoma (HCC) cells proliferation, but the detailed mechanism is still unknown. In the present study, we verified that TLR4 was functionally expressed on HCC cells, and TLR4 agonist lipopolysaccharide (LPS) could stimulate the proliferation and clone formation of HCC cells. Most importantly, we found a COX-2/PGE2/STAT3 positive feedback loop exists in HCC cells, which could be provoked by TLR4 activation. Consistently, the expression of TLR4, COX-2 and p-STAT3Y705 was positively correlated with each other in liver tumor tissues from patients with primary HCC. Further investigation demonstrated this loop played a dominant role in TLR4-induced HCC cell proliferation and multidrug resistance (MDR) to chemotherapy. Inhibition of TLR4 or COX-2/PGE2/STAT3 loop would attenuate LPS-induced inflammation and proliferation of HCC cells, and enhance the sensitivity of HCC cells to chemotherapeutics in vitro. By using a primary HCC model, we observed COX-2/PGE2/STAT3 loop was significantly blocked in TLR4−/− mice compared to wild type mice, and there was no obvious tumorgenesis sign in TLR4−/− mice. Therefore, these findings provided the precise molecular mechanism of TLR4 signaling pathway involved in HCC progress, and suggested that TLR4 may be a promising target for HCC treatment. PMID:27057441

  3. AVALIAÇÃO DA DISPENSAÇÃO DE FÁRMACOS PARCIALMENTE SELETIVOS PARA COX-2

    Directory of Open Access Journals (Sweden)

    Cícero Cardoso VALLE FILHO

    2015-12-01

    Full Text Available Uma pesquisa foi realizada com o objetivo de avaliar um potencial aumento na venda de fármacos anti-inflamatórios não esteroidais (AINEs parcialmente seletivos para a COX-2 durante o período de julho de 2009 a junho de 2011, em uma drogaria localizada no município de Itaperuna, estado do Rio de Janeiro. Durante o período estudado foi dispensado um total de 802 AINEs parcialmente seletivos para a COX-2, dentre os quais 59,85% foram de nimesulida, 5,74% de etodolaco e 34,41% de meloxicam.   No primeiro semestre avaliado a dispensação total de AINEs parcialmente seletivos foi equivalente a 92, no segundo semestre a dispensação total foi equivalente a 159, no terceiro semestre a dispensação total foi de 219 AINEs parcialmente seletivos para COX-2 e no quarto semestre foram dispensados 332.  Os resultados indicaram maior dispensação dos medicamentos desta classe no mês de abril de 2011 sendo que tanto a nimesulida, quanto o meloxicam e o etodolaco foram mais dispensados no último semestre do estudo. De acordo com a metodologia utilizada pode-se concluir que a dispensação dos AINEs parcialmente seletivos vem crescendo a cada ano e que a nimesulida apresenta o maior índice de crescimento; a maior indicação da nimesulida tem sido para crianças; os meses correspondentes ao período de inverno apresentam maior dispensação de AINEs parcialmente seletivos para a COX-2.

  4. Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes.

    Science.gov (United States)

    Du, Ye; Zhu, Yihao; Teng, Xiaojie; Zhang, Kun; Teng, Xiaohua; Li, Shu

    2015-11-01

    Manganese (Mn) pollution can cause tissue and organ dysfunction and structural damage. The toxicity of Mn in poultry was reported, but inflammatory damage that Mn induced in the testicular tissue has not been reported. The aim of this study was to investigate the effect of Mn poisoning on NF-κB/iNOS-COX-2 signaling pathway in chicken testes. One hundred eighty Hyline male chickens at 7 days of age were fed either commercial diet or MnCl2-added commercial diet containing 600, 900, and 1800 mg/kg Mn for 30, 60, and 90 days, respectively. The messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), nitric oxide (NO) content, iNOS activity, and histopathology were examined in chicken testes. The results showed that excess Mn upregulated mRNA expression of NF-κB, COX-2, TNF-α, and iNOS, NO content, and iNOS activity at 60th and 90th day. Mn had a time-dependent effect on NF-κB and TNF-α mRNA expression. Mn had a dose- and time-dependent effect on NO content and iNOS activity. Mn exposure induced chicken testis histological changes in dose- and time-dependent manner. It indicated that Mn exposure resulted in inflammatory injury of chicken testis tissue through NF-κB/iNOS-COX-2 signaling pathway.

  5. The Effect of Bee Venom on COX-2, P38, ERK and JNK in RAW 264.7 Cells

    Directory of Open Access Journals (Sweden)

    Jae-Young Sim

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate the effect of Bee Venom on the lipopolysaccharide(LPS, sodium nitroprusside(SNP, hydrogen peroxide(H2O2-induced expressions of cyclooxygenase-2(COX-2, p38, jun N-terminal Kinase(JNK and extra-signal response kinase(ERK in RAW 264.7 cells, a murine macrophage cell line. Methods : The expressions of COX-2, p38, JNK and ERK were determined by western blotting with corresponding antibodies.\\ Results : 1. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited significantly LPS and SNP-induced expression of COX-2 compared with control, respectively. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited insignificantly H2O2-induced expression of COX-2 compared with control, respectively. 2. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited significantly LPS, SNP and H2O2-induced expression of p38 compared with control, respectively. 3. The 1 and 5 ㎍/㎖ of bee venom inhibited significantly SNP-induced expression of JNK compared with control, respectively. All of bee venom inhibited insignificantly LPS and H2O2-induced expression of JNK compared with control, respectively. 4. The 5 ㎍/㎖ of bee venom inhibited significantly SNP-induced expression of ERK, the 0.5 ㎍/㎖ of bee venom increased significantly H2O2-induced expression of ERK compared with control. The 0.5, 1 and 5 ㎍/㎖ of bee venom inhibited insignificantly LPS-induced expression of ERK compared with control, respectively.

  6. Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1β Proteins in a Rat Model of Cerebral Ischemia.

    Science.gov (United States)

    Nia, Alireza Mousavi; Kalantaripour, Taj Pari; Basiri, Mohsen; Vafaee, Farzaneh; Asadi-Shekaari, Majid; Eslami, Azam; Zadeh, Fatemeh Darvish

    2017-03-01

    Nepeta dschuparensis Bornm (NP) is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2) and interleukin-1β (IL-1β) protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. Twenty-six male rats were randomly divided into 3 groups: 1) sham (n=6): no middle cerebral artery occlusion (MCAO) procedure, 2) control (n=10): MCAO procedure and treatment with normal saline, and 3) NP extract (n=10): MCAO procedure and treatment with the NP extract (20 mg/kg, i.p.) at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1β and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01). Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1β and COX-2 protein levels too (P<0.01). The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1β and COX-2.

  7. Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1β Proteins in a Rat Model of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Alireza Mousavi Nia

    2017-03-01

    Full Text Available Background: Nepeta dschuparensis Bornm (NP is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2 and interleukin-1β (IL-1β protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. Methods: Twenty-six male rats were randomly divided into 3 groups: 1 sham (n=6: no middle cerebral artery occlusion (MCAO procedure, 2 control (n=10: MCAO procedure and treatment with normal saline, and 3 NP extract (n=10: MCAO procedure and treatment with the NP extract (20 mg/kg, i.p. at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1β and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01. Results: Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1β and COX-2 protein levels too (P<0.01. Conclusion: The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1β and COX-2.

  8. Mn and Co Charge and Spin Evolutions in LaMn1-xCoxO3 Nanoparticles

    NARCIS (Netherlands)

    Ghiasi Kabiri, Mahnaz; Delgado-Jaime, Mario Ulises; Malekzadeh, Azim; Wang, Ru Pan; Miedema, Piter S.; Beye, Martin; De Groot, Frank M F

    2016-01-01

    The charge and spin-state evolution of manganese and cobalt in the LaMn1-xCoxO3 (x = 0.00, 0.25, 0.50, 0.75, and 1.00) perovskite nanoparticles have been studied with soft X-ray absorption spectroscopy. The results show a gradual increase in the average oxidation state of both Mn and Co ions with co

  9. ADI FD schemes for the numerical solution of the three-dimensional Heston-Cox-Ingersoll-Ross PDE

    Science.gov (United States)

    Haentjens, Tinne

    2012-09-01

    This paper deals with the numerical solution of the time-dependent, three-dimensional Heston-Cox-Ingersoll- Ross PDE, with all correlations nonzero, for the fair pricing of European call options. We apply a finite difference dis-cretization on non-uniform spatial grids and then numerically solve the semi-discrete system in time by using an Alternating Direction Implicit scheme. We show that this leads to a highly efficient and stable numerical solution method.

  10. Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning.

    Science.gov (United States)

    van Dijk, M R; Steyerberg, E W; Stenning, S P; Dusseldorp, E; Habbema, J D F

    2004-03-22

    The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility. We aimed to examine the extent of any loss in discrimination within the IGCC classification in comparison with alternative modelling by formal weighing of the risk factors. We analysed survival of 3048 NSGCT patients with Cox regression and recursive partitioning for alternative classifications. Good, intermediate and poor prognosis groups were based on predicted 5-year survival. Classifications were further refined by subgrouping within the poor prognosis group. Performance was measured primarily by a bootstrap corrected c-statistic to indicate discriminative ability for future patients. The weights of the risk factors in the alternative classifications differed slightly from the implicit weights in the IGCC classification. Discriminative ability, however, did not increase clearly (IGCC classification, c=0.732; Cox classification, c=0.730; Recursive partitioning classification, c=0.709). Three subgroups could be identified within the poor prognosis groups, resulting in classifications with five prognostic groups and slightly better discriminative ability (c=0.740). In conclusion, the IGCC classification in three prognostic groups is largely supported by Cox regression and recursive partitioning. Cox regression was the most promising tool to define a more refined classification. British Journal of Cancer (2004) 90, 1176-1183. doi:10.1038/sj.bjc.6601665 www.bjcancer.com Published online 24 February 2004

  11. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    Science.gov (United States)

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  12. Molecular characterization of Sarcocystis species from Polish roe deer based on ssu rRNA and cox1 sequence analysis.

    Science.gov (United States)

    Kolenda, Rafał; Ugorski, Maciej; Bednarski, Michał

    2014-08-01

    Sarcocysts from four Polish roe deer were collected and examined by light microscopy, small subunit ribosomal RNA (ssu rRNA), and the subunit I of cytochrome oxidase (cox1) sequence analysis. This resulted in identification of Sarcocystis gracilis, Sarcocystis oviformis, and Sarcocystis silva. However, we were unable to detect Sarcocystis capreolicanis, the fourth Sarcocystis species found previously in Norwegian roe deer. Polish sarcocysts isolated from various tissues differed in terms of their shape and size and were larger than the respective Norwegian isolates. Analysis of ssu rRNA gene revealed the lack of differences between Sarcocystis isolates belonging to one species and a very low degree of genetic diversity between Polish and Norwegian sarcocysts, ranging from 0.1% for Sarcocystis gracilis and Sarcocystis oviformis to 0.44% for Sarcocystis silva. Contrary to the results of the ssu rRNA analysis, small intraspecies differences in cox1 sequences were found among Polish Sarcocystis gracilis and Sarcocystis silva isolates. The comparison of Polish and Norwegian cox1 sequences representing the same Sarcocystis species revealed similar degree of sequence identity, namely 99.72% for Sarcocystis gracilis, 98.76% for Sarcocystis silva, and 99.85% for Sarcocystis oviformis. Phylogenetic reconstruction and genetic population analyses showed an unexpected high degree of identity between Polish and Norwegian isolates. Moreover, cox1 gene sequences turned out to be more accurate than ssu rRNA when used to reveal phylogenetic relationships among closely related species. The results of our study revealed that the same Sarcocystis species isolated from the same hosts living in different geographic regions show a very high level of genetic similarity.

  13. Magnetocaloric properties of LaFe13−x−yCoxSiy and commercial grade Gd

    DEFF Research Database (Denmark)

    Bjørk, Rasmus; Bahl, Christian Robert Haffenden; Katter, M.

    2010-01-01

    The magnetocaloric properties of three samples of LaFe13−x−yCoxSiy have been measured and compared to measurements of commercial grade Gd. The samples have (x=0.86, y=1.08), (x=0.94, y=1.01) and (x=0.97, y=1.07) yielding Curie temperatures in the range 276–288 K. The magnetization, specific heat...

  14. Single Exposure of Human Oral Mucosa Fibroblasts to Ultraviolet B Radiation Reduces Proliferation and Induces COX-2 Expression and Activation

    Directory of Open Access Journals (Sweden)

    Y Boza

    2010-12-01

    Full Text Available The lip vermillion constitutes a transition tissue, between oral mucosa and skin, where oral mucosal cells from epithelial and connective tissue compartments are exposed to ultraviolet (UV sunlight. Fibroblasts are abundant resident cells of the connective tissue which are key regulators of extracellular matrix composition, as well as, epithelial and endothelial cell function. UVB light, an inherent component of sunlight, causes several alterations in skin fibroblasts, including premature senescence and increased cyclooxygenase (COX-2 expression. To assess if UVB irradiation had similar effects on fibroblasts derived from human oral mucosa (HOM, primary cultures of HOM fibroblasts were irradiated with a single dose of 30 or 60 mJ/cm²of UVB light or sham-irradiated. Fibroblast proliferation was assessed from 3 to 48 hrs after UVB-irradiation utilizing [³H]-thymidine incorporation and MTT assays. In addition, COX-2 mRNA expression was detected by RT-PCR, and PGE2 production was assessed using enzyme immunoassay from 0.5 to 24 hrs after UVB-irradiation. The results showed a significant decrease in proliferation of UVB-irradiated HOM fibroblasts as compared to controls as measured by both [³H]-thymidine incorporation and MTT assays (p<0.001. HOM fibroblasts had increased COX-2 mRNA expression at 0.5 and 12 hrs after irradiation, and PGE2 production was elevated at 12 and 24 hrs post-irradiation as compared to controls (p<0.05. The results showed an inhibitory effect of a single dose of UVB irradiation on HOM fibroblast proliferation with an increase in COX-2 expression and activation. Therefore, photodamaged fibroblasts may play and important role in the pathogenesis of UV-induced lesions of the lip.

  15. Analyzing Left-truncated and Right-censored Data under Cox Models with Long-term Survivors

    Institute of Scientific and Technical Information of China (English)

    Fei-peng ZHANG; YONG ZHOU

    2013-01-01

    We analyze left-truncated and right-censored data using Cox proportional hazard models with long-term survivors.The estimators of covariate coefficients and the long-term survivor proportion are obtained by the partial likelihood method,and their asymptotic properties are also established.Simulation studies demonstrate the performance of the proposed estimators,and an application to a real dataset is provided.

  16. Survival analysis of gastric cancer patients using Cox model: a five year study

    Directory of Open Access Journals (Sweden)

    Biglarian A

    2009-08-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Gastric cancer is the second most common cancer and known as the second cause of death due to cancers worldwide. Adenocarcinoma is the most fatal cancer in Iran and a patient with this kind of cancer, has a lower lifetime than others. In this research, the survival of patients with gastric carcinoma who were registered at Taleghani Hospital, were studied."n"nMethods: 291 patients with Gastric carcinoma who had received care, chemotherapy or chemoradiotherapy, at Taleghani Hospital in Tehran from 2002 to 2007 were studied as a historical cohort. Their survival rates and its relationship with 12 risk factors were assessed."n"nResults: Of the 291 patients with Gastric carcinoma, 70.1 percent were men and others (29.9% were women. The mean age of men was 62.26 years and of women was 59.32 years at the time of diagnosis. Most of patients (93.91% were advanced stage and metastasis. The Cox proportional hazards model showed that age at diagnosis, tumor stage and histology type with survival time had significant relationships (p=0.039, p=0.042 and p=0.032 respectively."n"n Conclusion: The five-year survival rate and median lifetime of gastric cancer patients who underwent chemotherapy or chemoradiotherapy are very

  17. Effect of the major glycosides of Harpagophytum procumbens (Devil's Claw) on epidermal cyclooxygenase-2 (COX-2) in vitro.

    Science.gov (United States)

    Abdelouahab, Nassima; Heard, Charles

    2008-05-01

    Harpagophytum procumbens, commonly known as Devil's Claw, is indigenous to southern Africa, and extracts of the tubers have been used for centuries in the treatment of a variety of inflammatory disorders. Its major active components, harpagoside (1), harpagide (2), 8-coumaroylharpagide (3), and verbascoside (4), are believed to interact either synergistically or antagonistically in modulating the enzymes responsible for inducing inflammation, although this has not been probed hitherto. In the current work, the ability of these compounds to inhibit the expression of COX-2 following administration to freshly excised porcine skin has been investigated. An ethanol-soluble extract of H. procumbens tubers and two of the pure compounds tested showed promising activity in Western blotting and immunocytochemical assays, with harpagoside (1) and 8-coumaroylharpagide (3) exhibiting greater reductions in COX-2 expression than verbascoside (4). Harpagide (2) caused a significant increase in the levels of COX-2 expression after 6 h of topical application. The data suggest that the efficacy of H. procumbens is dependent upon the ratios of compounds 1-4 present, which is inconsistent with some current official monograph specifications based solely on harpagoside (1) content.

  18. Decreased Tissue COX5B Expression and Mitochondrial Dysfunction during Sepsis-Induced Kidney Injury in Rats

    Science.gov (United States)

    Böhm, Lennert; Braunecker, Stefan; Adler, Christoph; De Robertis, Edoardo; Cirillo, Fabrizio

    2017-01-01

    Background. Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is the dominant cause of acute kidney injury (AKI), accounting for nearly 50% of episodes of acute renal failure. Signaling cascades and pathways within the kidney are largely unknown and analysis of these molecular mechanisms may enhance knowledge on pathophysiology and possible therapeutic options. Material and Methods. 26 male Wistar rats were assigned to either a sham group (control, N = 6) or sepsis group (N = 20; cecal ligature and puncture model, 24 and 48 hours after CLP). Surviving rats (n = 12) were decapitated at 24 hours (early phase; n = 6) or 48 hours (late phase; n = 6) after CLP and kidneys removed for proteomic analysis. 2D-DIGE and DeCyder 2D software (t-test, P cytochrome c oxidase subunit B (COX5b), myosin-6 (MYH6), and myosin-7 (MYH7). A significant correlation with the proteins was found for mitochondrial energy production and electron transport. Conclusions. COX5B could be a promising biomarker candidate since a significant association was found during experimental sepsis in the present study. For future research, COX5B should be evaluated as a biomarker in both human urine and serum to identify sepsis. PMID:28246552

  19. Modulation of COX2 and hTERT expression by photodynamic therapy in human colon cancer cells

    Science.gov (United States)

    Yow, Christine Li Miu N.; Chu, Ellie Shihng M.

    2009-06-01

    Photodynamic therapy (PDT) was employed as a cancer therapy with photosensitizer (PS)-loaded cancer cells, eradicated by the reactive oxygen species after light activation. Cyclo-oxygenase 2 (COX2) is an enzyme expressed in 80% of colon adenocarcinoma and is one of the targets for effective cancer treatment. There is also uprising evidence that the human telomerase reverse transcriptase (hTERT), a catalytic component of telomerase, is reported as a promising indicator for monitoring cancer treatment. In this study, NPe6 mediated PDT on COX2 induced apoptosis in HT-29 was investigated. The cell cycle changes was analysed by flow cytometry and the hTERT expression at pre and post PDT was evaluated at transcription level by Taqman real time PCR. NPe6-PDT in HT-29 cells demonstrated anti-proliferating effect in a drug and light dose dependent manner. LD50 was achieved at 16μg/mL and 2J/cm2 at 4 hour-post treatment with a significant down-regulation of COX2 expression at LD30 and LD50 by immunohistochemical staining (IHC) (pcancer treatment efficacy.

  20. A Note Comparing Component-Slope, Scheffé, and Cox Parameterizations of the Linear Mixture Experiment Model

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F.

    2006-05-01

    A mixture experiment involves combining two or more components in various proportions and collecting data on one or more responses. A linear mixture model may adequately represent the relationship between a response and mixture component proportions and be useful in screening the mixture components. The Scheffé and Cox parameterizations of the linear mixture model are commonly used for analyzing mixture experiment data. With the Scheffé parameterization, the fitted coefficient for a component is the predicted response at that pure component (i.e., single-component mixture). With the Cox parameterization, the fitted coefficient for a mixture component is the predicted difference in response at that pure component and at a pre-specified reference composition. This paper presents a new component-slope parameterization, in which the fitted coefficient for a mixture component is the predicted slope of the linear response surface along the direction determined by that pure component and at a pre-specified reference composition. The component-slope, Scheffé, and Cox parameterizations of the linear mixture model are compared and their advantages and disadvantages are discussed.

  1. Mitochondrial toxicity of selective COX-2 inhibitors via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2016-01-01

    Cyclooxygenase-2 (COX-2) inhibitors (coxibs) are non-steroidal anti-inflammatory drugs (NSAIDs) designed to selectively inhibit COX-2. However, drugs of this therapeutic class are associated with drug induced liver injury (DILI) and mitochondrial injury is likely to play a role. The effects...... of selective COX-2 inhibitors on inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria were investigated. The order of potency of inhibition of ATP synthesis was: lumiracoxib (IC50: 6.48 ± 2.74 μM)>celecoxib (IC50: 14.92 ± 6.40 μM)>valdecoxib (IC50: 161.4 ± 28.6 μM)>rofecoxib (IC50...... correlation (with r(2)=0.921) was observed between the potency of inhibition of ATP synthesis and the log P values. The in vitro metabolism of coxibs in rat liver mitochondria yielded for each drug substance a major single metabolite and identified a hydroxy metabolite with each of the coxibs...

  2. Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis.

    Science.gov (United States)

    Tong, Dali; Liu, Qiuli; Liu, Gaolei; Xu, Jing; Lan, Weihua; Jiang, Yao; Xiao, Hualiang; Zhang, Dianzheng; Jiang, Jun

    2017-03-28

    Castration is the standard therapeutic treatment for advanced prostate cancer but with limited benefit due to the profound relapse and metastasis. Activation of inflammatory signaling pathway and initiation of epithelial-mesenchymal transition (EMT) are closely related to drug resistance, tumor relapseas well as metastasis. In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin. These effects have also been observed in our animal model as well as prostate cancer patients. In addition, we showed the effects of metformin on the expression of genes involved in EMT through repressing the levels of COX2, PGE2 and phosphorylated STAT3. Furthermore, inactivating COX2 abolishes metformin's regulatory effects and exogenously administered PGE2 is capable of enhancing STAT3 phosphorylation and expression of EMT biomarker. We propose that metformin represses prostate cancer EMT and metastasis through targeting the COX2/PGE2/STAT3 axis. These findings suggest that metformin by itself or in combination with other anticancer drugs could be used as an anti-metastasis therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Research of MIF,COX-2,NGF in chemical prostatitis of SD rats%大鼠化学性前列腺炎的MIF、COX-2、NGF实验研究

    Institute of Scientific and Technical Information of China (English)

    杨宇; 周辉良; 余鹏; 关胜; 陈志鹏; 刘启祥; 曹林升

    2012-01-01

    目的 通过了解巨噬细胞游走抑制因子(MIF)和环加氧酶(COX-2)、神经生长因子(NGF)在化学性前列腺炎大鼠模型前列腺、膀胱、尿道中的表达及这些器官的炎症情况,以探讨前列腺炎是否引起临近盆腔脏器炎症,以及引起前列腺炎临床症状的机制.方法 (1)实验动物分组:20只健康成年雄性SD大鼠随机分成两组,即福尔马林(formalin)组和生理盐水(saline)组,每组10只.(2)采用腹侧前列腺内注射福尔马林法建立化学性前列腺炎模型.(3)用HE染色法检测前列腺、膀胱、尿道的炎症情况.(4)用免疫组织化学方法、Western blot法检测各标本MIF、NGF和COX-2的表达.结果 观察到前列腺注射福尔马林引起了前列腺、膀胱和尿道炎症的组织学改变.包括前列腺注射福尔马林后膀胱和尿道MIF蛋白量降低,而COX-2蛋白和NGF蛋白量增加.结论 大鼠化学性前列腺炎通过神经反射引起膀胱、尿道上皮细胞释放P物质,促使MIF释放,诱导其他炎性介质如COX-2,NGF的活化,进而引起临近脏器如膀胱、尿道出现炎症,并维持炎症循环,出现临床症状.%Objective To investigate the expression of MIF, COX-2 (cyclooxygenase-2) and NGF (nerve growth factor) in the prostate, bladder and urethra of chemical prostatitis rat models and the cause of some symptoms. Methods 1. Twenty rats were randomly divided into two groups-the formalin group and saline group, 10 in each group. 2. The inflammation condition of the bladder and prostate was verified histologically by HE staining. 3.The protein level expression of MIF.COX-2 and NGF were examined by the immunohistochemical and Western blot. Results Rats injected with formalin mixed with dye showed restriction of the dye to the prostate. Intraprostatic formalin produced inflammation in the prostate, and bladder and urethra inflammation was detected using HE. The amount of MIF protein in the bladder and urethra were decreased, while COX

  4. HER2 induces cell proliferation and invasion of non-small-cell lung cancer by upregulating COX-2 expression via MEK/ERK signaling pathway

    Directory of Open Access Journals (Sweden)

    Chi F

    2016-05-01

    Full Text Available Feng Chi, Rong Wu, Xueying Jin, Min Jiang, Xike Zhu Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: HER2 positivity has been well studied in various cancers, but its importance in non-small-cell lung cancer (NSCLC is still being explored. In this study, quantitative reverse transcription polymerase chain reaction (qRT-PCR was performed to detect HER2 and COX-2 expression in NSCLC tissues. Then, pcDNA3.1-HER2 was used to overexpress HER2, while HER2 siRNA and COX-2 siRNA were used to silence HER2 and COX-2 expression. MTT assay and invasion assay were used to detect the effects of HER2 on cell proliferation and invasion. Our study revealed that HER2 and COX-2 expression were upregulated in NSCLC tissues and HER2 exhibited a significant positive correlation with the levels of COX-2 expression. Overexpression of HER2 evidently elevated COX-2 expression, while silencing of HER2 evidently decreased COX-2 expression. Furthermore, overexpressed HER2 induced the ERK phosphorylation, and this was abolished by the treatment with U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. HER2-induced expression and promoter activity of COX-2 were also suppressed by U0126, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, HER2 induced activation of AKT signaling pathway, which was reversed by pretreatment with U0126 and COX-2 siRNA. MTT and invasion assays revealed that HER2 induced cell proliferation and invasion that were reversed by pretreatment with U0126 and COX-2 siRNA. In this study, our results demonstrated for the first time that HER2 elevated COX-2 expression through the activation of MEK/ERK pathway, which subsequently induced cell proliferation and invasion via AKT pathway in NSCLC tissues. Keywords: HER2, MEK/ERK, COX-2, AKT signaling pathway, non-small-cell lung cancer

  5. Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP Kinase-dependent and -independent mechanisms in mouse RAW264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Lee Jong

    2012-05-01

    Full Text Available Abstract Background Carbon nanotubes (CNTs are engineered graphene cylinders with numerous applications in engineering, electronics and medicine. However, CNTs cause inflammation and fibrosis in the rodent lung, suggesting a potential human health risk. We hypothesized that multi-walled CNTs (MWCNTs induce two key inflammatory enzymes in macrophages, cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS, through activation of extracellular signal-regulated kinases (ERK1,2. Methods RAW264.7 macrophages were exposed to MWCNTs or carbon black nanoparticles (CBNPs over a range of doses and time course. Uptake and subcellular localization of MWCNTs was visualized by transmission electron microscopy (TEM. Protein levels of COX-2, iNOS, and ERK1,2 (total ERK and phosphorylated ERK were measured by Western blot analysis. Prostaglandin-E2 (PGE2 and nitric oxide (NO levels in cell supernatants were measured by ELISA and Greiss assay, respectively. Results MWCNTs, but not CBNPs, induced COX-2 and iNOS in a time- and dose-dependent manner. COX-2 and iNOS induction by MWCNTs correlated with increased PGE2 and NO production, respectively. MWCNTs caused ERK1,2 activation and inhibition of ERK1,2 (U0126 blocked MWCNT induction of COX-2 and PGE2 production, but did not reduce the induction of iNOS. Inhibition of iNOS (L-NAME did not affect ERK1,2 activation, nor did L-NAME significantly decrease COX-2 induction by MWCNT. Nickel nanoparticles (NiNPs, which are present in MWCNTs as a residual catalyst, also induced COX-2 via ERK-1,2. However, a comparison of COX-2 induction by MWCNTs containing 4.5 and 1.8% Ni did not show a significant difference in ability to induce COX-2, indicating that characteristics of MWCNTs in addition to Ni content contribute to COX-2 induction. Conclusion This study identifies COX-2 and subsequent PGE2 production, along with iNOS induction and NO production, as inflammatory mediators involved in the macrophage response to

  6. Effects of melatonin on the expression of iNOS and COX-2 in rat models of colitis

    Institute of Scientific and Technical Information of China (English)

    Wei-Guo Dong; Qiao Mei; Jie-Ping Yu; Jian-Ming Xu; Li Xiang; Yu Xu

    2003-01-01

    AIM: To investigate the effects of melatonin (MT) on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat models of colitis. METHODS: Healthy adult Sprague-Dawlay (SD) rats of both sexes, weighing 280±30 g, were employed in the present study. The rat models of colitis were induced by either acetic acid or 2,4,6-trinitrobenzene sulfonic acid (TNBS) enemas. The experimental animals were randomly divided into melatonin treatment and model control group that were intracolicly treated daily with melatonin at doses of 2.5, 5.0, 10.0 mg.kg-1 and equal amount of saline respectively from 24 h following induction of colitis in rats inflicted with acetic acid enema and the seventh day in rats with TNBS to the end of study. A normal control group of rats treated with neither acetic acid nor TNBS but saline enema was also included in the study. On the 28th day of the experiment, the rat colon mucosal damage index (CDMI) was calculated, and the colonic prostaglandin E2(PGE2), nitric oxide (NO), as well as the iNOS and COX-2expression were also determined biochemically or immunohistochemically. RESULTS: CDMI increased to 2.87±0.64 and 3.12±1.12respectively in rats treated with acetic acid and TNBS enema,which was in accordance with the significantly elevated colonic NO and PGE2 contents, as well as the up-regulated colonic iNOS and COX-2 expression in both of the two rat models of colitis. With treatment by melatonin at the doses of 5.0 and 10.0 mg@kg-1, CDMI in both models of rat colitis was significantly decreased (P<0.05-0.01), which accorded synchronously and unanimously with the reduced colonic NO and PGE2 content, as well as the down-regulated expression of colonic iNOS and COX-2. CONCLUSION: Melatonin has a protective effect on colonic injury induced by both acetic acid and TNBS enemas, which is probably via a mechanism of local inhibition of iNOS and COX-2 expression in colonic mucosa.

  7. Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers.

    Science.gov (United States)

    Hougee, Sander; Faber, Joyce; Sanders, Annemarie; de Jong, Romy B; van den Berg, Wim B; Garssen, Johan; Hoijer, Maarten A; Smit, H Friso

    2005-05-01

    In this study, an extract of Pterocarpus marsupium Roxb. containing pterostilbene has been evaluated for its PGE2-inhibitory activity in LPS-stimulated PBMC. In addition, the COX-1/2 selective inhibitory activity of P. marsupium (PM) extract was investigated. Biological activity, as well as safety of PM extract was evaluated in healthy human volunteers. PM extract, pterostilbene and resveratrol inhibited PGE2 production from LPS-stimulated human peripheral blood mononuclear cells (PBMC) with IC50 values of 3.2 +/- 1.3 microg/mL, 1.0 +/- 0.6 microM and 3.2 +/- 1.4 microM, respectively. When pterostilbene content of PM extract is calculated, PGE2 production inhibition of PM extract is comparable to PGE2 production inhibition of purified pterostilbene. Furthermore, in a COX-1 whole blood assay (WBA) PM extract was not effective while in a COX-2 WBA, PM extract decreased PGE2 production indicating COX-2 specific inhibition. In healthy human volunteers, the oral use of 450 mg PM extract did not decrease PGE2 production ex vivo in a WBA. Pterostilbene levels in serum were increased, but were 5-fold lower than the observed IC50 for PGE2 inhibition in LPS-stimulated PBMC. No changes from base-line of the safety parameters were observed and no extract-related adverse events occurred during the study. In conclusion, this is the first study to describe the selective COX-2 inhibitory activity of a Pterocarpus marsupium extract. Moreover, the PGE2 inhibitory activity of PM extract was related to its pterostilbene content. In humans, 450 mg PM extract resulted in elevated pterostilbene levels in serum, which were below the active concentration observed in vitro. In addition, short-term supplementation of 450 mg PM extract is considered to be a safe dose based on the long history of use, the absence of abnormal blood cell counts and blood chemistry values and the absence of extract-related adverse events. This strongly argues for a dose-finding study of PM extract in humans to

  8. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Hiroshi, E-mail: htomita@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574 (Japan); Tabata, Kitako, E-mail: ktabata@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Takahashi, Maki, E-mail: mqdelta@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Nishiyama, Fumiaki, E-mail: t2114018@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Sugano, Eriko, E-mail: sseriko@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan)

    2016-05-13

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  9. Saturated fatty acids up-regulate COX-2 expression in prostate epithelial cells via toll-like receptor 4/NF-κB signaling.

    Science.gov (United States)

    Liu, Jie; Hu, Shuai; Cui, Yun; Sun, Meng-Kui; Xie, Feng; Zhang, Qian; Jin, Jie

    2014-04-01

    Cyclooxygenase-2 (COX-2) has been implicated in prostate carcinogenesis, and recently it has been confirmed to be a molecular target of saturated fatty acids (SFAs). In the present study, we investigated the effect of stearic acid (SA) and palmitic acid (PA), two of the most abundant SFAs contained in dietary fat, on COX-2 expression in prostate epithelial cells and the signaling transduction pathway involved. First, we demonstrated that both SA and PA increased the mRNA and protein expression of COX-2, and consistently induced the activation of NF-κB in RWPE-1, BPH-1 and PC-3 prostate epithelial cell lines. The effect of SA and PA on COX-2 over-expression and NF-κB activation was in a dose-dependent manner, and PA was more potent than SA at the same concentration. Then, we demonstrated inhibition of NF-κB using its specific inhibitor strikingly attenuated PA-induced COX-2 expression. Toll-like receptor 4 (TLR4) was revealed to be expressed on RWPE-1, BPH-1 and PC-3 cell lines by PCR and immunofluorescence staining, and blocking its signaling significantly inhibited PA induced COX-2 over-expression and NF-κB activation. Taken together, we demonstrated that SFAs can up-regulate COX-2 expression in prostate epithelial cells, and this effect was mediated mainly through the TLR4/NF-κB signaling pathway.

  10. Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice.

    Science.gov (United States)

    Kiraly, Alex J; Soliman, Eman; Jenkins, Audrey; Van Dross, Rukiyah T

    2016-01-01

    Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. NMSC overexpresses cyclooxygenase-2 (COX-2). COX-2 synthesizes prostaglandins such as PGE2 which promote proliferation and tumorigenesis by engaging G-protein-coupled prostaglandin E receptors (EP). Apigenin is a bioflavonoid that blocks mouse skin tumorigenesis induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the effect of apigenin on the COX-2 pathway has not been examined in the DMBA/TPA skin tumor model. In the present study, apigenin decreased tumor multiplicity and incidence in DMBA/TPA-treated SKH-1 mice. Analysis of the non-tumor epidermis revealed that apigenin reduced COX-2, PGE2, EP1, and EP2 synthesis and also increased terminal differentiation. In contrast, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors. Since fewer tumors developed in apigenin-treated animals which contained reduced epidermal COX-2 levels, our data suggest that apigenin may avert skin tumor development by blocking COX-2.

  11. Expression of COX-2 on Reed-Sternberg cells is an independent unfavorable prognostic factor in Hodgkin lymphoma treated with ABVD.

    Science.gov (United States)

    Mestre, Francisco; Gutierrez, Antonio; Ramos, Rafael; Martinez-Serra, Jordi; Sánchez, Lydia; Matheu, Gabriel; Ros, Teresa; Garcia, Juan Fernando; Rodriguez, Jose

    2012-06-21

    Cyclooxygenase 2 (COX-2) is an inflammatory enzyme involved in the pathogenesis and prognosis of several malignancies. In the present study, we investigated the prognostic value of COX-2 expression in a large (N = 242), uniformly treated Hodgkin lymphoma (HL) population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analysis was done, including comparing the most recognized clinical variables: the early- and advanced-stage subgroups. COX-2 was expressed on Reed-Sternberg cells in 37% of patients. There were no differences in the distribution of clinical variables according to COX-2 expression. With a median follow-up time of 58 months, PFS at 5 years was 60% and 79% for COX-2(+) and COX-2(-) patients, respectively (P = .003). The overall survival was 73% and 91%, respectively (P Sternberg cells in one-third of HL patients and was a major independent, unfavorable prognostic factor in early-stage HL. We conclude that COX-2 may be a major prognostic variable in HL and a potential therapeutic target.

  12. GRACILARIA VERMICULOPHYLLA (RHODOPHYTA, GRACILARIALES) IN THE VIRGINIA COASTAL BAYS, USA: COX1 ANALYSIS REVEALS HIGH GENETIC RICHNESS OF AN INTRODUCED MACROALGA.

    Science.gov (United States)

    Gulbransen, Dana J; McGlathery, Karen J; Marklund, Maria; Norris, James N; Gurgel, Carlos Frederico D

    2012-10-01

    Gracilaria vermiculophylla (Ohmi) Papenfuss is an invasive alga that is native to Southeast Asia and has invaded many estuaries in North America and Europe. It is difficult to differentiate G. vermiculophylla from native forms using morphology and therefore molecular techniques are needed. In this study, we used three molecular markers (rbcL, cox2-cox3 spacer, cox1) to identify G. vermiculophylla at several locations in the western Atlantic. RbcL and cox2-cox3 spacer markers confirmed the presence of G. vermiculophylla on the east coast of the USA from Massachusetts to South Carolina. We used a 507 base pair region of cox1 mtDNA to (i) verify the widespread distribution of G. vermiculophylla in the Virginia (VA) coastal bays and (ii) determine the intraspecific diversity of these algae. Cox1 haplotype richness in the VA coastal bays was much higher than that previously found in other invaded locations, as well as some native locations. This difference is likely attributed to the more intensive sampling design used in this study, which was able to detect richness created by multiple, diverse introductions. On the basis of our results, we recommend that future studies take differences in sampling design into account when comparing haplotype richness and diversity between native and non-native studies in the literature.

  13. Resveratrol inhibits BK-induced COX-2 transcription by suppressing acetylation of AP-1 and NF-κB in human rheumatoid arthritis synovial fibroblasts.

    Science.gov (United States)

    Yang, Chuen-Mao; Chen, Yu-Wen; Chi, Pei-Ling; Lin, Chih-Chung; Hsiao, Li-Der

    2017-05-15

    Bradykinin (BK) induces inflammation in rheumatoid arthritis (RA). Resveratrol is a potent activator of Sirt1 which could modulate inflammation through deacetylating histones of transcription factors. Here, we investigated the mechanisms underlying BK-induced COX-2 expression which is modulated by resveratrol/Sirt1 in human rheumatoid arthritis synovial fibroblasts (RASFs). We found that BK-induced COX-2 protein and mRNA expression associated with PGE2 synthesis, and promoter activity was mediated through B2R receptors, which were attenuated by selective B2R antagonist Hoe140 or transfection with B2R siRNA. BK-induced responses were mediated through PKCμ, MAPKs, AP-1 and NF-κB which were inhibited by their respective inhibitors or siRNAs. Up-regulation of Sirt1 by resveratrol suppressed the BK-induced COX-2/PGE2 production through inhibiting the interaction of AP-1 and NF-κB with COX-2 promoter in RASFs. BK-induced COX-2/PGE2 expression is mediated through a B2R-PKCμ-dependent MAPKs, AP-1, and NF-κB cascade. Resveratrol inhibited the phosphorylation and acetylation of p65, c-Jun, and Fos and reduced the binding to the COX-2 promoter, thereby attenuated the COX-2 expression. Therefore, resveratrol may be a promising therapeutic intervention for treatment of inflammatory arthritis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

    2015-08-01

    Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

  15. Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-κB pathway in mouse brain microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Lin Chih-Chung

    2013-01-01

    Full Text Available Abstract Background Endothelin-1 (ET-1 is a proinflammatory mediator and elevated in the regions of several brain injury and inflammatory diseases. The deleterious effects of ET-1 on endothelial cells may aggravate brain inflammation mediated through the regulation of cyclooxygenase-2 (COX-2/prostaglandin E2 (PGE2 system in various cell types. However, the signaling mechanisms underlying ET-1-induced COX-2 expression in brain microvascular endothelial cells remain unclear. Herein we investigated the effects of ET-1 in COX-2 regulation in mouse brain microvascular endothelial (bEnd.3 cells. Results The data obtained with Western blotting, RT-PCR, and immunofluorescent staining analyses showed that ET-1-induced COX-2 expression was mediated through an ETB-dependent transcriptional activation. Engagement of Gi- and Gq-protein-coupled ETB receptors by ET-1 led to phosphorylation of ERK1/2, p38 MAPK, and JNK1/2 and then activated transcription factor NF-κB. Moreover, the data of chromatin immunoprecipitation (ChIP and promoter reporter assay demonstrated that the activated NF-κB was translocated into nucleus and bound to its corresponding binding sites in COX-2 promoter, thereby turning on COX-2 gene transcription. Finally, up-regulation of COX-2 by ET-1 promoted PGE2 release in these cells. Conclusions These results suggested that in mouse bEnd.3 cells, activation of NF-κB by ETB-dependent MAPK cascades is essential for ET-1-induced up-regulation of COX-2/PGE2 system. Understanding the mechanisms of COX-2 expression and PGE2 release regulated by ET-1/ETB system on brain microvascular endothelial cells may provide rationally therapeutic interventions for brain injury or inflammatory diseases.

  16. AtCOX10, a protein involved in haem o synthesis during cytochrome c oxidase biogenesis, is essential for plant embryogenesis and modulates the progression of senescence.

    Science.gov (United States)

    Mansilla, Natanael; Garcia, Lucila; Gonzalez, Daniel H; Welchen, Elina

    2015-11-01

    Cytochrome c oxidase (CcO) biogenesis requires several accessory proteins implicated, among other processes, in copper and haem a insertion. In yeast, the farnesyltransferase Cox10p that catalyses the conversion of haem b to haem o is the limiting factor in haem a biosynthesis and is essential for haem a insertion in CcO. In this work, we characterized AtCOX10, a putative Cox10p homologue from Arabidopsis thaliana. AtCOX10 was localized in mitochondria and was able to restore growth of a yeast Δcox10 null mutant on non-fermentable carbon sources, suggesting that it also participates in haem o synthesis. Plants with T-DNA insertions in the coding region of both copies of AtCOX10 could not be recovered, and heterozygous mutant plants showed seeds with embryos arrested at early developmental stages that lacked CcO activity. Heterozygous mutant plants exhibited lower levels of CcO activity and cyanide-sensitive respiration but normal levels of total respiration at the expense of an increase in alternative respiration. AtCOX10 seems to be implicated in the onset and progression of senescence, since heterozygous mutant plants showed a faster decrease in chlorophyll content and photosynthetic performance than wild-type plants after natural and dark-induced senescence. Furthermore, complementation of mutants by expressing AtCOX10 under its own promoter allowed us to obtain plants with T-DNA insertions in both AtCOX10 copies, which showed phenotypic characteristics comparable to those of wild type. Our results highlight the relevance of haem o synthesis in plants and suggest that this process is a limiting factor that influences CcO activity levels, mitochondrial respiration, and plant senescence.

  17. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-κB-signaling pathways

    Science.gov (United States)

    Suh, Yewseok; Afaq, Farrukh; Johnson, Jeremy J.; Mukhtar, Hasan

    2009-01-01

    Overexpression of cyclooxygenase 2 (COX2) and uncontrolled wingless and Int (Wnt)-signaling pathway have long been suggested to play crucial roles in colorectal cancer. Studies show that selective COX2 inhibitors possess great potential as chemopreventive agents for colon cancer. Recent studies suggest that targeting COX2 and epidermal growth factor receptor (EGFR) may provide better therapeutic strategy than inhibiting either single target and that this may alleviate the problem of COX2 inhibitor-associated side effects. Therefore, there have been intensive efforts to develop novel dietary substances that target COX2 and EGFR activation. Fisetin is a naturally occurring flavonoid commonly found in various vegetables and fruits. We found that the treatment of COX2-overexpressing HT29 human colon cancer cells with fisetin (30–120 μM) resulted in induction of apoptosis, downregulation of COX2 protein expression without affecting COX1 and inhibited the secretion of prostaglandin E2. Treatment of cells with fisetin also inhibited Wnt-signaling activity through downregulation of β-catenin and T cell factor 4 and decreased the expression of target genes such as cyclin D1 and matrix metalloproteinase 7. Fisetin treatment of cells also inhibited the activation of EGFR and nuclear factor-kappa B (NF-κB). Finally, the formation of colonies in soft agar was suppressed by fisetin treatment. Taken together, we provide evidence that the plant flavonoid fisetin can induce apoptosis and suppress the growth of colon cancer cells by inhibition of COX2- and Wnt/EGFR/NF-κB-signaling pathways. We suggest that fisetin could be a useful agent for prevention and treatment of colon cancer. PMID:19037088

  18. EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

    Directory of Open Access Journals (Sweden)

    Panagiotis A. Konstantinopoulos

    2007-01-01

    Full Text Available Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN, p-Iκ:B-α (phosphorylated Iκ:B-α, EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.

  19. Evaluation of Cytotoxicity Effects of Chalcone Epoxide Analogues as a Selective COX-II Inhibitor in the Human Liver Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Pouran Makhdoumi

    2017-09-01

    Full Text Available Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2 is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2 cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2 production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.

  20. Effects of COX-2 and COX-2 inhibitors in the vascular targeted therapy of pancreatic cancer%环氧合酶-2及其抑制剂在胰腺癌血管靶向治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    刘丽燕; 高苏俊; 李雷

    2011-01-01

    胰腺癌的诊治目前仍是医学界的难题,血管生成是胰腺癌生长和转移的必要因素.环氧合酶(cyclooxygenase,COX)为花生四烯酸代谢过程中的关键酶,存在COX-1及COX-2两种同工酶,其中COX-2在胰腺癌的发生发展及胰腺癌血管生成中发挥重要作用.COX-2抑制剂可分为非选择性及选择性两种,两种COX-2抑制剂都对胰腺癌及其血管形成的发生与进展存在抑制作用,COX-2抑制剂抗肿瘤血管形成的机制可能是抑制血管内皮生长因子(VEGF)、缺氧诱导因子-1及基质金属蛋白酶(MMP)的表达、降低前列腺素(PGs)及其他血管生成因子的表达、促进内皮细胞凋亡、抑制内皮细胞侵袭力和影响一氧化氮合酶(NOS)的表达.%The diagnosis and treatment of pancreatic cancers are still a difficult subject in the medical profession at present.Angiogenesis is necessary for the growth and metastasis of pancreatic cancers.Cyclooxygenase (COX) is a key enzyme in the process of arachidonic acid metabolism; there are two isoenzymes of COX ( COX-1 and COX-2).COX-2 plays an important role in the development and angiogenesis of pancreatic cancers.COX-2 inhibitors can be classified into selective and non-selective types.The occurrence, progression and angiogenesis of pancreatic cancers are inhibited by both COX-2 inhibitors.The mechanism underlying anti-angiogenesis of COX-2 inhibitors includes down-regulating VEGF, hypoxia inducible factor-1 and matrix metalloproteinase (MMP) expres sions, reducing the expression of prostaglandins (PGs) and other angiogenic factors, promoting endothelial cells apoptosis, inhibiting invasion of endothelial cells and modulating the nitric oxide synthase (NOS) expression.