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Sample records for ciclooxigenase-2 cox-2 aspectos

  1. Antiinflamatórios não esteróides inibidores da ciclooxigenase-2 (COX-2: aspectos atuais Antiinflamatorios no esteróides inhibidores de la ciclooxigenasa-2 (COX-2: aspectos actuales Cycloxygenase-2 inhibitors nonsteroid anti-inflammatory drugs: current issues

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    Carmen Luize Kummer

    2002-07-01

    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.JUSTIFICATIVA Y OBJETIVOS: Debido a la alta incidencia de efectos colaterales relacionados a los antiinflamatorios no hormonales (AINES, la descubierta de dos isoformas de la enzima ciclooxigenasa, clasificadas como: COX-1

  2. Experimental study of the action of COX-2 selective nonsteroidal anti-inflammatory drugs and traditional anti-inflammatory drugs in bone regeneration Estudo experimental da ação dos anti-inflamatórios não hormonais inibidores seletivos da ciclooxigenase 2 (COX-2 e anti-inflamatórios tradicionais na regeneração óssea

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    Bruno C. Tiseo

    2006-06-01

    Full Text Available OBJECTIVE: The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2 inhibitors in the process of bone regeneration in a rat model. MATERIALS AND METHODS: Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo. Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed. RESULTS: No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue. CONCLUSIONS: Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.OBJETIVO: Comparar os efeitos do uso de antiinflamatórios não-esteróides tradicionais (AINES e AINES que são inibidores seletivos da ciclooxigenase-2 (COX-2, no processo de regeneração óssea em ratos. MATERIAL E MÉTODO: Quarenta e quatro ratos da linhagem Wistar submetidos a osteotomia do femur direito e divididos em três grupos, conforme o medicamento que receberam (diclofenaco, rofecoxib e placebo. Cada grupo foi dividido em dois subgrupos, conforme o tempo até o sacrifício, após a cirurgia. Os animais do subgrupo 1 foram sacrificados duas semanas após a cirurgia e os do subgrupo 2, quatro semanas após a cirurgia. Foram analisados exames radiográficos e a histomorfometria do calo

  3. 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

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    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.

  4. The role of Phosphatidylinositol 3 kinase (PI3K and Cycloxygenase-2 (COX2 in carcinogenesis of colorectal polyps

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    Raul Alberto Anselmi Júnior

    2018-01-01

    Fosfatase homóloga a tensina (PTEN, Fosfatidilinositol-3-cinase (PI3K, Ciclooxigenase-2 (COX2 e um marcador de proliferação (Ki67 em pólipos colorretais e correlacionar com dados clínicos e patológicos buscando sua correspondência na carcinogênese. Métodos: Revisados 297 pólipos diagnosticados através de endoscopia quanto a idade, gênero, história de câncer colorretal, número, localização, aparência e tamanho dos pólipos. Realizadas as avaliações morfométricas computadorizadas das expressões imuno-histoquímicas dos marcadores selecionados, que foram correlacionadas com variáveis clínicas e patológicas. Resultados: A expressão do marcador de proliferação e da Fosfatidilinositol-3-cinase foi maior nos pólipos do cólon direito (p = <0,0001 e 0.057 respectivamente. Ciclooxigenase-2 e Fosfatase homóloga a tensina demonstraram maior imunoexpressão em pólipos pediculados (p = 0,009 e 0,002, respectivamente. Ciclooxigenase-2 expressou mais em pólipos maiores (p = 0,005. Fosfatidilinositol-3-cinase, Ciclooxigenase-2, Fosfatase homóloga a tensina e o marcador de proliferação expressaram mais em pólipos com displasia de alto grau (p = 0,031, 0,013, 0,044 e <0,001, respectivamente. Fosfatase homóloga a tensina marcou mais pólipos com displasia de alto grau que lesões serrilhadas (p = 0,044. Conclusões: A maior expressão do marcador de proliferação e Fosfatidilinositol-3-cinase à direita pode estar relacionada à carcinogênese do lado direito do cólon. Os resultados do marcador de proliferação, Ciclooxigenase-2 e Fosfatidilinositol-3-cinase podem ser associados à progressão dos pólipos para câncer. A expressão aumentada de Fosfatase homóloga a tensina sugere tentativa de controle do ciclo celular. Keywords: PI3K, COX2, Colorectal cancer, Adenoma, Palavras-chave: PI3K, COX2, Câncer colorretal, Adenoma

  5. Expressão de p53, p16 E COX-2 em carcinoma escamoso de esôfago e associação histopatológica p53, p16 E COX-2 expression in esophageal squamous cell carcinoma and histopathological association

    OpenAIRE

    Izabella Paz Danezi Felin; Ivana Grivicich; Carlos Roberto Felin; Andrea Regner; Adriana Brondani da Rocha

    2008-01-01

    RACIONAL: O câncer de esôfago representa cerca de 2% dos tumores malignos e a terceira causa mais comum de câncer do trato gastrointestinal. A associação do prognóstico do câncer de esôfago com alguns marcadores imunoistoquímicos, como as proteínas p53, p16 e a ciclooxigenase 2 (COX-2) tem sido relatada. A detecção de marcadores moleculares através de imunoistoquímica pode ser utilizada para avaliação prognóstica. OBJETIVOS: Investigar a associação entre a expressão das proteínas p53, p16 e a...

  6. 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.

  7. Adverse Effects of COX-2 Inhibitors

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    Jagdish N. Sharma

    2005-01-01

    Full Text Available Cyclooxygenase-2 selective inhibitors (COXIBs were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs. Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2 and other prostaglandin (PG metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2. These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF, promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.

  8. Analgésicos inibidores específicos da ciclooxigenase-2: avanços terapêuticos Analgésicos inhibidores específicos de la ciclooxigenase-2: avanzos terapéuticos Specific cyclooxygenase-2 inhibitor analgesics: therapeutic advances

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    Wilson Andrade Carvalho

    2004-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Os antiinflamatórios não-esteroidais (AINE estão entre as drogas mais prescritas e usadas no mundo, incluindo a utilização em Anestesiologia. O propósito desta revisão é discutir alguns aspectos atuais da bioquímica da ciclooxigenase, que vem servindo de base para o desenvolvimento dos novos AINE. CONTEÚDO: Estas drogas exercem suas ações principalmente através da inibição da ciclooxigenase (COX, a enzima chave que catalisa a conversão de ácido araquidônico em prostaglandinas e tromboxanos. Pelo menos duas isoformas da COX já foram identificadas, a COX-1, que é constitutivamente expressa na maioria dos tecidos, e a COX-2, que é uma forma induzível da enzima localizada principalmente nas células e tecidos envolvidos em processos inflamatórios. Com a descoberta da COX-2 e a determinação de sua estrutura, foi possível desenvolver drogas mais seletivas que reduzem a inflamação sem afetar a COX-1, protetora do estômago e rins, dando origem a uma nova geração de compostos antiinflamatórios denominados de inibidores específicos da COX-2. CONCLUSÕES: Embora estes compostos de última geração apresentem menor toxicidade para o trato gastrintestinal, outros efeitos adversos graves têm sido observados, incluindo insuficiência renal e efeitos cardiovasculares, como o infarto agudo do miocárdio e a trombose. A despeito destes efeitos colaterais, estes novos fármacos estão sendo testados em outras condições clínicas, principalmente no tratamento preventivo do câncer e da doença de Alzheimer.JUSTIFICATIVA Y OBJETIVOS: Los antiinflamatorios no-esteroidales (AINE están entre las drogas más prescritas y usadas en el mundo, incluyendo la utilización en Anestesiología. El propósito de esta revisión es discutir algunos aspectos actuales de la bioquímica de la ciclooxigenasis, que viene sirviendo de base para el desenvolvimiento de los nuevos AINE. CONTENIDO: Estas drogas ejercen su acci

  9. Expressão de p53, p16 E COX-2 em carcinoma escamoso de esôfago e associação histopatológica

    OpenAIRE

    Felin,Izabella Paz Danezi; Grivicich,Ivana; Felin,Carlos Roberto; Regner,Andrea; Rocha,Adriana Brondani da

    2008-01-01

    RACIONAL: O câncer de esôfago representa cerca de 2% dos tumores malignos e a terceira causa mais comum de câncer do trato gastrointestinal. A associação do prognóstico do câncer de esôfago com alguns marcadores imunoistoquímicos, como as proteínas p53, p16 e a ciclooxigenase 2 (COX-2) tem sido relatada. A detecção de marcadores moleculares através de imunoistoquímica pode ser utilizada para avaliação prognóstica. OBJETIVOS: Investigar a associação entre a expressão das proteínas p53, p16 e a...

  10. Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade Inhibition of cyclooxygenase 2 expression in NOD mice cutaneous wound by low-level laser therapy

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    Carolina de Lourdes Julião Vieira Rocha

    2012-09-01

    Full Text Available CONTEXTO: A terapia a laser de baixa intensidade (LLLT tem sido relatada como importante moduladora da cicatrização de feridas cutâneas aumentando a proliferação fibroblástica associada ao aumento da expressão da citocina fator transformador de crescimento- β2 (TGF-βB2. OBJETIVO: No presente estudo foram avaliados os efeitos da LLLT sobre a expressão da enzima ciclooxigenase 2 (COX2 no sítio do reparo tecidual utilizando o modelo experimental com camundongos diabéticos não obesos (NOD para estudar a cicatrização de feridas cutâneas. MÉTODOS: Foram utilizados 30 camundongos NOD, destes 14 ficaram diabéticos e foram divididos em dois grupos: o grupo I (n=7 foi submetido a um procedimento cirúrgico de feridas cutâneas e o grupo II (n=7 foi submetido a um procedimento cirúrgico de feridas cutâneas e tratados com LLLT. O grupo II foi submetido à LLLT nos seguintes parâmetros: 15 mW de potência, dose de 3,8 J/cm² e tempo de aplicação de 20 segundos. Após sete dias do ato cirúrgico e após aplicação do laser, os animais foram eutanasiados com sobredose de anestesia e amostras das feridas foram colhidas para posterior análise histopatológica, histomorfométrica e imuno-histoquímica. RESULTADOS: A LLLT promoveu a inibição da expressão da COX2 em feridas cutâneas de camundongos diabéticos. CONCLUSÃO: Em conjunto, os resultados sugeriram que a LLLT é capaz de modular negativamente a expressão da enzima COX2 contribuindo para o controle da resposta inflamatória em feridas cutâneas de camundongos NOD.BACKGROUND: Low-level laser therapy (LLLT has been reported to modulate the healing of wounds by inducing an increase in fibroblast number associated with increased expression of the cytokine transforming growth factor-β2 (TGF-β2. OBJECTIVE: In the present study, the effect of LLLT on expression of COX2 at the site of tissue repair was evaluated, using an experimental model with non obese diabetic mice (NOD to study

  11. 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

  12. Uso combinado da laserterapia de baixa potência e da inibição da ciclooxigenase-2 na reepitelização de ferida incisional em pele de camundongos: um estudo pré-clínico

    OpenAIRE

    Santuzzi,Cíntia Helena; Buss,Hygor Franca; Pedrosa,Diego França; Freire,Martha Oliveira Vieira Moniz; Nogueira,Breno Valentim; Gonçalves,Washington Luiz Silva

    2011-01-01

    FUNDAMENTOS: A laserterapia de baixa potência e os inibidores seletivos da ciclooxigenase-2 (ICOX2) vem sendo muito utilizados para modular a resposta inflamatória, entretanto, os seus efeitos na reepitelização de feridas não são bem compreendidos. OBJETIVO: Avaliar os efeitos isolados e combinados da laserterapia de baixa potência e da ICOX2 na reepitelização de ferida incisional na pele de camundongos. MÉTODO: Foi induzida uma ferida de 1 cm no dorso de cada camundongo, que foram divididos ...

  13. Expressão de p53, p16 E COX-2 em carcinoma escamoso de esôfago e associação histopatológica p53, p16 E COX-2 expression in esophageal squamous cell carcinoma and histopathological association

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    Izabella Paz Danezi Felin

    2008-12-01

    Full Text Available RACIONAL: O câncer de esôfago representa cerca de 2% dos tumores malignos e a terceira causa mais comum de câncer do trato gastrointestinal. A associação do prognóstico do câncer de esôfago com alguns marcadores imunoistoquímicos, como as proteínas p53, p16 e a ciclooxigenase 2 (COX-2 tem sido relatada. A detecção de marcadores moleculares através de imunoistoquímica pode ser utilizada para avaliação prognóstica. OBJETIVOS: Investigar a associação entre a expressão das proteínas p53, p16 e a COX-2 com o estádio do carcinoma escamoso de esôfago. MÉTODOS: Foram analisadas 31 amostras de ressecção cirúrgica por esofagectomia diagnosticadas como carcinoma de células escamosas de esôfago e 31 amostras não-tumorais referentes a cada caso. Realizou-se a revisão histopatológica e o estádio pTNM. Amostras tumorais e não-tumorais adjacentes foram submetidas a análise imunoistoquímica para avaliar o conteúdo das proteínas p53, p16 e COX-2. Foi considerada positiva a expressão nuclear para p53 em quantidade igual ou superior a 10,00% das células e presença da expressão citoplasmática de acordo com três escores (1, 2, 3 de intensidade (leve, moderada, acentuada de imunocoloração para COX-2. RESULTADOS: Em área tumoral, as análises revelaram 48,38% de positividade para p53, 16,12% de positividade para p16, e 100,00% de positividade escores 1+, 2+ ou 3+ para COX-2. No entanto, quando se avaliou possível relação da expressão destes marcadores com o estádio, apenas a COX-2, escore 3+ intensidade acentuada mostraram associação significativa. CONCLUSÃO: O presente estudo demonstrou que existe relação positiva entre a expressão de COX-2, escore 3+ e estádio mais avançado no carcinoma de esôfago.BACKGROUND: The esophageal carcinoma represents about 2% of malignant tumors and is the third most common cause of gastrointestinal cancer. The correlation between immunohistochemistry markers, such as p53, p16

  14. COX-2 and p53 in human sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Cyr, Diane; Luce, Danièle

    2008-01-01

    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...... to development of cancer. Many signals that activate COX-2 also induce tumor suppressor p53, a transcription factor central in cellular stress response. We investigated COX-2 and p53 expressions by immunohistochemistry in 50 SNCs (23 adenocarcinomas, and 27 squamous cell carcinomas (SCC); 48 analyzed for COX-2...... displayed adenocarcinoma. COX-2 was expressed at higher levels in adenocarcinoma as compared to SSC (p COX-2 expression showed significant association with occupational exposure to wood dust (p = 0.024), and with nonsmoking status (p = 0.001). No statistically significant associations between...

  15. Antiinflamatórios não-hormonais: inibidores da ciclooxigenase 2 Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Maria Odete Esteves Hilário

    2006-11-01

    Full Text Available OBJETIVO: Analisar os antiinflamatórios não-hormonais (AINH inibidores seletivos da Cox 2 quanto ao mecanismo de ação, principais indicações, posologia e efeitos adversos mais comuns. FONTES DOS DADOS: MEDLINE e LILACS, sites da Food and Drug Administration (FDA e da Agência Nacional de Vigilância Sanitária (ANVISA. Foram selecionados os artigos mais importantes, com destaque para as publicações dos últimos 5 anos. SÍNTESE DOS DADOS: As principais indicações dos AINH são o controle da dor e da inflamação aguda e crônica. Não existem evidências que demonstrem maior efetividade de um AINH sobre outro. Até a presente data, nenhum inibidor da Cox2 foi liberado para uso na faixa etária pediátrica. Apenas o meloxicam e o etoricoxibe podem ser prescritos para adolescentes (13 e 16 anos, respectivamente. Os inibidores seletivos da Cox 2 são indicados em pacientes com efeitos adversos comprovadamente relacionados aos AINH não seletivos. Em alguns casos de alergia à aspirina, os Cox 2 seletivos podem ser prescritos, mas seu uso deve ser cuidadoso. Os principais efeitos adversos incluem os cardiovasculares e os fenômenos trombóticos. CONCLUSÕES: Os inibidores seletivos da Cox 2 são medicamentos que vêm sendo utilizados em algumas situações clínicas bem determinadas e podem oferecer algumas vantagens com relação aos AINH não seletivos. No entanto, devido ao custo mais elevado e aos potenciais efeitos adversos cardiovasculares, seu emprego deve ser criterioso.OBJECTIVE: To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID in terms of their mechanism of action, principal indications, posology and most common adverse effects. SOURCES: MEDLINE and LILACS databases and Food and Drug Administration (FDA and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária websites. The most important articles were selected and preference was given to articles published

  16. 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...... time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible...

  17. 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

  18. 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.

  19. Inhibition of cyclooxygenase-2 in experimental severe acute pancreatitis Inibição da Ciclo-Oxigenase-2 na pancreatite aguda grave experimental

    Directory of Open Access Journals (Sweden)

    José Luiz Jesus de Almeida

    2006-08-01

    Full Text Available BACKGROUND: The standard treatment for acute pancreatitis (AP is still based on supportive care. The search for a new drug that could change the natural history of the disease is a continuing challenge for many researchers. The aim of this study is to evaluate the effect of a cyclooxygenase-2 (COX-2 inhibitor on experimental AP in rats. METHODS: The animals were divided into 2 groups: Group 1 (n = 30-animals with taurocholate-induced AP treated with parecoxib (40 mg/kg. Group 2 (n = 30-animals with taurocholate-induced AP that received saline. The COX-2 inhibitor (parecoxib was injected immediately after AP induction, through the penis dorsal vein. The parameters evaluated were histology, serum levels of amylase, IL-6 and IL-10, and mortality rate. RESULTS: The serum levels of IL-6 and IL-10 in the parecoxib-treated group were lower than the control group. The amylase serum levels and the mortality rate remained unchanged in the treated animals. Histologic morphology also was unaltered, except for fat necrosis, which was higher in parecoxib-treated rats. CONCLUSION: Inhibition of Cox-2 decreases the systemic release of inflammatory cytokines, but has a poor effect on the direct pancreas injury caused by taurocholate.INTRODUÇÃO: O tratamento padrão para a pancreatite aguda permanece baseado em medidas de suporte. A busca por uma droga que altere a história natural da doença ainda é um desafio para muitos pesquisadores. O objetivo deste estudo é avaliar o efeito de um inibidor da COX-2 na pancreatite aguda grave experimental (PA em ratos. MÉTODO: Os animais foram divididos em dois Grupos: Grupo 1 (n=30 - animais com PA induzida por taurocolato e tratados com parecoxib (40mg/Kg. Grupo 2 (n=30 - animais com PA induzida por taurocolato que receberam solução salina. O inibidor de COX-2 (parecoxib foi injetado imediatamente após a indução, através da veia dorsal do pênis. Os parâmetros avaliados foram histologia, níveis séricos de

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

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    Valentina Arnao

    2017-01-01

    Full Text Available 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.

  2. 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.

  3. Immunohistochemical Expression of COX-2 in Uterine Serous Carcinoma Tissue

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    Joseph Menczer

    2016-03-01

    Material and methods. Cox-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks of consecutive available USC uterine specimens of patients diagnosed from 2000 to 2014. Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0 and ndash;3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was equal to 1 or less and high when it was more than 1. Clinicopathological data were retrospectively abstracted from the records of the study group patients Results. The study comprised uterine specimens of 31 USC patients. Positive immunohistochemical staining was observed in 25 (80.6% USC specimens and a high score in 6 (19.4% of them. No association between immunohistochemical staining parameters and clinicopathological prognostic factors was observed. Conclusion. Although our findings should be verified in larger series, it seems that in view of the lack of association between immunohistochemical Cox-2 staining parameters in USC tissue and clinicopathological prognostic factors, this aggressive tumor is not a candidate for the use of selective Cox-2 inhibitors. Key words: Cox-2 expression, uterine carcinosarcoma, clinicopathological prognostic factors [J Interdiscipl Histopathol 2016; 4(1.000: 9-12

  4. COX-2 inhibition in osteoarthritis:effects on cartilage

    NARCIS (Netherlands)

    Mastbergen, Simon Carl

    2005-01-01

    The topic of this thesis was to provide more insight in the direct effects of one of the selective COX-2 inhibitors, celecoxib on articular cartilage. Issues of major relevance to clinical practice since it is essential that compounds used to treat osteoarthritis do not impair the ability of

  5. 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.

  6. 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 m...... osmolality in COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2......(-/-) mice, but after WD plasma AVP was unchanged between COX-2(-/-) and WT mice (43 ± 11 vs. 70 ± 16 pg/ml). Renal V2 receptor abundance was downregulated in COX-2(-/-) mice. Medullary interstitial osmolality increased and did not differ between COX-2(-/-) and WT after WD. Aquaporin-2 (AQP2; cortex...

  7. Cell-type-specific roles for COX-2 in UVB-induced skin cancer

    Science.gov (United States)

    Herschman, Harvey

    2014-01-01

    In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

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

    International Nuclear Information System (INIS)

    Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

    2011-01-01

    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. 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. 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. 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. 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.

  10. Expression of Beta-catenin, COX-2 and iNOS in Colorectal Cancer: Relevance of COX-2 and iNOS Inhibitors for Treatment in Malaysia

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    Seok Kwan Hong

    2004-01-01

    Conclusions: The accumulation of β-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.

  11. Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice.

    Science.gov (United States)

    Kim, Joohwee; Vaish, Vivek; Feng, Mingxiao; Field, Kevin; Chatzistamou, Ioulia; Shim, Minsub

    2016-10-07

    Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process. However, it is not clear whether the increased COX2 expression is causal to or a result of aging. We have now addressed this question by creating an inducible COX2 transgenic mouse model. Here we show that post-natal expression of COX2 led to a panel of aging-related phenotypes. The expression of p16, p53, and phospho-H2AX was increased in the tissues of COX2 transgenic mice. Additionally, adult mouse lung fibroblasts from COX2 transgenic mice exhibited increased expression of the senescence-associated β-galactosidase. Our study reveals that the increased COX2 expression has an impact on the aging process and suggests that modulation of COX2 and its downstream signaling may be an approach for intervention of age-related disorders.

  12. 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.

  13. 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.

  14. 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.

  15. Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

    International Nuclear Information System (INIS)

    Pachkoria, Ketevan; Zhang Hong; Adell, Gunnar; Jarlsfelt, Ingvar; Sun Xiaofeng

    2005-01-01

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p ≤ 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors

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

    DEFF Research Database (Denmark)

    Kolko, Miriam; Nielsen, Marianne; Bazan, Nicolas G

    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...

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

    African Journals Online (AJOL)

    Amani Kazem

    2013-07-17

    Jul 17, 2013 ... (wingless type) signaling pathway, increased protein concentrations promote transcription of genes .... under a light microscope and the histological type of colorectal .... of signet ring cell carcinoma showed weak COX-2 positivity. 3.2. Analysis .... COX-2 expression was detected in other tumors, and was be-.

  18. 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.

  19. 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.

  20. 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

    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......), such that variant allele carriers with low alcohol intake had the lowest lipid levels. No statistically significant associations were observed in females. Conclusion: This study suggests that genetically determined COX-2 levels are associated with risk of ACS and blood lipid levels among males. No consistent......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...

  1. 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

  2. COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

    International Nuclear Information System (INIS)

    Smith, Fraser M.; Reynolds, John V.; Kay, Elaine W.; Crotty, Paul; Murphy, James O.; Hollywood, Donal; Gaffney, Eoin F.; Stephens, Richard B.; Kennedy, M. John

    2006-01-01

    Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates

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

    Directory of Open Access Journals (Sweden)

    Patrick Leclerc

    2008-05-01

    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.

  4. 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.

  5. O PAPEL DA CICLOOXIGENASE-2 E DA PRESSÃO ARTERIAL NA LESÃO RENAL DE RATOS SUBMETIDOS À INFUSÃO CONTÍNUA DE ANGIOTENSINA II

    Directory of Open Access Journals (Sweden)

    Flávia Santin

    2010-12-01

    Full Text Available Angiotensin II (ANGII is a vasoconstrictor which action on inflammation has been studied. The objective of this study was to verify the stimulation of cyclooxigenase-2 and blood pressure on renal damage by ANGII. Wistar rats were distributed into four groups, as follows: group 1 – control; group 2 – ANGII; group 3 – ANGII + celecoxib; and group 4 – celecoxib. The ANGII was infused in the animals by subcutaneous osmotic mini-pumps during 72 hours. After that, euthanasia was performed. The blood pressure was measured before the drugs administration and before the euthanasia. Histopathological and immunohistochemical evaluations were performed in kidneys to assess the expression of COX-2. It was concluded that ANGII caused renal damage, regardless of blood pressure values. ANGII associated with celeboxib increased blood pressure. Celecoxib did not protect the kidneys against ANGII activities.

  6. 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.

  7. Direct-to-consumer advertising of COX-2 inhibitors: effect on appropriateness of prescribing.

    Science.gov (United States)

    Spence, Michele M; Teleki, Stephanie S; Cheetham, T Craig; Schweitzer, Stuart O; Millares, Mirta

    2005-10-01

    Spending on direct-to-consumer advertising (DTCA) of prescription drugs has increased dramatically in the past several years. An unresolved question is whether such advertising leads to inappropriate prescribing. In this study, the authors use survey and administrative data to determine the association of DTCA with the appropriate prescribing of cyclooxygenase-2 (COX-2) inhibitors for 1,382 patients. Treatment with either a COX-2 or a traditional nonsteroidal anti-inflammatory drug (NSAID) was defined as appropriate or not according to three different definitions of gastrointestinal risk. Patients who saw or heard a COX-2 advertisement and asked their physician about the advertised drug were significantly more likely to be prescribed a COX-2 (versus a NSAID, as recommended by evidence-based guidelines) than all other patients. Findings also suggest that some patients may benefit from DTCA. The authors discuss the need for balanced drug information for consumers, increased physician vigilance in prescribing appropriately, and further study of DTCA.

  8. The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates.

    Science.gov (United States)

    McCann, Nicole C; Lynch, Terrie J; Kim, Soon Ok; Duffy, Diane M

    2013-12-01

    Cyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. Ultrasound studies in women demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse associated with ovulation. The goal of this study was to determine if oral administration of a COX-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates. The COX-2 inhibitor meloxicam (or vehicle) was administered orally to proven fertile female cynomolgus macaques using one emergency contraceptive model and three monthly contraceptive models. In the emergency contraceptive model, females were bred with a proven fertile male once 2±1 days before ovulation, returned to the females' home cage, and then received 5 days of meloxicam treatment. In the monthly contraceptive models, females were co-caged for breeding with a proven fertile male for a total of 5 days beginning 2±1 days before ovulation. Animals received meloxicam treatment (1) cycle days 5-22, or (2) every day, or (3) each day of the 5-day breeding period. Female were then assessed for pregnancy. The pregnancy rate with meloxicam administration using the emergency contraception model was 6.5%, significantly lower than the pregnancy rate of 33.3% when vehicle without meloxicam was administered. Pregnancy rates with the three monthly contraceptive models (75%-100%) were not consistent with preventing pregnancy. Oral COX-2 inhibitor administration can prevent pregnancy after a single instance of breeding in primates. While meloxicam may be ineffective for regular contraception, pharmacological inhibition of COX-2 may be an effective method of emergency contraception for women. COX-2 inhibitors can interfere with ovulation, but the contraceptive efficacy of drugs of this class has not been directly tested. This study, conducted in nonhuman primates, is the first to suggest that a COX-2 inhibitor may be effective as an emergency contraceptive.

  9. 2-Chlorohexadecanal and 2-chlorohexadecanoic acid induce COX-2 expression in human coronary artery endothelial cells

    OpenAIRE

    Messner, Maria C.; Albert, Carolyn J.; Ford, David A.

    2008-01-01

    2-Chlorohexadecanal (2-ClHDA), a 16-carbon chain chlorinated fatty aldehyde that is produced by reactive chlorinating species attack of plasmalogens, is elevated in atherosclerotic plaques, infarcted myocardium, and activated leukocytes. We tested the hypothesis that 2-ClHDA and its metabolites, 2-chlorohexadecanoic acid (2-ClHA) and 2-chlorohexadecanol (2-ClHOH), induce COX-2 expression in human coronary artery endothelial cells (HCAEC). COX-2 protein expression increased in response to 2-Cl...

  10. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

    Science.gov (United States)

    Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

  11. DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB

    International Nuclear Information System (INIS)

    Morris, R.H.K.; Tonks, A.J.; Jones, K.P.; Ahluwalia, M.K.; Thomas, A.W.; Tonks, A.; Jackson, S.K.

    2008-01-01

    The major phospholipid in pulmonary surfactant dipalmitoyl phosphatidylcholine (DPPC) has been shown to modulate inflammatory responses. Using human monocytes, this study demonstrates that DPPC significantly increased PGE 2 (P < 0.05) production by 2.5-fold when compared to untreated monocyte controls. Mechanistically, this effect was concomitant with an increase in COX-2 expression which was abrogated in the presence of a COX-2 inhibitor. The regulation of COX-2 expression was independent of NF-κB activity. Further, DPPC increased the phosphorylation of the cyclic AMP response element binding protein (CREB; an important nuclear transcription factor important in regulating COX-2 expression). In addition, we also show that changing the fatty acid groups of PC (e.g. using L-α-phosphatidylcholine β-arachidonoyl-γ-palmitoyl (PAPC)) has a profound effect on the regulation of COX-2 expression and CREB activation. This study provides new evidence for the anti-inflammatory activity of DPPC and that this activity is at least in part mediated via CREB activation of COX-2

  12. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

    Science.gov (United States)

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-Qian; Wu, Yan; Yang, Hongwei; Tang, Ya-Ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-11-21

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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

  14. 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.

  15. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

    Science.gov (United States)

    de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

    2009-02-01

    Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P IAS tone.

  16. Early increased density of cyclooxygenase-2 (COX-2 immunoreactive neurons in Down syndrome

    Directory of Open Access Journals (Sweden)

    Maria Mulet

    2017-06-01

    Full Text Available Neuroinflammation is one of the hallmarks of Alzheimer’s disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer’s disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer’s disease.

  17. Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

    OpenAIRE

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-qian; Wu, Yan; Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmaco...

  18. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    2014-03-01

    Mar 1, 2014 ... Its underlying biological mechanism remains unclear and no well-documented drug and ... Objectives: To explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi. (GST-Pi) in the ..... in an animal model of Parkinson's disease: Therapeutic perspectives. Nutri-.

  19. Cyclo-oxygenase(COX)-2-remming bij de preventie en de behandeling van colorectaal carcinoom

    NARCIS (Netherlands)

    Tuynman, J. B.; Hulscher, J. B.; Steller, E. Ph; van Lanschot, J. J.; Richel, D. J.

    2003-01-01

    Epidemiological studies have found that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal cancer (CRC). Cyclooxygenase (COX)-2 expression is present in colorectal cancer and overexpression is associated with metastases and poorer prognosis

  20. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    Objectives: This study was performed to explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi (GST-Pi) in the pathogenesis of HCC risk. Methods: 120 Wistar rats were divided into three groups at random: normal control group (control group), HCC risk group without ...

  1. Dual Regulating Effect of Shaoyao-Gangcao-Tang on COX- 2 ...

    African Journals Online (AJOL)

    through the differential regulation of cell adhesion molecules and chemokines expression [9]. These data indicate that 15d-PGJ2 can tightly regulate the resolution of acute inflammation. As the key enzyme of regulating PGE2 generation, COX-2 has been thought to be a pro- inflammatory mediator. However, Gilroy et al [10].

  2. Do the COX-2 inhibitors still have a role to play? : guest editorial ...

    African Journals Online (AJOL)

    Do the COX-2 inhibitors still have a role to play? : guest editorial. A Beeton. Abstract. No Abstract Available Southern African Journal of Anaesthesia & Analgesia Vol.11(2) 2005: 55-60. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics. Metrics ...

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

    International Nuclear Information System (INIS)

    Chen, Huimin; Ma, Feng; Hu, Xiaona; Jin, Ting; Xiong, Chuhui; Teng, Xiaochun

    2013-01-01

    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. Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs

    NARCIS (Netherlands)

    Gorissen, B.M.C.; Uilenreef, J.J.; Bergmann, W.; Meijer, E.; van Rietbergen, B.; van der Staay, F.J.; van Weeren, P.R.; Wolschrijn, C.F.

    2017-01-01

    Meloxicam, a preferential COX-2 inhibitor, is a commonly used nSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term

  5. Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs

    NARCIS (Netherlands)

    Gorissen, Ben M C|info:eu-repo/dai/nl/372825788; Uilenreef, Joost J|info:eu-repo/dai/nl/30483095X; Bergmann, Willie|info:eu-repo/dai/nl/36275585X; Meijer, Ellen|info:eu-repo/dai/nl/375288015; van Rietbergen, Bert; van der Staay, Franz Josef|info:eu-repo/dai/nl/074262653; Weeren, P René van; Wolschrijn, Claudia F|info:eu-repo/dai/nl/271539496

    2017-01-01

    Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term

  6. Cytotoxic of Ganoderma lucidum in Colon Cancer through Cyclooxygenase 2 (COX-2 as Its Molecular Target

    Directory of Open Access Journals (Sweden)

    Agustina Setiawati

    2017-05-01

    Full Text Available Many studies were designed explore chemopreventive activity of natural products on colon cancer especially addressing COX-2 as molecular target. Another promising source of natural product that potentially exhibit anticancer activity on colon cancer is Ganoderma lucidum. This study assessed selectivity of cytotoxic effect of G. lucidum extract on WiDr to Vero cells and investigated molecular mechanism on COX-2. G. lucidum ex-tract was prepared by reflux extraction method; in vitro anticancer was assayed by MTT method on WiDr and Vero cell line. This study applied apoptosis induction assay to observe cell death mechanism using double staining method; further COX-2 expression was stained by immunocytochemistry method. G. lucidum extract has cytotoxic effect on WiDr cells with IC50 135 µg/mL. However, the cytotoxic effect had low selectivity to-wards Vero cells with Selectivity Index (SI 3.66. The extract induced apoptosis and suppressed COX-2 ex-pression in WiDr cells. G. lucidum extract was potential to be developed as anticancer agent towards colon cancer.

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

    International Nuclear Information System (INIS)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

    2013-01-01

    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

  8. 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.

  9. 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.

  10. [Specific inhibitors of cyclooxygenase-2 (COX-2): current knowledge and perspectives].

    Science.gov (United States)

    Rioda, W T; Nervetti, A

    2001-01-01

    The Authors summarize the current knowledge on a new class of nonsteroidal anti-inflammatory drugs (NSAIDs), the coxib (celecoxib and rofecoxib), in the treatment of rheumatic diseases. Celecoxib and rofecoxib are selective cyclooxygenase-2 (COX-2) inhibitors which possess the same anti-inflammatory and analgesic activities, but a better gastric tolerability compared to the non-selective COX-1 and COX-2 inhibitors. The Authors also report other possible therapeutic effects of these NSADIs as evidenced by the more recent data of the literature. Celecoxib seems to reduce the incidence of new polyps in patients with familial adenomatous polyposis. It has been suggested the use of celecoxib as a protective drug against the development of colorectal cancer. Other (neoplastic) or pre-neoplastic conditions, such as bladder dysplasia, Barret esophagus, attinic keratosis and Alzheimer's disease seem to have benefit from this class of drugs.

  11. NSAIDs and serious cardiovascular disorders: especially cox-2 inhibitors and diclofenac.

    Science.gov (United States)

    2016-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) used as analgesics expose patients to cardiovascular risks that can be predicted from their pharmacological properties. As of mid-2015, what is known about the cardiovascular harms of the NSAIDs of choice, ibuprofen and naproxen? Most of the data from comparative trials of NSAIDs concern cox-2 inhibitors, diclofenac, ibuprofen and naproxen. Few studies have addressed the serious cardiovascular effects of other NSAIDs. In 2013, a U.K. team published a large meta-analysis of hundreds of randomised trials comparing NSAIDs with placebo or one NSAID with another NSAID. Compared with placebo, a statistically significant increase in the risk of serious cardiovascular adverse effects was demonstrated with cox-2 inhibitors and with diclofenac (about +40%). This risk is mainly due to an increase in myocardial infarctions and vascular deaths. Another meta-analysis found similar results in terms of cardiovascular deaths. The results of epidemiological studies are consistent with those of randomised clinical trials. According to meta-analyses of randomised trials, high-dose ibuprofen increases cardiovascular risks to the same degree as diclofenac or cox-2 inhibitors. The risk seems to mainly apply to daily doses of 2400 mg, a finding borne out by epidemiological studies that showed no increased risk with ibuprofen 1200 mg. Two meta-analyses of clinical trials showed that all NSAIDs roughly double the risk of heart failure. One meta-analysis showed a small, statistically significant increase in the risk of atrial fibrillation. In practice, from a cardiovascular perspective, the NSAIDs of choice are ibuprofen, on condition that the dose does not exceed 1200 mg per day, and naproxen. In contrast, it would appear from the study data that cox-2 inhibitors, diclofenac and high-dose ibuprofen (2400 mg per day) are best avoided. As for other NSAIDs, the clinical data are too sparse to allow a meaningful comparison with the better studied

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

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    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.

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

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    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.

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

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    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.

  15. Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines.

    Science.gov (United States)

    Seo, Kyoung-Won; Coh, Ye-Rin; Rebhun, Robert B; Ahn, Jin-Ok; Han, Sei-Myung; Lee, Hee-Woo; Youn, Hwa-Young

    2014-06-01

    Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2. Celecoxib induced a significant anti-proliferative effect in both LMeC and CMeC-1 cells. In the CMeC cells, treatment of 50 μM celecoxib caused an increase in cells in the G0/G1 and a decreased proportion of cells in G-2 phase. In the LMeC cells, 50 μM of celecoxib led to an increase in the percentage of cells in the sub-G1 phase and a significant activation of caspase-3 when compared to CMeC-1 cells. In conclusion, these results demonstrate that celecoxib exhibits antitumor effects on canine melanoma LMeC and CMeC-1 cells by induction of G1-S cell cycle arrest and apoptosis. Our data suggest that celecoxib might be effective as a chemotherapeutic agent against canine malignant melanoma. Copyright © 2014. Published by Elsevier Ltd.

  16. Pregnancy induced changes in Cox-1, Cox-2 and NOSIII vascular and renal expression.

    Science.gov (United States)

    Bobadilla, Rosa A; Bracho, Ismael; Alvarez, Victor M Pérez; Anguiano, Liliana; López, Pedro

    2004-01-01

    In order to establish if there is a mutual regulation between COX and NOS in vascular and renal tissue during pregnancy, we measured the protein expression of COX-1, COX-2 and NOSIII by Western blot comparing the thoracic and abdominal aorta and the renal cortex and medulla of non pregnant and pregnant (21st day) Wistar rats. We found there was no difference in the quantity of protein of any of the two isoforms of COX between the two segments of the aorta of non pregnant animals while an increased expression of both COX-1 And COX-2 was found in the abdominal compared to the thoracic segment of the pregnant rats. An increased expression of NOS III was found in the abdominal segment of the aorta form pregnant rats. No changes were found between pregnant and no pregnant animals in the expression of COX-1 and COX-2 in the renal cortex or medulla while an increased expression of NOS III was found in the cortex from pregnant compared to non pregnant animals. These results suggest the influence of pregnancy is not homogeneous along the aorta and also that a balance between prostaglandins and nitric oxide is responsible of the blunted vascular reactivity during pregnancy in the rat.

  17. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Yingting, E-mail: yitizhu@yahoo.com [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States); Tissue Tech Inc., Miami, FL 33173 (United States); Zhu, Min; Lance, Peter [Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE{sub 2}. Black-Right-Pointing-Pointer The fibroblasts interact with human colonic epithelial cancer cells. Black-Right-Pointing-Pointer Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. Black-Right-Pointing-Pointer Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

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

    International Nuclear Information System (INIS)

    Glynn, Sharon A; Ambs, Stefan; Prueitt, Robyn L; Ridnour, Lisa A; Boersma, Brenda J; Dorsey, Tiffany M; Wink, David A; Goodman, Julie E; Yfantis, Harris G; Lee, Dong H

    2010-01-01

    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. 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. 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. 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

  19. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    International Nuclear Information System (INIS)

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-01-01

    Highlights: ► Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE 2 . ► The fibroblasts interact with human colonic epithelial cancer cells. ► Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. ► Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.

  20. 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

  1. Involvement of COX-2 in nickel elution from a wire implanted subcutaneously in mice.

    Science.gov (United States)

    Sato, Taiki; Kishimoto, Yu; Asakawa, Sanki; Mizuno, Natsumi; Hiratsuka, Masahiro; Hirasawa, Noriyasu

    2016-07-01

    Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA in the surrounding tissues. Immunostaining analysis showed that cells expressing COX-2 were mainly fibroblast-like cells 8h after implantation of a Ni wire, but were mainly infiltrated leukocytes at 24h. NiCl2 induced the expression of COX-2 mRNA in primary fibroblasts, neutrophils, RAW 264 cells, and THP-1 cells, indicating that Ni ions can induce COX-2 expression in various types of cells. The elution of Ni ions from the implanted Ni wire at 8h was reduced by dexamethasone (Dex), indomethacin (Ind), or celecoxib (Cel) treatment. Ni wire implantation induced an increase in mRNA levels for anaerobic glycolytic pathway components glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4); the expression of these genes was also inhibited by Dex, Ind, and Cel. In primary fibroblasts, the expression of these mRNAs and the production of lactate were induced by NiCl2 and further potentiated by PGE2. Furthermore, Ni wire-induced infiltration of inflammatory leukocytes was significantly reduced by Dex, Ind, or Cel. Depletion of neutrophils with a specific antibody caused reduction of both leukocyte infiltration and Ni elution. These results indicate that Ni ions eluted from wire induced COX-2 expression, which further promoted elution of Ni ions by increasing lactate production and leukocyte infiltration. Since COX inhibitors and Dex reduced the elution of Ni ions, these drugs may be

  2. Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

    International Nuclear Information System (INIS)

    Kang, Ju-Hee; Song, Ki-Hoon; Jeong, Kyung-Chae; Kim, Sunshin; Choi, Changsun; Lee, Chang Hoon; Oh, Seung Hyun

    2011-01-01

    A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX). We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells. We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. In vitro invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells. We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in

  3. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

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    Mandar Dave

    2017-12-01

    Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

  4. IL1β-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

    International Nuclear Information System (INIS)

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-01-01

    COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1β in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1β, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1β. Further analysis indicated that the major COX-2 product, prostaglandin E 2 , directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1β. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1β in the fibroblasts.

  5. Screening of Missense SNPs in Coding Regions of COX-2 as a Key Enzyme Involved in Cancer

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    Sodabeh Jahanbakhsh-Godehkahriz

    2013-09-01

    Full Text Available Background & Objectives: Non-synonymous single nucleotide polymorphism (nsSNPs which results in disruption of protein function are used as markers in linkage and association of human proteins that might be involved in diseases and cancers .   Methods: To study the functional effect of nsSNP in cyclooxygenase-2 (COX2 amino acids, the nucleotide sequences encoding COX-2 gene in cancers were extracted from the NCBI (gi|223941909 data bank (283 cases and analyzed by SIFT, I-Mutant 2.0, SNP and GO, PANTHER and FASTSNP servers. These servers involve programs that predict the effects of amino acid substitution on protein function, stability and missense .   Results: COX-2 is an essential enzyme for the production of pro-inflammatory prostaglandins which are relevant to cancer development and progression. The substitutions in some positions such as R228H and S428A of COX-2 in most of cancers linked to reformed protein function through disruption in enzyme active site.   Conclusion: Amino acid substitutions as a consequence of COX-2 nsSNPs have important role in human disease. Substitutions which are located in catalytic domain are important for the enzymatic function of COX-2 and associated with higher expression of COX-2.

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

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    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. LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

    International Nuclear Information System (INIS)

    Sun Haipeng; Xu Beibei; Sheveleva, Elena; Chen, Qin M.

    2008-01-01

    Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca 2+ concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes

  8. Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression

    Science.gov (United States)

    Liu, Fei; Mih, Justin D.; Shea, Barry S.; Kho, Alvin T.; Sharif, Asma S.; Tager, Andrew M.

    2010-01-01

    Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome of fibrosis, not a contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative to normal lung parenchyma. Across this pathophysiological stiffness range, cultured lung fibroblasts transition from a surprisingly quiescent state to progressive increases in proliferation and matrix synthesis, accompanied by coordinated decreases in matrix proteolytic gene expression. Increasing matrix stiffness strongly suppresses fibroblast expression of COX-2 (cyclooxygenase-2) and synthesis of prostaglandin E2 (PGE2), an autocrine inhibitor of fibrogenesis. Exogenous PGE2 or an agonist of the prostanoid EP2 receptor completely counteracts the proliferative and matrix synthetic effects caused by increased stiffness. Together, these results demonstrate a dominant role for normal tissue compliance, acting in part through autocrine PGE2, in maintaining fibroblast quiescence and reveal a feedback relationship between matrix stiffening, COX-2 suppression, and fibroblast activation that promotes and amplifies progressive fibrosis. PMID:20733059

  9. Epithelial-mesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib.

    Science.gov (United States)

    Kirane, Amanda; Toombs, Jason E; Larsen, Jill E; Ostapoff, Katherine T; Meshaw, Kathryn R; Zaknoen, Sara; Brekken, Rolf A; Burrows, Francis J

    2012-09-01

    Although cyclooxygenase-2 (COX-2) inhibitors, such as the late stage development drug apricoxib, exhibit antitumor activity, their mechanisms of action have not been fully defined. In this study, we characterized the mechanisms of action of apricoxib in HT29 colorectal carcinoma. Apricoxib was weakly cytotoxic toward naive HT29 cells in vitro but inhibited tumor growth markedly in vivo. Pharmacokinetic analyses revealed that in vivo drug levels peaked at 2-4 µM and remained sufficient to completely inhibit prostaglandin E(2) production, but failed to reach concentrations cytotoxic for HT29 cells in monolayer culture. Despite this, apricoxib significantly inhibited tumor cell proliferation and induced apoptosis without affecting blood vessel density, although it did promote vascular normalization. Strikingly, apricoxib treatment induced a dose-dependent reversal of epithelial-mesenchymal transition (EMT), as shown by robust upregulation of E-cadherin and the virtual disappearance of vimentin and ZEB1 protein expression. In vitro, either anchorage-independent growth conditions or forced EMT sensitized HT29 and non-small cell lung cancer cells to apricoxib by 50-fold, suggesting that the occurrence of EMT may actually increase the dependence of colon and lung carcinoma cells on COX-2. Taken together, these data suggest that acquisition of mesenchymal characteristics sensitizes carcinoma cells to apricoxib resulting in significant single-agent antitumor activity.

  10. Synthesis and evaluation of ortho-[18F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

    Directory of Open Access Journals (Sweden)

    Chang CW

    2018-05-01

    Full Text Available Chi-Wei Chang,1,* Chun-Nan Yeh,2,* Yi-Hsiu Chung,3,* Yong-Ren Chen,4 Shi-Wei Tien,4 Tsung-Wen Chen,2 Shiou-Shiow Farn,4,5 Ying-Cheng Huang,6 Chung-Shan Yu4,7 1Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Surgery, Liver Research Center, Chang-Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; 3Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu, Taiwan; 5Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan; 6Department of Neurosurgery, Chang-Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; 7Institute of Nuclear Engineering and Science, National Tsinghua University, Hsinchu, Taiwan *These authors contributed equally to this work Background: An 18F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development. Methods: The in vivo uptake of celecoxib was monitored with ortho-[18F]fluorocelecoxib using positron emission tomography (PET. The binding affinity of ortho-[18F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib. Results: The IC50 values were 0.039 μM and 0.024 μM, respectively. A selectivity index of 1.63 was obtained (COX-2 vs COX-1. COX-2 overexpressed cholangiocarcinoma (CCA murine cells took up more ortho-[18F]fluorocelecoxib than that by usual CCA cells from 10 to 60 minutes post incubation. Competitive inhibition (blocking of the tracer uptake of ortho-[18F]fluorocelecoxib in the presence of celecoxib by the COX-2 overexpressed CCA cells and the usual CCA cells gave the IC50 values of 0.5 μM and 46.5 μM, respectively. Based on the in vitro accumulation data and in vivo metabolism half-life (30 min, PET scanning was performed 30–60 min after the

  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....... RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI...

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

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    Tiziana Angrisano

    Full Text Available 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.

  13. Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: Inefficacy of genetic or pharmacological disruption of COX-2

    Science.gov (United States)

    Fong, Louise Y.Y.; Jiang, Yubao; Riley, Maurisa; Liu, Xianglan; Smalley, Karl J.; Guttridge, Denis C.; Farber, John L.

    2009-01-01

    Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced for-estomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive bio-markers COX-2, nuclear factor (NF)-κ B p65 and leukotriene A4 hydrolase (LTA4H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-2−/− forestomachs displayed strong LTA4H immunostaining, indicating activation of an alter-native pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. PMID:17985342

  14. Autocrine prostaglandin E2 signaling promotes promonocytic leukemia cell survival via COX-2 expression and MAPK pathway

    Science.gov (United States)

    Lee, Jaetae; Lee, Young Sup

    2015-01-01

    The COX-2/PGE2 pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, PGE2, in cancer survival remain unknown. Herein, we investigated PGE2-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with PGE2 activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. PGE2 not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of PGE2, and restored the menadione-induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the PGE2-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that PGE2 signaling acts in an autocrine manner, and specific inhibition of PGE2 will provide a novel approach for the treatment of leukemia. [BMB Reports 2015; 48(2): 109-114] PMID:24965577

  15. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Science.gov (United States)

    Pang, Lisa Y; Gatenby, Emma L; Kamida, Ayako; Whitelaw, Bruce A; Hupp, Ted R; Argyle, David J

    2014-01-01

    Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  16. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Directory of Open Access Journals (Sweden)

    Lisa Y Pang

    Full Text Available Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs, which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05, and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  17. FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.

    Science.gov (United States)

    Liu, Shuo; Zhang, Cun; Zhang, Kuo; Gao, Yuan; Wang, Zhaowei; Li, Xiaoju; Cheng, Guang; Wang, Shuning; Xue, Xiaochang; Li, Weina; Zhang, Wei; Zhang, Yingqi; Xing, Xianghui; Li, Meng; Hao, Qiang

    2017-07-04

    Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

  18. 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.

  19. MiR-26b Mimic Inhibits Glioma Proliferation In Vitro and In Vivo Suppressing COX-2 Expression.

    Science.gov (United States)

    Chen, Zheng-Gang; Zheng, Chuan-Yi; Cai, Wang-Qing; Li, Da-Wei; Ye, Fu-Yue; Zhou, Jian; Wu, Ran; Yang, Kun

    2017-08-11

    Glioma is the most common malignant tumor of the nervous system. Studies have shown the microRNA (miR)-26b/cyclooxygenase (COX)-2 axis in the development and progression in many tumor cells. Our study aims to investigate the effect and mechanism of miR-26b/COX-2 axis in glioma. Decreased expression of miR-26b with increased level of COX-2 was found in glioma tissues compared with matched normal tissues. A strong negative correlation was observed between the level of miR-26b and COX-2 in 30 glioma tissues. The miR-26b was then overexpressed by transfecting miR-26b mimic into U-373 cells. The invasive cell number and wounld closing rate were reduced in U-373 cells transfected with miR-26b mimic. Besides, COX2 siRNA enhanced the effect of miR-26b mimic in suppressing the expression of p-ERK1 and p-JNK. Finally, the in vivo experiment revealed that miR-26b mimic transfection strongly reduced the tumor growth, tumor volume and the expression of matrix metalloproteinase (MMP)-2, MMP-9). Taken together, our research indicated a miR-26b/COX-2/ERK/JNK axis in regulating the motility of glioma in vitro and in vivo, providing a new sight for treatment of glioma.

  20. Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer

    International Nuclear Information System (INIS)

    Aggarwal, Anshu; Al-Rohil, Rami N; Batra, Anupam; Feustel, Paul J; Jones, David M; DiPersio, C Michael

    2014-01-01

    Expression of integrin α3β1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin α3β1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin α3β1 and COX2 by testing for their correlated expression among various forms of human breast cancer. Immunohistochemistry was performed to assess co-expression of α3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin α3 subunit or COX2 was scored, and Spearman’s rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria. Although expression of integrin α3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between α3 and COX2 in both tissue microarrays (r s = 0.49, p < 0.001, n = 59) and archived samples (r s = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage. COX2 and α3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin α3β1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of α3β1

  1. Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

    Science.gov (United States)

    Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

    2006-07-01

    Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

  2. COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

    Science.gov (United States)

    Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas, M Teresa; Salazar, F Javier

    2014-03-01

    This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

  3. 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.

  4. Convergent synthesis and evaluation of {sup 18}F-labeled azulenic COX2 probes for cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Peterson, Todd E. [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Department of Physics and Astronomy, Vanderbilt University, Nashville, TN (United States); Crews, Brenda C. [Department of Chemistry, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Marnett, Larry [Department of Chemistry, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Gore, John C. [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Department of Physics and Astronomy, Vanderbilt University, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN (United States); Pham, Wellington, E-mail: wellington.pham@vanderbilt.edu [Department of Radiology, Institute of Imaging Science, Vanderbilt University, Nashville, TN (United States); Vanderbilt Institute of Chemical Biology, Nashville, TN (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (United States); Department of Neuroscience, Vanderbilt University, Nashville, TN (United States)

    2013-01-03

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (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 {sup 18}F-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 {sup 18}F 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 {sup 18}F labeling strategy that employed a much milder phosphate buffer. The {sup 18}F-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

  5. Histamine, carbachol, and serotonin induce hyperresponsiveness to ATP in guinea pig tracheas: involvement of COX-2 pathway.

    Science.gov (United States)

    Montaño, Luis M; Carbajal, Verónica; Vargas, Mario H; García-Hernández, Luz M; Díaz-Hernández, Verónica; Checa, Marco; Barajas-López, Carlos

    2013-08-01

    Extracellular ATP promotes an indirect contraction of airway smooth muscle via the secondary release of thromboxane A2 (TXA2) from airway epithelium. Our aim was to evaluate if common contractile agonists modify this response to ATP. Tracheas from sensitized guinea pigs were used to evaluate ATP-induced contractions before and after a transient contraction produced by histamine, carbachol, or serotonin. Epithelial mRNA for COX-1 and COX-2 was measured by RT-PCR and their expression assessed by immunohistochemistry. Compared with the initial response, ATP-induced contraction was potentiated by pretreatment with histamine, carbachol, or serotonin. Either suramin (antagonist of P2X and P2Y receptors) plus RB2 (antagonist of P2Y receptors) or indomethacin (inhibitor of COX-1 and COX-2) annulled the ATP-induced contraction, suggesting that it was mediated by P2Y receptor stimulation and TXA2 production. When COX-2 was inhibited by SC-58125 or thromboxane receptors were antagonized by SQ-29548, just the potentiation was abolished, leaving the basal response intact. Airway epithelial cells showed increased COX-2 mRNA after stimulation with histamine or carbachol, but not serotonin, while COX-1 mRNA was unaffected. Immunochemistry corroborated this upregulation of COX-2. In conclusion, we showed for the first time that histamine and carbachol cause hyperresponsiveness to ATP by upregulating COX-2 in airway epithelium, which likely increases TXA2 production. Serotonin-mediated hyperresponsiveness seems to be independent of COX-2 upregulation, but nonetheless is TXA2 dependent. Because acetylcholine, histamine, and serotonin can be present during asthmatic exacerbations, their potential interactions with ATP might be relevant in its pathophysiology.

  6. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis.

    Science.gov (United States)

    Kirkby, Nicholas S; Tesfai, Abel; Ahmetaj-Shala, Blerina; Gashaw, Hime H; Sampaio, Walkyria; Etelvino, Gisele; Leão, Nádia Miricéia; Santos, Robson A; Mitchell, Jane A

    2016-12-01

    Nonsteroidal antiinflammatory drugs, including ibuprofen, are among the most commonly used medications and produce their antiinflammatory effects by blocking cyclooxygenase (COX)-2. Their use is associated with increased risk of heart attacks caused by blocking COX-2 in the vasculature and/or kidney, with our recent work implicating the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), a cardiotoxic hormone whose effects can be prevented by l-arginine. The ibuprofen salt ibuprofen arginate (Spididol) was created to increase solubility but we suggest that it could also augment the NO pathway through codelivery of arginine. Here we investigated the idea that ibuprofen arginate can act to simultaneously inhibit COX-2 and preserve the NO pathway. Ibuprofen arginate functioned similarly to ibuprofen sodium for inhibition of mouse/human COX-2, but only ibuprofen arginate served as a substrate for NOS. Ibuprofen arginate but not ibuprofen sodium also reversed the inhibitory effects of ADMA and N G -nitro-l-arginine methyl ester on inducible NOS (macrophages) and endothelial NOS in vitro (aorta) and in vivo (blood pressure). These observations show that ibuprofen arginate provides, in one preparation, a COX-2 inhibitor and NOS substrate that could act to negate the harmful cardiovascular consequences mediated by blocking renal COX-2 and increased ADMA. While remarkably simple, our findings are potentially game-changing in the nonsteroidal antiinflammatory drug arena.-Kirkby, N. S., Tesfai, A., Ahmetaj-Shala, B., Gashaw, H. H., Sampaio, W., Etelvino, G., Leão, N. M., Santos, R. A., Mitchell, J. A. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis. © The Author(s).

  7. Uso combinado da laserterapia de baixa potência e da inibição da ciclooxigenase-2 na reepitelização de ferida incisional em pele de camundongos: um estudo pré-clínico Combined use of low level laser therapy and cyclooxygenase-2 selective inhibition on skin incisional wound reepithelialization in mice: a preclinical study

    Directory of Open Access Journals (Sweden)

    Cíntia Helena Santuzzi

    2011-04-01

    Full Text Available FUNDAMENTOS: A laserterapia de baixa potência e os inibidores seletivos da ciclooxigenase-2 (ICOX2 vem sendo muito utilizados para modular a resposta inflamatória, entretanto, os seus efeitos na reepitelização de feridas não são bem compreendidos. OBJETIVO: Avaliar os efeitos isolados e combinados da laserterapia de baixa potência e da ICOX2 na reepitelização de ferida incisional na pele de camundongos. MÉTODO: Foi induzida uma ferida de 1 cm no dorso de cada camundongo, que foram divididos em quatro grupos (N=20: Controle, Laserterapia, Tratados com celecoxib e Terapia conjugada. Os animais dos grupos celecoxib e Terapia conjugada foram tratados com celecoxib por 10 dias antes da incisão cutânea. As feridas experimentais foram irradiadas com laserterapia de baixa potência He-Ne (632nm, dose: 4J/cm2 em varredura, por 12 segundos durante três dias consecutivos nos grupos Laserterapia e Terapia conjugada. Os animais foram sacrificados no 3º dia de pós-operatório. Amostras das feridas foram coletadas e coradas (Tricromio de Masson para análise histomorfométrica. RESULTADOS: Tanto o grupo Laserterapia, quanto o grupo celecoxib, mostrou aumento da reepitelização cutânea em relação ao grupo Controle, entretanto, o grupo Terapia conjugada não apresentou diferenças. Quanto à queratinização o grupo Laserterapia e Terapia conjugada apresentaram redução dos queratinócitos, comparados com o grupo Controle. CONCLUSÕES: Os resultados mostram que o uso da laserterapia de baixa potência e da ICOX2 isoladamente aumentam as células epiteliais, mas somente a laserterapia de baixa potência reduziu os queratinócitos cutâneos. O tratamento conjugado restabelece a reepitelização inata e dimunui a queratinização, embora ocorra uma acelerada contração da ferida com melhora na organização da ferida na pele de camundongos.BACKGROUND: Low level laser therapy and cyclooxygenase-2 (ICOX2 selective inhibitors have been widely used

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  9. 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

  10. 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

  11. Cycloxygenase-2(cox-2) - a potential target for screening of small molecules as radiation countermeasure agents: an in silico study

    International Nuclear Information System (INIS)

    Joshi, Jayadev; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul Shubhra; Prem Kumar, I.; Barik, Tapan Kumar

    2012-01-01

    COX-2 is well established for its role in inflammation and cancer, and has also been reported to play a significant role in radiation induced inflammation and by standard effect. It's already reported to have a role in protection against radiation induced damage suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopoeia using COX-2 as target in-silico. Systematic search of the reported molecules exhibiting radiation protection revealed lat around 29 % (40 in 138) of them have a role in inflammation and a small percentage of these molecules (20 %; 8 in 40) are reported to as non steroidal anti-inflammatory drugs (NSAIDS). Docking studies performed further clarified that all these 8 radioprotective molecules shows high binding affinity and inhibit COX-2. Further Johns Hopkins clinical compound library (JHCCL), a collection of small molecule clinical compounds, were screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2 lead to identification of a number of previously unreported molecules which are likely to act as radioprotectors. (author)

  12. Cycloxygenase-2(cox-2) - a potential target for screening of small molecules as radiation countermeasure agents: an in silico study

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Jayadev; Shrivastava, Nitisha; Dimri, Manali; Ghosh, Subhajit; Mandal, Rahul Shubhra; Prem Kumar, I., E-mail: prem_indra@yahoo.co.in [Radiation Biosciences Division, Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Barik, Tapan Kumar [P.G. Department of Zoology, Berhampur University, Berhampur (India)

    2012-07-01

    COX-2 is well established for its role in inflammation and cancer, and has also been reported to play a significant role in radiation induced inflammation and by standard effect. It's already reported to have a role in protection against radiation induced damage suggesting it to be an important target for identifying novel radiation countermeasure agents. Present study aims at identifying novel small molecules from pharmacopoeia using COX-2 as target in-silico. Systematic search of the reported molecules exhibiting radiation protection revealed lat around 29 % (40 in 138) of them have a role in inflammation and a small percentage of these molecules (20 %; 8 in 40) are reported to as non steroidal anti-inflammatory drugs (NSAIDS). Docking studies performed further clarified that all these 8 radioprotective molecules shows high binding affinity and inhibit COX-2. Further Johns Hopkins clinical compound library (JHCCL), a collection of small molecule clinical compounds, were screened virtually for COX-2 inhibition by docking approach. Docking of around 1400 small molecules against COX-2 lead to identification of a number of previously unreported molecules which are likely to act as radioprotectors. (author)

  13. Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs.

    Science.gov (United States)

    Gorissen, Ben M C; Uilenreef, Joost J; Bergmann, Wilhelmina; Meijer, Ellen; van Rietbergen, Bert; van der Staay, Franz Josef; Weeren, P René van; Wolschrijn, Claudia F

    2017-11-25

    Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term meloxicam treatment on growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4 mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce (vehicle control)) were subjected to visual and objective gait analysis by pressure plate measurements at several time points. Following euthanasia a complete postmortem examination was performed and samples of the talus and distal tibia, including the distal physis, were collected. Trabecular bone microarchitecture was analysed by microCT scanning, bone stiffness by compression testing and growth plate morphology using light microscopy. Animals were not lame and gait patterns did not differ between the groups. Pathological examination revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone microarchitecture and growth plate morphology did not differ between the two groups. The findings of this in vivo study reduce concerns regarding the long-term use of meloxicam in young, growing piglets. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. COX-2 Gene Promoter Polymorphism and Coronary Artery Disease in Middle-Aged Men: The Helsinki Sudden Death Study

    Directory of Open Access Journals (Sweden)

    Kati H. Huuskonen

    2008-01-01

    Full Text Available Cyclooxygenase (COX catalyzes formation of prostaglandins that contribute to the inflammation in atherosclerosis. Our objective was to study whether the functional C variant of the −765G→C polymorphism in the human COX-2 gene associates with the severity of coronary atherosclerosis measured at the coronary artery level. The Helsinki sudden death study autopsy material (n = 300 comprised of Finnish men who died suddenly. The area of atherosclerotic lesions in the coronary arteries was quantitated, and coronary narrowing was measured. The occurrence of myocardial infarction (MI was assessed. Genotyping was by restriction endonuclease analysis. Men carrying the minor C allele had larger areas of complicated lesions (P = .024 and a higher number of coronary arteries that had over 50% stenosis (P = .036 compared to men representing the common GG genotype. The COX-2 polymorphism was not associated with MI. Our data suggest that COX-2 may be involved in plaque growth.

  15. 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.

  16. Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

    Directory of Open Access Journals (Sweden)

    Borhane Annabi

    2012-01-01

    Full Text Available The occurrence of a functional relationship between the release of metalloproteinases (MMPs and the expression of cyclooxygenase (COX-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB, increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA, a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1.

  17. 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.

  18. 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-controll......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...

  19. Bcr-Abl-independent mechanism of resistance to imatinib in K562 cells: Induction of cyclooxygenase-2 (COX-2) by histone deacetylases (HDACs).

    Science.gov (United States)

    Kalle, Arunasree M; Sachchidanand, Sachchidanand; Pallu, Reddanna

    2010-09-01

    Our previous studies have shown that overexpression of MDR1 and cyclooygenase-2 (COX-2) resulted in resistance development to imatinib in chronic myelogenous leukemia (CML) K562 (IR-K562) cells. In the present study, the regulatory mechanism of MDR1 induction by COX-2 was investigated. A gradual overexpression of MDR1 and COX-2 during the process of development was observed. Furthermore, down regulation of MDR1 upon COX-2 knockdown by siRNA showed a decrease in the PKC levels and activation of PKC by addition of PGE(2) to K562 cells, suggesting a role for PKC in the COX-2 mediated induction of MDR1. The present study demonstrates COX-2 induction by HDACs and MDR1 induction by COX-2 via PGE(2)-cAMP-PKC-mediated pathway. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. A STUDY OF COX-2 INHIBITOR CELECOXIB AND CHEMORADIATION IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    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

  1. ST6Gal1, Cox-2 and HB-EGF mRNA Expression in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Aliakbar Taherian

    2015-01-01

    Full Text Available Background: ST6Gal1, Cox-2 and HB-EGF genes are involved in different tumors and their enhanced expressions often correlate with poor prognosis. In this study we assay the expressions of these genes by reverse transcriptase-PCR in 54 breast cancer samples. Methods: Tissue samples were either formalin-fixed for histopathological examination or frozen for reverse transcriptase-PCR. Image program was used for the densitometry of the image of the gels and the expression of different genes was normalized with beta actin expression. The student's t-test and correlation matrix were used for data analyses. Results: We observed significantly higher expressions of ST6Gal1 (P= 0.040, Cox- 2 (P= 0.001 and HB-EGF (P= 0.009 in the tumor region compared to the margin samples. A significant correlation was found between HB-EGF and Cox-2 expression (P= 0.001. There was a positive correlation between total score, tumor size, histology grade and nuclear grade but there was a reverse correlation between age and tumor size, histology grade and total score. Conclusion: Expressions of ST6Gal1, Cox-2 and HB-EGF in breast tumor samples in this and a number of other studies emphasize their role as important markers in breast cancer. The use of medications to inhibit either their individual expressions or the possible inhibition of all three genes may improve patient survival and prevent metastasis.

  2. Cox-2 Plays a Vital Role in the Impaired Anxiety Like Behavior in Colchicine Induced Rat Model of Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Susmita Sil

    2016-01-01

    Full Text Available The anxiety status is changed along with memory impairments in intracerebroventricular colchicine injected rat model of Alzheimer Disease (cAD due to neurodegeneration, which has been indicated to be mediated by inflammation. Inducible cox-2, involved in inflammation, may have important role in the colchicine induced alteration of anxiety status. Therefore, the present study was designed to investigate the role of cox-2 on the anxiety behavior (response to novelty in an elevated open field space of cAD by inhibiting it with three different doses (10, 20, and 30 mg of etoricoxib (a cox-2 blocker in two time points (14 and 21 days. The results showed anxiolytic behavior in cAD along with lower serum corticosterone level, both of which were recovered at all the doses of etoricoxib on day 21. On day 14 all of the anxiety parameters showed similar results to that of day 21 at high doses but not at 10 mg/kg body weight. Results indicate that the parameters of anxiety were dependent on neuronal circuitries that were probably sensitive to etoricoxib induced blocking of neurodegeneration. The present study showed that anxiolytic behavior in cADr is predominantly due to cox-2 mediated neuroinflammation induced neurodegeneration in the brain.

  3. WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

    Directory of Open Access Journals (Sweden)

    Xiangshu Xian

    2016-11-01

    Full Text Available Background: Cannabinoids (the active components of Cannabis sativa and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN was associated with gastric cancer (GC metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2 expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

  4. 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

    Cancer often originates from a site of persistent inflammation, and the mechanisms turning chronic inflammation into a driving force of carcinogenesis are intensely investigated. Cyclooxygenase-2 (COX-2) is an inducible key modulator of inflammation that carries out the rate-limiting step...

  5. 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...

  6. Prognostic implications of tumor volume response and COX-2 expression change during radiotherapy in cervical cancer patients

    International Nuclear Information System (INIS)

    Noh, Jae Myoung; Park, Won; Huh, Seung Jae; Cho, Eun Yoon; Choi, Yoon La; Bae, Duk Soo; Kim, Byoung Gie

    2012-01-01

    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.

  7. COX-2 and PPARγ expression are potential markers of recurrence risk in mammary duct carcinoma in-situ

    International Nuclear Information System (INIS)

    Kulkarni, Swati; Patil, Deepa B; Diaz, Leslie K; Wiley, Elizabeth L; Morrow, Monica; Khan, Seema A

    2008-01-01

    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. 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). 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). 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

  8. 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.

  9. Ubiquitin-proteasomal degradation of COX-2 in TGF-β stimulated human endometrial cells is mediated through endoplasmic reticulum mannosidase I.

    Science.gov (United States)

    Singh, Mohan; Chaudhry, Parvesh; Parent, Sophie; Asselin, Eric

    2012-01-01

    Cyclooxygenase (COX)-2 is a key regulatory enzyme in the production of prostaglandins (PG) during various physiological processes. Mechanisms of COX-2 regulation in human endometrial stromal cells (human endometrial stromal cells) are not fully understood. In this study, we investigate the role of TGF-β in the regulation of COX-2 in human uterine stromal cells. Each TGF-β isoform decreases COX-2 protein level in human uterine stromal cells in Smad2/3-dependent manner. The decrease in COX-2 is accompanied by a decrease in PG synthesis. Knockdown of Smad4 using specific small interfering RNA prevents the decrease in COX-2 protein, confirming that Smad pathway is implicated in the regulation of COX-2 expression in human endometrial stromal cells. Pretreatment with 26S proteasome inhibitor, MG132, significantly restores COX-2 protein and PG synthesis, indicating that COX-2 undergoes proteasomal degradation in the presence of TGF-β. In addition, each TGF-β isoform up-regulates endoplasmic reticulum (ER)-mannosidase I (ERManI) implying that COX-2 degradation is mediated through ER-associated degradation pathway in these cells. Furthermore, inhibition of ERManI activity using the mannosidase inhibitor (kifunensine), or small interfering RNA-mediated knockdown of ERManI, prevents TGF-β-induced COX-2 degradation. Taken together, these studies suggest that TGF-β promotes COX-2 degradation in a Smad-dependent manner by up-regulating the expression of ERManI and thereby enhancing ER-associated degradation and proteasomal degradation pathways.

  10. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

    Science.gov (United States)

    2013-01-01

    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 (pdiclofenac 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. PMID:23289871

  11. Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

    Science.gov (United States)

    Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

    2017-01-01

    Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

  12. QSAR Modeling of COX -2 Inhibitory Activity of Some Dihydropyridine and Hydroquinoline Derivatives Using Multiple Linear Regression (MLR) Method.

    Science.gov (United States)

    Akbari, Somaye; Zebardast, Tannaz; Zarghi, Afshin; Hajimahdi, Zahra

    2017-01-01

    COX-2 inhibitory activities of some 1,4-dihydropyridine and 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives were modeled by quantitative structure-activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R 2 ) of 0.972 and 0.531 for training and test groups, respectively. The quality of the model was evaluated by leave-one-out (LOO) cross validation (LOO correlation coefficient (Q 2 ) of 0.943) and Y-randomization. We also employed a leverage approach for the defining of applicability domain of model. Based on QSAR models results, COX-2 inhibitory activity of selected data set had correlation with BEHm6 (highest eigenvalue n. 6 of Burden matrix/weighted by atomic masses), Mor03u (signal 03/unweighted) and IVDE (Mean information content on the vertex degree equality) descriptors which derived from their structures.

  13. Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1β Proteins in a Rat Model of Cerebral Ischemia

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    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.

  14. 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

  15. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: An intravital microscopy study in mice

    International Nuclear Information System (INIS)

    Klenke, Frank Michael; Gebhard, Martha-Maria; Ewerbeck, Volker; Abdollahi, Amir; Huber, Peter E; Sckell, Axel

    2006-01-01

    The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases

  16. The Effect of Bee Venom on COX-2, P38, ERK and JNK in RAW 264.7 Cells

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    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.

  17. AVALIAÇÃO DA DISPENSAÇÃO DE FÁRMACOS PARCIALMENTE SELETIVOS PARA COX-2

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    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.

  18. -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.

  19. 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...

  20. Combined Analysis of COX-2 and p53 Expressions Reveals Synergistic Inverse Correlations with Microsatellite Instability and CpG Island Methylator Phenotype in Colorectal Cancer

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    Shuji Ogino

    2006-06-01

    Full Text Available Cyclooxygenase-2 (COX-2 overexpression and mutations of p53 (a known COX-2 regulator are inversely associated with microsatellite instability—high (MSI-H and CpG island methylator phenotype (CIMP, characterized by extensive promoter methylation, is associated with MSI-H. However, no studies have comprehensively examined interrelations between COX-2, p53, MSI, and CIMP. Using MethyLight, we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A, CRABP1, MLH1, and NEUROG1] in relatively unbiased samples of 751 colorectal cancer cases obtained from two large prospective cohorts; 115 (15% tumors were CIMP-high (≥ 4 of 5 methylated promoters, 251 (33% were CIMP-low (1 to 3 methylated promoters, and the remaining 385 (51% were CIMP-0 (no methylated promoters. CIMP-high tumors were much less frequent in COX-2+/p53+ tumors (4.6% than in COX-2+/p53- tumors (19%; P < .0001, COX-2-/p53+ tumors (17%; P = .04, and COX-2-/p53- tumors (28%; P < .0001. In addition, COX-2+/p53+ tumors were significantly less common in MSI-H CIMP-high tumors (9.7% than in non-MSI-H CIMP-low/CIMP-0 tumors (44–47%; P < .0001. In conclusion, COX-2 and p53 alterations were synergistically inversely correlated with both MSI-H and CIMP-high. Our data suggest that a combined analysis of COX-2 and p53 may be more useful for the molecular classification of colorectal cancer than either COX-2 or p53 analysis alone.

  1. Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC.

    Science.gov (United States)

    Yang, Cheng-Chieh; Tu, Hsi-Feng; Wu, Cheng-Hsien; Chang, Hsiu-Chuan; Chiang, Wei-Fan; Shih, Nai-Chia; Lee, Yong-Syu; Kao, Shou-Yen; Chang, Kuo-Wei

    2016-05-01

    When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan-Meier disease free survival. Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice.

    Science.gov (United States)

    Philip, Bincy; Roland, Christina L; Daniluk, Jaroslaw; Liu, Yan; Chatterjee, Deyali; Gomez, Sobeyda B; Ji, Baoan; Huang, Haojie; Wang, Huamin; Fleming, Jason B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

    2013-12-01

    Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This

  3. Nano-gold displayed anti-inflammatory property via NF-kB pathways by suppressing COX-2 activity.

    Science.gov (United States)

    Khan, Mahmood Ahmad; Khan, Mohd Jahir

    2018-03-19

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, affecting almost 1% of world population. Although the exact cause of RA is not known but the complex interaction between inflammatory mediators like tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) is accountable for cartilage destruction in joints. Gold is used for arthritis treatment since long without knowing its mechanism of action. Hence, the present study was designed to assess antiarthritic activity of nanogold (AuNGs) in collagen-induced arthritic (CIA) rat model by virtue of decreasing inflammatory mediators and oxidative stress. After induction CIA rats were treated with AuNGs in phosphate buffer at a dose of 20 μg/kg body weight for 20 days and found a significant decrease in the level of inflammatory mediators like TNF-α, IL-1β, COX-2 and transcription factor NF-kB (Nuclear factor-kB), which was found to be elevated in CIA rats. Additionally imbalance in oxidant and antioxidant status were determined and perceived that AuNGs remarkably attenuates the imbalance in level of antioxidant and oxidant near to normal. In consistent to biochemical results, mRNA expression of NF-kB, TNF-α, COX-2, and iNOS were also up-regulated in CIA rats, which were considerably down regulated by AuNGs treatment. These findings were positively correlated with the histological results of joints, displayed reduced inflammation and bone erosion in treated group. This study demonstrates the ability of AuNGs to ameliorate production of inflammatory mediators and oxidative stress in CIA rats. Induction of arthritis in rats showed increased inflammation, which activate the transcription factor NF-kB through activation of of IkB kinases (IKK) and ubiquination/proteosome degradation of IKB and transportation of activated NF-kB from cytoplasm to nucleus. In nucleus activated NF-kB bind to the promoter region of target gene and up regulate the production of

  4. A recombination point is conserved in the mitochondrial genome of higher plant species and located downstream from the cox2 pseudogene in Solanum tuberosum L.

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    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.

  5. Detection of EGFR and COX-2 Expression by Immunohistochemical Method on a Tissue Microarray Section in Lung Cancer and Biological Significance

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    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.

  6. [Small interfering RNA-mediated COX-2 gene silencing enhances chemosensitivity of KB/VCR cells by suppressing MDR-1 gene expression and P-glycoprotein activity].

    Science.gov (United States)

    Mo, Xianchao; Li, Weizhong

    2014-05-01

    To investigate the effect of small interfering RNA (siRNA)-mediated COX-2 gene silencing in enhancing the chemosensitivity of KB/VCR cell lines. KB/VCR cells were trasnfected with COX-2 siRNA were examined for expressions of COX-2 and MDR-1 mRNAs with RT-PCR and for Rho-123 accumulation using flow cytometry. MTT assay was used to analyze the proliferation of the transfected KB/VCR cells. Compared with the negative and blank control groups, COX-2 siRNA transfection resulted in significant growth inhibition of KB/VCR cells exposed to vincristine (PKB/VCR cells. COX-2 gene silencing can enhance the chemosensitivity of KB/VCR cells to vincristine, the mechanism of which may involve down-regulated MDR-1 gene expression and inhibition of P-glycoprotein activity.

  7. La ciclooxigenasa-2 (COX-2 y el factor de crecimiento epidérmico (EFG en lesiones epiteliales orales premalignas Cyclooxygenase-2 (COX-2 and epidermal growth factor (EGF in oral premalignant epithelial lesions

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    S. Díaz Prado

    2009-06-01

    Full Text Available Las lesiones premalignas orales incluyen eritroplasias (manchas rojas y leucoplasias (manchas blancas, las cuales se desarrollan a lo largo de superficies epiteliales. Estas lesiones son considerados marcadores en la "carcinogénesis de campo" ya que pacientes con lesiones premalignas orales pueden desarrollar carcinoma de células escamosas (CCS en el sitio de las lesiones, así como en otros lugares de tracto aerodigestivo superior. Se está haciendo un gran esfuerzo para identificar nuevos biomarcadores SEBs (surrogate endpoint biomarkers para el carcinoma de células escamosas de cabeza y cuello. Los SEBs candidatos para el carcinoma de células escamosas invasivo en el trato aerodigestivo superior deben ser detectables con los cambios moleculares celulares y tisulares que tienen lugar durante la formación del tumor. Entre los diferentes marcadores que se han propuesto hasta la actualidad, la ciclooxigenasa- 2 (COX-2 y el receptor del factor de crecimiento epidérmico (EGFR parecen ser los más prometedores. COX-2 se sobre expresa durante el proceso tumoral, desde hiperplasia temprana a enfermedad metastásica. EGFR también está anormalmente activado en tumores epiteliales, pues las células de casi todas estas neoplasias expresan altos niveles de este receptor, una característica asociada con un peor pronóstico clínico. En este sentido el tracto aerodigestivo superior proporciona un sistema o modelo único para el estudio de CCS y para la investigación de nuevos candidatos SEBs.Oral premalignant lesions include leukoplakia (white patch and erythroplakia (red patch, which develop on epithelial surfaces. These lesions are markers for field cancerization because patients with oral premalignancy can develop squamous cell carcinoma at the site of the lesion(s and at other sites in the upper aerodigestive tract. An effort is being made to identify surrogate endpoint biomarkers (SEBs for head and neck squamous cell carcinoma (HNSCC

  8. 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

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    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.

  9. BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

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    Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

    2015-11-01

    Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

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    II Kim Jae

    2010-10-01

    Full Text Available Abstract Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB. Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight and histological analysis of the lung metastasis (gross analysis and histological staining. Reduced expression of Cox-2 (mRNA and protein from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  11. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity.

    Science.gov (United States)

    Lee, Choong-Gu; Kwon, Ho-Keun; Ryu, Jae Ha; Kang, Sung Jin; Im, Chang-Rok; Ii Kim, Jae; Im, Sin-Hyeog

    2010-10-20

    Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB). Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight) and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight) and histological analysis of the lung metastasis (gross analysis and histological staining). Reduced expression of Cox-2 (mRNA and protein) from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  12. Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain.

    Science.gov (United States)

    Rummel, Christoph; Sachot, Christelle; Poole, Stephen; Luheshi, Giamal N

    2006-11-01

    Interleukin (IL)-6 is an important humoral mediator of fever following infection and inflammation and satisfies a number of criteria for a circulating pyrogen. However, evidence supporting such a role is diminished by the moderate or even absent ability of the recombinant protein to induce fever and activate the cyclooxygenase-2 (COX-2) pathway in the brain, a prerequisite step in the initiation and maintenance of fever. In the present study, we investigated the role of endogenous circulating IL-6 in a rodent model of localized inflammation, by neutralizing its action using a specific antiserum (IL-6AS). Rats were injected with LPS (100 microg/kg) or saline into a preformed air pouch in combination with an intraperitoneal injection of either normal sheep serum or IL-6AS (1.8 ml/rat). LPS induced a febrile response, which was accompanied by a significant rise in plasma IL-6 and nuclear STAT3 translocation in endothelial cells throughout the brain 2 h after treatment, including areas surrounding the sensory circumventricular organs and the median preoptic area (MnPO), important regions in mediating fever. These responses were abolished in the presence of the IL-6AS, which also significantly inhibited the LPS-induced upregulation of mRNA expression or immunoreactivity (IR) of the inducible form of COX, the rate-limiting enzyme for PGE2-synthesis. Interestingly, nuclear signal transducer and activator of transcription (STAT)3-positive cells colocalized with COX-2-IR, signifying that IL-6-activated cells are directly involved in PGE2 production. These observations suggest that IL-6 is an important circulating pyrogen that activates the COX-2-pathway in cerebral microvasculature, most likely through a STAT3-dependent pathway.

  13. HER2 induces cell proliferation and invasion of non-small-cell lung cancer by upregulating COX-2 expression via MEK/ERK signaling pathway

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    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

  14. Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2 inhibitors

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    Deema A. Al-Turki

    2017-01-01

    Full Text Available New series of 3,4-diaryl-2-thioxoimidazolidin-4-ones and 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles were designed, synthesized and evaluated for their activity as anti-inflammatory agents. Compounds 20, 21, 23 and 34 are highly selective inhibitors of COX-2 enzyme at a concentration of 100 mM relative to celecoxib, the standard reference. (±-3-(4-Phenoxy-phenyl-5-phenyl-2-thioxoimidazolidin-4-ones 23 exhibited the most active anti-inflammatory agent.

  15. 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).

  16. Aggravation of Alzheimer's disease due to the COX-2-mediated reciprocal regulation of IL-1β and Aβ between glial and neuron cells.

    Science.gov (United States)

    Wang, Pu; Guan, Pei-Pei; Wang, Tao; Yu, Xin; Guo, Jian-Jun; Wang, Zhan-You

    2014-08-01

    Alzheimer's disease (AD) is the most common form of dementia and displays the characteristics of chronic neurodegenerative disorders; amyloid plaques (AP) that contain amyloid β-protein (Aβ) accumulate in AD, which is also characterized by tau phosphorylation. Epidemiological evidence has demonstrated that long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) markedly reduces the risk of AD by inhibiting the expression of cyclooxygenase 2 (COX-2). Although the levels of COX-2 and its metabolic product prostaglandin (PG)E2 are elevated in the brain of AD patients, the mechanisms for the development of AD remain unknown. Using human- or mouse-derived glioblastoma and neuroblastoma cell lines as model systems, we delineated the signaling pathways by which COX-2 mediates the reciprocal regulation of interleukin-1β (IL-1β) and Aβ between glial and neuron cells. In glioblastoma cells, COX-2 regulates the synthesis of IL-1β in a PGE2 -dependent manner. Moreover, COX-2-derived PGE2 signals the activation of the PI3-K/AKT and PKA/CREB pathways via cyclic AMP; these pathways transactivate the NF-κB p65 subunit via phosphorylation at Ser 536 and Ser 276, leading to IL-1β synthesis. The secretion of IL-1β from glioblastoma cells in turn stimulates the expression of COX-2 in human or mouse neuroblastoma cells. Similar regulatory mechanisms were found for the COX-2 regulation of BACE-1 expression in neuroblastoma cells. More importantly, Aβ deposition mediated the inflammatory response of glial cells via inducing the expression of COX-2 in glioblastoma cells. These findings not only provide new insights into the mechanisms of COX-2-induced AD but also initially define the therapeutic targets of AD. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

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    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.

  18. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    Science.gov (United States)

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

  19. 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

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    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.

  20. Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2-Inhibitory Activities from Marine-Derived Fungus Aspergillus niger.

    Science.gov (United States)

    Fang, Wei; Lin, Xiuping; Wang, Jianjiao; Liu, Yonghong; Tao, Huaming; Zhou, Xuefeng

    2016-07-20

    Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC50 > 30 μM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2-inhibitory activities, with the IC50 values being 11.1, 4.2, and 6.4 μM, respectively. This is the first time the COX-2-inhibitory activities of BNPs have been reported.

  1. Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice

    Science.gov (United States)

    Chai, Y; Calaf, G M; Zhou, H; Ghandhi, S A; Elliston, C D; Wen, G; Nohmi, T; Amundson, S A; Hei, T K

    2013-01-01

    Background: Although radiation-induced bystander effects have been confirmed using a variety of endpoints, the mechanism(s) underlying these effects are not well understood, especially for in vivo study. Methods: A 1-cm2 area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays, and changes in out-of-field lung and liver were observed. Results: Compared with sham-treated controls, the Spi− mutation frequency increased 2.4-fold in non-targeted lung tissues at 24 h after partial body irradiation (PBIR). Consistent with dramatic Cyclooxygenase 2 (COX-2) induction in the non-targeted bronchial epithelial cells, increasing levels of prostaglandin, together with 8-hydroxydeoxyguanosine, in the out-of-field lung tissues were observed after PBIR. In addition, DNA double-strand breaks and apoptosis were induced in bystander lung tissues after PBIR. Conclusion: The PBIR induces DNA damage and mutagenesis in non-targeted lung tissues, especially in bronchial epithelial cells, and COX-2 has an essential role in bystander mutagenesis. PMID:23321513

  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...... by antiferromagnetic collinear long-range order (k=0) at low temperatures. Upon substitution of Al3+ by Co3+ in the octahedral B site the temperature range occupied by the spin-liquid regime narrows and TN increases. To explain the experimental observations we considered magnetic anisotropy D or third......-neighbor exchange coupling J3 as degeneracy-breaking perturbations. We conclude that Co(Al1−xCox)2O4 is below the theoretical critical point J2/J1=1/8, and that magnetic anisotropy assists in selecting a collinear long-range ordered ground state, which becomes more stable with increasing x due to a higher...

  3. Disruption of COX-2 and eNOS does not confer protection from cardiovascular failure in lipopolysaccharide-treated conscious mice and isolated vascular rings

    DEFF Research Database (Denmark)

    Stæhr, Mette; Madsen, Kirsten; Vanhoutte, Paul M

    2011-01-01

    (NS 398), disruption of COX-2, endothelium removal, or eNOS deletion (eNOS(-/-)) did not improve vascular reactivity after LPS, while the NO synthase blockers 1400W and N(G)-nitro-l-arginine methyl ester prevented loss of tone. COX-2 and eNOS activities are not necessary for LPS-induced decreases...... in blood pressure, heart rate, and vascular reactivity. Inducible NOS activity appears crucial. COX-2 and eNOS are not obvious therapeutic targets for cardiovascular rescue during gram-negative endotoxemic shock....

  4. To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination with Vitamin D, in Vitro and in Vivo

    National Research Council Canada - National Science Library

    Lee, Yi-Fen

    2008-01-01

    .... We have identified a cross-talk between vitamin D and COX-2 inhibitor, two chemopreventative agents for prostate cancer, and conducted series investigations of their anti-prostate cancer effects...

  5. A Cross-Talk Between NFAT and NF-κB Pathways is Crucial for Nickel-Induced COX-2 Expression in Beas-2B Cells

    Science.gov (United States)

    Cai, T.; Li, X.; Ding, J.; Luo, W.; Li, J.; Huang, C.

    2013-01-01

    Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways leading to nickel-induced COX-2 expression are not well understood. In the current study, we found that the exposure of Beas-2B cells to nickel compounds resulted in the activation of both nuclear factor of activated T cell (NFAT) and nuclear factor-κB (NF-κB). The expression of COX-2 induced upon nickel exposure was inhibited by either a NFAT pharmacological inhibitor or the knockdown of NFAT3 by specific siRNA. We further found that the activation of NFAT and NF-κB was dependent on each other. Since our previous studies have shown that NF-κB activation is critical for nickel-induced COX-2 expression in Beas-2B cells exposed to nickel compounds under same experimental condition, we anticipate that there might be a cross-talk between the activation of NFAT and NF-κB for the COX-2 induction due to nickel exposure in Beas-2B cells. Furthermore, we showed that the scavenging of reactive oxygen species (ROS) by introduction of mitochondrial catalase inhibited the activation of both NFAT and NF-κB, and the induction of COX-2 due to nickel exposure. Taken together, our results defining the evidence showing a key role of the cross-talk between NFAT and NF-κB pathways in regulating nickel-induced COX-2 expression, further provide insight into the understanding of the molecular mechanisms linking nickel exposure to its lung carcinogenic effects. PMID:21486220

  6. Muramyl dipeptide (MDP) induces reactive oxygen species (ROS) generation via the NOD2/COX-2/NOX4 signaling pathway in human umbilical vein endothelial cells (HUVECs).

    Science.gov (United States)

    Kong, Ling-Jun; Liu, Xiao-Qian; Xue, Ying; Gao, Wei; Lv, Qian-Zhou

    2018-03-20

    Vascular endothelium dysfunction caused by oxidative stress accelerates the pathologic process of cardiovascular diseases. NOD2, an essential receptor of innate immune system, has been demonstrated to play a critical role in atherosclerosis. Here, the aim of our study was to investigate the effect and underlying molecular mechanism of muramyl dipeptide (MDP) on NOX4-mediated ROS generation in human umbilical vein endothelial cells (HUVECs). 2,7-dichlorofluorescein diacetate staining was to measure the intracellular ROS level and showed MDP promoted ROS production in a time- and dose-dependent manner. The mRNA and protein levels of NOX4 and COX-2 were detected by real-time PCR and western blot. Small interfering RNA (siRNA) was used to silence NOD2 or COX-2 gene expression and investigate the mechanism of NOD2-mediated signaling pathway in HUVECs. Data showed that MDP induced NOX4 and COX-2 expression in a time- and dose-dependent manner. NOD2 knock-down suppressed up-regulation of COX-2 and NOX4 in HUVECs treated with MDP. Furthermore, silence of COX-2 in HUVECs down-regulated the NOX4 expression after MDP stimulation. Collectively, we indicated that NOD2 played a leading role in MDP-induced COX-2/NOX4/ROS signaling pathway in HUVECs, which was a novel regulatory mechanism in the progress of ROS generation.

  7. Relationship between serum levels of triglycerides and vascular inflammation, measured as COX-2, in arteries from diabetic patients: a translational study

    Science.gov (United States)

    2013-01-01

    Background Inflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP. Methods Through a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA. Results Only a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression .Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r2 = 0.214, P < 0.04). Conclusions We conclude that is not the glucose blood levels but the triglicerydes leves what increases the expression of COX-2 in arteries from DP. PMID:23642086

  8. The effects of a cyclooxygenase-2 (COX-2 expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production

    Directory of Open Access Journals (Sweden)

    Marshall Jean-Claude

    2007-01-01

    Full Text Available Abstract Background Cyclooxygenase-2 (COX-2 expression has previously been identified in uveal melanoma although the biological role of COX-2 in this intraocular malignancy has not been elucidated. This study aimed to investigate the effect of a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as well as its effect on the cytotoxic response of macrophages. Methods Human uveal melanoma cell lines were transfected to constitutively express COX-2 and the proliferative rate of these cells using two different methods, with and without the addition of Amfenac, was measured. Nitric oxide production by macrophages was measured after exposure to melanoma-conditioned medium from both groups of cells as well as with and without Amfenac, the active metabolite of Nepafenac. Results Cells transfected to express COX-2 had a higher proliferation rate than those that did not. The addition of Amfenac significantly decreased the proliferation rate of all cell lines. Nitric oxide production by macrophages was inhibited by the addition of melanoma conditioned medium, the addition of Amfenac partially overcame this inhibition. Conclusion Amfenac affected both COX-2 transfected and non-transfected uveal melanoma cells in terms of their proliferation rates as well as their suppressive effects on macrophage cytotoxic activity.

  9. Mechanisms of ceramide-induced COX-2-dependent apoptosis in human ovarian cancer OVCAR-3 cells partially overlapped with resveratrol

    DEFF Research Database (Denmark)

    Lin, Hung-Yun; Delmas, Dominique; Vang, Ole

    2013-01-01

    -2 appears at the apex of the p38 kinase-mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide-treated cells....... Ceramide-treated cells underwent a dose-dependent reduction in trans-membrane potential. Although both ceramide and resveratrol induced the expressions of caspase-3 and -7, the effect of inducible COX-2 was different in caspase-7 expression induced by ceramide compared to resveratrol. In summary......, resveratrol and ceramide converge on an endocytosis-requiring, ERK1/2-dependent signal transduction pathway and induction of COX-expression as an essential molecular antecedent for subsequent p53-dependent apoptosis. In addition, expressions of caspase-3 and -7 are observed. However, a p38 kinase...

  10. Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo

    Directory of Open Access Journals (Sweden)

    Wei Kevin Zhang

    2016-04-01

    Full Text Available Background: Chronic pain, or sometimes referred to as persistent pain, reduces the life quality of patients who are suffering from chronic diseases such as inflammatory diseases, cancer and diabetes. Hence, herbal medicines draw many attentions and have been shown effective in the treatment or relief of pain. Methods and Results: Here in this study, we used the CFA-injected rats as a sustainable pain model to test the anti-inflammatory and analgesic effect of nutmeg oil, a spice flavor additive to beverages and baked goods produced from the seed of Myristica fragrans tree. Conclusions: We have demonstrated that nutmeg oil could potentially alleviate the CFA-injection induced joint swelling, mechanical allodynia and heat hyperanalgesia of rats through inhibition of COX-2 expression and blood substance P level, which made it possible for nutmeg oil to be a potential chronic pain reliever.

  11. Optimization of a nonviral transfection system to evaluate Cox-2 controlled interleukin-4 expression for osteoarthritis gene therapy in vitro.

    Science.gov (United States)

    Lang, Annemarie; Neuhaus, Johannes; Pfeiffenberger, Moritz; Schröder, Erik; Ponomarev, Igor; Weber, Yvonne; Gaber, Timo; Schmidt, Michael F G

    2014-01-01

    Gene therapy appears to have the potential for achieving a long-term remedy for osteoarthritis (OA). However, there is a risk of adverse reactions, especially when using cytomegalovirus-controlled expression. To provide a safe application, we focused on the expression of therapeutic cytokines [e.g. interleukin (IL)-4] in a disease-responsive manner by use of the previously cloned Cox-2 promoter as 'genetic switch'. In the present study, we report the functionality of a controlled gene therapeutic system in an equine osteoarthritic cell model. Different nonviral transfection reagents were tested for their efficiency on equine chondrocytes stimulated with equine IL-1β or lipopolysaccharide to create an inflammatory environment. To optimize the transfection, we successfully redesigned the vector by excluding the internal ribosomal entry site (IRES). The functionality of our Cox-2 promoter construct with respect to expressing IL-4 was proven at the mRNA and protein levels and the anti-inflammatory potential of IL-4 was confirmed by analyzing the expression of IL-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3 and tumor necrosis factor (TNF)-α using a quantitative polymerase chain reaction. Nonviral transfection reagents yielded transfection rates from 21% to 44% with control vectors with and without IRES, respectively. Stimulation of equine chondrocytes resulted in a 20-fold increase of mRNA expression of IL-1β. Such exogenous stimulation of chondrocytes transfected with pNCox2-IL4 led to an increase of IL-4 mRNA expression, whereas expression of inflammatory mediators decreased. The timely link between these events confirms the anti-inflammatory potential of synthesized IL-4. We consider that this approach has significant potential for translation into a useful anti-inflammation therapy. Molecular tools such as the described therapeutic plasmid pave the way for a local-controlled, self-limiting gene therapy. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Prognosis value of the COX-2 expression on radiotherapy efficiency and on survival without progression of patients reached by an unoperative glioblastoma; Valeur pronostique de l'expression de COX-2 sur l'efficacite de la radiotherapie et sur la survie sans progression des patients atteints d'un glioblastome inoperable

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.M.; Mazeron, J.J. [Groupe Hospitalier de la Pitie-Salepetriere, APHP, Service de Radiotherapie Oncologique, 75 - Paris (France); Mokhtari, K. [Groupe Hospitalier de la Pitie-Salepetriere, APHP, Lab. de Neuropathologie, 75 - Paris (France); Genestie, C. [Groupe Hospitalier de la Pitie-Salepetriere, APHP, Lab. d' Anatomie Pathologique, 75 - Paris (France); Bissery, A. [Groupe Hospitalier de la Pitie-Salepetriere, APHP, Dept. de biostatistiques et d' Anformation Medicale, 75 - Paris (France); Jaillon, P. [Hopital Saint-Antoine, Service de Pharmacologie, 75 - Paris (France)

    2006-11-15

    The expression of COX-2 is a prediction factor of the lack of response to the radiotherapy of glioblastomas and a less good survival rate without tumor progression, aside other known prognosis factors. These results suggest a selective treatment by an anti-COX-2 could have a radiosensitizer contribution during the radiotherapy of glioblastomas. (N.C.)

  13. Correlation analysis between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer.

    Science.gov (United States)

    Qiu, Xiaoming; Mei, Jixin; Yin, Jianjun; Wang, Hong; Wang, Jinqi; Xie, Ming

    2017-09-01

    This study investigated expression of proliferating cell nuclear antigen (PCNA), proliferation-associated nuclear antigen (Ki-67) and cyclooxygenase-2 (COX-2) in tissues of breast invasive ductal carcinoma, and analyzed the correlations between these indexes and X-ray features in mammography. A total of 90 patients who were admitted to Huangshi Central Hospital and diagnosed as breast invasive ductal carcinoma from January 2014 to January 2016 were selected. The expression of PCNA, Ki-67 and COX-2 in cancer tissues and cancer-adjacent normal tissues of patients were detected by immunohistochemical staining, and X-ray features in mammography of patients were observed. By using Spearman correlation analysis, the correlations between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer were investigated. As a result, the positive expression rates of PCNA, Ki-67 and COX-2 in cancer tissues of the patient groups were respectively 42.2, 45.6 and 51.1%, which were significantly higher than those in cancer-adjacent normal tissues of the control group (pcorrelation with age and tumor size (p>0.05). PCNA, Ki-67 and COX-2 expression in cancer tissues of the patient group had no correlation with the existence of lumps and localized density-increased shadows (p>0.05), but were associated with manifestations of architectural distortion, calcification as well as skin and nipple depression (pcorrelation analysis revealed that there was a significantly positive correlation between the expression of PCNA and COX-2 in cancer tissues of the patient group (r=0.676, pcorrelation between the expression of Ki-67 and COX-2 (r=0.724, pcorrelation with the expression of Ki-67 (p>0.05). In conclusion, PCNA, Ki-67 and COX-2 expression is of great significance in the occurrence, invasion and metastasis of breast invasive ductal carcinoma. There is a strong correlation between PCNA, Ki-67 and COX-2 expression levels and X-ray features in mammography in breast

  14. Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

    Science.gov (United States)

    Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

    2016-03-09

    It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results

  15. Aspectos gerais do poliestireno

    OpenAIRE

    Montenegro, Ricardo Sá Peixoto; Serfaty, Moysés Elias

    2002-01-01

    O presente trabalho pretende dar uma visão geral e atualizada do poliestireno, o mais antigo termoplástico fabricado comercialmente no mundo. Apresenta-se uma visão simplificada do cenário mundial, da América do Sul e do Brasil, bem como alguns aspectos das tecnologias de fabricação e ambiental. Bibliografia: p. 136

  16. ATP mediates NADPH oxidase/ROS generation and COX-2/PGE2 expression in A549 cells: role of P2 receptor-dependent STAT3 activation.

    Directory of Open Access Journals (Sweden)

    Shin-Ei Cheng

    Full Text Available BACKGROUND: Up-regulation of cyclooxygenase (COX-2 and its metabolite prostaglandin E(2 (PGE(2 are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE(2 release remain unclear. PRINCIPAL FINDINGS: Here, we showed that ATPγS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin, PKC (Gö6983, Gö6976, Ro318220, and Rottlerin, ROS (Edaravone, NADPH oxidase [diphenyleneiodonium chloride (DPI and apocynin], Jak2 (AG490, and STAT3 [cucurbitacin E (CBE] and transfection with siRNAs of PKCα, PKCι, PKCμ, p47(phox, Jak2, STAT3, and cPLA(2 markedly reduced ATPγS-induced COX-2 expression and PGE(2 production. In addition, pretreatment with the inhibitors of P2 receptor attenuated PKCs translocation from the cytosol to the membrane in response to ATPγS. Moreover, ATPγS-induced ROS generation and p47(phox translocation was also reduced by pretreatment with the inhibitors of P2 receptor, PKC, and NADPH oxidase. On the other hand, ATPγS stimulated Jak2 and STAT3 activation which were inhibited by pretreatment with PPADS, suramin, Gö6983, Gö6976, Ro318220, GF109203X, Rottlerin, Edaravone, DPI, and apocynin in A549 cells. SIGNIFICANCE: Taken together, these results showed that ATPγS induced COX-2 expression and PGE(2 production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA(2 signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation will create opportunities for the development of anti-inflammation therapeutic strategies.

  17. Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?

    International Nuclear Information System (INIS)

    Clarkin, Claire E.; Garonna, Elena; Pitsillides, Andrew A.; Wheeler-Jones, Caroline P.D.

    2008-01-01

    In bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE 2 on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure of ECs to PGE 2 increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF 1α release and EC proliferation. In contrast, PGE 2 attenuated VEGF 165 -induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE 2 restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH 2 (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling

  18. Ekspresi COX-2 dan Jumlah Neutrofil Fase Inflamasi pada Proses Penyembuhan Luka Setelah Pemberian Sistemik Ekstrak Etanolik Rosela (Hibiscus sabdariffa (studi in vivo pada Tikus Wistar

    Directory of Open Access Journals (Sweden)

    Endah Kusumastuti

    2014-06-01

    Full Text Available Inflamasi merupakan respon alami tubuh terhadap adanya kerusakan jaringan. Salah satu medikamen untuk mengatasi inflamasi adalah antiinflamasi non steroid (AINS. Penggunaan AINS mempunyai beberapa efek samping dan dalam beberapa hal penggunaan tanaman obat dinilai lebih aman. Rosela merupakan salah satu tanaman obat yang mempunyai potensi sebagai antiinflamasi. Penelitian ini bertujuan untuk mengetahui efek pemberian sistemik ekstrak etanolik rosela terhadap ekspresi COX-2 dan jumlah neutrofil fase inflamasi pada proses penyembuhan luka. Bunga rosela didapatkan dari perkebunan di Dusun Bulusari Desa Pojok Kecamatan Tarokan Kabupaten Kediri Jawa Timur. Pembuatan ekstrak rosela dilakukan di LPPT unit I UGM Yogjakarta dengan cara perkolasi. Tikus putih galur Wistar sebanyak 36 ekor diberi perlukaan dengan punch biopsi ɵ 3 mm pada mukosa bukal. Subjek dibagi menjadi 3 kelompok, masing-masing kelompok 12 ekor tikus. Pembagian kelompok terdiri dari kontrol negatif (saline, kontrol positif (ibuprofen 20 mg/kg BB dan perlakuan (ekstrak rosela 500 mg/kg BB. Pemberian minum sesuai kelompoknya sehari sekali selama 4 hari. Pada hari ke-1, ke-2, ke-3 dan ke-4 tikus dikorbankan lalu jaringan mukosa yang mengalami perlukaan dibuat preparat histologis. Pewarnaan Hematoksilin Eosin (HE dilakukan untuk mengamati jumlah neutrofil. Ekspresi COX-2 diamati pada preparat dengan pewarnaan imunohistokimia menggunakan rabbit polyclonal antibody COX-2 (Lab Vision, USA. Jumlah neutrofil dan ekspresi COX-2 dihitung di bawah mikroskop cahaya lalu data dianalisi menggunakan ANAVA dan LSD. Hasil penelitian menunjukkan bahwa ekspresi COX-2 dan jumlah neutrofil lebih rendah pada kelompok perlakuan dibanding kontrol. Pengamatan klinis pada hari ke-4 juga tampak luka seluruh subjek telah menutup sempurna setelah pemberian minum rosela. Disimpulkan bahwa ekstrak etanolik rosela mempunyai kemampuan menghambat ekspresi COX-2 dan menurunkan jumlah neutrofil sehingga dapat digunakan

  19. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

    International Nuclear Information System (INIS)

    Jönsson, Maria E.; Kubota, Akira; Timme-Laragy, Alicia R.; Woodin, Bruce; Stegeman, John J.

    2012-01-01

    The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P450 1 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swim bladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependence of the effect of PCB126 on swim bladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swim bladder inflation. The effects of PCB126 were concentration-dependent with EC 50 values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swim bladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swim bladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos failed to inflate the swim bladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swim bladder. Our results indicate that PCB126 blocks swim bladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swim bladder cells. -- Highlights: ► PCB126 caused cellular changes in the developing swim bladder. ► Swim bladder inflation was not related to expression of CYP1 or cox-2.

  20. Signal Transduction Pathways (MAPKs, NF-κB, and C/EBP) Regulating COX-2 Expression in Nasal Fibroblasts from Asthma Patients with Aspirin Intolerance

    Science.gov (United States)

    Garcia-Garcia, Francesc Josep; Mullol, Joaquim; Perez-Gonzalez, Maria; Pujols, Laura; Alobid, Isam

    2012-01-01

    Background Recent studies have revealed that cyclooxygenase-2 (COX-2) expression is down-regulated in aspirin-induced asthma (AIA). Various signal pathways (MAPKs, NF-κB and C/EBP) are involved in COX-2 regulation. Objective To investigate the regulation of COX-2 expression through MAP-kinase pathway activation and nuclear factor translocation in aspirin-induced asthma (AIA). Methods Fibroblasts were isolated from specimens of nasal mucosa (NM, N = 5) and nasal polyps (NP, N = 5). After IL-1β (1 ng/ml) incubation, COX-2 and phosphorylated forms of ERK, JNK and p38 MAPK were measured by Western blot. MAPK’s role in IL-1β-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1–10 µM) prior to IL-1β exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAM® after IL-1β (10 ng/ml) exposure. Results No differences were observed in the MAPK phosphorylation time-course between NM and NP-AIA fibroblasts. The p38 MAPK inhibitor at 10 µM significantly reduced IL-1β-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 µM was not statistically significant compared to non-treated cells. ERK and JNK inhibitors had no significant effect in either the NM or NP-AIA cultures. The effect of IL-1β on NF-κB and C/EBP subunits’ nuclear translocation was similar between NM and NP-AIA fibroblasts. Conclusions These results suggest that p38 MAPK is the only MAPK involved in IL-1β-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-κB and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation. PMID:23240010

  1. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Jönsson, Maria E., E-mail: maria.jonsson@ebc.uu.se [Dept. of Environmental Toxicology, Evolutionary Biology, Centre, Uppsala University, Norbyvägen 18A, 752 36 Uppsala (Sweden); Biology Department, Redfield 3-42 MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543 (United States); Kubota, Akira, E-mail: akubota@whoi.edu [Biology Department, Redfield 3-42 MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543 (United States); Timme-Laragy, Alicia R., E-mail: atimmelaragy@whoi.edu [Biology Department, Redfield 3-42 MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543 (United States); Division of Environmental Health, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, 01003 (United States); Woodin, Bruce, E-mail: bwoodin@whoi.edu [Biology Department, Redfield 3-42 MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543 (United States); Stegeman, John J., E-mail: jstegeman@whoi.edu [Biology Department, Redfield 3-42 MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA, 02543 (United States)

    2012-12-01

    The teleost swim bladder is assumed a homolog of the tetrapod lung. Both swim bladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR) agonists; in zebrafish (Danio rerio) the swim bladder fails to inflate with exposure to 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P450 1 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swim bladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependence of the effect of PCB126 on swim bladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swim bladder inflation. The effects of PCB126 were concentration-dependent with EC{sub 50} values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swim bladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swim bladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos failed to inflate the swim bladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swim bladder. Our results indicate that PCB126 blocks swim bladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swim bladder cells. -- Highlights: ► PCB126 caused cellular changes in the developing swim bladder. ► Swim bladder inflation was not related to expression of CYP1 or cox

  2. Expression of COX-2, CD44v6 and CD147 and relationship with invasion and lymph node metastasis in hypopharyngeal squamous cell carcinoma.

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    Qing Yang

    Full Text Available To assess the expression of COX-2,CD44v6 and CD147 in hypopharyngeal squamous cell carcinomas and the three biomarkers correlation with tumor invasion and lymph node metastasis of Chinese people. 101 cases of surgically excised primary tumor were included in this study, and 40 tissues of epithelium adjacent to carcinoma were used as controls. We characterized the immunohistochemical expression of COX-2, CD44v6, and CD147 in 141 formalin-fixed, paraffin-embedded tissues, and measured the mean optical density (OD of the positive area to identify the expression of the three bio-markers and relationship with tumor invasion and lymph node metastasis. Our study demonstrates that the expression of the COX-2 and CD147 were significantly increased in carcinoma tissues compared to the epithelium adjacent to carcinoma. We also observed that the expression of COX-2, CD44v6, and CD147 were significantly associated with T classification, lymph node metastasis and clinical stage. There was strong significant correlation among the three biomarkers as well. Additionally, we indicated that recurrence and ≥ P50 level of COX-2 expression had an independent prognostic effect on prognosis. In conclusion, the three biomarkers play important roles in tumor invasion and lymph node metastases and might be valuable indicators of tumor metastasis in hypopharyngeal squamous cell carcinoma.

  3. Inhibitory Effects of Culinary Herbs and Spices on the Growth of HCA-7 Colorectal Cancer Cells and Their COX-2 Expression.

    Science.gov (United States)

    Jaksevicius, Andrius; Carew, Mark; Mistry, Calli; Modjtahedi, Helmout; Opara, Elizabeth I

    2017-09-21

    It is unclear if the anti-inflammatory properties of culinary herbs and spices (CHS) are linked to their ability to inhibit Colorectal cancer cell (CRC) growth. Furthermore, their therapeutic potential with regards to CRC is unknown. The aim of this study was to establish if the inhibition of HCA-7 CRC cell growth by a selection of culinary herbs and spices (CHS) is linked to the inhibition of the cells' cyclooxygenase-2 (COX-2 )expression, and to investigate their therapeutic potential. CHS inhibited the growth of Human colon adenocarcinoma-7 (HCA-7) cells; the order of potency was turmeric, bay leaf, ginger, sage, and rosemary; their combinations had a synergistic or additive effect on cell growth inhibition. CHS also inhibited COX-2 expression and activity; this action was comparable to that of the specific COX-2 inhibitor Celecoxib. Coincident with COX-2 inhibition was the accumulation of cells in the sub G1 phase of the HCA-7's cell cycle and, using bay leaf and turmeric, the cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP). This latter effect showed that the effect of these CHS on growth arrest was irreversible, and was comparable to that of the caspase activator Etoposide. This study provides evidence of a link between the inhibition of HCA-7 growth, and its COX-2 expression, by CHS, and their therapeutic potential.

  4. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

    International Nuclear Information System (INIS)

    Corona, Giulia; Deiana, Monica; Incani, Alessandra; Vauzour, David; Assunta Dessi, M.; Spencer, Jeremy P.E.

    2007-01-01

    We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 μg/ml) the number of cells in the G2/M phase increased to 51.82 ± 2.69% relative to control cells (15.1 ± 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 μg/ml) to exert rapid inhibition of p38 (38.7 ± 4.7%) and CREB (28.6 ± 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 ± 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development

  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

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    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. Curcumin inhibits interferon-α induced NF-κB and COX-2 in human A549 non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Lee, Jeeyun; Im, Young-Hyuck; Jung, Hae Hyun; Kim, Joo Hyun; Park, Joon Oh; Kim, Kihyun; Kim, Won Seog; Ahn, Jin Seok; Jung, Chul Won; Park, Young Suk; Kang, Won Ki; Park, Keunchil

    2005-01-01

    The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-α treatment. The IFN-α-treated A549 cells showed increase in protein expression levels of NF-κB and COX-2. IFN-α induced NF-κB binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-α-induced COX-2 expression in A549 cells. Within 10 min, IFN-α rapidly induced the binding activity of a γ- 32 P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-α-induced activations of NF-κB and COX-2 were inhibited by the addition of curcumin in A549 cells

  7. Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

    International Nuclear Information System (INIS)

    Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.; Raju, Uma; Andratschke, Nickolaus H.; Milas, Luka; Rodemann, H. Peter

    2008-01-01

    Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by γH 2 AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observed radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual γH2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2

  8. Growth and adherence of Staphylococcus aureus were enhanced through the PGE2 produced by the activated COX-2/PGE2 pathway of infected oral epithelial cells.

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    Yuxia Wang

    Full Text Available Staphylococcus aureus is a major pathogen of varieties of oral mucous infection. Prostaglandin E2 (PGE2 is a pro-inflammatory factor and Cyclooxygenase 2 (COX-2 is a critical enzyme of PGE2 biosynthesis. The purpose of this study is to investigate whether Staphylococcus aureus can increase PGE2 production of oral epithelial cells and how PGE2 functions in the growth and adherence of Staphylococcus aureus. mRNA levels of COX-2, fnbpA and fnbpB were estimated by quantitative PCR. PGE2 production was measured by Enzyme Linked Immunosorbent Assay (ELISA. The binding biomass of Staphylococcus aureus to human fibronectin was investigated by crystal violet staining and confocal laser scanning microscopy and the adherent force was measured by atomic force microscope (AFM. The COX-2 mRNA level and PGE2 production were increased by Staphylococcus aureus. PGE2 promoted the growth and biofilm formation of Staphylococcus aureus, enhanced the attachment of Staphylococcus aureus to the human fibronectin as well as to the HOK cells. The transcription of fnbpB was up-regulated by PGE2 in both early and middle exponential phase but not fnbpA. These results suggest that the activation of COX-2/PGE2 pathway in oral epithelial cell by Staphylococcus aureus can in turn facilitate the growth and the ability to adhere of the pathogen. These findings uncover a new function of PGE2 and may lead to the potential of COX-2/PGE2 targeting in the therapy of inflammation and cancer in both which the COX-2/PGE2 pathway were observed activated.

  9. Role of IL-1 beta and COX2 in silica-induced IL-6 release and loss of pneumocytes in co-cultures.

    Science.gov (United States)

    Herseth, Jan I; Refsnes, Magne; Låg, Marit; Schwarze, Per E

    2009-10-01

    The pro-inflammatory cytokines IL-1 beta, TNF-alpha and IL-6 are of great importance in the development of silica-induced lung damage and repair. In this study we investigated the role of IL-1 beta, TNF-alpha and COX2 in silica-induced regulation of IL-6 release and pneumocyte loss in various mono- and co-cultures of monocytes, pneumocytes and endothelial cells. All co-cultures with monocytes, and especially cultures including endothelial cells, showed an increase of silica-induced release of IL-6 compared to the respective monocultures. Treatment with the antagonist IL-1 ra strongly decreased IL-1 beta and IL-6 release in contact co-cultures of monocytes and pneumocytes. COX2 up-regulation by silica and IL-1 beta was eliminated by IL-1 ra. Inhibition of COX2 markedly reduced both IL-1 beta and IL-6 release. IL-1 ra was more effective than COX2-inhibition in reduction of IL-6, but not of IL-1 beta. Silica-induced pneumocyte loss was reduced by IL-1 beta, but this effect was not counteracted by the IL-1 receptor antagonist. Our findings suggest that silica-induced IL-6 release from pneumocytes is mainly mediated via IL-1 beta release from the monocytes, via both COX2-dependent and -independent pathways. Notably, COX2-derived mediators seem crucial for a positive feed-back regulation of IL-1 beta release from the monocytes. In contrast to silica-induced IL-6, the reduction in pneumocyte loss by IL-1 beta does not seem to be regulated through an IL-1R1-dependent mechanism.

  10. Ahr2-dependance of PCB126 effects on the swimbladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish

    Science.gov (United States)

    Jönsson, Maria E.; Kubota, Akira; Timme-Laragy, Alicia; Woodin, Bruce; Stegeman, John J.

    2012-01-01

    The teleost swimbladder is assumed a homolog of the tetrapod lung. Both swimbladder and lung are developmental targets of persistent aryl hydrocarbon receptor (AHR1) agonists; in zebrafish (Danio rerio) the swimbladder fails to inflate with exposure to 3,3’,4,4’,5-pentachlorobiphenyl (PCB126). The mechanism for this effect is unknown, but studies have suggested roles of cytochrome P4501 (CYP1) and cyclooxygenase 2 (Cox-2) in some Ahr-mediated developmental effects in zebrafish. We determined relationships between swimbladder inflation and CYP1 and Cox-2 mRNA expression in PCB126-exposed zebrafish embryos. We also examined effects on β-catenin dependent transcription, histological effects, and Ahr2 dependance of the effect of PCB126 on swimbladder using morpholinos targeting ahr2. One-day-old embryos were exposed to waterborne PCB126 or carrier (DMSO) for 24 h and then held in clean water until day 4, a normal time for swimbladder inflation. The effects of PCB126 were concentration-dependent with EC50 values of 1.4 to 2.0 nM for induction of the CYP1s, 3.7 and 5.1 nM (or higher) for cox-2a and cox-2b induction, and 2.5 nM for inhibition of swimbladder inflation. Histological defects included a compaction of the developing bladder. Ahr2-morpholino treatment rescued the effect of PCB126 (5 nM) on swimbladder inflation and blocked induction of CYP1A, cox-2a, and cox-2b. With 2 nM PCB126 approximately 30% of eleutheroembryos2 failed to inflate the swimbladder, but there was no difference in CYP1 or cox-2 mRNA expression between those embryos and embryos showing inflated swimbladder. Our results indicate that PCB126 blocks swimbladder inflation via an Ahr2-mediated mechanism. This mechanism seems independent of CYP1 or cox-2 mRNA induction but may involve abnormal development of swimbladder cells. PMID:23036320

  11. Kaempferol attenuates COX-2 expression in IL-6-induced macrophages and carrageenan-induced mouse paw edema by targeting STAT3 and NF-kB

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    Anandita Basu

    2017-10-01

    Full Text Available Dietary polyphenols are reported to possess varied pharmacological activities, viz. antioxidant, anti-inflammatory, anti-cancer, anti-allergic actions. Here, we report the efficacy of Kaempferol (kae to attenuate expression of IL-6 induced cycloxygenase-2 (COX-2, an inducible isoform of cycloxygenase enzyme family that catalyzes synthesis of inflammatory mediators, prostanoids and prostaglandins. IL-6 is a pleiotropic cytokine involved in both acute and chronic inflammation. Our results showed that kae attenuated COX-2 expression at both mRNA and protein level in IL-6-induced THP1 macrophages. This attenuation of COX-2 expression by kae involved dose-dependent inhibition of phosphorylation of STAT3 (Tyr 705 and NF-kB p65 (Ser 536 leading to their deactivation and reduced nuclear localization in THP-1 macrophages. Moreover, kae modulates COX-2 expression as well as STAT3 and NF-kB activation in carrageenan-induced mouse paw edema model. RT-PCR and western blot analysis from paw tissues were harvested after kae injection (i.p followed by carrageenan-treatment in sub-plantar region of right hind paw. Results showed that kae attenuated COX-2 expression and STAT3 and NF-kB activation in carrageenan-induced mouse paw edema, suggesting that inhibition of both IL-6-STAT3-COX-2 and IL-6-NFkB-COX-2 axes by kae might be stimulus-independent. To understand binding affinity of kae with NF-kB and STAT3, docking analysis was performed using Patchdock server. From our findings, we observed strong binding affinity and transient interaction in both NF-kB/kae and STAT3/kae complexes. We noticed negative atomic contact energy and greater interface area for both the complexes. Selected complexes obtained from Patchdock were refined using Firedock online server which also suggested similar negative binding energy profile. It is plausible that kae attenuates COX-2 expression by directly binding to both STAT3 and NF-kB proteins and inhibiting their activation and

  12. Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

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    Lee Jang-Ming

    2009-05-01

    Full Text Available Abstract Background Overexpression of Cyclooxygenase-2 (COX-2 was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC. One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP, H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9. COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3. The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5. Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9, and the effect was observed to be enhanced for the lower third ESCC

  13. Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study.

    Science.gov (United States)

    Hu, Huang-Ming; Kuo, Chao-Hung; Lee, Chien-Hung; Wu, I-Chen; Lee, Ka-Wo; Lee, Jang-Ming; Goan, Yih-Gang; Chou, Shah-Hwa; Kao, Ein-Long; Wu, Ming-Tsang; Wu, Deng-Chyang

    2009-05-23

    Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 - 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 - 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 - 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 - 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 - 0.47, p for

  14. Exploring QSAR with E-state index: selectivity requirements for COX-2 versus COX-1 binding of terphenyl methyl sulfones and sulfonamides.

    Science.gov (United States)

    Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

    2004-09-20

    An attempt has been made to explore selectivity requirements for cyclooxygenase-2 (COX-2) versus cyclooxygenase-1 (COX-1) binding of terphenyl methyl sulfones and sulfonamides using electrotopological state (E-state) index and suitable indicator parameters. Multiple linear regression analyses produced statistically acceptable equations: the best relation based on 'all-possible-subsets regression' for COX-1 binding (n=18) showed predicted variance and explained variance of 0.675 and 0.777, respectively, while in case of the best equation for COX-2 binding (n=38), these values rose to 0.842 and 0.874, respectively. For the selectivity relation (n=17), predicted variance and explained variance values were 0.601 and 0.687, respectively. Based on the results of the analyses, three important sites have been suggested: sites A (methylsulfonyl or aminosulfonyl moiety), B (central phenyl ring), and C (terminal phenyl ring containing different substituents). All three sites are important for COX-2 binding while sites B and C are important for COX-1 binding. For COX-2 selectivity, only site C plays an important role. The study shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance.

  15. Perioperative Pain Relief by a COX-2 Inhibitor Affects Ileal Repair and Provides a Model for Anastomotic Leakage in the Intestine

    NARCIS (Netherlands)

    van der Vijver, R.J.; Laarhoven, C.J. van; de Man, B.M.; Lomme, R.M.L.M.; Hendriks, T.

    2013-01-01

    The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or

  16. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  17. Antiproliferative effect of a novel nitro-oxy derivative of celecoxib in human colon cancer cells: role of COX-2 and nitric oxide.

    Science.gov (United States)

    Bocca, Claudia; Bozzo, Francesca; Bassignana, Andrea; Miglietta, Antonella

    2010-07-01

    It has been shown previously that a novel nitrooxy derivative of celecoxib exerts antiproliferative and pro-apoptotic effects in human colon cancer cells. The aim of this study was to elucidate whether these biological properties depend on COX-2 inhibition and/or NO release. Therefore, the derivative was decomposed into the parent compound celecoxib and the NO donor benzyl nitrate and the biological role of each was tested in COX-2-positive (HT-29) and -negative (SW-480) colon cancer cells. The main findings were that the nitro-oxy derivative behaved like celecoxib in HT-29 cells in terms of COX-2 and ERK/MAPK inhibition, as well as induction of apoptosis, while the benzyl nitrate had no such effects. Interestingly, the beta-catenin system was activated by the nitro-oxy derivative as well as by benzyl nitrate alone more potently than by the parent compound celecoxib, suggesting a possible regulatory role for NO. In SW480 cells, these activities were substantially less pronounced, suggesting the presence of COX-2-dependent mechanisms in the modulation of these parameters.

  18. COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data

    International Nuclear Information System (INIS)

    Leng, Wei-Dong; Wen, Xiu-Jie; Kwong, Joey S. W.; Huang, Wei; Chen, Jian-Gang; Zeng, Xian-Tao

    2016-01-01

    Numerous case–control studies have been performed to investigate the association between three cyclooxygenase-2 (COX-2) polymorphisms (rs20417 (−765G > C), rs689466 (−1195G > A), and rs5275 (8473 T > C)) and the risk of head and neck squamous cell carcinoma (HNSCC). However, the results were inconsistent. Therefore, we conducted this meta-analysis to investigate the association. We searched in PubMed, Embase, and Web of Science up to January 20, 2015 (last updated on May 12, 2016). Two independent reviewers extracted the data. Odds ratios (ORs) with their 95 % confidence intervals (CIs) were used to assess the association. All statistical analyses were performed using the Review Manager (RevMan) 5.2 software. Finally 8 case–control studies were included in this meta-analysis. For unadjusted data, an association with increased risk was observed in three genetic models in COX-2 rs689466 polymorphism; however, COX-2 rs5275 and rs20417 polymorphisms were not related to HNSCC risk in this study. The pooled results from adjusted data all revealed non-significant association between these three polymorphisms and risk of HNSCC. We also found a similar result in the subgroup analyses, based on both unadjusted data and adjusted data. Current results suggest that COX-2 rs689466, rs5275, and rs20417 polymorphisms are not associated with HNSCC. Further large and well-designed studies are necessary to validate this association

  19. Lasiodin inhibits proliferation of human nasopharyngeal carcinoma cells by simultaneous modulation of the Apaf-1/caspase, AKT/MAPK and COX-2/NF-κB signaling pathways.

    Directory of Open Access Journals (Sweden)

    Lianzhu Lin

    Full Text Available Rabdosia serra has been widely used for the treatment of the various human diseases. However, the antiproliferative effects and underlying mechanisms of the compounds in this herb remain largely unknown. In this study, an antiproliferative compound against human nasopharyngeal carcinoma (NPC cells from Rabdosia serra was purified and identified as lasiodin (a diterpenoid. The treatment with lasiodin inhibited cell viability and migration. Lasiodin also mediated the cell morphology change and induced apoptosis in NPC cells. The treatment with lasiodin induced the Apaf-1 expression, triggered the cytochrome-C release, and stimulated the PARP, caspase-3 and caspase-9 cleavages, thereby activating the apoptotic pathways. The treatment with lasiodin also significantly inhibited the phosphorylations of the AKT, ERK1/2, p38 and JNK proteins. The pretreatment with the AKT or MAPK-selective inhibitors considerably blocked the lasiodin-mediated inhibition of cell proliferation. Moreover, the treatment with lasiodin inhibited the COX-2 expression, abrogated NF-κB binding to the COX-2 promoter, and promoted the NF-κB translocation from cell nuclei to cytosol. The pretreatment with a COX-2-selective inhibitor abrogated the lasiodin-induced inhibition of cell proliferation. These results indicated that lasiodin simultaneously activated the Apaf-1/caspase-dependent apoptotic pathways and suppressed the AKT/MAPK and COX-2/NF-κB signaling pathways. This study also suggested that lasiodin could be a promising natural compound for the prevention and treatment of NPC.

  20. Nuclear factor κB (NFκB) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes

    International Nuclear Information System (INIS)

    Yeoh, Ann S.J.; Bowen, Joanne M.; Gibson, Rachel J.; Keefe, Dorothy M.K.

    2005-01-01

    Purpose: Recent studies have proposed that mucositis development is the same throughout the gastrointestinal tract (GIT), as it is formed from one structure embryologically. Radiation-induced oral mucositis studies have outlined the key involvement of nuclear factor κB (NFκB) and cyclooxygenase-2 (Cox-2) in its pathobiology. The purpose of this study was therefore to investigate the expression of NFκB and Cox-2 in the irradiated colorectum and to correlate these with the associated histopathologic changes. Methods and Materials: Colorectal tissues from 28 colorectal cancer patients treated with preoperative radiotherapy were analyzed for histopathologic changes using a variety of tissue staining methods. The expression of NFκB and Cox-2 in these tissues was investigated using immunohistochemistry. Changes in expression of these proteins were then correlated with the histopathologic changes. Results: Radiation therapy caused injury to the normal colorectal tissue surrounding tumor site, particularly around the blood vessels. These changes were reflected in changes in NFκB and Cox-2 expression. Conclusions: We conclude that different regions of the GIT, the colorectum, and oral cavity have similar underlying mechanisms of radiation-induced mucositis. Understanding these mechanisms will allow new approaches to be developed to specifically target steps in the evolution of alimentary mucositis

  1. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    International Nuclear Information System (INIS)

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung

    2012-01-01

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  2. A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting

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    Hanning Liu

    2017-01-01

    Full Text Available As a particular severe phenotype of coronary artery disease (CAD, left main coronary artery disease (LMCAD is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2, a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral coronary artery disease (MPCAD. In this study, we genotyped COX-2 rs5275, rs5277, and rs689466 of 1544 CAD patients undergoing coronary artery bypass grafting (CABG and found that rs5277 C allele carriage was associated with LMCAD (adjusted OR: 1.590; 95% CI: 1.103~2.291; p=0.013. Furtherly, long-term follow-up data suggested that rs5277 C allele carriage increased risk of major adverse cardiac and cerebrovascular events (MACCE in the whole cohort (adjusted HR: 1.561; 95% CI: 1.025~2.377; p=0.038 and LMCAD subgroup (adjusted HR: 2.014; 95% CI: 1.036~3.913; p=0.039 but not in MPCAD subgroup (adjusted HR: 1.375; 95% CI: 0.791~2.392; p=0.259. In conclusion, we demonstrate that COX-2 rs5277 C allele increases the risk of left main coronary artery lesion and is also correlated with poor prognosis of LMCAD patients with CABG therapy.

  3. Hormophysa triquerta polyphenol, an elixir that deters CXCR4- and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells.

    Science.gov (United States)

    Aravindan, Sheeja; Ramraj, Satishkumar; Kandasamy, Kathiresan; Thirugnanasambandan, Somasundaram S; Somasundaram, Dinesh Babu; Herman, Terence S; Aravindan, Natarajan

    2017-01-24

    Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro,and residual PC in vivo. Human PC cells exposed to ionizing radiation (IR), with/without HT-EA pre-treatment were examined for the alterations in the tumor invasion/metastasis (TIM) transcriptome (93 genes, QPCR-profiling). Utilizing a mouse model of residual PC, we investigated the benefit of HT-EA in the translation regulation of crucial TIM targets (TMA-IHC). Radiation activated 30, 50, 15, and 38 TIM molecules in surviving Panc-1, Panc-3.27, BxPC3, and MiaPaCa-2 cells. Of these, 15, 44, 12, and 26 molecules were suppressed with HT-EA pre-treatment. CXCR4 and COX2 exhibited cell-line-independent increases after IR, and was completely suppressed with HT-EA, across all PC cells. HT-EA treatment resulted in translational repression of IR-induced CXCR4, COX2, β-catenin, MMP9, Ki-67, BAPX, PhPT-1, MEGF10, and GRB10 in residual PC. Muting CXCR4 or COX2 regulated the migration/invasion potential of IR-surviving cells, while forced expression of CXCR4 or COX2 significantly increased migration/invasion capabilities of PC cells. Further, treatment with HT-EA significantly inhibited IR-induced and CXCR4/COX2 forced expression-induced PC cell migration/invasion. This study (i) documents the TIM blueprint in therapy-resistant PC cells, (ii) defines the role of CXCR4 and COX2 in induced metastatic potential, and (iii) recognizes the potential of HT-EA in deterring the CXCR4/COX2-dependent dissemination destiny of therapy-resistant residual PC cells.

  4. Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells

    International Nuclear Information System (INIS)

    Looby, Eileen; Abdel-Latif, Mohamed MM; Athié-Morales, Veronica; Duggan, Shane; Long, Aideen; Kelleher, Dermot

    2009-01-01

    The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate

  5. Canolol inhibits gastric tumors initiation and progression through COX-2/PGE2 pathway in K19-C2mE transgenic mice.

    Directory of Open Access Journals (Sweden)

    Donghui Cao

    Full Text Available 4-Vinyl-2, 6-dimethoxyphenol (canolol is an antioxidant phenolic compound extracted from crude canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-inflammation and anti-tumor effects of canolol. Tg mice receiving canolol diet had a reduced tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric tumor (P=0.002. Besides that, the mean tumor diameter was decreased from 6.5 mm to 4.5 mm (P<0.001 after canolol administration. COX-2/PGE2 pathway is known to play pivotal role in inflammation-induced gastric tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the mRNA levels of the proinflammatory cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-catenin, key factors involving in PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1% canolol (P<0.001. In addition, tumor-suppressor miR-7 was reactivated after canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the tumor progression. In conclusion, canolol could inhibit the gastritis-related tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/PGE2 signaling pathway and might be regulated by miR-7.

  6. Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells

    Directory of Open Access Journals (Sweden)

    Long Aideen

    2009-06-01

    Full Text Available Abstract Background The progression from Barrett's metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. Methods Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. Results DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1/2- and p38 MAPK while Erk1/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. Conclusion DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.

  7. Effect of a hormone-releasing intrauterine system (Mirena® on aromatase and Cox-2 expression in patients with adenomyosis submitted or not, to endometrial resection

    Directory of Open Access Journals (Sweden)

    Maia R

    2012-04-01

    Full Text Available Hugo Maia Jr1,2, Clarice Haddad1, Julio Casoy1, Rebeca Maia1, Nathanael Pinheiro3, Elsimar M Coutinho11Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH, 2Itaigara Memorial Day Hospital, 3IMAGEPAT, Salvador, Bahia, BrazilObjective: To investigate the effect of a levonorgestrel-releasing intrauterine system (Mirena® on aromatase and cyclooxygenase-2 (Cox-2 expression in the endometrium of patients with adenomyosis who were submitted to endometrial resection at the time of insertion, compared to a group not submitted to endometrial resection and a group of controls with adenomyosis not submitted to any previous hormonal treatment.Patients and methods: Patients with adenomyosis (n = 89 were included in this study. Twenty-two patients had been using Mirena® for 5 years but had not been submitted to endometrial resection prior to insertion of the device. Twenty-four patients were submitted to endometrial resection at the time of Mirena® insertion. The remaining 43 patients with adenomyosis had undergone no previous hormonal treatment and served as a control group. Cox-2 and aromatase expression were determined in the endometrium by immunohistochemistry.Results: Use of Mirena® for 5 years reduced aromatase expression in the endometrium; however, this reduction was significantly greater in the uteri previously submitted to endometrial resection. The reduction in Cox-2 expression was significant only in the uteri submitted to endometrial resection followed by the insertion of Mirena®.Conclusion: Endometrial resection followed by the insertion of Mirena® was associated with greater rates of amenorrhea in patients with adenomyosis, which in turn were associated with a more effective inhibition of aromatase and Cox-2 expression in the endometrium.Keywords: aromatase, Mirena®, adenomyosis, Cox-2, endometrium, levonorgestrel

  8. Deoxycholate induces COX-2 expression via Erk1/2-, p38-MAPK and AP-1-dependent mechanisms in esophageal cancer cells.

    LENUS (Irish Health Repository)

    Looby, Eileen

    2009-01-01

    BACKGROUND: The progression from Barrett\\'s metaplasia to adenocarcinoma is associated with the acquirement of an apoptosis-resistant phenotype. The bile acid deoxycholate (DCA) has been proposed to play an important role in the development of esophageal adenocarcinoma, but the precise molecular mechanisms remain undefined. The aim of this study was to investigate DCA-stimulated COX-2 signaling pathways and their possible contribution to deregulated cell survival and apoptosis in esophageal adenocarcinoma cells. METHODS: Following exposure of SKGT-4 cells to DCA, protein levels of COX-2, MAPK and PARP were examined by immunoblotting. AP-1 activity was assessed by mobility shift assay. DCA-induced toxicity was assessed by DNA fragmentation and MTT assay. RESULTS: DCA induced persistent activation of the AP-1 transcription factor with Fra-1 and JunB identified as the predominant components of the DCA-induced AP-1 complex. DCA activated Fra-1 via the Erk1\\/2- and p38 MAPK while Erk1\\/2 is upstream of JunB. Moreover, DCA stimulation mediated inhibition of proliferation with concomitant low levels of caspase-3-dependent PARP cleavage and DNA fragmentation. Induction of the anti-apoptotic protein COX-2 by DCA, via MAPK\\/AP-1 pathway appeared to balance the DCA mediated activation of pro-apoptotic markers such as PARP cleavage and DNA fragmentation. Both of these markers were increased upon COX-2 suppression by aspirin pretreatment prior to DCA exposure. CONCLUSION: DCA regulates both apoptosis and COX-2-regulated cell survival in esophageal cells suggesting that the balance between these two opposing signals may determine the transformation potential of DCA as a component of the refluxate.

  9. 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.

  10. Deletions in cox2 mRNA result in loss of splicing and RNA editing and gain of novel RNA editing sites.

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    Stefanie Grüttner

    Full Text Available As previously demonstrated, the maize cox2 RNA is fully edited in cauliflower mitochondria. Use of constructs with a deleted cox2 intron, however, led to a loss of RNA editing at almost all editing sites, with only a few sites still partially edited. Likewise, one deletion in exon 1 and three in exon 2 abolish RNA editing at all cox2 sites analyzed. Furthermore, intron splicing is abolished using these deletions. Mutation of a cytosine residue, which is normally edited and localized directly adjacent to the intron, to thymidine did not result in restoration of splicing, indicating that the loss of splicing was not due to loss of RNA editing. One deletion in exon 2 did not lead to loss of splicing. Instead, most editing sites were found to be edited, only three were not edited. Unexpectedly, we observed additional RNA editing events at new sites. Thus it appears that deletions in the cox2 RNA sequence can have a strong effect on RNA processing, leading to loss of splicing, loss of editing at all sites, or even to a gain of new editing sites. As these effects are not limited to the vicinity of the respective deletions, but appear to be widespread or even affect all editing sites, they may not be explained by the loss of PPR binding sites. Instead, it appears that several parts of the cox2 transcript are required for proper RNA processing. This indicates the roles of the RNA sequence and structural elements in the recognition of the editing sites.

  11. Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis

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    Dai P

    2018-02-01

    Full Text Available Ping Dai, Jing Li, Xiao-Ping Ma, Jian Huang, Juan-Juan Meng, Ping Gong Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China Background: The study of cyclooxygenase-2 (COX-2 inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.Results: Six eligible trials (1,794 patients were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48. Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib and treatment line (first or second chemotherapy. The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin, GP (double fluorine cytidine + cisplatin or carboplatin, or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin. The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25 and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50. However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1

  12. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

    Science.gov (United States)

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-06-15

    Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1

  13. Involvement of nitrergic system in anticonvulsant effect of zolpidem in lithium-pilocarpine induced status epilepticus: Evaluation of iNOS and COX-2 genes expression.

    Science.gov (United States)

    Eslami, Seyyed Majid; Ghasemi, Maryam; Bahremand, Taraneh; Momeny, Majid; Gholami, Mahdi; Sharifzadeh, Mohammad; Dehpour, Ahmad Reza

    2017-11-15

    This study aims to investigate the role of zolpidem in lithium-pilocarpine induced status epilepticus (SE) and probable mechanisms involved in seizure threshold alteration. In the present study, lithium chloride (127mg/kg) was administered 20h prior to pilocarpine (60mg/kg) to induce SE in adult male Wistar rats. Different doses of zolpidem (0.1, 1, 2, 5, 10mg/kg) were injected 30min before pilocarpine administration. Furthermore, to find out whether nitric oxide (NO) plays a role in the observed effect, L-arginine and L-NAME were injected 15min before zolpidem. Afterward, we identified the particular NO isoform mediating the effect of zolpidem by injecting aminoguanidine (AG) and 7-Nitroindazole (7-NI) 15min prior to zolpidem. Moreover, in both 6 and 24h after pilocarpine injection, experimental groups underwent hippocampectomy to evaluate cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes expression by quantitative reverse transcription-PCR (qRT-PCR). Pre-treatment with zolpidem significantly prevented the onset of SE in a dose-dependent manner. AG and L-NAME significantly potentiated the anticonvulsant effect of zolpidem while L-arginine inverted this effect. Our qRT-PCR exerted that there was a continuous elevation of iNOS and COX-2 genes expression over 6 and 24h after pilocarpine administration in SE and L-arginine+Zolpidem groups while in AG/L-NAME+Zolpidem and zolpidem groups this upregulation was prevented. Our study indicates that zolpidem prevents the onset of SE through inhibition of iNOS/COX-2 genes upregulation following lithium-pilocarpine administration. Consistent with our results, we suggest that iNOS activation could be probably upstream of COX-2 gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. COX-2 and Prostaglandin EP3/EP4 Signaling Regulate the Tumor Stromal Proangiogenic Microenvironment via CXCL12-CXCR4 Chemokine Systems

    Science.gov (United States)

    Katoh, Hiroshi; Hosono, Kanako; Ito, Yoshiya; Suzuki, Tatsunori; Ogawa, Yasufumi; Kubo, Hidefumi; Kamata, Hiroki; Mishima, Toshiaki; Tamaki, Hideaki; Sakagami, Hiroyuki; Sugimoto, Yukihiko; Narumiya, Shuh; Watanabe, Masahiko; Majima, Masataka

    2010-01-01

    Bone marrow (BM)–derived hematopoietic cells, which are major components of tumor stroma, determine the tumor microenvironment and regulate tumor phenotypes. Cyclooxygenase (COX)−2 and endogenous prostaglandins are important determinants for tumor growth and tumor-associated angiogenesis; however, their contributions to stromal formation and angiogenesis remain unclear. In this study, we observed that Lewis lung carcinoma cells implanted in wild-type mice formed a tumor mass with extensive stromal formation that was markedly suppressed by COX-2 inhibition, which reduced the recruitment of BM cells. Notably, COX-2 inhibition attenuated CXCL12/CXCR4 expression as well as expression of several other chemokines. Indeed, in a Matrigel model, prostaglandin (PG) E2 enhanced stromal formation and CXCL12/CXCR4 expression. In addition, a COX-2 inhibitor suppressed stromal formation and reduced expression of CXCL12/CXCR4 and a fibroblast marker (S100A4) in a micropore chamber model. Moreover, stromal formation after tumor implantation was suppressed in EP3−/− mice and EP4−/− mice, in which stromal expression of CXCL12/CXCR4 and S100A4 was reduced. The EP3 or EP4 knockout suppressed S100A4+ fibroblasts, CXCL12+, and/or CXCR4+ stromal cells as well. Immunofluorescent analyses revealed that CXCL12+CXCR4+S100A4+ fibroblasts mainly comprised stromal cells and most of these were recruited from the BM. Additionally, either EP3- or EP4-specific agonists stimulated CXCL12 expression by fibroblasts in vitro. The present results address the novel activities of COX-2/PGE2-EP3/EP4 signaling that modulate tumor biology and show that CXCL12/CXCR4 axis may play a crucial role in tumor stromal formation and angiogenesis under the control of prostaglandins. PMID:20110411

  15. Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

    Science.gov (United States)

    Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

    2018-03-01

    Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

  16. Inhibition of COX-2 does not affect therapeutical result of photodynamic therapy with hypericin despite of its increased activity and expression

    International Nuclear Information System (INIS)

    Mikes, J.; Kleban, J.; Kulikova, L.; Sackova, V.; Fedorocko, P.

    2006-01-01

    A photodynamic therapy (PDT) is a very promising, flexible and multifarious therapeutical approach for the treatment of malignant as well as non-malignant disorders. It is beholden on a nature of a photosensitive compound, its concentration and an incubation time, on a wavelength of light radiation, a fluence rate and a light dose as well as on a histological origin of the tissue and an oxygen pressure in it. Although PDT is of use in clinical practice, new promising photosensitive compounds with advantageous attributes are discovered continuously. PDT with hypericin, one of promising photosensitizers, activates p38 MAPK signalling pathway which induces expression of COX-2 and thereby increases concentration of its main product PGE2. Elevated activity of COX-2 as such is considered as contradictory to photo-cytotoxic effect of PDT with hypericin which should negatively influence an efficacy of PDT. In our experiment, effect of rofecoxib, a specific COX-2 inhibitor, as a post-treatment after PDT with hypericin in HeLa and HT29 cells have been evaluated. 24 as well as 48 hour treatment with 1 μM rofecoxib applied immediately after PDT did not induce significant decrease in cell proliferation, surprisingly. Purpose of failure to increase efficacy of PDT might be an activation of anti-apoptotic signalling pathways. Levels of Bcl-2 family proteins, especially Mcl-1 (HT29 and HeLa) and Bcl-2 (not expressed in HT29) have been evaluated. Considering our results, we can predict, that activity of COX-2 and its inhibition does not play crucial task in PDT experiments in vitro however its importance manifests in vivo as it affects angiogenesis of tumor. (authors)

  17. Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX-2 expression in patients with chronic gastritis and gastric cancer.

    Science.gov (United States)

    Bartchewsky, Waldemar; Martini, Mariana Rocha; Masiero, Mariana; Squassoni, Aline Candido; Alvarez, Marisa Claudia; Ladeira, Marcelo Sady; Salvatore, Daisy; Trevisan, Miriam; Pedrazzoli, José; Ribeiro, Marcelo Lima

    2009-01-01

    Helicobacter pylori infection is related to gastric cancer development, and chronic inflammation is presumed to be the main cause. The aim of the present study was to evaluate the influence of H. pylori cagA, vacA, iceA, and babA genotypes on COX-2, IL-1beta, and IL-8 expression. Of the 217 patients included in the study, 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression values were determined by quantitative real-time PCR and immunohistochemistry. An association was found between the infection with cagA, vacA s1m1 strains and gastric cancer development. Regarding the 3' region of the cagA gene, we also found an association between the infection with cagA EPIYA-ABCCC strains and clinical outcome. Higher levels of IL-8, IL-1beta, and COX-2 were detected in gastric mucosa from infected patients with chronic gastritis, and they were also associated with the infection by cagA, vacA s1m1 strains. The IL-8 and IL-1beta levels decrease significantly from chronic gastritis to gastric cancer, while the relative expression remained unaltered when COX-2 expression was analyzed among patients with gastritis and cancer. Since inflammatory response to H. pylori infection plays an important role in cellular proliferation and gastric mucosal damage, the up-regulation of IL-1beta, IL-8, and COX-2 in patients with chronic gastritis has an important clinical implication in gastric carcinogenesis.

  18. Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET(B) receptor cascade.

    Science.gov (United States)

    El-Gowelli, Hanan M; Helmy, Maged W; Ali, Rabab M; El-Mas, Mahmoud M

    2014-03-01

    Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β₁, TGF-β₁). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET(B) receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth

    International Nuclear Information System (INIS)

    Tsai, C.-S.; Chen, F.-H.; Wang, C.-C.; Huang, H.-L.; Jung, Shih-Ming; Wu, C.-J.; Lee, C.-C.; McBride, William H.; Chiang, C.-S.; Hong, J.-H.

    2007-01-01

    Purpose: To investigate the effects of single and fractionated doses of radiation on tumors and tumor-associated macrophages (TAMs), and to elucidate the potential of TAMs to influence tumor growth. Methods and Materials: A murine prostate cell line, TRAMP-C1, was grown in C57Bl/6J mice to 4-mm tumor diameter and irradiated with either 25 Gy in a single dose, or 60 Gy in 15 fractions. The tumors were removed at the indicated times and assessed for a variety of markers related to TAM content, activation status, and function. Results: In tumors receiving a single radiation dose, arginase (Arg-I), and cycloxygenase-2 (COX-2) mRNA expression increased as a small transient wave within 24 h and a larger persistent wave starting after 3 days. Inducible nitric oxide synthase (iNOS) mRNA was elevated only after 3 days and continued to increase up to 3 weeks. After fractionated irradiation, Arg-1 and COX-2 mRNA levels increased within 5 days, whereas iNOS was increased only after 10 fractions of irradiation had been given. Increased levels of Arg-I, COX-2, and, to a lesser extent, iNOS protein were found to associate with TAMs 1-2 weeks after tumor irradiation. Function of TAMs were compared by mixing them with TRAMP-C1 cells and injecting them into mice; TRAMP-C1 cells mixed with TAMs from irradiated tumors appeared earlier and grew significantly faster than those mixed with TAMs from unirradiated tumors or TRAMP-C1 alone. Conclusions: Tumor-associated macrophages in the postirradiated tumor microenvironment express higher levels of Arg-1, COX-2, and iNOS, and promote early tumor growth in vivo

  20. Effects of hypo- and hyperthyroidism on proliferation, angiogenesis, apoptosis and expression of COX-2 in the corpus luteum of female rats.

    Science.gov (United States)

    Silva, J F; Ocarino, N M; Vieira, A L S; Nascimento, E F; Serakides, R

    2013-08-01

    Although thyroid dysfunction occurs frequently in humans and some animal species, the mechanisms by which hypo- and hyperthyroidism affect the corpus luteum have not been thoroughly elucidated. This study evaluated the levels of proliferative activity, angiogenesis, apoptosis and expression of cyclooxygenase-2 in the corpus luteum of female rats with thyroid dysfunction. These processes may be important in understanding the reproductive changes caused by thyroid dysfunction. A total of 18 adult female rats were divided into three groups (control, hypothyroid and hyperthyroid) with six animals per group. Three months after treatment to induce thyroid dysfunction, the rats were euthanized in the dioestrus phase. The ovaries were collected and immunohistochemically analysed for expression of the cell proliferation marker CDC-47, vascular endothelial growth factor (VEGF), VEGF receptor Flk-1 and cyclooxygenase-2 (COX-2). Apoptosis was evaluated using the TUNEL assay. Hypothyroidism reduced the intensity and area of COX-2 expression in the corpus luteum (p hyperthyroidism did not alter COX-2 expression in the dioestrus phase. Hypothyroidism significantly reduced the expression of CDC-47 in endothelial cells and pericytes in the corpus luteum, whereas hyperthyroidism did not induce a detectable change in CDC-47 expression (p > 0.05). Hypothyroidism reduced the level of apoptosis in luteal cells (p hyperthyroidism increased the level of apoptosis in the corpus luteum (p < 0.05). In conclusion, thyroid dysfunction differentially affects the levels of proliferative activity, angiogenesis and apoptosis and COX-2 expression in the corpus luteum of female rats. © 2013 Blackwell Verlag GmbH.

  1. Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE2 pathways in human M4Beu melanoma cancer cells

    International Nuclear Information System (INIS)

    Hassan, Lama; Pinon, Aline; Limami, Youness; Seeman, Josiane; Fidanzi-Dugas, Chloe; Martin, Frederique; Badran, Bassam; Simon, Alain; Liagre, Bertrand

    2016-01-01

    Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-κB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE 2 pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Our study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention.

  2. Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

    Directory of Open Access Journals (Sweden)

    Marcella Goetz MORO

    Full Text Available Abstract The consumption of low-dose aspirin (LDA to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib and a non-selective COX-2 inhibitor (ibuprofen nonsteroidal anti-inflammatory drug (NSAID in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p 0.05. These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

  3. Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE{sub 2} pathways in human M4Beu melanoma cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, Lama; Pinon, Aline [Laboratory of Chemistry of Natural Substances, Faculty of Pharmacy, University of Limoges, FR 3503 GEIST, EA1069, Limoges (France); Limami, Youness [Laboratoire National de Référence (LNR), Université Mohammed VI des Sciences de la Santé, Casablanca (Morocco); Seeman, Josiane; Fidanzi-Dugas, Chloe; Martin, Frederique [Laboratory of Chemistry of Natural Substances, Faculty of Pharmacy, University of Limoges, FR 3503 GEIST, EA1069, Limoges (France); Badran, Bassam [Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences, Lebanese University, Beirut (Lebanon); Simon, Alain [Laboratory of Chemistry of Natural Substances, Faculty of Pharmacy, University of Limoges, FR 3503 GEIST, EA1069, Limoges (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Laboratory of Chemistry of Natural Substances, Faculty of Pharmacy, University of Limoges, FR 3503 GEIST, EA1069, Limoges (France)

    2016-07-01

    Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-κB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE{sub 2} pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Our study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention.

  4. GluN2B/CaMKII mediates CFA-induced hyperalgesia via HDAC4-modified spinal COX2 transcription.

    Science.gov (United States)

    Lai, Cheng-Yuan; Hsieh, Ming-Chun; Ho, Yu-Cheng; Chen, Gin-Den; Chou, Dylan; Ruan, Ting; Lee, An-Sheng; Wang, Hsueh-Hsiao; Chau, Yat-Pang; Peng, Hsien-Yu; Lai, Cheng-Hung

    2018-06-01

    Histone deacetylase 4 (HDAC4), which actively shuttles between the nucleus and cytoplasm, is an attractive candidate for a repressor mechanism in epigenetic modification. However, the potential role of HDAC4-dependent epigenetics in the neural plasticity underlying the development of inflammatory pain has not been well established. By injecting complete Freund's adjuvant (CFA) into the hind-paw of Sprague-Dawley rats (200-250 g), we found animals displayed behavioral hyperalgesia was accompanied with HDAC4 phosphorylation and cytoplasmic redistribution in the dorsal horn neurons. Cytoplasmic HDAC4 retention led to its uncoupling with the COX2 promoter, hence prompting spinal COX2 transcription and expression in the dorsal horn. Moreover, the GluN2B-bearing N-methyl-d-aspartate receptor (GluN2B-NMDAR)/calmodulin-dependent protein kinase II (CaMKII) acted as an upstream cascade to facilitate HDAC4 phosphorylation/redistribution-associated spinal COX2 expression after inflammatory insults. The results of this pilot study demonstrated that the development and/or maintenance of inflammatory pain involved the spinal HDAC4-dependent epigenetic mechanisms. Our findings open up a new avenue for the development of a novel medical strategy for the relief of inflammatory pain. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2.

    Science.gov (United States)

    Li, Xiao-Jun; Yang, Yan-Jing; Li, Yu-Sang; Zhang, Wei Kevin; Tang, He-Bin

    2016-02-17

    Frankincense oil and water extracts (FOE, FWE) have long been used for external treatment of inflammation and pain. The present study was conducted to identify the active ingredients responsible for the anti-inflammatory and analgesic effects and to determine the underlying mechanisms. The compositions of FOE and FWE were identified and compared by GC-MS. The anti-inflammatory and analgesic activities of the two extracts and their possible active ingredients (α-pinene, linalool, and 1-octanol) were evaluated and compared in a xylene-induced ear edema model and a formalin-inflamed hind paw model. Inflammatory infiltrates and cyclooxygenase-2 (COX-2) expression in hind paw skin were investigated by histological staining. The contents of α-pinene, linalool, and 1-octanol in FOE were much higher than those in FWE. Mice treated with FOE exhibited greater and faster lessening of swelling and pain than mice treated with FWE. The combination of the three components had more potent pharmacological effects on hind paw inflammation and COX-2 overexpression than the three components used alone. These findings suggest that topical application of FOE or its active ingredients (including α-pinene, linalool, and 1-octanol) exhibit significantly anti-inflammatory and analgesic effects through inhibiting nociceptive stimulus-induced inflammatory infiltrates and COX-2 overexpression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Vitual screening and binding mode elucidation of curcumin analogues on Cyclooxygenase-2 using AYO_COX2_V1.1 protocol

    Science.gov (United States)

    Mulatsari, E.; Mumpuni, E.; Herfian, A.

    2017-05-01

    Curcumin is yellow colored phenolic compounds contained in Curcuma longa. Curcumin is known to have biological activities as anti-inflammatory, antiviral, antioxidant, and anti-infective agent [1]. Synthesis of curcumin analogue compounds has been done and some of them had biological activity like curcumin. In this research, the virtual screening of curcumin analogue compounds has been conducted. The purpose of this research was to determine the activity of these compounds as selective Cyclooxygenase-2inhibitors in in-silico. Binding mode elucidation was made by active and inactive representative compounds to see the interaction of the amino acids in the binding site of the compounds. This research used AYO_COX2_V.1.1, a structure-based virtual screening protocol (SBVS) that has been validated by Mumpuni E et al, 2014 [2]. AYO_COX2_V.1.1 protocol using a variety of integrated applications such as SPORES, PLANTS, BKchem, OpenBabel and PyMOL. The results of virtual screening conducted on 49 curcumin analogue compounds obtained 8 compounds with 4 active amino acid residues (GLY340, ILE503, PHE343, and PHE367) that were considered active as COX-2 inhibitor.

  7. Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors

    Science.gov (United States)

    Yatam, Satayanarayana; Gundla, Rambabu; Jadav, Surender Singh; Pedavenkatagari, Narayana reddy; Chimakurthy, Jithendra; Rani B, Namratha; Kedam, Thyagaraju

    2018-05-01

    Mercapto benzothiazole linked 1,2,4-oxadiazole derivatives were designed (4a-u) as new anti-inflammatory agents using bioisosteric approach and docking studies. The docking results clearly indicated that the compounds 4a-u shown good docking interaction towards COX-2 enzyme. In silico drug-like properties were also calculated for compounds (4a-u) and exhibited significant H-bond acceptor ratio. All compounds were synthesized and biologically evaluated using in vitro COX-1, COX-2 and 5-LOX assays. Compound 4k and 4q (IC50 = 6.8 μM and IC50 = 5.0 μM) found to be potent, selective COX-2 inhibitors and display better anti-inflammatory activity than standard Ibuprofen. Compound 4l and 4e found to be potent inhibitors against 5-LOX (IC50 = 5.1 μM and IC50 = 5.5 μM). The in vivo anti-inflammatory activity studies shown that the compounds 4q and 4k effectively reducing the paw edema volume at 3h and 5h than standard drug Ibuprofen. The DPPH radical scavenging activity provided anti-oxidant activity of compound 4e (IC50 = 25.6 μM) than reference standard Ascorbic acid.

  8. Exploring selectivity requirements for COX-2 versus COX-1 binding of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines using topological and physico-chemical parameters.

    Science.gov (United States)

    Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

    2005-04-01

    Considering the current need for development of selective cyclooxygenase-2 (COX-2) inhibitors, an attempt has been made to explore physico-chemical requirements of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines for binding with COX-1 and COX-2 enzyme subtypes and also to explore the selectivity requirements. In this study, E-states of different common atoms of the molecules (calculated according to Kier & Hall), first order valence connectivity and physicochemical parameters (hydrophobicity pi, Hammett sigma and molar refractivity MR of different ring substituents) were used as independent variables along with suitable dummy parameters in the stepwise regression method. The best equation describing COX-1 binding affinity [n = 25, Q2 = 0.606, R(a)2 = 0.702, R2 = 0.752, R = 0.867, s = 0.447, F = 15.2 (df 4, 20)] suggests that the COX-1 binding affinity increases in the presence of a halogen substituent at R1 position and a p-alkoxy or p-methylthio substituent at R2 position. Furthermore, a difluoromethyl group is preferred over a trifluoromethyl group at R position for the COX-1 binding. The best equation describing COX-2 binding affinity [n = 32, Q2 = 0.622, R(a)2= 0.692, R2 = 0.732, R = 0.856, s = 0.265, F = 18.4 (df 4, 27)] shows that the COX-2 binding affinity increases with the presence of a halogen substituent at R1 position and increase of size of R2 substituents. However, it decreases in case of simultaneous presence of 3-chloro and 4-methoxy groups on the phenyl nucleus and in the presence of highly lipophilic R2 substituents. The best selectivity relation [n = 25, Q2 = 0.455, R(a)2 = 0.605, R2 = 0.670, R = 0.819, s = 0.423, F = 10.2 (df 4, 20)] suggests that the COX-2 selectivity decreases in the presence of p-alkoxy group and electron-withdrawing para substituents at R2 position. Again, a trifluoro group is conductive for the selectivity instead of a difluoromethyl group at R position. Furthermore, branching may also play significant role in

  9. Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

    Energy Technology Data Exchange (ETDEWEB)

    Phookphan, Preeyaphan; Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Post-graduate Program in Environmental Toxicology, Chulabhorn Graduate Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health, Toxicology (EHT), Office of the Higher Education Commission, Ministry of Education (Thailand); Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Ruchirawat, Mathuros, E-mail: mathuros@cri.or.th [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health, Toxicology (EHT), Office of the Higher Education Commission, Ministry of Education (Thailand)

    2017-02-01

    Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is

  10. Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

    International Nuclear Information System (INIS)

    Phookphan, Preeyaphan; Navasumrit, Panida; Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat; Ruchirawat, Mathuros

    2017-01-01

    Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is

  11. Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

    Directory of Open Access Journals (Sweden)

    Qiliu Peng

    Full Text Available OBJECTIVE: Cyclooxygenase-2 (COX-2 is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs. RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004 and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004. In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for

  12. The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Fei Zhou

    Full Text Available BACKGROUND AND OBJECTIVE: Overexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Two hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP methods. RESULTS: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (-1195G/A polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26-4.84 and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28-6.20. No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39-0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39-0.94, respectively while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14-2.56 and P value = 0.025; OR = 1.65; 95%CI  = 1.06-2.57, respectively. CONCLUSION: This investigation for the first time

  13. The NF-κB family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 protein expression in lung fibroblasts.

    Science.gov (United States)

    Zago, Michela; Rico de Souza, Angela; Hecht, Emelia; Rousseau, Simon; Hamid, Qutayba; Eidelman, David H; Baglole, Carolyn J

    2014-04-21

    Diseases due to cigarette smoke exposure, including chronic obstructive pulmonary disease (COPD) and lung cancer, are associated with chronic inflammation typified by the increased expression of cyclooxygenase-2 (COX-2) protein. RelB is an NF-κB family member that suppresses cigarette smoke induction of COX-2 through an unknown mechanism. The ability of RelB to regulate COX-2 expression may be via miR-146a, a miRNA that attenuates COX-2 in lung fibroblasts. In this study we tested whether RelB attenuation of cigarette smoke-induced COX-2 protein is due to miR-146a. Utilizing pulmonary fibroblasts deficient in RelB expression, together with siRNA knock-down of RelB, we show the essential role of RelB in diminishing smoke-induced COX-2 protein expression despite robust activation of the canonical NF-κB pathway and subsequent induction of Cox-2 mRNA. RelB did not regulate COX-2 protein expression at the level of mRNA stability. Basal levels of miR-146a were significantly lower in Relb-deficient cells and cigarette smoke increased miR-146a expression only in Relb-expressing cells. Inhibition of miR-146a had no effects on Relb expression or induction of Cox-2 mRNA by cigarette smoke but significantly increased COX-2 protein. These data highlight the potential of a RelB-miR-146a axis as a novel regulatory pathway that attenuates inflammation in response to respiratory toxicants. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Doping evolution of spin fluctuations and their peculiar suppression at low temperatures in Ca(Fe 1 -xCox)2As2

    Science.gov (United States)

    Sapkota, A.; Das, P.; Böhmer, A. E.; Ueland, B. G.; Abernathy, D. L.; Bud'ko, S. L.; Canfield, P. C.; Kreyssig, A.; Goldman, A. I.; McQueeney, R. J.

    2018-05-01

    Results of inelastic neutron scattering measurements are reported for two annealed compositions of Ca(Fe 1 -xCox)2As2,x =0.026 and 0.030, which possess stripe-type antiferromagnetically ordered and superconducting ground states, respectively. In the AFM ground state, well-defined and gapped spin waves are observed for x =0.026 , similar to the parent CaFe2As2 compound. We conclude that the well-defined spin waves are likely to be present for all x corresponding to the AFM state. This behavior is in contrast to the smooth evolution to overdamped spin dynamics observed in Ba(Fe 1 -xCox)2As2 , wherein the crossover corresponds to microscopically coexisting AFM order and SC at low temperature. The smooth evolution is likely absent in Ca(Fe 1 -xCox)2As2 due to the mutual exclusion of AFM ordered and SC states. Overdamped spin dynamics characterize paramagnetism of the x =0.030 sample and high-temperature x =0.026 sample. A sizable loss of magnetic intensity is observed over a wide energy range upon cooling the x =0.030 sample, at temperatures just above and within the superconducting phase. This phenomenon is unique amongst the iron-based superconductors and is consistent with a temperature-dependent reduction in the fluctuating moment. One possible scenario ascribes this loss of moment to a sensitivity to the c -axis lattice parameter in proximity to the nonmagnetic collapsed tetragonal phase and another scenario ascribes the loss to a formation of a pseudogap.

  15. ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

    Science.gov (United States)

    Wu, Bin; Chen, Xihua; He, Bin; Liu, Shuyan; Li, Yunfeng; Wang, Qianxing; Gao, Haijun; Wang, Shufang; Liu, Jianbing; Zhang, Shucheng; Xu, Xiangbo; Wang, Jiedong

    2014-09-01

    Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.

  16. Prostaglandin E2-Induced COX-2 Expressions via EP2 and EP4 Signaling Pathways in Human LoVo Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hsi-Hsien Hsu

    2017-05-01

    Full Text Available Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC. The expression of matrix metalloproteinases (MMPs has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 μM promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane. The Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K/Akt cell survival pathway was upregulated by EP2 and EP4 activation. Following the activation of the PI3K/Akt pathway, β-catenin translocated into the nucleus and triggered COX2 transcription via LEF-1 and TCF-4 and its subsequent translation. COX2 expression correlated with the elevation in the migration ability of LoVo cells. The experimental evidence shows a possible mechanism by which PGE2 induces cancer cell migration and further suggests PGE2 to be a potential therapeutic target in colon cancer metastasis. On inhibition of PGE2, in order to determine the downstream pathway, the levels of PI3K/Akt pathway were suppressed and the β-catenin expression was also modulated. Inhibition of EP2 and EP4 shows that PGE2 induces protein expression of COX-2 through EP2 and EP4 receptors in LoVo colon cancer cells.

  17. Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2 inhibitor, in the management of pain and osteoarthritis

    Directory of Open Access Journals (Sweden)

    Piet Geusens

    2008-04-01

    Full Text Available Piet Geusens1, Willem Lems21Department of Internal Medicine, Subdivision of Rheumatology, University Hospital, Maastricht, The Netherlands and Biomedical Research Institute, University Hasselt, Belgium; 2Vrije Universiteit Medical Centre, Department of Rheumatology, Amsterdam, the NetherlandsAbstract: Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA, with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver.Keywords: lumiracoxib, NSAIDs, COX2 inhibitors, gastro-intestinal and cardiovascular safety

  18. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function

    International Nuclear Information System (INIS)

    Veltman, Joris D; Lambers, Margaretha EH; Nimwegen, Menno van; Hendriks, Rudi W; Hoogsteden, Henk C; Aerts, Joachim GJV; Hegmans, Joost PJJ

    2010-01-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumour-derived factors (e.g. prostaglandins) and have a critical role in immune suppression. MDSC suppress T and NK cell function via increased expression of arginase I and production of reactive oxygen species (ROS) and nitric oxide (NO). Immune suppression by MDSC was found to be one of the main factors for immunotherapy insufficiency. Here we investigate if the in vivo immunoregulatory function of MDSC can be reversed by inhibiting prostaglandin synthesis by specific COX-2 inhibition focussing on ROS production by MDSC subtypes. In addition, we determined if dietary celecoxib treatment leads to refinement of immunotherapeutic strategies. MDSC numbers and function were analysed during tumour progression in a murine model for mesothelioma. Mice were inoculated with mesothelioma tumour cells and treated with cyclooxygenase-2 (COX-2) inhibitor celecoxib, either as single agent or in combination with dendritic cell-based immunotherapy. We found that large numbers of infiltrating MDSC co-localise with COX-2 expression in those areas where tumour growth takes place. Celecoxib reduced prostaglandin E2 levels in vitro and in vivo. Treatment of tumour-bearing mice with dietary celecoxib prevented the local and systemic expansion of all MDSC subtypes. The function of MDSC was impaired as was noticed by reduced levels of ROS and NO and reversal of T cell tolerance; resulting in refinement of immunotherapy. We conclude that celecoxib is a powerful tool to improve dendritic cell-based immunotherapy and is associated with a reduction in the numbers and suppressive function of MDSC. These data suggest that immunotherapy approaches benefit from simultaneously blocking cyclooxygenase-2 activity

  19. Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use.

    Science.gov (United States)

    Taurisano, Paolo; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Romano, Raffaella; Porcelli, Annamaria; Masellis, Rita; Colizzi, Marco; Quarto, Tiziana; Torretta, Silvia; Di Giorgio, Annabella; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

    2016-08-01

    The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. In-plane anisotropy of the electric field gradient in Ba(Fe 1 -xCox)2As2 observed by 75As NMR

    Science.gov (United States)

    Toyoda, Masayuki; Ichikawa, Akihiro; Kobayashi, Yoshiaki; Sato, Masatoshi; Itoh, Masayuki

    2018-05-01

    We have performed 75As NMR measurements on single crystals to investigate the nematic behavior via the in-plane anisotropy of the electronic state at the As site far from Co impurities in the representative iron arsenides Ba (Fe1-xCox) 2As2 . From the analysis of the angular dependence of the NMR satellites in the c plane using the binominal distribution, we find that there is the in-plane fourfold symmetry breaking, namely, the orthorhombic-type anisotropy in the electric field gradient (EFG) at the As site with no Co atom at the nearest neighboring Fe sites even in the tetragonal phase of both BaFe2As2 and Ba (Fe1-xCox) 2As2(x ≠0 ) . The NMR spectrum in the antiferromagnetically ordered state of BaFe2As2 is shown not to support a nanotwin model on the basis of the nematic order proposed from the pair-distribution analysis of neutron scattering data. Based on results of the x and temperature T dependences of the in-plane anisotropy in the wide x and T ranges, the symmetry breaking is concluded to come from the local orthorhombic domains induced by disorder such as Co impurities or lattice imperfections. Furthermore, we find that the asymmetry parameter of EFG η obeys the Curie-Weiss law which may be governed by nematic susceptibility, and the Weiss temperature becomes zero at xc˜0.05 in Ba (Fe1-xCox) 2As2 .

  1. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

    International Nuclear Information System (INIS)

    Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon

    2013-01-01

    Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin

  2. Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways.

    Directory of Open Access Journals (Sweden)

    Canhui Yi

    Full Text Available Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy.

  3. Flavonoids targeting of IκB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Tahanian E

    2011-05-01

    Full Text Available Elizabeth Tahanian¹, Luis Arguello Sanchez¹, Tze Chieh Shiao², René Roy², Borhane Annabi¹¹Centre de Recherche BioMED, ²Centre de Recherche PharmaQAM, Département de chimie, Université du Québec à Montréal, QC, CanadaAbstract: Brain endothelial cells play an essential role as structural and functional components of the blood–brain barrier (BBB. Increased BBB breakdown and brain injury are associated with neuroinflammation and are thought to trigger mechanisms involving matrix metalloproteinase upregulation. Emerging evidence also indicates that cyclooxygenase (COX inhibition limits BBB disruption, but the mechanisms linking metalloproteinase to COX remain unknown. In this study, we sought to investigate the nuclear factor-kappa B (NF-κB signaling pathway, a common pathway in both the regulation of matrix metalloproteinase-9 (MMP-9 and COX-2 expression, and the inhibitory properties of several chemopreventive flavonoids. Human brain microvascular endothelial cells were treated with a combination of phorbol 12-myristate 13-acetate (PMA, a carcinogen documented to increase MMP-9 and COX-2 through NF-κB, and several naturally occurring flavonoids. Among the molecules tested, we found that fisetin, apigenin, and luteolin specifically and dose-dependently antagonized PMA-induced COX-2 and MMP-9 gene and protein expressions as assessed by qRT-PCR, immunoblotting, and zymography respectively. We further demonstrate that flavonoids impact on IκK-mediated phosphorylation activity as demonstrated by the inhibition of PMA-induced IκB phosphorylation levels. Our results suggest that BBB disruption during neuroinflammation could be pharmacologically reduced by a specific class of flavonoids acting as NF-κB signal transduction inhibitors.Keywords: blood–brain barrier, flavonoids, neuroinflammation, NF-κB signal transduction inhibitors

  4. Melatonin Enhances the Anti-Tumor Effect of Fisetin by Inhibiting COX-2/iNOS and NF-κB/p300 Signaling Pathways

    Science.gov (United States)

    Yu, Zhenlong; Xiao, Yao; Wang, Jingshu; Qiu, Huijuan; Yu, Wendan; Tang, Ranran; Yuan, Yuhui; Guo, Wei; Deng, Wuguo

    2014-01-01

    Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy. PMID:25000190

  5. Celecoxib Alleviates Memory Deficits by Downregulation of COX-2 Expression and Upregulation of the BDNF-TrkB Signaling Pathway in a Diabetic Rat Model.

    Science.gov (United States)

    Yang, Ying; Gao, Ling

    2017-06-01

    Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed. Western blotting and immunohistochemical staining were performed to determine cyclooxygenase 2 (COX-2) expression in hippocampus. The results showed that a rat model of STZ-induced diabetes was successfully established and that celecoxib treatment significantly improved the associated nephropathy and inflammation. Moreover, spatial memory and hippocampal long-term potentiation (LTP) were impaired in diabetic model (P memory deficit and hippocampal LTP in the diabetic rats. To understand the underlying mechanisms, the expression of some important pathways involved in memory impairment was determined. We found that brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase (p-TrkB) were decreased in diabetic rats but were effectively reversed by celecoxib treatment. As evidenced by western blotting and immunohistochemical staining, the expression of COX-2 in hippocampus was significantly upregulated in diabetic rat (P memory deficits via probable downregulation of hippocampal COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a

  6. D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS, and NFκB in kidneys of Wistar rats.

    Science.gov (United States)

    Rehman, Muneeb U; Tahir, Mir; Khan, Abdul Quaiyoom; Khan, Rehan; Oday-O-Hamiza; Lateef, Abdul; Hassan, Syed Kazim; Rashid, Sumaya; Ali, Nemat; Zeeshan, Mirza; Sultana, Sarwat

    2014-04-01

    D-limonene is a naturally occurring monoterpene and has been found to posses numerous therapeutic properties. In this study, we used D-limonene as a protective agent against the nephrotoxic effects of anticancer drug doxorubicin (Dox). Rats were given D-limonene at doses of 5% and 10% mixed with diet for 20 consecutive days. Dox was give at the dose of 20 mg/kg body weight intraperitoneally. The protective effects of D-limonene on Dox-induced oxidative stress and inflammation were investigated by assaying oxidative stress biomarkers, lipid peroxidation, serum toxicity markers, proinflammatory cytokines, and expression of nuclear factor kappa B (NFκB), cyclo-oxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and Nitrite levels. Administration of Dox (20 mg/kg body weight) in rats enhanced renal lipid peroxidation; depleted glutathione content and anti-oxidant enzymes; elevated levels of kidney toxicity markers viz. kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine; enhanced expression of NFκB, COX-2, and iNOS and nitric oxide. Treatment with D-limonene prevented oxidative stress by restoring the levels of antioxidant enzymes, further both doses of 5% and 10% showed significant decrease in inflammatory response. Both the doses of D-limonene significantly decreased the levels of kidney toxicity markers KIM-1, BUN, and creatinine. D-limonene also effectively decreased the Dox induced overexpression of NF-κB, COX-2, and iNOS and nitric oxide. Data from the present study indicate the protective role of D-limonene against Dox-induced renal damage.

  7. Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.

    Science.gov (United States)

    Lu, Chieh-Hua; Chung, Chi-Hsiang; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Hung, Yi-Jen; Lin, Fu-Huang; Tsao, Chang-Huei; Hsieh, Po-Shiuan; Chien, Wu-Chien

    2018-01-01

    Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601-0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination

  8. Association of folate intake, dietary habits, smoking and COX-2 promotor-765G > C polymorphism with K-ras mutation in patients with colorectal cancer

    International Nuclear Information System (INIS)

    Kamal, M.M.; Youssef, O.Z.; Lotfy, A.N.; Elsaed, E.T.; Fawzy, M.M.T.

    2012-01-01

    Background: Understanding the role of environmental and molecular influences on the nature and rate of K-ras mutations in colorectal neoplasms is crucial. COX-2 polymorphisms -765G > C may play a role in carcinogenic processes in combination with specific life-style conditions or dependent on the racial composition of a particular population. If mutational events play an important role in colorectal carcinogenesis sequence, one can hypothesize that modification of these events by life-style or other factors would be a useful prevention strategy. Aim of work: To explore the association between K-ras mutation and potential variables known or suspected to be related to the risk of colorectal cancer (CRC) as well as determining the possible modulating effect of the COX-2 polymorphism, —765G > C. Subjects and methods: The study was conducted on 80 patients with colorectal cancer from Tropical Medicine and Gastrointestinal Tract endoscopy Departments and those attending clinic of the National Cancer Institute, Cairo University during the period extending from April 2009 to March 2010. Full history taking with emphasis on the risk factors of interest, namely age, sex, family history, smoking and dietary history. Serum CEA and CA19-9, RBCs folic acid and occult blood in stool were done to all samples. K-ras protooncogene mutation at codon 12 (exon 1) and cyclooxygenase 2 (COX-2) —765G > C polymorphism were determined by PCR-RFLP. Results: The K-ras mutation was positive in 23 (28.7%) patients. COX-2 polymorphism revealed GG in 62.5%, GC in 26.2 % and CC genotype was found in 11.3 % of cases. The mean red blood cell folic acid level was lower in the K-ras positive group (100.96 ± 51.3 ng/ml) than the negative group (216.6 ± 166.4 ng/ml), (P < 0.01). Higher folate levels were found in males than females (median = 173 ng/ml and 85 ng/ml; respectively, P = 0.002) with adjusted odds ratio (OR) of 0.984. Only, the RBCs folate (P = 0.0018) followed by gender (P = 0

  9. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Hao; Li, Ying [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Yue, Jiang [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Guo, Austin M., E-mail: Austin_Guo@nymc.edu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Flavonoids exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Anoikis resistance occurs at multiple key stages of the metastatic cascade. Here, we demonstrate that isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, inhibits human breast cancer metastasis by preventing anoikis resistance, migration and invasion through downregulating cyclooxygenase (COX)-2 and cytochrome P450 (CYP) 4A signaling. ISL induced anoikis in MDA-MB-231 and BT-549 human breast cancer cells as evidenced by flow cytometry and the detection of caspase cleavage. Moreover, ISL inhibited the mRNA expression of phospholipase A2, COX-2 and CYP 4A and decreased the secretion of prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE) in detached MDA-MB-231 cells. In addition, it decreased the levels of phospho-PI3K (Tyr{sup 458}), phospho-PDK (Ser{sup 241}) and phospho-Akt (Thr{sup 308}). Conversely, the exogenous addition of PGE{sub 2}, WIT003 (a 20-HETE analog) and an EP4 agonist (CAY10580) or overexpression of constitutively active Akt reversed ISL-induced anoikis. ISL exerted the in vitro anti-migratory and anti-invasive activities, whereas the addition of PGE{sub 2}, WIT003 and CAY10580 or overexpression of constitutively active Akt reversed the in vitro anti-migratory and anti-invasive activities of ISL in MDA-MB-231 cells. Notably, ISL inhibited the in vivo lung metastasis of MDA-MB-231 cells, together with decreased intratumoral levels of PGE{sub 2}, 20-HETE and phospho-Akt (Thr{sup 308}). In conclusion, ISL inhibits breast cancer metastasis by preventing anoikis resistance, migration and invasion via downregulating COX-2 and CYP 4A signaling. It suggests that ISL could be a promising multi-target agent for preventing breast cancer metastasis, and anoikis could represent a novel mechanism through which flavonoids may exert the anti-metastatic activities. - Highlights: • Isoliquiritigenin induces anoikis and suppresses

  10. Association of folate intake, dietary habits, smoking and COX-2 promotor -765G>C polymorphism with K-ras mutation in patients with colorectal cancer.

    Science.gov (United States)

    Kamal, Manal M; Youssef, Omar Z; Lotfy, Ahmed N; Elsaed, Eman T; Fawzy, May M T

    2012-09-01

    Understanding the role of environmental and molecular influences on the nature and rate of K-ras mutations in colorectal neoplasms is crucial. COX-2 polymorphisms -765G>C may play a role in carcinogenic processes in combination with specific life-style conditions or dependent on the racial composition of a particular population. If mutational events play an important role in colorectal carcinogenesis sequence, one can hypothesize that modification of these events by life-style or other factors would be a useful prevention strategy. To explore the association between K-ras mutation and potential variables known or suspected to be related to the risk of colorectal cancer (CRC) as well as determining the possible modulating effect of the COX-2 polymorphism, -765G>C. The study was conducted on 80 patients with colorectal cancer from Tropical Medicine and Gastrointestinal Tract endoscopy Departments and those attending clinic of the National Cancer Institute, Cairo University during the period extending from April 2009 to March 2010. Full history taking with emphasis on the risk factors of interest, namely age, sex, family history, smoking and dietary history. Serum CEA and CA19-9, RBCs folic acid and occult blood in stool were done to all samples. K-ras protooncogene mutation at codon 12 (exon 1) and cyclooxygenase 2 (COX-2) -765G>C polymorphism were determined by PCR-RFLP. The K-ras mutation was positive in 23 (28.7%) patients. COX-2 polymorphism revealed GG in 62.5%, GC in 26.2 % and CC genotype was found in 11.3 % of cases. The mean red blood cell folic acid level was lower in the K-ras positive group (100.96±51.3 ng/ml) than the negative group (216.6±166.4 ng/ml), (P<0.01). Higher folate levels were found in males than females (median=173 ng/ml and 85 ng/ml; respectively, P=0.002) with adjusted odds ratio (OR) of 0.984. Only, the RBCs folate (P=0.0018) followed by gender (P=0.036) contributed significantly in the discrimination between patients prone to develop K

  11. Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

    Science.gov (United States)

    Oak, Nikhil R; Gumucio, Jonathan P; Flood, Michael D; Saripalli, Anjali L; Davis, Max E; Harning, Julie A; Lynch, Evan B; Roche, Stuart M; Bedi, Asheesh; Mendias, Christopher L

    2014-12-01

    The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers. Controlled laboratory study. Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses. Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%. The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development

  12. COX-2–prostacyclin signaling through endothelial nitric oxide is not necessary for lipopolysaccharide-induced hypotension and bradycardia in conscious unrestrained mice

    DEFF Research Database (Denmark)

    Stæhr, Mette

    Cardiovascular collapse with fatal drop in arterial blood pressure is a hallmark of gram-negative septic chock. In the present study we hypothesized a serial induction of cyclooxygenase-2 and activation of eNOS as responsible for the decrease in blood pressure, cardiac performance and vascular re......NOS is not necessary for LPS-induced systemic decrease in blood pressure and heart rate and suppression of vascular reactivity in mice whereas iNOS appears to be of central importance. COX-2 and eNOS do not appear as attractive therapeutic cardiovascular targets....

  13. Thiocarbamate-Directed Tandem Olefination-Intramolecular Sulfuration of Two Ortho C-H Bonds: Application to Synthesis of a COX-2 Inhibitor.

    Science.gov (United States)

    Li, Wendong; Zhao, Yingwei; Mai, Shaoyu; Song, Qiuling

    2018-02-16

    A palladium-catalyzed dual ortho C-H bond activation of aryl thiocarbamates is developed. This tandem reaction initiates by thiocarbamate-directed ortho C-H palladation, which leads to favorable olefin insertion rather than reductive elimination. The oxidative Heck reaction followed by another C-H activation and sulfuration affords the dual-functionalized products. This reaction provides a concise route to the S,O,C multisubstituted benzene skeleton which could be successfully applied for the synthesis of a COX-2 inhibitor.

  14. γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages.

    Science.gov (United States)

    Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Kim, Jung-Bong; Lim, Yoongho; Lee, Young Han

    2017-09-16

    Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Density functional theory analysis and molecular docking evaluation of 1-(2, 5-dichloro-4-sulfophenyl)-3-methyl-5-pyrazolone as COX2 inhibitor against inflammatory diseases

    Science.gov (United States)

    Kavitha, T.; Velraj, G.

    2017-08-01

    The molecular structure of 1-(2, 5-Dichloro-4-Sulfophenyl)-3-Methyl-5-Pyrazolone (DSMP) was optimized using DFT/B3LYP/6-31++G(d,p) level and its corresponding experimental as well as theoretical FT-IR, FT-Raman vibrational frequencies and UV-Vis spectral analysis were carried out. The vibrational assignments and total energy distributions of each vibration were presented with the aid of Veda 4xx software. The molecular electrostatic potential, HOMO-LUMO energies, global and local reactivity descriptors and natural bond orbitals were analyzed in order to find the most possible reactive sites of the molecule and it was found that DSMP molecule possess enhanced nucleophilic activity. One of the common known COX2 inhibitor, celecoxib (CXB) was also found to exhibit similar reactivity properties and hence DSMP was also expected to inhibit COX enzymes. In order to detect the COX inhibition nature of DSMP, molecular docking analysis was carried out with the help of Autodock software. For that, the optimized structure was in turn used for docking DSMP with COX enzymes. The binding energy scores and inhibitory constant values reveal that the DSMP molecule possess good binding affinity and low inhibition constant towards COX2 enzyme and hence it can be used as an anti-inflammatory drug after carrying out necessary biological tests.

  16. Síntese e modelagem molecular do novo derivado indolinônico como candidato a antiinflamatório COX-2 seletivo

    Directory of Open Access Journals (Sweden)

    J. L. SANTOS

    2009-01-01

    Full Text Available

    Os fármacos antiinflamatórios são sabidamente os mais comercializados em todo o mundo, e apesar disto apresentam sérios efeitos colaterais, sobretudo no que se refere ao trato gastrintestinal. A descoberta de novos protótipos com atividade e segurança terapêutica melhoradas continua sendo uma busca constante. Com o advento da química computacional torna-se mais fácil o estudo teórico do comportamento fisiológico de uma nova substância bem como a compreensão do possível mecanismo de ação destas novas moléculas. Assim, através de modelos matemáticos de moléculas e receptores estudouse neste trabalho o composto I (1-(2,6- diclorofenilindolin-2-ona quanto à sua possibilidade de inibir seletivamente a isoforma COX-2 da enzima prostaglandina endoperóxido sintase (PGHS, e também as melhores posições para a introdução de grupamentos químicos e modificações moleculares. Palavras-chave: indolinônico; COX-2; antiinflamatório.

  17. Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun Ju Shin

    2015-04-01

    Full Text Available Poly-γ-glutamic acid (PGA is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose polymerase (PARP and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2 and inducible nitric oxide synthase (iNOS. Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study.

  18. Dynamics of COX-2 Content in Mucosa of the Stomach and Duodenum on the Background of Medical Correction of NSAID Gastropathy

    Directory of Open Access Journals (Sweden)

    Yu.M. Stepanov

    2013-02-01

    Full Text Available The results of immune histochemical study of cyclooxygenase type 2 (COX-2 level in 120 patients with inflammatory and erosive lesions of the stomach and duodenum on the background of long-term use of non-steroid anti-inflammatory drugs (NSAIDs before and after treatment of damages of gastroduodenal zone are presented. Average level of COX-2 in patients with gastroduodenal lesions, caused by NSAIDs, decreased by 1.5 times and made up (2.02 ± 0.11 c.u. before treatment and (1.27 ± 0.09 c.u after treatment by the regimen № 1; it decreased by 2 times and made up (2.00 ± 0.16 c.u and (0.95 ± 0.09 c.u. relatively before and after the treatment by regimen № 2. Findings indicate the decrease of protective properties of the stomach and duodenum mucosa in case of a long-term use of NSAIDs.

  19. Effects of Six Weeks Endurance Training and Aloe Vera Supplementation on COX-2 and VEGF Levels in Mice with Breast Cancer

    Science.gov (United States)

    Shirali, Saeed; Barari, Alireza; Hosseini, Seyed Ahmad; Khodadi, Elaheh

    2017-01-01

    The aim of this study was to determine effects of six weeks endurance training and Aloe Vera supplementation on COX-2 and VEGF levels in mice with breast cancer. For this purpose, 35 rats were randomly divided into 5 groups: control (healthy) and 4 cancer groups: control (cancer only), training, Aloe Vera and Aloe Vera + training. Breast cancer tumors were generated in mice by implantind. The training program comprised six weeks of swimming training accomplished in three sessions per week. Training time started with 10 minutes on the first day and increased to 60 minutes in the second week and the water flow rate was increased from 7 to 15 liters per minute at a constant rate. Aloe Vera extract at a dose of 300 mg/kg BW was administrated to rats by intraperitoneal injection. At the end of the study period, rats were anesthetized and blood samples were taken. Significant differences were concluded at pAloe Vera extract caused significant decrease in the COX-2 level in the cancer group. Also, in the training (swimming exercise) and Aloe Vera + training cancer groups, we observed significant decrease in the VEGF level as compared to controls. Our results suggest that Aloe Vera and training inhibit the COX pathway and cause decrease production of prostaglandin E2. Hence administration of Aloe Vera in combination with endurance training might synergistically improve the host milieu in mice bearing breast cancers. Creative Commons Attribution License

  20. Non-invasive assessment of animal exercise stress: real-time PCR of GLUT4, COX2, SOD1 and HSP70 in avalanche military dog saliva.

    Science.gov (United States)

    Diverio, S; Guelfi, G; Barbato, O; Di Mari, W; Egidi, M G; Santoro, M M

    2015-01-01

    Exercise has been shown to increase mRNA expression of a growing number of genes. The aim of this study was to assess if mRNA expression of the metabolism- and oxidative stress-related genes GLUT4 (glucose transporter 4), COX2 (cyclooxygenase 2), SOD1 (superoxide dismutase 1) and HSP70 (heat shock protein 70) in saliva changes following acute exercise stress in dogs. For this purpose, 12 avalanche dogs of the Italian Military Force Guardia di Finanza were monitored during simulation of a search for a buried person in an artificial avalanche area. Rectal temperature (RT) and saliva samples were collected the day before the trial (T0), immediately after the descent from a helicopter at the onset of a simulated avalanche search and rescue operation (T1), after the discovery of the buried person (T2) and 2 h later (T3). Expressions of GLUT4, SOD1, COX2 and HSP70 were measured by real-time PCR. The simulated avalanche search and rescue operation was shown to exert a significant effect on RT, as well as on the expression of all metabolism- and oxidative stress-related genes investigated, which peaked at T2. The observed expression patterns indicate an acute exercise stress-induced upregulation, as confirmed by the reductions in expression at T3. Moreover, our findings indicate that saliva is useful for assessing metabolism- and oxidative stress-related genes without the need for restraint, which could affect working dog performance.

  1. Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy.

    Science.gov (United States)

    Nagy, Viorica Magdalena; Buiga, R; Brie, Ioana; Todor, N; Tudoran, Oana; Ordeanu, Claudia; Virág, Piroska; Tarta, Oana; Rus, Meda; Bălăcescu, O

    2011-01-01

    Despite the improvement in the treatment results due to modern irradiation techniques and to the association of chemo-radiotherapy, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Efforts to implement new therapeutic strategies in order to obtain better results in patients with cervical cancer appear justified. Neovascularization is an important step in the tumor progression and the therapeutic targeting of the tumor blood vessels appears to be a good strategy to follow in the anti-cancer treatment. Thus, even in an incipient phase of the clinical research process, the combination between the anti-angiogenic aimed therapies and the current radio-chemotherapy seems to represent a new, feasible and promising approach. The aim of the present study was to determine the prognostic and/or predictive value of some biological markers of tumor angiogenesis and of their implication in increasing the efficacy of current treatments for this cancer. So far, 54 women were included in a prospective trial: 44 having an advanced cervical carcinoma and 10 healthy women, as controls. A tumor biopsy and a blood sample were obtained from each patient before the start of therapy. The density of microvascularization was assessed using CD34 monoclonal antibody (hot spot technique), the expression of angiogenic factors VEGFR, EGFR and COX-2 were determined in tumor biopsies by specific immunohistochemistry techniques, using primary antibodies anti-EGFR, anti-VEGF and anti-COX-2 respectively. The quantitative polymerase chain reaction (Real Time PCR) was employed for assessing the expression level of the genes involved. Serum VEGF was determined by quantitative ELISA technique. Among the studied clinical and molecular factors, we found to be predictive for the type of response the following factors: tumor size at diagnosis (p=0.01), VEGFR2 expression (p=0.02) and a tendency to significance for patients

  2. STAT3 and NF-κB are common targets for kaempferol-mediated attenuation of COX-2 expression in IL-6-induced macrophages and carrageenan-induced mouse paw edema

    Directory of Open Access Journals (Sweden)

    Anandita Basu

    2017-12-01

    Full Text Available Cycloxygenase-2 (COX-2 is the inducible isoform of cycloxygenase enzyme family that catalyzes synthesis of inflammatory mediators, prostanoids and prostaglandins, and therefore, can be targeted by anti-inflammatory drugs. Here, we showed a plant polyphenol, kaempferol, attenuated IL-6-induced COX-2 expression in human monocytic THP-1 cells suggesting its beneficial role in chronic inflammation. Kaempferol deactivated and prevented nuclear localization of two major transcription factors STAT3 and NF-κB, mutually responsible for COX-2 induction in response to IL-6. Moreover, STAT3 and NF-κB were simultaneously deactivated by kaempferol in acute inflammation, as shown by carrageenan-induced mouse paw edema model. The concomitant reduction in COX-2 expression in paw tissues suggested kaempferol’s role in mitigation of inflammation by targeting STAT3 and NF-κB.

  3. The modulation of radiosensitivity by combined treatment of selective COX-2 inhibitor, NS 398 and EGF receptor blocker AG 1478 in HeLa cell line

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Seon Min; Oh, Young Kee; Kim, Joo Heon; Park, Mi Ja; Seong, In Ock [Eulji University School of Medicine, Daejeon (Korea, Republic of); Kang, Ki Mun; Chai, Gyu Yong [Gyeongsang National University College of Medicine, Jinju (Korea, Republic of)

    2005-03-15

    Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy (SF{sub 2}) and dose enhancement radio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. A cooperative effect were observed on the apoptosis of the HeLa cell line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of 22.70% compare with combination of the one drug with radiation, apoptosis of 8.49%. In cell cycle analysis, accumulation of cell on G{sub 0}/G{sub 1} phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity in a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and SF{sub 2} of 0.12 but the combination of one drug with radiation was not enhanced radiosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 ({rho} = 0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation

  4. The modulation of radiosensitivity by combined treatment of selective COX-2 inhibitor, NS 398 and EGF receptor blocker AG 1478 in HeLa cell line

    International Nuclear Information System (INIS)

    Youn, Seon Min; Oh, Young Kee; Kim, Joo Heon; Park, Mi Ja; Seong, In Ock; Kang, Ki Mun; Chai, Gyu Yong

    2005-01-01

    Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy (SF 2 ) and dose enhancement radio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. A cooperative effect were observed on the apoptosis of the HeLa cell line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of 22.70% compare with combination of the one drug with radiation, apoptosis of 8.49%. In cell cycle analysis, accumulation of cell on G 0 /G 1 phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity in a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and SF 2 of 0.12 but the combination of one drug with radiation was not enhanced radiosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (ρ = 0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell

  5. Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-κB inactivation.

    Science.gov (United States)

    Wang, Qiang-Song; Xiang, Yaozu; Cui, Yuan-Lu; Lin, Ke-Ming; Zhang, Xin-Fang

    2012-01-01

    The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported. The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB) activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo. These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new health-enhancing nutritional food

  6. Dietary blue pigments derived from genipin, attenuate inflammation by inhibiting LPS-induced iNOS and COX-2 expression via the NF-κB inactivation.

    Directory of Open Access Journals (Sweden)

    Qiang-Song Wang

    Full Text Available The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported.The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO and prostaglandin E(2 (PGE(2 were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, interleukin (IL-6, and tumor necrosis factor alpha (TNF-α was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB α, Inhibitor of NF-κB Kinase (IKK α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo.These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new health-enhancing nutritional

  7. Competing superconducting and magnetic order parameters and field-induced magnetism in electron doped Ba(Fe1-xCox)2As2

    DEFF Research Database (Denmark)

    Larsen, Jacob; Uranga, B. Mencia; Stieber, G.

    2015-01-01

    We have studied the magnetic and superconducting properties of Ba(Fe1-xCox)2As2 as a function of temperature and external magnetic field using neutron scattering and muon spin rotation. Below the superconducting transition temperature the magnetic and superconducting order parameters coexist...... and compete. A magnetic field can significantly enhance the magnetic scattering in the superconducting state, roughly doubling the Bragg intensity at 13.5 T. We perform a microscopic modelling of the data by use of a five-band Hamiltonian relevant to iron pnictides. In the superconducting state, vortices can...... slow down and freeze spin fluctuations locally. When such regions couple they result in a long-range ordered antiferromagnetic phase producing the enhanced magnetic elastic scattering in agreement with experiments....

  8. A Semimetal Model of the Normal State Susceptibility and Transport Properties of Ba(Fe1-xCox)2As2 Superconductors

    Science.gov (United States)

    Sales, Brian; Sefat, Athena; McGuire, Michael; Mandrus, David

    2010-03-01

    A simple two-band 3D model of a semimetal is constructed to see which normal state features of the Ba(Fe1-xCox)2As2 superconductors can be qualitatively understood within this framework. The model is able to account in a semiquantitative fashion for the measured magnetic susceptibility, Hall, and Seebeck data, and the low temperature Sommerfeld coefficient for 0 general conclusion from the model is that the magnetic susceptibility of most semimetals should increase with temperatures. This is indeed found to be the case for two well-known semimetals Bi and TiSe2. Research supported by the US DOE, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering.

  9. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE.

    Science.gov (United States)

    Giurdanella, Giovanni; Lazzara, Francesca; Caporarello, Nunzia; Lupo, Gabriella; Anfuso, Carmelina Daniela; Eandi, Chiara M; Leggio, Gian Marco; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

    2017-10-15

    Diabetic retinopathy is characterized by the breakdown of endothelial blood-retinal barrier. We tested the hypothesis that sulodexide (SDX), a highly purified glycosaminoglycan composed of 80% iduronylglycosaminoglycan sulfate and 20% dermatan sulfate, protects human retinal endothelial cells (HREC) from high glucose (HG)-induced damage, through the suppression of inflammatory ERK/cPLA2/COX-2/PGE 2 pathway, by blocking the effect of advanced glycation end-products (AGEs). HREC were treated with HG (25mM) or AGEs (glycated-BSA, 2mg/ml) for 48h, with or without SDX (60μg/ml) or aflibercept (AFL, 40μg/ml), a VEGF-trap. SDX protected HREC from HG-induced damage (MTT and LDH release) and preserved their blood-retinal barrier-like properties (Trans Endothelial Electrical Resistance and junction proteins, claudin-5, VE-cadherin and occludin, immunofluorescence and immunoblot) as well as their angiogenic potential (Tube Formation Assay). Both HG and AGEs increased phosphoERK and phospho-cPLA 2 , an effect counteracted by SDX and, less efficiently, by AFL. Both HG and exogenous VEGF (80ng/ml) increased PGE 2 release, an effect partially reverted by SDX for HG and by AFL for VEGF. Analysis of NFκB activity revealed that HG increased the abundance of p65 in the nuclear fraction (nuclear translocation), an effect entirely reverted by SDX, but only partially by AFL. SDX, AFL and SDX+AFL protected HREC even when added 24h after HG. These data show that SDX protects HREC from HG damage and suggest that it counteracts the activation of ERK/cPLA2/COX-2/PGE 2 pathway by reducing AGE-related signaling and downstream NFκB activity. This mechanism, partially distinct from VEGF blockade, may contribute to the therapeutic effect of SDX. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Diclofenac, a selective COX-2 inhibitor, inhibits DMH-induced colon tumorigenesis through suppression of MCP-1, MIP-1α and VEGF.

    Science.gov (United States)

    Kaur, Jasmeet; Sanyal, S N

    2011-09-01

    Angiogenesis is a physiological process involving growth of new blood vessels from pre-existing ones; however, it also plays a critical role in tumor progression. It favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore targeting angiogenesis will be profitable as a mechanism to inhibit tumor's lifeline. Further, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF)-master switch in angiogenesis and other molecules in the neoplastic and pro-inflammatory milieu. We studied the role of two important chemokines [monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-lα] alongwith VEGF and matrix metalloproteinases (MMPs) in non-steroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effect in experimental colon cancer in rat. 1,2-Dimethylhydrazine (DMH, 30 mg/kg body weight, subcutaneously (s.c.) once-a-week) for 18 wk was used as pro-carcinogen and diclofenac (8 mg/kg body weight, orally daily) as the preferential cyclooxygenase-2 (COX-2) inhibitor. Expression of COX-2 and VEGF was found to be significantly elevated in the DMH-treated group as compared to the control, which was lowered notably by Diclofenac co-administration with DMH. Gelatin zymography showed prominent MMP-9 activity in the DMH-treated rats, while the activity was nearly absent in all the other groups. Expression of MCP-1 was found to be markedly increased whereas MIP-1α expression was found to be decreased in colonic mucosa from DMH-treated rats, which was reversed in the DMH + Diclofenac group. Our results indicate potential role of chemokines alongwith VEGF in angiogenesis in DMH-induced cancer and its chemoprevention with diclofenac. Copyright ©2011 Wiley-Liss, Inc.

  11. Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8

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    Abdulamir Ahmed S

    2010-09-01

    Full Text Available Abstract Background Colorectal cancer (CRC has long been associated with bacteremia and/or endocarditis by Streptococcus gallolyticus member bacteria (SGMB but the direct colonization of SGMB along with its molecular carcinogenic role, if any, has not been investigated. We assessed the colonization of SGMB in CRC patients with history of bacteremia (CRC-w/bac and without history of bacteremia (CRC-wo/bac by isolating SGMB from feces, mucosal surfaces of colorectum, and colorectal tissues and detecting SGMB DNA, via PCR and in situ hybridization (ISH assays targeting SodA gene in colorectal tissues. Moreover, mRNA of IL1, IL-8, COX-2, IFN-γ, c-Myc, and Bcl-2 in colorectal tissues of studied groups was assessed via ISH and RT-PCR. Results SGMB were found to be remarkably isolated in tumorous (TU and non-tumorous (NTU tissues of CRC-w/bac, 20.5% and 17.3%, and CRC-wo/bac, 12.8% and 11.5%, respectively while only 2% of control tissues revealed SGMB (P 10 CN/g respectively, showed higher colonization in TU than in NTU and in CRC-w/bac than in CRC-wo/bac (P Conclusions The current study indicated that colorectal cancer is remarkably associated with SGMB; moreover, molecular detection of SGMB in CRC was superior to link SGMB with CRC tumors highlighting a possible direct and active role of SGMB in CRC development through most probably inflammation-based sequel of tumor development or propagation via, but not limited to, IL-1, COX-2, and IL-8.

  12. Wine polyphenols exert antineoplasic effect on androgen resistant PC-3 cell line through the inhibition of the transcriptional activity of COX-2 promoter mediated by NF-kβ.

    Science.gov (United States)

    Ferruelo, A; de Las Heras, M M; Redondo, C; Ramón de Fata, F; Romero, I; Angulo, J C

    2014-09-01

    Mediterranean diet may play a role in the prevention of prostate cancer (PCa) development and progression. Cyclooxygenase-2 (COX-2) expression is associated with increased cellular proliferation, prevents apoptosis and favors tumor invasion. We intend to clarify whether resveratrol and other polyphenols effectively inhibit COX-2 activity and induce apoptosis in hormone-resistant PC-3 cell line. PC-3 cells were cultured and treated with different concentrations of gallic acid, tannic acid, quercetin, and resveratrol in presence of phorbol myristate acetate (PMA; 50 μg/ml) that induces COX-2 expression. Total RNA was extracted and COX-2 expression was analyzed by relative quantification real-time PCR (ΔΔCt method). COX-2 activity was determined by PGE-2 detection using ELISA. Caspase 3/7 luminescence assay was used to disclose apoptosis. Transitory transfection with short human COX-2 (phPES2 -327/+59) and p5xNF-kβ-Luc plasmids determined COX-2 promoter activity and specifically that dependant of NF-kβ. COX-2 expression was not modified in media devoid of PMA. However, under PMA induction tannic acid (2.08 ±.21), gallic acid (2.46 ±.16), quercetin (1.78 ±.14) and resveratrol (1.15 ±.16) significantly inhibited COX-2 mRNA with respect to control (3.14 ±.07), what means a 34%, 23%, 46% and 61% reduction, respectively. The inhibition in the levels of PGE-2 followed a similar pattern. All compounds studied induced apoptosis at 48 h, although at a different rate. PMA caused a rise in activity 7.4 ±.23 times phPES2 -327/+59 and 2.0 ±.1 times p5xNF-kβ-Luc at 6h compared to basal. Resveratrol suppressed these effects 17.1 ±.21 and 32.4 ±.18 times, respectively. Similarly, but to a lesser extent, the rest of evaluated polyphenols diminished PMA inductor effect on the activity of both promoters. Polyphenols inhibit transcriptional activity of COX-2 promoter mediated by NF-kβ. This effect could explain, at least in part, the induction of apoptosis in vitro by

  13. Aspectos psicosociales en universitarias embarazadas

    OpenAIRE

    Estupiñán-Aponte, María R.; Rodríguez-Barreto, Lucía

    2009-01-01

    Objetivo Determinar los aspectos psicosociales relacionados con el embarazo en estudiantes universitarias.Metodología A partir de la revisión de archivos y el muestreo intencional, se seleccionaron 68 estudiantes que tuvieron un embarazo adolescente. Mediante relatos de vida y entrevistas en profundidad se analizan las implicaciones del embarazo en la condición personal, familiar y académica.Resultados Durante el primer trimestre de embarazo, se generan crisis y ajustes en la estructura famil...

  14. 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.

  15. Licochalcone A, a Polyphenol Present in Licorice, Suppresses UV-Induced COX-2 Expression by Targeting PI3K, MEK1, and B-Raf

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    Nu Ry Song

    2015-02-01

    Full Text Available Licorice is a traditional botanical medicine, and has historically been commonly prescribed in Asia to treat various diseases. Glycyrrhizin (Gc, a triterpene compound, is the most abundant phytochemical constituent of licorice. However, high intake or long-term consumption of Gc has been associated with a number of side effects, including hypertension. However, the presence of alternative bioactive compounds in licorice with anti-carcinogenic effects has long been suspected. Licochalcone A (LicoA is a prominent member of the chalcone family and can be isolated from licorice root. To date, there have been no reported studies on the suppressive effect of LicoA against solar ultraviolet (sUV-induced cyclooxygenase (COX-2 expression and the potential molecular mechanisms involved. Here, we show that LicoA, a major chalcone compound of licorice, effectively inhibits sUV-induced COX-2 expression and prostaglandin E2 PGE2 generation through the inhibition of activator protein 1 AP-1 transcriptional activity, with an effect that is notably more potent than Gc. Western blotting analysis shows that LicoA suppresses sUV-induced phosphorylation of Akt/ mammalian target of rapamycin (mTOR and extracellular signal-regulated kinases (ERK1/2/p90 ribosomal protein S6 kinase (RSK in HaCaT cells. Moreover, LicoA directly suppresses the activity of phosphoinositide 3-kinase (PI3K, mitogen-activated protein kinase kinase (MEK1, and B-Raf, but not Raf-1 in cell-free assays, indicating that PI3K, MEK1, and B-Raf are direct molecular targets of LicoA. We also found that LicoA binds to PI3K and B-Raf in an ATP-competitive manner, although LicoA does not appear to compete with ATP for binding with MEK1. Collectively, these results provide insight into the biological action of LicoA, which may have potential for development as a skin cancer chemopreventive agent.

  16. Amplification of cox2 (approximately 620 bp) from 2 mg of up to 129 years old herbarium specimens, comparing 19 extraction methods and 15 polymerases.

    Science.gov (United States)

    Telle, Sabine; Thines, Marco

    2008-01-01

    During the past years an increasing number of studies have focussed on the use of herbarium specimens for molecular phylogenetic investigations and several comparative studies have been published. However, in the studies reported so far usually rather large amounts of material (typically around 100 mg) were sampled for DNA extraction. This equals an amount roughly equivalent to 8 cm(2) of a medium thick leaf. For investigating the phylogeny of plant pathogens, such large amounts of tissue are usually not available or would irretrievably damage the specimens. Through systematic comparison of 19 DNA extraction protocols applied to only 2 mg of infected leaf tissue and testing 15 different DNA polymerases, we could successfully amplify a mitochondrial DNA region (cox2; approximately 620 bp) from herbarium specimens well over a hundred years old. We conclude that DNA extraction and the choice of DNA polymerase are crucial factors for successful PCR amplification from small samples of historic herbarium specimens. Through a combination of suitable DNA extraction protocols and DNA polymerases, only a fraction of the preserved plant material commonly used is necessary for successful PCR amplification. This facilitates the potential use of a far larger number of preserved specimens for molecular phylogenetic investigation and provides access to a wealth of genetic information in preserved in specimens deposited in herbaria around the world without reducing their scientific or historical value.

  17. Improved anti-tumor activity of a therapeutic melanoma vaccine through the use of the dual COX-2/5-LO inhibitor licofelone

    Directory of Open Access Journals (Sweden)

    Silke Neumann

    2016-12-01

    Full Text Available Immune-suppressive cell populations impair anti-tumor immunity and can contribute to the failure of immune therapeutic approaches. We hypothesized that the non-steroidal anti-inflammatory drug (NSAID licofelone, a dual COX-2/5-LO inhibitor, would improve therapeutic melanoma vaccination by reducing immune-suppressive cell populations. Therefore, licofelone was administered after tumor implantation, either alone or in combination with a peptide vaccine containing a long tyrosinase-related protein (TRP2-peptide and the adjuvant α-galactosylceramide, all formulated into cationic liposomes. Mice immunized with the long-peptide vaccine and licofelone showed delayed tumor growth compared to mice given the vaccine alone. This protection was associated with a lower frequency of immature myeloid cells (IMCs in the bone marrow (BM and spleen of tumor-inoculated mice. When investigating the effect of licofelone on IMCs in vitro, we found that the prostaglandin E2-induced generation of IMCs was decreased in the presence of licofelone. Furthermore, pre-incubation of BM cells differentiated under IMC-inducing conditions with licofelone reduced the secretion of cytokines interleukin (IL-10 and -6 upon LPS stimulation as compared to untreated cells. Interestingly, licofelone increased IL-6 and IL-10 secretion when administered after the LPS stimulus, demonstrating an environment-dependent effect of licofelone. Our findings support the use of licofelone to reduce tumor-promoting cell populations.

  18. Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells.

    Science.gov (United States)

    Oh, Young Taek; Lee, Jung Yeon; Lee, Jinhwa; Lee, Ju Hie; Kim, Ja-Eun; Ha, Joohun; Kang, Insug

    2010-05-03

    Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia. 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Direct observation of in-plane anisotropy of the superconducting critical current density in Ba (Fe1-xCox) 2As2 crystals

    Science.gov (United States)

    Hecher, J.; Ishida, S.; Song, D.; Ogino, H.; Iyo, A.; Eisaki, H.; Nakajima, M.; Kagerbauer, D.; Eisterer, M.

    2018-01-01

    The phase diagram of iron-based superconductors exhibits structural transitions, electronic nematicity, and magnetic ordering, which are often accompanied by an electronic in-plane anisotropy and a sharp maximum of the superconducting critical current density (Jc) near the phase boundary of the tetragonal and the antiferromagnetic-orthorhombic phase. We utilized scanning Hall-probe microscopy to visualize the Jc of twinned and detwinned Ba (Fe1-xCox) 2As2 (x =5 %-8 % ) crystals to compare the electronic normal state properties with superconducting properties. We find that the electronic in-plane anisotropy continues into the superconducting state. The observed correlation between the electronic and the Jc anisotropy agrees qualitatively with basic models, however, the Jc anisotropy is larger than predicted from the resistivity data. Furthermore, our measurements show that the maximum of Jc at the phase boundary does not vanish when the crystals are detwinned. This shows that twin boundaries are not responsible for the large Jc, suggesting an exotic pinning mechanism.

  20. Crocetin Downregulates the Proinflammatory Cytokines in Methylcholanthrene-Induced Rodent Tumor Model and Inhibits COX-2 Expression in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Bing Chen

    2015-01-01

    Full Text Available The effect of crocetin (C20H24O4 on methylcholanthrene- (MCA- induced uterine cervical cancer in mice was studied in this paper. After the mice were treated orally with crocetin, maleic dialdehyde (MDA, polymorphonuclear cells (PMN, interleukin-1β (IL-1β, and tumor necrosis factor-α (TNF-α were examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase (iNOS activation in HeLa cells was analyzed using fluorescence microscopy for light microscopic examination. The MCA mice showed a significant increase in plasma MDA, PMN, IL-1β, TNF-α, and nitrates levels. At the same time, the mRNA level of COX-2 in HeLa cells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent.

  1. Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in ApcMin/+ mice

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    Brudvik Kristoffer W

    2011-12-01

    Full Text Available Abstract Background The adenomatous polyposis coli (APC protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer. The destruction complex is inhibited by Wnt-Frz and prostaglandin E2 (PGE2 - PI-3 kinase pathways. Recent reports show that PGE2-induced phosphorylation of β-catenin by protein kinase A (PKA increases nuclear translocation indicating two mechanisms of action of PGE2 on β-catenin homeostasis. Findings Treatment of ApcMin/+ mice that spontaneously develop intestinal adenomas with a PKA antagonist (Rp-8-Br-cAMPS selectively targeting only the latter pathway reduced tumor load, but not the number of adenomas. Immunohistochemical characterization of intestines from treated and control animals revealed that expression of β-catenin, β-catenin nuclear translocation and expression of the β-catenin target genes c-Myc and COX-2 were significantly down-regulated upon Rp-8-Br-cAMPS treatment. Parallel experiments in a human colon cancer cell line (HCT116 revealed that Rp-8-Br-cAMPS blocked PGE2-induced β-catenin phosphorylation and c-Myc upregulation. Conclusion Based on our findings we suggest that PGE2 act through PKA to promote β-catenin nuclear translocation and tumor development in ApcMin/+ mice in vivo, indicating that the direct regulatory effect of PKA on β-catenin nuclear translocation is operative in intestinal cancer.

  2. COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancer in two independent populations

    Science.gov (United States)

    Makar, Karen W; Poole, Elizabeth M; Resler, Alexa J; Seufert, Brenna; Curtin, Karen; Kleinstein, Sarah E; Duggan, David; Kulmacz, Richard J; Hsu, Li; Whitton, John; Carlson, Christopher S; Rimorin, Christine F; Caan, Bette J; Baron, John A; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

    2014-01-01

    Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and -2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy. Methods We genotyped candidate polymorphisms and tagSNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case-control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n=1470 cases/1837 controls) and rectal cancer (n=583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n= 959/1535, rectal n= 505/839). Results In PTGS2, a functional polymorphism (−765G>C; rs20417) was associated with a 2-fold increased rectal cancer risk (p=0.05) in the DALS study. This association replicated with a significant nearly 5-fold increased risk of rectal cancer in the CCFR study (ORCC vs GG=4.88; 95%CI=1.54–15.45; ORGC vs GG=1.36; 95%CI: 0.95–1.94). Genotype-NSAID interactions were observed in the DALS study for PTGS1 and rectal cancer risk, and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed. Conclusions These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs. PMID:24022467

  3. Aspectos moleculares da anemia falciforme

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    Galiza Neto Gentil Claudino de

    2003-01-01

    Full Text Available No presente artigo abordaram-se vários aspectos relacionados à natureza molecular da anemia falciforme, desordem hematológica de caráter hereditário que acomete expressivo número de indivíduos em várias regiões do mundo. As pesquisas realizadas em torno desta patologia da hemácia, ao longo de quase um século, a partir de 1910, cooperaram para a criação de um novo e importante segmento da ciência, denominado biologia molecular. A descoberta dos polimorfismos da mutação (GAT->GTG no gene que codifica a cadeia beta da hemoglobina, originando diferentes haplótipos da doença, permitiu um melhor e mais amplo conhecimento em torno da heterogeneidade clínica nos pacientes falcêmicos. Analisando a hemoglobina na sua estrutura normal e mutante, sua produção e evolução, pode-se ter um entendimento mais completo da fisiopatologia desta doença e da sua complexidade clínica.

  4. TGF-β1 downregulates COX-2 expression leading to decrease of PGE2 production in human lung cancer A549 cells, which is involved in fibrotic response to TGF-β1.

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    Erina Takai

    Full Text Available Transforming growth factor-ß1 (TGF-β1 is a multifunctional cytokine that is involved in various pathophysiological processes, including cancer progression and fibrotic disorders. Here, we show that treatment with TGF-β1 (5 ng/mL induced downregulation of cyclooxygenase-2 (COX-2, leading to reduced synthesis of prostaglandin E2 (PGE2, in human lung cancer A549 cells. Treatment of cells with specific inhibitors of COX-2 or PGE2 receptor resulted in growth inhibition, indicating that the COX-2/PGE2 pathway contributes to proliferation in an autocrine manner. TGF-β1 treatment induced growth inhibition, which was attenuated by exogenous PGE2. TGF-β1 is also a potent inducer of epithelial mesenchymal transition (EMT, a phenotype change in which epithelial cells differentiate into fibroblastoid cells. Supplementation with PGE2 or PGE2 receptor EP4 agonist PGE1-alcohol, as compared with EP1/3 agonist sulprostone, inhibited TGF-β1-induced expression of fibronectin and collagen I (extracellular matrix components. Exogenous PGE2 or PGE2 receptor agonists also suppressed actin remodeling induced by TGF-β1. These results suggest that PGE2 has an anti-fibrotic effect. We conclude that TGF-β1-induced downregulation of COX-2/PGE2 signaling is involved in facilitation of fibrotic EMT response in A549 cells.

  5. Interactions between Diet, Lifestyle and IL10, IL1B, and PTGS2/COX-2 Gene Polymorphisms in Relation to Risk of Colorectal Cancer in a Prospective Danish Case-Cohort Study

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Holst, René; Kopp, Tine Iskov

    2013-01-01

    Genetically determined low COX-2 and high IL-1β activity were associated with increased risk of CRC in this northern Caucasian cohort. Furthermore, interactions were found between IL10, IL1b, and PTGS2 and diet and lifestyle factors in relation to CRC. The present study demonstrates that gene...

  6. Genistein inhibits phorbol ester-induced NF-κB transcriptional activity and COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Myung-Hoon; Kim, Do-Hee [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Na, Hye-Kyung [Department of Food and Nutrition, Sungshin Women' s University, Seoul (Korea, Republic of); Kim, Jung-Hwan; Kim, Ha-Na [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Haegeman, Guy [LEGEST, University of Gent (Belgium); Surh, Young-Joon, E-mail: surh@snu.ac.kr [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2014-10-15

    Genistein, an isoflavone present in soy products, has chemopreventive effects on mammary carcinogenesis. In the present study, we have investigated the effects of genistein on phorbol ester-induced expression of cyclooxygenase-2 (COX-2) that plays an important role in the pathophysiology of inflammation-associated carcinogenesis. Pretreatment of cultured human breast epithelial (MCF10A) cells with genistein reduced COX-2 expression induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). There are multiple lines of evidence supporting that the induction of COX-2 is regulated by the eukaryotic transcription factor NF-κB. Genistein failed to inhibit TPA-induced nuclear translocation and DNA binding of NF-κB as well as degradation of IκB. However, genistein abrogated the TPA-induced transcriptional activity of NF-κB as determined by the luciferase reporter gene assay. Genistein inhibited phosphorylation of the p65 subunit of NF-κB and its interaction with cAMP regulatory element-binding protein-binding protein (CBP)/p300 and TATA-binding protein (TBP). TPA-induced NF-κB phosphorylation was abolished by pharmacological inhibition of extracellular signal-regulated kinase (ERK). Likewise, pharmacologic inhibition or dominant negative mutation of ERK suppressed phosphorylation of p65. The above findings, taken together, suggest that genistein inhibits TPA-induced COX-2 expression in MCF10A cells by blocking ERK-mediated phosphorylation of p65 and its subsequent interaction with CBP and TBP.

  7. Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47{sup phox} pathway

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Ming-Horng [Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin, Taiwan (China); Lin, Zih-Chan [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liang, Chan-Jung [Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yen, Feng-Lin [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Institute of Biomedical Sciences, Sun Yat-Sen University, 70 Lienhai Rd., Kaohsiung, Taiwan (China); Chiang, Yao-Chang [Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan (China); China Medical University, Taichung, Taiwan (China); Lee, Chiang-Wen, E-mail: cwlee@gw.cgust.edu.tw [Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, Taiwan (China); Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China)

    2014-09-01

    Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases. - Highlights: • LPS activates the Nox2/p47{sup phox}/JNK/AP-1 and induces COX2 expression in Hs68 cells. • Eupafolin inhibits LPS-induced COX-2 expression via Nox2/p47{sup phox} inhibition. • Eupafolin may be used in the treatment of skin diseases involving inflammation.

  8. Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47phox pathway

    International Nuclear Information System (INIS)

    Tsai, Ming-Horng; Lin, Zih-Chan; Liang, Chan-Jung; Yen, Feng-Lin; Chiang, Yao-Chang; Lee, Chiang-Wen

    2014-01-01

    Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases. - Highlights: • LPS activates the Nox2/p47 phox /JNK/AP-1 and induces COX2 expression in Hs68 cells. • Eupafolin inhibits LPS-induced COX-2 expression via Nox2/p47 phox inhibition. • Eupafolin may be used in the treatment of skin diseases involving inflammation

  9. The Differential Impact of High-Intensity Swimming Exercise and Inflammatory Bowel Disease on IL-1β, TNF-α, and COX-2 Gene Expression in the Small Intestine and Colon in Mice

    Directory of Open Access Journals (Sweden)

    Eun-Ju Choi

    2018-04-01

    Full Text Available Background and Objective: We aimed to examine the impact of high-intensity swimming exercise and inflammatory bowel disease (IBD on IL-1β, TNF-α, and COX-2 gene expression in the small intestine and colon of mice. Material and Methods: Forty male C57BL/6 mice were divided into 4 groups: the control group (CON, swimming exercise group (EX, 50% ethanol (EtoH control group (50%EtoH CON, and 2,4,6-trinitrobenzene sulfonic acid group (TNBS. The EX group performed 4 weeks of exercise. Intrarectal TNBS injection induced IBD in the TNBS group; the 50%EtoH CON group received control injections. Reverse transcription and real-time polymerase chain reaction were used to examine IL-1β, TNF-α, and COX-2 mRNA expression in the small intestine and colon. Results: IL-1β, TNF-α, and COX-2 mRNA expression was significantly increased in the EX group compared to that in the CON group (p’s<0.05. IL-1β and COX-2 mRNA expression was significantly increased in the TNBS group compared to that in the 50%EtoH CON group (p’s<0.05. Conclusion: Thus, inflammatory cytokine IL-1β and COX-2 expression in the small intestine and colon was increased in both high-intensity swimming exercise and IBD models. However, TNF-α was increased only in the swimming exercise model. Further research is required to confirm these observations and establish swimming exercise regimes appropriate for patients with IBD.

  10. Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes

    International Nuclear Information System (INIS)

    Chien, Peter Tzu-Yu; Lin, Chih-Chung; Hsiao, Li-Der; Yang, Chuen-Mao

    2015-01-01

    Carbon monoxide (CO) is one of the cytoprotective byproducts of heme oxygenase (HO)-1 and exerts anti-inflammatory action in various models. However, the detailed mechanisms underlying CO-induced HO-1 expression in primary human cardiomyocytes remain largely unidentified. We used primary left ventricle myocytes as a model and applied CO releasing molecule (CORM)-2 to investigate the relationship of CO and HO-1 expression. We herein used Western blot, real-time PCR, promoter activity and EIA to investigate the role of HO-1 expression protecting against thrombin-mediated responses. We found that thrombin-induced COX-2 expression, PGE 2 release and cardiomyocyte hypertrophy markers (increase in ANF/BNP, α-actin expression and cell surface area) was attenuated by pretreatment with CORM-2 which was partially reversed by hemoglobin (Hb) or ZnPP (an inhibitor of HO-1 activity), suggesting that HO-1/CO system may be of clinical importance to ameliorate heart failure through inhibition of inflammatory responses. CORM-2-induced HO-1 protein expression, mRNA and promoter was attenuated by pretreatment with the inhibitors of Pyk2 (PF431396), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), p38 (SB202530), JNK1/2 (SP600125), FoxO1 (AS1842856) and Sp1 (mithramycin A). The involvement of these signaling components was further confirmed by transfection with respective siRNAs, consistent with those of pharmacological inhibitors. These results suggested that CORM-2-induced HO-1 expression is mediated through a Pyk2/PDGFR/PI3K/Akt/FoxO1/Sp1-dependent manner and exerts a cytoprotective effect in human cardiomyocytes. - Graphical abstract: In summary, CORM-2 treatment induces Pyk2 transactivated PDGFR, which induces PI3K/Akt/MAPK activation, and then recruits Sp1/Foxo1 transcriptional factors to regulate HO-1 gene expression in primary human cardiomyocytes. - Highlights: • CORM-2 induces HO-1 expression. • Pyk2-dependent PDGFR activates PI3K/Akt/MAPK pathway in CORM-2-induced HO-1

  11. Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-specific NSAIDs and COX-2 inhibitors: a systematic review and network analyses

    Directory of Open Access Journals (Sweden)

    Datto C

    2013-02-01

    Full Text Available Catherine Datto,1 Richard Hellmund,1 Mohd Kashif Siddiqui21AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA; 2HERON PVT India, Chandigarh, UT, IndiaAbstract: Non-steroidal anti-inflammatory drugs (NSAIDs, such as non-selective NSAIDs (nsNSAIDs or selective cyclooxygenase-2 (COX-2 inhibitors, are commonly prescribed for arthritic pain relief in patients with osteoarthritis (OA, rheumatoid arthritis (RA, or ankylosing spondylitis (AS. Treatment guidelines for chronic NSAID therapy include the consideration for gastroprotection for those at risk of gastric ulcers (GUs associated with the chronic NSAID therapy. The United States Food and Drug Administration has approved naproxen/esomeprazole magnesium tablets for the relief of signs and symptoms of OA, RA, and AS, and to decrease the risk of developing GUs in patients at risk of developing NSAID-associated GUs. The European Medical Association has approved this therapy for the symptomatic treatment of OA, RA, and AS in patients who are at risk of developing NSAID-associated GUs and/or duodenal ulcers, for whom treatment with lower doses of naproxen or other NSAIDs is not considered sufficient. Naproxen/esomeprazole magnesium tablets have been compared with naproxen and celecoxib for these indications in head-to-head trials. This systematic literature review and network meta-analyses of data from randomized controlled trials was performed to compare naproxen/esomeprazole magnesium tablets with a number of additional relevant comparators. For this study, an original review examined MEDLINE®, Embase®, and the Cochrane Controlled Trials Register from database start to April 14, 2009. Using the same methodology, a review update was conducted to December 21, 2009. The systematic review and network analyses showed naproxen/esomeprazole magnesium tablets have an improved upper gastrointestinal tolerability profile (dyspepsia and gastric or gastroduodenal ulcers over several active comparators (naproxen

  12. Clathrin-dependent internalization of the angiotensin II AT₁A receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells.

    Science.gov (United States)

    Morinelli, Thomas A; Walker, Linda P; Velez, Juan Carlos Q; Ullian, Michael E

    2015-02-05

    The major effects of Angiotensin II (AngII) in vascular tissue are mediated by AngII AT1A receptor activation. Certain effects initiated by AT1A receptor activation require receptor internalization. In rat aortic vascular smooth muscle cells (RASMC), AngII stimulates cyclooxygenase 2 protein expression. We have previously shown this is mediated by β-arrestin-dependent receptor internalization and NF-κB activation. In this study, a specific inhibitor of clathrin-mediated endocytosis (CME), pitstop-2, was used to test the hypothesis that clathrin-dependent internalization of activated AT1A receptor mediates NF-κB activation and subsequent cyclooxygenase 2 expression. Radioligand binding assays, real time qt-PCR and immunoblotting were used to document the effects of pitstop-2 on AngII binding and signaling in RASMC. Laser scanning confocal microscopy (LSCM) was used to image pitstop-2׳s effects on AT1 receptor/GFP internalization in HEK-293 cells and p65 NF-κB nuclear localization in RASMC. Pitstop-2 significantly inhibited internalization of AT1A receptor (44.7% ± 3.1% Control vs. 13.2% ± 8.3% Pitstop-2; n=3) as determined by radioligand binding studies in RASMC. Studies utilizing AT1A receptor/GFP expressed in HEK 293 cells and LSCM confirmed these findings. Pitstop-2 significantly inhibited AngII-induced p65 NF-κB phosphorylation and nuclear localization, COX-2 message and protein expression in RASMC without altering activation of p42/44 ERK or TNFα signaling. Pitstop-2, a specific inhibitor of clathrin-mediated endocytosis, confirms that internalization of activated AT1A receptor mediates AngII activation of cyclooxygenase 2 expression in RASMC. These data provide support for additional intracellular signaling pathways activated through β-arrestin mediated internalization of G protein-coupled receptors, such as AT1A receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Peter Tzu-Yu [Department of Physiology and Pharmacology and Health Ageing Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Lin, Chih-Chung; Hsiao, Li-Der [Department of Anesthetics, Chang Gung Memorial Hospital at Lin-Kou and College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan (China); Yang, Chuen-Mao, E-mail: chuenmao@mail.cgu.edu.tw [Department of Physiology and Pharmacology and Health Ageing Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan (China); Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan (China)

    2015-12-01

    Carbon monoxide (CO) is one of the cytoprotective byproducts of heme oxygenase (HO)-1 and exerts anti-inflammatory action in various models. However, the detailed mechanisms underlying CO-induced HO-1 expression in primary human cardiomyocytes remain largely unidentified. We used primary left ventricle myocytes as a model and applied CO releasing molecule (CORM)-2 to investigate the relationship of CO and HO-1 expression. We herein used Western blot, real-time PCR, promoter activity and EIA to investigate the role of HO-1 expression protecting against thrombin-mediated responses. We found that thrombin-induced COX-2 expression, PGE{sub 2} release and cardiomyocyte hypertrophy markers (increase in ANF/BNP, α-actin expression and cell surface area) was attenuated by pretreatment with CORM-2 which was partially reversed by hemoglobin (Hb) or ZnPP (an inhibitor of HO-1 activity), suggesting that HO-1/CO system may be of clinical importance to ameliorate heart failure through inhibition of inflammatory responses. CORM-2-induced HO-1 protein expression, mRNA and promoter was attenuated by pretreatment with the inhibitors of Pyk2 (PF431396), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), p38 (SB202530), JNK1/2 (SP600125), FoxO1 (AS1842856) and Sp1 (mithramycin A). The involvement of these signaling components was further confirmed by transfection with respective siRNAs, consistent with those of pharmacological inhibitors. These results suggested that CORM-2-induced HO-1 expression is mediated through a Pyk2/PDGFR/PI3K/Akt/FoxO1/Sp1-dependent manner and exerts a cytoprotective effect in human cardiomyocytes. - Graphical abstract: In summary, CORM-2 treatment induces Pyk2 transactivated PDGFR, which induces PI3K/Akt/MAPK activation, and then recruits Sp1/Foxo1 transcriptional factors to regulate HO-1 gene expression in primary human cardiomyocytes. - Highlights: • CORM-2 induces HO-1 expression. • Pyk2-dependent PDGFR activates PI3K/Akt/MAPK pathway in CORM-2-induced HO

  14. Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki, E-mail: devakit@yahoo.co.uk

    2012-05-15

    -α, IL-1β, i-NOS and NF-κBp65 at protein levels. ► BE modulates the expressions of MMP-2, MMP-9 and COX-2 at protein and mRNA levels. ► BE decreases LPO levels and enhances antioxidant status.

  15. Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

    Directory of Open Access Journals (Sweden)

    Dexter L. Lee

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor-alpha (PPAR-α activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6. Fenofibrate also induces cytochrome P450 4A (CYP4A and increases 20-hydroxyeicosatetraenoic acid (20-HETE production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2, while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically. Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23 and soluble expoxide hydrolase (sEH expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.

  16. Aspectos que interfieren en la movilidad estudiantil

    Directory of Open Access Journals (Sweden)

    María Mercedes Ramírez-Ordoñez

    2014-12-01

    Full Text Available Objetivo: Identificar los aspectos que interfieren en la realización de movilidad estudiantil. Materiales y Métodos: Esta investigación es cuantitativa de tipo descriptivo transversal por conveniencia, constituida por 243 estudiantes que hacen parte de un programa de enfermería en una institución de educación superior X, de los cuales se entrevistaron a 237. Para la recolección de la información se diseñó un cuestionario donde se evalúa el aspecto económico, académico y familiar y su interferencia con el programa de movilidad de la institución. Para su estructuración se realizó revisión bibliográfica, evaluación de expertos, alfa de cronbach y prueba piloto. Resultados: El aspecto económico ocupa el primer lugar en interferir en la movilidad estudiantil con un 73%, es importante resaltar que la población encuestada pertenece al estrato 2 por lo tanto cuentan con pocos recursos. El segundo lugar fue para el aspecto académico con un 63.45% y en menor dimensión el aspecto familiar con 26%; el 77% manifiesta tener un interés por participar del programa de movilidad, de los cuales el 43.78% prefiere el nivel internacional, el 29,79 % nacional y ambas opciones el 25,95%. Conclusiones: Al relacionar los aspectos económicos, académicos y familiares con el total de la población se encontró que solo el 12% de los estudiantes cumplen la totalidad de estos requisitos y pueden participar de la movilidad estudiantil.

  17. Hacia lenguajes de metamodelado orientados a aspectos

    OpenAIRE

    Reina Quintero, Antonia María; Torres Valderrama, Jesús; Toro Bonilla, Miguel

    2006-01-01

    En este artículo se propone la extensión de los lenguajes de metamodelado con constructores de la orientación a aspectos. Tras justificar brevemente el interés que en la actualidad está teniendo el metamodelado, y sentar las bases necesarias para entender la propuesta, se presenta, a través de ejemplos, la necesidad de extender un lenguaje de metamodelado como Kermeta con conceptos introducidos en el ámbito de la orientación a aspectos

  18. Osteossarcoma parosteal: aspectos na radiologia convencional

    OpenAIRE

    Nanci Neto,Francisco; Marchiori,Edson; Vianna,Alberto Domingues; Aymoré,Ierecê Lins; Almeida,Ana Luiza Brito de; Irion,Klaus L.; Collares,Felipe Birchal

    2007-01-01

    OBJETIVO: Avaliar os achados clínicos mais importantes do osteossarcoma parosteal e descrever os seus aspectos mais comuns na radiologia convencional. MATERIAIS E MÉTODOS: Estudo retrospectivo com 26 pacientes com osteossarcoma parosteal, provenientes do arquivo do Clube do Osso, Rio de Janeiro, RJ, e análise dos principais achados clínicos e aspectos radiológicos. RESULTADOS: A doença predominou em pacientes do sexo feminino e teve idade média de acometimento na terceira década de vida. Os a...

  19. Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug

    Science.gov (United States)

    Ranjbar, Mohammad Mehdi; Assadolahi, Vahideh; Yazdani, Mohsen; Nikaein, Donya; Rashidieh, Behnam

    2016-01-01

    Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse model. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of α-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in cancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is shown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This study was conducted based on Cordia species' α-amyrins as a safer natural anti-cancer compound for inhibition of COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes and α-amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes were detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA). Finally drug likeness, molecular pharmacokinetic properties and toxicity of α-amyrins was calculated. Molecular Docking revealed hydrogen and hydrophobic interactions between α-amyrins with both active sites of COX-2 and 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule. Base on binding energies (∆G) α-amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than COX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that α-amyrins complied with most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity score showed α-amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR and protease inhibitor ligand. These results clearly demonstrate that α-amyrins could act as potential highly selective COX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal anti-inflammatory drugs (NSAIDs

  20. Pleurotus giganteus (Berk. Karun & Hyde), the giant oyster mushroom inhibits NO production in LPS/H2O2 stimulated RAW 264.7 cells via STAT 3 and COX-2 pathways.

    Science.gov (United States)

    Baskaran, Asweni; Chua, Kek Heng; Sabaratnam, Vikineswary; Ravishankar Ram, Mani; Kuppusamy, Umah Rani

    2017-01-13

    Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H 2 O 2 )-induced inflammation on RAW 264.7 macrophages was investigated. The effect of EPG on nitric oxide (NO) production as an indicator of inflammation in RAW 264.7 macrophages was estimated based on Griess reaction that measures nitrite level. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NF-kB activating protein (NKAP), signal transducer and activator of transcription 3 protein (STAT 3) and glutathione peroxidase (GPx) genes were assessed using real time reverse transcription polymerase chain reaction (RT-PCR) approach. EPG (10 μg/ml) showed the highest reduction in the LPS-induced NO production in RAW 264.7 macrophages and significantly suppressed (p < 0.05) the expression iNOS, STAT 3 and COX-2. There was a significant increase (p < 0.05) in combination of LPS and H 2 O 2 - induced iNOS production when compared to the LPS-induced iNOS production in RAW 264.7 macrophages and this concurred with the NO production which was attenuated by EPG at 10 μg/ml. A significant (p < 0.05) down regulation was observed in the combination of LPS and H 2 O 2 -induced iNOS and GPx expression by EPG. Our data suggest that the anti-inflammatory activity of EPG is mediated via the suppression of the STAT 3 and COX-2 pathways and can serve as potential endogenous antioxidant stimulant.

  1. Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit), and YKL-40

    Science.gov (United States)

    DAUGAARD, SØREN; CHRISTENSEN, LISE H; HØGDALL, ESTRID

    2009-01-01

    Chondroid tumors comprise a heterogenous group of benign to overt malignant neoplasms, which may be difficult to differentiate from one another by histological examination. A group of 43 such tumors was stained with nine relevant antibodies in an attempt to find consistent marker profile(s) for the different subgroups. Archival material from three extraskeletal myxoid chondrosarcomas, five chordomas, five chondromyxoid fibromas, five chondroblastomas and 25 chondrosarcomas was stained with antibodies against osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit) and YKL-40. All 25 chondrosarcomas showed a positive staining reaction for D2-40, none for actin and CD117, and a partial reactivity for bcl-2 (36%). Chondroblastomas (5/5) and chondromyxoid fibromas (2/5) were the only tumors with a positive reaction for actin, and all chondroblastomas (n=5) and extraskeletal myxoid chondrosarcomas (n=3) were positive for bcl-2. In contrast to all other tumors, two of three extraskeletal myxoid chondrosarcomas were also positive for CD17 and negative for osteonectin, cox-2, mdm-2 and actin. All five chordomas were negative for D2-40 and positive for mdm-2 and YKL-40. The diagnosis of chondrosarcoma may be aided by its positivity for D2-40 and YKL-40 and its lack of reactivity for actin and CD117. This should be seen in the light of no reaction for D2-40 in chordomas and a corresponding lack of reaction for osteonectin, cox-2, mdm-2 and actin in extraskeletal myxoid chondrosarcomas. A convincing immunoreactivity for calponin and/or actin in chondromyxoid fibromas and chondroblastomas may also be helpful in differentiating these tumors from chondrosarcomas. PMID:19594492

  2. MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

    Directory of Open Access Journals (Sweden)

    G. K. Chimal-Ramírez

    2013-01-01

    Full Text Available Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

  3. Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling.

    Science.gov (United States)

    Raj, Vinit; Bhadauria, Archana S; Singh, Ashok K; Kumar, Umesh; Rai, Amit; Keshari, Amit K; Kumar, Pranesh; Kumar, Dinesh; Maity, Biswanath; Nath, Sneha; Prakash, Anand; Ansari, Kausar M; Jat, Jawahar L; Saha, Sudipta

    2018-03-23

    We attempted a preclinical study using DMH-induced CRC rat model to evaluate the antitumor potential of our recently synthesized 1,3,4-thiadiazoles. The molecular insights were confirmed through ELISA, qRT-PCR and western blot analyses. The CRC condition was produced in response to COX-2 and IL-6 induced activation of JAK2/STAT3 which, in turn, was due to the enhanced phosphorylation of JAK2 and STAT3. The treatment with 1,3,4-thiadiazole derivatives (VR24 and VR27) caused the significant blockade of this signaling pathway. The behavior of STAT3 populations in response to IL-6 and COX-2 stimulations was further confirmed through data-based mathematical modeling using the quantitative western blot data. Finally, VR24 and VR27 restored the perturbed metabolites associated to DMH-induced CRC as evidenced through 1 H NMR based serum metabolomics. The tumor protecting ability of VR24 and VR27 was found comparable or to some degree better than the marketed chemotherapeutics, 5-flurouracil. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sakane, K.K. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Monteiro, C.J.; Silva, W.; Silva, A.R. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Santos, P.M. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Lima, K.F. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Moraes, K.C.M. [Instituto de Biociências, Departamento de Biologia, Universidade Estadual Paulista ‘‘Júlio de Mesquita Filho’’, Rio Claro, SP (Brazil)

    2013-11-29

    Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

  5. Aspectos biopsicosociales asociados al embarazo adolescente

    Directory of Open Access Journals (Sweden)

    Regina Cogollo Jiménez

    2012-12-01

    Full Text Available Introducción: El embarazo en la adolescencia, es un evento inesperado, sorpresivo. Este artículo establece la importancia de identificar los aspectos biopsicosociales asociados al embarazo adolescente en las embarazadas asistentes al programa de Control Prenatal de una Empresa Social del Estado de nivel 1 en Montería en 2009, para comprender las actitudes y los comportamientos asociados a esta etapa tan temprana. Materiales y Métodos: Es un estudio descriptivo, cuantitativo, de corte transversal. Población y muestra: 30 adolescentes embarazadas asistentes al Programa, el muestreo por conveniencia. Se utilizó la encuesta y la observación directa, previa autorización del Director de la empresa. Resultados: Caracterización de la población: predominó la edad de 15 a 19 años (adolescencia tardía, uniones libres, baja escolaridad debido a la deserción escolar, ingreso económico menor al salario mínimo legal vigente. Aspectos Biológicos: la menarquía a temprana edad (9 a 14 años, y en ella la mitad de los embarazos. La mayoría de los segundos embarazos terminaron en parto, la minoría en cesárea y aborto. La captación para los controles prenatales fue tardía, algunas no cumplieron con las citas programadas. Aspectos Psicológicos: inestabilidad con la pareja al enterarse del embarazo, tuvieron soporte familiar moral y económico, abandonaron sus estudios y presentaron malestares como estrés, depresión y tristeza. Aspectos Sociales: predominó la convivencia con la familia extensa. Hubo aceptación en el colegio y en los amigos. Discusión y Conclusiones: Se plantean estrategias para disminuir estos aspectos: elaboración de una cartilla sobre “Cuidado de la adolescente embarazada”, creación de espacios de reflexión, jornadas lúdicas educativas, entre otros. (Rev Cuid 2012; 3(3:385-93.Palabras clave: Embarazo en Adolescencia, Bienestar Materno, Atención Prenatal. (Fuente: De

  6. Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling.

    Directory of Open Access Journals (Sweden)

    Mei-Chi Chang

    Full Text Available Chewing of betel quid (BQ increases the risk of oral cancer and oral submucous fibrosis (OSF, possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa.Primary gingival keratinocytes (GK cells were exposed to areca nut (AN components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays.Areca nut extract (ANE stimulated PGE2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2, cytochrome P450 1A1 (CYP1A1 and hemeoxygenase-1 (HO-1, but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR, Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α-naphthoflavone (a CYP 1A1/1A2 inhibitor, PD153035 (EGFR inhibitor, pp2 (Src inhibitor, and manumycin A (a Ras inhibitor. ANE-induced PGE2 production was suppressed by piper betle leaf (PBL extract and hydroxychavicol (two major BQ components, dicoumarol (aQuinone Oxidoreductase--NQO1 inhibitor and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2α production.CYP4501A1, reactive oxygen species (ROS, EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response.

  7. In vitro antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone induced apoptosis against COLO320 cells through cytochrome c release caspase mediated pathway with PI3K/AKT and COX-2 inhibition.

    Science.gov (United States)

    Balachandran, C; Emi, N; Arun, Y; Yamamoto, N; Duraipandiyan, V; Inaguma, Yoko; Okamoto, Akinao; Ignacimuthu, S; Al-Dhabi, N A; Perumal, P T

    2016-04-05

    The present study investigated the anticancer activity of 2,3-dihydroxy-9,10-anthraquinone against different cancer cells such as MCF-7, COLO320, HepG-2, Skov-3, MOLM-14, NB-4, CEM, K562, Jurkat, HL-60, U937, IM-9 and Vero. 2,3-dihydroxy-9,10-anthraquinone showed good antiproliferative activity against COLO320 cells when compared to other tested cells. The cytotoxicity results showed 79.8% activity at the dose of 2.07 μM with IC50 value of 0.13 μM at 24 h in COLO320 cells. So we chose COLO320 cells for further anticancer studies. mRNA expression was confirmed by qPCR analysis using SYBR green method. Treatment with 2,3-dihydroxy-9,10-anthraquinone was found to trigger intrinsic apoptotic pathway as indicated by down regulation of Bcl-2, Bcl-xl; up regulation of Bim, Bax, Bad; release of cytochrome c and pro-caspases cleaving to caspases. Furthermore, 2,3-dihydroxy-9,10-anthraquinone stopped at G0/G1 phase with modulation in protein levels of cyclins. On the other hand PI3K/AKT signaling plays an important role in cell metabolism. We found that 2,3-dihydroxy-9,10-anthraquinone inhibits PI3K/AKT activity after treatment. Also, COX-2 enzyme plays a major role in colorectal cancer. Our results showed that the treatment significantly reduced COX-2 enzyme in COLO320 cells. These results indicated antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone involving apoptotic pathways, mitochondrial functions, cell cycle checkpoint and controlling the over expression genes during the colorectal cancer. Molecular docking studies showed that the compound bound stably to the active sites of Bcl-2, COX-2, PI3K and AKT. This is the first report of anticancer mechanism involving 2,3-dihydroxy-9,10-anthraquinone in COLO320 cells. The present results might provide helpful suggestions for the design of antitumor drugs toward colorectal cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Aspectos nutricionales de la anorexia nerviosa

    OpenAIRE

    Delgado Santirso, Pablo

    2017-01-01

    El estudio que se presentará en las siguientes líneas pretende la actualización de los datos sobre los aspectos nutricionales de uno de los principales Trastornos de la Conducta Alimentaria (TCA), la Anorexia Nerviosa (AN), así como aportar información acerca de sus características generales, etiopatogenia, evaluación y diagnóstico y tratamiento. Se centrará fundamentalmente en las medidas higiénico-dietéticas necesarias del tratamiento nutricional y en el establecimiento de la función del di...

  9. Aspectos éticos de la obesidad

    OpenAIRE

    de Santiago Martín, Sandra

    2016-01-01

    El sobrepeso y la obesidad se están convirtiendo en uno de los problemas de salud de mayor preocupación, convirtiéndose en los últimos años en una verdadera pandemia mundial. Los objetivos de esta revisión bibliográfica son analizar los aspectos éticos de la obesidad, desde el punto de vista de la familia y la sociedad, las buenas prácticas sanitarias, los principios bioéticos y de los derechos del paciente obeso. Para realizar este trabajo de investigación se accedieron a las bases de ...

  10. Contenedores: Aspectos tecnicos, biologicos y economicos

    Science.gov (United States)

    Tara Luna; Thomas D. Landis; R. Kasten Dumroese

    2012-01-01

    La elección del contenedor es una de las consideraciones más importantes al establecer un nuevo vivero o empezar a producir una especie nueva. El tipo y tamaño de contenedor no sólo determina la cantidad de agua y nutrientes minerales que están disponibles para el crecimiento de una planta, sino que también afecta otros aspectos operativos del vivero, como el tamaño de...

  11. Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit), and YKL-40

    DEFF Research Database (Denmark)

    Daugaard, Søren; Christensen, Lise H; Høgdall, Estrid

    2009-01-01

    (s) for the different subgroups. Archival material from three extraskeletal myxoid chondrosarcomas, five chordomas, five chondromyxoid fibromas, five chondroblastomas and 25 chondrosarcomas was stained with antibodies against osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit) and YKL......-40. All 25 chondrosarcomas showed a positive staining reaction for D2-40, none for actin and CD117, and a partial reactivity for bcl-2 (36%). Chondroblastomas (5/5) and chondromyxoid fibromas (2/5) were the only tumors with a positive reaction for actin, and all chondroblastomas (n=5...... chondrosarcomas. A convincing immunoreactivity for calponin and/or actin in chondromyxoid fibromas and chondroblastomas may also be helpful in differentiating these tumors from chondrosarcomas....

  12. Criptococose pulmonar: aspectos na tomografia computadorizada

    Directory of Open Access Journals (Sweden)

    Silva Ana Carina Gamboa da

    2003-01-01

    Full Text Available A criptococose pulmonar é uma doença causada pelo Criptococcus neoformans, um fungo unimórfico que possui distribuição mundial, existindo na mesma forma tanto no seu habitat natural quanto em animais e humanos. A doença possui apresentações clínica e patológica variáveis e pode manifestar-se tanto em pacientes com a imunidade normal como em imunocomprometidos, que representam a maioria dos casos. Neste trabalho são analisados os aspectos encontrados nas tomografias computadorizadas do tórax de 14 pacientes com criptococose pulmonar confirmada. Os achados mais freqüentes na tomografia do tórax foram as massas e os nódulos pulmonares. Outros aspectos observados foram as áreas de escavação, as consolidações, o espessamento do interstício peribroncovascular e o reticulado difuso. Massa pulmonar foi o achado isolado mais comum (64,2%, seguido dos nódulos isolados ou múltiplos (35,7%. Doença pulmonar difusa foi vista em apenas 14,2% dos casos. Os lobos superiores foram os mais comprometidos, sendo a doença mais comum nas regiões anteriores. A tomografia do tórax permitiu avaliar com precisão o grau de comprometimento do parênquima pulmonar.

  13. Randomized controlled trials of COX-2 inhibitors

    DEFF Research Database (Denmark)

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

    2011-01-01

    trials after the 2004 market withdrawal of rofecoxib were excluded. RESULTS: Median defined daily dose (DDD) of celecoxib (2.00) was higher than the median DDD of rofecoxib (1.00; p ... celecoxib after the withdrawal of rofecoxib because the overall median DDD of celecoxib was substantially higher than the median DDD of rofecoxib, while non-selective NSAID DDDs were comparable....

  14. Aspectos puntuales del estado vegetativo persistente

    OpenAIRE

    Hodelín Tablada, Ricardo

    2013-01-01

    El estado vegetativo persistente es una condición clínica caracterizada por la ausencia completa de conciencia sobre uno mismo y el entorno, unido a ciclos de sueño-vigilia, con preservación total o parcial de las funciones hipotalámicas y autonómicas del tallo encefálico. En el presente artículo, el autor discute aspectos puntuales sobre la entidad clínica, basado en su experiencia y en la revisión de la bibliografía sobre el tema; igualmente se exponen elementos clínicos y epidemiológicos d...

  15. LABORATORIO DE HORMONAS: ASPECTOS PRÁCTICOS

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    René E. Díaz T., DR.

    2015-11-01

    Full Text Available Las técnicas de laboratorio de análisis hormonales han experimentado grandes progresos en las últimas décadas, actualmente se pueden realizar determinaciones hormonales con gran precisión y automatización, sin embargo, existen muchos elementos que es necesario tener en consideración al momento de interpretar un examen hormonal. El elegir el examen adecuado para la condición que estamos estudiando, el conocer sus limitaciones y potenciales falsos positivos y negativos es parte del conocimiento que es fundamental tener como clínicos. En este artículo se pretende entregar una breve revisión de las principales determinaciones hormonales, orientado a aspectos que puedan ser de utilidad al médico no especialista en su práctica clínica.

  16. Interactions between diet, lifestyle and IL10, IL1B, and PTGS2/COX-2 gene polymorphisms in relation to risk of colorectal cancer in a prospective Danish case-cohort study.

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    Full Text Available BACKGROUND & AIMS: Diet contributes to colorectal cancer development and may be potentially modified. We wanted to identify the biological mechanisms underlying colorectal carcinogenesis by assessment of diet-gene interactions. METHODS: The polymorphisms IL10 C-592A (rs1800872, C-rs3024505-T, IL1b C-3737T (rs4848306, G-1464C (rs1143623, T-31C (rs1143627 and PTGS2 (encoding COX-2 A-1195G (rs689466, G-765C (rs20417, and T8473C (rs5275 were assessed in relation to risk of colorectal cancer (CRC and interaction with diet (red meat, fish, fibre, cereals, fruit and vegetables and lifestyle (non-steroid-anti-inflammatory drug use and smoking status was assessed in a nested case-cohort study of nine hundred and seventy CRC cases and 1789 randomly selected participants from a prospective study of 57,053 persons. RESULTS: IL1b C-3737T, G-1464C and PTGS2 T8473C variant genotypes were associated with risk of CRC compared to the homozygous wildtype genotype (IRR=0.81, 95%CI: 0.68-0.97, p=0.02, and IRR=1.22, 95%CI: 1.04-1.44, p=0.02, IRR=0.75, 95%CI: 0.57-0.99, p=0.04, respectively. Interactions were found between diet and IL10 rs3024505 (P-value for interaction (P(int; meat=0.04, fish=0.007, fibre=0.0008, vegetables=0.0005, C-592A (P(int; fibre=0.025, IL1b C-3737T (Pint; vegetables=0.030, NSAID use=0.040 and PTGS2 genotypes G-765C (P(int; meat=0.006, fibre=0.0003, fruit 0.004, and T8473C (P(int; meat 0.049, fruit=0.03 and A-1195G (P(int; meat 0.038, fibre 0.040, fruit=0.059, vegetables=0.025, and current smoking=0.046. CONCLUSIONS: Genetically determined low COX-2 and high IL-1β activity were associated with increased risk of CRC in this northern Caucasian cohort. Furthermore, interactions were found between IL10, IL1b, and PTGS2 and diet and lifestyle factors in relation to CRC. The present study demonstrates that gene-environment interactions may identify genes and environmental factors involved in colorectal carcinogenesis.

  17. Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

    Directory of Open Access Journals (Sweden)

    Cristina Mihaela Ghiciuc

    2017-11-01

    Full Text Available Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI and sodium form (NaCLI—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2 and cyclooxygenase 2 (cox-2 protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems.

  18. Toxicologia do tolueno: aspectos relacionados ao abuso

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    Forster Letícia M.K.

    1994-01-01

    Full Text Available O tolueno está presente em muitos produtos de uso doméstico e industrial e é o principal solvente envolvido no abuso de substâncias e na exposição ocupacional. O problema mais grave no estudo de patologias relacionadas ao tolueno é que este está geralmente associado, em suas preparações comerciais, a outras substâncias. O potencial tóxico do tolueno foi abordado nos seguintes aspectos: parâmetros farmacológicos; características físico-químicas; exposição; estudos clínicos; diagnóstico; pesquisa experimental; tolerância e dependência; efeitos agudos e crônicos; neurotoxicidade; teratogenicidade; doenças psiquiátricas; carcinogenicidade e tratamento. Conclui-se ser de grande importância e urgência que se realizem estudos clínicos com amostras maiores para definição mais precisa das conseqüências do uso crônico

  19. Toxicologia do tolueno: aspectos relacionados ao abuso

    Directory of Open Access Journals (Sweden)

    Letícia M.K. Forster

    1994-04-01

    Full Text Available O tolueno está presente em muitos produtos de uso doméstico e industrial e é o principal solvente envolvido no abuso de substâncias e na exposição ocupacional. O problema mais grave no estudo de patologias relacionadas ao tolueno é que este está geralmente associado, em suas preparações comerciais, a outras substâncias. O potencial tóxico do tolueno foi abordado nos seguintes aspectos: parâmetros farmacológicos; características físico-químicas; exposição; estudos clínicos; diagnóstico; pesquisa experimental; tolerância e dependência; efeitos agudos e crônicos; neurotoxicidade; teratogenicidade; doenças psiquiátricas; carcinogenicidade e tratamento. Conclui-se ser de grande importância e urgência que se realizem estudos clínicos com amostras maiores para definição mais precisa das conseqüências do uso crônico

  20. ASPECTOS FINANCIEROS DE LA REFORMA LOCAL

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    Amable Corcuera Torres

    2015-01-01

    Full Text Available En este trabajo se analizan los aspectos jurídico-financieros más relevantes que incluye la Ley 27/2013, de 27 de diciembre, de racionalización y sostenibilidad de la Administración Local. Las nuevas medidas incluidas en la citada Ley afectan tanto a los ingresos de los entes locales como a sus gastos. Al respecto, se abordan cuestiones relativas a los efectos económicos de la fusión de municipios, la supresión general de licencias, el contenido de los planes económico-financieros, el cálculo del coste efectivo de los servicios, el redimensionamiento del sector público local, la novedosa atribución a la Junta de Gobierno Local de la competencia para aprobar ciertos actos financieros, la disolución de entidades de ámbito territorial inferior al Municipio que no presenten sus cuentas antes de 31 de diciembre de 2014 o la posibilidad de reducir la deuda comercial o financiera a través de la venta de patrimonio público del suelo. In this work the most important legal and financial aspects including the Law 27/2013, of 27 December, rationalization and sustainability of local government are analyzed. The new measures included in that Act affect both the income of local authorities and their expenses. In this regard, issues concerning the economic effects of the merger of municipalities, the general abolition of licenses, the content of financial plans, the calculation of the actual cost of services, the local public sector downsizing, the novel addresses allocation to the Local Government of the power to grant certain financial actions, the dissolution of entities below the Municipality territory who do not submit their accounts before December 31, 2014 or the possibility of reducing the commercial or financial debt through the sale of public land heritage.

  1. Biphasic Modulation of NOS Expression, Protein and Nitrite Products by Hydroxocobalamin Underlies Its Protective Effect in Endotoxemic Shock: Downstream Regulation of COX-2, IL-1β, TNF-α, IL-6, and HMGB1 Expression

    Science.gov (United States)

    Sampaio, André L. F.; Dalli, Jesmond; Brancaleone, Vincenzo; D'Acquisto, Fulvio; Perretti, Mauro; Wheatley, Carmen

    2013-01-01

    Background. NOS/•NO inhibitors are potential therapeutics for sepsis, yet they increase clinical mortality. However, there has been no in vivo investigation of the (in vitro) •NO scavenger, cobalamin's (Cbl) endogenous effects on NOS/•NO/inflammatory mediators during the immune response to sepsis. Methods. We used quantitative polymerase chain reaction (qPCR), ELISA, Western blot, and NOS Griess assays, in a C57BL/6 mouse, acute endotoxaemia model. Results. During the immune response, pro-inflammatory phase, parenteral hydroxocobalamin (HOCbl) treatment partially inhibits hepatic, but not lung, iNOS mRNA and promotes lung eNOS mRNA, but attenuates the LPS hepatic rise in eNOS mRNA, whilst paradoxically promoting high iNOS/eNOS protein translation, but relatively moderate •NO production. HOCbl/NOS/•NO regulation is reciprocally associated with lower 4 h expression of TNF-α, IL-1β, COX-2, and lower circulating TNF-α, but not IL-6. In resolution, 24 h after LPS, HOCbl completely abrogates a major late mediator of sepsis mortality, high mobility group box 1 (HMGB1) mRNA, inhibits iNOS mRNA, and attenuates LPS-induced hepatic inhibition of eNOS mRNA, whilst showing increased, but still moderate, NOS activity, relative to LPS only. experiments (LPS+D-Galactosamine) HOCbl afforded significant, dose-dependent protection in mice Conclusions. HOCbl produces a complex, time- and organ-dependent, selective regulation of NOS/•NO during endotoxaemia, corollary regulation of downstream inflammatory mediators, and increased survival. This merits clinical evaluation. PMID:23781123

  2. Purification of a peptide from seahorse, that inhibits TPA-induced MMP, iNOS and COX-2 expression through MAPK and NF-kappaB activation, and induces human osteoblastic and chondrocytic differentiation.

    Science.gov (United States)

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Se-Kwon

    2010-03-30

    Ongoing efforts to search for naturally occurring, bioactive substances for the amelioration of arthritis have led to the discovery of natural products with substantial bioactive properties. The seahorse (Hippocampus kuda Bleeler), a telelost fish, is one source of known beneficial products, yet has not been utilized for arthritis research. In the present work, we have purified and characterized a bioactive peptide from seahorse hydrolysis. Among the hydrolysates tested, pronase E-derived hydrolysate exhibited the highest alkaline phosphatase (ALP) activity, a phenotype marker of osteoblast and chondrocyte differentiation. After its separation from the hydrolysate by several purification steps, the peptide responsible for the ALP activity was isolated and its sequence was identified as LEDPFDKDDWDNWK (1821Da). We have shown that the isolated peptide induces differentiation of osteoblastic MG-63 and chondrocytic SW-1353 cells by measuring ALP activity, mineralization and collagen synthesis. Our results indicate that the peptide acts during early to late stages of differentiation in MG-63 and SW-1353 cells. We also assessed the concentration dependence of the peptide's inhibition of MMP (-1, -3 and -13), iNOS and COX-2 expression after treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), a common form of phorbol ester. The peptide also inhibited NO production in MG-63 and SW-1353 cells. To elucidate the mechanisms by which the peptide acted, we examined its effects on TPA-induced MAPKs/NF-kappaB activation and determined that the peptide treatment significantly reduced p38 kinase/NF-kappaB in MG-63 cells and MAPKs/NF-kappaB in SW-1353 cells.

  3. Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats.

    Science.gov (United States)

    Tabassum, Rizwana; Vaibhav, Kumar; Shrivastava, Pallavi; Khan, Andleeb; Ahmed, Mohd Ejaz; Ashafaq, Mohammad; Khan, M Badruzzaman; Islam, Farah; Safhi, Mohammed M; Islam, Fakhrul

    2015-01-15

    Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia-reperfusion (I-R) injury, this study was designed to elucidate the potential effects of PA against I-R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2h followed by 22h reperfusion in Wistar male rats (250-280g, 14-16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I-R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1β, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I-R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Aspectos nutricionais e ambientais da obesidade canina

    Directory of Open Access Journals (Sweden)

    Karina Preising Aptekmann

    2014-11-01

    Full Text Available A obesidade é a doença nutricional mais frequente em cães, leva a uma série de alterações nas funções corporais e limita a longevidade dos animais. Vários fatores contribuem para o desenvolvimento da obesidade em cães, como genética, raça, idade, falta de atividade física, composição calórica dos alimentos, tipo e a forma de alimentação, distúrbios hormonais, medicamentos e fatores relacionados com os proprietários. Devido à falta de estudos sobre os aspectos nutricionais e ambientais envolvidos no desenvolvimento da obesidade canina, o presente trabalho objetivou obter estas informações por meio de enquetes a proprietários. Foram realizadas 254 entrevistas com proprietários de cães com sobrepeso ou obesos, atendidos em Hospitais Veterinários Universitários. Selecionaram-se cães com escore de condição corporal (ECC de 6 a 9, de acordo com escala descrita por LAFLAMME (1997. A maioria dos cães acometidos eram fêmeas adultas castradas, sem raça definida (33% ou Poodles (17%. De acordo com 36% dos respondentes, o excesso de alimento era a possível razão do ganho de peso dos animais. Apenas 52% dos proprietários tentaram realizar controle de peso do seu animal, principalmente reduzindo a quantidade de alimento. Não houve correlação entre a condição corporal do proprietário, nível de escolaridade, renda familiar e ambiente domiciliar dos proprietários com o ECC dos animais. As informações obtidas podem auxiliar na identificação dos fatores nutricionais e ambientais envolvidos no desenvolvimento da obesidade em cães, podendo adotar medidas preventivas e desenvolver melhores estratégias para o tratamento

  5. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade

    Energy Technology Data Exchange (ETDEWEB)

    El-Gowelli, Hanan M., E-mail: dr_Hanan_el_gowali@hotmail.com; Saad, Evan I.; Abdel-Galil, Abdel-Galil A.; Ibrahim, Einas R.

    2015-11-01

    cyclosporine in protection against colitis. • Lipoic acid elevates colon antioxidant defensive mechanism and reduces inflammation. • Co-administration of lipoic acid and cyclosporine aggravates colon damage. • NO/COX-2/miR-210 elevations mediate cyclosporine–lipoic acid interaction.

  6. Aspectos nutricionales del búfalo

    Directory of Open Access Journals (Sweden)

    André Mendes Jorge

    2011-11-01

    necesario para mantener al animal en un estado saludable donde puedan expresar su potencial reproductivo de acuerdo con el nivel de producción deseado en condiciones específicas de ambientales y de alimentación (Paul & Lal, 2010. El presente texto fue escrito con la intención de abordar algunos aspectos nutricionales del búfalo, exponiendo lo más actual sobre el tema y de esa forma aclarar las posibles dudas sobre las normas de alimentación para esta especie.

  7. Aspectos del dengue investigados en Santander

    Directory of Open Access Journals (Sweden)

    Ruth Martínez

    2004-03-01

    Full Text Available

    Entre 1998 y 2003 se registraron en Colombia 256,831 casos de dengue (22,834 de dengue hemorrágico DH de los cuales 41,325 (36% fueron en Santander (3,265 DH (1,2. En este período ocurrieron brotes en 1998 y 2001 observándose incremento de casos severos en el segundo (2. Por otro lado, existen inconvenientes con el diagnóstico que dificultan el manejo clínico oportuno y la vigilancia epidemiológica. Como consecuencia, los siguientes aspectos han sido investigados:

    1 Contribución de la circulación de los serotipos/genotipos al incremento del dengue hemorrágico, considerando que la entrada o emergencia de éstos se han asociado con epidemias (3. Entre 1998 y 2004 se hicieron 1,180 intentos de aislamiento viral en células C6/36 (4, detectándose los 4 serotipos. El DEN-2 se aisló todos los años con mayor frecuencia durante los brotes (43% y 40% de los cepas; el DEN-1 se detectó entre 1998 y 2001, siendo el prevalente en el primer brote (57%, pero el menos en el segundo (4%; el DEN-3 se detectó en el brote del 2001 con similar frecuencia al DEN-2 (36%, por primera vez en Colombia luego de 23 años ausente, y fue el prevalerte entre 2002-2004 (92% de los aislados, aunque en estos años no se reportó incremento del DH (2; el DEN-4 se aisló solo en el 2000 (27% y en el brote del 2001 (20%. El genotipo de cada serotipo se identificó por análisis de RSS-PCR (5,6. Se encontraron el subtipo A (ó III, C (ó I y B (ó II de los serotipos 2, 1 y 4, similares a los que están circulando en países de América y oriundos del Asia. Los DEN-3 fueron del subtipo C (ó III iguales al virus que entró en América en 1994 oriundo de Sri-Lanka, India. Los genotipos del 2 y 3 encontrados en Santander producen con mayor frecuencia DH (3,7.

    ASPECTOS ERGONÔMICOS E POSTURAIS EM CENTRO DE MATERIAL

    Directory of Open Access Journals (Sweden)

    Neusa Maria Cosía Alexandre

    Full Text Available Determinados fatores ambientais inadequados podem provocar lesões na coluna vertebral. Este trabalho discute certos aspectos ergonômicos e posturais específicos em Centro de Material com o objetivo de desenvolver uma consciência crítica a respeito dos efeitos do local de trabalho sobre a saúde.

  8. Meningites bacterianas no lactente aspectos neurológicos

    Directory of Open Access Journals (Sweden)

    M. Valeriana L. de Moura-Ribeiro

    1990-06-01

    Full Text Available Aspectos clínicos, neurológicos e laboratoriais das meningites bacterianas agudas no lactente são criticamente analisados em função da experiência da autora. São apresentadas considerações fisiopatológicas sobre os eventos que ocorrem na fase aguda desses processos.

  9. Presentación del Libro, “Epilepsia. Aspectos Clínicos y Psicosociales”.

    Directory of Open Access Journals (Sweden)

    Carlos Medina Malo

    2006-12-01

    aspectos biológicos. Es excelente porque muestra el equipo que reunió el Dr. Medina, a los integrantes de la Liga contra la Epilepsia, que se ve reflejada en ese aspecto biopsicosocial de la persona con epilepsia.

  10. Aspectos sociotécnicos das TI & Relacionamento Humano & Sinergia

    Directory of Open Access Journals (Sweden)

    Sergio Vieira Holtz Filho

    2008-06-01

    Full Text Available As Tecnologias de Informação (TI estão entre os principais agentes de mudança sociais. Para gerir tais mudanças, uma miríade de áreas do conhecimento humano têm muito a contribuir para a abordagem dos aspectos sociotécnicos das TI e promover sinergia. Como uma organização empresarial atua no sentido de provocar mudanças no comportamento das pessoas, visando a melhoria contínua, esse processo de mudança provocada chama-se aprendizagem. Isto posto, neste artigo apresentaremos resultados observados em empresas em processo de reengenharia e submetidas a utilização de metodologias integradas (PDCA, Método Paulo Freire e Roteiro Integração de Equipes, abordando os aspectos sociotécnicos das TI & relacionamentos humanos pela praxe da pedagogia como elemento de sinergia.

  11. Aspectos de regulación sanitaria en Brasil

    Directory of Open Access Journals (Sweden)

    Jose Carlos Buzanello

    2016-06-01

    Full Text Available Mira a algunos aspectos de la regulación de los servicios de saneamiento en Brasil, específicamente la política de regulación resultante del proceso de reforma del Estado de 1995. Cuestiona los resultados de la productividad de los servicios de agua y alcantarillado de los concesionarios y el alcance de estas medidas al consumismo usuario.

  12. Responsabilidad de directores de sociedades en Estados Unidos. Aspectos procesales

    Directory of Open Access Journals (Sweden)

    Héctor José Miguens

    2015-01-01

    El objeto de este artículo es describir este régimen en su totalidad y realizar un juicio crítico de las normas que rigen las acciones procesales de la responsabilidad de los directores de sociedades comerciales en el derecho societario en Estados Unidos. La metodología utilizada en este trabajo responde a la sistemática de los autores norteamericanos citados, que se caracteriza por centrarse en los aspectos prácticos, la solución de problemas particulares y el comentario crítico de la jurisprudencia aplicable a la cuestión.

  13. Tabaco y salud infantil: un aspecto no suficientemente valorado

    OpenAIRE

    Rubio, Ivonne; Kanopa, Virginia

    2015-01-01

    La campaña que se desarrolla en Uruguay contra el consumo de tabaco enfatiza sobre los efectos nocivos que produce el cigarrillo en la salud de la población adulta que fuma y en fumadores pasivos. La disminución de afecciones cardiovasculares como el infarto de miocardio y del cáncer de pulmón ha mostrado resultados alentadores en relación a la disminución del número de consumidores, si bien aún no se ha logrado el descenso esperado. La campaña enfoca varios aspectos dirigidos a la presentaci...

  14. Linguagem e aspectos visuo-espaciais : uma abordagem neurolinguistica

    OpenAIRE

    Carla Queiroz Pereira

    2006-01-01

    Resumo: O objetivo deste trabalho de pesquisa é investigar como o sujeito JS - não afásico após sofrer três acidentes vasculares cerebrais isquêmicos (AVCi?s) que lesionaram regiões parieto-occipitais de ambos os hemisférios cerebrais - realiza determinadas atividades lingüístico-cognitivas que envolvem aspectos vísuo-espaciais relacionados ao corpo, à escrita, à leitura de textos e de horas. Com base na Neurolingüística discursivamente orientada, na Neuropsicologia luriana e nas bases biológ...

  15. La obesidad: aspectos psicológicos y conductuales

    OpenAIRE

    Bersh, Sonia

    2006-01-01

    Introducción: La obesidad es un problema médico de creciente gravedad por su morbilidad y su alta y creciente prevalencia. Objetivo: Realizar una revisión actualizada acerca de la obesidad y su tratamiento, con énfasis en los aspectos de mayor interés para la práctica psiquiátrica. Resultados: La obesidad es una enfermedad crónica de difícil manejo y alta tasa de recurrencia, que se asocia con complicaciones médicas graves. Los factores psicológicos y conductuales son muy relevantes en el cur...

  16. ASPECTOS BASICOS DEL DERECHO ADUANERO PARA ESTUDIANTES DE PREGRADO

    OpenAIRE

    Castro Rangel, Jesus David; Garcia Vargas, Kristhell; Sepulveda Mora, Myriam

    2008-01-01

    La presente investigación comprende un estudio en un grado fundamental y a nivel general del Derecho Aduanero y una herramienta pedagógica dirigida a facilitar, a los alumnos de Pregrado de la Universidad Libre de Cúcuta, el entendimiento y aprendizaje de los aspectos básicos del Derecho Aduanero, teniendo en cuenta que Cúcuta es una zona fronteriza. El estudiante a través del presente trabajo encontrará las herramientas que le permitirán ubicarse dentro del contexto aduanero y...

  17. Aspectos prosódicos da fala de sujeitos parkinsonianos

    Directory of Open Access Journals (Sweden)

    Lourenço Chacon

    2001-02-01

    Full Text Available

    Problemas de prosódia na fala de parkinsonianos têm sido apontados nos estudos sobre parkinsonismo. Contudo, nesses estudos a prosódia é freqüentemente desvinculada dos fatores comunicativos da fala. O propósito deste artigo foi investigar fatores comunicativos relacionados a aspectos prosódicos da fala de sujeitos com doença de Parkinson. As amostras 'de fala foram extraídas de conversas espontâneas de dois sujeitos parkinsonianos, do sexo masculino. A análise mostrou que os elementos prosódicos ocorreram em diversas combinações, possibilitando a identificação de: a atos de fala; b alguns aspectos da organização conversacional; e c diferentes vozes no discurso. Foram destacadas algumas implicações desses resultados para uma melhor compreensão da atividade verbal em condições patológicas, bem como para avaliação, diagnóstico e terapia de parkinsonianos.

  18. ALGUNOS ASPECTOS A CONSIDERAR SOBRE LA SEXUALIDAD DEL ADULTO MAYOR

    Directory of Open Access Journals (Sweden)

    Zoila Edith Hernández Zamora

    2008-12-01

    Full Text Available La presente investigación expone, a partir de una serie de entrevistas realizadas a una muestra de adultos mayores, aspectos relativos a la satisfacción general en la vida, así como las actitudes, conocimientos y prácticas de la sexualidad de un grupo de adultos mayores que asisten regularmente a una estancia diurna de la ciudad de Xalapa, Veracruz, México, misma que fue diseñada especialmente para este grupo etario. Se encontraron diferencias estadísticamente significativas entre la actitud hacia el ejercicio de la sexualidad de las personas mayores entre los hombres y las mujeres de la muestra, y entre .las personas que tienen pareja con relación a las que no tienen; así como que hay una diferencia estadísticamente significativa entre aquellas personas que tiene una o ninguna enfermedad y las que tienen dos o más enfermedades con respecto a su frecuencia de actividad sexual. Es de resaltar la escasez de conocimientos sobre aspectos básicos de la sexualidad que poseen estas personas mayores, lo que hace necesario el establecimiento de programas educativos que incluyan al personal de salud y a los mismos senectos.

  19. Ethyl acetate extract from Asparagus cochinchinensis exerts anti-inflammatory effects in LPS-stimulated RAW264.7 macrophage cells by regulating COX-2/iNOS, inflammatory cytokine expression, MAP kinase pathways, the cell cycle and anti-oxidant activity

    Science.gov (United States)

    Lee, Hyun Ah; Koh, Eun Kyoung; Sung, Ji Eun; Kim, Ji Eun; Song, Sung Hwa; Kim, Dong Seob; Son, Hong Joo; Lee, Chung Yeoul; Lee, Hee Seob; Bae, Chang Joon; Hwang, Dae Youn

    2017-01-01

    Asparagus cochinchinesis (A. cochinchinesis) is a medicine traditionally used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although numerous studies of the anti-inflammatory effects of A. cochinchinesis have been conducted, the underlying mechanisms of such effects in macrophages remain to be demonstrated. To investigate the mechanism of suppressive effects on the inflammatory response in macrophages, alterations of the nitric oxide (NO) level, the cell viability, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels, inflammatory cytokine expression, the mitogen-activated protein kinase (MAPK) signaling pathway, cell cycle arrest and reactive oxygen species (ROS) levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following treatment with ethyl acetate extract from A. cochinchinesis root (EaEAC). RAW264.7 cells pretreated two different concentrations of EaEAC prior to LPS treatment exhibited no significant toxicity. The concentration of NO was significantly decreased in the EaEAC + LPS treated group compared with the vehicle + LPS treated group. A similar decrease in mRNA transcript level of COX-2, iNOS, pro-inflammatory cytokines [tumor necrosis factor-α and interleukin (IL)-1β] and anti-inflammatory cytokines (IL-6 and IL-10) was detected in the EaEAC + LPS treated group compared with the vehicle + LPS treated group, although the decrease rate varied. Enhancement of the phosphorylation of MAPK family members following LPS treatment was partially rescued in the EaEAC pretreated group, and the cell cycle was arrested at the G2/M phase. Furthermore, the EaEAC pretreated group exhibited a reduced level of ROS generation compared with the vehicle + LPS treated group. Taken together, these results suggest that EaEAC suppresses inflammatory responses through inhibition of NO production, COX-2 expression and ROS production, as well as

  1. Jeroky Mbaekua - aspectos da etnoarte indígena.

    Directory of Open Access Journals (Sweden)

    Oseias de Oliveira

    2015-06-01

    Full Text Available A idéia de arte compartilhada na cultura ocidental tradicionalmente tem sido entendida a partir de elementos conceituais e categorizações que não podem ser aplicados na cultura indígena. Assim, considerar a arte indígena significa observar sua complexidade, de forma a perpassar todas as instâncias da vida desses sujeitos. Desta forma, o texto busca discutir aspectos da etnoarte indígena que não é focada em uma noção de arte centralizada e homogeneizadora mas, sim atenta à uma perspectiva que busca contemplar melhor o seu modo de construção de símbolos, significados e representações culturais.

  2. Aspectos sociopsicológicos del climaterio y la menopausia

    Directory of Open Access Journals (Sweden)

    Dayana Couto Núñez

    2014-10-01

    Full Text Available El climaterio y la menopausia adquieren mayor trascendencia con el transcurso del tiempo. Al respecto, el concepto de calidad de vida se ha ido convirtiendo en un aspecto importante cuando la mujer climatérica se presenta ante el especialista, en busca de un mayor bienestar posible. En la edad mediana, el organismo se torna más frágil como consecuencia de las variaciones fisiológicas naturales del climaterio y la repercusión del contexto social sobre la persona, cuya sobrecarga física y mental favorece la aparición de procesos que deterioran la salud femenina y hacen más crítico el cuadro sintomático en este período, todo lo cual puede agravarse si existen un trastorno psicogénico previo y algunos elementos desfavorables del medio circundante

  3. Aspectos legales al utilizar las principales redes sociales en Colombia

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    Manuel Adolfo Alvarado Carmona

    2017-01-01

    Full Text Available Se analizaron los aspectos legales al utilizar las dos principales redes sociales en Colombia como los son facebook y twitter. Cuando un usuario se conecta a cualquiera de las redes sociales debe hacerlo de forma responsable porque de lo contrario puede incurrir en la violación de la normatividad Colombiana en la cual se encuentran los delitos informáticos, la protección de la información y los datos, injuria y calumnia, ciberacoso y derechos de autor. Se determinaron los problemas que conllevan cuando no se utiliza bien la información en las redes sociales en el ámbito jurídico.

  4. La Entomofagia en México. Algunos aspectos culturales

    Directory of Open Access Journals (Sweden)

    Felipe Carlos Viesca González

    2009-01-01

    Full Text Available En este trabajo se abordan aspectos culturales del consumo de insectos con fines alimenticios en México y el mundo; particularmente se analiza la entomofagia en la época prehispánica y nuestros días, así como las causas por las cuales ha disminuido el consumo de estos artrópodos. Se explica porqué se ha creado una aversión hacia los insectos en diversos países y algunas regiones de México. Se reflexiona acerca del valor nutritivo de los insectos y las distintas culturas que han hecho posible que sobreviva esta práctica culinaria en el centro y sur del territorio nacional, algunas formas de preparar platillos basados en insectos, así como los problemas que enfrenta actualmente esta costumbre alimenticia entre los mexicanos y sus perspectivas.

  5. Aspectos Comportamentais no Julgamento Profissional dos Auditores Independentes

    Directory of Open Access Journals (Sweden)

    José Emerson Firmino

    2013-12-01

    Full Text Available Alguns estudos evidenciam que a adoção das International Financial Reporting Standards (IFRS proporcionou melhorias na qualidade das informações contábeis. Mas, o conjunto de Procedimentos descritos nas IFRSs é fortemente afetado pelo julgamento profissional dos contadores. O mesmo fato ocorre com o auditor, que deve avaliar se a aplicação das normas resulta em fair presentation. Esse julgamento dependerá da interpretação do auditor sobre o nível de probabilidade associada a determinadas expressões presentes no texto das normas contábeis. Alguns autores evidenciam que existem diferenças significativas na interpretação das expressões verbais de probabilidade entre os auditores e que aspectos comportamentais estão influenciando a emissão do parecer de auditoria. Diante desse cenário, o objetivo deste estudo foi investigar como se comportam os auditores no julgamento de situações subjetivas, inseridos em um cenário pessimista ou otimista, no momento da avaliação dos critérios de reconhecimento e/ou mensuração, quando da execução dos trabalhos da auditoria. A amostra desta pesquisa é composta por 258 auditores independentes com registro de responsáveis técnicos junto à Comissão de Valores Mobiliários (CVM. Os resultados obtidos, por intermédio da análise das respostas dos auditores para situações subjetivas, sugerem que o julgamento do auditor em situações de subjetividade é influenciado por aspectos comportamentais, sendo que eles podem apresentar opiniões distintas em seus relatórios.

  6. Increased COX-2 expression in patients with ovarian cancer

    African Journals Online (AJOL)

    ajl yemi

    2011-10-26

    Oct 26, 2011 ... 10%) subtypes (Kristensen et al., 2003; Green et al.,. 1999). The disease ... history of ovarian and/or breast cancer, and nulliparity, whereas the oral ... and molecular mechanisms of ovarian cancer remain unclear. It is most ..... chemotherapy on the prognosis in advanced epithelial ovarian cancer. N. Engl.

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

    Science.gov (United States)

    2013-10-01

    consideration) APPENDICES: Manuscript under final consideration-conditional accepted. ( pdf file is attached) Chenggang Li*, Po-Shun Lee*, Yang...levels of PGE2 causes enhanced aromatase expression and local estradiol production in breast tissue (Subbaramaiah et al.). However, the relationship...Goat Anti- Rabbit IgG (H+L) antibody (Invitrogen). Metabolomic profiling. 100 µg of frozen biopsy tissue was submitted to Metabolon, Inc. (Durham, NC

  8. Relacionamentos de Marketing em Empresas Varejistas: Aspectos Positivos e Negativos

    Directory of Open Access Journals (Sweden)

    Cléria Donizete da Silva Lourenço

    2013-09-01

    Full Text Available O objetivo deste trabalho é compreender as relações de trocas comerciais sob a ótica dos clientes, funcionários e proprietários de empresas varejistas. A pesquisa, de natureza qualitativa, foi feita utilizando-se como método a etnografia. Os dados foram coletados em cinco empresas varejistas de um município de pequeno porte no Sul de Minas Gerais – um supermercado, uma farmácia, uma panificadora, um posto de combustíveis e uma loja de hortifrutigranjeiros – durante o período de um ano (dez/2008 a dez/2009. A observação participante e a entrevista em profundidade foram utilizadas como técnicas de coleta de dados. Para tratamento dos mesmos, utilizou-se a análise de conteúdo. Por meio da análise empreendida, identificou-se que os relacionamentos de marketing são compostos tanto por aspectos positivos quanto negativos. Contudo, os aspectos positivos são predominantes, especialmente pelo fato de que o cultivo de relacionamentos nas empresas varejistas analisadas é uma ocorrência natural, podendo, portanto, ser caracterizado como “genuíno”. Em termos teóricos, uma das principais descobertas feitas nesta pesquisa é que o relacionamento de marketing pode trazer também implicações negativas para as empresas confirmando as descobertas de Grayson and Ambler (1999 quando eles afirmam que o marketing de relacionamento pode trazer benefícios, mas também desvantagens inerentes. Em termos gerenciais, há que se ressaltar o papel fundamental que os funcionários exercem na construção de relacionamentos duradouros. Sendo assim, maior atenção deveria ser dispensada ao desenvolvimento de habilidades de relacionamentos daqueles que estão face a face com o cliente. DOI: 10.5585/remark.v12i3.2513

  9. Tillandsia recurvata L. (Bromeliaceae: aspectos farmacognósticos

    Directory of Open Access Journals (Sweden)

    Alex Lucena de Vasconcelos

    2013-01-01

    Full Text Available A cobertura superior das florestas tropicais, formada pelas copas das árvores, constitui um ambiente de extrema diversidade vegetal. Contribuindo com a grande riqueza dessas florestas encontram-se as espécies botânicas epífitas, cuja importância pode ser observada do ponto de vista ecológico, faunístico, etnobotânico e até mesmo farmacológico. Dentre as espécies adaptadas à vida epifítica podemos citar as bromeliáceas, que compõem uma das famílias mais representativas dessa flora com elevada variabilidade genética. Tillandsia recurvata é uma espécie epífita cosmopolita, nativa, adaptada a habitats áridos, utilizada para o tratamento de diversas doenças, mas pouco se tem publicado a respeito das comprovações científicas de suas propriedades. O presente trabalho revisa os aspectos etnofarmacológicos, atividades biológicas e compostos químicos relacionados à espécie em questão, pertencente à Bromeliaceae. A partir do levantamento de dados realizado, observa-se que esta se trata de uma espécie de conhecido uso popular no tratamento de diferentes distúrbios, com alguns estudos farmacológicos que comprovam suas propriedades terapêuticas. Do ponto de vista químico observa-se a presença de terpenos, flavonoides e derivados cinâmicos em sua constituição, em que alguns compostos isolados ilustram a potencialidade desta espécie como fonte de biomoléculas de interesse. Todos estes aspectos considerados nesta revisão contribuem para o conhecimento a respeito da importância biológica e o potencial terapêutico acerca dos metabólitos desta promissora espécie.

  10. Aspectos económicos del aislamiento acústico

    Directory of Open Access Journals (Sweden)

    Amarilla, Beatriz C.

    1990-12-01

    Full Text Available The general objective of this study was to analyze the soundproofing/cost ratio with different building alternatives for interior walls and floors. This technical-economic study was divided into three parts: — Dividing walls (environmental noises — Floors (impact noises — Special Solutions (double walls, floating floors, etcetera The results show that in developing countries the most costly solutions are not always the best for housing, as far as soundproofing is concerned. A good knowledge of the economic aspects related to this matter allows obtaining a good quality at a moderate cost, which is a priority in this type of country.

    El objetivo general de este trabajo fue el de analizar el comportamiento de la relación costo-aislamiento acústico en soluciones constructivas alternativas para muros interiores y entrepisos. Este estudio técnico-económico comprende tres partes: * Muros divisorios (ruidos aéreos. * Entrepisos (ruidos de impacto. * Soluciones especiales (muros de doble hoja, pisos flotantes, etc. Se llega a la conclusión que, en los países en desarrollo, no siempre las mejores soluciones para la vivienda, desde el punto de vista acústico, son las de mayor costo. Conocer en profundidad los aspectos económicos de esta cuestión significa poder lograr una buena calidad con costos moderados, lo cual constituye una prioridad en este tipo de países.

  11. Revisión de algunos aspectos importantes

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    J. A. Ávila

    2012-01-01

    Full Text Available El soporte nutricional adecuado y oportuno contribuye en la reducción del riesgo de infecciones, mejora la función inmune y el pronóstico del paciente; es por esto que se destaca la importancia de mantener un adecuado estado nutricional en los pacientes críticamente enfermos. Con este propósito, el presente documento resalta el valor de la nutrición parenteral y su papel en aquellos animales con desnutrición presente o prevista, siempre y cuando la vía enteral no esté disponible o sea insuficiente; esto, en razón de su metabolismo alterado, el cual predispone a un mayor catabolismo mus-cular. La correcta elaboración de un plan nutricional debe tener en cuenta aspectos de gran importancia como la evaluación integral de los hallazgos históricos, clínicos y paraclínicos, con el fin de detectar el grado o riesgo de desnutrición; por su parte, la selección del tipo de nutrición más adecuada y el tipo de solución por emplear, son variables igualmente relevantes pues varían según cada caso particular, dependiendo de la condición del paciente y el tipo de patologías asociadas. Así pues, el cálculo de los requerimientos calóricos y la manera en que estos serán suplementados, son variables que deben manejarse con cautela, con el fin de no exceder la capacidad metabólica y desencadenar complicaciones que representen mayor morbilidad y mortalidad. Por úl-timo, es importante resaltar que la nutrición parenteral debe descontinuarse tan pronto como sea posible para disminuir los problemas relacionados con la misma, como la atrofia gastrointestinal.

  12. Aspectos técnicos da psicoterapia de grupo

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    Bernardo Blay Neto

    1959-09-01

    Full Text Available São estudados os mecanismos psíquicos que se desenvolvem em agrupamentos humanos e a sua utilização para fins terapêuticos, sendo focalizado o fenômeno da interação como o dinamismo básico dessas reações. O autor compara a forma pela qual encara o grupo com as idéias de Bion, Moreno e Sullivan, encarando a hipótese de que os sentimentos de amor e hostilidade se manifestem em função do bom ou do mau funcionamento dos contactos primários que caracterizam a dependência. O autor comenta resultados que obteve usando o psicodrama, mediante o qual estudou reações emocionais de inveja, ódio, agressividade e amor. O autor analisa as técnicas de Slavson e Pratt baseando-se nos dinamismos inerentes ao grupo e refere os estudos de Beukemkamp para a compreensão do fenômeno transferenciai que, no grupo, tem características próprias. As diferenças entre a terapia de grupo e a individual são apontadas, sendo a contra-transferência considerada como elemento construtivo. Pensa o autor que o aspecto dramático vivenciado pelo grupo ou por um dos seus componentes tem alto valor, pois engloba a verbalização, os componentes emocionais e os componentes posturais. O tono emocional vivenciado pelo grupo é mais intenso e opressivo que o que é despertado na terapêutica individual, o que é explicável pela somação de efeitos provocada pela reação circular. Segundo o autor, a Psicoterapia de Grupo e a Psicoterapia Individual não se opõem, mas se completam.

  13. Conocimientos de los adolescentes sobre aspectos de la sexualidad

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    Ileana García Imia

    2002-12-01

    Full Text Available Se realizó un estudio descriptivo retrospectivo, de corte transversal, en el área del Policlínico Docente "Wilfredo Pérez Pérez" del municipio San Miguel del Padrón, de Ciudad de La Habana, con el fin de explorar los conocimientos sobre algunos aspectos de la sexualidad, en un grupo de 100 adolescentes en edades entre 10 y 19 años y de uno y otro sexos, en el año 2001. Se apreció un elevado tanto por ciento de jóvenes que tenían conocimientos sobre la anatomía del aparato genital, la mejor edad para tener hijos y la anticoncepción. En general, no tenían conocimientos de todas las enfermedades de transmisión sexual, no así el método más eficaz para evitarlas. El grupo de edad de mayor relevancia lo constituyó el de 10 a 13 años por sus escasos conocimientos sobre sexualidad.A retrospective, descriptive and crosswise study was made in the health areas of "Wilfredo Pérez Pérez" Teaching Polyclinics in San Miguel del Padrón municipality, Havana City province, with the objective of exploring what a group of 100 adolescents aged 10-19 years of both sexes knows about sexuality in the year 2001. A high percentage of them had knowledge about anatomy of the genital system, the most suitable age for having children and contraception. In general, they did not know all the sexually-transmitted diseases but they did know the most efficient method to prevent them. The most relevant age group was 10-13 years old because of their poor knowledge about sexuality.

  14. Refractarios: un aspecto clave en la industria del cemento

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    Castillo Neira, Percy

    1985-09-01

    Full Text Available To sit in judgement values of the technic level reached in a cement plant, it is surprisingly objetive to analyse work, planning and control development about Refractories subject. Considering and recognizing the validity of this pragmatic axiom it will offer unexpected improvement perspectives of the productivity rates and production records. This work pretends to be a contribution for this purpose, bringing some theoretic and practical accounts about de conditions offered by the Kiln-Exchanger-Cooler most diffused system, analyzing the characteristics that refractory material must have, in accordance with each zone, and finally, including some appraisals and recommendations regarding some of the manifold aspects which belongs to one of the most interesting ad complex fields of cement industry.

    Para establecer un juicio de valor respecto al nivel técnico alcanzado en una planta cementera resulta sorprendentemente objetivo analizar el trabajo, planificación y control que se desarrolla alrededor del tema de Refractarios. Considerarlo y reconocer la validez de este axioma pragmático ofrecerá inusitadas perspectivas de superación de índices de productividad y récords de producción. En este trabajo se pretende un aporte a tal objetivo proporcionando algunas consideraciones teórico-prácticas sobre las condiciones que se presentan en el sistema Horno Intercambiador-Enfriador, más difundido, analizando las características que debe reunir el material refractario para cada zona y, finalmente, incluyendo algunas apreciaciones y recomendaciones principalmente de criterio, respecto a algunos de los múltiples aspectos que forman parte de uno de los campos más interesantes y complejos de la industria del cemento.

  15. Aspectos históricos dos estudos caso-controle

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    Rêgo Marco Antônio Vasconcelos

    2001-01-01

    Full Text Available Este texto apresenta um relato da evolução dos estudos de caso-controle (ECC até o final dos anos 80. A comparação de dois grupos quanto à exposição a um fator de risco é verificada desde o século XVII. A segunda metade do século XIX significou o declínio da Epidemiologia das "populações", e os primeiros ECC só foram realizados na década de 20. O avanço do método ocorreu na segunda metade do século, com destaque para as investigações sobre câncer de pulmão e hábito de fumar. As principais contribuições dos estudiosos do método foram o uso da odds ratio como estimativa do risco relativo; a definição dos aspectos estatísticos da análise de dados de estudos retrospectivos; o cálculo do risco atribuível e da fração etiológica para ECC; e a discussão da essência dos ECC. Os críticos referiam as fragilidades do método e a susceptibilidade aos bias. Conclui-se que os ECC tiveram aplicação crescente nas últimas décadas, sendo utilizados em diversas áreas da epidemiologia, constituindo-se em um importante instrumento para as ações de Saúde Pública.

  16. Aspectos fisiológicos do mountain biking competitivo

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    Ricardo Dantas de Lucas

    2010-12-01

    Full Text Available A prática do ciclismo off-road (mountain biking - MTB, cresceu muito nas últimas duas décadas, sendo incluído como esporte olímpico, nos Jogos de Atlanta em 1996, na modalidade Cross Country. Na última década, houve um aumento no número de publicações científicas que verificaram a demanda fisiológica durante competições, assim como o estudo de possíveis preditores da performance nesta modalidade. O objetivo deste estudo de revisão foi descrever alguns aspectos fisiológicos específicos do MTB Cross Country (MTB CC competitivo (intensidade de provas, perfil fisiológico de atletas de elite, uso de suspensões e determinantes da performance em subidas. Observa-se na literatura analisada que as provas de MTB CC parecem impor uma sobrecarga fisiológica maior, quando analisada através da frequência cardíaca, do que provas de ciclismo de estrada com duração semelhante. Entretanto, quando analisada pela potência de pedalada, observa-se claramente a característica intermitente da modalidade, com variações de potência durante a prova entre zero e 500W, e potência média relativamente baixa em comparação aos valores de FC encontrados. Outro fator importante levantado neste estudo são as alterações fisiológicas decorrentes do uso de suspensões nas bicicletas de MTB CC. O uso deste equipamento reduz o estresse muscular provocado pelo terreno acidentado, embora pareça não afetar o gasto energético total, tanto em percurso plano como em subidas. Entretanto, é fato que o desempenho em circuitos acidentados é melhorado com o uso das suspensões. Com base nos estudos abordados nessa revisão, conclui-se que o MTB CC enquanto modalidade competitiva apresenta uma grande variação de intensidade (avaliada através da potência, sendo esta atribuída principalmente ao tipo de terreno (irregular e com muitas aclives e declives acentuados em que as provas de MTB CC acontecem.

  17. Aspectos institucionales del proceso latinoamericano de integración

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    Felipe Herrera

    2014-09-01

    Full Text Available La formación de un espacio económico que abarque los territorios de varios Estados requiere de dos elementos esenciales: la voluntad política de los países de participar en un proceso de integración de sus economías y la existencia de instrumentos jurídicos e institucionales adecuados para traducir las decisiones políticas en programas concretos de acción oportuna y coordinadamente ejecutados. El estudio de los aspectos institucionales de la integración latinoamericana ha adquirido especial importancia a partir de las decisiones adoptadas en abril de 1967 en Punta del Este por los presidentes latinoamericanos, en el sentido de crear un mercado común regional a partir de 1970. La necesidad de contar con instrumentos institucionales adecuados para llevar a la práctica las decisiones presidenciales confronta a los países con la necesidad de analizar profundamente los instrumentos que ahora existen a fin de perfeccionarlos y adaptarlos a las tareas propias de una comunidad económica. Este análisis debe basarse en un planteamiento muy claro de tipo institucional que -aprovechando la experiencia acumulada a través de la integración económica europea y prestando la debida consideración a las características que reviste este proceso en el caso de América Latina- contemple y defina el rol que están llamados a desempeñar en la promoción de este proceso los gobiernos y las administraciones de los países participantes, las instituciones creadas especialmente por los instrumentos jurídicos de la integración y los organismos internacionales especializados que colaboran en el desarrollo de la región. Este texto apareció por primera vez en Osvaldo Sunkel (Comp. Integración Política y Económica (pp. 311-344, Santiago de Chile, Editorial Universitaria, 1970.

  18. Aspectos relevantes sobre tuberculose para profissionais de saúde

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    Alexandre Daronco

    2012-01-01

    Full Text Available A Tuberculose (TB é uma patologia infectocontagiosa com clínica ampla cujo agentecausador é o Mycobacterium tuberculosis (Bacilo de Koch, uma micobactéria aeróbia estrita. Apesar de tratar-se dedoença antiga, que acomete seres humanos há séculos, sendo uma importante causa de morte no mundo inteiro,diferentes pesquisas do Ministério da Saúde apontam números preocupantes no tocante a novos casos. Materiais eMétodos: O presente artigo de revisão procura, de forma objetiva e clara, explicitar os principais aspectos de interessepara profissionais de saúde no tocante a Tuberculose doença. O artigo divide-se em tópicos: Defi nição, Sintomatologia,Diagnóstico, Tratamento, Multirresistência, Profi laxia, Formas de Contágio e Formas de Prevenção. Foram utilizadasreferências atuais sobre o tema, incluindo Manuais, Guidelines e Artigos científicos diversos de bases de dados comoUp to Date e Science Direct. Discussão: Sinais e sintomas da doença aumentam o grau de suspeição da mesma, oque torna o pedido de exames para confirmação da infecção dentro de tempo hábil para instituição da terapêuticaadequada. Assim como diagnóstico e tratamento, medidas para evitar o contágio, em serviços de saúde, locaiscom aglomerações humanas e em residências, são de fundamental importância no combate a tuberculose. Osprofissionais de saúde devem atentar para possíveis casos de resistência aos fármacos e as indicações de profilaxia,pois tais variáveis são de extrema relevância no controle da disseminação da doença. Conclusão: Por tratar-se dedoença infecciosa que pode acometer todas as classes sociais, além de possuir formas diferentes de acometimento,o conhecimento básico acerca da Tuberculose é deveras imprescindível em serviços de saúde, desde a atençãoprimária até os centros de saúde com alta tecnologia.

  19. ASPECTOS CIENTÍFICOS Y BENEFICIOSOS DEL CULTO TANTRICO

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    Ratan Lal Basu

    2016-07-01

    Full Text Available Este artículo se propone identificar y aislar lo científico y beneficioso de la falsedad, superstición y misticismo que envuelve al tantrismo. De todas las prácticas religiosas y semireligiosas antiguas de la India, el culto tántrico es el que ha conseguido el mayor reconocimiento y la mayor popularidad en todo el mundo. La razón de esta popularidad no ha sido el interés académico, espiritual o filosófico. Por el contrario, se lo ha asociado con promesas de obtener poderes mágicos y sobrenaturales, como también promesas de mejorar la potencia sexual y la intensidad del disfrute sexual y restablecer la potencia sexual perdida en las personas mayores. En la India, la gente común le confirió una mala reputación al culto tántrico. El misterio, la psicosis de culpa y temor también se asocian a este culto esotérico. El tantra en sí no es una religión pero ha penetrado en la mayoría de las comunidades religiosas y subreligiosas no solo de la India sino también de Tíbet, China, Japón y muchos otros países (especialmente asiáticos. En la India, son innumerables las asociaciones de tantra y los tántricos individuales en calidad de gurús (maestros con sus círculos de discípulos. Sin embargo, son muchos los aspectos del tantra que son científicamente demostrables y sus efectos son beneficiosos tanto para los individuos como la sociedad en su conjunto. En esta línea, al final del artículo se destacan algunos estudios que demuestran la reducción de los niveles de estrés como resultado de las prácticas tántricas. Este trabajo también apunta a inspirar a más investigadores competentes y eruditos a continuar con la tarea aquí iniciada. Abstract This article endeavors to identify and isolate the scientific and beneficial from falsehood, superstition and mysticism surrounding tantrism. Among the various ancient Indian religious and semi-religious practices, tantra cult has got the most widespread recognition and popularity

  20. Aspectos subjetivos relacionados con la violencia intrafamiliar. Caso municipio de Sabaneta Antioquia

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    Naidalis Yadira Martínez

    2016-01-01

    Full Text Available El artículo identifica las interacciones en aspectos familiares y subjetivos. En el artículo se desarrollan los aspectos subjetivos de las dinámicas familiares que justifican el uso y la implementación de la violencia intrafamiliar, se da cuenta de la naturalización de la violencia intrafamiliar en la interacción de los grupos familiares, convirtiéndola en un elemento de la relación que se establece entre los miembros de la familia. En el análisis realizado se identifican aspectos coyunturales asociados a situaciones que se vivieron en la dinámica de la familia de origen, pero que al momento han sido pocas las condiciones que permiten la modi- ficación de estas conductas ya que las familias han asumido estas expresiones de violencia intrafamiliar como parte de sus vidas.

  1. La gestión por procesos, su surgimiento y aspectos teóricos

    OpenAIRE

    Daysi Ruiz-Fuentes; Rosa Mercedes Almaguer-Torres; Isabel Cristina Torres-Torres; Alejandro Miguel Hernández-Peña

    2014-01-01

    Abordó aspectos históricos y teóricos relacionados con la gestión por procesos, se precisa las potencialidades de su aplicación para el perfeccionamiento de la dirección de las empresas. Presentó un análisis de diferentes definiciones de este término a partir del c ual se determinan las regularidades que lo caracterizan. Se puntualizan algunos aspectos teóricos vinculados con esta forma de gestión empresarial.

  2. La gestión por procesos, su surgimiento y aspectos teóricos

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    Daysi Ruiz - Fuentes

    2013-01-01

    Full Text Available Abordó aspectos históricos y teóricos relacionados con la gestión por procesos, se precisa las potencialidades de su aplicación para el perfeccionamiento de la dirección de las empresas. Presentó un análisis de diferentes definiciones de este término a partir del c ual se determinan las regularidades que lo caracterizan. Se puntualizan algunos aspectos teóricos vinculados con esta forma de gestión empresarial.

  3. Aspectos geopolíticos en el desarrollo de la zona franca industrial de Ilo

    OpenAIRE

    Cardenas Nuñez, Gilberto; Cardenas Nuñez, Gilberto

    1994-01-01

    El presente trabajo de Tesis enfatiza el aspecto geopolítico en el desarrollo de la Zona franca Industrial de Ilo (ZOFRI-IL0). La razón de tal énfasis es simple: por este aspecto específicamente es que se creó la ZOFRI-ILO. En consecuencia, el tratamiento del tema tiene que ver con la influencia geopolítica en las sucesivas etapas de su desarrollo, considerando sus posibilidades de desarrollo a futuro en el marco de las tendencias internacionales de la globalización de la economía mundial. ...

  4. Aspectos relativos a la salud laboral y los riesgos psicosociales de los equipos de proyectos

    OpenAIRE

    Donate Fernández, Alejandro

    2013-01-01

    Es el objetivo del presente trabajo presentar una serie de directrices relacionadas con la salud laboral y los riesgos psicosociales de los equipos de proyectos y, en algunos aspectos centrándose en el principal responsable: el director de proyecto.

  5. Aspectos cuantitativos de los programas universitarios de administración de empresas en Colombia

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    Carlos Henao Restrepo

    1991-05-01

    Full Text Available RESUMEN La estabilización o el crecimiento en la oferta universitaria de este programa, en términos  cuantitativos como cualitativos, es uno de los aspectos críticos para las instituciones que postulan mejoras de calidad dentro de las nuevas reglas del mercado educativo.

  6. ASPECTOS NORTEADORES NA ORIENTAÇÃO DE MONOGRAFIA A DISTÂNCIA

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    monica seixas mello

    2012-12-01

    Full Text Available O objetivo do presente estudo é analisar os aspectos norteadores na orientação de monografia na modalidade a distância a partir de relato de experiência em curso de pó-graduação Lato Sensu em Gestão Pública., constatando-se que na orientação a distância em ambientes virtuais de aprendizagem as interações entre professor e aluno observam os seguintes aspectos: pedagógico, gerencial, social e técnico Palavras-chaves: educação, distância, orientação, monografia, pos-graduação.

  7. Estilo de vida materno e aspectos nutricionais do pré-escolar

    OpenAIRE

    Érica Bezerra Nobre

    2016-01-01

    INTRODUÇÃO: Muitos dos comportamentos de saúde envolvidos no aparecimento das doenças crônicas não comunicáveis são originados na infância sob influência dos pais. A mãe é a pessoa mais envolvida na educação e nos cuidados de saúde da criança. O estilo de vida (EdV) é um determinante social da saúde. Nunca se compreendeu características de EdV materno associadas com aspectos da nutrição infantil. OBJETIVO: Verificar a associação dos EdV materno comportamental e não comportamental com aspectos...

  8. Eugenia vinculada a aspectos bioéticos: uma revisão integrativa

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    Vanessa Cruz Santos

    Full Text Available O objetivo do estudo é analisar o que versam as produções científicas sobre eugenia, vinculando-as com aspectos bioéticos. Trata-se de uma revisão integrativa de literatura. Os dados foram coletados nas bases de dados Lilacs e SciELO, por meio dos descritores: eugenia, etnia e saúde, ética e bioética. Para a análise e posterior síntese dos artigos foi utilizada figura sinóptica. Verificou-se que a eugenia viola os direitos humanos, contradiz com o princípio da solidariedade e coloca em risco a diversidade humana. Conclui-se que houve déficit de artigos que abordem aspectos bioéticos vinculados à eugenia, assim, este estudo poderá contribuir para a reflexão sobre essa articulação.

  9. Aspectos Técnicos en la Producción de Caucho Hevea

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    Uribe Henao Alfonso

    1950-09-01

    Full Text Available El propósito primordial de este trabajo es el de hacer una exposición de los principales factores o aspectos técnicos que deben tenerse en cuenta en el planeamiento y desarrollo del cultivo de la Hevea, para poder obtener de él en la forma más económica el máximo beneficio. Se ha dacio preferencia a los aspectos técnicos concernientes al Hevea de mayor importancia, sin pretender exponerlos todos. No es pues su objetivo dar a conocer todos aquellos detalles y sistemas aconsejables y necesarios en su explotación que pudieran considerarse como principios elementales, y que más bien vienen a ser prácticas corrientes del cultivo.

  10. Aspectos da tomografia computadorizada craniana na neurocisticercose na infância

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    Marilisa M. Guerreiro

    1989-06-01

    Full Text Available Os autores relatam aspectos tomográficos da neurocisticercose na infância a propósito da análise de 27 exames em 18 pacientes, que foram distribuídos em três grupos segundo o quadru clínico e os achados tomográficos. O grupo 1 foi caracterizado basicamente por epilepsias e calcificações. O grupo 2 caracterizou-se por hipertensão intracraniana e diversos aspectos tomográficos: edema, cistos e nódulos em três pacientes; hidrocefalia e calcificações em dois pacientes e normal em um paciente. O grupo 3 consistiu clinicamente de epilepsia e cefaléia, com vários padrões tomográficos. Os resultados são discutidos à luz da literatura disponível.

  11. Una plataforma multiagente para la búsqueda de recursos educacionales considerando aspectos culturales

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    Bender, Cristina

    2006-01-01

    Full Text Available En este trabajo se propone una arquitectura multiagente para la recuperación de recursos educacionales, que ayude a los usuarios a encontrar cursos que se adecuen a sus características personales y aspectos culturales. En este trabajo, se considera como aspectos culturales a las características que permiten distinguir las preferencias de estudiantes pertenecientes a distintas regiones geográficas. La plataforma multiagente planteada incluye varios tipos de agentes que tienen funcionalidades diferentes. En particular, se modela el Educational Resources Finder Agent como un agente BDI Graduado. Este agente se encarga de la recuperación de los mejores cursos de acuerdo al perfil de cada estudiante. Se describe el sistema multiagente completo y se presenta un ejemplo ilustrativo del proceso de búsqueda.

  12. Algunos aspectos éticos en la práctica de la obstetricia

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    DR. P. Sergio Valenzuela

    2014-11-01

    Full Text Available La obstetricia ejercida en el contexto clínico asistencial es una fuente permanente de cuestionamientos éticos para los especialistas. En este artículo, que tiene carácter de ensayo, se aborda una primera parte introductoria, que da cuenta de la dimensión antropológica del cuidado obstétrico. Luego se destaca la necesidad de referirse a un número mayor de principios en la fundamentación del quehacer obstétrico. Por último, profundiza principalmente en los aspectos éticos de su ejercicio como obstetricia de urgencia y la ética del diagnóstico; quedando aspectos importantes para discutir en una futura oportunidad.

  13. Los aspectos socioculturales de la migración en la frontera norte

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    Oscar Priego Hernández

    2011-12-01

    Full Text Available México se considera el país de emigrantes más importante del mundo y Estados Unidos el principal país de inmigrantes. Su posición geográfica en la frontera Norte lo convierten atractivo para los flujos migratorios de los países centroamericanos. Hoy enfrenta los retos de la crisis financiera internacional de los últimos años que afecta las economías y las relaciones bilaterales. Este trabajo consiste en realizar un estudio de la problemática de los aspectos socioculturales provocada por la migración de personas, analizar fortalezas y debilidades, identificar los nuevos aspectos de la migración y proponer alternativas para mejorar las condiciones de vida de los migrantes mexicanos.

  14. Aspectos ultra-estruturais da forma epimastigota do Trypanosoma cruzi em meio LIT

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    Wanderley de Souza

    1975-06-01

    Full Text Available E feito um estudo da ultra-estrutura da forma epismastigota do Trypanosoma cruzi mantida em meio de cultivo acelular. O núcleo das formas em divisão apresenta um aspecto homogêneo. Microtúbulos intranucleares são observados durante a divisão. No entanto, a membrana nuclear permanece íntegra. O citoplasma apresenta-se com vacúolos de dimensões e aspectos variados. Com o método do ácido periódico-tiosemicarbazida-proteinato de prata, polissacaríáeos e/ou glicoproteínas foram localizados na membrana celular e na membrana que delimita certos vacúolos citoplasmáticos.

  15. ANÁLISIS DE LA TRAZABILIDAD DESDE LA PERSPECTIVA DE LA ORIENTACIÓN A ASPECTOS

    Directory of Open Access Journals (Sweden)

    Marta Silvia Tabares

    Full Text Available En este artículo se presenta un análisis acerca de la trazabilidad de los intereses de un sistema de software, desde el enfoque del desarrollo de software orientado a aspectos. Para esto se abordarán los conceptos generales de trazabilidad, de la orientación a aspectos y de las características que esta técnica puede proveer para verificar la fiabilidad y evolución de los requisitos en el proceso de desarrollo de software. Tratar la trazabilidad desde este enfoque pretende orientar al desarrollador a identificar elementos generales para determinar la traza de los intereses de corte transversal cuando estos afectan otros intereses del sistema y a su vez cómo diferentes piezas de un artefacto de software asociadas a este tipo de intereses han evolucionado y afectado a otras a lo largo del ciclo de vida de desarrollo.

  16. Planificación estratégica: aspectos introductorios (I)

    OpenAIRE

    Galindo Reyes, Fuensanta Carmen; De la Varga Salto, José María

    2016-01-01

    Transparencias como material docente para la asignatura de Administración de Organizaciones. Se corresponden con la etapa primera del proceso administrativo de las organizaciones, la planificación estratétiga. En concreto, incluyen aspectos introductorios relacionados con los conceptos y elementos principales de la planificación estratégica. Planificación estratégica

  17. Planificación estratégica: aspectos introductorios (II)

    OpenAIRE

    Galindo Reyes, Fuensanta Carmen; De la Varga Salto, José María

    2016-01-01

    Transparencias como material docente para la asignatura de Administración de Organizaciones. Se corresponden con la etapa primera del proceso administrativo de las organizaciones, la planificación estratégica. En concreto, incluyen aspectos introductorios relacionados con el análisis del entorno y el análisis interno, así como con el concepto y las características de los objetivos estratégicos.

  18. Calidad de servicio (QoS en procesos: Escenarios de procesamiento con aspectos

    Directory of Open Access Journals (Sweden)

    Hector Manuel Soto Pérez

    2016-12-01

    En resumen el presente trabajo estudia conceptos básicos de calidad de servicio y algunos de sus marcos de aplicación siguiendo un enfoque aspectual. Planteando posibles casos de uso genéricos para aplicar mejoras en la prestación de la QoS mediante aspectos en la planificación y gestión de recursos de aplicaciones tradicionales.

  19. El maltrato infantil: aspectos psicológicos y programas de tratamientos

    OpenAIRE

    González Díaz, Adriana

    2013-01-01

    La presente revisión recoge los aspectos psicológicos derivados del maltrato infantil. Expone la tipología, así la evaluación psicológica de los menores en estos casos y las patologías asociadas al maltrato. Finalmente se exponen los principales programas de intervención y tratamiento en estos casos

  20. Sobressalto patológico: aspectos clínicos e eletrencefalográficos

    Directory of Open Access Journals (Sweden)

    Frederico Dahne Kliemann

    1967-06-01

    Full Text Available Os autores relatam o caso de um paciente apresentando crises de sobressalto provocadas por estímulos auditivos, sensitivos e visuais, sem crises epilépticas espontâneas nem retardo psicomotor. Estudam os aspectos clínicos e eletrencefalográficos e revisam a situação da entidade entre as assim chamadas epilepsias reflexas.

  1. Aspectos valorizados por porfissionais de enfermagem na higiene pessoal e na higiene corporal do paciente

    Directory of Open Access Journals (Sweden)

    Elóide André Oliveira

    2003-10-01

    Full Text Available Survey descritivo, com o qual se objetivou identificar que aspectos da higiene corporal são valorizados pelos componentes da equipe de enfermagem, na higiene corporal pessoal e na higiene corporal do paciente. A pesquisa foi desenvolvida em oito instituições públicas de saúde e a amostra foi composta por 126 profissionais de enfermagem, correspondendo a 12,8% do total de 986 componentes das equipes de enfermagem destas instituições. Na higiene corporal pessoal, chamou a atenção o fato de que os cuidados com as unhas e com os cabelos tenham suplantado, no número de citações dos profissionais de enfermagem, aspectos básicos como o cuidado com as mãos. Na higiene corporal do paciente, o banho foi o aspecto considerado mais importante pelas três categorias profissionais; a higiene oral, pelas(os enfermeiras(os e auxiliares de enfermagem; e as unhas, pelas(os enfermeiras(os e técnicas(os de enfermagem.

  2. Aspectos de diseño de un entorno de programación colaborativo

    Directory of Open Access Journals (Sweden)

    David Bracho

    2008-12-01

    Full Text Available ResumenLa programación colaborativa, o programación en par, es una de las áreas más estudiadas actualmente debido a su impacto en el proceso de desarrollo de software. El propósito de la presente investigación consistió en determinar los aspectos básicos de diseño que un entorno de programación colaborativo debe ofrecer a los desarrolladores. La metodología utilizada consistió en realizar un análisis documental sobre la propuesta de Lussier acerca de la programacióncolaborativa con la finalidad de determinar los aspectos de diseño, estructura e implementación de este tipo de entornos. Como resultado se obtuvo que desde el punto de vista del diseño, la comunicación entre desarrolladores, la revisión de código y la construcción del proyecto de software son los principales aspectos a considerar, y desde el punto de vista de la implementación se propone utilizar el modelo cliente - servidor y una arquitectura multiplataforma.AbstractCollaborative programming or pair programming is today one of the most studied areas, because of its impact on the software developing process. The purpose of the present investigation was to determine the basic design aspects that a collaborative programming environment must offer to developers. The methodology used was a documental review of Lussier’s work about collaborative programming, to determine the design aspects, the structure and the implementation aspects of this type of environments. As result, from the design point of view, the communication between developers, code review and the construction of software project are the basic aspects to consider, and from the implementation point of view, the use of the client - server model and a multiplatform architecture are proposed.

  3. Satisfacción con el aspecto dental general y tratamientos deseados en estudiantes universitarios

    Directory of Open Access Journals (Sweden)

    Clarisse Virginia Díaz Reissner

    2015-08-01

    Full Text Available La apariencia dental es considerada un componente de la belleza facial, que al ser restaurada por el odontólogo, podría influir con un efecto positivo en la valoración personal y la calidad de vida. El objetivo del estudio fue determinar la satisfacción general con la apariencia dental en estudiantes de las carreras de Artes Visuales y Diseño de Indumentaria del Instituto Superior de Arte de la Facultad de Arquitectura Diseño y Arte de la Universidad Nacional de Asunción, matriculados en el 2014. Se aplicó un cuestionario que contenía preguntas sobre datos demográficos, satisfacción con el aspecto dental general y con diversos aspectos dentales, así como también sobre el tratamiento estético deseado. La muestra quedó conformada por 108 estudiantes, que corresponde al 49,1% de la población. Se observó que el 48,2% se encontraba insatisfecho con el aspecto general de sus dientes, siendo los tratamientos de elección: blanqueamiento (63,9% y ortodoncia (47,2%. Los factores predisponentes a la insatisfacción fueron residir en Gran Asunción e interior del país y percibir sus dientes como desalineados. Por otro lado, favoreció la satisfacción el haberse sentirse a gusto con el color de sus dientes.

  4. Impacto de las redes sociales e internet en la adolescencia: aspectos positivos y negativos

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    L. Elías Arab, Dr.

    2015-01-01

    Full Text Available Este artículo presenta una revisión teórica del impacto, tanto positivo como negativo, de las redes sociales en los adoles- centes y de la relación directa entre esto y el uso o abuso de las nuevas tecnologías. A su vez, se establece el vínculo entre las formas de utilizarlas y las características psicológi- cas individuales, los desarrollos previos de personalidad y el control parental. Se toma como punto de partida el desa- rrollo adolescente asociado a la construcción de la identidad juvenil en el contexto de un nuevo paradigma comunica- cional (cibercomunicación, donde el límite entre lo públi- co y lo privado se torna cada vez más difuso. Se expone la terminología propia de las redes sociales y se pone énfasis en las estrategias de supervisión y control adulto. Se deta- llan los aspectos positivos que las nuevas tecnologías ofre- cen (diversas oportunidades de aprendizaje, entretención, socialización, desarrollo de habilidades, creatividad y me- jora de la motivación al aprendizaje especialmente en ado- lescentes, entre otros y los aspectos negativos asociados (distanciamiento afectivo, pérdida de límites en la comuni- cación y pérdida de la capacidad de escucha, entre otros. Este artículo destaca la necesidad de entregar y estimular modelos de comunicación social reales y una educación en el uso de las nuevas tecnologías. El objetivo es actualizar y orientar a profesionales de la salud sobre los aspectos posi- tivos y/o negativos de las redes sociales en los adolescentes.

  5. Conjecturas da Epistemológia Jurídica e Aspectos da Teoria da Linguagem

    OpenAIRE

    Oliveira, Rita de Cássia Cartelli de; Cesumar; Motta, Ivan Dias; Cesumar

    2008-01-01

    Apresentar-se-ão reflexões em torno da epistemologia jurídica e alguns aspectos da teoria da linguagem; a necessidade de acompanhamento e aprimoramento da linguagem jurídica, para que o direito não se distancie da realidade, mantendo-se apenas como um sistema do status quo; uma breve análise de algumas teorias da ciência do direito e da linguagem; as especificidades dos termos lingüísticos para a análise da ciência do direito, pautada na contemporaneidade sob a perspectiva humanista, buscando...

  6. EMPREENDEDORISMO CORPORATIVO - ASPECTOS DE INOVAÇÃO E MUDANÇA ORGANIZACIONAL

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    Luciana Gehlen

    2016-11-01

    Full Text Available Este artigo analisa o conceito de empreendedorismo corporativo – conhecido também como empreendedorismo interno ou intra-empreendedorismo, seus aspectos relacionados aos fatores de criatividade, inovação e mudança organizacional como fatores de competitividade das organizações, bem como o perfil do empreendedor corporativo e o ambiente organizacional necessário para que o empreendedorismo interno aconteça. Palavras-chave: empreendedorismo corporativo, empreendedorismo interno, intra-empreendedorismo, inovação, mudança organizacional.

  7. Algunos aspectos de la Reforma al Código de Procedimiento Laboral (Ley 712 de 2001

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    Armando Rojas

    2002-01-01

    Full Text Available El pasado 9 de junio entró en vigencia la ley 712 del 2001, ley quereformó algunos aspectos del código procesal del trabajo que ahora sellama código procesal del trabajo y de la seguridad social. La razón desu creación obedeció a la necesidad de actualizar un estatuto procesal demás de cincuenta años a la práctica procesal de la actualidad, necesitadade la urgente descongestión de los procesos en los despachos judiciales

  8. Aspectos biopsicossociais na surdocegueira Bio psycho social aspects in deaf blindness

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    Susana Maria Mana de Aráoz

    2008-04-01

    Full Text Available O presente artigo tem por objetivo discutir aspectos biopssicossociais referentes a pessoas com surdocegueira e suas famílias com o objetivo trazer a tona estas questões que se tem mostrado importantes para o desenvolvimento dos atendimentos aos surdocegos. Está baseado em dados bibliográficos de pesquisas com pais e outras divulgações abordando as causas que são, principalmente, Rubéola Congênita, prematuridade, infecções, acidentes, síndromes genéticas ou não. Coloca as conseqüências das mesmas, o desenvolvimento educacional alcançado e as necessidades das famílias em aspectos ligadas às áreas da saúde, educação, lazer, segurança e inclusão social. Também trata da adaptação das famílias ao impacto produzido pela surdocegueira tendo em conta aspectos orgânicos, afetivo-relacional, sócio-culturais e de produtividade. Reflete sobre a necessidade da divulgação dos conhecimentos e da ação conjunta de todas as partes envolvidas nos mais diversos aspectos da vida dos surdocegos para conseguir o desenvolvimento dos atendimentos para os surdocegos.The objective of the present article is to discuss bio-psycho-social aspects related to people with deaf blindness and their families so as to highlight those issues that have become important for the development of working methods in deaf blindness. It is based on bibliographic data found in research with parents of deaf blind children and other publications that deal with the causes of the condition. The main causes are congenital German measles, prematurity, infection, genetic or non genetic syndromes. The authors discuss the results of the various presentations, the expected educational development and the needs of the families in aspects related to health, education, leisure, safety and social inclusion. They also discusses issues of family adaptation to the impact produced by deaf blindness, taking into account organic, social-cultural, affect and inter

  9. Aspectos da aposentadoria por tempo de serviço nos estados-partes do Mercosul

    OpenAIRE

    Oliveira, Aldemir de.

    2008-01-01

    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Jurídicas. Programa de Pós-Graduação em Direito. O objeto desta tese são os aspectos da Aposentadoria por tempo de serviço nos Estados-Partes do MERCOSUL. A escolha do tema é dar uma contribuição jurídica, para que os trabalhadores mercosulinos, em especial argentinos, paraguaios e uruguaios, na qualidade de segurados obrigatórios, por prestarem, ou terem prestado serviços, nesses territórios, e sujeitos à legis...

  10. Aspectos das relações interpessoais em Freud: questionamentos morais

    OpenAIRE

    Virginia Helena Ferreira da Costa

    2014-01-01

    O objetivo principal da dissertação é problematizar, a partir de textos de Freud, o prolongamento de expectativas e fantasias próprias da infância em aspectos sociais e políticos da vida adulta. Para tanto, as relações interpessoais são consideradas mediante dois pontos de vista da teoria freudiana, a saber, o do desenvolvimento individual e das relações e estruturas sociais. Como pano de fundo para tal problemática, são abordadas a experiência edípica infantil e a situação de desamparo como ...

  11. Aspectos psicológicos del paciente con cáncer

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    R. Labarca B.

    2017-05-01

    Full Text Available El profundo cambio que ha experimentado lamedicina en los últimos años, ha traído como consecuencia un deterioro en la relación médico-paciente. La consecuencia de este hecho es un distanciamiento entre médico y enfermo, situación que afecta seriamente a los pacientes con enfermedades incurables o terminales. El presente artículo revisa los aspectos psicológicos principales del enfermo con cáncer y concluye que la única actitud que cabe ante el enfermo canceroso es la verdadera relación médico-paciente.

  12. ASPECTOS REPRODUCTIVOS EN MUJERES PORTADORAS DE MUTACIONES GENÉTICAS BRCA

    OpenAIRE

    Dr. Octavio Peralta; Dr. Tulio Rodríguez; Dra. Adela Camus

    2017-01-01

    Se analizan diferentes aspectos reproductivos en mujeres portadoras de mutaciones genéticas BRCA. Se revisa la evidencia científica del riesgo que agrega el uso de anticoncepción hormonal a mujeres con diferentes niveles de riesgo concluyendo que con las formulaciones recientes después del 2010 no hay aumento del riesgo de cáncer de mama. En portadoras de mutaciones BRCA, el uso prolongado antes de los 25 años se asocia a un leve mayor riesgo de diagnóstico temprano de cáncer de mama. Se a...

  13. A import??ncia dos aspectos psicomotores na educa????o infantil

    OpenAIRE

    Silva, ??talo Cardoso Barreto da

    2016-01-01

    Introdu????o: Os aspectos psicomotores proporcionam atribui????es significativas para o desenvolvimento do aluno e pode ainda contribuir para sua evolu????o cognitiva, o tornando h??bil para realiza????o de diferentes movimentos. A educa????o f??sica escolar tem o poder de criar, estimular uma ampla gama de a????es motoras, novas viv??ncias que iriam estimular e desenvolver as crian??as. Criando tamb??m a capacidade de inclus??o, diversidade, respeito entre elas e quem as cerca. Objetivo: O p...

  14. Prótesis dental en el paciente anciano: aspectos relevantes

    OpenAIRE

    Almeida, Erika Oliveira de; Silva, Eulália Maria Martins da; Falcón Antenucci, Rosse Mary; Freitas Junior, Amílcar Chagas

    2014-01-01

    Para el paciente anciano la prótesis dental es una integradora familiar, social, mantenedora de la salud general y elevadora de la expectativa de vida. Algunos cambios fisiológicos, patológicos y funcionales que ocurren con los elementos dentales en la tercera edad pueden repercutir en el tratamiento protésico. La siguiente revisión de literatura destaca los aspectos  fundamentales que deben ser considerados en el tratamiento protésico de pacientes ancianos. Se destacan las particularidades d...

  15. Sindrome de Landau Kleffner aspectos clinicos, eletrencefalograficos e psicossociais : estudo de seguimento a longo prazo

    OpenAIRE

    Marcos Henrique Coelho Duran

    2008-01-01

    Resumo: Objetivos: A Síndrome de Landau-Kleffner (SLK) é uma entidade rara, caracterizada por epilepsia e afasia. Ocorre em crianças com aquisição normal da linguagem, geralmente, entre 3 e 7 anos de idade. A evolução a longo prazo é controversa e pouco estudada. O presente estudo tem como objetivo verificar a evolução em uma série de sujeitos com diagnóstico de SLK, enfocando os aspectos clínicos, eletrencefalográficos, psicossociais e da qualidade de vida. Métodos: Trata-se de um estudo tra...

  16. Aspectos discursivos em As Bruxas de Salem: peça e filme

    OpenAIRE

    Pinheiro, Eder Sergio

    2009-01-01

    Esta pesquisa, cujo título é Aspectos Discursivos em As Bruxas de Salem: eça e Filme, propõe discutir a transposição da linguagem escrita, neste caso, as rubricas da peça de teatro para a linguagem fílmica, devido a problemática das duas linguagens se diferenciarem, convergirem-se e cruzarem-se ao mesmo tempo. Deste modo, dois fragmentos foram escolhidos para análise, sendo eles: um trecho da peça escrita As Bruxas de Salem (1953) e outro do filme (1976), ambos os trechos são correspondent...

  17. CLIMATERIO Y POSTMENOPAUSIA: ASPECTOS EDUCATIVOS A CONSIDERAR SEGUN LA ETAPA DEL PERIODO

    OpenAIRE

    ARAYA GUTIERREZ,ALEJANDRA; URRUTIA SOTO,MARIA TERESA; CABIESES VALDES,BALTICA

    2006-01-01

    El periodo del climaterio es una etapa de transición en la vida de la mujer caracterizada por cambios físicos, psicológicos y sociales. Es una etapa dinámica marcada por la repercusión de los cambios hormonales, principalmente por la paulatina disminución de los estrógenos. La presente revisión bibliográfica describe las características generales del periodo, cambios que ocurren y aspectos a educar en las mujeres durante el climaterio y la postmenopausia, con el propósito de dar una visión ac...

  18. Tumores em animais de produção: aspectos comparativos

    OpenAIRE

    Ramos,Adriano Tony; Souza,Arlete Benta de; Norte,Diego Mollerke; Ferreira,João Luiz Montiel; Fernandes,Cristina Gevehr

    2008-01-01

    Com o objetivo de realizar um estudo retrospectivo de tumores em animais de produção (bovinos, ovinos, eqüinos e suínos), foi realizada uma revisão nos casos suspeitos de neoplasmas recebidos pelo Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas num período de 24 anos (1978-2002). Os aspectos epidemiológicos dos neoplasmas nessas espécies foram relatados, e uma classificação concisa para padronizar a nomenclatura, seguindo padrões internaciona...

  19. Tres reformas educativas europeas: Reino Unido, Francia y España: aspectos comparativos.

    Directory of Open Access Journals (Sweden)

    Inmaculada Egido Gálvez

    1997-01-01

    Full Text Available Desde una perspectiva unicamente aproximativa, este trabajo lleva a cabo un breve repaso de las reforrnas realizadas en los ultimos afios en el sistema educativo de tres paises europeos: Reino Unido, Francia y Espana. Tras la consideracion de los principales cambios introducidos por las leyes de reforma en relaci6n con la estructura del sistema, el curriculum, el profesorado y el gobiemo y la administraci6n de la educacion, se presenta lavaloraci6n crftica de algunos de los aspectos mas relevantes de las reformas. Por ultimo, se realizan algunas reflexiones globales derivadas de la comparaci6n entre los tres casos tratados

  20. Audición espacial en ambientes reverberantes: aspectos teóricos relevantes

    OpenAIRE

    Claudia Arias; Oscar A. Ramos

    2003-01-01

    En ambientes reverberantes el sonido se propaga en múltiples direcciones sufriendo cambios físicos de importancia. El sistema auditivo debe se capaz de resolver la competencia perceptual que se produce entre el sonido original y sus reflexiones. En este artículo se presentan aspectos teóricos relevantes de la audición espacial con especial tratamiento del efecto precedente. Se trata de una estrategia inconciente que el individuo utiliza para enfrentar la información sonora conf...

  1. Aspectos psicosociales en el embarazo en mujeres menores de edad en España

    OpenAIRE

    Ibáñez Blanco, Raquel

    2015-01-01

    Me decidí a realizar mi Trabajo de Fin de Grado sobre los aspectos fisiológicos y emocionales en mujeres menores de edad porque considero que la gestación es uno de los momentos claves en la vida de cualquier mujer. Esta situación se ve llevada al extremo cuando tiene lugar en una menor de edad. Aunque en principio pueda parecer algo lejano y puntual, podremos comprobar que es una situación más habitual de lo que esperamos. Además de los importantes cambios anatómicos y fisiológicos que se pr...

  2. Aspectos claves relacionados con la gestión del e.Learning

    OpenAIRE

    Francisco Lupiáñez Villanueva

    2006-01-01

    La introducción y uso de las Tecnologías de la Información y la Comunicación, especialmente Internet, en el ámbito de la salud, la medicina y los sistemas sanitarios enfrenta a todos los agentes e instituciones ante numerosos retos. La educación y la formación, como actividades claves tanto de la sociedad de la información como de los sistemas sanitarios, también se ven afectadas por este proceso de cambio. La finalidad de este artículo es identificar y analizar algunos de los aspectos claves...

  3. Aspectos morfológicos da placenta da preguiça, Bradypus variegatus Shinz, 1825

    OpenAIRE

    Marleyne José Afonso Accyoli Lins Amorin; Maria Angélica Miglino; Adelmar Afonso Amorin Júnior; Tatiana Carlesso dos Santos

    2003-01-01

    Estudaram-se os aspectos morfológicos da placenta e das membranas fetais de 03 placentas de bichos-preguiça (Bradypus variegatus), adultas e prenhes, originárias da Zona da Mata do Estado de Pernambuco. Essas estruturas foram obtidas de 03 fêmeas doadas pela Universidade Federal de Pernambuco, das quais duas encontravam-se congeladas e a terceira foi colhida mediante realização de cirurgia cesariana, onde mãe e feto foram preservados. Depois de descongeladas, as placentas foram fixadas em sol...

  4. Caracterização do insumo ibuprofeno e a correlação com propriedades de dissolução e de fluxo

    OpenAIRE

    Andrea Andrioli; Livia Deris Prado; Maíra Assis da Costa; Helvécio Vinícius Antunes Rocha

    2014-01-01

    O ibuprofeno é um agente anti-inflamatório não esteróide, derivado do ácido fenilpropiônico que possui atividade anti-inflamatória de ação moderada. Sua ação analgésica está relacionada às propriedades anti-inflamatórias devido à redução da produção da ciclooxigenase-1 (COX-1) e da ciclooxigenase-2 (COX-2). O ibuprofeno exibe diferentes morfologias quando cristalizado em diferentes solventes. Neste estudo, se avaliaram as características de matériasprimas do ibuprof...

  5. Exploración de repositorios de software y análisis de potenciales extensiones a aspectos

    Directory of Open Access Journals (Sweden)

    Graciela Beatriz Vidal

    2014-06-01

    Full Text Available Tanto el Desarrollo basado en Componentes como el Desarrollo de Software orientado a Aspectos son enfoque propuestos para abordar diversos problemas que surgen en el proceso de desarrollo de aplicaciones. Ambos enfoques tienen como objetivo el reuso de software, ante esta situación surge la necesidad de que componentes y aspectos compartan un espacio común en el cual puedan ser publicados, recuperados y reutilizados. Los repositorios actuales parecen no proveer aspectos de manera explícita, en ocasiones los aspectos son utilizados para especificar el componente, pero no son reusables. La tarea de publicar y recuperar componentes es muy compleja, existen diversos métodos de publicación y recuperación a tal fin. En este trabajo se exploraron diferentes repositorios analizando criterios al igual que se exponen los métodos de publicación y recuperación con el fin de determinar si es posible la adaptación o extensión de los repositorios a aspectos.

  6. Medicina Genómica Aspectos éticos, legales y sociales del Genoma Humano

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    Rodolfo E. Ávila

    2011-01-01

    Full Text Available La Medicina Genómica es el uso de la inf ormación de los genomas y sus deriv ados (ARN, proteínas y met abolitos que permite guiar la toma de decisiones médicas, es un c omponente clave de la medicina personalizada. La Medicina Genómica permite conocer la cartografía del genoma hum ano y proporciona una valiosa información a tener en cuenta a la hora de detect ar genes implicados en ciert as enfermedades. Esto conlleva a que en la actualidad nos centremos más en la predicción de patologías que en l a prevención, por lo que la tendencia es que en el futuro la Medicina Genómica acabe desbancando a la Medicina P reventiva. El Proyecto Genoma Humano presenta diversas aplicaciones que, al no tener una clara cobert ura legal, traen consigo un nuevo paradigma con problemas éticos, sociales y legales que la comunidad científica trat a de resolver para compaginar los aspectos morales con el progreso en la investigación. El objetivo del presente trabajo es describir brevemente los aspectos éticos, legales y sociales del Genoma Humano.

  7. Aspectos éticos en Pediatría, las inmunodeficiencias primarias

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    Martha Leonor Paradoa Pérez

    2012-12-01

    Full Text Available Las inmunodeficiencias primarias son enfermedades genéticas, caracterizadas por infecciones crónicas devastadoras que conllevan a la muerte, al desarrollo de tumores y a enfermedades autoinmunes, y la mayoría de estas enfermedades cursan en la edad pediátrica. Desde la última década del pasado siglo, el desarrollo de la tecnología, el surgimiento del Proyecto del Genoma Humano y la profundización en los aspectos bioéticos, han dado lugar a especificidades en la atención médica e investigativa del paciente pediátrico y del que desarrolla una enfermedad inmunológica. Este trabajo recoge los aspectos bioéticos más importantes y los dilemas éticos con los que se enfrenta el inmunólogo pediátrico en la atención al paciente con inmunodeficiencia primaria, el cual demanda la atención de, prácticamente, todas las especialidades pediátricas.

  8. Aspectos motivacionais e afetivos na mediação de professores alfabetizadores

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    Azevedo, Cleomar

    2010-01-01

    Full Text Available Este artigo é o resultado de uma pesquisa que parte da seguinte questão: o que diferencia o professor que obtém sucesso no processo de alfabetização? Levanto a hipótese que na mediação os aspectos motivacionais e afetivos são componentes que se fazem presente na atuação desses professores alfabetizadores. O objetivo desta pesquisa foi o de levantar os aspectos motivacionais e afetivos na mediação do processo de alfabetização, através da fala de professores alfabetizadores. Foram entrevistados 18 professores com a premissa de serem bons alfabetizadores. Investigar o que mobiliza e caracteriza a ação dos docentes, que mesmo possuindo inúmeras variáveis que interfiram negativamente nesse processo, conseguem obter êxito no desenvolvimento da alfabetização de seus alunos é uma possibilidade de levantar questões voltadas à problemática da aprendizagem do processo de alfabetização

  9. Aspectos significativos surgidos de la experiencia de haber sido responsable de un evento adverso en salud

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    Augusto Hernán Ferreira-Umpiérrez

    2014-01-01

    Full Text Available Objetivo: conocer los aspectos significativos para las enfermeras sobre su experiencia de haber sido responsables de un evento ad- verso en salud. Materiales y métodos: estudio cualitativo exploratorio, con el enfoque de la hermenéutica dialéctica. Se utilizó la técnica de análisis de contenido. Muestra constituida por doce enfermeras que tuvieron al menos una experiencia de responsabilidad ante un evento adverso con un paciente, y por cuatro supervisores de enfermería con responsabilidad de supervisión al ocurrir el evento adverso. Resultados: bajo el enfoque de la hermenéutica dialéctica, el análisis de los datos permitió construir las siguientes categorías relacio- nadas con la organización de salud y los recursos humanos: el contexto organizacional, el desconocimiento del proceso de notifi cación, la sobrecarga de trabajo, la ausencia de descanso. Conclusiones: reconocer la importancia del contexto organizacional donde se desarrollan los cuidados, el desconocimiento del proceso de notificación como aspecto por mejorar, la sobrecarga de trabajo y la ausencia d e descanso del personal. Es necesario profundizar en el tema mediante investigaciones y desarrollo de intervenciones que promuevan la cult ura de seguridad en la atención sanitaria, con implicaciones en la práctica y para la formación de las enfermeras.

  10. Aspectos sociales de la malaria importada en Latinoamérica

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    Alfonso J. Rodríguez-Morales

    2008-04-01

    Full Text Available La malaria continúa siendo un grave problema de salud pública mundial, ya no sólo en países endémicos, sino comenzando a representar un dilema médico en países distantes por la llegada de casos importados. Ahora bien, aun cuando en términos de las disciplinas médicas convencionales se ha publicado muchos estudios clínico-epidemiológicos y reportes de caso, los aspectos sociales, que parecerían obvios en el contexto de la malaria importada por supeditarse a la migración de la población, no han sido exhaustivamente explorados en relación con este fenómeno. Por estas razones, en esta revisión se analiza los aspectos sociales relacionados con el fenómeno de la malaria importada con énfasis al contexto epidemiológico de América Latina.

  11. Roman wall-painting technical aspects | Aspectos técnicos de la pintura mural romana | Aspectos técnicos de la pintura mural romana

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    Lorenzo Abad Casal

    1982-12-01

    Full Text Available Se estudian diversos aspectos técnicos de la pintura mural romana: composición de los morteros, sistemas de unión entre las diversas capas, trazados previos, técnica pictórica y técnicas de conservación y restauración. Todo ello se plasma en una serie de gráficas que ilustran las técnicas romanas y su evolución a través de los siglos. | Etude des divers aspects techniques de la peinture murale romainne: composition des mortiers, systèmes d'union entre les différents couches, dessins préparatoires, technique de la peinture et procedés de conservation et de restauration. Un resumé sous forme graphique permet une vision synoptique de l'évolution des techniques de peinture romaine au cours des siècles.

  12. Aspectos “Subjetivos” do Fetichismo da Mercadoria Cultural no Ensaio Sobre Música Popular de T. W. Adorno

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    Fábio César da Silva

    2017-05-01

    Full Text Available Neste artigo, apresento uma leitura do ensaio Sobre Música Popular (1941 de T. W. Adorno (1903-1969, enfatizando os aspectos “subjetivos” do fetichismo da mercadoria cultural. Considero aspectos “subjetivos” do fetichismo quando se enfatiza o consumo de mercadorias. Esse ensaio fez parte dos resultados de pesquisa de rádio da Universidade de Princeton, feita nos Estados Unidos entre 1938 a 1940, cujo objetivo era analisar as programações radiofônicas. Focarei a leitura na seção Teoria do Ouvinte, pois nela Adorno enfatizou esses aspectos “subjetivos” por meio de análises específicas do consumo da música popular americana supondo seus modos de recepção.

  13. Aspectos ergonômicos e estatísticos no projeto de um carro do metrô

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    Costa Neto Pedro Luiz de Oliveira

    2002-01-01

    Full Text Available Este artigo descreve experimentos realizados como parte de um trabalho envolvendo aspectos do projeto de um carro para uma nova linha do Metrô de São Paulo. Nele são considerados aspectos ergonômicos relacionados com a posição de barras de segurança e assentos, bem como aspectos estatísticos relacionados com o fluxo de passageiros entrando e saindo do carro na estação. Nesse estudo, é de particular interesse o uso da técnica do quadrado latino na análise de regressão múltipla, como forma de reduzir o porte do experimento.

  14. Direito a moradia e inclusão social: aspectos positivos e negativos do "programa minha casa minha vida"

    OpenAIRE

    Desordi, Jordana Laís; Strücker, Bianca

    2016-01-01

    O presente artigo pretende analisar aspectos conceituais e doutrinários referentes ao direito à moradia e à inclusão social, fazendo referência aos aspectos positivos e negativos do programa habitacional brasileiro “Minha Casa Minha Vida” (PMCMV). A pesquisa dá ênfase ao PMCMV, momento em que é analisada a legislação que cria e institui o Programa em suas duas versões existentes até este momento. Destaca-se, ainda, os reflexos que o programa causou ao proporcionar o acesso do indivíduo a sua ...

  15. Aspectos podológicos en la Encuesta Nacional de Salud

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    Antonio Martínez Sabater

    Full Text Available Objetivo: la Encuesta Nacional de Salud (ENS es el instrumento para detectar el nivel de salud de la población, por lo que se plantea como objetivo el análisis de las diferentes ediciones para valorar la presencia de los aspectos podológicos y de la figura del profesional de podología en la atención a las personas mayores. Metodología: se ha realizado un análisis de contenido de las diferentes ENS tras la recopilación de las diferentes ediciones (8. Después de la lectura en profundidad y análisis por parte de dos investigadores, se han cumplimentado las fichas de análisis y se han categorizado los diferentes transcriptores, y se ha realizado el análisis e interpretación de la información encontrada. Resultados: en las diferentes ediciones no aparece ninguna mención a la profesión de podología; sí que aparecen referencias a otras figuras como naturópatas, quiroprácticos, entre otros. En relación con los descriptores sobre las afecciones de los pies, solo aparece una referencia en la edición de 1987. No obstante, la referencia a aspectos podológicos es prácticamente inexistente. Conclusiones: la ENS es el instrumento básico para conocer el estado de salud de la población general, pero presenta limitaciones al omitir los aspectos podológicos que suponen una merma en el diagnóstico de las necesidades y, por consiguiente, en la calidad de vida de las personas, principalmente mayores. Al igual que ocurre con la cartera de servicios del SNS, obvia a los/as profesionales formados para la atención básica de los problemas podológicos en el equipo de salud.

  16. Aspectos neuropsicológicos da depressão Aspectos neuropsicológicos de la depresión Neuropsychological aspects of depression

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    Marcia Rozenthal

    2004-08-01

    Full Text Available Este artigo objetiva rever os principais achados neuropsicológicos na depressão, procurando diferenciar o tipo unipolar do bipolar, com ou sem psicose, tanto nos períodos de fase aguda quanto nos períodos intercríticos. Procurou-se, ainda, correlacionar os achados neuropsicológicos descritos na literatura consultada com os seus correlatos neuroanatômicos e neurofuncionais, ressaltando-se as áreas frontais e seus principais circuitos. Considerando-se estudos neuropsicológicos dos transtornos afetivos, algumas alterações têm se mostrado mais consistentes, sendo descritas disfunções importantes nas fases críticas, mas também no paciente assintomático. Nestas, interessam principalmente os aspectos atentivos e mnêmicos e o funcionamento executivo. Estudos desta natureza têm profundas implicações terapêuticas, apontando para a necessidade de desenvolver outras técnicas coadjuvantes, tais como reabilitação cognitiva e intervenções psicossociais, tornando o tratamento mais abrangente e incisivo nestes casos.Este artículo tiene por objetivo revisar los principales hallazgos neuropsicológicos en la depresión, procurando diferenciar sus formas de presentación unipolar y bipolar, con o sin sintomatología psicótica, tanto en el cuadro agudo como en los periodos inter-críticos. Busca, además, correlacionar los hallazgos neuropsicológicos descritos en la literatura consultada con los aspectos neuroanatómicos y neurofuncionales, destacando el área cortical frontal y sus circuitos principales. Considerándose estudios neuropsicológicos en trastornos afectivos, algunas alteraciones de atención, memoria y de funciones ejecutivas se han presentado más frecuentemente, siendo descritas en los periodos de crisis y también en el paciente asintomático. Estudios de esa naturaleza tienen profundas implicaciones terapéuticas, señalando además la necesidad de desarrollar otras técnicas terapéuticas coadyuvantes, tales como la

  17. Historical and social aspects of halitosis Los aspectos históricos y sociales de halitosis Aspectos históricos e sociais da halitose

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    Marina Sá Elias

    2006-10-01

    Full Text Available Buccal odors have always been a factor of concern for society. This study aims to investigate the historical and social base of halitosis, through systematized research in the database BVS (biblioteca virtual em saúde - virtual library in health and also in books. Lack of knowledge on how to prevent halitosis allows for its occurrence, limiting quality of life. As social relationships are one of the pillars of the quality of life concept, halitosis needs to be considered a factor of negative interference. Education in health should be accomplished with a view to a dynamic balance, involving human beings' physical and psychological aspects, as well as their social interactions, so that individuals do not become jigsaw puzzles of sick parts.Los olores bucales siempre han sido un factor de preocupación para la sociedad, y ellos todavía son ahora. El objetivo de este estudio es hacer una base histórica y social en la halitosis. Fue efectuada una investigación sistematizada en la base de datos BVS (biblioteca virtual em saúde - la biblioteca virtual en salud y también en los libros. La ignorancia en cómo prevenir la halitosis permite su ocurrencia, que limita la calidad de vida. Siendo las relaciones sociales uno de los pilares del concepto de calidad de vida, es necesario considerar la halitosis un factor de interferencia negativa. La educación en salud se debe llevar a cabo buscando un equilibrio dinámico, involucrando los aspectos físicos y psicológicos del ser humano, así como sus interacciones sociales, para que los individuos no se vuelvan rompecabezas de partes enfermas.O problema referente aos odores bucais sempre foi fator de preocupação para a sociedade e ainda hoje se mostra presente. O objetivo do presente estudo foi realizar um embasamento histórico e social sobre a halitose. Para tanto, foi feita busca sistematizada, selecionando artigos por meio da base de dados BVS (Biblioteca Virtual em Saúde e também pesquisa em

  18. Importancia de los aspectos psicosociales en la enfermedad celíaca

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    Trini Fragoso Arbelo

    2002-06-01

    Full Text Available Se revisan los conceptos clínicos actuales sobre la enfermedad celíaca. Se definen con precisión los términos enfermedad celíaca activa, silente, latente y potencial. Se enfatiza en los aspectos psicosociales que influyen en su tratamiento y se trazan pautas generales acerca del manejo integral de los pacientes afectados, dada la importancia de la dieta sin gluten de por vida como único tratamiento.The current clinical concepts of celiac disease are reviewed. The terms active, silent, latent and potential related to celiac disease are accurately defined. Emphasis is made on the psychosocial aspects influencing its treatment and general guidelines are drawn on the comprehensive management of the patients suffering from this disease, given the importance of diet without gluten as the only lifelong treatment.

  19. La dispepsia funcional: Aspectos biopsicosociales, evaluación y terapia psicológica

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    Stefano Vinaccia Alpi

    2008-09-01

    Full Text Available Se abordan los aspectos conceptuales del trastorno gastrointestinal Dispepsia funcional (DP, en lo que se refiere a su definición, prevalencia, clasificación y diagnóstico.; las causas y consecuencias de la DF desde una perspectiva biopsicosocial (variables socioeconómicas, demandas psicosociales, evaluación cognitiva y estrategias de afrontamiento, personalidad y comportamiento, mecanismos psicobiológicos, calidad de vida, tratamiento y evolución; la evaluación psicológica de la DF desde la perspectiva procesual; y la intervención psicológica, con énfasis en el enfoque cognitivo conductual.

  20. Aspectos claves-tiempo dependientes que amenazan la vida en el prehospitalario

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    Patricio A. Cortés P., Dr.

    2011-09-01

    En esta misma perspectiva, la resolución de oportunidad y calidad se logra apuntando hacia los aspectos claves-tiempo dependientes que amenazan la vida del paciente, siendo estos clínicos (parocardiorespiratorio, compromiso de la vía aérea y la ventilación, compromiso de la perfusión tisular y el enfrentamiento al dolor torácico con su expresión máxima que es el síndrome coronario agudo, como también organizacionales (entre algunos la presencia de médicos en el Prehospitalario (Ph o el uso de determinados recursos sensibles como el traslado heliportado.

  1. Miastenia grave: aspectos históricos Myasthenia gravis: historical aspects

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    FRANCISCO MARCOS B. CUNHA

    1999-06-01

    Full Text Available Foram pesquisados aspectos históricos da miastenia grave desde as primeiras descrições da doença em 1672, pelo clínico inglês Thomas Willis. São descritas as dificuldades encontradas no manuseio dos primeiros pacientes diagnosticados. Pesquisaram-se fatos históricos ligados à investigação da doença, o tratamento, bem como curiosidades pouco citadas na literatura.We studied historical aspects of myasthenia gravis starting from its first description by the English physician, Sir Thomas Willis, in 1672. We also describe the difficulties in managing triating the first diagnosed patient. Historical facts related to the investigation and the initial treatment of this disorder as well as curiosities seldom mentioned in the literature are part of this paper.

  2. Um aspecto da diversidade cultural do caboclo amazônico: a religião

    OpenAIRE

    Maués, Raymundo Heraldo

    2005-01-01

    ESTE TRABALHO trata de um aspecto da diversidade cultural do caboclo amazônico, isto é, a religião. Esta se constitui numa espécie de catolicismo popular, que mantém relações com o xamanismo nativo - a pajelança cabocla -, e que se originou de antigas práticas e crenças dos índios Tupinambás, que habitaram parte da região amazônica no período colonial, bem como de influências portuguesas e africanas.HIS PAPER deals with a particular aspect of the Amazon caboclo's cultural diversity, namely, r...

  3. Depressão na infância e adolecência: aspectos sociais

    OpenAIRE

    Lúcia Helena Siqueira Barbosa

    1987-01-01

    Este trabalho contém três partes. Uma primeira intitulada Introdução. Uma segunda focalizada sob o título de Material Clínico :apresentação, comentários e considerações sobre a prática do Serviço Social e, uma terceira, Considerações Finais. A primeira tenta discutir dois pontos: - algumas considerações sobre o conceito de depressão na infância e adolescência: caracterização de quadros clínicos com aspectos depressivos nítidos, mais ou menos "puros" e de "reações depressivas", em que tais asp...

  4. El aspecto lúdico en la enseñanza del ELE

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    Varela, Patricia

    2010-10-01

    Full Text Available Jugar y aprender son dos acciones íntimamente relacionadas, de forma que su complementación da lugar a un ambiente ameno en clase haciendo que el alumno se sienta más cómodo y abierto al aprendizaje. El objetivo de este artículo es analizar la importancia de la motivación en el alumno y los medios con los que contamos los docentes para desarrollarla de la forma más amena posible. Tendremos en cuenta la importancia del aspecto lúdico en la enseñanza del español como lengua extranjera y a la vez poner en práctica diversas posibilidades de aplicación del mismo

  5. Aspectos psicológicos en el cáncer ginecológico

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    María Eugenia Olivares Crespo

    2004-01-01

    Full Text Available En el presente trabajo se abordan los aspectos psicológicos concomitantes a la patologíaoncológica ginecológica. De forma habitual estas pacientes están sometidas a diferentes modalidadesterapéuticas que provocan efectos acumulativos. En términos generales, el tratamiento deelección es quirúrgico, principalmente mastectomía e histerectomía. Estos tratamientos quirúrgicosprovocan efectos antes, durante y después de los mismos. Entre los que cabe citar: alteraciones sexuales, cambios en la imagen corporal, infertilidad y menopausia inducida. Para concluir, seespecifican los procedimientos terapéuticos psicológicos del proceso, tanto del diagnóstico como deltratamiento quirúrgico y de los efectos derivados del mismo.

  6. Estudo dos aspectos éticos dos transplantes na América Latina

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    Virgínia Maria Coelho de Holanda

    1994-06-01

    Full Text Available Respeitando recomendações da OMS, foi feito estudo retrospectivo comparativo das Legislações de 16 Países da América Latina, a saber Argentina, Bolívia, Brasil, Colômbia, Costa Rica, Chile, Cuba, Equador, Guatemala, Honduras, México, Panamá, Paraguai, Peru, República Dominicana e Venezuela, do período de 1963 a 1992, enfatizando-se os aspectos éticos referentes a doação, determinação da morte, conflito de interesses, seleção do receptor, comercialização e intercâmbio internacional de órgãos.

  7. ASPECTOS SEMÁNTICOS EN LOS ENTORNOS VIRTUALES DE FORMACIÓN

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    Ana Vanessa Leguízamo León

    2010-07-01

    Full Text Available La semántica es un elemento necesario en cualquier actividad de aprendizaje, independientemente del contexto en el que nos encontremos. Los entornos virtuales de formación, como instituciones sociales mediadas por tecnología, tienen también una semántica asociada, que muchas veces es poco valorada por las personas que los diseñan. El componente semántico en estos entornos facilita la negociación de significados, que debe ocurrir para que los estudiantes puedan apropiarse de conocimiento y asociarlo con alguno de los patrones semánticos que ya posee, o crear uno nuevo. Se muestran aquí los aspectos semánticos que deben estar presentes en los entornos virtuales de formación, para situar al estudiante en el contexto semántico propuesto por el docente y que lo conduzca a un aprendizaje significativo.

  8. TRANSPORTE PÚBLICO DO MUNICÍPIO DE NATAL: aspectos de parafiscalidade do caso SETURN

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    Manoel Damião Machado da Silva

    2015-12-01

    Full Text Available A proposta deste trabalho é compreender como os aspectos da gestão parafiscal do Sindicato das Empresas de Transporte Urbano de Passageiros do Município do Natal – SETURN contribuem para a eficiência do transporte público e para a melhoria a mobilidade urbana, visando contribuir na qualidade de vida da população local. A pesquisa foi desenvolvida no Sindicato, baseada no estudo de caso, por meio de entrevista semiestruturada, onde foram feitas análises, com o objetivo de descrever a situação do transporte coletivo relativo à eficiência que, na visão da pesquisa, fica comprometida, uma vez que os automóveis particulares disputam o mesmo espaço nas vias, juntamente com os transportes coletivos, impedindo assim, agilidade nas viagens.

  9. Formación en recreación en Colombia: aspectos fundamentales para el estudio

    OpenAIRE

    Juan Manuel Carreño Cardozo; Narda Dioselina Robayo Fique

    2010-01-01

    El escrito presenta la reflexión fundamental de la investigación Estado del arte de los conceptos de recreación en Colombia, en Instituciones de educación técnica-tecnológica y de pregrado en recreación y afines originado en la línea de Investigación formar - Formación de Maestros en Recreación3 del programa Licenciatura en Recreación de la Facultad de Educación Física en la Universidad Pedagógica Nacional. La reflexión contiene los aspectos fundamentales que se postulan en la investigación p...

  10. Aspectos do Desenvolvimento Político e Econômico da Guyana

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    Iuri Cavlak

    2014-07-01

    Full Text Available Este artigo visa analisar alguns aspectos do desenvolvimento político e econômico da Guyana, pequeno país sul-americano situado no extremo norte do subcontinente. Tendo seu passado ligado a Holanda e a Inglaterra, a Guyana só conquistou sua independência em 1966, num contexto de avanço dos movimentos sociais, empolgados na construção de uma nova nação, e oposição dos Estados Unidos, tentando frear a difusão das ideias socialistas e o apego da política externa guianense ao bloco soviético. A busca por uma economia nacionalizada e planejada foi constante, embora com resultados deveras aquém do esperado.

  11. Aspectos históricos da vulcanização Historical aspects of vulcanization

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    Helson M. da Costa

    2003-06-01

    Full Text Available As borrachas, para serem convertidas em materiais úteis do ponto de vista de aplicações, precisam ser misturadas a alguns ingredientes, os quais vão lhes dar as características desejadas para, então, serem vulcanizadas. Neste artigo, os aspectos históricos da vulcanização são abordados bem como a evolução dos aditivos essenciais à maioria das formulações.Rubbers, to be turned into useful materials from the commercial applications point of view, need the addition of a few other ingredients which, upon vulcanization, will impart the desired characteristics to the material. In this paper, historical aspects of vulcanization are revised as well as the evolution of the additives used in most of the formulations.

  12. Modelo integral de productividad, aspectos importantes para su implementación

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    Jorge Eduardo Medina Fernández de Soto

    2010-08-01

    Full Text Available El Modelo Integral busca la optimización de la productividad, a partir de los objetivos estratégicos empresariales y el análisis y mejoramiento de la propuesta de valor para el cliente, identificando el nivel de operación óptimo y los recursos tangibles realmente necesarios. También identifica los procesos empresariales de creación de valor y es una guía hacia el desarrollo de la propuesta de valor. Además, analiza las inversiones necesarias para las nuevas propuestas de valor, buscando un crecimiento estratégico sostenible. El artículo explica en primer lugar los fundamentos y componentes del modelo y luego algunos aspectos importantes para su implementación.

  13. Globalización: aspectos políticos, económicos y sociales

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    Jambell García

    2010-01-01

    Full Text Available En el artículo se exploran las dimensiones políticas, económicas y sociales del proceso de globalización. La revisión documental, bibliográfica y hemerográfica, permite identificar los aspectos que involucra este fenómeno mundial. Como resultado se observa que mientras persista el actual esquema de reproducción capitalista a escala global, la globalización tenderá a favorecer más a un pequeño grupo de países altamente desarrollados, en detrimento de la mayoría de la población del planeta, haciendo difícil superar los retos del desarrollo humano. Se concluye la necesidad de un cambio de paradigma y de comportamiento por parte de la sociedad para alcanzar un desarrollo económico y social equitativo.

  14. Aspectos de la respuesta inmune innata en las infecciones intramamarias causadas por Staphylococcus aureus en bovinos

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    Elizabet A.L Pereyra

    2014-12-01

    Full Text Available Staphylococcus aureus es el principal agente causante de mastitis bovina en Argentina y en el mundo. Esta bacteria ocasiona infecciones crónicas que generan importantes pérdidas a los productores y la industria lechera. El objetivo de este artículo es caracterizar los mecanismos que intervienen en la infección causada por S. aureus en la glándula mamaria bovina, evaluando dos aspectos diferentes del proceso infeccioso: por un lado, lo vinculado con la respuesta inmune innata por parte del hospedador, y por otro, la capacidad de la bacteria para evadir el sistema inmune e interactuar con diferentes tipos celulares. La exploración de la interacción de S. aureus con el sistema inmune de la glándula mamaria bovina permitirá identificar blancos para delinear nuevas alternativas preventivas o curativas, que contribuyan a evitar o eliminar las infecciones causadas por este organismo.

  15. Aspectos teóricos para el estudio sociodemográfico del embarazo adolescente

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    Humberto Gónzalez Galbán

    2000-01-01

    Full Text Available El embarazo adolescente se presenta como un tópico de interés en una buena parte de los países del mundo actualmente. Ello se explica tanto por la gran incidencia que tiene en numerosas regiones como por las implicaciones sociales, familiares y personales a que es vinculado. Esta situación ha motivado la realización de investigaciones en las que las gestaciones en edades tempranas son centro de atención, sin embargo, en estos estudios el tema es presentado generalmente de manera inadecuada. En este articulo se retoma, desde el punto de vista sociodemográfico, el análisis de aspectos teóricos sobre el embarazo adolescente, presentando críticamente la forma en que es problematizado, así como los diferentes supuestos que es posible encontrar en la literatura especializada sobre el tema.

  16. Game, game, game and again game, de Jason Nelson: aspectos da contemporaneidade

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    Flavio Pereira Senra

    2016-01-01

    Full Text Available Embora pensadores como o escritor Mario Vargas Llosa afirmem que os tempos hodiernos têm como característica principal a frivolidade, por conta da velocidade e quantidade de informações a serem digeridas diariamente, artistas em sua pulsão criativa exploram tais paradoxos de grandeza/pequenez em suas obras de arte. Este artigo visa apreender na obra Game, game, game and again game aspectos da contemporaneidade, como o conceito de lúdico e a enorme gama de entretenimentos voltados a um público imerso na indústria da cultura, através da forma como eles são trabalhados junto a conceitos como interatividade como forma de coautoria da obra de arte, finitude artística e permanência no meio digital, e transmidialidade na criação estética.

  17. Audición espacial en ambientes reverberantes: aspectos teóricos relevantes

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    Claudia Arias

    2003-01-01

    Full Text Available En ambientes reverberantes el sonido se propaga en múltiples direcciones sufriendo cambios físicos de importancia. El sistema auditivo debe se capaz de resolver la competencia perceptual que se produce entre el sonido original y sus reflexiones. En este artículo se presentan aspectos teóricos relevantes de la audición espacial con especial tratamiento del efecto precedente. Se trata de una estrategia inconciente que el individuo utiliza para enfrentar la información sonora conflictiva de los espacios reverberantes. Es el fenómeno perceptual de fusión espacial que ocurre cuando dos sonidos similares se presentan desde diferentes lugares, separados por un breve retardo de tiempo. El individuo escucha sólo un sonido que localiza según la dirección del sonido que llegó primero

  18. Equilibrio liquido-liquido-vapor de misturas ternarias : algoritimo de calculo e aspectos termodinamicos

    OpenAIRE

    Maria Helena Cano de Andrade

    1991-01-01

    Resumo: Este trabalho é uma contribuição ao estudo de processos de separação envolvendo fases em equilibrio liquido-liquido-vapor. Os seguintes aspectos são abordados: (1) desenvolvimento de um algoritmo eficiente de cálculo de flash liquido-liquido-vapor e sua aplicação para gerar diagramas de fases e em cálculos de destilação; (2) avaliação da utilização de parâmetros binários do modelo UNIQUAC obtidos de dados bifásicos em cálculos trifásicos de misturas ternárias; (3) medidas experimentai...

  19. Estudo dos aspectos éticos dos transplantes na América Latina

    OpenAIRE

    Virgínia Maria Coelho de Holanda; Francélia Loureiro Nery; Marta Barrozo Azevedo; Tânia Cristina Botelho Mendes

    1994-01-01

    Respeitando recomendações da OMS, foi feito estudo retrospectivo comparativo das Legislações de 16 Países da América Latina, a saber Argentina, Bolívia, Brasil, Colômbia, Costa Rica, Chile, Cuba, Equador, Guatemala, Honduras, México, Panamá, Paraguai, Peru, República Dominicana e Venezuela, do período de 1963 a 1992, enfatizando-se os aspectos éticos referentes a doação, determinação da morte, conflito de interesses, seleção do receptor, comercialização e intercâmbio internacional de órgãos. ...

  20. A imagem do Brasil no discurso do New York Times. Aspectos sociais

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    Maria Inez Mateus Dota

    2010-01-01

    Full Text Available Este texto presenta un análisis de las noticias publicadas en el periódico The New York Times, versión digital, entre los meses de enero y junio de 2004. Al relacionarlas con los aspectos sociales del Brasil se intenta ver cuál es la imagen que ese periódico muestra del Brasil. El artículo adopta como fundamentos teóricos y metodológicos el análisis del discurso, principalmente las contribuiciones de Bell (1991, Fairclough (1995 y 2001, Fowler (1991 y Sousa (2004, discute las estrategias discursivas usadas para representar al Brasil y examina qué elementos escoge y los recursos de lenguaje que son empleados para la producción de los textos analizados.

  1. Aspectos genéticos del procesamiento de antígenos intracelulares

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    Beatriz Martínez

    1993-03-01

    Full Text Available La activación de los linfocitos T (LT, un aspecto fundamental en la generación de la respuesta inmune (RI, se produce mediante el contacto de sus receptores antigénicos (TCR con un complejo formado por un péptido derivado del antígeno y una molécula del complejo mayor de Histocompatibilidad (MHC, HLA en el humano sobre la superficie de una célula presentadora de antígenos (APC. El origen del péptido puede ser exógenooextracelular, como sucede con la mayoría de los antígenos presentados por las moléculas MHC clase II, o endógeno (intracelular, como es el caso de las proteínas virales. sintetizadas por la célula y presentadas por las moléculas MHC Clase.

  2. USO DE ANIMALES DE LABORATORIO EN COLOMBIA: REFLEXIONES SOBRE ASPECTOS NORMATIVOS Y ÉTICOS

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    L. Botero

    2013-01-01

    Full Text Available El uso de modelos animales para la experimentación se ha incrementado considerablemente en Colombia. Mientras en países desarrollados estos animales se producen en ambientes controlados bajo normas estrictas que garantizan la validez de los resultados de investigación, en Colombia la normatividad al respecto es precaria e imprecisa lo que ha llevado a que pocas instituciones mantengan los animales con los estándares requeridos para obtener resultados de investigación con el rigor que la comunidad científica internacional exige. En este artículo presentamos una breve revisión de la normatividad en el tema a nivel mundial y, finalmente, se mencionan algunas recomendaciones sobre ajgunos aspectos que debería integrar la normatividad colombiana para que se adecúe a las regulaciones internacionales.

  3. Aspectos fundamentais no desenvolvimento de sistemas microemulsionados contendo anfotericina B para uso oftálmico

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    Walteçá Louis Lima Silveira

    2013-01-01

    Full Text Available A exemplo do que ocorre com outros fármacos, a biodisponibilidade da anfotericina B (AmB através da via ocular repreesenta um grande desafio para a pesquisa científica. Na verdade, a baixa biodisponibilidade apresentada por tal molécula é devido, principalmente, a presença das barreiras oculares que impedem a absorção deste fármaco para os tecidos internos. A toxicidade associada a este fármaco, assim como a sua baixa capacidade em permear a córnea íntegra também consiste em um problema associado ao seu uso clínico. Novos veículos seguros e eficazes para a liberação ocular da AmB são, portanto, necessários. As microemulsões (MEs aparecem como um interessante sistema devido à sua transparência, estabilidade termodinâmica e favorável viscosidade. O conhecimento do processo de formação das MEs contendo AmB, assim como a compreensão de toda a sua caracterização físicoquímica correspondem a aspectos importantes para se determinar as condições favoráveis para que estes sistemas venham a ser empregados como colírios. Esta revisão tem como objetivo, portanto, abordar este tema enfatizando os principais aspectos relacionados com a utilização de MEs como sistemas de liberação para a AmB através da via tópica oftálmica.

  4. Aspectos Contábeis dos Créditos de Carbono: Estudo com Autores Nacionais

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    Vanderlei dos Santos

    2013-12-01

    Full Text Available O estudo objetiva verificar o entendimento de autores nacionais no que concerne à classificação, forma de reconhecimento e mensuração das operações com créditos de carbono. O estudo de natureza descritiva foi realizado em 2011, por meio de pesquisa de levantamento ou survey, com abordagem quantitativa. Utilizou-se o questionário como instrumento de coleta de dados, que foi enviado a 23 pesquisadores nacionais que possuem publicação de artigos relacionados à contabilização dos créditos de carbono em periódicos nacionais. Obtiveram-se nove respostas, que constituíram numa amostra por acessibilidade. Para a análise dos dados obtidos optou-se pelo uso da técnica da entropia informacional. Os resultados do estudo mostraram que, quanto à classificação dos créditos de carbono, há um entendimento maior entre os autores de que se trata de ativos especiais e que não podem ser considerados como commodity. Observou-se que não há consenso entre os autores em classificar os créditos de carbono como ativo intangível ou estoque. Deste modo, concluiu-se que ainda existem divergências no entendimento dos autores analisados no que concerne aos aspectos contábeis das operações com créditos de carbono. O artigo contribui principalmente na medida em que busca consolidar diferentes opiniões de autores, que pesquisam sobre a temática, demonstrando aspectos convergentes e divergentes, além de enfatizar lacunas para desenvolver pesquisas futuras.

  5. Aspectos éticos en la investigación cualitativa con niños

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    Luisa Fernanda Moscoso Loaiza

    2018-01-01

    Full Text Available La incorporación de los niños como participantes de estudios investigativos es una práctica más frecuente en la actualidad debido a la necesidad de conocer y entender su visión acerca de las experiencias de vida, lo que plantea nuevos retos y responsabilidades que se centran principalmente en las consideraciones éticas y metodológicas de la investigación. Este artículo describe los aspectos éticos que deben ser tenidos en cuenta en la investigación cualitativa con niños. Es un artículo de revisión con búsqueda sistemática en bases de datos, incluyendo artículos científicos, libros y literatura gris. Asimismo, se abordan las consideraciones éticas que se encuentran implicadas desde la vinculación de los niños como participantes, hasta la obtención de la información y la socialización de los resultados. Para la investigación se seleccionó la información relevante en torno a ocho temas conforme al proceso investigativo. Con esto se evidenció que la cuestión ética constituye un aspecto central en el momento de iniciar y desarrollar cualquier estudio investigativo, por lo que está presente desde su planteamiento hasta su finalización. Pudo concluirse que el cumplimiento de los criterios de rigor metodológico, como la dependencia, credibilidad, transferibilidad y confirmación, asegura la calidad de la investigación cualitativa con niños, y esto permite la adecuada aplicación de los principios éticos de beneficencia y no maleficencia, justicia, autonomía y confidencialidad.

  6. Aspectos socioeconómicos y familiares asociados en niños y adolescentes obesos

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    William José González Cabriles

    2013-01-01

    Full Text Available El estudio es transversal y correlacional donde se analizaron las variables socioeconómicas y familiares de una muestra no probabilística, constituida por 528 familias de niños con obesidad exógena, de 2 a 18 años, provenientes de diversos sectores del país, atendidos en la consulta de primera del Centro de Atención Nutricional Infantil Antímano. El objetivo fue determinar los aspectos socioeconómicos y familiares asociados en niños y adolescentes con obesidad que asistieron al Centro. Los datos se procesaron con el programa SPSS 9.0. Se analizaron las distribuciones de frecuencias y el estadístico Chi-cuadrado para probar asociación entre las variables. El nivel de significancia fue 95%. En las familias de niños obesos se encontró que la mayoría de los jefes de familia eran obesos; las familias con pobreza extrema y la población infantil mayor de 15 años presentaron mayor sedentarismo; por último, las madres en general no participaron en la toma de decisiones en la compra de alimentos y no poseían nociones de alimentación equilibrada que les permitieran planificar la compra de alimentos. Estos aspectos se erigen como claves para ser abordados y resueltos por el trabajador social durante la intervención con el fin de favorecer la recuperación nutricional del niño obeso y su familia.

  7. La actitud crítica un aspecto fundamental en la educación

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    Eduard Mauricio Wong Jaramillo

    2016-03-01

    Full Text Available En este artículo se reflexiona sobre el papel de la actitud crítica en la educación, dado que la capacidad de pensar por sí mismo y decidir de acuerdo con criterios racionales son aspectos decisivos que todo estudiante debe desarrollar, con el fin de propiciar sujetos que evalúen el saber. Otra razón que la hace necesaria es que la enseñanza pretende incentivar la formación de personas autónomas, que participen activamente en la vida política, social y cultural, aspectos que implican el ejercicio crítico y reflexivo. En la primera parte del documento se presentan algunos rasgos que identifican a la educación crítica, en tanto modelo que propende por formar seres humanos que piensen por sí mismos. Luego, se indaga acerca del fomento de prácticas educativas que permiten el desarrollo de competencias lógicas y argumentativas dado que la actitud crítica implica una evaluación racional. Por último, se resalta el papel de la filosofía y de la ciencia, pues en ellas se promueven deliberaciones sobre problemas teóricos y prácticos. En conclusión, la necesidad de estimular la actitud crítica es un elemento prioritario que la educación debe tener en cuenta, si lo que desea es promover seres humanos y sociedades que enfrenten de forma racional los problemas actuales

  8. Los Derechos de admisión y permanencia en los partidos políticos : aspectos constitucionales

    OpenAIRE

    Escobar Roca, Guillermo

    1993-01-01

    En este trabajo se estudia un doble aspecto del Derecho de partidos (la admisión y permanencia en los mismos), seguramente no central, pero cuyo correcto tratarniento jurídico puede coadyuvar a la ruptura de la impermeabilidad característica de estas organizaciones, formalmente privadas pero que desempeñan funciones públicas.

  9. ASPECTOS TAXONÔMICOS, FITOGEOGRÁFICOS E USOS DE Pectis uniaristata DC. var. jangadensis (S.Moore) Keil (ASTERACEAE)

    OpenAIRE

    PEREIRA, ARILDO GONÇALO; NETO, GERMANO GUARIM

    2014-01-01

    Este trabalho discute os aspectos taxonômicos, fitogeográficos e outros relacionados à Pectis uniaristata var. jangadensis (S. Moore) Keil (Asteraceae) uma planta de ocorrência na vegetação do cerrado e do pantanal de Mato Grosso.

  10. Aspectos clínico-patológicos e controle da paratuberculose em rebanho bovino leiteiro

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    Elise M Yamasaki

    2010-11-01

    Full Text Available A paratuberculose ou doença de Johne é uma enterite granulomatosa causada por Mycobacterium avium subsp. paratuberculosis. Descrevem-se os aspectos epidemiológicos, clínico-patológicos e laboratoriais da paratuberculose em rebanho bovino leiteiro no município de Rio Claro, região Sul do Estado do Rio de Janeiro. No período de 2006 a 2009, oito vacas adultas da raça Girolanda apresentaram diarreia crônico-intermitente e perda progressiva de peso. À necropsia, observaram-se linfonodos mesentéricos aumentados de volume e úmidos ao corte, vasos linfáticos subserosos das alças intestinais proeminentes, serosa do intestino com aspecto anelado e cerebroide e a mucosa espessada, pregueada e com aspecto microgranular. À microscopia havia, desde o duodeno até o reto, inflamação granulomatosa difusa, marcada dilatação dos vasos linfáticos no ápice das vilosidades, linfangiectasia e linfangite granulomatosa na submucosa, muscular e serosa. A inflamação granulomatosa também foi vista nos linfonodos mesentéricos. A coloração de Ziehl-Neelsen revelou variável quantidade de bacilos álcool-ácido resistentes no interior de macrófagos, de células gigantes de Langhans e livres na mucosa e submucosa dos intestinos delgado e grosso e em linfonodos mesentéricos. Em alguns animais, a lâmina própria da mucosa, principalmente do jejuno e íleo exibia acentuada hipertrofia. Mycobacterium avium subsp. paratuberculosis foi isolado em cultivo bacteriano de Herrold com micobactina, a partir de amostras de fezes, de raspado de mucosa intestinal e de leite e identificado pela técnica de PCR IS900. Através da avaliação sorológica semestral, foram analisadas 298 vacas do mesmo rebanho a partir de três anos de idade, observou-se cerca de 40% de animais reagentes ao teste ELISA indireto no período estudado. O diagnóstico da paratuberculose foi baseado nos dados clínico-patológicos, na sorologia, no isolamento e identificação do

  11. Aspectos psicobiológicos do comportamento alimentar Psychobiological aspects of feeding behavior

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    Rosana Passos Beinner Cambraia

    2004-06-01

    Full Text Available Esta revisão aborda alguns aspectos psicobiológicos ligados à manifestação do comportamento alimentar, e tem como objetivo evidenciar a relação entre os principais processos neuropsicológicos e a neurociência nutricional. Algumas estruturas neurais estão associadas ao controle alimentar por mecanismos distintos e correlatos que ocorrem no hipotálamo, hipocampo e em outras áreas como no cerebelo, bulbo olfatório, glândulas pituitária e pineal que exercem funções distintas, porém influênciam o comportamento alimentar, intermediadas geralmente por neurotransmissores comuns. Os precursores dos neuroquímicos apresentam funções específicas, sendo a influência na alimentação relevante no contexto comportamental da escolha de alimentos. Os processos sensoriais na alimentação como paladar, olfato, visão e audição interagem entre si e com outras estruturas e vias neurais, participando também do controle do apetite e da saciedade, que culminam na iniciação e no término da alimentação. A interação entre aspectos neurais no processo de consumo de alimento promove a manifestação do comportamento alimentar específico para cada espécie em seu ambiente.This review shows how some psychobiological aspects are related to feeding behavior manifestation, and has as it objective to provide evidence as to the relation between neuropsychological processes and nutritional neuroscience. Several neural structures are associated with alimentary controls, which are distinct but correlated mechanisms; for example: hypothalamus, hypocampus, cerebellum, olfactory bulb, pituitary and pineal glands, all presenting distinct functions, but affecting feeding behavior directly or indirectly through common neurotransmitters. Neurochemical precursors present specific functions and their influence on feeding is evident in behavioral food selection. The sensory processes in feeding, principally taste, olfaction, vision and hearing, interact with

  12. Aspectos psicosociales del embarazo en la adolescencia, año 2000

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    Elena Ávila Gálvez

    2002-12-01

    Full Text Available Se realizó un estudio explicativo-observacional, de tipo estudio de casos y controles, en adolescentes entre 10 y 19 años, del sexo femenino, provenientes del Policlínico Docente "Wilfredo Pérez Pérez", en el año 2000, compartidos en 2 grupos: el estudio, con 53 casos que se embarazaron, y el control con 106 adolescentes que no lo hicieron. Se compararon diferentes aspectos de la sexualidad, esfera familiar y sociodemográficos, con el fin de determinar la influencia de algunos aspectos psicosociales del embarazo en la adolescencia. La mayoría de las adolescentes del grupo estudio se incluían en la adolescencia tardía, con inestabilidad en la pareja, mejor nivel de instrucción de los padres, mayor porcentaje que no estudiaba ni trabajaba, con padres divorciados, criadas solamente por la madre, de familias disfuncionales, con inicio precoz de la actividad sexual sin anticonceptivos, con problemas psicológicos que se enmarcaban en el hogar y la familia.An explanatory-observational case-control type-study was performed on female adolescents aged 10-19 years from "Wilfredo Pérez Pérez Teaching Polyclinics in the year 2000. They were divided into two groups: the study group comprising 53 pregnant patients and the control group including 106 adolescents who were not pregnant. Several aspects related to sexuality, family environment and also socio-demographic questions were compared to determine the impact of some psychosocial aspects of pregnancy in adolescence. Most of the adolescents in the study group were in their late adolescence, they had no permanent partner, their parents had a higher level of education; a high number of them neither studied nor worked, their parents were mostly divorced, they were raised by their mothers only, they were from dysfunctional families, with early beginning of sexual intercourse without contraceptives and psychological problems involving the family and the house.

  13. Aspectos nutricionais relacionados ao ciclo menstrual Nutritional aspects related to menstrual cycle

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    Helena Alves de Carvalho SAMPAIO

    2002-09-01

    Full Text Available O objetivo da presente revisão é apresentar os principais tópicos discutidos na literatura quanto à associação da nutrição com o ciclo menstrual, contribuindo para a implementação do atendimento nutricional de mulheres. São revisados aspectos referentes à fisiologia da menstruação, alterações metabólicas durante o ciclo menstrual e comportamentos alimentares associados a ele. Considerando-se o ciclo menstrual dividido em duas fases, a folicular e a lútea, é nesta última que são descritas mais alterações, como retenção de água, elevação de peso, aumento de demanda energética, modificações no perfil lipídico e no metabolismo de vitamina D, cálcio, magnésio e ferro, hipersensibilidade emocional, dores generalizadas e mudança do comportamento alimentar. Em relação a este último item, podem ocorrer maior ingestão energética e o desenvolvimento de compulsões alimentares, principalmente por chocolate, doces e alimentos muito salgados. É fundamental que todos os aspectos citados sejam investigados durante a consulta nutricional, a fim de serem adotadas condutas mais específicas.The aim of the present review is to show the most important topics discussed in literature about the association between nutrition and menstrual cycle, contributing to improve the nutritional care for women. Aspects related to physiology of the menstruation, metabolic changes and feeding behavior during the menstrual cycle are reviewed. Considering the menstrual cycle divided in two phases, follicular and luteal, it is in this last one that more alterations are described, like fluid retention, weight gain, increase in caloric needs, modifications in the lipid profile and in the metabolism of vitamin D, calcium, magnesium and iron, emotional hypersensitivity, aches and changes in feeding behavior. In relation to this last item, it can occur a higher caloric intake and the development of food cravings, mainly for chocolate, candies and

  14. Atores profissionais e estudantes de teatro: aspectos vocais relacionados à prática

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    Juliana Richinitti Vilanova

    Full Text Available RESUMO Objetivo: identificar e comparar, em atores profissionais e estudantes de teatro, os aspectos relacionados à prática profissional, ao uso profissional da voz, hábitos e cuidados vocais, hábitos de saúde e condições ambientais no trabalho. Métodos: participaram 60 sujeitos de ambos os sexos, subdivididos em 2 grupos: Grupo Profissional - atores profissionais de teatro e Grupo Alunos - alunos de teatro sem experiência profissional teatral. Ambos os grupos responderam a um questionário que abordou aspectos relacionados à prática profissional, à voz, hábitos vocais, de saúde, condições ambientais e cuidados vocais. Resultados: os indivíduos do Grupo Profissional apresentaram maior ocorrência de rouquidão; maior ocorrência dos hábitos de usar a voz profissional quando está gripado, em posturas corporais e com respiração inadequadas, gritar, e permanecer em local com mofo ou pouca ventilação, fechado e empoeirado, e realizar ensaio em local diferente do local do espetáculo. O hábito de saúde de ingerir bebidas geladas foi maior no Grupo Alunos. O número de sujeitos que não possuem dificuldade em cena e que realizam aquecimento vocal é significantemente maior no Grupo Profissional. O tipo de aquecimento realizado significantemente mais pelo Grupo Profissional foi som de "s", respiração costo-diafragmática, som basal e vogais. Conclusão: constatou-se que ambos os grupos realizam hábitos prejudiciais e estão expostos a ambiente de trabalho inadequado para saúde vocal. Estes dados apontam a necessidade de ações de saúde vocal, a fim de minimizar o risco de alterações vocais nos profissionais e preparar os estudantes para o aumento da demanda vocal.