Дисертації: "Cox-2 expression"

1

Sun, Haipeng. "Regulation of Cyclooxygenase Gene Expression by Glucocorticoids in Cardiomyocytes." Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/194896.

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Glucocorticoids (GCs) are endogenous steroid hormones that regulate a number of critical physiological processes. Psychological stress increases the level of GCs in the circulating system. The biological effect of elevated GCs on the heart is not well understood. We found that GCs induced Cyclooxygenase-1 (COX-1) and COX-2 gene expression in cardiomyocytes. COX-1 or COX-2 encodes the rate-limiting enzyme in the biosynthesis of prostanoids, which modulate crucial physiological and pathophysiological responses. The present studies aim to elucidate the signaling transduction pathway and the mechanism underlying GC induced COX expression.Our data demonstrate that GCs activate COX-1 gene expression through transcriptional regulation. COX-1 gene promoter studies support a role of Sp binding site in CT induced COX-1 gene expression. The nuclear protein binding to this site appears to be Sp3 transcription factor. Co-immunoprecipitation assays indicated a physical interaction between GR and Sp3 protein. Silencing of Sp3 transcription factor with small interfering RNA suppressed CT-induced COX-1 promoter activation. These data suggest that the activated GR interacts with Sp3 transcription factor that binds to COX-1 promoter to up-regulate COX-1 gene expression in cardiomyocytes.We also found that administration of GC in adult mice increased the level of COX-2 in the ventricles. With isolated neonatal cardiomyocytes, corticosterone (CT) induces the transcription of COX-2 gene. This response appears to be cardiomyocyte cell type specific and GC receptor (GR)-dependent. CT causes activation of p38 MAPK and subsequently CREB phosphorylation that mediates COX-2 gene expression. Mifepristone, a GR antagonist, failed to inhibit p38 and CREB activation and p38 inhibition failed to prevent activation of GR. These data suggest that two parallel signaling pathways, GR and p38 MAPK, act in concert to regulate the expression of COX-2 gene in cardiomyocytes.In addition to the investigation of mechanism and signaling transduction pathway, I have explored pharmacological agents that modulate COX expression. LY294002, a commonly used PI3K inhibitor, inhibited COX-2 gene expression via a PI3K-independent mechanism. Whereas GSK-3 inhibitors, such as lithium chloride, upregulated COX-2 gene expression, but suppressed GC-induced COX-1 expression. These data have paved the foundation for pharmacological manipulation of COX-1 and COX-2 gene expression in the heart.

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2

Fritzsche, Julia. "Expression von EGFR, HER-2 und COX-2 beim Zervixkarzinom: Vergleich von Primärtumoren und Rezidiven." Doctoral thesis, Universitätsbibliothek Leipzig, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-119352.

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Ziel dieser Studie war es, die Häufigkeit der Expression von EGFR, HER-2 sowie COX-2 im Zervixkarzinom zu eruieren. Dabei galt es herauszufinden, ob Unterschiede hinsichtlich des Nachweises dieser drei, möglicherweise therapeutisch relevanten Moleküle zwischen den primären, nicht vortherapierten und operierten Karzinomen und den multimodal vorbehandelten Rezidiven gab. In der vorliegenden retrospektiven Arbeit wurden 45 TMMR-operierte Primärtumoren und 28 LEER-operierte Rezidivtumoren der Universitätsfrauenklinik Leipzig (Triersches Institut) einbezogen und zusätzlich hinsichtlich der prognostischen Überlebensanalyse durch das Tumorstadium, Lymphknotenmetastasen und Rezidivauftreten sowie histologischer Charakteristika untersucht. Dazu wurden Tissue - Microarrays angefertigt mit anschließender immunhistochemischer Untersuchung dieser. Die Ergebnisse zeigten, dass die TMMR-Operation die Überlebensprognose signifikant verbessert, denn lediglich bei den LEER-therapierten Rezidivtumoren erlitten die Patientinnen sowohl Fernmetastasen als auch erneute Rezidive. Weder die Expression der drei untersuchten Moleküle noch die histopathologischen Parameter haben eine prognostische Relevanz. Es gibt keine signifikanten Zusammenhänge zwischen der Häufigkeit der Expression von EGFR, HER-2 sowie COX-2 und Primär-, bzw. Rezidivtumoren, sodass diese Moleküle keine Targets für eine individualisierte, zielgerichtete Therapie beim Zervixkarzinom darstellen.

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3

Kim, Janet Heejung. "Cyclooxygenase-2 Expression in Post-Mastectomy Chest Wall Relapse." Yale University, 2006. http://ymtdl.med.yale.edu/theses/available/etd-06282006-104942/.

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The purpose of this study was to assess the prognostic significance and clinical correlations of cyclooxgenase-2 expression (COX) in a cohort of patients treated with radiation (RT) for post-mastectomy chest wall relapse (PMCWR). Between 1975 and 1999, 113 patients were treated for isolated PMCWR. All patients were treated with biopsy and/or excision of the CWR followed by RT. Median follow-up was 10 years. All clinical data including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy were entered into a computerized database. Paraffin-embedded CWR specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0-3+. A score of 2-3+ was considered positive. Overall survival from original diagnosis for the entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after CWR was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after CWR. COX was considered positive in 13 of 38 cases. COX was inversely correlated with ER (p= .045) and PR (p = .028), and positively correlated with HER-2/neu (p =.003). COX was also associated with a shorter time to PMCWR. The distant metastasis-free rate for COX negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2 positive patients (p = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative (p = 0.003). Outcome following RT for PMCWR is relatively poor. Positive COX correlated with other markers of poor outcome including a shorter time to local relapse, negative ER/PR and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for PMCWR.

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4

Kim, Youngsoo. "Molecular characterization of cyclooxygenase-2 (COX-2) expression in murine skin carcinoma cells /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.

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5

Rowe, Kherie Sheheda Janelle. "Cox-2 expression : interaction of Neisseria meningitidis with human cells." Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519420.

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6

Abdalla, Salem Ishtiwi. "Cyclooxygenase-2 (cox-2) expression in Barrett's oesphageal epithelium : relationship to inflammation and cancer." Thesis, Queen Mary, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418127.

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7

Lysitsa, Stella. "Evolution du lichen plan buccal et expression de la COX-2 /." Genève : [s.n.], 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253996.

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8

Huppes, Rafael Ricardo [UNESP]. "Expressão gênica de MMP-2 e 9, TIMP-1 e 2, ATM, TP53, VEGF, COX-2 e CDH-1 no TVT canino." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/122030.

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Made available in DSpace on 2015-04-09T12:28:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-06-20Bitstream added on 2015-04-09T12:47:47Z : No. of bitstreams: 1 000814346.pdf: 1337951 bytes, checksum: 9ed960afb83960e3296a726e4541f251 (MD5) A literatura cita que 1 a 5% dos casos de tumor venéreo transmissível (TVT) primário são metastáticos. Sendo assim, é importante estudar os mecanismos que colaborem para a invasão metastática assim como para sua implantação. Dentre estes mecanismos as metaloproteinases (MMP-2 e MMP-9) e seus inibidores (TIMP-1 e TIMP-2), assim como o ATM, COX-2, VEGF e CDH-1 podem explicar a implantação tumoral no sítio primário e a ocorrência da invasão metastática do TVT no cão. O objetivo do presente trabalho é avaliar a expressão gênica dos marcadores acima e correlacionar a sua expressão com o poder de implantação e invasão metastática no TVT. Para este estudo foram avaliadas 32 amostras tumorais, que foram congeladas e delas extraídos RNAm. Utilizou-se o método de qRT-PCR para todos os transcritos. Os resultados foram comparados com sangue periférico de 10 cães saudáveis (grupo controle) com o teste de Mann Whitney. A expressão gênica de MMP-2 e TIMP-1 foi significativamente maior do que o grupo controle (p < 0,001; p = 0,037; respetivamente). A expressão dos transcritos dos genes MMP-9 e TIMP-2 não apresentou diferença estatística entre o TVT e grupo controle (p = 0,535; p = 0, 906; respetivamente). A avaliação de expressão de transcritos do ATMapresentou aumento significativo (p < 0,0001) de sua expressão no tecido tumoral (TVT) quando comparado com o grupo controle, enquanto a expressão dos transcritos do gene TP53 não apresentou diferença estatística entre os grupos (p = 0,26). Na avaliação da COX-2, VEGF, CDH-1 foi verificado aumento significativo (p < 0,0001; p < 0,0001; p = 0,04, respectivamente) da expressão de transcritos dos genes no tecido tumoral (TVT) em relação ao grupo controle. A super-expressão de MMP-2 e o TIMP-1 pode explicar a capacidade de implantação das células tumorais assim como a maior expressão de VEGF e COX-2 pode explicar o crescimento rápido local do tumor e ... The literature reports that 1-5% of cases of primary trasmissible venereal tumor (TVT) are metastatic. Thus, it is interesting to study the mechanisms that collaborate to the metastatic invasion and implantation of TVT. Among these mechanisms, the metalloproetinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2), as well as ATM, COX-2, VEGF and CDH-1 may explain the tumoral implantation in the primary site and metastatic invasion of TVT in dogs. The objectives of this study are to evaluate the gene expression of these markers and to correlate their expression with the high ability of deployment and metastatic invasion of TVT. For this study, 32 tumor samples were frozen and their mRNA were extract using the qRT-PCR method for all transcripts. The results were compared with peripheral blood of 10 healthy dogs (control group) using the Mann Whitney test. The expression of MMP-2 and TIMP-1 were significantly higher than the control group (p <0.001, p = 0.037, respectively). The expression of MMP-9 and TIMP-2 showed no statistical difference between the TVT and the control group (p = 0.535, p = 0, 906, respectively). The expression of ATM was increased in tumor tissue (TVT) when compared with the control group, while the expression of TP53 had no statistical difference between groups (p = 0.26). The evaluation of COX-2, VEGF and CDH-1 were increas in tumor tissue when compared with control group. The over expression of MMP-2 and TIMP-1 may explain the implantation ability of the tumor cells, as well as the increase of VEGF and COX-2 may explain the rapid tumor growth and the rich vasculatization. While the over expression of ATM, TP53 and CDH-1 may contribute to the low metastatic capacity of the TVT tumor

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9

Huppes, Rafael Ricardo. "Expressão gênica de MMP-2 e 9, TIMP-1 e 2, ATM, TP53, VEGF, COX-2 e CDH-1 no TVT canino /." Jaboticabal, 2014. http://hdl.handle.net/11449/122030.

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Orientador: Renée Laufer Amorim Coorientador: Andrigo Barboza De Nardi Coorientador: Mirela Tinucci Costa Banca: Rosemere de Oliveira Vasconcelos Banca: Geórgia Mode Magalhães Banca: Rafael Torres Neto Banca: Bruno Watanabe Minto Resumo: A literatura cita que 1 a 5% dos casos de tumor venéreo transmissível (TVT) primário são metastáticos. Sendo assim, é importante estudar os mecanismos que colaborem para a invasão metastática assim como para sua implantação. Dentre estes mecanismos as metaloproteinases (MMP-2 e MMP-9) e seus inibidores (TIMP-1 e TIMP-2), assim como o ATM, COX-2, VEGF e CDH-1 podem explicar a implantação tumoral no sítio primário e a ocorrência da invasão metastática do TVT no cão. O objetivo do presente trabalho é avaliar a expressão gênica dos marcadores acima e correlacionar a sua expressão com o poder de implantação e invasão metastática no TVT. Para este estudo foram avaliadas 32 amostras tumorais, que foram congeladas e delas extraídos RNAm. Utilizou-se o método de qRT-PCR para todos os transcritos. Os resultados foram comparados com sangue periférico de 10 cães saudáveis (grupo controle) com o teste de Mann Whitney. A expressão gênica de MMP-2 e TIMP-1 foi significativamente maior do que o grupo controle (p < 0,001; p = 0,037; respetivamente). A expressão dos transcritos dos genes MMP-9 e TIMP-2 não apresentou diferença estatística entre o TVT e grupo controle (p = 0,535; p = 0, 906; respetivamente). A avaliação de expressão de transcritos do ATMapresentou aumento significativo (p < 0,0001) de sua expressão no tecido tumoral (TVT) quando comparado com o grupo controle, enquanto a expressão dos transcritos do gene TP53 não apresentou diferença estatística entre os grupos (p = 0,26). Na avaliação da COX-2, VEGF, CDH-1 foi verificado aumento significativo (p < 0,0001; p < 0,0001; p = 0,04, respectivamente) da expressão de transcritos dos genes no tecido tumoral (TVT) em relação ao grupo controle. A super-expressão de MMP-2 e o TIMP-1 pode explicar a capacidade de implantação das células tumorais assim como a maior expressão de VEGF e COX-2 pode explicar o crescimento rápido local do tumor e ... Abstract: The literature reports that 1-5% of cases of primary trasmissible venereal tumor (TVT) are metastatic. Thus, it is interesting to study the mechanisms that collaborate to the metastatic invasion and implantation of TVT. Among these mechanisms, the metalloproetinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2), as well as ATM, COX-2, VEGF and CDH-1 may explain the tumoral implantation in the primary site and metastatic invasion of TVT in dogs. The objectives of this study are to evaluate the gene expression of these markers and to correlate their expression with the high ability of deployment and metastatic invasion of TVT. For this study, 32 tumor samples were frozen and their mRNA were extract using the qRT-PCR method for all transcripts. The results were compared with peripheral blood of 10 healthy dogs (control group) using the Mann Whitney test. The expression of MMP-2 and TIMP-1 were significantly higher than the control group (p <0.001, p = 0.037, respectively). The expression of MMP-9 and TIMP-2 showed no statistical difference between the TVT and the control group (p = 0.535, p = 0, 906, respectively). The expression of ATM was increased in tumor tissue (TVT) when compared with the control group, while the expression of TP53 had no statistical difference between groups (p = 0.26). The evaluation of COX-2, VEGF and CDH-1 were increas in tumor tissue when compared with control group. The over expression of MMP-2 and TIMP-1 may explain the implantation ability of the tumor cells, as well as the increase of VEGF and COX-2 may explain the rapid tumor growth and the rich vasculatization. While the over expression of ATM, TP53 and CDH-1 may contribute to the low metastatic capacity of the TVT tumor Doutor

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10

Laube, Markus. "Synthese von Cyclooxygenase-2-Inhibitoren als Grundlage für die funktionelle Charakterisierung der COX-2-Expression mittels PET." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-160091.

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Eine erhöhte COX-2-Expression wird bei Krankheiten wie rheumatoider Arthritis aber auch Parkinson, Alzheimer und Krebs beobachtet. Die nichtinvasive Visualisierung und Quantifizierung der COX 2-Expression in vivo mittels Positronen-Emissions-Tomographie (PET) könnte wertvolle Beiträge zur Diagnose dieser Krankheiten liefern. Zur Nutzung der PET-Technik werden geeignete COX-2-adressierende Radiotracer benötigt, deren Entwicklung auch die Identifizierung neuer, der Radiomarkierung zugänglicher COX-2-Inhibitoren als Leitstrukturen voraussetzt. Ziel dieser Arbeit war die Synthese von selektiven, der Radiomarkierung zugänglichen COX 2-Inhibitoren und deren In-vitro-Evaluierung, um Verbindungen zu identifizieren, die für eine weitere Entwicklung zu COX-2-adressierenden Radiotracern geeignet sind. Im Rahmen dieser Arbeit wurden ausgehend von literaturbekannten COX-2-Inhibitoren zwei grundlegende Strategien verfolgt: die Derivatisierung an der Peripherie sowie der Austausch von Strukturelementen im Grundgerüst der COX-2-selektiven Inhibitoren. In dieser Arbeit wird zum einen die Synthese der Zielverbindungen (Diphenyl-substituierte Indol-, Pyrazolo[1,5-b]pyridazin-, 1,2-Dihydropyrrolo[3,2,1-hi]indol- und Pyrrolo[3,2,1-hi]indol-Derivate sowie 2-Carbaboranyl-substituierte Indol-Derivate) und deren strukturanalytische Charakterisierung vorgestellt. Es konnte die McMurry-Cyclisierung als neuer Zugang für die Synthese von Carbaboranyl-substituierten Verbindungen und 1,2-Dihydropyrrolo[3,2,1-hi]indol-Derivaten sowie die Dehydrogenierung mittels DDQ als neue Variante zur Synthese von Pyrrolo[3,2,1-hi]indol-Derivaten etabliert werden. Durch Röntgeneinkristallstrukturanalyse wurde die Molekülstruktur von sechs Zwischenverbindungen und neun Zielverbindungen aufgeklärt. Zum anderen erfolgte die Charakterisierung der Verbindungen in vitro, wobei die COX-inhibitorischen Eigenschaften mit einem Fluoreszenz-basierten, einem Enzymimmunoassay (EIA)-basierten und einem [14C]Arachidonsäure-basierten COX-Assay bestimmt und zudem viele Verbindungen hinsichtlich ihrer Redoxeigenschaften untersucht wurden. Im Besonderen die hergestellten Indol-Derivate besitzen antioxidative Eigenschaften, die bei der Untersuchung der COX inhibitorischen Eigenschaften beachtet werden müssen. Die Derivatisierung an der Peripherie der bekannten Inhibitoren führte zur Identifizierung von zwei Aminosulfonyl-substituierten Indol-Derivaten und einem Fluorethoxy-substituierten Pyrazolo[1,5 b]pyridazin-Derivat, die grundsätzlich geeignete Kandidaten für eine weitere Entwicklung zum Radiotracer darstellen. Das Fluorethoxy-substituierte Pyrazolo[1,5 b]pyridazin-Derivat wurde im Rahmen dieser Arbeit mit Fluor-18 markiert und die initiale Charakterisierung des Radiotracers in vitro durchgeführt. Der Austausch von Strukturelementen im Grundgerüst der literaturbekannten COX-2-Inhibitoren mit voluminöseren Gruppen führte zum einen bei Austausch eines Phenylrings gegen einen Carbaboranyl-Cluster zum Verlust der COX-inhibitorischen Eigenschaften, was eine weitere Entwicklung dieser Verbindungen zum Radiotracer ausschließt. Zum anderen wurde ausgehend von 2,3-Diphenyl-1H-indol-Derivaten die bicyclische auf eine tricyclische Kernstruktur vergrößert. Dies lieferte hoch affine und selektive COX-2-Inhibitoren. Unter den hergestellten Verbindungen wurden ein 1,2-Dihydropyrrolo[3,2,1-hi]indol- und drei Pyrrolo[3,2,1-hi]indol-Derivate als vielversprechende Kandidaten für die weitere Entwicklung zum Radiotracer identifiziert.

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11

Laube, Markus. "Synthese von Cyclooxygenase-2-Inhibitoren als Grundlage für die funktionelle Charakterisierung der COX-2-Expression mittels PET." Doctoral thesis, Technische Universität Dresden, 2014. https://tud.qucosa.de/id/qucosa%3A28510.

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Eine erhöhte COX-2-Expression wird bei Krankheiten wie rheumatoider Arthritis aber auch Parkinson, Alzheimer und Krebs beobachtet. Die nichtinvasive Visualisierung und Quantifizierung der COX 2-Expression in vivo mittels Positronen-Emissions-Tomographie (PET) könnte wertvolle Beiträge zur Diagnose dieser Krankheiten liefern. Zur Nutzung der PET-Technik werden geeignete COX-2-adressierende Radiotracer benötigt, deren Entwicklung auch die Identifizierung neuer, der Radiomarkierung zugänglicher COX-2-Inhibitoren als Leitstrukturen voraussetzt. Ziel dieser Arbeit war die Synthese von selektiven, der Radiomarkierung zugänglichen COX 2-Inhibitoren und deren In-vitro-Evaluierung, um Verbindungen zu identifizieren, die für eine weitere Entwicklung zu COX-2-adressierenden Radiotracern geeignet sind. Im Rahmen dieser Arbeit wurden ausgehend von literaturbekannten COX-2-Inhibitoren zwei grundlegende Strategien verfolgt: die Derivatisierung an der Peripherie sowie der Austausch von Strukturelementen im Grundgerüst der COX-2-selektiven Inhibitoren. In dieser Arbeit wird zum einen die Synthese der Zielverbindungen (Diphenyl-substituierte Indol-, Pyrazolo[1,5-b]pyridazin-, 1,2-Dihydropyrrolo[3,2,1-hi]indol- und Pyrrolo[3,2,1-hi]indol-Derivate sowie 2-Carbaboranyl-substituierte Indol-Derivate) und deren strukturanalytische Charakterisierung vorgestellt. Es konnte die McMurry-Cyclisierung als neuer Zugang für die Synthese von Carbaboranyl-substituierten Verbindungen und 1,2-Dihydropyrrolo[3,2,1-hi]indol-Derivaten sowie die Dehydrogenierung mittels DDQ als neue Variante zur Synthese von Pyrrolo[3,2,1-hi]indol-Derivaten etabliert werden. Durch Röntgeneinkristallstrukturanalyse wurde die Molekülstruktur von sechs Zwischenverbindungen und neun Zielverbindungen aufgeklärt. Zum anderen erfolgte die Charakterisierung der Verbindungen in vitro, wobei die COX-inhibitorischen Eigenschaften mit einem Fluoreszenz-basierten, einem Enzymimmunoassay (EIA)-basierten und einem [14C]Arachidonsäure-basierten COX-Assay bestimmt und zudem viele Verbindungen hinsichtlich ihrer Redoxeigenschaften untersucht wurden. Im Besonderen die hergestellten Indol-Derivate besitzen antioxidative Eigenschaften, die bei der Untersuchung der COX inhibitorischen Eigenschaften beachtet werden müssen. Die Derivatisierung an der Peripherie der bekannten Inhibitoren führte zur Identifizierung von zwei Aminosulfonyl-substituierten Indol-Derivaten und einem Fluorethoxy-substituierten Pyrazolo[1,5 b]pyridazin-Derivat, die grundsätzlich geeignete Kandidaten für eine weitere Entwicklung zum Radiotracer darstellen. Das Fluorethoxy-substituierte Pyrazolo[1,5 b]pyridazin-Derivat wurde im Rahmen dieser Arbeit mit Fluor-18 markiert und die initiale Charakterisierung des Radiotracers in vitro durchgeführt. Der Austausch von Strukturelementen im Grundgerüst der literaturbekannten COX-2-Inhibitoren mit voluminöseren Gruppen führte zum einen bei Austausch eines Phenylrings gegen einen Carbaboranyl-Cluster zum Verlust der COX-inhibitorischen Eigenschaften, was eine weitere Entwicklung dieser Verbindungen zum Radiotracer ausschließt. Zum anderen wurde ausgehend von 2,3-Diphenyl-1H-indol-Derivaten die bicyclische auf eine tricyclische Kernstruktur vergrößert. Dies lieferte hoch affine und selektive COX-2-Inhibitoren. Unter den hergestellten Verbindungen wurden ein 1,2-Dihydropyrrolo[3,2,1-hi]indol- und drei Pyrrolo[3,2,1-hi]indol-Derivate als vielversprechende Kandidaten für die weitere Entwicklung zum Radiotracer identifiziert.

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12

Scheer, Martin-Jürgen [Verfasser]. "Die Rolle der Cyclooxygenase-2-(COX-2)-Expression auf Prognose und Therapie oraler Plattenepithelkarzinome / Martin-Jürgen Scheer." Köln : Deutsche Zentralbibliothek für Medizin, 2011. http://d-nb.info/1017871841/34.

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13

Sheridan, Jared. "Partnership between the aryl hydrocarbon receptor (AHR) and RELB regulates cigarette smoke-induced cyclooxygenase-2 (COX-2) expression." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123307.

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Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lungs caused by cigarette smoke exposure; COPD is also now the third leading cause of death worldwide. Controlling lung inflammation is a priority in COPD patients, but currently-available medications offer little relief. Thus, new therapeutic targets represent a major unmet need. Previously, the aryl hydrocarbon receptor (AHR) has been shown to suppress cigarette smoke-induced inflammation. The AHR is a ligand-activated transcription factor, and well-established for its response to xenobiotic ligands. AHR-mediated suppression of smoke-induced inflammation requires the NF-κβ family member RELB. To date, nothing is known about the expression of AHR or RELB in subjects with COPD. Therefore, we investigated the expression of the AHR and RELB in human lung fibroblasts derived from Control (Non-smoker), Smoker and COPD subjects, as well as the mechanism through which they repress the production of the inflammatory protein cycloxygenase-2 (COX-2) in response to cigarette smoke extract (CSE). There was reduced AHR expression in COPD subjects, which was associated with increased expression of COX-2 protein (but not mRNA) in quiescent COPD fibroblasts. Inhibition of AHR activity in lung fibroblasts by the pharmacological AHR antagonist CH-223191 increased COX-2 protein induction by CSE. Mechanistically, this increase in COX-2 protein corresponded with increased cytoplasmic shuttling of the RNA binding protein HUR which is known to prolong the half-life of RNA transcripts - including COX-2. HUR was observed to be cytoplasmically-localized in lung tissue from COPD subjects, but not Control, suggesting altered regulation of HUR in COPD subjects. Another protein associated with the suppressive function of the AHR- RElB, was reduced in both Smoker and COPD lung fibroblasts, suggesting cigarette smoke may contribute to the reduced expression. siRNA-knockdown of RELB increased the production of Cox-2 mRNA in response to CSE or IL-1β, supporting that RELB contributes to the suppression of Cox-2. We hypothesized this may be due to miR-146a, an anti-inflammatory microRNA (miRNA) which targets Cox-2 mRNA for degradation. miR-146a basal expression was not significantly different between the subject groups. However, only Control fibroblasts increased miR-146a expression in response to CSE. siRNA knockdown of RELB abrogated the expression of miR-146a in response to IL-1β, but not CSE, suggesting RELB repression of Cox-2 mRNA does not involve miR-146a, but that RELB may regulate miR-146a under certain stimuli. Collectively, these data support the regulatory role of AHR and RELB in cigarette smoke-induced inflammation, and thus represent promising new cellular targets with the potential for controlling inflammation characteristic of COPD. La maladie pulmonaire obstructive chronique (MPOC) est une maladie inflammatoire chronique des poumons causée par l'exposition à la fumée de cigarette, maintenant au troisième rang des causes de mortalité mondiaux. Le contrôle de l'inflammation pulmonaire est hautement prioritaire pour les patients atteints de MPOC, mais les médicaments actuellement disponibles ne réduisent guère cette inflammation. Les nouvelles cibles thérapeutiques restent donc un important besoin non satisfait. La RAH est bien établi comme une réponse à des ligands xénobiotiques toxiques. La suppression par l'entremise de RAH de l'inflammation causée par la fumée de cigarette nécessite un membre de la famille NFκβ. Jusqu'à date, rien n'est connu de l'expression de RAH ou RELB parmi les patients atteints de MPOC. Par conséquent nous avons examiné ci-dessus la relation entre l'expression de RAH et RELB dans les fibroblastes de poumon humains dérivés des sujets témoins (non-fumeurs), fumeurs, et sujets atteints de MPOC, ainsi que le mécanisme par lequel ils répriment la production de la protéine inflammatoire cyclo-oxygénase 2 (COX-2) en réponse à l'extrait de la fumée de cigarette (EFC). L'expression des protéines RAH a été réduite parmi les fibroblastes des sujets atteints de MPOC, qui était aussi associée avec une expression accrue de la protéine COX-2 (mais pas ARNm) parmi les fibroblastes quiescents. L'inhibition de l'activité de RAH dans les fibroblastes pulmonaires par l'antagoniste pharmacologique CH-223191 a augmenté l'induction de COX-2 par EFC. Mécaniquement, cette augmentation de la protéine COX-2 a correspondu avec un accroissement du transport cytoplasmique de la protéine de liaison d'ARN HUR, qui est connu pour prolonger la demi-vie des transcrits d'ARN, y compris COX-2. Il a été observé que HUR est cytoplasmiquement localisé dans le tissu pulmonaire des sujets atteints de MPOC, mais non pas les témoins, suggérant une régulation altérée de HUR parmi les sujets atteints de MPOC. Une autre protéine associée avec cette fonction de suppression de la RAH=RElB a été réduite parmi les fibroblastes pulmonaires des sujets-fumeurs et sujets atteints de COP, suggérant que la fumée de cigarette puisse contribuer à cette expression réduite. pARNi (ou siRNA) anéantissement de RELB accroissait la production de COX-2 ARNm en réponse à CSE ou IL-1, appuyant l'observation que RELB contribue à la suppression de COX-2. Nous avons formulé l'hypothèse que cela pourrait être du à miR-146a, un micro-ARN (miARN) qui cible COX-2 mRNA pour dégradation. L'expression basale de miR-146a ne fut pas significativement différente parmi les divers groupes de sujets. Pourtant seulement les fibroblastes des sujets témoins ont accru l'expression de miR-146 en réponse à l'EFC. pARNi (ou siRNA) anéantissement de RELB a abrogé l'expression de miR-146 en réponse à IL-1β, mais pas l'EFC, suggérant que la répression par RELB de COX-2 ARNm n'entraîne pas miR-146a, mais que RELB pourrait réglementer miR-146a soumis à certains stimuli. Collectivement, ces données étayent le rôle régulateur de RAH et RELB dans l'inflammation induite par la fumée de cigarette, et donc représentent de nouvelles cibles cellulaires prometteuses, pleines de potentiel de contrôler l'inflammation caractéristique de MPOC.

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Kommareddy, Madhavi. "Upregulation of COX-2 protein expression in porcine macula densa with L-NAME treatment." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/6073.

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Thesis (M.S.)--University of Missouri-Columbia, 2008. The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.

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15

Pacelli, Anna. "Development of a PET probe for the imaging of COX-2 expression in cancers." Thesis, University of Hull, 2015. http://hydra.hull.ac.uk/resources/hull:15192.

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The COX-2 isozyme is overexpressed in several kinds of cancer, including colorectal, lung, breast, and oesophageal cancer. High levels of COX-2 are usually associated with poor prognosis and advanced disease. Furthermore, studies have suggested that co-administering COX-2 inhibitors along with classic chemotherapy can improve disease outcome. Therefore, COX-2 is an attractive PET imaging biomarker for patient stratification. A first library of potential COX-2 inhibitors with a 5,5-diphenyl hydantoin core was synthesised and screened for its affinity for COX isozymes. This structure was chosen for its novelty, its potential to improve the biodistribution of the tracer, due its lipophilicity, and its possible in vivo metabolic stability. However, these compounds showed no affinity for COX-2, therefore its further development into PET probes was no longer pursued. A second library with a 1,5-diphenyl imidazole structure was designed and synthesised, based on previous literature data with optimistic IC50 values for COX inhibition. A candidate for fluorine-18 radiolabelling was identified, therefore nitro and trimethyl ammonium triflate precursors were synthesised. A variety of conditions were tested for the fluorine-18 radiolabelling reactions, which identified the trimethyl ammonium precursor as a better choice. Further experiments, however, are needed in order to fully optimise the conditions of the reaction and to calculate the specific activity. In conclusion, two libraries of potential COX-2 inhibitors were designed, synthesised and tested in order to develop a PET imaging probe. A possible compound was identified, precursors were synthesised and radiolabelled with fluorine-18 in a variety of conditions, though further tests are necessary.

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Benderro, Girriso Futara. "AMBIENT OXYGEN AVAILABILITY MODULATES EXPRESSION OF VASCULAR ANGIOGENIC FACTORS AND CAPILLARY REMODELING (ANGIOPLASTICITY) IN THE MOUSE BRAIN." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1350159484.

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17

Yeoh, Ann Suk Jing. "Nuclear factor kB (NFkB) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is association with subsequent histopathologic changes /." Title page and abstract only, 2004. http://web4.library.adelaide.edu.au/theses/09MSB/09msby46.pdf.

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18

Carpenter, Oliver L. "Ultraviolet Light-Induced Regulation of Transcription and Translation, COX-2 Expression and Noncanonical NF-κB Activation". Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1382624015.

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19

Gu, Baoying. "Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy : effects of nimesulide." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112627.

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Wernicke's encephalopathy is a neuropsychiatric disorder resulting from thiamine deficiency (TD) and is characterized by neuronal loss, astrocytic proliferation and microglial activation. Cyclooxygenases (COX) are enzymes which catalyze the first step in the synthesis of prostanoids. COX-1 is expressed constitutively and COX-2 is the inducible isoform. Groups of TD rats and pair-fed controls were killed at presymptomatic and symptomatic stages of encephalopathy. Cresyl violet and NeuN staining showed decreased numbers of neuronal cells in vulnerable regions (medial thalamus and inferior colliculus) but not in a spared region (frontal cortex). Numbers of GFAP-positive and OX-42-positive cells were increased at symptomatic stage of encephalopathy. Expression of COX-2 mRNA and neuronal COX-2 immunoreactivity were selectively increased in vulnerable regions of TD rats at symptomatic stages of encephalopathy. Nimesulide, a highly selective COX-2 inhibitor, lowered PGE2 levels and precipitated the progression of encephalopathy suggesting that COX-2 in this model is conferring neuroprotection.

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20

Fallatah, Hafsah M. "Regulation of COX-2 expression by the BCL-3:NF-KappaB homodimeric complex : implications for colorectal carcinogenesis." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.685143.

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Cyclooxygenase-2 (COX-2) is an enzyme that plays a key role in the synthesis of prostaglandin (PGE2). COX-2 has been widely investigated in cancer progression studies generally and in colorectal cancer (CRC) specifically, not only because it is regulated by various signalling pathways, but also because it is one of the main players in the inflammation/cancer link. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) is among the transcription factors that have been repOlied to regulate the transcriptional activity of the COX-2 gene. Constitutive activity of NF-KB clearly results in the over-expression observed of COX-2. Although there are two KB sites localised at the promoter region of COX-2, the definitive mechanism by which COX-2 is regulated by NF-KB needs more elucidation. Several modulators have been repOlied that control NF-KB activity in order to maintain the selectivity or specificity of responses to the trigger. B-cell lymphoma-3 (BCL-3) is an oncogene that is up-regulated by inflammatory cytokines, such as tumour necrosis factor-a (TNF-a) and interleukin-l ~ (IL-l ~). It functions as a co-activator protein that binds favourably to the homodimer' subunits of NF-KB, namely pSO/pSO or pS2/pS2. Those two dimers are found to have repressor roles in the regulation of NF-KB target genes. However, when they bind to BCL-3, their action switches to an activator role. Therefore, understanding the exact role ofBCL-3: NF-KB homodimers complex in the context ofCOX-2 regulation by NF-KB signalling is crucial. Initially, I investigated the expression of BCL-3 and COX-2 in a range of different adenoma and carcinoma cells. I chose HCA 7/P and HT29 cells to be included in subsequent studies. In studying the effect of BCL-3 suppression in the level of COX-2 protein and its activity, potential regulation of COX-2 and PGE2 by BCL-3 has been revealed. This regulation has also been observed after the treatment of cells with TNF-a. Interestingly, the mRNA level of COX-2 has also been regulated by BCL-3 suppression, especially at 48 hours of BCL-3 silencing. Dual-Luciferase assay results of COX-2 gene also support this finding. Transfecting the cells with mutant BCL-3 (which cannot bind the homodimer pSO/pSO) has shown no change to the promoter activity of COX-2 as compared with cells transfected with wild-type BCL-3 protein; this suggests an addition to requirement amount of pSO to regulate COX-2 by BCL-3. Results obtained from Chromatin Immunoprecipitation (ChIP) experiments emphasised the presence of both BCL-3 and pSO in the predicted KB site of the COX-2 promoter. In vivo, there was a marked increase of both BCL-3 and COX-2 expression in carcinoma tissue as compared to healthy normal tissue, indicating the important role they play in the progression from adenoma to carcinoma. Because BCL-3 has been shown to regulate the level of PGE2, it was important to investigate whether this had . any consequence on the role played by PGE2 in the proliferation and sternness of the adenoma cell RG/C2. It was also significant to study the effect of Nonsteroidal anti-inflammatory drugs (NSAIDs) on the function of BCL-3 in regards to the COX-2/PGE2 signalling pathway. Treating cells with aspirin results in a decrease in the protein level of BCL-3 and COX-2, which strengthens the notion of aspirin chemoprevention 's role in tumour regression. This study is proposing, for the first time, the potential use of BCL-3: COX-2/PGE2 as a therapeutic target of CRC prevention and treatment.

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21

László, Csaba F. "Translation regulation of UV-light-induced transcription factor NF-kappa-B and oncogene COX-2." View abstract, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3353542.

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22

Weinheimer, Eileen M. "The effect of acute resistance exercise on the expression of the COX-1 variants and COX-2 in human skeletal muscle : implicaitons [sic] for protein synthesis." Virtual Press, 2006. http://liblink.bsu.edu/uhtbin/catkey/1339598.

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Cyclooxygenase (COX) is the enzyme that catalyzes the rate-limiting step in prostaglandin (PG) synthesis. In skeletal muscle, PGF2a, has been shown to regulate protein synthesis, and ibuprofen and acetaminophen have been shown to block the normal increase in PGF2a and muscle protein synthesis following resistance exercise in humans. The purpose of this investigation was to determine the expression of the COX-1 (COX-1 variants: COX-1 v1, -1v2, -1 b,, -1 b2, and -1b3) and COX-2 isoforms following resistance exercise to help elucidate the isoform or variant through which PGF2a, ibuprofen, and acetaminophen regulate muscle protein synthesis. Human skeletal muscle biopsy samples were taken from 16 individuals (8M, 8F) before, 4 h, and 24 h following a single bout of resistance exercise and analyzed using real-time RT-PCR. COX-Iv1 and COX-1v2 were the most abundant COX mRNA before exercise and remained unchanged (P>0.05) following exercise (i.e., constitutively expressed). Relatively few individuals expressed the intron 1-retaining COX-1 b variants (COX-1 b,, - 1b2, and -1 b3) at any time point, and when expressed these variants were in very low abundance. COX-2 was not expressed in any subject before exercise, but increased significantly (P<0.05) at 4 and 24 h following exercise. These results suggest that the intron 1-retaining COX-1 b,, -1 b2, and -lb3 variants are likely not the COX through which PGF2a is produced to stimulate skeletal muscle protein synthesis. PGF2a, stimulation, as well as ibuprofen and acetaminophen inhibition of skeletal muscle protein synthesis likely work through COX-2, or one of the constitutively expressed COX-1 variants (COX-lv1 or -1v2). School of Physical Education, Sport, and Exercise Science

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23

Fritzsche, Julia [Verfasser], Lars-Christian [Akademischer Betreuer] Horn, and Christian [Gutachter] Wittekind. "Expression von EGFR, HER-2 und COX-2 beim Zervixkarzinom: Vergleich von Primärtumoren und Rezidiven / Julia Fritzsche ; Gutachter: Christian Wittekind ; Betreuer: Lars-Christian Horn." Leipzig : Universitätsbibliothek Leipzig, 2013. http://d-nb.info/1238524877/34.

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24

Mattsson, Johanna. "An integrative strategy for targeted evaluation of biomarker expression in non-small cell lung cancer." Doctoral thesis, Uppsala universitet, Molekylär och morfologisk patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-285844.

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Despite improvements in therapy, the prognosis for non-small cell lung cancer (NSCLC) patients remains poor, and cure is only possible in localized tumors after surgical resection. A new generation of targeted cancer drugs has led to the expectation that lung cancer therapy can be significantly improved, but these drugs are today only an option in a small subset of NSCLC patients, and their effect is temporary. Therefore, the aim of this thesis was to characterize NSCLC in order to find new treatment targets and to evaluate biomarkers that further optimize therapy selection. In Paper I, the expression of the potential treatment targets claudin 6 and claudin 18.2 were evaluated based on immunohistochemical- and gene expression analysis. High ectopic protein and gene expression were demonstrated for both claudins in small subgroups of NSCLC. Clinical trials using humanized monoclonal antibodies against both proteins are ongoing in other cancer forms and may be extended to NSCLC. In Paper II, the prognostic impact of the inflammatory mediator cyclooxygenase 2 (COX-2) was evaluated. No prognostic significance was found in a meta-analysis incorporating gene expression data of 1337 NSCLC patients. Likewise, COX-2 protein expression in tumor cells was not associated with survival in two independent NSCLC cohorts. However, in one of the analyzed cohorts, higher COX-2 expression in the tumor stroma was associated with longer survival and may therefore be a subject for further investigation. In Paper III, tumor and stromal COX-2 protein expression was examined in patients treated with the COX-2 inhibitor celecoxib in order to evaluate if COX-2 expression is a predictive biomarker for benefit of celecoxib therapy. Celecoxib did not prolong overall survival neither in the whole cohort nor in patients stratified according to COX-2 expression in tumor or stromal cells. Noteworthy, a tendency towards longer survival was again demonstrated in patients with high COX-2 stromal expression. In Paper IV, the diagnostic methods for identification of ALK rearrangements were assessed in a large representative Swedish NSCLC population. Fluorescence in situ hybridization (FISH), as the diagnostic standard, was compared to two immunohistochemical assays. ALK gene expression levels were incorporated to supplement the molecular data. The frequency of ALK rearrangements was lower than previously reported. The different methods to detect the ALK fusion demonstrated overlapping results. However, the overlap was poor, so the methods cannot be regarded as interchangeable and should thereby be interpreted with caution when used in clinical diagnostics. In summary, this thesis applied an integrative translational approach to characterize potential new treatment targets and to evaluate the detection of existing predictive biomarkers in NSCLC.

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25

[Verfasser], Kanokwan Kaewmala. "Association and expression study of CD9, PLCz and COX-2 as candidate genes to improve boar sperm quality and fertility traits / Kanokwan Kaewmala." Bonn : Universitäts- und Landesbibliothek Bonn, 2011. http://d-nb.info/1016156766/34.

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26

Ferguson, Shawn. "Non-steriodal anti-inflammatory drug-mediated regulation of COX-2 and EP3 receptor expression in the M-1 murine cortical collecting duct cell line." Thesis, University of Ottawa (Canada), 1999. http://hdl.handle.net/10393/8909.

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The cortical collecting duct (CCD) is a major site of intrarenal prostaglandin E2 (PGE2) synthesis. By indirect immunofluorescence using isoform specific antibodies, we have localized COX-1 and -2 immunoreactivity to all cell types of the murine M-1 CCD cell line. By, immunohistochemistry, both COX-1 and COX-2 were localized to the intercalated cells of the collecting duct on paraffin embedded mouse kidney sections. When COX enzyme activity was measured in the M-1 cells, both indomethacin (COX-1 and -2 inhibitor) and the specific COX-2 inhibitor NS-398 effectively blocked PGE2 synthesis. These results demonstrate that COX-2 is a major contributor to the pool of PGE2 synthesized by the CCD. PGE2 exerts predominantly diuretic and natriuretic effects upon the CCD. Our results which document the expression of COX-2 in the CCD provide a mechanism through which the newly developed class of COX-2 specific inhibitors could exert side effects with respect to the regulation of fluid and electrolyte homeostasis. (Abstract shortened by UMI.)

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27

Laube, Markus [Verfasser], Torsten Akademischer Betreuer] Kniess, Jens [Akademischer Betreuer] [Pietzsch, Jörg Akademischer Betreuer] Steinbach, and Thomas [Akademischer Betreuer] [Henle. "Synthese von Cyclooxygenase-2-Inhibitoren als Grundlage für die funktionelle Charakterisierung der COX-2-Expression mittels PET / Markus Laube. Gutachter: Jörg Steinbach ; Thomas Henle. Betreuer: Torsten Kniess ; Jens Pietzsch ; Jörg Steinbach." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/1069093106/34.

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Laube, Markus Verfasser], Torsten [Akademischer Betreuer] Kniess, Jens [Akademischer Betreuer] [Pietzsch, Jörg Akademischer Betreuer] Steinbach, and Thomas [Akademischer Betreuer] [Henle. "Synthese von Cyclooxygenase-2-Inhibitoren als Grundlage für die funktionelle Charakterisierung der COX-2-Expression mittels PET / Markus Laube. Gutachter: Jörg Steinbach ; Thomas Henle. Betreuer: Torsten Kniess ; Jens Pietzsch ; Jörg Steinbach." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/1069093106/34.

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Ferguson, Shawn. "Non-steriodal anti-inflammatory drug mediated regulation of COX-2 and EP¦3 receptor expression in the M-1 murine cortical collecting duct cell line." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0029/MQ67814.pdf.

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30

Vorsprach, Monique [Verfasser], Marino [Gutachter] Venerito, and Marek [Gutachter] Lommatzsch. "Expression von Cyclooxygenasen (COX-1 und COX-2) und Lipoxygenase (5-LOX) in Nasenpolypen und Bronchialschleimhaut bei Patienten mit Asthma bronchiale, rezidivierender Polyposis nasi und Analgetikainteroleranz : Korrelation mit klinischen und funktionellen Parametern / Monique Vorsprach ; Gutachter: Marino Venerito, Marek Lommatzsch." Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2020. http://d-nb.info/1220035637/34.

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31

Cunha, Daniela Erica de Horta e. Goes Ribeiro da. "Avaliação da expressão de Cox-2 em tumores mamários da gata por imunohistoquímica : correlação com aspetos clinicopatológicos, classificação histopatológica e possíveis implicações clínicas." Master's thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2013. http://hdl.handle.net/10400.5/6098.

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Dissertação de Mestrado Integrado em Medicina Veterinária A cicloxigenase-2 (Cox-2) é uma enzima que desempenha um papel importante na tumorigénese e encontrando-se sobrexpressa em várias neoplasias humanas, incluindo o cancro da mama. Em medicina veterinária, alguns trabalhos mostram existir uma sobrexpressão da Cox-2 em certas neoplasias da espécie felina, incluindo nos tumores mamários, estando esta associada a pior prognóstico. Tendo em conta estas evidências, a utilização de fármacos anti-Cox-2 como agentes terapêuticos nas neoplasias mamárias é uma hipótese que poderá trazer benefícios importantes. A utilização destes fármacos poderá assumir particular interesse no caso da gata, devido à elevada frequência de tumores mamários nesta espécie e ao seu prognóstico pouco favorável. Desta forma, para além de poder funcionar como alvo terapêutico, a Cox-2 poderá também ser um bom indicador de prognóstico. Neste trabalho pretendeu-se analisar os níveis de expressão da Cox-2, de modo a melhor equacionar a sua importância como futuro alvo terapêutico. Assim, procedeu-se à avaliação dos níveis desta enzima numa amostra de 21 carcinomas mamários felinos de diversos tipos histológicos e graus de malignidade, pela técnica de imunohistoquímica (IHQ), recorrendo ao uso de dois anticorpos anti-Cox-2 distintos. Foi ainda analisada a correlação dos níveis de expressão desta enzima com diversos parâmetros clinicopatológicos e imunohistoquímicos. Com o Clone 33, todas as neoplasias estudadas revelaram expressão de COX-2, apesar de apenas um tumor ter sido classificado de positivo, tendo mostrado um padrão de imunomarcação perinuclear e citoplasmático. Pelo contrário, com o Clone SP21 a maioria dos tumores (20/21) foram considerados positivos, apresentando um padrão predominantemente membranar, mas também marcação citoplasmática e perinuclear. Este padrão citoplasmático e perinuclear foi observado nos mesmos tumores, em ambos os anticorpos. Verificou-se ainda a existencia de uma correlação entre os níveis de marcação da Cox-2 (Clone SP21) e a classificação histológica segundo a OMS. Ainda que mais investigação seja necessária, é possível concluir que o padrão de marcação da Cox-2, associado à classificação histológica poderá ter um papel na identificação de pacientes que irão beneficiar da utilização terapêutica de fármacos anti-Cox-2. ABSTRACT - Immunohistochemical Evaluation of Cox-2 Expression in Feline Mammary Tumours – Correlation with Clinicopathological Features, Histologic Type and Possible Clinical Implications - Cyclooxygenase-2 (COX-2) is an enzyme that plays an important role in tumorigenesis and is overexpressed in several types of human neoplasia, including breast cancer. In veterinary medicine, some studies show that Cox-2 is overexpressed in several tumours of the cat, including mammary tumours. This overexpression is associated with poor prognosis. All this facts lead to the conclusion that the use of anti-Cox-2 drugs in mammary tumours may yield important benefits. The use of such drugs in the queen is especially attractive since this type of neoplasia is highly frequent and also because of its less favourable prognosis. Cox-2 expression may also be a good prognostic indicator. In the present study the goal was to evaluate Cox-2 expression levels in order to explore its importance as a future therapeutic target. The expression of COX-2 was analysed in 21 tumour samples that included several histological types and grades, by immunohistochemistry (IHQ), using two different anti-Cox-2 antibodies. The correlation between Cox-2 expression and several clinicopathological and immunohistochemical parameters was also investigated. With Clone 33 all samples revealed Cox-2 expression, even though only one tumour was classified as positive, showing perinuclear and cytoplasmic labelling. Conversely, with Clone SP21 most tumours (20/21) were positive, showing mainly membrane labelling but also perinuclear and cytoplasmic staining. The cytoplasmic and perinuclear pattern was constant in the same tumours with both antibodies. A statistically significant correlation between Cox-2 expression levels and histological type according to the WHO classification was also found. Although, more investigation is necessary, it is possible to conclude that immunolabelling pattern associated with the histological classification may play an important role in selecting the patients that can benefit from the therapeutic use of anti-Cox-2 drugs.

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Junior, Sérgio de Melo Alves. "\"Análise da expressão e mecanismos de ação da proteína COX-2 em cultura de células de carcinoma epidermóide bucal humano\"." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-13032007-085956/.

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Celecoxib é um antiinflamatório não esteroidal (AINE), inibidor seletivo da ciclooxigenase-2 (COX-2) usado em pesquisas recentes como agente anticarcinogênico. Os seus efeitos anti-neoplásicos dependem por um lado da sua capacidade de inibir a COX-2, mas por outro lado também age por mecanismos que independem da COX-2, em resumo o seu mecanismo de ação ainda não é completamente conhecido. O objetivo desta tese foi estudar os efeitos do celecoxib sobre as taxas de apoptose e os índices de proliferação celular de quatro linhagens celulares, Hn-6, Hn-19, Hn-30, Hn-31, de CECP e uma linhagem de queratinócitos mutada (HaCat), além de verificar se há correlação entre a expressão das proteínas COX-2, pAkt, ß-catenina, CD1 e NFKB e a inibição da proliferação celular. As células foram divididas em dois grupos: a, grupo controle; b, células cultivadas tratadas com celecoxib. A análise da expressão das proteínas pAkt, NFKB, ß-catenina, COX-2 e CD1 foi feita através da técnica de Western-blot. A indução de apoptose foi estudada com o Kit de Anexina. A proliferação celular foi monitorada através de curva de crescimento, com contagem celular na câmara de Neubauer e com o teste de viabilidade celular (Kit Cell Titer96) e a localização intracelular das proteínas foi avaliada por imunofluorescência. Os resultados mostraram significante aumento no índice celular de apoptose e diminuição da proliferação celular. Após o tratamento com celecoxib, a imunofluorescência mostrou que a proteína CD1 teve diminuição da expressão nuclear, a ß-catenina exibiu discreto aumento citoplasmático, o pAkt também passou a ser expresso no citoplasma da Hn6, enquanto as outras proteínas estudadas mantiveram o mesmo padrão de localização na célula. O western blot complementou os resultados da imunofluorescência indicando uma diminuição nos níveis de CD1. Celecoxib, a cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drug, is a new anticarcinogenic agent. Its antitumor effects depend on the one hand on its COX-2-inhibiting potency, but on the other hand on COX-2-independent mechanisms, which until now have not been fully understood. The aim of this research was to study the effects of celecoxib in growth inhibition and apoptosis induction in four Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines, HN6, HN19, HN30, HN31 and HaCat an immortalized keratinocyte cell line, and verify if there is a correlation between the growth inhibition and the expression of COX-2, pAkt, ß-catenin, CD1 and NFKB. The Western Blot was used to analyze the COX-2, pAkt, ß-catenin, CD1 and NFKB protein expression level. Apoptosis induction was studied with the Annexin V kit. The cell lines proliferation will be measured through a growth curve with the Neubauer chamber and MTS method (KitCell Titer96), the proteins intracellular site was assed by immunofluorescence technic. The same cell lines without any treatment were used as controls. Results showed a significant increase in apoptotic cells index, and growth inhibition in cell lines treated with celecoxib. The proteins localization was determined through immunofluorescence. In control group the CD1 was located mostly in nucleus, after treatment CD1 nuclear localization was reduced, it could also be noticed an increase in cytoplasmic expression of ß-catenin in all cell lines while pAkt cytoplasmic increase was present exclusevely in Hn6, the other proteins maintained their cellular localization,. The Western Blot results showed considerable reduction in CD1 levels with exception of Hn19 cell line.

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Maia, Filho Hugo da Silva. "Expressão de aromatase no endométrio e seu papel no desenvolvimento de patologias uterinas." reponame:Repositório Institucional da UFBA, 2013. http://www.repositorio.ufba.br/ri/handle/ri/13092.

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p. 1-78 Submitted by Antonio Geraldo Couto Barreto (ppgms@ufba.br) on 2013-10-02T18:05:28Z No. of bitstreams: 1 Hugo Maia.pdf: 4715178 bytes, checksum: 067aa12a42b4bcfc56dd4ac8e4173ab8 (MD5) Approved for entry into archive by Rodrigo Meirelles(rodrigomei@ufba.br) on 2013-10-02T22:07:53Z (GMT) No. of bitstreams: 1 Hugo Maia.pdf: 4715178 bytes, checksum: 067aa12a42b4bcfc56dd4ac8e4173ab8 (MD5) Made available in DSpace on 2013-10-02T22:07:54Z (GMT). No. of bitstreams: 1 Hugo Maia.pdf: 4715178 bytes, checksum: 067aa12a42b4bcfc56dd4ac8e4173ab8 (MD5) Previous issue date: 2013 A expressão de aromatase no endométrio eutópico é desencadeada pela constante exposição a mediadores inflamatórios, que são produzidos durante o período menstrual e proliferativo do ciclo menstrual. A presença de aromatase nas células endometriais é um dos fatores desencadeantes de endometriose na cavidade peritonial, miomas submucosos e intra-murais, pólipos endometriais e adenomiose. Diante disso, esta tese tem como objetivo investigar os efeitos da expressão de aromatase no endométrio, compreendendo a ação desta e como se evitar o desenvolvimento das patologias endometriais. Para isso, foram analisados resultados de biopsias de pacientes submetidas à histerectomia e laparoscopia, no período de janeiro de 2007 a março de 2009 de dois centros de tratamento da cidade de Salvador- Bahia, as quais apresentavam algumas das patologias citadas, seguindo os critérios da American Sciety of Reproductive Medicine. Por fim concluiu-se que a diminuição da expressão de aromatase induzida por progestínicos foi acompanhada por uma redução na expressão de enzimas como ciclooxigenase-2 (Cox-2) ou de fatores angiogênicos como VEGF no endométrio. A inflamação no endométrio também foi reduzida pela progesterona ou por progestínicos e este mecanismo envolveu a inibição da ativação do NF-kappa B. Estes achados sustentam a hipótese do papel que teriam os progestínicos como agentes anti-aromatase e anti-inflamatórios no manejo atual da endometriose e de outras patologias ginecológicas. E que o uso contínuo de contraceptivos orais combinados contendo gestodeno ou o uso de sistemas intra-uterinos liberadores de levonorgetsrel são efetivos na prevenção tanto da recorrência de endometriose, quanto da menorragia associada a miomas. Salvador

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Monteiro, Cíntia Júnia. "Análise da expressão de COX-2 em células H9c2 infectadas com T. cruzi cepa Berenice-62." reponame:Repositório Institucional da UFOP, 2013. http://www.repositorio.ufop.br/handle/123456789/4138.

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Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa e Pós Graduação, Universidade Federal de Ouro Preto. Submitted by Oliveira Flávia (flavia@sisbin.ufop.br) on 2014-12-09T18:58:02Z No. of bitstreams: 1 DISSERTAÇÃO_AnáliseExpressãoCOX-2.pdf: 1502334 bytes, checksum: d6e0f3cd743292f155280ff733f23955 (MD5) Approved for entry into archive by Gracilene Carvalho (gracilene@sisbin.ufop.br) on 2014-12-09T21:07:52Z (GMT) No. of bitstreams: 1 DISSERTAÇÃO_AnáliseExpressãoCOX-2.pdf: 1502334 bytes, checksum: d6e0f3cd743292f155280ff733f23955 (MD5) Made available in DSpace on 2014-12-09T21:07:52Z (GMT). No. of bitstreams: 1 DISSERTAÇÃO_AnáliseExpressãoCOX-2.pdf: 1502334 bytes, checksum: d6e0f3cd743292f155280ff733f23955 (MD5) Previous issue date: 2013 O protozoário intracelular Trypanosoma cruzi é o agente etiológico da doença de Chagas, a principal causadora de cardiomiopatia e insuficiência cardíaca em regiões de endemicidade na América Latina. A miocardite aguda, uma das consequências da doença, é caracterizada por uma resposta inflamatória intensa com envolvimento de mediadores inflamatórios; dentre estes imunomoduladores, a prostaglandina E2 (PGE2) apresenta um importante papel no desenvolvimento da doença contribuindo para o remodelamento cardíaco e deficiências funcionais deste órgão após a infecção pelo T. cruzi. Os níveis de produção deste eicosanoide estão diretamente relacionados com a expressão e atividade da enzima ciclooxigenase-2 (COX-2). A regulação da expressão desta proteina pode se dar a nível transcricional, envolvendo a participação de fatores de transcrição, ou pós-transcricional, envolvendo proteínas que se ligam a RNAm, como a CUGBP2 e também por microRNAs. Desta forma, considerando-se que as respostas iniciais dos cardiomiócitos frente a invasão pelo T. cruzi desempenham um papel fundamental no estabelecimento da infecção a longo prazo e, assim, influenciam na progressão da doença, objetivou-se, neste estudo, avaliar a regulação e expressão de COX-2 em células H9c2 nos períodos iniciais após a infecção pela cepa Berenice-62 do T. cruzi. Para isso, foram estudados tempos de interação (período em que o parasito encontra-se no meio intracelular) de 0, 2, 6, 12, 24 e 48 horas após a infecção que foi realizada no período de 2 horas; células não infectadas foram utilizadas como controle. Foram realizadas análises da expressão dos transcritos e proteinas de COX-2, CUGBP2 e NF-kB; dos níveis de PGE2 produzidos durante a infecção; da expressão dos transcritos de Bcl-2, BAX e caspases 3 e 9, genes envolvidos na apoptose; da expressão de c-Myc, c-Jun e c-Fos (cujas proteinas se dimerizam para formarem o fator de transcrição AP1) e expressões de microRNAs envolvidos na modulação da expressão de COX-2, CUGBP2 e fosfolipase A2. Além disso, foi realizada microscopia de fluorescência para verificar a localização das proteinas COX-2, CUGBP2 e do RNAm de COX-2. Como resultados, observou-se que a infecção pela cepa Berenice-62 induz várias alterações celulares, dentre elas, o aumento da expressão e da atividade da proteina COX-2. O parasito também induz translocação desta proteina da região perinuclear para o núcleo e também para o citoplasma. Os fatores de transcrição NFkB, AP1 e c-Myc parecem não estar envolvidos na expressão de COX-2. Em relação a regulação pós-transcricional, a CUGBP2 parece regular a tradução de COX-2, porém, os miRNAs estudados não parecem estar envolvidos nesta regulação. O parasito apresenta-se co-localizado à COX-2 e à CUGBP2, levantando a hipótese do parasito se aderir a estas moléculas, ou até mesmo, internalizá-las. ______________________________________________________________________________________________ ABSTRACT: The intracellular protozoan Trypanosoma cruzi is the etiologic agent of Chagas disease, the leading cause of cardiomyopathy and heart failure in regions of endemicity in Latin America. The acute myocarditis, one of the consequences of the disease, is characterized by an intense inflammatory response involving inflammatory mediators like prostaglandin E2 (PGE2) that plays an important role in disease development contributing to cardiac remodeling and functional failure of this organ after infection with T. cruzi. The PGE2 production is directly related to the cyclooxygenase-2 (COX-2) protein expression and enzymatic activity. The control of cox-2 expression basically occurs at two levels, prior to transcription, involving transcription factors and post-transcriptionally, involving microRNAs and proteins which bind to mRNA, as well as CUGBP2. Thus, considering that the initial responses of cardiomyocytes against invasion by T. cruzi play a key role in the establishment of long-term infection and thus influence the progression of the disease, the aim of this study was to evaluate the regulation and expression of COX-2 in H9c2 cells in the initial periods after infection by T. cruzi, Berenice -62 strain. In this regard, we studied the interaction time (period in which the parasite is intracellularly) 0, 2, 6, 12, 24 and 48 hours after the infection, which one was performed within 2 hours; uninfected cells were used as control. Analyses of the expression of transcripts and proteins COX-2, NF-kB and CUGBP2; levels of PGE2 produced during the infection, the expression of gene transcripts involved in apoptosis, Bcl-2, BAX and caspases-3 and -9; expression of c-Myc, c-Jun and c-Fos (which proteins dimerize to form the transcription factor AP1) and expression of microRNAs involved in the expression’s modulation of COX-2, phospholipase A2 and CUGBP2. Moreover, fluorescence microscopy was performed to verify localization of COX-2 protein and mRNA and CUGBP2. As a result, we observed that infection by Berenice-62 strain induces several cellular changes, among them, increased expression and activity of COX-2 protein. The parasite also induces translocation of this protein from the nucleus to the perinuclear region and also to the cytoplasm. The transcription factors NFkB, c-Myc and AP1 don’t seem to be involved in the expression of COX-2. In relation to post-transcriptional regulation, the CUGBP2 seems to regulate the translation of COX-2, but not miRNAs. The parasite presents co-located to COX-2 and CUGBP2, raising the possibility of parasites adhering to these molecules, or even thought, internalize them.

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Kirkby, N. S., A. K. Zaiss, Paula Urquhart, et al. "LC-MS/MS Confirms That COX-1 Drives Vascular Prostacyclin whilst Gene Expression Pattern Reveals Non-Vascular Sites of COX-2 Expression." 2013. http://hdl.handle.net/10454/7245.

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no 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.

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Santos, Mariana Flórida. "COX-2 immunohistochemical expression conjunctival nevus and melanoma." Master's thesis, 2016. http://hdl.handle.net/10316/36692.

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Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de oftalmologia) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina. Introduction: Conjunctival melanomas are extremely rare tumours, representing only 2% of all malignant lesions of the eye. Both classification and correct diagnosis of ocular melanocytic lesions can be a challenge and ambiguity in diagnosis can result in severe misguidance of management and prognosis. Cyclooxygenase-2 is a prostaglandin synthase linked to tumour proliferation and metastization. COX-2 overexpression has been found in many tumours, including uveal melanoma, where it seems to be a marker of poor prognosis. Furthermore, it has also been proposed as a tool in differential diagnosis between cutaneous melanomas and nevi. Objectives: The main goal of this study is to report the results of immunohistochemical COX-2 expression in human conjunctival melanomas and nevi and discuss its potential use for differential diagnosis between benign and malignant conjunctival lesions. Materials and Methods: Twenty specimens of melanocytic nevi and 20 conjunctival melanomas were collected from the archives of the Ophthalmic Pathology Laboratory from Coimbra University Hospital. Immunohistochemistry detection of COX-2 was performed using a monoclonal antibody and 34 samples were classified, in terms of intensity of staining and percentage of cells with positive reactivity, to achieve a COX-2 total score. Results: Comparing the total score values for group, we were able to conclude that a total number of 3 cases presented a score value = 0 (1 melanoma and 2 nevi), 11 cases a score = 1 (6 nevi and 5 melanomas), 12 cases a score = 2 (5 nevi and 7 melanomas) and 8 cases a score = 4 (3 nevi and 5 melanomas). Four nevi and 2 melanoma samples were not evaluated. There was no statistically significant difference for the immunohistochemical expression of COX-2 in the 2 groups. 87.5% of all nevi showed positive expression for COX-2, 62.5% with moderate/intense scores (2 and 4). 94% of all melanomas showed positive expression for COX-2, 67% with moderate/intense scores (2 and 4). Overall, more than 90% of melanocytic conjunctival lesions express COX-2. Discussion: Accordingly to what was expected, our series showed positive expression of COX-2 in 17 out of 18 melanoma specimens (94.4%). However, our study we were not able to establish a significant difference in COX-2 expression between conjunctival nevi and melanomas. Consequently, COX-2 expression is not exclusive of conjunctival melanomas and cannot be used as a differentiating tool for the more challenging melanocytic conjunctival lesions. Introdução: Os melanomas da conjuntiva são tumores extremamente raros, que representam apenas 2% de todas as lesões melanocítica malignas do olho. Tanto a classificação como o diagnóstico correcto destas lesões parecem ser ainda pode ser um desafio, e a ambiguidade no diagnóstico pode ter um impacto grave no tratamento e no prognóstico. A Ciclooxigenase- 2 é uma sintase das prostaglandinas ligada à proliferação tumoral e à metastização. A sobrexpressão de COX-2 tem sido evidenciada em muitos tumores, incluindo o melanoma da úvea, onde parece ser um marcador de prognóstico reservado, e tem sido também proposta como uma ferramenta de diagnóstico diferencial entre melanomas cutâneos e nevus. Objectivos: O principal objectivo deste estudo foi a avaliação da marcação imuno-histoquímica de COX- 2 em melanomas da conjuntiva e nevus melanocíticos, discutindo as suas potencialidades no diagnóstico diferencial entre lesões benignas e malignas da conjuntiva. Materiais e Métodos: Vinte casos de nevus melanocítico e vinte casos de melanoma da conjuntiva, previamente identificadas por patologia, foram recolhidos dos arquivos do Laboratório de Patologia Oftálmica do Centro Hospitalar e Universitário de Coimbra. Através do uso de um anticorpo monoclonal, foi feita a detecção imunohistoquímica de COX-2 e as 34 amostras foram classificadas em termos de intensidade de coloração e percentagem de células com reactividade positiva, tendo sido aplicado um sistema de pontuação de COX-2. Resultados: Comparando os valores totais do score atribuído a cada doente, em ambos os grupos, conseguimos observar que se verificaram 3 casos de score = 0 (1 melanoma e 2 nevus), 11 casos com score = 1 (6 nevus e 5 melanomas), 12 casos de score = 2 (5 nevus e 7 melanomas), e 8 casos de score = 4 (3 nevus e 5 melanomas). Quatro nevus e 2 melanomas não foram avaliados. Não foi encontrada uma diferença estatisticamente significativa entre os scores de expressão imunohistoquímica de COX-2 nos dois grupos. 87.5% de todos os nevus apresentaram uma expressão positiva para COX-2, 62,5% com scores moderados/intensos (2 e 4) e 94% de todos os melanomas apresentaram uma expressão positiva de COX-2, 67% com scores moderados/intensos (2 e 4). No global, mais de 90% das lesões melanocíticas da conjuntiva expressam COX-2. Discussão: De acordo com o que era esperado, os nossos resultados mostraram a existência de expressão de COX-2 em 17 de 18 melanoma marcados (94,4%). Ainda assim, o nosso estudo não foi capaz de estabelecer uma diferença estatisticamente significativa entre a expressão de COX-2 entre nevus da conjuntiva e melanomas e por isso não podemos considerar a esta expressão exclusiva dos melanomas da conjuntiva nem usar o score de expressão de COX-2 como uma ferramenta de diagnóstico diferencial para casos mais ambíguos de lesões melanocíticas conjuntivais.

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LIPARI, Luana. "Expression of metalloproteinases (MMP-2, MMP-9) and cycloxygenases (COX-1, COX-2) in salivary glands tumors." Doctoral thesis, 2011. http://hdl.handle.net/10447/105499.

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LIN, JUN-TING, and 林俊廷. "The effects of celecoxib on astroglial COX-2 expression." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/3fv7wa.

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碩士 慈濟大學 藥理暨毒理學碩士班/博士班 106 Astrocytes are the most abundant glial cell in the central nervous system (CNS) and play important physiological roles in the brain homeostasis. They can provide nutrition and growth factors to neuronal cells and remove extracellular glutamate. Remove of glutamate from extracellular space by astrocytic glutamate transporters can terminate its action and prevent receptors over stimulation-induced excitotoxicity in neuronal cells. In addition, astrocytes also play a critical role in pathological states-induced inflammation such as trauma or infection. Upon these pathological states, astrocytes express cyclooxygenase-2 (COX-2) to mediate inflammation in CNS. Celecoxib, a selective COX-2 inhibitor, can effectively alleviate the symptoms of inflammatory pain by inhibiting COX-2 expression in many pathological conditions. However, in an unexpectable result, we found that exposure of cultured astrocyte to celecoxib (20μM) for 24h resulted in a significant increase in expression of COX-2 and astrocyte activation marker GFAP (glial fibrillary acidic protein). These results can also be observed in brain region of cortex, hippocampus and striatum of celecoxib-treated SD rat. More importantly, expression and function of glutamate transporters in celecoxib-treated cultured astrocytes was significant inhibited. We thus further investigated the mechanisms underlying celecoxib-induced COX-2 expression and its role in astrocytic glutamate transporter dysfunction. Our results revealed that exposure of cultured astrocytes to celecoxib for 10~60 min resulted in a significant increase in protein levels of phosphorylated ERK and JNK. Furthermore, Celecoxib also induced activation and nuclear translocation of transcription factor AP-1 (Activator protein-1). Pretreatment both of ERK and JNK inhibitors effectively prevented COX-2 expression and activation of AP-1 and dysfunction of glutamate transporter induced by celecoxib. Inhibition of AP-1 activity by pharmacological inhibitor can completely abolish celecoxib-induced COX-2 expression in cultured astrocytes. These results suggested that celecoxib can induce COX-2 expression by ERK/JNK/AP-1 pathway to regulate function and expression of glutamate transporters in cultured astrocytes.

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Fritzsche, Julia. "Expression von EGFR, HER-2 und COX-2 beim Zervixkarzinom: Vergleich von Primärtumoren und Rezidiven." Doctoral thesis, 2012. https://ul.qucosa.de/id/qucosa%3A12022.

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Ziel dieser Studie war es, die Häufigkeit der Expression von EGFR, HER-2 sowie COX-2 im Zervixkarzinom zu eruieren. Dabei galt es herauszufinden, ob Unterschiede hinsichtlich des Nachweises dieser drei, möglicherweise therapeutisch relevanten Moleküle zwischen den primären, nicht vortherapierten und operierten Karzinomen und den multimodal vorbehandelten Rezidiven gab. In der vorliegenden retrospektiven Arbeit wurden 45 TMMR-operierte Primärtumoren und 28 LEER-operierte Rezidivtumoren der Universitätsfrauenklinik Leipzig (Triersches Institut) einbezogen und zusätzlich hinsichtlich der prognostischen Überlebensanalyse durch das Tumorstadium, Lymphknotenmetastasen und Rezidivauftreten sowie histologischer Charakteristika untersucht. Dazu wurden Tissue - Microarrays angefertigt mit anschließender immunhistochemischer Untersuchung dieser. Die Ergebnisse zeigten, dass die TMMR-Operation die Überlebensprognose signifikant verbessert, denn lediglich bei den LEER-therapierten Rezidivtumoren erlitten die Patientinnen sowohl Fernmetastasen als auch erneute Rezidive. Weder die Expression der drei untersuchten Moleküle noch die histopathologischen Parameter haben eine prognostische Relevanz. Es gibt keine signifikanten Zusammenhänge zwischen der Häufigkeit der Expression von EGFR, HER-2 sowie COX-2 und Primär-, bzw. Rezidivtumoren, sodass diese Moleküle keine Targets für eine individualisierte, zielgerichtete Therapie beim Zervixkarzinom darstellen.

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Cheng, Chun-Ming, and 陳俊銘. "Homocysteine up-regulates COX-2 expression in Jurkat T lymphocytes." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/44495860190380884224.

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碩士 國立嘉義大學 生化科技學系研究所 99 The aims of this study are to investigate the molecular mechanisms of homocysteine-induce COX-2 expression of T lymphocyte. The effect of homocysteine on T lymphocyte cell line (Jurkat cell) COX-2 expression was examined in vitro. The result from this study may provide insight into the mechanisms contributing to inflammatory response in patients with hyperhomocysteinemia. Experimental results showed that homocysteine can induce T lymphocytes resulting from inflammation, but one of the major regulatory mechanisms is not clear . This study found that the T lymphocytes induced by homocysteine may increase the inflammatory COX-2 gene expression, and induced after 4 hours , COX-2 gene expression had the max expression. Next, further investigate whether hyperhomocystein will induce the increase of intracellular ROS and NO expression, producing the downstream MAPK kinase p38 and JNK phosphorylation and entering nucleus to induce transcription factors NF-κB and Sp1 producing activation, leading COX-2 gene expression, and leading severe inflammation in atherosclerosis . Therefore we believe homocystein play an important role in inducing T lymphocytes inflammatory gene COX-2 expression in atherosclerosis .

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Chi, Hsin-I., and 紀欣怡. "The COX-2 expression of oral cancer and its precancerous lesions and the inhibition of propolis on COX-2." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/59503365216970145479.

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碩士 中山醫學大學 營養科學研究所 90 Oral cancer has been one of the ten major cancers in Taiwan. This study was to know the COX-2 expression in precancerous lesions tissue and to evaluated the inhibition of propolis on COX-2 expression. By Western blot assay, the COX-2 expression was great in the oral cancer tissue followed by leukoplakia and OSF. The levels of COX-2 expression also showed positive correlation with the severity of each lesions. Immunohistochemistry analysis showed that COX-2 expression in oral cancer tissue was very strong and much higher than in leukoplakia and OSF tissue. Furthermore, Oral cancer tissue indicated higher COX-2 level when compared to its adjacent inflammatory tissue. In vitro study demonstrated that proplis markedly suppressed COX-2 expression of KB cell which was induced by TPA (50ng/ml). All the results showed that moderate leukoplakia could play an important role in the malignant mutation. Moreover, the COX-2 expression of KB cell was decreased by propolis extract. This also suggested that propolis extract was probably a chemopreventive material for oral cancer. Keywrods: COX-2, OSF, leukoplakia, oral cancer, propolis

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Ping, Peng Jyh, and 彭治平. "Expression of cyclooxygenase-2(COX-2) in hypopharyngeal cancer and modulation of apoptosis and cell cycle progression by COX-2- specific inhibitors." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/37189137185833560059.

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碩士 長庚大學 臨床醫學研究所 91 Recent studies demonstrate that cyclooxygenase-2(COX-2) plays a crucial role in tumorigenesis of human cancers. Hypopharyngeal cancer is one of head and neck cancers with very poor prognosis in Taiwan. Betel nut chewing is the major contributory factor of hypopharyngeal cancer. The aim of this study was investigated the expression of COX-2 in primary tumor tissues of hypopharyngeal cancer and examined the effect of betel nut ingredient on COX-2 expression in normal hypopharyngeal and cancer cells. In addition, we addressed the effect of COX-2-specific inhibitor on hypopharyngeal cancer cells to evaluate whether these inhibitors might be useful for the prevention or treatment of this cancer. Betel nut ingredients promoted COX-2 expression in normal hypophaygeal and hypopharyngeal cancer cells. Our results also showed that COX-2 was overexpressed in hypophaygeal tumor tissues. Transfection of COX-2 expression vector in hypopharyngeal cells or cancer cells stimulated the expression of matrix metalloproteinases and vascular endothelial growth factor. We next tested the effect of COX-2- specific inhibitor NS398 on the proliferation, apoptosis, and cell cycle progression of hypopharyngeal cancer cells. Results showed that specific COX-2 inhibitor (NS398) inhibited growth of cancer cell in a dose-dependent manner and arrested hypopharyngeal cancer cells in G1/S phase. Immunoblotting analysis indicated that expression of G1 cyclins was not change by NS398. Conversely, NS398 obviously increased expression of cyclin-dependent kinases inhibitors p21Waf1 and p27Kip1. Pretreatment of NS398 potently enhanced the cytocidal activity of chemotherapeutic drugs. This effect is possibly mediated via enhancement of apoptosis. Taken together, COX-2 is involved in tumorigenesis of hypophaygeal cancer and COX-2 inhibitors exert anti-proliferative effect on hypopharyngeal cancer cells and may be used in combination with chemotherapeutic drugs for the treatment of hypopharyngeal carcinoma.

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43

Pei-TingWu and 吳沛庭. "EGF-induced COX-2 enhances ANGPTL4 expression and promotes HNSCC metastasis." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/k8sq39.

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碩士 國立成功大學 藥理學研究所 103 Overexpression of EGFR is a common phenomenon in head and neck cancer squamous cancer cell (HNSCC). Activation of EGFR signaling pathway contributes to HNSCC metastasis and reduces patients’ survival. In our previous studies we found that EGF-induced angiopoietin-like 4 (ANGPTL4) was involved in tumor metastasis. However, the mechanisms of EGF-induced ANGPTL4 and the functional roles of ANGPTL4 in HNSCC metastasis remain unclear. In this study, we found that EGF activated ERK, but not NF-κB signaling pathway was involved in the regulation of ANGPTL4 expression. In addition, the expression of COX-2 was also induced in cells treated with EGF. Furthermore, we found that either inhibition of COX-2 activity using celecoxib or knockdown of COX-2 in cells inhibited EGF-induced ANGPTL4 expression. PGE2 significantly induced the expression of ANGPTL4 mRNA and protein in time-dependent manners. Inhibition of ERK activation dramatically blocked PGE2-induced ANGPTL4 mRNA expression. In addition, ANGPTL4 promoter containing with PPARE was enhanced by PGE2. In summary, we found that EGF-induced ANGPTL4 expression via ERK and COX-2 signaling pathways. Activation of ERK and the involvement of PPAR signaling may be essential for PGE2 enhanced ANGPTL4 expression. The functional roles of ANGPTL4 regulated by COX-2 in HNSCC metastasis will be further studied.

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Shih, Wanyi, and 施宛宜. "Effects of Adlay Seed Extracts on COX-2 and iNOS Expression." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/58640217318387677057.

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碩士 國立臺灣大學 食品科技研究所 89 According to the Chinese traditional therapy, adlay is used as an anti-inflammatory herb. In recent researches, adlay was also found that it has anti-tumor property in animal model. Chronic inflammation with a variety of epithelial malignancies has been recognized for centuries and it is thought that the key enzymes, COX-2 and iNOS, which are over- expressed during inflammation may be a general link between inflammation and cancer. In the present study, the effect of adlay extracts on COX-2 or iNOS expression was investigated in RAW264.7 cell and HT-29 cell. In a murine macrophage cell line, RAW264.7, 4 adlay extracts (methanol extracts of adlay hull(AHM), testa(ATM) and bran(ABM), and high- temperatured water extract of adlay testa(ATHW)) significantly attenuated the LPS-induced the increased level of both COX-2 and iNOS proteins. Furthermore, RT-PCR analysis indicated that these 4 adlay extracts inhibit LPS-induced iNOS mRNA expression, and except ATHW, 3 adlay extracts also inhibit LPS-induced COX-2 mRNA. Coixamide, a pure compound from adlay testa, also showed the inhibitory effect on iNOS expression. In human colonic adenocarcinoma cell, HT-29, ABM decreased both COX-2 mRNA and protein induced by TNF-alpha. Result from this study suggested that inhibition of COX-2 and iNOS expression by adlay extracts may be one of the mechanisms responsible for their anti-inflammatory effects and it also indicated that adlay extracts may be potential for colon cancer prevention.

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Galuschka, Libusa. "Untersuchung der Expression von Cyclooxygenase-2, VEGF und der Gefäßdichte im Nierenzellkarzinom." Doctoral thesis, 2010. http://hdl.handle.net/11858/00-1735-0000-0006-AFBE-7.

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46

Kuo, Chi-Li, and 郭啟利. "Berberine Inhibits COX-2 Expression and Induces Apoptosis in Oral Cancer Cells." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/26080155993251749508.

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博士 國立陽明大學 藥理學研究所 92 Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation, yet the exact mechanism is unknown. Because cyclooxygenase-2 (COX-2) plays a key role in prostaglandins (PGs) synthesis which is elevated in inflammation, this thesis examined whether the anti-inflammatory mechanism of berberine is mediated through COX-2 regulation. In oral cancer cell line OC2 and KB cells, a 12 hr berberine treatment (1, 10, and 100 μM) reduced prostaglandin E2 (PGE2) production dose-dependently with or without 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 nM) induction. This berberine induced effect occurred rapidly in 3 hr treatment as a result of reduced COX-2 protein, but not enzyme activity. The electrophoretic mobility shift assay (EMSA) revealed that activator protein 1 (AP-1) binding was decreased in oral cancer cells treated with berberine for 2 hr. Further analysis showed that berberine inhibited AP-1 binding directly. These anti-inflammatory effects paralleled to the in vivo results where berberine pretreatment of Wistar rat inhibited the production of exudates and PGE2 in carrageenan induced air pouch. Biochemical influence of berberine-induced COX-2 reduction and apoptosis was also explored. Berberine induced apoptosis in KB cells after 12 hr treatment, and was partially reversed by incorporation of PGE2. A three hour and 6 hr berberine treatment inhibited COX-2 and MCL-1 expression dose-dependently but not BCL-2. PGE2 induced COX-2 and MCL-1 expression and reversed the repressive effect of berberine on MCL-1. In addition, PGE2 treatment had no effect on the total level of AKT, but slightly reversed the phosphorylated AKT, which were decreased by berberine. These results suggest that berberine-induced apoptosis might be COX-2 dependent and are related to decreased AKT phosphorylation and MCL-1 expression.

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Yang, Wan-Yu, and 楊婉瑜. "CTGF inhibits cell motility and COX-2 expression in oral cancer cells." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/32336297242513709309.

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碩士 中國醫藥大學 醫學檢驗生物技術學系碩士班 99 Oral squamous cell carcinoma (SCC) has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin synthase, has been implicated in tumor metastasis. Connective tissue growth factor (CTGF), a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells. However, the effect of CTGF on migration activity and COX-2 expression in human oral cells is mostly unknown. Here we found that CTGF reduced the migration and expression of COX-2 in human oral cancer cells.?n ?庮??5 integrin?叮onoclonal antibody, phosphatidylinositol 3-kinase inhibitor (Ly294002 and wortmannin) and Akt inhibitor reversed the migration activity and COX-2 expression which were inhibited by CTGF. CTGF stimulation decreased the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt. In addition, c-Jun siRNA also antagonized the CTGF-inhibited migration and COX-2 expression. Moreover, CTGF decreased the binding of c-Jun to the AP-1 element on the COX-2 promoter. Taken together, our results indicated that CTGF inhibits the migration of oral cancer cells by decreasing COX-2 expression through the ?庮??5 integrin receptor, FAK, PI3K, Akt, c-Jun and AP-1 signal transduction pathway.

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48

Lai, Szu-Chai, and 賴思嘉. "Mechanisms of Endothelin-1-induced COX-2 Expression in Osteoblast MC3T3 cells." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/48214439014294292334.

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碩士 長庚大學 基礎醫學研究所 96 Abstract Mature bone homeostasis is maintained by bone remodeling cycle involved in osteoblast bone formation and osteoclast bone resorption. Under physiological conditions, the bone matrix is constantly renewed with bone remodeling to restructure itself in response to stimulation. Endothelin-1(ET-1), a potent vasoconstrictor, has been shown to be a pro-inflammatory cytokine like TNF- and IL-1β. ET-1 may cause a variety of inflammatory diseases, including airway inflammation, cutaneous inflammation, Crohn’s disease, ulcerative colitis, and liver cirrhosis. Under mechanical stresses, COX-2 and PGE2 expression would be induced in osteoblastic-like cells to modulate osteoblastic activities. However, the mechanisms underlying ET-1-induced COX-2 expression in osteoblastic-like cells were still unknown. Here, the mechanisms underlying ET-1-induced COX-2 expression were investigated in murine osteoblast- like cell line (MC3T3-E1). Results revealed that ET-1-induced COX-2 expression was mediated through p42/p44 MAPK, p38 MAPK, JNK, c-Src, PDGFR, PI3K/Akt phosphorylation, NF-B and AP-1 activity in MC3T3 cells. These responses were attenuated by pretreatment with the inhibitors of MEK1/2(PD98059), p38 MAPK (SB202190), JNK(SP600125), Ca2+ (BAPTA/EDTA and TG), Camodulin (CaMI and KN62), PLC (D609 and U73122), PKC-δ(Rottlerin), c-Src (PP1), PDGFR (AG1296), PI3K/AKT (LY294002 and SH-5), NF-B (Bay-117082) and AP-1 (Curcumin). The involvements of MAPKs, RTK and PI3K/AKT were also confirmed by tansfection with dominant negative mutants of MEK, ERK1, p38, JNK, PKC-δ, c-Src, p85, NIK, and IKK. Tansfection with these mutants significantly inhibited ET-1-induced COX-2 expression. Moreover, ET-1 induced transcriptional activity of a COX-2/reporter, NF-B/reporter, and AP-1/reporter constructs in MC3T3 cells. The implication of NF-kB in ET-1-mediated responses was supported by translocation of NF-kB into the nucleus and degradation of IkB-a stimulated by ET-1 with cell fraction isolation, immunofluorescence staining and Western blot. And NF-kB translocation was inhibited by LY294002. In addition, pretreatments with BQ123 (an inhibitor of ETA receptor), GPAnt2A, PTX and GPAnt2 (inhibitors of Gq and Gi-protein) attenuated ET-1-induced COX-2 expression and phosphorylation of these kinases indicating the involvements of ETA , Gq and Gi proteins, and cross linkage between MAPKs and RTK transactivation. Taken together, these results suggested that in MC3T3 osteoblast cells, ET-1 might activate a GPCR (i.e. ETA) coupling to Gq protein and Gi proteins, activating MAPKs and PDGFR-PI3K/Akt pathways, leading to NF-kB (p65) nuclear translocation and AP-1 activity to induce COX-2 expression. These results provide new insights into the mechanisms by which ET-1-induced COX-2 expression may promote inflammatory responses and will create chances for the development new therapeutic strategies for bone diseases.

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Chuang, Chun-Wei, and 莊峻偉. "Study of the molecular mechanism by which COX-2 regulates CCR7 expression." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/10298599344514498978.

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碩士 國立中山大學 生物醫學研究所 98 The metastatic spread of tumor cells is the major lethal aspect of cancer, and lymphatic metastasis is one of the most important routes. Recent studies indicated that cyclooxygenase-2 (COX-2) expression is frequently associated with lymph node metastasis and over-expression of COX-2 can enhance lymphatic invasion of cancer cells. The interaction of chemokines and their cognate receptors also plays a critical role in cancer metastasis. Previous results of our laboratory demonstrated that CCR7 is a downstream target for COX-2 and COX-2 up-regulated CCR7 expression via the EP2 and EP4 receptor. We also found that protein kinase A (PKA) and AKT kinase are involved in COX-2-induced CCR7. In this study, we provided further evidences that COX-2 directly stimulates CCR7 expression via promoter activation. Promoter deletion and mutation assay indicated that COX-2 stimulated CCR7 promoter via the Sp1 binding site located at the -61/-52 bp region upstream of the transcription start site. Increase of Sp1 binding to CCR7 promoter by COX-2 was confirmed by chromatin immunoprecipitation (ChIP) assay. Furthermore, knockdown of Sp1 expression resulted in inhibition of PGE2-induced CCR7, and over-expression of Sp1 potently up-regulated CCR7 in MCF-7 cells. In vitro kinase assay indicated that AKT could directly phosphorylate Sp1 at S42, T679 and S698 sites. And the phosphorylation of Sp1 by AKT led to enhanced protein stability and DNA binding affinity of Sp1. The results of immunohistochemistry indicated that CCR7 expression was significantly associated with Sp1 and phosphor-AKT. Taken together, COX-2 may act via the EP receptor/PKA/AKT/Sp1 signaling pathway to stimulate CCR7 expression in breast cancer cells to promote lymphatic spread.

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Chang, Cheng-Chi, and 張証棋. "Mechanisms of EV71-induced iNOS and COX-2 expression in rat brain astrocytes." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/48141919574903955869.

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碩士 長庚大學 天然藥物研究所 94 Enterovirus 71 (EV71), a neurotropic virus with undefined pathogenesis, has caused significant morbidity and mortality worldwide. The central nervous system (CNS) is the most vulnerable target of EV71 infection. Many reports have indicated that viral infection induced iNOS and COX-2 expression. Therefore, we used rat brain astrocyte cells (RBA cells) as a model to investigate p42/p44 MAPK, PDGFR, PI3K/Akt, PKC, NF-κB and AP-1 involved in EV71-induced iNOS and COX-2 expression using Western blotting, Reverse transcriptase-polymerase chain reaction (RT-PCR), and immunofluorescene (IF). EV71 stimulated the expression of iNOS and COX-2 and the phosphorylation of p42/p44 MAPK, PDGFR, and Akt. EV71-induced responses were attenuated by pretreatment with selective pharmacological inhibitors PD98059 (MEK1/2), PP1 (c-Src), AG1296 (PDGFR), wortmannin (PI3K), helenalin (NF-B), curcumin (AP-1), Gö6976 (Ca2+-dependent PKC), and rottlerin (PKC-δ). iNOS and COX-2 mRNA expression were inhibited by these inhibitors. The translocation of NF-kB was proved by IF and cytosolic and nuclear fractions prepared from RBA cells exposed to EV71. Only Gö6976 and helenalin inhibited NF-kB tranlocation. AP-1 mRNA expression induced by EV71 in a time-dependent manner. To establish the relationship between PDGFR, Akt, and c-Src, we used immunoprecipitation to investigate this purpose. We demonstrated that c-Src was the upstream of PDGFR and Akt was downstream of both c-Src and PDGFR. Finally, NO release was determined by Griess reagent. The activation of p42/p44 MAPK, PDGFR, and Akt was associated with the expression of iNOS induced by EV71. The signaling pathways involved in RBA cells have been demonstrated that the expression of iNOS and COX-2 induced by EV71 was mediated through the phosphorylation of p42/p44 MAPK, the transactivation of receptor tyrosine kinase, the translocation of NF-B. In addition, PKC and AP-1 may play an important role in EV71-induced iNOS and COX-2 expression. These results established a new model that EV71 induced inflammatory responses and increased the understanding of EV71-induced iNOS and COX-2 expression. These results may provide a potential therapeutic value in the treatment of EV71 infection.

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