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Translation, Editing/proofreading
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English to Spanish: Mechanisms of COX-2–Associated Tumorigenesis General field: Medical Detailed field: Medical: Pharmaceuticals
Source text - English (English – Medicine)
Mechanisms of COX-2–Associated Tumorigenesis
COX-2 is over expressed along the continuum of on cogenesis and is likely to be a key player in a number of biologic pathways leading to cancer. Current evidence indicates that COX-2 promotes tumor-specific angiogenesis,53-56 inhibits apoptosis,57-60 and induces proangiogenic factors such as VEGF,61,62 inducible nitrogen oxide synthetase promoter (iNOS),63 IL-6,64 IL-8,65 and TIE-2.66
COX-2-derived metabolites from infiltrating inflammatory cells undoubtedly contribute to the tumorigenic process as well. For example, enhanced prostaglandin synthesis may contribute to oncogenesis by directly stimulating mitogenesis in fibroblasts,67 osteoblasts,68,69 and mammary epithelial cells.70 Excessive local synthesis of prostaglandins has also been shown to disrupt immune surveillance that may otherwise suppress tumor growth.71,72 In addition,the direct product of COX-2, PGH2, can isomerize by both enzymatic and nonenzymatic reactions to form the potent mutagen malondialdehyde, which can induce frame shifts and base pair substitutions.73 Additional free radical damage may occur via the peroxidative activity of COX-2, which can efficiently oxidize aromatic and heterocyclic amines and dihydrodiol derivatives.74
Increased prostaglandin levels may be particularly important during the progression of breast cancer. PGE2 has recently been shown to stimulate aromatase transcription,75,76 leading to supraphysiologic local estrogen levels, which in turn leads to the subsequent release of growth factors and enhanced proliferation.77 Immunohistochemical analysis by Brueggemeier et al78 supports the association between COX-2 and aromatase. The cytochrome P450 enzyme aromatase (CYP19) and COX- 2 were coexpressed in all cases of human breast cancer, and a significant linear association was found between levels of CYP19 gene expression and COX-2 gene expression (R - 0.80, P
Translation - Spanish Mecanismos de tumorigénesis asociados con la COX-2
La COX-2 se sobrexpresa a lo largo del sector de la oncogénesis y probablemente juegue un papel primordial en cierto número de vías biológicas que conducen al cáncer. Los datos actuales indican que la COX-2 promueve la angiogénesis específica a tumores,53-56 inhibe la apoptosis,57-60 e induce factores proangiogénicos tales como VEGF,61,62 el promotor de sintetasa de óxido de nitrógeno inducible (iNOS),63 IL-6,64 IL-8,65 y TIE-2.66
Los metabolitos derivados de la COX-2 procedentes de células inflamatorias infiltrantes también contribuyen indudablemente al proceso tumorigénico. Por ejemplo, la síntesis de la prostaglandina mejorada puede contribuir a la oncogénesis mediante un estímulo directo de la mitogénesis en los fibroblastos,67 los osteoblastos68,69 y las células epiteliales mamarias.70 Una síntesis local excesiva de prostaglandinas también ha demostrado desbaratar la vigilancia inmune que de otro modo podría suprimir el desarrollo tumoral.71,72 Además, el producto directo de la COX-2, PGH2, puede isomerizarse mediante reacciones tanto enzimáticas como no enzimáticas para formar el potente malondialdehído mutagénico capaz de inducir cambios estructurales y sustituciones de pares base.73 Puede ocurrir daño radical libre adicional a través de la actividad peroxidativa de la COX-2 capaz de oxidar eficazmente aminas aromáticas y heterocíclicas y derivados de dihidrodiol.74
El incremento en los niveles de la prostaglandina puede revestir particular importancia durante la evolución del cáncer de mama. Recientemente se ha demostrado que la PGE2 estimula la transcripción de aromatasa,75,76 lo cual conduce a niveles de estrógenos locales suprafisiológicos que a su vez desembocan en la subsiguiente liberación de los factores del desarrollo y en una proliferación mejorada.77 Los análisis inmunohistoquímicos realizados por Brueggemeier et al78 apoyan la asociación existente entre la COX-2 y la aromatasa. La enzima aromatasa del citocromo P450 (CYP19) y la COX- 2 fueron coexpresadas en todos los casos de cáncer de mama humano, además de descubrirse una asociación lineal significativa entre los niveles de expresión génica de la CYP19 y expresión génica de la COX-2 (R – 0,80, P
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Translation education
Other - Final Exam - Chartered Institute of Linguists, London
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Years of experience: 30. Registered at ProZ.com: Jan 2010.