ABSTRACT
Nerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteins is controlled by microRNAs (miRs), such as miR-145, whose dysregulation has been related to cancer. The aims of this work were to evaluate in EOC cells whether NGF/TRKA decreases miR-145 levels, and the effect of miR-145 upregulation. The levels of miR-145-5p were assessed by qPCR in ovarian biopsies and ovarian cell lines (human ovarian surface epithelial cells (HOSE), A2780 and SKOV3) stimulated with NGF. Overexpression of miR-145 in ovarian cells was used to evaluate cell proliferation, migration, invasion, c-MYC and VEGF protein levels, as well as tumor formation and metastasis in vivo. In EOC samples, miR-145-5p levels were lower than in epithelial ovarian tumors. Overexpression of miR-145 decreased cell proliferation, migration and invasion of EOC cells, changes that were concomitant with the decrease in c-MYC and VEGF protein levels. We observed decreased tumor formation and suppressed metastasis behavior in mice injected with EOC cells that overexpressed miR-145. As expected, ovarian cell lines stimulated with NGF diminished miR-145-5p transcription and abundance. These results suggest that the tumoral effects of NGF/TRKA depend on the regulation of miR-145-5p levels in EOC cells, and that its upregulation could be used as a possible therapeutic strategy for EOC.
Subject(s)
Carcinoma/metabolism , MicroRNAs/genetics , Nerve Growth Factor/metabolism , Ovarian Neoplasms/metabolism , Receptor, trkA/metabolism , Aged , Carcinoma/genetics , Carcinoma/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Humans , MicroRNAs/metabolism , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Up-Regulation , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Resumen La asociación entre parálisis cordal y nódulo tiroideo es sugestiva de malignidad; por lo general, se trata de un carcinoma de la glándula tiroides con un tumor avanzado. Presentamos el caso de una paciente con carcinoma papilar de tiroides, parálisis cordal izquierda con aspiración bronquial y complicaciones pulmonares severas, a quien se le realizó hemitiroidectomía izquierda más tiroplastia con anestesia local y control endoscópico utilizando injerto de politetrafluoroetileno en forma artesanal. La evolución quirúrgica mostró buen resultado a corto plazo (13 meses), sin complicaciones relacionadas, fonación aceptable, con ganancia ponderal y sin nuevas complicaciones pulmonares. No existen hasta el momento de realizar este manuscrito reportes de cirugía de tiroides más tiroplastia con anestesia local. Se requiere una serie con mayor número de casos para llegar a conclusiones de validez.
Abstract The association between chordal paralysis and thyroid nodule is suggestive of malignancy, and it is usually a carcinoma of the thyroid gland with an advanced tumor. We present the case of a patient with papillary carcinoma of the thyroid, left cordal paralysis with bronchial aspiration and severe pulmonary complications who underwent left hemithyroidectomy plus thyroplasty with local anesthesia and endoscopic control using handcrafted polytetrafluoroethylene graft. The surgical evolution showed good short-term results (13 months) without related complications, acceptable phonation, with weight gain and without new pulmonary complications. There are no reports of thyroid surgery plus thyroplasty with local anesthesia at the time of this manuscript. A series with a greater number of cases is required in order to draw valid conclusions.
ABSTRACT
Contiene: Marco general - Luis Espinal Camps - Lucha democracia en Bolivia - Lucha al interior de la iglesia - La obra - La muerte - A la muerte de un Ayoreo - Requiem por un numero - No queremos martires - La vida humana - El hijo del hombre - Los fosiles - Las crisis - Gastar la vida - La huelga de hambre - El analisis del contenido - Metodologia: dos alternativas - Mecanismo de Interpelacion - Mecanismo de desplazamiento - Mecanismo de accion - Mecanismo de temporalidad - Mecanismo de articulacion - Aplicacion de los 4 mecanismos - El mecanismo de articulacion - El mensaje - 15 años despues - A los jovenes.
