10 research outputs found
Microscopía confocal en las enfermedades ampollosas subepidérmicas autoinmunes
Las enfermedades ampollosas subepidérmicas autoinmunes constituyen un complejo grupo de trastornos cutáneos en cuya patogenia se rompe la unión dermoepidérmica. Su alta morbilidad se debe a la afectación de grandes áreas cutáneas por ampollas, erosiones o cicatrices y a la posible afectación de las mucosas oral, conjuntival, laríngea, esofágica y genitourinaria. Además, se ha demostrado su asociación con enfermedades neurológicas degenerativas y neoplasias. Existe un gran solapamiento clínico e histológico entre múltiples enfermedades, ya que varios antígenos de la membrana basal pueden estar implicados. En las dos últimas décadas se han producido grandes avances para intentar descubrir todos los antígenos implicados y la posible correlación clínico-inmunológica entre manifestaciones clínicas y antígenos diana. La inmunofluorescencia directa e indirecta y técnicas serológicas como el ELISA se realizan ya de rutina en centros de referencia. Sin embargo, estas técnicas no siempre llegan al diagnóstico de certeza. El desarrollo de nuevas técnicas inmunológicas más sensibles, específicas y reproducibles contribuirá a que los diagnósticos sean más exactos y por tanto el manejo terapéutico y pronóstico de los enfermos sea mejor. La microscopía confocal es una técnica prometedora en este campo..
Inhibition of PI3K-AKT-mTOR Signaling Sensitizes Melanoma Cells to Cisplatin and Temozolomide
In melanoma, the PI3K-AKT-mTOR (AKT) and RAF-MEK-ERK (MAPK) signaling pathways are constitutively activated and appear to play a role in chemoresistance. Herein, we investigated the effects of pharmacological AKT and MAPK pathway inhibitors on chemosensitivity of melanoma cells to cisplatin and temozolomide. Chemosensitivity was tested by examining effects on growth, cell cycle, survival, expression of antiapoptotic proteins, and invasive tumor growth of melanoma cells in monolayer and organotypic culture, respectively. MAPK pathway inhibitors did not significantly increase chemosensitivity. AKT pathway inhibitors consistently enhanced chemosensitivity yielding an absolute increase of cell growth inhibition up to 60% (P<0.05, combination therapy vs monotherapy with inhibitors or chemotherapeutics). Cotreatment of melanoma cells with AKT pathway inhibitors and chemotherapeutics led to a 2- to 3-fold increase of apoptosis (P<0.05, combination therapy vs monotherapy) and completely suppressed invasive tumor growth in organotypic culture. These effects were associated with suppression of the antiapoptotic Bcl-2 family protein Mcl-1. These data suggest that inhibition of the PI3K-AKT-mTOR pathway potently increases sensitivity of melanoma cells to chemotherapy
Adams-Oliver syndrome with unusual central nervous system findings and an extrahepatic portosystemic shunt
We report a case of a premature neonate girl with scalp and skull defects and brachydactyly of the feet consistent with an Adams-Oliver syndrome (AOS). The patient had central nervous system abnormalities, such as periventricular calcifications, hypoplastic corpus callosum, and bilateral hemispheric corticosubcortical hemorrhagic lesions. A muscular ventricular septal defect and a portosystemic shunt were diagnosed. To our knowledge, this is the first report of congenital supratentorial grey-white matter junction lesions without dural sinus thrombosis in association with AOS. Some of these lesions may be secondary to birth trauma (given the skull defect) whilst others have a watershed location, perhaps as further evidence of vascular disruption and decreased perfusion during critical periods of fetal brain development as the previously proposed pathogenesis of this syndrome