RESUMEN
OBJECTIVE: Infantile hemangiomas (IHs) are the most common benign vascular neoplasms of infancy, characterized by a rapid growth phase followed by a spontaneous involution, or triggered by propranolol treatment by poorly understood mechanisms. LIN28/let-7 axis plays a central role in the regulation of stem cell self-renewal and tumorigenesis. However, the role of LIN28B/let-7 signaling in IH pathogenesis has not yet been elucidated. APPROACH AND RESULTS: LIN28B is highly expressed in proliferative IH and is less expressed in involuted and in propranolol-treated IH samples as measured by immunofluorescence staining and quantitative RT-PCR. Small RNA sequencing analysis of IH samples revealed a decrease in microRNAs that target LIN28B, including let-7, and an increase in microRNAs in the mir-498(46) cistron. Overexpression of LIN28B in HEK293 cells induced the expression of miR-516b in the mir-498(46) cistron. Propranolol treatment of induced pluripotent stem cells, which express mir-498(46) endogenously, reduced the expression of both LIN28B and mir-498(46) and increased the expression of let-7. Furthermore, propranolol treatment reduced the proliferation of induced pluripotent stem cells and induced epithelial-mesenchymal transition. CONCLUSIONS: This work uncovers the role of the LIN28B/let-7 switch in IH pathogenesis and provides a novel mechanism by which propranolol induces IH involution. Furthermore, it provides therapeutic implications for cancers in which the LIN28/let-7 pathway is imbalanced.
Asunto(s)
Antineoplásicos/farmacología , Hemangioma/tratamiento farmacológico , Células Madre Pluripotentes Inducidas/efectos de los fármacos , MicroARNs/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Propranolol/farmacología , Proteínas de Unión al ARN/metabolismo , Transducción de Señal/efectos de los fármacos , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Hemangioma/genética , Hemangioma/metabolismo , Hemangioma/patología , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas de Unión al ARN/genéticaRESUMEN
Endovascular repair of thoracoabdominal aneurysms using fenestrated and/or branched stent grafts is technically feasible and efficacious but carries a steep learning curve. This innovative surgical approach is associated with less perioperative morbidity than traditional open repair and its early and mid-term outcomes are very favorable. Spinal cord ischemia remains a devastating complication after these procedures, hence the importance of various neuroprotective strategies. Widespread applicability remains limited in the United States, as no custom-made or off-the-shelf endografts are commercially available. Access to these devices remains limited to physician-sponsored or industry-sponsored clinical trials, but results from the Cook p-Branch and Gore Thoracoabdominal Branch Endoprosthesis trials are on the horizon.
Asunto(s)
Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Humanos , Complicaciones Posoperatorias , Diseño de Prótesis , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
We describe a 41-year-old man with De Mosier's syndrome who presented with exercise intolerance and dyspnea on exertion caused by a giant hiatal hernia compressing the heart with relief by surgical treatment.