RESUMO
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.
Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Complicações Pós-Operatórias , Desenho de Prótese , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
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.
Assuntos
Antineoplásicos/farmacologia , Hemangioma/tratamento farmacológico , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Propranolol/farmacologia , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Hemangioma/genética , Hemangioma/metabolismo , Hemangioma/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas de Ligação a RNA/genéticaRESUMO
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.
