Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndr...Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.展开更多
BACKGROUND Tracheoesophageal fistula(TEF)is a congenital anomaly characterized by interruptions in esophageal continuity with or without fistulous communication to the trachea.Anesthetic management during TEF repair i...BACKGROUND Tracheoesophageal fistula(TEF)is a congenital anomaly characterized by interruptions in esophageal continuity with or without fistulous communication to the trachea.Anesthetic management during TEF repair is challenging because of the difficulty of perioperative airway management.It is important to determine the appropriate position of the endotracheal tube(ETT)for proper ventilation and to prevent excessive gastric dilatation.Therefore,the tip of the ETT should be placed immediately below the fistula and above the carina.CASE SUMMARY A full-term,one-day-old,2.4 kg,50 cm male neonate was diagnosed with TEF type C.During induction,an ETT was inserted using video laryngoscope and advanced deeply to ensure that the tip passed over the fistula,according to known strategies.The passage of the ETT through the vocal cords was confirmed via video laryngoscope.However,after inflating the ETT cuff,breath sounds were not heard on bilateral lung auscultation.Instead,gastric sounds were heard.Considering that a large fistula(approximately 6.60 mm×4.54 mm)located 10.2mm above the carina was confirmed on preoperative tracheal computed tomography,the possibility of unintentional esophageal intubation was highly suspected.Therefore,we decided to uncuff and withdraw the ETT carefully for repositioning,while monitoring auscultation and end-tidal CO2 simultaneously.At a certain point(9.5 cm from the lip),clear breath sounds and proper end-tidal CO_(2) readings were suddenly achieved,and adequate ventilation was possible.CONCLUSION Preanesthetic anatomical evaluation with imaging studies in TEF is necessary to minimize complications related to airway management.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean Government,Ministry of Science and ICT(MSIT)(2016R1C1B102207,2022R1A2C1004141 and 2022R1A2C-1091712)the National R&D Program for Cancer Control through the National Cancer Center(NCC)funded by the Ministry of Health&Welfare,Republic of Korea(HA22C0053000022).
文摘Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.
文摘BACKGROUND Tracheoesophageal fistula(TEF)is a congenital anomaly characterized by interruptions in esophageal continuity with or without fistulous communication to the trachea.Anesthetic management during TEF repair is challenging because of the difficulty of perioperative airway management.It is important to determine the appropriate position of the endotracheal tube(ETT)for proper ventilation and to prevent excessive gastric dilatation.Therefore,the tip of the ETT should be placed immediately below the fistula and above the carina.CASE SUMMARY A full-term,one-day-old,2.4 kg,50 cm male neonate was diagnosed with TEF type C.During induction,an ETT was inserted using video laryngoscope and advanced deeply to ensure that the tip passed over the fistula,according to known strategies.The passage of the ETT through the vocal cords was confirmed via video laryngoscope.However,after inflating the ETT cuff,breath sounds were not heard on bilateral lung auscultation.Instead,gastric sounds were heard.Considering that a large fistula(approximately 6.60 mm×4.54 mm)located 10.2mm above the carina was confirmed on preoperative tracheal computed tomography,the possibility of unintentional esophageal intubation was highly suspected.Therefore,we decided to uncuff and withdraw the ETT carefully for repositioning,while monitoring auscultation and end-tidal CO2 simultaneously.At a certain point(9.5 cm from the lip),clear breath sounds and proper end-tidal CO_(2) readings were suddenly achieved,and adequate ventilation was possible.CONCLUSION Preanesthetic anatomical evaluation with imaging studies in TEF is necessary to minimize complications related to airway management.
