RESUMEN
Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.
Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Proteína Forkhead Box O1 , Ácidos Hidroxámicos , Neoplasias Pulmonares , Proteínas de Uniones Estrechas , Humanos , Células A549 , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Células Epiteliales/metabolismo , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Background and Objective: Thymectomy with median sternotomy is the gold standard for thymoma and myasthenia gravis, although minimally invasive procedures such as robot-assisted surgery have recently become more common. However, the superiority of these approaches has not been established, and they are infrequently recommended for localized lesions. The International Thymic Malignancies Interest Group warned that despite the perceived reduction in length of hospital stay and pain, the benefits of these approaches compared to the open approach have not been fully substantiated and that prospective collaborative data collection is critical in defining the value of these techniques. Whether thymectomy is necessary for stage I thymomas in the absence of myasthenia gravis or anti-acetylcholine receptor antibodies is also unclear. This study reviews and discusses the literature on this subject. Methods: A narrative review was conducted using PubMed and Scopus databases. Original research articles comparing robotic to video-assisted thoracic surgery or to open thymectomy for thymomas were included. A comparison of partial resection and total thymectomy (thymothymectomy) for thymomas was also conducted. Key Content and Findings: Perioperative outcomes such as blood loss, operative duration, complications, and length of hospital stay were better for robot-assisted resection of early-stage thymomas than for open thymoma surgery. It would be premature to consider partial resection as an appropriate treatment option for thymomas. Conclusions: Robotic thymothymectomy is safe with effective and promising long-term results and oncological and surgical outcomes in patients with thymoma. Robotic thymectomy can become the standard procedure in patients with early-stage thymomas.
RESUMEN
OBJECTIVES: We analysed our clinical experience using silk sutures [the double-loop technique (DLT)] or DeBakey type vascular clamp (DeBakey clamp) for pulmonary artery (PA) troubles during anatomical lung resection to validate its practicality and safety. METHODS: We retrospectively reviewed the records of patients who underwent either of the above clamping techniques during anatomical lung resection at our hospital between April 2007 and August 2022. We measured the PA diameter at the occlusion site on computed tomography images acquired within 1 year pre- and postoperatively. The difference between pre- and postoperative diameters of the occlusion sites was calculated as the change in the PA diameter. We zoned the occlusion site of the PA to adjust for variation. PA deformation was evaluated as an adverse event caused by clamping. RESULTS: Ultimately, 27 and 26 patients who underwent the DLT and DeBakey clamp, respectively, were included. No additional injury due to the clamp procedure was found in either group. For zone R1/L1, defined as the main PA, the median changes in the PA diameter were 0.02 (-0.7 to 0.27) mm for the DLT and 0.36 (-0.28 to 0.89) mm for the DeBakey clamp. No significant differences were observed between the 2 groups (P = 0.106). Furthermore, no aneurysms, dissections, or stenoses were found in either group. CONCLUSIONS: The DLT and DeBakey clamp had only minimal effects on the occlusion site of the PA. The DLT is a practical thoracoscopic technique for PA bleeding when primary haemostasis has been achieved.