RESUMEN
Thyroid cancer is a common endocrine cancer, of which papillary thyroid cancer (PTC) is the most common type. Neuregulin 1 (NRG1), a glycoprotein mediating cellcell signaling, plays vital roles in cellular activities; however, its role in PTC progression remains poorly understood. In this study, we performed immunohistochemistry in 196 samples from patients and found that NRG1, a potential prognostic marker is highly expressed in PTC compared with adjacent normal tissues. Cell Counting kit8 (CCK8) and clone formation assays indicated that NRG1 is essential for PTC cell viability and proliferation, probably by regulating redox homeostasis, which was implied by ROS generation analysis and intracellular GSH activity assay. Western blot analysis and RTqPCR revealed that NRG1 regulates ERK pathway and the pivotal regulator of cellular redox status, nuclear factor E2related factor 2 (NRF2), which maintains moderate reactive oxygen species (ROS) levels through a set of antioxidant response element (ARE)containing genes. The immunohistochemical scoring of 196 PTC samples and the analysis of the data of 490 patients from The Cancer Genome Atlas (TCGA) reveled a positive association between the expression of NRG1 and NRF2. Since the presence of NRG1 regulates redox homeostasis through NRF2, protecting PTC cells from the accumulation of ROS and ROSinduced cell death, NRG1 may thus prove to be a potential therapeutic target in the treatment of thyroid cancer.
Asunto(s)
Carcinoma Papilar/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Neurregulina-1/metabolismo , Neoplasias de la Tiroides/metabolismo , Regulación hacia Arriba , Carcinoma Papilar/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Homeostasis , Humanos , Masculino , Neurregulina-1/genética , Oxidación-Reducción , Pronóstico , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genéticaRESUMEN
KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis. Transwell assays revealed that cell migration and invasion were suppressed in KMT5A-knockdown cells. Moreover, the inhibition of KMT5A arrested the cell cycle in the G1/S phase of papillary thyroid cancer cells. The TCGA data revealed that elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. Furthermore, we observed that inhibition of KMT5A suppressed the expression of SREBP1, SCD, FASN and ACC, key molecules involved in lipid metabolism and decreased the level of malondialdehyde in papillary thyroid cancer cells. In conclusion, KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.
Asunto(s)
Carcinoma Papilar/patología , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Metabolismo de los Lípidos , Neoplasias de la Tiroides/patología , Carcinoma Papilar/enzimología , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Técnicas In Vitro , Metástasis Linfática , Masculino , Malondialdehído/metabolismo , Estadificación de Neoplasias , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/enzimología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismoRESUMEN
In this study, we present a case of a 52-year-old male with a chondrosarcoma of the left lamina of the thyroid cartilage. Pre-operative evaluations detected typical calcifications and delineated the extent of the tumor. The patient underwent a total laryngectomy to ensure the complete resection of the tumor. The tumor was histopathologically found to consist of chondrocytes in a hyaline cartilage matrix. The patient's post-operative course has been successful apart from the permanent tracheostomy. Herien, we discuss the methods and rationales for the diagnosis and management of and recovery from this rare tumor, and also provide a review of the literature.
RESUMEN
BACKGROUND: The aim of this study is to evaluate the safety and feasibility of laparoscopic common bile duct exploration and primary closure of choledochotomy for the patients with common bile duct stones (CBDS) who failed in endoscopic sphincterotomy (EST). METHODS: Between January 2007 and June 2012, a total of 78 patients who subjected to endoscopic retrograde cholangiopancreatography (ERCP) and EST, but failed in endoscopic stone extraction, were referred to us. The following day, laparoscopic cholecystectomy, laparoscopic common bile duct exploration (LCBDE) and primary closure of choledochotomy were performed in all patients. RESULTS: No intraoperative complications were experienced in the patients. 6 patients required conversion to open cholecystectomy due to impacted stones. The mean operative time was 145 min. The mean postoperative hospital stay was 6d. All the patients achieved successful stone clearance. 13 cases had slight bile leaks, which resolved spontaneously. None of the patients experienced biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. CONCLUSION: If it is performed by experienced laparoscopic surgeons, primary closure following immediate laparoscopic common bile duct exploration (LCBDE) is safe and feasible for patients with CBDS who fail in endoscopic stone extraction.