RESUMO
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the common types of cancer that originate from the nasopharyngeal region. Recurrence and early metastasis represent major problems associated with NPC mortality. These are mainly caused by various molecular changes that take place during the conversion of normal stem cells into treatment-resistant stem cells. The aim of our study was to investigate the proliferative behavior of cancer stem cells in different stages of NPC and to identify the functional roles of SPLUNC1 and MLL3 associated with cancer stem cells. METHODS: We successfully developed a NPC mouse model using C666-1 cells. Immunohistochemistry and Western blotting were used to analyze the expression of SOX2, SPLUNC1 and MLL3. RESULTS: Null BALB/c mice developed initial and aggressive stages of NPC in 3 and 10 weeks, respectively. Histological results showed that the proliferative ability of cells increased as the tumor progressed to the next level. The SOX2 protein showed a peculiar pattern of upregulation in aggressive NPC when compared with control tissues and initial NPC. Remarkably, our study found that SPLUNC1 and MLL3 expression showed upregulation in initial NPC, which indicates their role in the tumor resistance mechanism even if their expression was downregulated in aggressive NPC. CONCLUSIONS: Our results conclude that SPLUNC1 and MLL3 expression control the resistance mechanism of cancer stem cells in initial NPC, but their downregulation in aggressive stages contributes to developing resistance in nasopharyngeal cancer stem cells.
Assuntos
Proteínas de Ligação a DNA/genética , Glicoproteínas/genética , Carcinoma Nasofaríngeo/genética , Fosfoproteínas/genética , Fatores de Transcrição SOXB1/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4/patogenicidade , Humanos , Camundongos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/virologia , Esferoides Celulares/metabolismo , Esferoides Celulares/virologiaRESUMO
The aim of this study was to summarize and analyze the outcomes of frontal sinus cerebrospinal fluid rhinorrhea (FS-CSFR) treated by transnasal endoscopic and combined intra-extranasal approach. Clinical data on 20 cases of FS-CSFR patients from 2005 to 2013, with emphasis on the postoperative complications, clinical outcomes, and key technology involved in the combined intra-extranasal procedure, were retrospectively reviewed. Among the 20 cases, 12 were treated by combined intra-extranasal procedure; the other eight cases were initially treated by trans-nasal endoscopic approach alone, and five of them (5/8, 62.5%) were successfully treated and three failed. The three failed cases subsequently underwent combined intra-extranasal approach. A total of 15 cases, who received combined procedure, experienced fast recovery, had mild complications, and had no significant facial scars, and no CSFR recurrence was observed. Combined intra-extranasal approach offers advantages in not only overcoming the difficulty of insufficient exposure of defects during transnasal endoscopic procedure but also improving the success rate of repair.
