No abstract

Nedaplatin, a cisplatin analog, was developed to reduce the toxicity of cisplatin, whereas it can be cross-resistant with cisplatin in some circumstances. This study aimed to investigate the role of autophagy in nedaplatin induced cell death in cisplatin-resistant nasopharyngeal carcinoma cells. Here, we showed that HNE1/DDP and CNE2/DDP cells were resistant to nedaplatin-induced cell death with reduced apoptotic activity. Nedaplatin treatment resulted in autophagosome accumulation and increased expression of LC3-II, indicating the induction of autophagy by nedaplatin in HNE1/DDP and CNE2/DDP cells. Inhibition of autophagy by Bafilomycin A1 (Baf A1) and 3-Methyladenine (3-MA) remarkably enhanced the antitumor efficacy of nedaplatin in HNE1/DDP and CNE2/DDP cells, suggesting that the resistance to nedaplatin-induced cell death was caused by enhanced autophagy in nedaplatin-resistant NPC cells. Additionally, Baf A1 enhanced reactive oxygen species (ROS) generation and apoptosis induced by nedaplatin in HNE1/DDP cells. Mechanistically, nedaplatin treatment caused activation of ERK1/2 and suppression of Akt/mTOR signaling pathways. While inhibition of ERK1/2 by MEK1/2 inhibitor, U0126, could reduce the expression of LC3-II in nedaplatin-resistant NPC cells. Furthermore, suppression of ROS could inhibit nedaplatin-induced ERK activation in HNE1/DDP cells, indicating that ROS and ERK were involved in nedaplatin-induced autophagy. Together, these findings suggested that autophagy played a cytoprotective role in nedaplatin-induced cytotoxicity of HNE1/DDP and CNE2/DDP cells. Furthermore, our results highlighted a potential approach to restore the sensitivity of cisplatin-resistant nasopharyngeal cancer cells to nedaplatin in combination with autophagy inhibitors.

PurposeSpecific immunotherapy (SIT) is a suitable but uncommon treatment option for allergic rhinitis (AR) in China. The current understanding and attitude of Chinese ENT (ear, nose, and throat) specialists in regards to SIT is unclear. This study investigates current trends in the awareness and application status of SIT among Chinese ENT specialists.MethodsWe performed a nationwide, cross-sectional survey with a specially designed questionnaire given to 800 ENT specialists in China. A member of the trained research group conducted face-to-face interviews with each respondent.ResultsMost of the respondents considered AR (96.0%) and allergic asthma (96.0%) the most suitable indications for SIT. Of all respondents, 77.0% recommended the application of SIT as early as possible; in addition, SIT was considered 'relatively controllable and safe' by most respondents (80.6%). The highest allergen-positive rate in AR was associated with house dust mite (47.7%) and obvious differences existed among geographical regions. Conventional subcutaneous immunotherapy was the most highly recommended treatment option (96.2%). 'The high cost of SIT' (86.6%) and 'lack of patient knowledge of SIT' (85.2%) were probably the main reasons for the lower clinical use of SIT in China.ConclusionsMost cases showed that the opinions of Chinese ENT specialists appeared to be in agreement with recent SIT progress and international guidelines; however, many areas still need to enhance the standardization and use of SIT in China. Clinical guidelines for SIT require improvement; in addition, Chinese ENT specialists need continuing medical education on SIT.