[Autophagy promotes recurrence of nasopharyngeal carcinoma via inducing the formation of dormant polyploid giant cancer cells].

Objective: To explore the effect of dormant polyploid giant cancer cells (PGCC) on nasopharyngeal carcinoma (NPC) recurrence and to clarify the role of inhibition of autophagy in inhibiting NPC-PGCC formation and preventing NPC recurrence. Methods: NPC cells-derived PGCC (NPC-PGCC) were induced by paclitaxel (PTX), and the morphology, polyploid characteristics and cell activity of PGCC were identified by light microscopy, immunofluorescence and Live/Dead cell double staining assays. RNA-seq was used to analyze the differentially expressed genes between NPC-PGCC and diploid nasopharyngeal carcinoma cells CNE2. Functional enrichment and pathway annotation analysis of differentially expressed genes were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). The level of autophagy in NPC-PGCC cells was assessed by Western Blot and transmission electron microscopy analysis. The role of autophagy in the formation of NPC-PGCC and the effect of NPC-PGCC on the recurrence of nasopharyngeal carcinoma were studied using a highly clinically relevant mouse nasopharyngeal carcinoma recurrence model. Statistical analysis was performed using GraphPad Prism 6 and P-values<0.05 were considered statistically significant. Results: NPC-PGCC induced by paclitaxel had the characteristics of burst-like division after dormancy. GO enrichment and KEGG pathway analyses identified the significant biological processes and pathways mainly concentrated in autophagy and related pathways involving the differentially expressed genes between NPC-PGCC and diploid nasopharyngeal carcinoma cells CNE2. The autophagy level was significantly enhanced in NPC-PGCC cells. In a highly clinically relevant mouse nasopharyngeal carcinoma recurrence model, the number of PGCC in the primary tumor of the nude mice treated with cisplatin were higher than those of the other groups. In nude mice pretreated with autophagy inhibitor and then co-treatment with autophagy inhibitor and cisplatin, the number of PGCC in primary tumors was less and the recurrence rate was significantly lower than in other groups. Conclusions: The mechanism of dormant polyploid giant cancer cells formation is related to autophagy. Inhibition of autophagy can inhibit the formation of PGCC and thus prevent the recurrence of nasopharyngeal carcinoma.

[Clinical epidemiological survey of primary liver cancer in Yunnan province from 2005 to 2014].

Objective: To investigate the clinical characteristics and changing trends of primary liver cancer in Yunnan province from 2005 to 2014, in order to provide theoretical basis for the prevention and treatment of liver cancer in this region. Methods: A retrospective survey was used to select inpatient cases of liver cancer who were initially diagnosed and treated in our hospital from 2005 to 2014 with simple random sampling. Patients socio-demographic and clinicopathological characteristics were extracted by a unified and standardized questionnaire, and the data were statistically analyzed. Results: A total of 1000 cases with liver cancer were included, aged (53.2±11.2) years, with a male-to-female ratio of 5.99/1.00. There was no significant change in the gender and age composition ratio of patients in the past 10 years. The proportion of patients with lower education level (primary or junior high school) were increased from 21.8% to 23.4%, and the proportion of patients with relatively higher education level were decreased from 58% to 38.2% (P<0.001). Smokers and non-smokers patients were decreased and increased from 58.8% to 44.4%, and 41.2% to 55.6% (P<0.001). The proportion of drinker patients were decreased from 46.4% to 35.2%. The proportion of patients with advanced liver cancer (stage C and D) were increased, while the proportion of patients with stage A and B showed a downward trend (P<0.001). The proportion of HBsAg-positive patients showed an upward trend, that is, rising from 69% in 2005 to 82% in 2014 (P=0.043). The proportion of HBeAg-positive patients showed a steady trend (P=0.008). The use rate of ultrasound examination in patients with liver cancer were decreased from 91.0% to 58.0% (P=0.001), while the use rate of computed tomography (CT), MRI, and PET/CT examinations were increased from 81.0% to 84.0% (P=0.05), 0 to 22% (P<0.001), and 0 to 3% (P=0.026) between 2005 to 2014. The proportion of surgical patients were increased (P=0.005), but the proportion of interventional patients did not change significantly (P=0.590). Surgery and interventional therapy were the most common treatment methods, and the proportion of patients treated with surgery over the past 10 years showed an upward trend (P=0.005), while the proportion of interventional therapy remained at a high level with no significant change (P=0.590). Conclusion: In Yunnan province, the incidence of liver cancer increases with age, and the proportion of male with liver cancer is almost six times that of women. Moreover, the low positive rate of alpha-fetoprotein levels and advanced clinical stage in this region are presently the main challenges against the liver cancer prevention and treatment. The application scope of CT, magnetic resonance imaging, PET-CT and other examination methods has gradually expanded, but the treatment methods are still mainly surgery and interventional therapy.

[Application of mini-flank open nephron sparing surgery via retroperitoneal route for centrally located renal tumor treatment: a single center experience].

Objective: To investigate the safety and feasibility of mini-flank open nephron sparing surgery (MI-OPN) via retroperitoneal route for the treatment of centrally located renal tumor. Methods: From May 2013 to April 2015, twenty-four cases of centrally located renal tumor were treated with MI-OPN via retroperitoneal route in Zhongshan Hospital. All cases were included in this study with whose clinical data and long term follow-up information retrospectively analyzed. Results: With the assistance of intraoperative ultrasonography to confirm tumor location and boundary, MI-OPN was successfully performed in all cases. Mean tumor maximum diameter was 3.3±0.6 cm, mean operation time was 113±16 minutes, mean ischemia time was 31±6 min, and mean estimated blood loss was 102±46 ml. Mean postoperative hospital stay was 5.0±0.8 days, postoperative complication was found in one patient (4%). The mean pre- and postoperative serum creatinine were 77.1±20.1 µmol/L and 90.3±20.0 µmol/L. Pathological examination confirmed negative surgical margin in all cases, with 18 cases of clear cell renal cell carcinoma, 2 cases of papillary renal cell carcinoma, 2 cases of chromophobe renal carcinoma, 1 case of renal oncocytoma and 1 case of renal angiomyolipoma. In up to 12-36 months postoperative follow-up, no local recurrence or systemic progression was witnessed. Conclusions: For the treatment of centrally localized renal tumor, MI-OPN via retroperitoneal route is a safe and feasible operation method. Importantly, rupture of the tumor capsule was effectively avoided during tumor resection with the assistance of ultrasonic position-setting. Furthermore, incidence of severe postoperative complications such as bleeding and damage of collection system were not found since surgical wound of kidney sewn tightly and finely. The last but not the least, by placing ice slush in retroperitoneal cavity, impairment of renal function caused by renal artery clamping can be alleviated due to decreased metabolism.

Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells.

The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1 week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis.