ObjectiveTo investigate the effect of arsenic trioxide-loaded CalliSpheres beads (CBATO) in transarterial chemoembolization (TACE) in the treatment of rabbits with VX2 liver tumor. MethodsA total of 120 tumor-bearing rabbits were divided into control group, CalliSpheres beads (CB) group (blank beads for TACE), CBATO group, and conventional TACE (cTACE) group (arsenic trioxide lipiodol for TACE) using a random number table, with 30 rabbits in each group. Five rabbits in each group were sacrificed at 12 hours and on days 3, 7, and 14 after TACE, and immunohistochemistry was used to measure the proliferation index and apoptosis percentage of tumor cells in the residual tumor area. The tumor necrotic volume was measure on day 7 after TACE, and the growth rate and necrosis rate of tumor cells were calculated. Ten rabbits were randomly selected from each group for the observation of survival time. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kaplan-Meier survival analysis was used to evaluate survival time, and the log-rank test was used for comparison. ResultsOn day 7 after TACE, the CBATO group had a significantly lower growth rate and a significantly higher necrosis rate of tumor cells than the cTACE group, the CB group, and the control group (all P＜0.05). At each time point after TACE, there were significant differences in the proliferation index and apoptosis percentage of tumor cells between the CBATO group and the other three groups (all P＜0.05). The median survival time was 26 days in the CBATO group, 18.5 days in the CB group, 22 days in the cTACE group, and 15.5 days in the control group, and the CBATO group had a significantly longer survival time than the other three groups (χ2=3.95, 8.99, and 13.47, P=0.049, P=0.003, and P＜0.01). ConclusionCBATO has a better effect than cTACE and CB in the treatment of rabbits with VX2 liver tumor and can significantly improve tumor necrosis rate, promote the apoptosis of tumor cells, and prolong the survival time of experimental animals.

Objective: To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC). Methods: The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. Results: Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group. Conclusion VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

Objective To evaluate the efficacy of double percutaneous nephrostomy combined with ureter occlusion stent in treating cervical cancer complicated with vesicovaginal fistula after radiotherapy. Method A prospective analysis was taken for 12 patients with cervical cancer complicated with vesicovaginal fistula after radiotherapy who were diagnosed by gynecological examination, imaging and cystoscopy. All patients received concurrent double percutaneous nephrostomy and ureter occlusion stent implantation.The improvement of symptoms and postoperative complications were observed.The number of white blood cells in urine,renal function,number of diapers in daily use(pieces),daily vaginal and urethral exudate, pain score,physical status (ECOG) score and quality of life score (KPS) before and 7 d after the procedure were compare by the paired Student's t test. Results Twelve patients were successfully implanted 24 ureter occlusion stents after successful nephrostomy. Postoperatively, urinary fistula immediately disappeared in all patients.One week after operation,bilateral hydronephrosis disappeared in 4 patients, renal insufficiency and renal function returned to normal in 4 patients. There were significant differences in the number of white blood cells in urine,the number of diapers in daily use,the daily vaginal and urethral exudate,pain score,KPS and ECOG score compared with before and 7 d after the procedure(all P<0.05).There was no significant difference in the creatinine and urea nitrogen (all P>0.05). No serious complications occurred after the operation.Conclusion Double percutaneous nephrostomy combined with ureter occlusion stent can effectively and safely treat cervical cancer complicated with vesicovaginal fistula after radiotherapy.

Objective To study pharmacokinetics and tissue distribution of CalliSpheres Beads (CB) loaded Arsenic trioxide (ATO) on rabbit VX2 liver tumor by transcatheter arterial chemoembolization (TACE). Method Sixty four rabbits with VX2 liver tumors were randomly divided into 4 groups: control group, CB group, CBATO group and cTACE group. Blood samples were taken at specific time points after TACE.The blood concentration of ATO,liver and kidney functions were examined respectively. In each group, every 4 rabbits were sacrificed on 1 days,3 days,7 days and 14 days after operation. The tumor,liver,kidney, lung,heart and muscle were taken to detect the drug concentration. Bilateral t?test was used to compare the drug concentration in blood and tissue between CBATO group and cTACE group. Results Statistically,The levels of ALT and AST in group CBATO and cTACE on 1st,3rd and 7th days after TACE were significantly higher than those in CB group(ALT: F=25.872, 17.69, 7.016, AST: F=46.365, 32.385, 12.548, P<0.05) respectively. The ALT and AST levels in CBATO group were statistically lower than those in cTACE group (ALT: t=0.369, 0.432, 0.169, 0.353, AST: t=0.488, 0.593, P>0.05). There were no statistically significant differences in the levels of BUN and Scr between the four experimental groups at each observation time point. Statistically, 10 minutes and 20 minutes after TACE, the blood drug concentration inCBATO was significantly lower than that in cTACE (t=7.675, 6.461, P<0.001). while 12 hours after operation,blood drug concentration in CBATO group was higher than that in cTACE group. In tumor tissue,the concentration of ATO in CBATO was higher than that in cTACE,and there was no statistical differences on the 1st day after TACE(t=2.155, P=0.068), but there was a statistical differences between 3rd, 7th and 14th days (t=11.462, 7.624, 2.649, P<0.05). Conclusion CBATO could prolong the time of drug metabolism,increase the drug concentration in tumor tissue,and didn′t aggravate the damage of liver and kidney function.