Objective To investigate the effect of berberine on the radiosensitivity of cervical cancer cells.Methods 5,10,15,20 μmol/L of berberine were used to treat cervical cancer cell lines of Siha,HeLa,Caski.DMSO was applied as control of drug treatment.Cell proliferation was detected by the CCK-8 method,and then the half inhibitory concentration of berberine was calculated.Cell apoptosis and cell cycle distribution were detected by flow cytometry.Protein expressions of Cleaved Caspase-3,Cyclin B1,CDK1,STAT3 and p-STAT3 were detected by Western blot.Cervical cancer cells of Siha were treated by berberine with a half inhibitory concentration for 24 h and then irradiated with 0,2,4,6,8 Gy of X-rays.Cell clone assay was used to detect cell survival.Results Berberine could inhibit the growth of cervical cancer cells with a half inhibition concentration of(16.84 ± 3.52),(23.54 ± 8.67),(21.86 ± 6.35)μmol/L for Siha,Caski,and HeLa cells,respectively.The berberine at 17 μmol/L could induce apoptosis (t =56.847,P ＜ 0.01) and G2/M phase arrest (t =47.251,P ＜ 0.01) in Siha cells,which also inhibited the expressions of Cyclin B1,CDK1 and p-STAT3 and promoted the expression of cleaved Caspase-3,but did not influence the expression of STAT3 in cervical cancer cells.Treatment of cells with 17 μmol/L berberine increased the radiosensitivity of cervical cancer cells with a sensitivity enhancement ratio of 1.55.Conclusions Berberine can inhibit cell proliferation,promote apoptosis,block cell cycle,and increase radiosensitivity of cervical cancer cells.

BACKGROUND AND OBJECTIVEResults of studies on genetic polymorphisms of ERCC1 gene in DNA repair pathway which may affect response to platinum-based chemotherapy and survival in patients with non-small cell lung cancer are conflicting. The aim of this study is to prospectively assess the association between single nucleotide polymorphisms of C8092A and codon118 in ERCC1 and drug response in 90 patients with advanced non-small cell lung cancer treated with cisplatin-based chemotherapy.

METHODSAll patients were treated with cisplatin-based chemotherapy. Genotypes of ERCC1 C8092A and codon118 were examined by sequencing, and the association between genotypes and response was evaluated.

RESULTSGenotype frequencies of ERCC1 C8092A were CC 40.0% (36/90), CA 48.9% (44/90) and AA 11.1% (10/90), frequencies of codon118 were CC 58.9% (53/90), CT 34.4% (31/90) and TT 6.7% (6/90). There was no significant difference in response rate of patients carrying with CC, compared with CA plus AA in C8092A (33.3% vs 29.6%, P = 0.71). Response rate of patients carrying with CC in ERCC1 118 was 32.1%, 24.3% with CT plus CC (P = 0.43). There was no difference in progression free survival between patients carrying with CC and CT plus TT in C8092A (5.2 months vs 5.4 months, P = 0.62). There was no difference in progression free survival between patients carrying with CC and CA plus AA (5.5 months vs 5.3 months, P = 0.59).

CONCLUSIONThe results suggest that there is no association between polymorphisms in ERCC1 C8092A and codon118 and response in patients with advanced non-small cell lung cancer receiving cisplatin-based chemotherapy.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; mortality ; Cisplatin ; therapeutic use ; DNA-Binding Proteins ; genetics ; Disease-Free Survival ; Endonucleases ; genetics ; Female ; Genotype ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; mortality ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Prospective Studies

Objective To investigate the effect of evodiamine on the proliferation and sensitivity of endometrial cancer cells to irradiation.Methods After administration of evodiamine,cell proliferations of human endometrial carcinoma cell lines of Ishikawa,HEC-1A,AN3CA were detected by MTT and the half maximal inhibitory concentration (IC50) of drug was calculated.The cell lines most sensitive to drug were screened for further experiment and administered with evodiamine (IC50) and 8 Gy irradiation.Then,cell apoptosis was detected by flow cytometry,the levels of Cleaved Caspase-3,p38 and p-p38 were measured by Western blot,and the level of intracellular ROS was detected by a ROS kit.Cell clone survival was also detected to evaluate cell radiosensitivity.Results 1,2,4,6 and 8 μmol/L evodiamine could inhibit the proliferation of the cell line of Ishikawa,HEC-1A,and AN3CA with IC50 of(8.32 ± 0.95),(3.98 ± 0.84) and (4.78 ± 0.64) μmol/L,respectively.Compared with radiation alone,after radiation in combination with 4 μmol/L evodiamine,the apoptosis rate of HEC-1A cells was increased from (45.54 ±4.25)％ to (65.87 ±2.93)％ (t =11.010,P ＜0.05) and cell viability decreased from (41.84±4.18)％ to (33.27 ± 3.52)％ (t =7.484,P ＜0.05),and the levels of ROS,Cleaved Caspase-3 and p-p38 were also enhanced.In addition,the sensitivity ratio of evodiamine for HEC-1A cells was calculated to be 1.628.Conclusions Evodiamine could inhibit the proliferation,promote apoptosis and enhance the radiosensitivity of endometrial carcinoma cells,in which the intracellular ROS and p38 signaling pathway may be involved.

BACKGROUNDTopotecan is one of active agents for relapsed small cell lung can-cer (SCLC), some studies have shown that it is effective against SCLC as the first-line drug. This study is to assess the efficacy, toxicity and survival rate of topotecan plus cisplatin (TP) versus etoposide plus carboplatin (CE) in patients with previously untreated SCLC.

METHODSSixty-four patients with previously untreated SCLC were randomly assigned to receive either TP or CE. Topotecan 0.75 mg/(m²×d) via a 30-min intravenous infusion on days 1 to 5 and cisplatin 25 mg/(m²×d) on days 1 to 3 with hydration were given to patients in TP group. Carboplatin 300 mg/m² on day 1 and etoposide 100 mg/d on days 1 to 5 were given to patients in CE group. Treatment was repeated every 21 days. Responses and toxicities were evaluated in patients who received two cycles of chemotherapy. Patients with limited disease SCLC received thoracic irradiation or operation after the completion of chemotherapy.

RESULTSOverall response rate was 75.0% in TP group and 68.8% in CE group. The median survival time was 10.5 months in TP group and 9.6 months in CE group. 1-, 2- and 3-year survival rate were 40.6%, 18.8% and 9.4% in TP group and 34.4%, 15.6% and 9.4% in CE group respectively. There were no significant differences in response rate, median survival time and survival rate between two groups (P > 0.05). Myelosuppression, nausea and vomiting, and alopecia were the most common toxicities, there was no significant difference in grade III and IV toxicities between two groups (P > 0.05).

CONCLUSIONSTP has similar response rate and survivals with CE, and its toxicities are acceptable. TP regimen is an effective first-line treatment for SCLC.

BACKGROUNDTo evaluate the efficacy and toxicity of combined chemotherapy of domestic paclitaxel and vinorelbine plus cisplatin and carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC).

METHODSA total of 181 initially treated patients with advanced NSCLC were enrolled in this study and treated by NP (vinorelbine plus cisplatin), TC (domestic paclitaxel plus carboplatin) and TP (domestic paclitaxel plus cisplatin). The efficacy and side effects were analysed after at least two cycles of chemotherapy.

RESULTSThe overall response rates (CR+PR) were 42.4% in the NP arm, 40.3% in the TC arm and 43.3% in the TP arm respectively. No significant statistical difference was found among the three groups ( Chi-square= 0.108 6 , P > 0.05). The median survival times were 8.4 months, 9.4 months and 8.9 months respectively in the NP, TC and TP groups ( P > 0.05). The 1-, 2-, 3-year survival rates were 39.0%, 16.9%, 5.1% in the NP group and 41.9%, 21.0%, 6.5% in the TC group and 40.0%, 18.3%, 5.0% in the TP group respectively. No significant statistical difference was found among the three groups ( Chi-square=0.140 4, P > 0.05). The major side effects were myelosuppression, alopecia and nausea/vomiting in the three groups. There were no chemotherapy-related death among the three groups.

CONCLUSIONSThe combined regimens of NP, TC and TP are effective and well-tolerated regimens for advanced NSCLC.

Objective:A kinetic model of the clearance of protein-bound uremic toxins (PBUTs) in maintenance hemodialysis patients is established to evaluate the effects of adding sorbents with different sorption efficiency to dialysate on the clearance rate of PBUTs, and to predict the sorption efficiency of sorbents using the model.Methods:The kinetic model was established by integrating the parameters of plasma flow rate ( Qp), dialysate flow rate ( Qd), free plasma fraction of PBUTs ( f1), free dialysate fraction of PBUTs ( f2), mass transfer coefficient of dialyzer ( K) and surface area of dialysis membrane ( A), and using the mass balance equation and Fick's first law. The model was also used to evaluate the relationship between the clearance rate of different PBUTs and the parameters of dialyzer and the sorption efficiency of sorbents. Results:The kinetic model of PBUTs clearance (CL): ?CL=Qp1-f1-f2γφf1-f2γ,?γ=QpQd,?φ=eKAf1Qp-f2Qd. The model was used to analyze the dialysis parameters of indoxyl sulfate and p-cresol sulfate dialysis.The clearance rate of PBUTs increased with the decrease of its binding capacity to albumin in plasma and the increase of plasma flow rate in dialyzer, dialysate flow rate, mass transfer coefficient of dialyzer, surface area of dialysis membrane, and sorption capacity of sorbents in dialysate. The increasing trend of PBUTs clearance rate was particularly obvious after applying sorbents. Further analysis of the dialysate flow rate and the sorption efficiency of sorbents in the dialysate showed that the increase of the dialysate flow rate could make up for the difference of the sorption efficiency of sorbents. When the dialysate flow rate tended to be infinite, the sorption efficiency of sorbents in the dialysate had no effect on the clearance rate of PBUTs. Conclusion:Adding sorbents of PBUTs to the dialysate during dialysis can significantly improve the clearance rate of PBUTs, suggesting a promising clinical application value.