A Meta-Analysis of Efficacy and Adverse Effects of Lobaplatin and Cisplatin in the Treatment of Malignant Pleural Effusion / 中国肺癌杂志

BACKGROUND@#The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion.@*METHODS@#The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software.@*RESULTS@#A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group.@*CONCLUSIONS@#Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.

Reversion of multi-drug resistance of gastric carcinoma cisplantin-resistant cell SCG7901/DDP by silencing caudal type homeobox 2 / 中华消化外科杂志

Objective To investigate the effects of caudal type homeobox 2 (Cdx2) silence on reservion of multi-drug resistance of gastric carcinoma cisplantin-resistant cell SGC7901/DDP.Methods Gastric carcinoma cisplantin-resistant cells SCG7901/DDP in the logarithmic phase were cultured in the plate,and were divided into the experimental group [gastric carcinoma cells of SGC7901/DDP were infected with a silent Cdx2-recombinanted lentiviral vector (pLL-Cdx2-shRNA)],the negative control group (gastric carcinoma cells of SGC7901/DDP were infected with empty lentiviral vector) and the blank control group (gastric carcinoma cells of SGC7901/DDP were not treated).The protein and mRNA expressions of Cdx2 and apoptosis related genes like c-myc,cyclin D1 and survivin were detected by the Western blot and reverse-transcription PCR,respectively.The sensitivity of the cells in the 3 groups to adriamycin,5-fluorouracil and cisplatium were assessed by MTT.The pump-out rate of adriamycin,cell cycle distribution and apoptosis of the 3 groups were analyzed using flow cytometry.All measurement data were expressed with mean ± standard deviation.Comparison among multi-groups was done by one-way analysis of variance,and comparison between 2 groups was done by SNK-q test.The enumeration data were analyzed using the chi-square test.Results The relative protein expression levels of Cdx2,c-myc,cyclin D1 and survivin were 0.187 ± 0.060,0.086 ± 0.004,0.016 ± 0.005 and 0.276 ± 0.012 in the experimental group,0.535 ± 0.033,0.379 ± 0.006,0.141 ± 0.003 and 0.672 ± 0.009 in the negative control group,and 0.567 ± 0.014,0.354 ± 0.004,0.162 ± 0.008 and 0.517 ± 0.313 in the blank control group,respectively.The relative protein expression levels of Cdx2,c-myc,cyclin D1 and survivin in the experimental group were significantly lower than those in the negative control group and the blank control group (F =247.385,3.353,597.882,98.628,P ＜0.05).The relative mRNA expression levels of Cdx2,c-myc,cyclin D1 and survivin were 0.184 ± 0.010,0.212 ± 0.022,0.045 ± 0.009 and 0.401 ± 0.027 in the experimental group,0.894 ± 0.056,0.538 ± 0.021,0.163 ±0.009 and 0.824 ± 0.016 in the negative control group,and 0.837 ±0.049,0.545 ±0.032,0.157 ±0.010 and 0.782 ±0.056 in the blank control group,respectively.The relative mRNA expression levels of Cdx2,c-myc,cyclin D1 and survivin in the experimental group were significantly lower than those in the negative control group and the blank control group (F =243.776,161.793,138.523,118.426,P ＜ 0.05).The IC50 values detected by MTT of adriamycin,5-flurouracile and cisplatin to gastroc carcinoma cisplantin-resistant cell SCG7901/DDP were (0.12 ± 0.05) mg/L,(0.52 ± 0.13) mg/L and (0.82 ± 0.13) mg/L in the experimental group,(0.33 ± 0.08) mg/L,(4.10.± 1.25) mg/L and (2.81 ± 0.50) mg/L in the negative control group,(0.39 ±0.15)mg/L,(4.05 ± 1.44) mg/L and (3.28 ± 1.03) rng/L in the blank control group,respectively.The pump-out rates of adriamycin of the experimental group,negative control group,and the blank control group were0.21％,0.37％ and 0.35％.Compared with the negative control group and the blank control group,the IC50values of adriamycin,5-fluorouracil and cisplatin in the experimental group were significantly increased,and thepump-out rate of adriamycin was significantly decreased (F =8.101,13.854,15.159,x2 =7.106,P ＜ 0.05).The ratios of cells in the G0/G1 phase were 17.87％,34.71％ and 37.20％ in the experimental group,negative control group and the blank control group,respectively.Compared with the negative control group and blank control group,the ratio of cells in the G0/Gt was significantly decreased (x2=1.055,P ＜ 0.05).The ratio of cells in the G2/M phase in the experimental group was 11.93％,and the apoptosis rate was 31.13％,which were significantly higher than the negative group (0.26％,16.58％) and the blank control group (0.35％,13.18％) (x2=2.249,11.030,P ＜ 0.05).Conclusions Silent Cdx2 can effectively enhance the sensitivity of the SGC7901/DDP cells and the intracellular accumulation concentration of the drugs.Silent Cdx2 can also reverse the multidrug resistance of the SGC7901/DDP cells.

Change of MDR Gene Expression and Glutathione Metabolism during Long Standing Low-dose Cisplatin Exposure in Bladder Carcinoma Cell Line / 대한비뇨기과학회지

Resistance to anticancer chemotherapeutic drugs remains a major obstacle in cancer chemotherapy. A variety of mechanisms responsible for drug resistance has been posed. Mdr gene overexpression and detoxification by glutathione are believed to be involved in such mechanisms. Recently, we established two low-dose cisplatin-resistant human bladder cancer cell lines, T24RO.5 and T24R1, which showed resistance at O.5 hg/ml and 1 hg/ml of cisplatin, respectively. The resistance of T24RO.5 and T24R1 cells to cisplatin were 9.4 and 9.37 fold compared to that of the parental T24 cells In this study, we investigated the total glutathione content and p-glycoprotein expression, a mdr gene product, in parent and resistant cell lines to elucidate the drug resistance mechanism to cisplatin. Glutathione content was measured by biochemical method. P-glycoprotein expression was measured by flowcytometry using monoclonal antibody to p-glycoprotein. Glutathione content and p-glycoprotein expression were not different between parental and all resistant cell lines. These results suggest that mdr gene and glutathione do not play a role in cisplatin resistance mechanism in these low-dose cisplatin-resistant cell lines. Further work will be necessary to determine the mechanism of drug resistance in this model.

Protective Effect of Several Metals Against cis-Diamminedichloroplatinum Toxicity to Mouse Survival and Kidney / 대한비뇨기과학회지

cis-Diamminedichloroplatinum(Cisplatin ; CDDP) intoxication has been known to be prevented by decrease of toxicity using pretreatment with small doses of some metals. In this study, 12 weeks of age, weighing approximately 30 gram male mature I.C.R. mice were used to investigate protective mechanism of combined treatment or pretreatment with small doses of metals(Cu, Se, Zn) against CDDP intoxication, and in the group treated with metals : 1. Survival effects against lethal dose of CDDP were observed and 2. The effects on the renal toxicity with administrating one third of lethal CDDP dose were observed by different preventive effect among each pretreated metals with blood chemistry, kidney weight and histopathologic finding, and we obtained the results as follows : 1. 15 days survival rates after administration of lethal CDDP dose were significantly increased in the group selenium combined treatment and in the copper combined treatment group compared to the group without combined treatment of metal. 2. At the day after administration of one third of lethal CDDP dose, BUN levels were significantly increased in the group without pretreatment and in the zinc pretreatment group compared to control group, but they were not increased in cases of pretreatment with selenium or copper, and serum creatinine levels were not significantly changed in the all experimental groups compared to control group. 3. At 5th day after administration of one third of lethal CDDP dose, relative kidney weights(kidney weight/body weight) were significantly increased in the group without pretreatment and in the zinc pretreatment group compared to control group, but they were not significantly increased in the pretreated group with selenium or copper. 4. At 5th day after administration of one third of lethal CDDP dose, renal histopathologic findings showed vacuolar changes and focal necrosis of proximal tubular cells at the corticomedullary junction in the group without pretreatment and in the zinc pretreatment group, but only swelling of those area in the selenium or copper pretreated group. 5 At 15th day after administration of one third of lethal CDDP dose, BUN levels, serum creatinine levels and relative kidney weights(kidney weight/body weight) were not significantly different between the all pretreated group and control group, and histopathologic findings also did not reveal any differences between the heavy metal pretreated group and control group.