Efficacy of S-1 vs capecitabine for the treatment of gastric cancer: A meta-analysis

AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients.Statistical analysis was performed by metaanalysis.Four randomized controlled trials met the inclusion criteria.RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80(95%CI: 0.52-1.21, P = 0.29).The overall response rate of S-1 vs capecitabine was 0.94(95%CI: 0.59-1.51, P = 0.93).Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia( O R = 0.9 9, 9 5 % C I : 0.6 5- 1.4 9, P = 0.9 4) a n d thrombocytopenia(OR = 0.72, 95%CI: 0.31-1.67, P = 0.44).The most frequent non-hematologic toxicities included nausea(OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome(OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.

Tumor suppressor function of ezrin-radixin-moesin-binding phosphoprotein-50 through β-catenin/E-cadher in pathway in human hepatocellular cancer

AIM:To determine the effect and molecular mechanism of ezrin-radixin-moesin-binding phosphoprotein-50(EBP50) in hepatocellular carcinoma(HCC).METHODS:Three human HCC cell lines,i.e.,SMMC7721,HepG2 and Hep3B,were used.We transfected the Pbk-CMV-HA-EBP50 plasmid into SMMC7721 cells with Lipofectamine 2000 to overexpress EBP50.Western blotting were performed to determine the effects of the plasmid on EBP50 expression and to detect the expression of β-catenin and E-cadherin before and after the transfection of the plasmid into SMMC7721 cells.In vitro cell proliferation was assessed with a Cell Counting Kit-8(CCK-8) assay.Cell cycle distribution was assessed with flow cytometry.Invasion and migration ability of before and after the transfection were determined with a transwell assay.Cell apoptosis was demonstrated with Annexin V-FITC.The effect of EBP50 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice.RESULTS:The transfection efficiency was confirmed with Western blotting(1.36 ± 0.07 vs 0.81 ± 0.09,P < 0.01).The CCK8 assay demonstrated that the growth of cells overexpressing EBP50 was significantly lower than control cells(P < 0.01).Cell cycle distribution showed there was a G0/G1 cell cycle arrest in cells overexpressing EBP50(61.3% ± 3.1% vs 54.0% ± 2.4%,P < 0.05).The transwell assay showed that cell invasion and migration were significantly inhibited in cells overexpressing EBP50 compared with control cells(5.8 ± 0.8 vs 21.6 ± 1.3,P < 0.01).Annexin V-FITC revealed that apoptosis was significantly increased in cells overexpressing EBP50 compared with control cells(14.8% ± 2.7% vs 3.4% ± 1.3%,P < 0.05).The expression of β-catenin was downregulated and E-cadherin was upregulated in cells overexpressing EBP50 compared with control cells(0.28 ± 0.07 vs 0.56 ± 0.12,P < 0.05;0.55 ± 0.08 vs 0.39 ± 0.07,P < 0.05).In vivo tumor growth assay confirmed that up-regulation of EBP50 could obviously slow the growth of HCC derived from SMMC7721 cells(28.9 ± 7.2 vs 70.1 ± 7.2,P < 0.01).CONCLUSION:The overexpression of EBP50 could inhibit the growth of SMMC7721 cells and promote apoptosis by modulating β-catenin,E-cadherin.EBP50 may serve asa potential therapeutic target in HCC.

Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo

AIM: To determine whether the human giant larvae homolog 1 gene (Hugl-1/Llg1/Lgl1) exerts tumor suppressor effects in esophageal cancer. METHODS: We constructed a Hugl-1 expression plasmid, pEZ-M29-Hugl1, for gene transfection. We transfected the pEZ-M29-Hugl1 plasmid into Eca109 esophageal cancer cell lines with Lipofectamine 2000 to overexpress Hugl-1. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the effects of the plasmid on Hugl-1 expression. In vitro cell proliferation and apoptosis were examined separately by cell counting Kit-8 (CCK-8) assay, flow cytometry, and Western blotting before and after the transfection of the plasmid into Eca109 cells. Cell cycle distribution was assessed with flow cytometry. The effect of Hugl-1 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. Expression of Hugl-1 in xenograft tumor was analyzed by immunohistochemistry.The transferase-mediated dUTP nick end-labeling (TUNEL) technique was performed to detect and quantitate apoptotic cell. RESULTS: The transfection efficiency was confirmed with real-time RT-PCR and Western blotting. Our results show that compared with control groups the mRNA levels and protein levels of Hugl-1 in pEZ-M29-Hugl1-treated group were remarkably increased (P < 0.05). The CCK-8 assay demonstrated that the growth of cells overexpressing Hugl-1 was significantly lower than control cells. Cell cycle distribution showed there was a G 0 /G 1 cell cycle arrest in cells overexpressing Hugl-1 (64.09% ± 3.14% vs 50.32% ± 4.60%, 64.09% ± 3.14% vs 49.13% ± 2.24%). Annexin V-fluorescein isothiocyanate revealed that apoptosis was significantly increased in cells overexpressing Hugl-1 compared with control group (17.33% ± 4.76% vs 6.90% ± 1.61%, 17.33% ± 4.76% vs 6.27% ± 0.38%). Moreover, we found that Hugl-1 changes the level of the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax and the activation of both caspase-3 and caspase-9. With a TUNEL assay, we found that Hugl-1 markedly increased the apoptosis rate of Eca109 cells in vivo (60.50% ± 9.11% vs 25.00% ± 12.25%). It was shown that Hugl-1 represents a significantly more effective tumor suppressor gene alone in a xenograft tumor mouse model. This data suggest that Hugl-1 inhibited tumor growth and induced cell apoptosis in vivo . CONCLUSION: These results suggest that Hugl-1 induces growth suppression and apoptosis in a human esophageal squamous cell carcinoma cell line both in vitro and in vivo .