Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells

AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.

Acute iatrogenic Budd-Chiari syndrome following hepatectomy for hepatolithiasis:A report of two cases

Budd-Chiari syndrome(BCS)is defined as hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava(IVC)and the right atrium,regardless of the cause of obstruction.We present two cases of acute iatrogenic BCS and our clinical management of these cases.The first case was a 43-year-old woman who developed acute BCS following the implantation of an IVC stent for the correction of stenosis in the IVC after hepatectomy for hepatolithiasis.The second case was a61-year-old woman with complete obstruction of the outflow of hepatic veins during bilateral hepatectomy for hepatolithiasis.Acute iatrogenic BCS should be con-sidered a rare complication following hepatectomy for hepatolithiasis.Awareness of potential hepatic outflow obstructions and timely management are critical to avoid poor outcomes when performing hepatectomy for hepatolithiasis.

Systematic review of laparoscopy-assisted versus open gastrectomy for advanced gastric cancer

Objective:The study compared laparoscopy-assisted gastrectomy(LAG) with open gastrectomy(OG) in the management of advanced gastric cancer(AGC).Methods:Literature search was performed in the Medline,Embase,and Cochrane Library databases to identify control studies that compared LAG and OG for AGC.A meta-analysis was conducted to examine the surgical safety and oncologic adequacy,using the random-effect model.Results:Seven eligible studies including 815 patients were analyzed.LAG was associated with less blood loss,less use of analgesics,shorter time of flatus and periods of hospital stay,but longer time of operation.The incidence of most complications was similar between the two groups.However,LAG was associated with a lower rate of pulmonary infection(odds ratio(OR) 0.19;95% confidence interval(CI) 0.05 to 0.68;P<0.05).No significant differences were noted in terms of the number of harvested lymph nodes(weighted mean difference(WMD) 1.165;95% CI-2.000 to 4.311;P>0.05),overall mortality(OR 0.65;95% CI 0.39 to 1.10;P>0.05),cancer-related mortality(OR 0.64;95% CI 0.32 to 1.25;P>0.05),or recurrence(OR 0.62;95% CI 0.33 to 1.16;P>0.05).Conclusions:LAG could be performed safely for AGC with adequate lymphadenectomy and has several short-term advantages compared with conventional OG.No differences were found in long-term outcomes.However,these results should be validated in large randomized controlled studies(RCTs) with sufficient follow-up.

HER-2 overexpression and survival in colorectal cancer: a meta-analysis

Objective： Numerous studies examining the relationship between human epidermal growth factor receptor 2 （HER-2） overexpression and survival in patients with colorectal cancer （CRC） have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value. Methods： Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios （HRs） and their corresponding 95% confidence intervals （95% Cls） were pooled in terms of disease-specific or overall survival. Results Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival （HR=1.10, 95% CI： 0.77-1.44）. Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival （HR=0.89, 95% CI： 0.50-1.29; HR=0.90, 95% Ch 0.43-1.37, respectively）, Conclusions： Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.