MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer.

BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover, miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328 expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05, Pearson's correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy.

Sequential therapy vs. standard triple therapies for Helicobacter pylori infection: a meta-analysis.

BACKGROUND: As standard triple therapies of achieve unsatisfactory eradication of Helicobacter pylori, several alternative regimens have been proposed. OBJECTIVES: To systematically evaluate whether sequential treatment eradicates H. pylori infection better than standard triple therapies and compare the risk of adverse events with these two regimens. METHODS: We searched electronic databases up to February 2008 for studies evaluating the efficacy of the 10-day sequential therapy vs. standard triple regimens for eradication of H. pylori. The pooled risk ratios (RR) and 95% confidence intervals (95% CI) were calculated. RESULTS: We identified 11 randomized trials, including eight full-text manuscripts and three abstracts. Pooled analysis demonstrated clear superiority of the sequential therapy over 7-day triple regimen with an RR of 1.23 (95% CI 1.19-1.27), and over 10-day triple regimen with a RR of 1.16 (95% CI 1.10-1.23). Adverse event rates were similar. For sequential therapy vs. 7-day triple therapies, RR = 0.96, 95% CI 0.70-1.31. CONCLUSIONS: Sequential therapy was associated with a higher eradication rate of H. pylori compared with both 7-day triple regimen and 10-day triple regimen.

Meta-analysis: The utility and safety of heparin in the treatment of active ulcerative colitis.

BACKGROUND: The use of heparin for the treatment of ulcerative colitis has been evaluated in several open and controlled trials, with varying outcomes. AIM: To evaluate the efficacy and safety of heparin as supplemental therapy compared with conventional therapy in patients with ulcerative colitis. METHODS: All randomized trials comparing heparin supplementation to conventional therapy were included from electronic databases. Statistical analysis was performed with review manager 4.2.8 (The Cochrane Collaboration, Oxford, UK). Sub-analysis and sensitivity analysis were also performed. RESULTS: Eight randomized-controlled trials, investigating a total of 454 participants, met the inclusion criteria. The odds ratio (OR) for the efficacy of heparin supplementation vs. conventional therapy was 0.78 (95% CI = 0.50-1.21). Few serious adverse events were observed. The OR for the efficacy of unfractionated heparin and low-molecular-weight heparin vs. conventional therapy was 0.26 (95% CI = 0.07-0.93) and 0.92 (95% CI = 0.57-1.47), respectively. The OR for the efficacy of heparin vs. conventional therapy with placebo was 0.87 (95% CI = 0.53-1.44). CONCLUSIONS: Our meta-analysis suggests that administration of heparin in patients with ulcerative colitis is safe, but no additive benefit over conventional therapy is indicated.

Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy.

BACKGROUND: Recent evidence found probiotics could inhibit Helicobacter pylori colonization from both in vitro and in vivo studies. AIM: To systematically evaluate whether adding probiotics to anti-H. pylori regimens could improve eradication rates and reduce side effects during anti-H. pylori treatment. METHODS: Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing probiotics supplementation to placebo or no treatment during anti-H. pylori regimens. Statistical analysis was performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also performed. RESULTS: We identified 14 randomized trials (n = 1671). Pooled H. pylori eradication rates were 83.6% (95% CI = 80.5-86.7%) and 74.8% (95% CI = 71.1-78.5%) for patients with or without probiotics by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34-2.54); the occurrence of total side effects were 24.7% (95% CI = 20.0-29.4%) and 38.5% (95% CI = 33.0-44.1%) for groups with or without probiotics, especially for diarrhoea, the summary OR was 0.44 (95% CI = 0.30-0.66). CONCLUSIONS: Our review suggests that supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy-related side effects.