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Circumferential extension and histological depth were reliable risk factors for postoperative stricture.

BACKGROUND: PIWI protein family was found to play an important role in stem cell self-renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear. METHODS: HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n ¼ 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n ¼ 168) for survival analysis. RESULTS: Levels of HIWI protein and mRNA were up-regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P ¼ .047) and intrahepatic metastasis (P ¼ .027) and was an independent risk factor for overall survival (P ¼ .007) and recurrence-free survival (P ¼ .036), particularly in patients with low serum afetoprotein and low Edmondson-Steiner grade. CONCLUSIONS: HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well-differentiated HCC.

Background & AimsmicroRNAs (miRNAs) have been reported to regulate angiogenesis by down-regulating the expression of pro-angiogenic or anti-angiogenic factors. The aims of this study were to investigate whether miR-26a inhibited angiogenesis by down-regulating vascular endothelial growth factor A (VEGFA) and its clinical relevance in hepatocellular carcinoma (HCC).MethodsThe expression of miR-26a was modified in HepG2 and HCCLM3 cell lines respectively, and a panel of angiogenic factors was measured by real-time PCR in the cells. A luciferase reporter assay was used to validate the target gene of miR-26a. Specific inhibitors of signal transduction pathway and siRNA approaches were used to explore the regulatory mechanism of miR-26a. Migration and tube forming assays were conducted to show the changes of angiogenesis induced by miR-26a and its target genes. Finally animal studies were used to further validate those findings.ResultsEctopic expression of miR-26a exhibited decreased levels of VEGFA in HepG2 cells. Migration and tube forming of human umbilical vein endothelial cells (HUVECs) were decreased in the conditioned medium from ectopic expression of miR-26a in HepG2 cells compared to control HepG2 cells. The pro-angiogenic effects of the conditioned medium of HepG2 cells on HUVECs were specifically decreased by LY294002, YC-1, and bevacizumab. Integrated analysis disclosed PIK3C2α as a downstream target gene of miR-26a. Ectopic expression of miR-26a suppressed ectopic and orthotopic tumor growth and vascularity in nude mice. The results in HCCLM3 were consistent with those in HepG2. miR-26a expression was inversely correlated with VEGFA expression in HCC patients.ConclusionsmiR-26a modulated angiogenesis of HCC through the PIK3C2α/Akt/HIF-1α/VEGFA pathway. The expression of VEGFA was inversely correlated with miR-26a expression in HCC tumors.

Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in cathelin-related antimicrobial peptide (CRAMP) were defective in the development of colon mucosa and highly sensitive to dextran sulfate sodium (DSS)-elicited colitis, as well as azoxymethane-mediated carcinogenesis. Pretreatment of CRAMP mice with antibiotics markedly reduced the severity of DSS-induced colitis, suggesting CRAMP as a limiting factor on dysbiosis in the colon. This was supported by observations that wild-type (WT) mice cohoused with CRAMP mice became highly sensitive to DSS-induced colitis, and the composition of fecal microbiota was skewed by CRAMP deficiency. In particular, several bacterial species that are typically found in oral microbiota, such as ,, and , were increased in feces of CRAMP mice and were transferred to WT mice during cohousing. When littermates of CRAMP parents were examined, the composition of the fecal microbiota of WT pups and heterozygous parents was similar. In contrast, although the difference in fecal microbiota between CRAMP and WT pups was small early on after weaning and single mouse housing, there was an increasing divergence with prolonged single housing. These results indicate that CRAMP is critical in maintaining colon microbiota balance and supports mucosal homeostasis, anti-inflammatory responses, and protection from carcinogenesis.

BackgroundMonoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown.MethodsIn this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines. Finally, we identified the NF-κB signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition (EMT) using HCC cell lines with different metastatic potentials.ResultsThe expression of MAGL was significantly higher in HCC tumors than in matched peritumor tissues. Specifically, high MAGL expression was found in tumors with larger tumor size, microvascular invasion, poor differentiation, or advanced TNM stage. In addition, the clinical prognosis for the MAGLhigh group was markedly poorer than that for the MAGLlow group in the 1-, 3-, and 5-year overall survival times and recurrence rates of HCC patients. MAGL expression was an independent prognostic factor for both survival and recurrence after curative resection. Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and invasiveness abilities, and accompanied by EMT. In contrast, downregulation of MAGL obviously inhibited these characteristics. Moreover, further investigations verified that MAGL facilitates HCC progression via NF-κB-mediated EMT process.ConclusionsOur findings demonstrate MAGL could promote HCC progression by the induction of EMT and suggest a potential therapeutic target, as well as a biomarker for prognosis, in patients with HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0361-3) contains supplementary material, which is available to authorized users.

Objectives: Inflammatory bowel disease (IBD) may be associated with oral diseases, but few relevant studies have been reported in China. This study aimed to compare the prevalence, severity and extent of dental caries and periodontal disease in Chinese IBD patients and healthy controls. Materials and methods: In this cross-sectional study, questionnaires and oral examinations were completed for 389 IBD patients [265 with Crohn's disease (CD) and 124 with ulcerative colitis (UC)] and 265 healthy controls based on the established criteria of the World Health Organization. Tobit regression, multiple linear regression and logistic regression were performed to analyse the data. Results: After adjusting for confounders, the decayed, missing and filled surfaces indices were significantly increased in the CD and UC patients compared with those in the controls (P < 0.001). Patients with CD [odds ratio (OR) = 4.27, 95% confidence interval (95% CI): 2.63-6.95, P < 0.001] and UC (OR = 2.21, 95% CI: 1.24-3.94, P = 0.007) had significantly higher risks of dental caries than controls. Significantly higher percentages of sites with probing pocket depth ≥ 5 mm and clinical attachment loss ≥ 4 mm were observed in CD and UC patients compared with controls (P < 0.001). A fully adjusted model revealed that CD and UC were risk indicators for periodontitis (OR = 4.46, 95% CI: 2.50-7.95, P < 0.001; OR = 4.66, 95% CI: 2.49-8.71, P < 0.001, respectively). No significant differences in dental caries and periodontal disease were observed between the CD and UC patients. Conclusions: Chinese IBD patients have a higher prevalence, severity and extent of dental caries and/or periodontal disease than controls, and require oral health education and multidisciplinary treatment.

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