ObjectiveThe roles of nonsteroidal anti-inflammatory drugs (NSAIDs) in the occurrence and prognosis of hepatocellular carcinoma (HCC) remain controversial. This analysis aimed to summarize the relationships between NSAIDs and HCC development.MethodsStudies published prior to October 1, 2017, in the PubMed, Embase, Ovid, Web of Science, and Cochrane Library databases were systematically searched and analyzed.ResultsEleven studies were included in this analysis. A meta-analysis of five studies revealed that aspirin use could significantly decrease the risk of HCC occurrence (hazards ratio [HR] = 0.64, 95% confidence interval [CI] = 0.45–0.91, P = 0.014). No significant difference was found for the use of NSAIDs (six studies) and non-aspirin NSAIDs (three studies) in HCC occurrence (HR = 0.74, 95%CI = 0.53–1.02, P = 0.064 and HR = 0.98, 95%CI = 0.87–1.12, P = 0.81, respectively). However, subgroup analysis of cohort studies demonstrated that NSAIDs significantly decreased the risk of HCC occurrence (HR = 0.58, 95%CI = 0.43–0.78, P < 0.001). HCC patients who received NSAIDs achieved better disease-free survival and overall survival compared with the non-NSAID users (HR = 0.79, 95%CI = 0.74–0.84, P<0.001 and HR = 0.60, 95%CI = 0.50–0.72, P<0.001, respectively). Additionally, a meta-analysis of two studies showed that aspirin treatment in HCC patients could significantly decrease the 2-year and 4-year mortalities (rate ratio [RR] = 0.50, 95%CI = 0.36–0.69, P < 0.001 and RR = 0.67, 95%CI = 0.45–0.998, P = 0.049, respectively). A meta-analysis of two studies showed that aspirin use was not associated with a higher risk of bleeding in HCC patients (HR = 0.71, 95%CI = 0.41–1.23, P = 0.223).ConclusionThe use of NSAIDs, especially aspirin, is linked to a lower risk of HCC development and better survival in HCC populations. High-quality, well-designed trials should be conducted to reevaluate the relationships between NSAIDs and HCC.

The roles of exonuclease 1 (EXO1) in hepatocellular carcinoma (HCC) tumorigenesis and progression remain unclear. This study aimed to assess the prognostic value and therapeutic potential of EXO1 in HCC. Exo1 gene copy numbers were obtained from three Oncomine microarray datasets (n = 447). EXO1 mRNA expression was validated by semi-quantitative PCR and QuantiGene® 2.0 assays. Cell growth curve and colony formation were performed to asses the cell proliferation. Clonogenic assay, flow cytometry, and immunofluorescence were adopted to acess the effects of EXO1 knockdown and radiation on cell survival, cell cycle distribution and DNA repair. Western blots were performed to reveal the related mechanism. A significant copy number variation (CNV) of the Exo1 gene was found in HCC specimens in three separate sets of published microarray data. In the 143 cases treated by our team, EXO1 expression levels were elevated (86.71%, 124/143). In addition, EXO1 overexpression was correlated with larger tumor size (P = 0.002), increased lymph node metastasis (P=0.033) and lower Edmondson grade (P = 0.018). High EXO1 expression unfavorably affected overall survival (OS) (P = 0.009). Both univariate and multivariate Cox regression analyses identified EXO1 as an independent predictor of OS (univariate, P = 0.012; multivariate, P = 0.039). Silencing of EXO1 in vitro reduced cell proliferation. EXO1 knockdown further suppressed clonogenic cell survival, abrogated radiation-induced G2/M phase arrest, and enhanced γ-H2AX foci after exposure to irradiation. The accumulation of ataxiatelangiectasia mutated (ATM) might partially regulate the EXO1 related radiosensitivity. In summary, EXO1 could be a promising prognostic marker, with a potential therapeutic value in HCC.

We aim to conduct a meta-analysis of studies on the effect of Aidi injection combined with TACE in the treatment of hepatocellular carcinoma (HCC). China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP), Allied and Complementary Medicine Database (AMED), EMBASE, Web of Science, PubMed, and Cochrane Library databases to October 1, 2017, were searched to collect the studies. The data analysis was performed using RevMan 5.3 software. Totally 20 clinical trials with 774 (the experimental group: 447 cases; the control group: 327 cases) HCC patients were finally included in this meta-analysis. Meta-analysis results showed that Aidi injection combined with TACE can, to some extent, enhance the clinical effect and improve the overall survival. Meanwhile, it can increase HCC patients' quality of life. Additionally, Aidi injection plus TACE can reduce adverse events including leukopenia, gastrointestinal reaction, and liver damage in HCC patients (all P < 0.05). Therefore, Aidi injection plus TACE may significantly enhance the clinical effect, suggesting that the combination of TCM and western medicine is promising. The exact outcome needs rigorously designed performances, multicenter, and large randomized controlled trials.

Tumor angiogenesis is one of the hallmarks of cancer as well as an attractive target for cancer therapy. Characterization of novel pathways that act in parallel with the VEGF/VEGFR axis to promote tumor angiogenesis may provide insights into novel anti‐angiogenic therapeutic targets. We found that the expression level of Nogo‐B is positively correlated with tumor vessel density in hepatocellular carcinoma (HCC). While Nogo‐B depletion inhibited tumor angiogenesis, Nogo‐B overexpression promoted tumor angiogenesis in a tumor xenograft subcutaneous model of the human HCC cell line. Mechanically, Nogo‐B regulates tumor angiogenesis based on its association with integrin αvβ3 and activation of focal adhesion kinase. Moreover, Nogo‐B antibody successfully abolished the function of Nogo‐B in tumor angiogenesis in vitro and in vivo. Collectively, our results strongly suggest that Nogo‐B is an important tumor angiogenic factor and blocking Nogo‐B selectively inhibits tumor angiogenesis.

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BackgroundRecent studies have shown that Toll-like receptors (TLRs) may be associated with cancers. The aim of this meta-analysis is to summarize the predicting role of TLRs for survival in patients with a variety of carcinomas.Materials and methodsEligible studies were identified and assessed for quality through multiple search strategies. We collected data from studies investigating the relationship between the expression level of TLRs and survival in cancer patients. Studies were pooled and combined hazard ratios (HRs) of TLRs for survival were analyzed.ResultsA total of 24 studies, including 2,812 patients with various cancers, were identified for the meta-analysis. Importantly, this meta-analysis showed that higher expression levels of TLR4 or TLR7 in tumor tissues could predict poorer survival, with the pooled HR being 1.29 (95% CI: 1.17, 1.42) and 1.71 (95% CI: 1.38, 2.12), respectively. However, higher expression of TLR9 had no significant association with outcome as HR was 0.84 (95% CI: 0.62, 1.115). Heterogeneity existed in TLR4 and TLR9 studies (P-value <0.001) but not in TLR7 studies (P-value >0.05).ConclusionThe expression level of TLR4 or TLR7 in cancerous tissue may have a prognosis value in patients with various cancers.