Zengjun Li

Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese

BackgroundRecent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population.MethodsWe genotyped three SNPs of the IL-10 promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade.ResultsNo significant differences in allele frequency or genotype distribution were observed for any of the IL-10 SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, P = 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, P = 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, P = 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively).ConclusionsOur results identify that IL-10 promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression.

Robotic versus laparoscopic right colectomy: a meta-analysis

BackgroundThe objective of this meta-analysis was to compare the clinical safety and efficacy of robotic right colectomy (RRC) with conventional laparoscopic right colectomy (LRC).MethodsA literature search was performed for comparative studies reporting perioperative outcomes of RRC and LRC. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, the fixed effects model or the random effects model were used for the meta-analysis. Operative time, estimated blood loss, length of hospital stay, conversion rates to open surgery, postoperative complications, and related outcomes were evaluated.ResultsSeven studies, including 234 RRC cases and 415 conventional LRC cases, were analyzed. The meta-analysis showed that RRC had longer operative times (P < 0.00001), lower estimated blood losses (P = 0.0002), lower postoperative overall complications (P = 0.02), and significantly faster bowel function recovery (P < 0.00001). There were no differences in the length of hospital stay (P = 0.12), conversion rates to open surgery (P = 0.48), postoperative ileus (P = 0.08), anastomosis leakage (P = 0.28), and bleeding (P = 0.95).ConclusionsCompared to LRC, RRC was associated with reduced estimated blood losses, reduced postoperative complications, longer operative times, and a significantly faster recovery of bowel function. Other perioperative outcomes were equivalent.

Effect of HMGB1 silencing on cell proliferation, invasion and apoptosis of MGC-803 gastric cancer cells.

High‐mobility group box 1 (HMGB1) is a multifunctional protein with intranuclear and extracellular functions. Although HMGB1 is overexpressed in approximately 85% of gastric cancers, the role of HMGB1 in gastric cancer biology remains unclear. In this study, we investigate the effect of downregulation of HMGB1 on the biological behavior of gastric cancer cells. MGC‐803 gastric cancer cells were transduced with HMGB1‐specific RNAi lentiviral vectors. Real‐time polymerase chain reaction and Western blot analysis of HMGB1 mRNA and protein, respectively, validated the silencing effects. HMGB1‐specific silencing significantly decreased cell proliferation. The impact on proliferation was observed at the cell cycle level—the number of cells in the G0/G1 phase increased, whereas that in S and G2/M phases decreased. Cell cycle changes were accompanied by decreases in cyclin D1 expression. Furthermore, HMGB1 silencing sensitized cells to apoptosis that was induced by oxaliplatin and mediated by the caspase‐3 pathway. Finally, silencing of HMGB1 expression significantly reduced cellular metastatic ability and MMP‐9 expression in MGC‐803 cells. In summary, HMGB1 not only plays an essential role in the proliferation and invasion of MGC‐803 cells but also represents a potential target for the therapeutic intervention of gastric cancer. Copyright

Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer

AIM To evaluate the association between of the interleukin-10 (IL-10) promoter polymorphisms and survival of advanced gastric cancer (GC) patients. METHODS The IL-10 (-1082, rs1800896; -819, rs1800871; and-592, rs1800896) genotypes in 234 patients with advanced gastric cancer and in 243 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression for the associations between IL-10 genotypes and the risk of GC. The Kaplan-Meier method with log-rank testing was used to evaluate the association between genotype and survival of the patients. RESULTS The IL-10 -1082 G allele and GCC (-1082, -819 and -592) haplotype were associated with increased gastric cancer risks (OR 1.2, 95% CI 0.6-3.2, P = 0.007, for -1082 G allele, OR = 2.3, 95% CI, 1.2-4.1, P = 0.005, for GCC haplotype, respectively). However, none of the three IL-10 gene polymorphisms (-1082, -819 and -592) was correlated with gastric cancer survival (P > 0.05), and none of the genotypes of the three IL-10 sites was found as independent prognostic risk factors in the multivariate test. CONCLUSION IL-10 gene promoter polymorphisms may not be associated with the prognosis of advanced gastric cancer.

Small interfering RNA-mediated downregulation of beta-catenin inhibits invasion and migration of colon cancer cells in vitro

Summary Background Abnormal regulation of Wnt/β-catenin signaling and subsequently increased β-catenin expression have been found to be involved in the proliferation and growth of colon cancer cells. Whether the down-regulation of β-catenin in colon cancer may result in compromised invasion and migration in vitro still remains to be determined. Material/Methods A human colon cancer cell line (LoVo cells) was transfected with small interfering RNA (siRNA) targeting β-catenin. RT-PCR, Western blot assay, flow cytometry, cell adhesion assay, scratch wound assay, and matrigel invasion assay were performed, and the correlation between cell invasion and migration and β-catenin expressions was analyzed. Results siRNA-mediated down-regulation of β-catenin elevated the E-cadherin expression but reduced the MMP-7 and CD44v6 expressions, which increased the adhesion between LoVo cells but decreased the adhesion of LoVo cells to fibronectin. Significant inhibition of cell invasion and migration was also observed following RNA interference with β-catenin siRNA. Conclusions siRNA-mediated downregulation of β-catenin could be valuable for defining gene expression and functional programs downstream of oncogenic β-catenin signals, which, in turn, may be helpful to isolate novel diagnostic markers, and for designing tumor-specific intervention at downstream targets of oncogenic β-catenin.

A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis

Background: Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Objective: Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. Methods: We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Results: Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75–0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63–1.27), 0.74 (95% CI: 0.62–0.89) and 0.86 (95% CI: 0.79–0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. Conclusions: The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.

BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer

Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.

Expression and mechanism of microRNA-181A on incidence and survival in late liver metastases of colorectal cancer

The emerging role of microRNA-181A (miR-181A) in CRC patients with late liver metastases was studied. In the present study we investigated the association between expression and mechanism of miRNA-181A, liver metastasis and prognosis of colorectal cancer (CRC). The expression of miR-181A and PTEN in CRC patients with late liver metastases was higher than that of the normal (control) group, whereas the expression of miR-181A and PTEN was lower in all pathological groups (TNM I-TNM IV). Overall survival (OS) of lower expression miR-181A CRC patients with late liver metastases was higher than that of higher expression miR-181A CRC patients with late liver metastases. The expression of miR-181A and PTEN in the colon cell line NCM460 was lower than that of the colon cancer SW620 cell line. Upregulation of miR-181A promoted cell viability and inhibited apoptosis of SW620 cells, suppressed PTEN expression and activated phosphorylation of AKT (p-AKT) in SW620 cells. Additionally, downregulation of miR-181A inhibited cell viability of SW620 cells through promotion of PTEN and inhibition of p-AKT. Together, our results indicate that miR-181A expression is associated with CRC patients with late liver metastases through PTEN/AKT signaling.

Relationship between high-mobility group box 1 overexpression in ovarian cancer tissue and serum: a meta-analysis.

Objective To implement a meta-analysis to investigate the relationship between high-mobility group box 1 (HMGB1) overexpression in the tissue and serum of ovarian cancer patients, and to evaluate its prognostic significance. Methods Searches were made of China National Knowledge Infrastructure, EMBASE, WanFang, PubMed, MEDLINE, and Web of Science databases up to August 2015, with no language or style restrictions. Reference lists of related studies were also carefully reviewed to identify additional articles. Results The literature search identified a total of 12 relevant studies on HMGB1 expression for inclusion in the meta-analysis: seven in ovarian tumor tissue, four in ovarian tumor patient serum, and one in both tissue and serum. HMGB1 protein levels in ovarian cancer tissues were notably higher than those in normal ovarian tissues with no evidence of heterogeneity between studies (RD=0.64, 95% confidence interval (CI): 0.57–0.70, Z=18.70, P<0.00001, I2=15%), and also higher than those in benign tumor tissues with no evidence of heterogeneity between studies (RD=0.52, 95% CI: 0.43–0.61, Z=11.14, P<0.00001, I2=0). Serum HMGB1 levels were similarly significantly higher in ovarian cancer patients than those with benign tumors or normal ovaries. Pooled mean differences of HMGB1 in ovarian cancer patients compared with patients with benign tumors or normal ovaries were 99.32 with 95% CI: 67.82–130.81, Z=6.18, P<0.00001, and 95.34 with 95% CI: 62.11–128.57, Z=5.62, P<0.0001. The pooled relative risk of ovarian cancer with high vs low HMGB1 expression levels was 1.40 with 95% CI: 1.09–1.79, Z=2.66, P=0.008, heterogeneity I2=50%. Conclusion This meta-analysis suggested that HMGB1 levels in both tissue and serum of ovarian cancer patients were significantly higher than those of benign tumor and normal ovarian samples. High serum or tissue HMGB1 expression may therefore be an effective molecular marker for ovarian benign or malignant tumor diagnosis and patient prognosis.

Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo

Background The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor. Materials and methods We investigated the cytopathic effects of oHSV2 in CRC cell lines using the MTT assay. Then, cell cycle progression and apoptosis of oHSV2 were examined by flow cytometry. We generated a model of CRC with mouse CRC cell CT26 in BALB/c mice. The antitumor effects and adaptive immune response of oHSV2 were assessed in tumor-bearing mice. The therapeutic efficacy of oHSV2 was compared with the traditional chemotherapeutic agent, 5-fluorouracil. Results The in vitro data showed that oHSV2 infected the CRC cell lines successfully and that the tumor cells formed a significant number of syncytiae postinfection. The oHSV2 killed cancer cells independent of the cell cycle and mainly caused tumor cells necrosis. The in vivo results showed that oHSV2 significantly inhibited tumor growth and prolonged survival of tumor-bearing mice without weight loss. With virus replication, oHSV2 not only resulted in a reduction of myeloid-derived suppressor cells and regulatory T cells in the spleen, but also increased the number of mature dendritic cells in tumor-draining lymph nodes and the effective CD4+T and CD8+T-cells in the tumor microenvironment. Conclusion Our study provides the first evidence that oHSV2 induces cell death in CRC in vitro and in vivo. These findings indicate that oHSV2 is an effective therapeutic cancer candidate that causes an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, thus providing a potential therapeutic tool for treatment of CRC.