Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial-Mesenchymal Transition in Esophageal Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) can act as promoters or inhibitors in cancer progression. Has_circ_0006948 (circ_0006948) was reported to aggravate the malignant behaviors of esophageal carcinoma (EC). AIMS: This study focused on investigating the molecular mechanism of circ_0006948 in EC progression. METHODS: The quantitative real-time polymerase chain reaction was performed to detect the expression of circ_0006948, microRNA-4262 (miR-4262) and fibronectin type III domain containing 3B (FNDC3B). Cell growth analysis was conducted by Cell Counting Kit-8 and colony formation assays. Cell migration and invasion were assessed by transwell assay. Epithelial-mesenchymal transition (EMT)-associated proteins and FNDC3B protein expression were assayed using western blot. Dual-luciferase reporter and RNA pull-down assays were performed to validate the target combination. Xenograft tumor assay was used for investigating the role of circ_0006948 in vivo. RESULTS: Circ_0006948 was upregulated in EC tissues and cells. Downregulating the expression of circ_0006948 or FNDC3B repressed cell growth, migration, invasion and EMT in EC cells. Target analysis indicated that miR-4262 was a target for circ_0006948 and FNDC3B was a downstream gene for miR-4262. Moreover, circ_0006948 could affect the expression of FNDC3B via sponging miR-4262. The effects of si-circ_0006948#1 on EC cells were partly restored by miR-4262 inhibition or FNDC3B overexpression. In addition, circ_0006948 also facilitated EC tumorigenesis in vivo by targeting the miR-4262/FNDC3B axis. CONCLUSION: Taken together, circ_0006948 functioned as an oncogenic factor in EC by the miR-4262-mediated FNDC3B expression regulation.

Pocket-creation method versus conventional method of endoscopic submucosal dissection for superficial colorectal neoplasms: a meta-analysis.

BACKGROUND AND AIMS: The pocket-creation method (PCM) is a newly developed strategy for colorectal endoscopic submucosal dissection (ESD). However, its superiority over the conventional method (CM) has not been established. The aim of this meta-analysis was to evaluate the efficacy and safety of PCM-ESD compared with CM-ESD for superficial colorectal neoplasms (SCNs). METHODS: Literature searches were conducted using the Pubmed, Embase, and Cochrane Library databases, and a meta-analysis was performed. The primary outcome was the R0 resection rate, and the secondary outcomes were the en bloc resection rate, dissection speed, procedure time, and adverse event rate. RESULTS: Five studies (2 randomized controlled trials and 3 retrospective studies) with 1481 patients were included in our meta-analysis. The pooled analysis showed that PCM-ESD achieved a higher R0 resection rate (93.5% vs 78.1%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.3-8.9; I2 = 58%), a higher en bloc resection rate (99.8% vs 92.8%; OR, 9.9; 95% CI, 2.7-36.2; I2 = 0), a shorter procedure time (minutes) (mean difference [MD], -11.5; 95% CI, -19.9 to -3.1; I2 = 72%), a faster dissection speed (mm2/min) (MD, 3.6; 95% CI, 2.8-4.5; I2 = 0), and a lower overall adverse event rate (4.4% vs 6.6%; OR, 0.6; 95% CI, 0.3-1.0; I2 = 0) compared with CM-ESD. CONCLUSIONS: This meta-analysis showed that PCM-ESD improves the efficacy and safety compared with CM-ESD for superficial colorectal neoplasms.

Comparison of efficacy and safety of ilaprazole and esomeprazole both in initial treatment regimen and retreatment regimen of Helicobacter pylori infection in chronic gastritis.

The aim of this study was to compare the efficacy and safety of ilaprazole and esomeprazole both in initial treatment regimen and retreatment regimen of H. pylori infection in chronic gastritis and to explore risk factors for eradication failure. A total of 330 patients with chronic gastritis who were confirmed of H. pylori infection were enrolled in this study. 290 of them were initially treated patients and the 40 remained were patients with retreatment. Eradication assessment was performed at least four weeks after the completion of eradication therapy. Results showed that the eradication rates of the ilaprazole group and esomeprazole group were 91.4 % and 88.4 % for per-protocol (PP) analysis (p=0.41) and 89.0 % and 86.2 % for intention-to-treat (ITT) analysis (p=0.48) in initially treated patients. Meanwhile, they were 75.0 % and 72.2 % for PP analysis (p=0.85) and 75.0 % and 70.0 % for ITT analysis (p=0.72) in patients with retreatment. The differences were not statistically significant. There was also no significant difference in safety between the two drugs. A multiple logistic regression analysis showed that demographic factors such as age, gender, alcohol, smoking, coronary heart disease (CHD), hypertension (HTN) and diabetes mellitus (DM) did not affect eradication rates. However, patients with higher DOB values and patients with atrophic gastritis had significantly lower eradication rates than patients with lower DOB values and with non-atrophic gastritis whether the proton pump inhibitor (PPI) in eradication regimens was ilaprazole or esomeprazole. In conclusion, our findings suggest that the efficacy and safety of ilaprazole and esomeprazole were not significantly different both in initial treatment regimen and retreatment regimen of H. pylori infection in chronic gastritis and DOB values and type of chronic gastritis were to be independent risk factors for eradication failure. In addition, we discovered that a new quadruple regimen containing furazolidone and minocycline which achieved good efficacy and safety can be a promising option for retreatment of H. pylori infection.

Endoscopic mucosal resection with suction vs. endoscopic submucosal dissection for small rectal neuroendocrine tumors: a meta-analysis.

OBJECTIVE: There are no guidelines or consensus on the optimal treatment measures for small rectal neuroendocrine tumors (NETs) at present. This meta-analysis was conducted to compare the efficacy and safety of endoscopic mucosal resection (EMR) with suction and endoscopic submucosal dissection (ESD) for the small rectal NETs. METHODS: The literature searches were conducted using Pubmed and Embase databases, and then a meta-analysis was performed. The primary outcome was complete resection rate, and the secondary outcomes were complication rate, procedure time, and recurrence rate. RESULTS: Fourteen studies with 823 patients were included in our meta-analysis. The overall complete resection rates in EMR with suction and ESD procedure were 93.65% (472/504) and 84.08% (243/289), respectively. The pooled analysis showed that EMR with suction could achieve a higher complete resection rate than ESD with significance (OR: 4.08, 95% CI: 2.42-6.88, p < .00001) when the outlier study was excluded, and procedure time was significantly shorter in the EMR with suction group than in the ESD group (SMD: -1.59, 95% CI: -2.27 to -0.90, p < .00001). Moreover, there was no significant difference in overall complication rate (OR: 0.56, 95% CI: 0.28-1.14, p = .11) and overall recurrence rate (OR: 0.76, 95% CI: 0.11-5.07, I2=48%) between EMR with suction and ESD group. CONCLUSIONS: The present meta-analysis mostly based on retrospective studies show that EMR with suction is superior to ESD for small rectal NETs (≤10 mm) with higher complete resection rate, shorter procedure time, and similar overall complication rate and recurrence.

Endoscopic ultrasonography for staging depth of invasion in early gastric cancer: A meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasonography (EUS) is a widely used imaging modality for detecting the depth of early gastric cancer (EGC) invasion. However, the studies pertaining to EUS for staging early gastric cancer have reported widely varied sensitivities and specificities. This study was conducted to estimate the overall diagnostic accuracy of EUS for staging the depth in EGCs. METHODS: The literatures were identified by searching in PubMed, Embase, and Web of Knowledge databases. Two reviewers independently extracted the information from the literatures for constructing 2 × 2 table. A random-effect model or a fixed-effect model was used to estimate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. A summary receiver operating characteristic curve also was constructed. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EUS for M staging were 76% (95% confidence interval [CI], 74-78%), 72% (95% CI, 69-75%), 3.67 (95% CI, 2.48-5.44), and 0.31 (95% CI, 0.24-0.40), respectively. For SM staging, these results were 62% (95% CI, 59-66%), 78% (95% CI, 76-80%), 2.99 (95% CI, 2.26-3.96), and 0.43 (95% CI, 0.32-0.57), respectively. For M/SM1 staging, they were 90% (95% CI, 88-92%), 67% (95% CI, 61-72%), 3.14 (95% CI, 2.08-4.73), and 0.12 (95% CI, 0.07-0.22), respectively. The area under the curve for mucosal, submucosal, and mucosal/minimal submucosal invasion staging were 0.85, 0.82, and 0.81, respectively. CONCLUSIONS: Endoscopic ultrasonography only has a relatively low accuracy for staging the depth of invasion in EGCs. Accordingly, EUS may be not indispensable in the staging of EGCs.

Solid-state fermentation of Acanthogobius hasta processing by-products for the production of antioxidant protein hydrolysates with Aspergillus oryzae

Functional properties and antioxidative activity of a protein hydrolysate prepared from Acanthogobius hasta processing by-product protein during solid-state fermentation with Aspergillus oryzae were investigated. Overall, protease activity increased with the degree of hydrolysis (DH) decreased during solid-state fermentation. All the protein hydrolysate had excellent solubility, possessed interfacial properties, and varying degrees of antioxidant activity which were governed by their concentrations and DH, molecular weight distribution and amino acid composition. After 5 days fermentation, the DH of the protein hydrolysate was 31.23%. The protein hydrolysate had the highest total hydrophobic amino acid content, the highest DPPH scavenging activity, reducing power, and the chelating activity. The radical-scavenging activity of the hydrolysates at 6 mg/mL was 78.6%. The reducing power of protein hydrolysate at the range of 0-6 mg/mL was lower than that of BHA at the range of 0-60 µg/mL, while the chelating activity of APs was similar to that of BHA at the range of 0-60 µg/mL. Moreover, the protein hydrolysate showed good emulsifying and foaming properties over a wide pH range from 2 to 12. Therefore, solid state fermentation provided a suitable and low-cost method for converting Acanthogobius hasta processing by-product protein into antioxidant protein hydrolysates.

Gemcitabine sensitizes pancreatic cancer cells to the CTLs antitumor response induced by BCG-stimulated dendritic cells via a Fas-dependent pathway.

BACKGROUND/OBJECTIVES: There are increasing evidences suggesting that chemotherapeutic agents can enhance the cytotoxic T lymphocytes (CTLs) antitumor effect, but the precise mechanism is not fully explained. This study aims to investigate whether gemcitabine (GEM) can sensitize pancreatic cancer cells to the CTLs antitumor response, and explore the potential mechanism. METHODS: Cell counting kit-8 assays (CCK-8) were performed to determine the tumor cell proliferation. Flow cytometric analysis was conducted to analyze maturation of DCs and the expression of Fas. An Annexin V FITC Apoptosis Detection Kit was performed to detect tumor cell apoptosis. CytoTox 96 Nonradioactive Cytotoxicity assays were used to determine T cell-mediated tumor cell lysis. RESULTS: First, it was demonstrated that Bacillus Calmette Guérin (BCG) could be used to induce effective CTLs antitumor response. Then, GEM inhibited the growth of SW1990 cells, induced apoptosis and upregulated the Fas expression even at a low concentration. When antagonistic anti-Fas mAb ZB4 was preincubated with GEM-treated SW1990 cells, the lysis induced by CTLs was reduced. Moreover, agonistic anti-Fas mAb CH11 induced more apoptosis of GEM-treated SW1990 cells. CONCLUSION: Our results show that GEM sensitizes pancreatic cancer cells to the CTLs antitumor response, and the sensitization is associated with upregulation of Fas on pancreatic cancer cells.

Triptolide induces apoptotic cell death of human cholangiocarcinoma cells through inhibition of myeloid cell leukemia-1.

BACKGROUND: Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers. METHODS: CCK-8 assay was performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry were used to analyze apoptosis. Western blot was performed to determine the expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1. Quantitative real-time PCR and immunofluorescence were used to detect the expression levels of Mcl-1. The nude mice xenograft model was used to evaluate the antitumor effect of triptolide in vivo. RESULTS: Triptolide reduced cell viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner, with IC50 values of 12.6 ± 0.6 nM, 20.5 ± 4.2 nM, and 18.5 ± 0.7 nM at 48 h for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA cell lines in part through mitochondrial pathway. Using quantitative real-time PCR, western blot and immunofluorescence, we have shown that triptolide downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited the CCA growth in vivo. CONCLUSIONS: Triptolide has profound antitumor effect on CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would be a promising therapeutic agent for CCA.

Gemcitabine-treated pancreatic cancer cell medium induces the specific CTL antitumor activity by stimulating the maturation of dendritic cells.

Gemcitabine (GEM) is a first line chemotherapeutic drug for advanced pancreatic cancer. Dendritic cell (DC) vaccine is a promising method of immunotherapy for malignant tumor. Recent research has indicated that gemcitabine can enhance the efficacy of DC vaccine, but precise mechanism is still unknown. Here, we aimed to investigate the effect of GEM on DCs. The results showed that GEM-treated pancreatic cancer cell medium stimulated maturation of DCs. When co-cultured with autologous T lymphocytes, the pulsed DCs promoted the proliferation of T cells, and exhibited specific cytotoxic T lymphocytes (CTLs) antitumor activity. Further research showed that stimulation of DC maturation may be related to the elevated level of Hsp70 induced by GEM. Our study indicates that GEM changes the immunogenicity of tumor cells, and enhances the efficacy of DC based immunotherapy for pancreatic cancer.