Exosomal NNMT from peritoneum lavage fluid promotes peritoneal metastasis in gastric cancer.

Peritoneal metastasis (PM) is the major cause of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. The oncogenic role of Nicotinamide N-methyltransferase (NNMT) in GC has been reported, but the role of secreted NNMT that is transported by exosomes remains unknown. In this study, exosomes were isolated from GC patients with or without PM and from GC cell line, including GC-114, GC-026, MKN45, and SNU-16 cells. The contents of NNMT were significantly enhanced in exosomes isolated from GC patients with PM compared with those from GC patients without PM. Furthermore, the levels of NNMT were significantly enhanced in exosomes from GC cell lines relative to those from normal human gastric epithelial cell line GES-1 cells. These data indicate that NNMT may be involved in intercellular communication for peritoneal dissemination. Moreover, colocalization of GC-derived exosomal NNMT was found in human peritoneal mesothelial cell line HMrSV5 cells. Additionally, relative to GES-1 exosomes, SNU-16 exosomes significantly activated TGF-ß/smad2 signaling in HMrSV5 cells. However, when NNMT was silenced, the activation of TGF-ß/smad2 by SNU-16 exosomes was abolished in HMrSV5 cells. We propose that NNMT-containing exosomes derived from GC cells could promote peritoneal metastasis via TGF-ß/smad2 signaling.

LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3ζ/TGFßR1 axis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it carries a poor prognosis. Clarifying the pathologic mechanisms of this disease will be beneficial for the diagnosis and treatment of HCC. LncRNA MEG8 is involved in several tumors but its role in HCC progression remains unknown. This study was designed to explore the role and regulatory mechanisms of MEG8 in HCC progression. MTT, EdU, wound-healing, and transwell assays were employed to analyze the proliferation, migration, and invasion of HCC cells. A luciferase assay was utilized to confirm the predicted binding site. RNA immunoprecipitation and co-immunoprecipitation were employed to verify the binding between MEG8 and miR-367-3p as well as 14-3-3ζ and TGFßR1. Real-time PCR and western blot were employed to detect the expression of interesting genes. Results revealed that MEG8 was increased in HCC tissues and cells, and was correlated with the poor prognosis of HCC patients. Inhibiting MEG8 significantly repressed the HCC cells' ability to proliferate, migrate, and invade. Moreover, MEG8 sponged miR-367-3p to upregulate 14-3-3ζ, the binding of which suppressed TGFßR1 degradation, thereby enhancing TGFß signaling. In conclusion, this work exposed a novel role and regulatory mechanism of MEG8 in HCC and provided new insight into the treatment of HCC.

Delta-shaped Billroth-I anastomosis in totally laparoscopic distal gastrectomy with D2 lymph node dissection for gastric cancer.

BACKGROUND: It is attractive to complete laparoscopic reconstruction of digestive tract as a part of totally laparoscopic distal gastrectomy for patients of distal gastric cancer with its obvious advantage of minimal invasiveness. Delta-shaped Billroth-I anastomosis provides a feasible option for these patients, as we herein describe. METHODS: A 61-year-old woman who was diagnosed with early gastric cancer (type III) of 1.0 cm in diameter at the gastric angle by gastroscopy underwent totally laparoscopic distal gastrectomy with D2 lymph node dissection and delta-shaped Billroth-I anastomosis. RESULTS: The operation lasted for about 120 min with blood loss of about 50 mL. The patient recovered well and was discharged from hospital on postoperative day 11. CONCLUSIONS: Delta-shaped Billroth-I anastomosis by laparoscopic linear staplers is a safe procedure of alimentary reconstruction for totally laparoscopic distal gastrectomy and preferred for patients with early gastric cancer at gastric angle.

The roles of APOBEC3B in gastric cancer.

Gastric cancer was the third cause of death in China. In this study, we found that the APOBEC3 (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3) expression was higher in gastric cancer tissues than that in normal tissues and confirmed APOBEC3B expression was correlated with the unfavorable prognosis of the patients with gastric cancer. Furthermore, APOBEC3B expression was associated with gender, tumor size, histological grade, T stage, and TNM staging of the patients with gastric cancer. Down-regulation of APOBEC3B expression in MNK28 cells could enhance the cytotoxicity of PDCD2. No editing took place in PDCD2 positive MKN28 cells with APOBEC3B shRNA. These results indicated that loss of function of PDCD2 may be partly caused by APOBEC3B-induced extensive mutagenesis.

Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

Prognostic significance of plasma chemerin levels in patients with gastric cancer.

Chemerin is a novel adipokine, which is linked to adipogenesis and chemotaxis of the innate immune system. This study aimed to evaluate the relationship between preoperative plasma chemerin level and prognosis of gastric cancers. One hundred ninety-six patients and 196 age- and gender-matched healthy individuals were recruited. Fasting venous blood samples were collected 2 days prior to surgery for the gastric cancer patients and at the physical examination day for the healthy volunteers. Recorded clinicopathological information included invasion depth, lymph node metastasis, distant metastasis, peritoneal dissemination, tumor size and tumor-node metastasis stage. Plasma chemerin levels were determined using enzyme-linked immunosorbent assay. Plasma chemerin levels were statistically significantly in all patients than in healthy controls (53.1 ± 19.0 ng/mL vs. 31.3 ± 11.3 ng/mL; P < 0.001). And it was identified as an independent predictor for 5-year mortality [odds ratio (OR), 2.718; 95% confidence interval (CI), 1.201-4.229; P = 0.005) and adverse event (OR, 2.982; 95% CI, 1.223-4.879; P = 0.003) of gastric cancer, and had high area under receiver operating characteristic curve (AUC) for prediction of 5-year mortality (AUC, 0.808; 95% CI, 0.745-0.860) and adverse event (AUC, 0.787; 95% CI, 0.723-0.842). It also emerged as an independent predictor for overall survival (Hazard ratios, 1.788; 95% CI, 1.200-2.663; P = 0.002) and disease-free survival (Hazard ratios, 2.016; 95% CI, 1.312-3.125; P = 0.004). Thus, our results suggest that high plasma chemerin levels are associated with long-term poor prognosis and survival of gastric cancer as well as may play a role as prognostic biomarker in gastric cancer survival.