HMGA2 promotes the migration and invasion of gallbladder cancer cells and HMGA2 knockdown inhibits angiogenesis via targeting VEGFA.

The high mobility group AT­hook 2 (HMGA2) protein has been found to be upregulated in the majority of tumor types and is associated with a poor prognosis. Previous studies have suggested the oncogenic role of HMGA2 in gallbladder cancer (GBC). The present study aimed to investigate the effects of HMGA2 on the invasion, migration and angiogenesis of GBC cells. To achieve this aim, HMGA2 was overexpressed or silenced in the GBC cell line, EH­GB1, and then the proliferation, migration, invasion and epithelial­mesenchymal transition (EMT) abilities of EH­GB1 cells were investigated using Cell Counting Kit­8, wound healing, Transwell and western blotting assays. In addition, the expression levels of VEGFA were determined in EH­GB1 cells using western blotting and reverse transcription­quantitative PCR following HMGA2 overexpression or silencing. Furthermore, HMGA2­silenced EH­GB1 cells were transfected with VEGFA overexpression plasmids to evaluate the tube formation ability of HUVECs using tube formation assay. The results demonstrated that HMGA2 silencing inhibited GBC cell proliferation, migration, invasion and EMT, as evidenced by the downregulated expression of Ki67, proliferating cell nuclear antigen, MMP2, MMP9, N­cadherin, snail family transcriptional repressor 2 and zinc finger E­box­binding homeobox 1, and attenuated cell migration and invasion. However, the opposite results were obtained following HMGA2 overexpression. Moreover, HMGA2 knockdown and overexpression downregulated and upregulated VEGFA expression, respectively. In addition, the tube formation ability of HUVECs and the expression levels of CD31, VEGFR1 and VEGFR2 were downregulated following HMGA2 silencing. However, these effects were partially rescued by simultaneous VEGFA overexpression. In conclusion, the findings of the present study revealed that HMGA2 may promote GBC cell migration, invasion, EMT and angiogenesis. Therefore, inhibiting HMGA2 expression could be considered as a possible therapeutic approach for GBC.

Predicting infected pancreatic necrosis based on influential factors among the most common types of acute pancreatitis: a retrospective cohort study.

BACKGROUND: Biliary and hypertriglyceridemic acute pancreatitis (BAP and HTGAP) are two of the leading etiologies in China. Infected pancreatic necrosis (IPN) is a particular and noticeable condition in the late stage of these diseases; however, the influential correlated factors on IPN and how to predict IPN are unclear. METHODS: In this retrospective study, 1,116 patients whose diagnosis was BAP or HTGAP met the inclusion criteria among 1,746 enrolled cases. Clinical characteristics were carefully recorded for further investigation of the factors influencing IPN. During a 6-month follow-up, we analyzed bacterial spectra and postoperative indicators related to minimally invasive necrosectomy. RESULTS: Gallstones and hypertriglyceridemia were the most prevalent causes (52.6% vs. 11.3%). The participants with HTGAP were younger (40 vs. 52 years, P<0.001), had a higher rate of severe acute pancreatitis (SAP) (51.8% vs. 32.0%, P<0.001), and had a higher prevalence of multiple organ dysfunction syndrome (MODS) (26.4% vs. 19.0%, P=0.020) than BAP patients. More IPN cases were noted in the BAP group than in the HTGAP group [20.2% vs. 13.7%; odds ratio (OR): 1.598, 95% confidence interval (CI): 1.027 to 2.451; P=0.034]. Etiologies, C-reactive protein (CRP) levels, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and MODS were the factors influencing IPN. The bacterial spectra and the rates of major postoperative complications were not significantly different. CONCLUSIONS: Patients with BAP more frequently developed IPN. Etiology was independently related to the occurrence of IPN. The APACHE II score, MODS, etiology, and CRP contributed to predicting IPN occurrence. Management of IPN substantially improved the prognosis.

Methyl-indole inhibits pancreatic cancer cell viability by down-regulating ZFX expression.

This study explored the effect of methyl-indole on pancreatic cancer cell viability and investigated the mechanism involved. The viability of pancreatic cells showed a significant suppression on treatment with methyl-indole in dose-based manner. Treatment with 5 µM methyl-indole suppressed Capan-1 cell viability to 23%. The viability of Aspc-1 cells was reduced to 20% and those of MIApaCa-2 cells to 18% by 5 µM methyl-indole. The apoptotic proportion of Capan-1 cells was 67%, while as those of Aspc-1 and MIApaCa-2 cells increased to 72 and 77%, respectively, on treatment with 5 µM methyl-indole. The level of P13K, p-Tyr, p-Crkl and p-Akt was inhibited in the cells by methyl-indole. Moreover, methyl-indole also suppressed zinc-finger protein, X-linked mRNA and protein expression in tested cells. In summary, methyl-indole exhibits anti-proliferative effect on pancreatic cancer cells and induces apoptosis. It targeted ZFX expression and down-regulated P13K/AKT pathway in pancreatic cancer cells. Therefore, methyl-indole acts as therapeutic agent for pancreatic cancer and may be studied further.

Hydroxypyridinone-Coumarin Inhibits the Proliferation of MHCC97 and HepG2 Human Hepatocellular Carcinoma Cells and Down-Regulates the Phosphoinositide-3 Kinase Pathway.

BACKGROUND Worldwide, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant diseases and is the third leading cause of cancer-related death. This study aimed to investigate the effect of hydroxypyridinone-coumarin (HPC) on MHCC97 and HepG2 human HCC cells and the mechanisms involved. MATERIAL AND METHODS MHCC97 and HepG2 human HCC cells were cultured in vitro. An MTT cytotoxicity assay was used to assess cell viability and proliferation, with and without treatment with HPC. Cell autophagosomes were labeled with GFP-LC3 using confocal fluorescence microscopy. Western blot was used to measure protein expression. RESULTS HPC significantly reduced the cell proliferation rate in a concentration-dependent manner, with 2 µM of HPC resulting in a reduced proliferation rate of MHCC97 cells (by 36%) and HepG2 cells (by 29%) (P<0.02). HPC significantly reduced autophagy in MHCC97 and HepG2 cells. Western blot showed that treatment with HPC significant upregulated Atg5, beclin-1, LC3-phosphatidylethanolamine conjugate (LC3-II), and Atg-3, reduced p62 and Akt protein expression, and induced phosphorylation of ERK1/2. GFP-LC3B labeling in MHCC97 and HepG2 cells was increased following HPC treatment. CONCLUSIONS HPC induced autophagy and inhibited the proliferation of MHCC97 and HepG2 HCC cells in vitro and involved activation of ERK1/2 and down-regulation of the Akt pathway.

Genetic polymorphisms and pancreatic cancer risk: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUNDS: Previous investigations yielded inconsistent results for the associations between pancreatic cancer (PC) risk and genetic polymorphisms. The study aimed to perform a systematic review and meta-analysis of studies exploring association of some genetic polymorphisms and PC risk. METHODS: We systematically searched on PubMed and Web of Science for association of genetic polymorphisms and PC risk published from 1969 to January 2019. We computed the multivariate odd ratio (OR) and 95% confidence intervals (CI), comparing different genetic types. RESULTS: The present meta-analysis showed significant associations between deoxyribonucleic acid (DNA) repair gene (X-ray repair cross-complementing group 1 (XRCC1) Arg399GIn and Arg194Trp, excision repair cross complementation 1 (ERCC1) rs11615 and rs3212986, ERCC2 rs13181) polymorphisms and PC risk. CONCLUSIONS: Because of the limited sample size and ethnicity enrolled in the present meta-analysis, further larger scaled studies should be performed to demonstrate the association.