Key Roles of p53 Signaling Pathway-Related Factors GADD45B and SERPINE1 in the Occurrence and Development of Gastric Cancer.

p53 can function as an independent and unfavorable prognosis biomarker in cancer patients. We tried to identify the key factors of the p53 signaling pathway involved in gastric cancer (GC) occurrence and development based on the genotype-tissue expression (GTEx) and the Cancer Genome Atlas (TCGA) screening. We downloaded gene expression data and clinical data of GC included in the GTEx and TCGA databases, followed by differential analysis. Then, the key factors in the p53 signaling pathway were identified, followed by an analysis of the correlation between key factors and the prognosis of GC patients. Human GC cell lines were selected for in vitro cell experiments to verify the effects of key prognostic factors on the proliferation, migration, invasion, and apoptosis of GC cells. We found 4,944 significantly differentially expressed genes (DEGs), of which 2,465 were upregulated and 2,479 downregulated in GC. Then, 27 DEGs were found to be involved in the p53 signaling pathway. GADD45B and SERPINE1 genes were prognostic high-risk genes. The regression coefficients of GADD45B and SERPINE1 were positive. GADD45B was poorly expressed, while SERPINE1 was highly expressed in GC tissues, highlighting their prognostic role in GC. The in vitro cell experiments confirmed that overexpression of GADD45B or silencing of SERPINE1 could inhibit the proliferation, migration, and invasion and augment the apoptosis of GC cells. Collectively, the p53 signaling pathway-related factors GADD45B and SERPINE1 may be key genes that participate in the development of GC.

Prognostic value of microRNA-21 in pancreatic ductal adenocarcinoma: a meta-analysis.

BACKGROUND: Recently, microRNA-21 (miR-21) has been reported to be associated with prognosis of pancreatic ductal adenocarcinoma (PDAC). The present studies aimed to evaluate the prognostic value of miR-21 for PDAC with meta-analysis. METHODS: A systematic search in the PubMed and other databases was conducted to identify eligible studies. The pooled hazard ratios (HRs) with 95% confidence interval (CI) were calculated. The meta-analysis was conducted using the STATA 12.0 software. RESULTS: A total of 12 articles (13 studies) which included 963 cases were selected for the meta-analysis. Elevated miR-21 expression was significantly predictive of poor overall survival (HR = 2.05, 95% CI 1.71-2.46, P < 0.001). In the subgroup analyses, similar results were observed in Asian (HR = 2.09, 95% CI 1.62-2.71, P < 0.001) and Caucasian (HR = 2.36, 95% CI 1.53-3.65, P < 0.001); in tissue sample (HR = 2.14, 95% CI 1.73-2.65, P < 0.001) and serum sample (HR = 1.84, 95% CI 1.30-2.60, P = 0.001); with quantitative real-time polymerase chain reaction assay method (HR = 2.31, 95% CI 1.86-2.86, P < 0.001); and in patients receiving adjuvant chemotherapy (HR = 2.37, 95% CI 1.88-3.00, P < 0.001). The association between miR-21 expression level and lymph node metastasis was statistically significant (OR = 1.45, 95% CI 1.02-2.06, P = 0.038). However, no significant relationship between miR-21 expression level and sex or vascular invasion or neural infiltration was observed (P > 0.05). CONCLUSIONS: Our meta-analysis indicated that elevated miR-21 expression level can predict poor prognosis in patients with PDAC.

miR-99b/let-7e/miR-125a cluster suppresses pancreatic cancer through regulation of NR6A1.

This experiment investigates how the miR-99b/let-7e/miR-125a cluster regulates the mechanism of NR6A1 involved in the invasive and metastatic effects of pancreatic cancer (PCa). Bioinformatics prediction and dual luciferase reporter gene assay were applied to verify the targeted relationship between miR-99b/let-7e/miR-125a and NR6A1. ASPC1 cells underwent transfection with lentiviruses to overexpress miR-99b/let-7e/miR-125a (individual or together) to explore functions of miR-99b/let-7e/miR-125a cluster governing NR6A1 in PCa. The detection of tumorigenesis was verified by tumor formation assay in nude mice in vivo, and mouse models of liver metastasis of PCa observed cell metastasis of PCa. MiR-99b/let-7e/miR-125a cluster was screened for differential expression in PCa. NR6A1 was confirmed as a target gene of the miR-99b/let-7e/miR-125a cluster. Findings demonstrated that overexpression of the miR-99b/let-7e/miR-125a cluster inhibited cell invasion, metastasis, proliferation, and tumorigenesis in PCa. Conversely, overexpressed NR6A1, a crucial gene in the miR-99b/let-7e/miR-125a cluster, promoted cell invasion, migration, and proliferation in PCa. Moreover, the overexpression of the miR-99b/let-7e/miR-125a cluster inhibited liver metastases and tumor formation. Thus, the study concludes that the miR-99b/let-7e/miR-125a cluster impedes the invasion and metastasis of PCa cells via targeting the NR6A1 gene.

Reproducibility and persistence of individual marks on 3000 fired bullets from five Chinese Norinco QSZ-92 9 × 19 mm pistols, and the search performance of Evofinder® to a 1000 firearm database of the same model firearm.

For firearm identification, foundational validity based on the reproducibility and persistence of characteristic marks must be established. We investigate the fired bullets of five Chinese Norinco QSZ-92 9 × 19 mm pistols over 3000 shots. The first 50 fired bullets are recovered, whereas every 50th fired bullet is recovered from the 51st to 3000th round. As such, 109 bullets are available for each pistol, and totally 545 bullets are introduced into the Evofinder® system. A large background database comprising 3000 bullets fired from 1000 registered QSZ92 9 × 19 mm pistols is used as interference. Both on-screen analysis and automatic comparison are performed. The first fired bullets from the five pistols are separately correlated with the database. The results show that although the similarity for known match bullets changes slightly as the shot number increases, the land-engraved area (LEA), groove-engraved area (GEA), and slippage marks can be reproducibly transferred to the fired bullets in consecutive shots. The Evofinder system ranks all known match bullets on the top of the correlation result with the combination of LEA, GEA, and slippage marks.

1H NMR-based urinary metabonomic study of the antidiabetic effects of Rubus Suavissimus S. Lee in STZ-induced T1DM rats.

Long-term hyperglycemia associated with diabetes mellitus (DM) causes damage to various organs and tissues, including the eyes, kidneys, heart, blood vessels and nerves. Rubus Suavissimus S. Lee (RS), a shrub whose leaves are used in traditional Chinese medicine (TCM), has been shown to exert hypoglycemic effects in DM patients. However, the underlying mechanism is unclear. This was investigated in the present study in a rat model of streptozotocin-induced type 1 diabetes mellitus (T1DM) by 1H NMR analysis. We identify 9 metabolites whose levels were altered in T1DM rats compared to control rats, namely, lactate, acetate, pyruvate, succinate, 2-oxoglutarate, citrate, creatinine, allantoin, and hippurate, which are mostly related to glycolysis/gluconeogenesis, pyruvate metabolism, TCA cycle, and other metabolism. The observed pathologic changes in the levels of these metabolites in T1DM rats were reversed by treatment with RS. Thus, RS exerts effects in T1DM rats by regulating the three abnormal metabolic pathways synergistically. These findings provide supporting evidence for the therapeutic efficacy of this TCM formulation in the treatment of DM.

Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis.

BACKGROUND: Dependent on the extent of adenosine triphosphate (ATP) hydrolysis and/or ATP/ADP exchange, the stress-induced phosphoprotein 1 (STIP1) mediates molecular interaction and complex formation between the molecular chaperones heat shock protein (Hsp)70 and Hsp90. The overexpression of STIP1 is increasingly being documented in various human malignancies, including ovarian, cholangiocellular, renal and gastric cancers. However, the role of STIP1 in pancreatic cancer (PANC) and probable molecular mechanism remains largely unexplored. METHODS & RESULTS: In the present study, using clinical samples (n = 88) and human PANC cell lines PANC-1, Capan-2, SW1990, and BxPC-3, we demonstrated that STIP1 is aberrantly expressed in human PANC tissues or cell lines compared to adjacent non-tumor pancreas samples or human pancreatic duct epithelial cells (HPDEC), respectively. Clinicopathological correlation studies revealed significant positive correlation between high STIP1 expression and lymph node involvement (p = 0.001), cancer metastasis (p = 0.002), microvascular invasion (p = 0.002), advance TNM stage (p = 0.024), perineural invasion (PNI; p = 0.013), and cancer-related death (p = 0.002) among patients with PANC. Univariate and multivariate analyses indicate that STIP1overexpression is an independent prognostic factor of PANC. Furthermore, STIP1 knockdown significantly inhibit the migration and invasive ability of PANC-1 and SW1990 cells, while downregulating N-cadherin and Vimentin, but upregulating E-cadherin mRNA expression levels, concurrently. We also demonstrated that STIP1 knockdown suppressed p-FAK, p-AKT, MMP2, MMP9, and Slug protein and mRNA expression levels, thus, indicating, at least in part, a role for STIP1 in the activation of FAK/AKT/MMP signaling. CONCLUSION: Taken together, our results demonstrate a critical role for STIP1 in cancer metastasis, disease progression and poor prognosis, as well as, provide evidence suggestive of the therapeutic efficacy of STIP1-mediated targeting of the FAK/AKT/MMP signaling axis in patients with PANC.

[Laparoscopic-assisted radical distal gastrectomy in treatment of invasive gastric cancer: analysis of 47 cases].

OBJECTIVE: To investigate the clinical effect of laparoscopic-assisted radical distal resection of invasive gastric cancer. METHODS: Forty-seven patients with advanced gastric cancer, 33 males and 14 females, aged 58.2 (36 - 77), underwent laparoscopic-assisted radical resection and then were followed up for 17 months (2 - 33 months). RESULTS: All the 47 patients survived. The operation time was (294 +/- 75) min (200 - 420 min). The blood loss was (150 +/- 65) ml (50 - 500 ml). The number of dissected lymph nodes was (32.4 +/- 22.3) (15 - 48). The gastrointestinal peristalsis recovery time after operation was (2.7 +/- 1.2) d (2 - 6 d). The hospital stay time was (9.0 +/- 3.5) d (5 - 19 d). Post-operational complications were seen in 3 cases: pulmonary infection in 2 cases and incision infection in 1 case, and all the 3 patients recovered well after proper treatment. CONCLUSION: Laparoscopic-assisted radical resection of invasive gastric cancer is safe and feasible, with the advantages as minimal invasion, less pain, shorter hospital stay, faster bowel function recovery.

Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality. Although advances have been made in understanding the pathogenesis of PDAC, the outcome still remains poor. The aim of this study is to conduct a meta-analysis to evaluate the precise association between SMAD4 loss and clinicopathological significance in PDAC. A literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, Odds Ratio or Hazard Ratio with corresponding confidence intervals was calculated and summarized. 12 relevant articles were included for full review in detail and meta-analysis. The frequency of SMAD4 protein loss was significantly increased in PDAC than in nonmalignant pancreatic tissue, Odd Ratio was 0.05 with 95% confidence interval 0.01-0.23, p<0.0001. SMAD4 loss was significantly associated with poor overall survival in patients with PDAC, Hazard Ratio was 0.61 with 95% confidence interval 0.38-0.99, p=0.05. SMAD4 loss was not correlated with the size, grades, and lymph node metastasis of PDAC. In conclusion, SMAD4 is a biomarker for the diagnosis of PDAC. SMAD4 loss is significantly related to poor prognosis in patients with PDAC.

Comparison of Delta-Shape Anastomosis and Extracorporeal Billroth I Anastomosis after Laparoscopic Distal Gastrectomy for Gastric Cancer: A Systematic Review with Meta-Analysis of Short-Term Outcomes.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate the safety and relative benefits of delta-shape anastomosis (DA) by comparing to conventional laparoscopy-assisted distal gastrectomy with Billroth I gastroduodenostomy (LADG BI). METHODS: Studies and relevant literature regarding DA versus LADG BI were searched in the electronic databases. Operation time, postoperative complications, estimated blood loss, number of retrieved lymph nodes, time to first flatus, time to oral intake, length of postoperative hospitalization in DA and LADG BI were pooled and compared using meta-analysis. Weighted mean differences (WMDs) and odds ratios (ORs) were calculated with 95% confidence intervals (CIs) to evaluate the effect of DA. RESULTS: Eight studies of 1739 patients were included in the meta-analysis. Compared with LADG BI, DA had shorter postoperative hospitalization (WMD = -0.47, 95%CI: -0.69 to -0.25, P<0.01), less blood loss (WMD = - 25.90, 95%CI: -43.11 to -8.70, P<0.01), shorter time to oral intake (WMD = -0.25, 95%CI: -0.49 to -0.01, P = 0.04), and more retrieved lymph nodes (WMD = 1.36, 95%CI: 0.30 to 2.43, P = 0.01). Operation time (WMD = -0.07, 95%CI -15.58 to 15.43, P = 0.99), overall postoperative complication rate (OR = 1.05, 95%CI: 0.74 to 1.49, P = 0.63), surgical complication rate (OR = 1.02, 95%CI: 0.70 to 1.49, P = 0.90), nonsurgical complication rate (OR = 1.21, 95%CI: 0.54 to 2.72, P = 0.64), leakage rate (OR = 2.54, 95%CI: 0.92 to 7.01, P = 0.07), stricture rate (OR = 0.36, 95%CI: 0.09 to 1.44, P = 0.15), wound complication rate (OR = 0.71, 95%CI: 0.33 to 1.55, P = 0.39), time to first flatus (WMD = -0.10, 95%CI: -0.27 to 0.07, P = 0.26), and proximal surgical margin (WMD = -0.25, 95%CI: -1.14 to 0.65, P = 0.59) was not statistically different. CONCLUSION: Compared with LADG BI, DA is a safe and feasible procedure, with significantly reduced blood loss, time to oral intake, and postoperative hospitalization.