microRNA-33a prevents epithelial-mesenchymal transition, invasion, and metastasis of gastric cancer cells through the Snail/Slug pathway.

Invasion and metastasis are responsible for the majority of deaths in gastric cancer (GC). microRNA-33a (miR-33a) might function as a tumor suppressor in multiple cancers. Here, we describe the regulation and function of miR-33a in GC and mechanisms involved in epithelial-mesenchymal transition (EMT) and metastasis. First, GC tissues and adjacent normal tissues were collected. miR-33a upregulation or SNAI2 depletion on GC cells were introduced to assess the detailed regulatory mechanism of them. We assessed the expression of miR-33a, SNAI2, Snail/Slug signaling pathway-related genes, and EMT-related markers in GC tissues and cells. miR-33a distribution in GC tissues and adjacent normal tissues was measured. Cell proliferation, migration and invasion, and cell cycle distribution were assessed. In nude mice, GC tumor growth and lymph node metastasis were observed. Furthermore, the predicative value of miR-33a in the prognosis of GC patients was evaluated. The obtained results indicated that lowly expressed miR-33a, highly expressed SNAI2, activated Snail/Slug, and increased EMT were identified in GC tissues. miR-33a was located mainly in the cytoplasm. miR-33a targeted and negatively regulated SNAI2. MKN-45 and MKN-28 cell lines were selected for in vitro experiments. Upregulated miR-33a expression or siRNA-mediated silencing of SNAI2 suppressed the activation of Snail/Slug, whereby GC cell proliferation, invasion and migration, EMT, tumor growth, and lymph node metastasis were inhibited. High expression of miR-33a was a protective factor influencing the prognosis of GC. This study suggests that miR-33a inhibited EMT, invasion, and metastasis of GC through the Snail/Slug signaling pathway by modulating SNAI2 expression.NEW & NOTEWORTHY miR-33a targets and inhibits the expression of SNAI2, overexpression of SNAI2 activates the Snail/Slug signaling pathway, the Snail/Slug signaling pathway promotes GC cell proliferation, invasion, and metastasis, and overexpression of miR-33a inhibits cell proliferation, invasion, and metastasis. This study provides a new therapeutic target for the treatment of GC.

OCIAD1 promoted pancreatic ductal adenocarcinoma migration by regulating ATM.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplastic disease, characterized with poor outcomes and a 5-year survival rate less than 5%. Dysregulation or dysfunction of immune response factors contribute to cancer development. In this study, we found that OCIAD1 is high expressed in pancreatic cancer gene chip, and verified OCIAD1 associating with cancer malignancy in specimens from patients with PDAC. OCIAD1 down-regulation inhibited PDAC cell lines migration and vice versa. Further analysis of pancreatic cancer gene chip found OCIAD1 high expression was associating with low ATM expression. Then we proved that OCIAD1 regulated ATM to affect the migration of PDAC. Thus we concluded that high OCIAD1 levels in PDAC promoted tumor cells migration. OCIAD1 exerted its effects by regulating ATM.

Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor.

Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.

Controlling Nutritional Status (CONUT) Score Is A Predictor Of Post-Operative Outcomes In Elderly Gastric Cancer Patients Undergoing Curative Gastrectomy: A Prospective Study.

PURPOSE: The Controlling Nutritional Status (CONUT) score is a recently developed measure that is calculated using the serum albumin level, total cholesterol level, and lymphocyte counts. The aim of this study was to examine whether the CONUT score can predict post-operative outcomes in elderly patients undergoing curative gastrectomy. PATIENTS AND METHODS: Pre-operative CONUT scores were evaluated from August 2014 to September 2016 in 357 gastric cancer patients who were scheduled to undergo curative gastrectomy. The patients were divided into three groups according to pre-operative CONUT scores: normal, light, moderate, and severe. We then calculated the association between the patient's CONUT score and post-operative complications. RESULTS: CONUT scores were statistically associated with age (P = 0.015), body mass index (P < 0.001), pre-operative hemoglobin level (P < 0.001), tumor-node-metastasis stage (P < 0.001), surgical method (P = 0.036), and post-operative complications (P < 0.001). Multivariate analysis showed that age and the CONUT score were independent predictors of post-operative complications and 1-year survival. CONCLUSION: CONUT scores can be used to predict post-operative complications and 1-year survival in elderly gastric cancer patients undergoing curative gastrectomy. They can also be used to classify the nutritional status of patients, which can be helpful for pre-and post-operative nutritional management.

Low periostin expression predicts poor survival in intestinal type gastric cancer patients.

BACKGROUND AND AIM: Periostin is a protein from the Fascilin family. It is commonly present in normal tissues and is responsible for cell adhesion. Evidence has emerged showing that changes in periostin expression play an important role in tumor initiation, development, and progression. This study aims to investigate the effect of periostin in gastric cancer (GC) patients who underwent gastrectomy. Seven hundred and forty-seven GC patients who underwent gastrectomy between December 2006 and July 2011 were included in this study. METHODS: Seven hundred and forty-seven cancer tissues and 70 paired adjacent normal tissues were collected. Periostin expression was evaluated by immunohistochemistry. The Gene Expression Omnibus database was used to study the association between the mRNA level and patient's overall survival. The tumor microenvironment was also studied. RESULTS: Periostin expression in stroma was downregulated in tumor tissues but it was upregulated in the epithelial cells. After dividing the tissues according to the Lauren Classification, we found that periostin expression in stroma and epithelial cells was higher in intestinal type than in diffuse type (P<0.001 and P=0.010, respectively). Periostin was an independent predictor of lymph node (LN) metastasis in GC patients. The study of CD163(+) tumor-associated macrophages (TAMs) revealed that in diffuse type GC, periostin expression was associated with CD163(+) TAMs. CONCLUSION: We found that the periostin expression can predict LN metastasis in patients undergoing curative gastrectomy. Intestinal type GC patients with high periostin level had both a favorable survival and lesser LN metastasis.

Gait speed predicts post-operative medical complications in elderly gastric cancer patients undergoing gastrectomy.

BACKGROUND: Gait speed is a clinical outcome that can measure the physical performance of elderly gastric patients. The purpose of this study was to determine the importance of gait speed in predicting post-operative morbidities in elderly patients undergoing curative gastrectomy. METHODS: We conducted a prospective study of 357 elderly patients (≥65 years old) undergoing curative gastrectomy. Preoperative gait speed was measured in a 6-m well-lit and unobstructed hallway. Patients were followed up for the post-operative clinical outcomes. Factors contributing to the post-operative morbidities were analysed using univariate and multivariate analyses. RESULTS: Slow gait speed was present in 95 out of 357 patients (26.61%) which was significantly associated with age (P < 0.001), gender (P = 0.016), plasma albumin (P < 0.001), American Society of Anesthesiologists grade (P = 0.012), tumour-node-metastasis grade (P = 0.007), sarcopenia (P < 0.001), handgrip (P < 0.001) and post-operative medical complications (P = 0.022). In univariate analysis, age (P = 0.015) and slow gait speed (P = 0.029) were risk factors of post-operative complications. In multivariate analysis, we found that age (P < 0.001) and slow gait speed (P = 0.029) were independent predictors of post-operative medical complications. CONCLUSION: Slow gait speed is an independent predictor of post-operative medical complications in elderly patients undergoing curative gastrectomy. Those patients should be managed with appropriate perioperative nutritional support and physical exercise which can improve gait speed and reduce the risk of post-operative medical complications.

Enhanced recovery after surgery decreases intestinal recovery time and pain intensity in patients undergoing curative gastrectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) reduces postoperative stress, increases patient satisfaction, and reduces postoperative stay and cost. In this study, we evaluated the feasibility and effectiveness of ERAS protocols compared with conventional perioperative care group and their effect in gastric cancer patients undergoing gastrectomy. METHODS: A cohort of 366 patients were analyzed from a prospectively maintained database. The patients' characteristics, tumor profile, surgical information data and postoperative complications were evaluated. RESULTS: Patients in the ERAS had a faster gastrointestinal function recovery and first flatus (3.26±0.64; P<0.001). Pain intensity of patients in the ERAS group was significantly lower than that of patients in the conventional care group on postoperative days 1 (2.33±0.98; P<0.001) and 3 (1.06±0.63; P<0.001). Postoperative hospital stays were significantly shorter in patients receiving ERAS program (6.66±3.36; P<0.001), than in those patients who received conventional perioperative care (9.02±2.61). CONCLUSION: ERAS can reduce postoperative stress, enhance the recovery of the gut, reduce the pain intensity, and increase satisfaction in gastric cancer patient undergoing curative gastrectomy.