MicroRNA-1275 inhibits cell migration and invasion in gastric cancer by regulating vimentin and E-cadherin via JAZF1.

BACKGROUND: Emerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer. In this study, we analysed the role and mechanism of miR-1275 in the progression and prognosis of gastric cancer (GC). METHODS: Target genes of miR-1275 were identified and verified by luciferase assay and Western blotting. The function of miR-1275 in invasion and metastasis was analysed in vitro and in vivo in nude mice. The signal pathway regulated by miR-1275 was examined by qRT-PCR, Western blotting and chromatin immunoprecipitation analyses. The expression of miR-1275and JAZF1 were measured in specimens of GC and adjacent non cancerous tissues. RESULTS: We identified JAZF1 as a direct miR-1275 target. miR-1275 supresses migration and invasion of GC cells in vitro and in vivo, which was restored by JAZF1 overexpression. Moreover, JAZF1 was recognized as a direct regulator of Vimentin. Knocking-down miR-1275 or overexpressing JAZF1 resulted in upregulation of Vimentin but downregulation of E-cadherin. Meanwhile, we validated in 120 GC patients specimens that low miR-1275expression and high JAZF1 mRNA expression levels were closely associated with lymph node metastasis and poor prognosis. The expression of JAZF1 in protein level displayed the correlations with Vimentin but inversely with E-cadherin. CONCLUSIONS: Increased miR-1275 expression inhibited GC metastasis by regulating vimentin/E-cadherin via direct suppression of JAZF1expression, suggesting that miR-1275 is a tumour-suppressor miRNA with the potential as a prognostic biomarker or therapeutic target in GC.

Carcinosarcoma of common bile duct: A case report.

BACKGROUND: Carcinosarcomas of the common bile duct (CBD) are an extremely rare finding in the clinical setting. Based on a review of 12 literatures, 3 cases had the imaging features of ossification. Carcinosarcomas are prone to distant metastasis, as they possess clinical features of both carcinoma and sarcoma, and generally have with a poor prognosis. Due to the small number of cases reported, clinical experience in the diagnosis and treatment of the disease is lacking. CASE SUMMARY: The patient was a 75-year-old woman who had experienced recurrent chills with nausea and vomiting for 3 mo. Computed tomography, magnetic resonance imaging, endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography led to the diagnosis of malignant tumor of the CBD. The patient ultimately underwent cholecystectomy, CBD resection, and choledochojejunostomy. Postoperative pathological examination revealed carcinosarcoma of the CBD, and the latest follow-up showed that the patient is recovering well. Based on previous case reports, some carcinosarcoma has ossification characteristics in imaging. If it is misdiagnosed as biliary calculi, the use of laser lithotripsy in surgery may lead to tumor diffusion. Choledochoscopy and narrow band staining of mucosa are very important for diagnosis. CONCLUSION: We herein present a rare case of carcinosarcomas of the CBD, we found the tumours may have imaging features of polypoid growth and ossification only when the sarcomal components are bone differentiation, while show soft tissue shadow when non bone differentiation. Confirmation of diagnosis depends greatly upon postoperative pathological examination and the adjuvant treatment has not been established, which leads to the poor prognosis.

The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats.

BACKGROUND: Hydrogen has been considered as a novel antioxidant that prevents injuries resulted from ischemia-reperfusion (I/R) injury in various tissues. The study was designed to determine the effect of hydrogen-rich saline on the smooth muscle contractile response to KCl, and on epithelial proliferation and apoptosis of intestine subjected to I/R. METHODS: Intestinal I/R injury was induced in Sprague-Dawley rats using bulldog clamps in superior mesenteric artery by 45 min ischemia followed by 1 h reperfusion. Rats were divided randomly into four groups: sham-operated, I/R, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment groups. Hydrogen-rich saline (>0.6 mM, 6 mL/kg) or saline (6 mL/kg) was administered, respectively, via tail vein 30 min prior to reperfusion. Following reperfusion, segments of terminal jejunum were rapidly taken and transferred into isolated organ bath and responses to KCl were recorded. Samples of terminal jejunum were also taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in intestinal epithelium was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression and distribution of proliferating cell nuclear antigen (PCNA) were detected with immunohistochemistry. RESULTS: Hydrogen-rich saline treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis, and promoting enterocytes proliferation. Moreover, Hydrogen-rich saline treatment significantly limited the neutrophil infiltration, lipid oxidation, and ameliorated the decreased contractility response to KCl in the intestine subjected to I/R. CONCLUSIONS: These results suggest that hydrogen treatment has a protective effect against intestinal contractile dysfunction and damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis, and to promote epithelial cell proliferation.

Hydrogen-rich saline ameliorates the severity of l-arginine-induced acute pancreatitis in rats.

Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the l-arginine (l-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of l-Arg, each at concentrations of 250mg/100g body weight, with an interval of 1h. Hydrogen-rich saline (>0.6mM, 6ml/kg) or saline (6ml/kg) was administered, respectively, via tail vein 15min after each l-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-kappaB) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of l-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-kappaB activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-kappaB activation and to promote acinar cell proliferation.

Expression of Fatty Acid Synthase Negatively Correlates with PTEN and Predicts Peritoneal Dissemination of Human Gastric Cancer.

BACKGROUND: This study aimed to examine the clinical significance of fatty acid synthase (FASN) expression in gastric cancer (GC), and investigate any prognostic role. MATERIALS AND METHODS: FASN expression was assessed in gastric cancers by immunohistochemistry using 60 paraffin-embedded tissue specimens, and clinical data were collected by retrospective chart review. Moreover, FASN mRNA expression in 15 fresh resected specimens was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of PTEN was performed to assess the correlation of PTEN with FASN in gastric cancer. RESULTS: Increased expression of FASN was noted in gastric cancers. The frequency of FASN gene amplification was also significantly higher in gastric cancer than in adjacent normal tissue. FASN expression in human gastric cancer tissues was significantly correlated with patient TNM stage and peritoneal dissemination (p<0.05). Moreover, higher FASN expression significantly correlated with shorter overall survival (p<0.05). Here, upregulation of FASN negatively correlated with PTEN expression in gastric cancer. CONCLUSIONS: These findings indicate that FASN expression is upregulated in gastric cancer, and increased FASN may be critical to th peritoneal metastasis and survival. Our results suggest that FASN upregulation and PTEN downregualtion may be involved in peritoneal dissemination for gastric cancer progression.

Long-term outcomes after radical gastrectomy in gastric cancer patients with overt bleeding.

AIM: To investigate the difference in long-term outcomes between gastric cancer patients with and without a primary symptom of overt bleeding (OB). METHODS: Consecutive patients between January 1, 2007 and March 1, 2012 were identified retrospectively by reviewing a gastric cancer database at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. A follow-up examination was performed on patients who underwent a radical gastrectomy. OB due to gastric cancer included hematemesis, melena or hematochezia, and gastric cancer was confirmed as the source of bleeding by endoscopy. Patients without OB were defined as cases with occult bleeding and those with other initial presentations, including epigastric pain, weakness, weight loss and obstruction. The 3-year overall survival (OS) rate, age, gender, AJCC T stage, AJCC N stage, overall AJCC stage, tumor size, histological type, macroscopic (Borrmann) type, lymphovascular invasion and R status were compared between patients with and without OB. Moreover, we carried out a subgroup analysis based on tumor location (upper, middle and lower). RESULTS: We identified 939 patients. Of these, 695 (74.0%) were hospitalized for potential radical gastrectomy and another 244 received palliative resection, rerouting of the gastrointestinal tract, chemotherapy, radiotherapy or no treatment due to the presence of unresectable tumors. Notably, there was no significant difference in the percentage of OB patients between resectable cases and unresectable cases (20.3% vs 22.1%, P = 0.541). Follow-up examination was performed on 653 patients (94%) who underwent radical gastrectomy. We found no significant difference in 3-year OS rate (68.2% vs 61.2%, P = 0.143) or clinicopathological characteristics (P > 0.05) between these patients with and without OB. Subgroup analysis based on tumor location showed that the 3-year OS rate of upper gastric cancer was significantly higher in patients with OB (84.6%) than in those without OB (48.1%, P < 0.01) and that AJCC stages I-II (56.4% vs 35.1%, P = 0.017) and T1-T2 category tumors (30.8% vs 13%, P = 0.010) were more frequent in patients with OB than in those without OB. There was no significant difference in 3-year OS rate or clinicopathological characteristics between patients with and without OB (P > 0.05) for middle or lower gastric cancer. CONCLUSION: Upper gastric cancer patients with OB exhibited tumors at less advanced pathological stages and had a better prognosis than upper gastric cancer patients without OB.

Cyclooxygenase-2 inhibition as a strategy for treating gastric adenocarcinoma.

Cyclooxygenase-2 (COX-2) has been proven to play critical roles in inflammation as well as in cancer. Some studies have shown that the anti-inflammatory, immunosuppressive and anti-arthritic effects of celecoxib are mainly attributed to the inhibition of COX-2 expression. The present study aimed to investigate the function of COX-2 in human gastric adenocarcinoma (GAC). Forty-five cases of human GAC tissues and corresponding adjacent non-cancerous tissues (ANCTs) were collected. The expression of COX-2 and proliferating cell nuclear antigen (PCNA) was assessed using immunohistochemical assay through a tissue microarray procedure. GAC cells (SGC-7901 and MKN-45) in vitro were treated with COX-2 siRNA or different concentrations of celecoxib to observe their effects on cell proliferation, invasion and the underlying molecular mechanisms. As a consequence, the expression of COX-2 and PCNA was found in cancer tissues with a higher strong reactivity rate, compared with the ANCTs (80.0 vs. 53.3%, P=0.011; 68.9 vs. 48.9%, P=0.047), and COX-2 was positively associated with lymph node metastasis of GAC patients (P=0.011). Targeted knockdown of COX-2 inhibited the proliferation, migration and invasion of GAC cells with decreased expression of PCNA. COX-2 inhibitor celecoxib also suppressed the proliferative activities of GAC cells with decreased expression of COX-2 and PCNA. In addition, the tumor volume in the MKN-45 subcutaneous tumor model treated with siCOX-2 was significantly smaller than that of the negative control (NC) group (P<0.01). Taken together, our findings offer a strong preclinical rationale to target COX-2 signaling as a therapeutic strategy to improve the treatment of gastric adenocarcinoma.

Randomized clinical trial of vessel sealing system (LigaSure) in esophagogastric devascularization and splenectomy in patients with portal hypertension.

BACKGROUND: The LigaSure vessel sealing system (Valleylab, Boulder, CO) has been tested, with excellent results, in different fields of surgery. However, no study has evaluated the efficiency of the LigaSure in open esophagogastric decongestion and splenectomy in a randomized trial to date. METHODS: Patients scheduled to undergo esophagogastric decongestion and splenectomy were assigned to the use of either the LigaSure or a conventional clamp-and-tie technique. Primary outcome measures were operating time and intraoperative blood loss. Secondary outcome measures were postoperative drainage volume, complications such as spleen fever, bleeding, portal vein thrombosis, length of incision, pain, and time to discharge. RESULTS: Sixty patients were randomized to the LigaSure (n = 30) and clamp-and-tie (n = 30) groups. The groups were well matched with respect to liver function, associated illnesses, and grading of esophageal varices. Postoperative outcomes in drainage and major complications did not differ between the groups, while operative time and the volume of blood loss were significantly decreased in the LigaSure group compared with the clamp-and-tie group (P < .001). CONCLUSIONS: The use of the LigaSure is safe and effective in vessel division and homeostasis in the esophagogastric decongestion and splenectomy, with statistically significant decreases in operative time and intraoperative blood loss and without significantly modifying postoperative results.