Systematic identification of Celastrol-binding proteins reveals that Shoc2 is inhibited by Celastrol.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer. Celastrol exhibits anti-tumor activities in a variety of cancers. However, the effect of Celastrol on human CRC and the underlying mechanisms still need to be elucidated. The present study aimed to use in vitro and in vivo methods to clarify the anti-tumor effect of Celastrol and use protein microarrays to explore its mechanisms. We demonstrated that Celastrol effectively inhibited SW480 CRC cell proliferation. Two weeks of Celastrol gavage significantly inhibited the growth of xenografts in nude mice. A total of 69 candidate proteins were identified in the protein microarray experiment, including the most highly enriched protein Shoc2, which is a scaffold protein that modulates cell motility and metastasis through the ERK pathway. Celastrol significantly inhibited ERK1/2 phosphorylation in cell lines and xenograft tumors. Down-regulation of Shoc2 expression using Shoc2 siRNA also inhibited ERK1/2 phosphorylation. Furthermore, down-regulation of Shoc2 expression also significantly inhibited proliferation, colony formation, and migration functions of tumor cells. In addition, the LD0 of Celastrol by gavage is equal or more than 80 mg/kg in C57 male mice. In summary, we unraveled the anti-CRC function of Celastrol and confirmed for the first time that it inhibited the ERK1/2 pathway through binding to Shoc2.

Simultaneous stenting in bile duct and duodenum under endoscope for treatment of malignant biliary and duodenal obstruction / 第二军医大学学报

Objective To investigate the therapeutic strategies, methods, safety and efficacy of simultaneous placement of sel--expanding metallic stent (SEMS) in the bile duct and duodenum under endoscope for treatment ofmalignant biliary and duodenal obstruction. Methods The clinical data of patients with obstructive jaundice combined with severe duodenal stricture, who were treated with simultaneous placement of biliary SEMS and duodental SEMS under endoscope during January 2009 to June 2012, were retrospectively analyzed. The success rate of endoscopic management, complications, relief of jaundice and results of gastric outlet obstruction scoring system (GOOSS) were analyzed. Results Totally ten patients meeting the criteria were analyzed in this study. The patients included 5 cases with pancreatic cancer, 2 with gallbladder cancer, 2 with cancer of bile duct and one with duodenal papilla caner. Five patients with type I duodenal stricture (without invading duodenal papilla) successfully received biliary stents through endoscopic retrograde cholangiopancreatography (ERCP) after placement of duodenal stents. One patient with type I duodenal stricture was implanted with a 9 cm duodenal stent before endoscopic anterograde cholangiopancreatography (EACP), then a SEMS was implanted in the bile duct through endoscopic ultrasonography-guided biliary drainage (EUS-BD). Three patientswith type H duodenal stricture (with invading duodenal papilla) underwent EACP and biliary stent placement through EUS-BD, and then the duodenal stent was deployed in duodenum after EACP. The patient with type m (away from the duodenal papilla) was implanted with biliary and duodenal stents. The success rate of endoscopic management was 100%. Two patients had self-controlled bleeding of intestinal mucosa, which was caused by endoscope friction when passing through the duodenal stricture, but without any continuous bleeding or perforation. Symptoms of jaundice and gastric outlet obstruction were greatly relieved after treatment. Conclusion For patients with unresectable malignant biliary obstruction combined with duodenal stricture, endoscopic placement of SEMS in the bile duct and duodenum simultaneously is a safe and effective method to palliate dual malignant obstruction via different endoscopic managements.

Application of fully-covered self-expandable metallic stent for treatment of pancreatic-biliary diseases / 第二军医大学学报

Objective To investigate the value, safety and efficacy of fully-covered self-expandable metallic stent (FCSEMS) in endoscopic retrograde cholangiopancreatography (ERCP) procedures for pancreatic-biliary diseases. Methods The clinical data of 56 patients with pancreatic-biliary diseases, who underwent FCSEMS treatment via ERCP from January 2008 to June 2012, were retrospectively analyzed. The stents of different lengths and types were chosen according to the condition of patients. The stentswere removed under endoscope. The therapeutic effects at end point, stent removing rate and associated complicationswere observed. Results FCSEMS was placed in 49 patients with benign stricture, including pos-- liver transplant stricture (32), iatrogenic biliary stricture (12) and chronic pancreatitis-associated stricture (5). The mean follow time was (15±8. 6) months (range 5-38 months), -the mean stent duration was (8.4±5. 3) months (1-15 months), and the effective rate was 89.8% (44/49). FCSEMS was placed in 7 patients with biliary complications, including bleeding after endoscopic sphincterotomy (EST) (4), perforation after EST (1), and bile leakage following liver transplantation (2). The mean follow time was (5±3. 7) months (range 1-12 months), themean stent duration was (1. 8±0. 5) months (1-8 months), and the effective rate was 100%. All FCSEMS were successfully retrieved. The short-term complication rate associated with stentwas 8.9% (5/56), including post-ERCP pancreatitis (2), early cholangitis (2) and cholecystitis (1). The long-term complication ratewas 12. 5% (7/56), including stent slip (2), stent translocation (3) and stent-associated cholangitis (2). Conclusion FCSEMS can not only be used to treat traditional benign pancreatic-biliary strictures, but alto serve as a potential substitute for safe and effective treatment of serious biliary complications.

Endoscopic management of biliary complications following liver transplantation: Strategies and skills / 第二军医大学学报

Liver transplantation (LT) has become an important treatment for end stage hepatobiliary disorders. However, biliary complications following LT are common and greatly hamper the clinical efficacy. Endoscopic therapy has been the first-line modality for these biliary problems, though technically difficult and complex. We have managed more than 1 000 cases of complications following LT via endoscopic approach. Here we summarized the therapeutic methods and strategies of our center, hoping to provide evidence for better clinical practice.

Retrospective study on preventive usage of metal clip after EST / 中华消化内镜杂志

Objective To study on the metal clip installation to avoid post-operative bleeding in pa- tients accepted papilla sphinctecotomy.Methods One hundred and eighty five patients who accepted ERCP +EST were divided into two groups:Group 1 was given routine regimen alone(N=95),group 2,given routine regimen and metal clip to prevent post-operative bleeding.Results The postoperative bleeding hap- pened in 3(3.2%)cases of Group 1 and none in Group 2,there is significant difference between these two groups(P＜0.05).The breeding cases in group 1 were controlled by metal clip under endoscopy successful- ly.Conclusion Preventive usage of metal clip was significantly decreased the incidence of post-operative bleeding in EST patients.