GRB10 is a novel factor associated with gastric cancer proliferation and prognosis.

GRB10 and its family members GRB7 and GRB14 were important adaptor proteins. They regulated many cellular functions by interacting with various tyrosine kinase receptors and other phosphorus-containing amino acid proteins. More and more studies have shown that the abnormal expression of GRB10 is closely related to the occurrence and development of cancer. In our current research, expression data for 33 cancers from the TCGA database was downloaded for analysis. It was found that GRB10 was up-regulated in cholangiocarcinoma, colon adenocarcinoma, head and neck squamous carcinoma, renal chromophobe, clear renal carcinoma, hepatocellular carcinoma, lung adenocarcinoma, lung squamous carcinoma, gastric adenocarcinoma and thyroid carcinoma. Especially in gastric cancer, the high GRB10 expression was closely associated with poorer overall survival. Further research showed that the knockdown of GRB10 inhibited proliferation and migration ability in gastric cancer. Also, there was a potential binding site for miR-379-5p on the 3'UTR of GRB10. Overexpression of miR-379-5p in gastric cancer cells reduced GRB10-regulated gastric cancer proliferation and migration capacity. In addition, we found that tumor growth was slower in a mice xenograft model with knock down of GRB10 expression. These findings suggested that miR-379-5p suppresses gastric cancer development by downregulating GRB10 expression. Therefore, miR-379-5p and GRB10 were expected to be potential targets for the treatment of gastric cancer.

Assessment of acute pancreatitis severity via determination of serum levels of hsa-miR-126-5p and IL-6.

Early assessment of acute pancreatitis (AP) severity is key to its treatment. The present study aimed to explore the role of microRNAs (miRNAs/miRs) combined with inflammatory factors in determining AP severity. For this, serum pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-8 and IL-10)] and miRNAs [Homo sapiens (hsa)-miR-548d-5p, hsa-miR-126-5p and hsa-miR-130b-5p] were detected in patients with mild AP (MAP), severe AP (SAP) and recurrent AP (RAP). High expression of IL-10, TNF-α, hsa-miR-126-5p, hsa-miR-548d-5p and hsa-miR-130b-5p was able to distinguish SAP from MAP and RAP (P<0.05). Multifactorial binary logistic regression analysis indicated that IL-1/IL-6 combined with hsa-miR-126-5p/hsa-miR-548d-5p had a significant influence on AP and AP severity (P<0.05). Receiver operating characteristic analysis revealed that IL-1 combined with hsa-miR-126-5p [area under the curve (AUC), 0.926; sensitivity, 90.0%; specificity, 86.7%, P<0.001] and IL-6 combined with hsa-miR-126-5p (AUC, 0.952; sensitivity, 93.3%; specificity, 90.0%; P<0.001) were able to better distinguish MAP from SAP than IL-1/IL-6 combined with hsa-miR-548d-5p, lipase, and amylase. IL-1 or IL-6 combined with hsa-miR-548d-5p (AUC, 0.924; sensitivity, 83.3%; specificity, 93.3%; P<0.001) were able to better distinguish SAP from RAP than IL-1/IL-6 combined with hsa-miR-126-5p, lipase, and amylase. IL-1 combined with hsa-miR-126-5p (AUC, 0.926; sensitivity, 90.0%; specificity, 86.7%; P<0.001) and IL-6 combined with hsa-miR-126-5p (AUC, 0.952; sensitivity, 93.3%; specificity, 90.0%; P<0.001) were able to better differentiate between MAP and RAP than IL-1/IL-6 combined with hsa-miR-548d-5p, lipase, and amylase. These results demonstrated that the combined detection of serum IL-6 and hsa-miR-126-5p may be useful for the early prediction of AP classification.

The impact of body mass index on laparoscopic cholecystectomy in Taiwan: an oriental experience.

BACKGROUND/PURPOSE: The outcome analysis of obese patients undergoing laparoscopic cholecystectomy (LC) in Asia-Pacific countries is rarely reported. This study examined associations between body mass index (BMI) and clinical outcomes of elective LC in Taiwan. METHODS: A total of 627 patients with gallbladder disease due to gallstones undergoing LC were divided into three groups based on BMI: <25.0 kg/m2 (normal, NO; n = 310), 25.0-29.9 kg/m2 (overweight, OW; n = 252), and >30 kg/m2 (obese, OB; n = 65). RESULTS: Both overweight and obesity were not associated with conversion and complication rates. The conversion rates of the three groups were 5.5 (NO), 6.0 (OW), and 4.6% (OB), and the complication rates were 3.2 (NO), 2.4% (OW), and 4.6% (OB), respectively. However, overweight and obesity were related to a trend toward longer operating time (NO 67.4 +/- 31.8; OW 77.8 +/- 35.6; OB 79.0 +/- 37.9 min) (P trend <0.001). One death (BMI 40.6 kg/m2) was due to septic complications. In the multivariable logistic analysis, only acute cholecystitis, but not BMI, was a predictor for conversion and complications. CONCLUSIONS: Based on these results, it appears that BMI was not associated with clinical outcomes and that LC is a safe procedure in obese patients with uncomplicated gallstone disease in Taiwan.

Induction of G2/M phase arrest by squamocin in chronic myeloid leukemia (K562) cells.

Squamocin is one of the annonaceous acetogenins and has been reported to have anticancer activity. Squamocin was found to inhibit the growth of K562 cells in a time- and dose-dependent manner. Cell cycle analysis showed G2/M phase arrest in K562 cells following 24 h exposure to squamocin. During the G2/M arrest, cyclin-dependent kinase inhibitors (CDKIs), p21 and p27 were increased in a dose-dependent manner. Analysis of the cell cycle regulatory proteins demonstrated that squamocin did not change the steady-state levels of Cdk2, Cdk4, cyclin A, cyclin B1, cyclin D3 and cyclin E, but decreased the protein levels of Cdk1 and Cdc25C. These results suggest that squamocin inhibits the proliferation of K562 cells via G2/M arrest in association with the induction of p21, p27 and the reduction of Cdk1 and Cdc25C kinase activities.

Bacteriology and antimicrobial susceptibility in biliary tract disease: an audit of 10-year's experience.

Cholelithiasis, choledocholithiasis and hepatolithiasis are common biliary tract diseases. These diseases may cause severe infection and/or sepsis. In addition to surgical treatments, prompt administration of appropriate antibiotic is important to control the biliary tract infection. The purpose of this study is to illustrate the bacteriology in biliary tract disease and provide information for antibiotic choices. From Jan 1991 to Aug 2000, 1394 patients including gallbladder (GB) stones, common bile duct (CBD) stones, intrahepatic duct (IHD) stones, GB polyps and biliary malignancy were subjects for this retrospective study. The overall positive rate of bile culture is 36% in this study while it was 25%, 66%, 67% and 9% for GB stones, CBD stones, IHD stones and biliary malignancy, respectively. A significantly higher (p = 0.001) positive culture rate was found for GB stones with acute cholecystits (47%) compared with that without inflammation (17%). Similarly, the culture rate for hepatolithiasis with acute cholangitis was higher than that without cholangitis (75% vs 51%, p = 0.011). Long-term external biliary drainage in biliary malignancy increased the risk of bacterial culture rate. For gallstone diseases, the most common organisms cultured were Gram negative bacteria (74%), in which Escherichia coli (36%) and Klebsiella (15%) were most commonly found, followed by Gram positive (15%) bacteria such as Enterococcus (6%), Staphylcoccus (3%), Streptococcus (2%). Bacteroides (5%) and Clostridium (3%) were occasionally found anaerobes (9%). Polymicrobial infection was encountered in 19%, 31% and 29% for patients with GB stones, CBD stones and IHD stones, respectively; frequency of mixed aerobic and anaerobic infection was 7%, 12% and 9%. In the current study, ampicillin in combination with sulbactam and aminoglycoside is still a suggestive empirical therapy. Antibiotic treatment should be adjusted based on later bacteriological cultures and clinical condition.

Bile duct cancer 25 years after choledochoduodenostomy: a case report.

We describe a 65-year-old man who had undergone choledochoduodenostomy (CDS) for choledocholithiasis 25 years prior to admission to our hospital for cholangitis. Abdominal sonography and computerized tomography (CT) scan revealed a tumor mass at the hilar region with bilateral intrahepatic duct dilatation. Upper gastrointestinal endoscopic examination indicated the site of the CDS. Biopsy was taken from the mucosa of the bile duct, and pathology revealed well-differentiated adenocarcinoma. CT scan and angiography further confirmed unresectable hilar bile duct cancer. Conservative treatment with intra-arterial chemotherapy was arranged. After briefly reviewing the hypothesized pathogenesis and radiographic diagnosis of this rare case, we recommend that chronic cholangitis consequent to CDS should be closely followed for late development of biliary tract malignancy.