The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), a member of the F-box family of proteins, which are substrate recognition components of the multisubunit ubiquitin ligase SCF (Skp1-Cdc53/ Cullin-F-box-protein), has been shown to mediate the ubiquitin-dependent proteolysis of several oncoproteins including cyclin E1, c-Myc, c-Jun, and Notch. The oncogenic potential of Fbxw7 substrates, frequent allelic loss in human cancers, and demonstration that mutation of FBXW7 cooperates with p53 in mouse tumorigenesis have suggested that Fbxw7 could function as a tumor suppressor in human cancer. Here, we carry out an extensive genetic screen of primary tumors to evaluate the role of FBXW7 as a tumor suppressor in human tumorigenesis. Our results indicate that FBXW7 is inactivated by mutation in diverse human cancer types with an overall mutation frequency of f6%. The highest mutation frequencies were found in tumors of the bile duct (cholangiocarcinomas, 35%), blood (T-cell acute lymphocytic leukemia, 31%), endometrium (9%), colon (9%), and stomach (6%). Approximately 43% of all mutations occur at two mutational ''hotspots,'' which alter Arg residues (Arg 465 and Arg 479 ) that are critical for substrate recognition. Furthermore, we show that Fbxw7Arg465 hotspot mutant can abrogate wild-type Fbxw7 function through a dominant negative mechanism. Our study is the first comprehensive screen of FBXW7 mutations in various human malignancies and shows that FBXW7 is a general tumor suppressor in human cancer.

Our data show that MSCs injection can be used for the treatment of end-stage liver disease with satisfactory tolerability. Furthermore, this treatment may improve clinical indices of liver function in end-stage liver disease.

No abstract

The goal of this study was to attempt to determine the rate of contamination of health-care workers' (HCWs) hands and environmental surfaces in intensive care units (ICU) by the main bacteria associated with hospital acquired infections (HAIs) in Tehran, Iran. A total of 605 and 762 swab samples were obtained from six ICU environments and HCWs' hands. Identification of the bacterial isolates was performed according to standard biochemical methods, and their antimicrobial susceptibility was determined based on the guidelines recommended by clinical and laboratory standards institute (CLSI). The homology of the resistance patterns was assessed by the NTSYSsp software. The most frequent bacteria on the HCWs' hands and in the environmental samples were Acinetobacter baumannii (1.4% and 16.5%, respectively), Staphylococcus aureus (5.9% and 8.1%, respectively), S. epidermidis (20.9% and 18.7%, respectively), and Enterococcus spp. (1% and 1.3%, respectively). Patients' oxygen masks, ventilators, and bed linens were the most contaminated sites. Nurses' aides and housekeepers were the most contaminated staff. Imipenem resistant A. baumannii (94% and 54.5%), methicillin-resistant S. aureus (MRSAs, 59.6% and 67.3%), and vancomycin resistant Enterococci (VREs, 0% and 25%) were detected on the hands of ICU staff and the environmental samples, respectively. Different isolates of S. aureus and Enterococcus spp. showed significant homology in these samples. These results showed contamination of the ICU environments and HCWs with important bacterial pathogens that are the main risk factors for HAIs in the studied hospitals.

Wang ZH, Mo JZ, Xiao SD. Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis. J. Gastroenterol. Hepatol. 2007; 22: 371-6. 18 He ZJ, Winston JH, Yusuf Te et al. Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats: implications for the pathogenesis and prevention of ERCP-induced pancreatitis. Pancreas 2003; 27: e13-7. 19 Khoshbaten M, Khorram H, Madad L, Ardakani MJE, Farzin H, Zali MR. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. Andriulli A, Leandro G, Federici T et al. Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis. Gastrointest. Endosc. 2007; 65: 624-32. 22 Rudin D, Kiss A, Wetz RV, Sottile VM. Somatostatin and gabexate for post-endoscopic retrograde cholangiopancreatography pancreatitis prevention: meta-analysis of randomized placebo controlled trials. J. Gastroenterol. Hepatol. 2007; 22: 977-83. 23 Thomopoulos KC, Pagoni NA, Vagenas KA, Margaritis VG, Theocharis GI, Nikolopoulou VN. Twenty-four hour prophylaxis with increased dosage of octreotide reduces the incidence of post-ERCP pancreatitis. Gastrointest. Endosc. 2006; 64: 726-31. 24 Singh P, Das A, Isenberg G et al. Do prophylactic stent placement reduces risk of post-ERCP acute pancreatitis: a meta-analysis of controlled trials. Gastrointest. Endosc. 2004; 60: 544-50. 25 Andriulli A, Forlano R, Napolitano G et al. Pancreatic duct stents in the prophylaxis of pancreatic damage after endoscopic retrograde cholangiopancreatography: a systematic analysis of benefits and associated risks. Digestion 2007; 75: 156-63. 26 Das A, Singh P, Sivak MV Jr et al. Pancreatic stent placement for prevention of post-ERCP pancreatitis: a cost effectiveness analysis. Gastrointest. Endosc. 2007; 65: 960-8. 27 Freeman ML, Overby C, Qi D. Pancreatic stent insertion: consequences of failure and results of a modified technique to maximize success. Gastrointest. Endosc. 2004; 59: 8-14. 28 Sherman S, Hawes RH, Savides TJ et al. Stent-induced pancreatic ductal and parenchymal changes: correlation of endoscopic ultrasound with ERCP. Gastrointest. Endosc. 1996; 44: 276-82. 29 Rashdan A, Fogel EL, McHenry L Jr, Sherman S, Temkit M, Lehman GA. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin. Gastroenterol. Hepatol. 2004; 2: 322-9. 30 Lawrence C, Cotton PB, Romagnuolo J, Payne KM, Rawls E, Hawes RH. Small prophylactic pancreatic duct stents: an assessment