Search

// Mohammed Soutto 1, 2 , Judith Romero-Gallo 3 , Uma Krishna 3 , M. Blanca Piazuelo 3 , M. Kay Washington 4 , Abbes Belkhiri 2 , Richard M. Peek Jr 3, 5 , Wael El-Rifai 1, 2, 5 1 Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA 2 Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA 3 Division of Gastroenterology, Hepatology, & Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA 4 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA 5 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA Correspondence to: Wael El-Rifai, e-mail: wael.el-rifai@vanderbilt.edu Keywords: TFF1, Helicobacter pylori, s-catenin, gastric cancer Abbreviations: TFF1; trefoil factor 1, H. pylori; Helicobacter pylori, knockout; KO, TCF/LEF; T cell factor/lymphoid Received: February 18, 2015 Accepted: April 14, 2015 Published: April 27, 2015 ABSTRACT Using in vitro and in vivo models, we investigated the role of TFF1 in suppressing H. pylori -mediated activation of oncogenic β-catenin in gastric tumorigenesis. A reconstitution of TFF1 expression in gastric cancer cells decreased H. pylori -induced β-catenin nuclear translocation, as compared to control ( p < 0.001). These cells exhibited significantly lower β-catenin transcriptional activity, measured by pTopFlash reporter, and induction of its target genes ( CCND1 and c-MYC) , as compared to control. Because of the role of AKT in regulating β-catenin, we performed Western blot analysis and demonstrated that TFF1 reconstitution abrogates H. pylori -induced p-AKT (Ser473), p-β-catenin (Ser552), c-MYC, and CCND1 protein levels. For in vivo validation, we utilized the Tff1 -KO gastric neoplasm mouse model. Following infection with PMSS1 H. pylori strain, we detected an increase in the nuclear staining for β-catenin and Ki-67 with a significant induction in the levels of Ccnd1 and c-Myc in the stomach of the Tff1 -KO, as compared to Tff1 -WT mice ( p < 0.05). Only 10% of uninfected Tff1 -KO mice, as opposed to one-third of H. pylori -infected Tff1 -KO mice, developed invasive adenocarcinoma ( p = 0.03). These findings suggest that loss of TFF1 could be a critical step in promoting the H. pylori -mediated oncogenic activation of β-catenin and gastric tumorigenesis.

The aim of this study was to assess the role of add-on devices for the prevention of phlebitis and other complications associated with the use of peripheral catheters. Patients admitted to an infectious diseases ward and requiring the insertion of a peripheral catheter for at least 24h were randomly allocated to be managed with or without add-on devices. Incidence of phlebitis and all complications were the primary outcomes. Extravasation, inadvertent withdrawal, obstruction and rupture were considered to be mechanical complications, and analysis was performed using survival methods. Of 683 evaluated catheters, 351 were allocated to the add-on device arm and 332 to the control arm. Despite randomisation, patients in the add-on device group were older (P=0.048), less likely to have human immunodeficiency virus (P=0.02) and more likely to have received antibiotics (P=0.05). After adjustment for these variables, the hazard ratio for phlebitis remained non-significant (hazard ratio: 0.95; 95% confidence interval: 0.7-1.3), but the risk of mechanical complications became lower in the add-on device arm (0.68; 0.5-0.94). This translated into a trend towards a lower risk of any complication (0.83; 0.67-1.01). The beneficial effect on mechanical or all complications was noticeable after six days of catheterisation. Add-on devices do not reduce the incidence of phlebitis but may prevent mechanical complications. However, the impact of add-on devices on the incidence of all complications is at most small and only apparent after the sixth day of catheter use.