title: Oral administration of the anti-proliferative substance taurolidine has no impact on dextran sulfate sodium induced colitis-associated carcinogenesis in mice.
abstract: BACKGROUND
  New chemopreventive strategies for ulcerative colitis (UC)-associated dysplasia and cancer have to be evaluated. Taurolidine (TRD) has anti-inflammatory, anti-proliferative and anti-neoplastic properties with almost absent toxicity. The aim of the study was to determine whether TRD decreases dysplasia in the well-characterized Dextran Sulfate Sodium - Azoxymethane (DSS-AOM) animal model for UC-associated carcinogenesis.
  
  
  METHODS
  The DSS-AOM model of carcinogenesis was induced in female inbred C57BL/6 mice. Half of the mice were treated with TRD, the other served as control. After 100 days macroscopic, histological and immunhistochemical (beta-Catenin, E-Cadherin, SOX9, Ki-67, Cyclin-D1) examination of the colon was performed.
  
  
  RESULTS
  Incidence, multiplicity, grading and growth pattern of adenomas did not differ significantly between TRD and control group. In all animals, inflammatory changes were absent. Immunhistochemistry revealed increased expression of Ki-67, beta-catenin, SOX9 and Cyclin-D1 in adenomas compared to normal mucosa - without significant difference between TRD and control treatment.
  
  
  CONCLUSIONS
  Oral administration of TRD has no impact on DSS-induced colitis-associated carcinogenesis. However, SOX9 and Cyclin-D1 representing key members of the Wnt pathway have not yet been described in the DSS-AOM model of carcinogenesis - underlining the importance of this oncogenic pathway in this setting.
authors.affiliation: Department of both authors contributed equally to this publication.
authors.forename: Ansgar Michael
authors.initials: AM
authors.lastname: Chromik
authors.forename: Sebastian
authors.initials: S
authors.lastname: Huss
authors.forename: Hayssam
authors.initials: H
authors.lastname: Osseili
authors.forename: Adrien
authors.initials: A
authors.lastname: Daigeler
authors.forename: Sabine
authors.initials: S
authors.lastname: Kersting
authors.forename: Dominique
authors.initials: D
authors.lastname: Sülberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mittelkötter
authors.forename: Thomas
authors.initials: T
authors.lastname: Herdegen
authors.forename: Waldemar
authors.initials: W
authors.lastname: Uhl
authors.forename: Annette M
authors.initials: AM
authors.lastname: Müller