title: Utilization of murine colonoscopy for orthotopic implantation of colorectal cancer.
abstract: BACKGROUND
  Colorectal-cancer (CRC) research has greatly benefited from the availability of small animal tumor models. Spontaneous and chemically-induced CRC models are widely used yet limited in their resemblance to human disease and are often prolonged, not accurately repetitive, and associated with inflammatory side effects. In-situ murine or human tumor implantation in the gastrointestinal tract of mice is extremely challenging, and limited by inter-animal variability and procedure-related complications and mortality. As a result, in frequent studies CRC is implanted in distal sites, most commonly the subcutaneous region, an approach that is greatly limited by the absence of normal gastrointestinal tumor milieu and has substantial effects on tumor development.
  
  
  OBJECTIVE
  In this study we aimed to develop a well-tolerated repetitive tool to study CRC in small animals by adapting the murine colonoscopy system to serve as a platform for colonic sub-mucosal orthotopic implantation of human and murine CRC tumor cells.
  
  
  RESULTS
  We report the establishment of a novel small-animal CRC model that is minimally invasive, rapid, well-tolerated, highly reproducible, and confers precise control of tumor number, location and growth rate. Moreover, we show that this model uniquely allows the side-by-side induction of distinct genetically manipulated tumors, enabling the mechanistic study of tumor interaction and cross-talk within the native intestinal microenvironment.
  
  
  CONCLUSIONS
  Employment of this new approach may represent a major technical advance for the in-vivo study of CRC.
authors.affiliation: The Research Center for Digestive Tract and Liver Diseases, Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Zigmond
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.forename: Eran
authors.initials: E
authors.lastname: Elinav
authors.forename: Eli
authors.initials: E
authors.lastname: Brazowski
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Chen
authors.initials: C
authors.lastname: Varol
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003113:Colonoscopy / Q000379:methods*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D023041:Xenograft Model Antitumor Assays