In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy

Becker, Christoph

doi:10.1136/gut.2004.061283

Cited by 245 publications

(215 citation statements)

References 13 publications

Supporting

Mentioning

212

Contrasting

Unclassified

Order By: Relevance

“…To create discrete mucosal injuries in the mouse colon and to monitor their regeneration, we used a high-resolution miniaturized colonoscope system (10,11). This system consisted of a miniature rigid endoscope (1.9-mm outer diameter), a xenon light source, a triple chip high resolution CCD camera, and an operating sheath with 3 Fr.…”

Section: Methodsmentioning

confidence: 99%

Efficient colonic mucosal wound repair requires Trem2 signaling

Seno

Miyoshi²,

Brown³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

252

254

View full text Add to dashboard Cite

The colonic epithelial lining undergoes constant replacement, driven by epithelial stem cells in crypts of Lieberkü hn. Stem cells lost because of damage or disease can be replaced by adjacent crypts that undergo fission. The close proximity of an extraordinary number of luminal microbes creates a challenge for this repair process; infection must be prevented while immune system activation and epithelial stem cell genetic damage must be minimized. To understand the factors that modulate crypt/stem cell replacement in the mouse colon, we developed an in vivo acute injury system analogous to punch biopsy of the skin. In contrast to epidermal stem cells, colonic epithelial progenitors did not migrate over the wound bed. Instead, their proliferative expansion was confined to crypts adjacent to wound beds and was delayed to the latter phase of healing. This increased epithelial proliferation was coincident with the infiltration of Trem2 expressing macrophages and increased expression of IL-4 and IL-13 in the wound bed. Interestingly, Trem2 ؊/؊ mice displayed slow and incomplete wound healing of colonic mucosal injuries. We found the latter phase of healing in Trem2 ؊/؊ mice showed a diminished burst of epithelial proliferation, increased expression of IFN-␥ and TNF-␣, diminished expression of IL-4 and IL-13, and increased markers of classical macrophage activation. Ablation of these cytokines in injured WT and Trem2 ؊/؊ mice demonstrated that their expression ultimately determined the rate and nature of wound healing. These studies show that Trem2 signaling is an important pathway to promote healing of wounds in the colon where stem cell replacement is necessary.biopsy injury ͉ epithelium ͉ macrophage ͉ stem cell ͉ wound healing

show abstract

Section: Methodsmentioning

confidence: 99%

Efficient colonic mucosal wound repair requires Trem2 signaling

Seno

Miyoshi²,

Brown³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

252

254

View full text Add to dashboard Cite

show abstract

“…High-resolution mouse endoscopy and murine endoscopic index of colitis severity (MEICS) scoring was performed, as previously described 57 , using a 'Coloview' endoscopic system (Karl Storz, Tuttlingen, Germany). Mice were anaesthetized with 2-2.5% isoflurane in oxygen during endoscopy.…”

Section: Methodsmentioning

confidence: 99%

A20 controls intestinal homeostasis through cell-specific activities

et al. 2014

View full text Add to dashboard Cite

The transcription factor NF-kB is indispensable for intestinal immune homeostasis, but contributes to chronic inflammation and inflammatory bowel disease (IBD). A20, an inhibitor of both NF-kB and apoptotic signalling, was identified as a susceptibility gene for multiple inflammatory diseases, including IBD. Despite absence of spontaneous intestinal inflammation in intestinal epithelial cell (IEC) specific A20 knockout mice, we found additional myeloid-specific A20 deletion to synergistically drive intestinal pathology through cell-specific mechanisms. A20 ensures intestinal barrier stability by preventing cytokine-induced IEC apoptosis, while A20 prevents excessive cytokine production in myeloid cells. Combining IEC and myeloid A20 deletion induces ileitis and severe colitis, characterized by IEC apoptosis, Paneth and goblet cell loss, epithelial hyperproliferation and intestinal microbiota dysbiosis. Continuous epithelial cell death and regeneration in an inflammatory environment sensitizes cells for neoplastic transformation and the development of colorectal tumours in aged mice.

show abstract

“…Previously, a safe method for performing endoscopy in mice was developed, permitting long-term studies in living mice (36). Using this method, further study may aid investigators to determine the success of their experiment in vivo at an early stage and to reduce the number of animals required for experiments examining prevention or interventions.…”

Section: Discussionmentioning

confidence: 99%

Stereomicroscopic features of colitis-associated tumors in mice: Evaluation of pit pattern

et al. 2017

View full text Add to dashboard Cite

Abstract.Patients with longstanding ulcerative colitis have an increased risk of colorectal cancer. Mouse models for colitis-associated tumors are indispensable for the development of novel strategies for prevention and intervention, as well as an improved understanding of the mechanisms underlying tumor formation. The present study examined whether stereomicroscopic observations with dye-application were able to detect and discriminate tumors in a colitis-associated tumor model in mice. Colonic tumors were induced in C57BL/6 mice by 15 cycles of treatment with dextran sulfate sodium (DSS) in drinking water. The mice were then divided into 4 groups: normal mice fed a control diet, normal mice fed an iron-supplemented diet, 0.7% DSS mice fed an iron diet and 1.5% DSS mice fed an iron diet. The entire colons were characterized with respect to both morphology and histology. The pit pattern architecture was analyzed using stereomicroscopy with dye agents (0.2% indigo carmine or 0.06% crystal violet). The tumor histology was graded as negative, indefinite or positive for dysplasia. The positive category was divided into two subcategories: low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The tumor incidences and multiplicity were significantly higher in mice fed an iron diet and 1.5% DSS compared with in mice fed an iron diet and 0.7% DSS. Compared with LGD, HGD was predominantly located in the distal colon, was larger in size and had a higher incidence of elevated lesions (Is and IIa) and a lower incidence of flat lesions (IIb). In regards to the pit pattern, HGD had a high incidence of V I pits and a low incidence of IV, III L and II pits. In conclusion, evaluation of the pit pattern using stereomicroscopy with dye-application is useful for detecting and discriminating neoplastic changes in DSS mice and may further our understanding of the mechanisms that induce tumor formation in patients with ulcerative colitis and the characterization of pharmaceutical responses. IntroductionUlcerative colitis (UC) is a chronic relapsing disorder associated with uncontrolled inflammation within the gastrointestinal tract (1). Patients with longstanding UC have an increased risk of colorectal cancer (2,3). The molecular pathway that induces cancer in UC appears to differ from the well-known 'adenoma-carcinoma sequence', as these types of cancer often develop in flat or mildly elevated lesions and are distributed multifocally within an area of intestinal inflammation, called the 'inflammation-dysplasia-carcinoma sequence' (4-6). Therefore, the timely colonoscopic detection and diagnosis of neoplasia during early phase is crucially important for treatment.Previously, chromoendoscopy with dye-spraying, which provides a more detailed visualization of the mucosa by enhancing its morphology, was developed to improve upon the accuracy afforded by conventional endoscopy (7-9). The authors of the present study (10,11) and other studies (12)(13)(14)(15)(16) have previously demonstrated that this imaging technique facilitates the de...

show abstract

In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy

Cited by 245 publications

References 13 publications

Efficient colonic mucosal wound repair requires Trem2 signaling

Efficient colonic mucosal wound repair requires Trem2 signaling

A20 controls intestinal homeostasis through cell-specific activities

Stereomicroscopic features of colitis-associated tumors in mice: Evaluation of pit pattern

Contact Info

Product

Resources

About