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

Abstract

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...

The indole compound MA-35 attenuates tumorigenesis in an inflammation-induced colon cancer model

“…We next examined gene expression in the middle colon, which showed dysplasia with different pit patterns and thicknesses 33 . The expression level of Tnfa in the AOM/DSS + MA-35 group showed a stronger tendency to decrease, and the expression of Il6 was significantly decreased in the AOM/DSS + MA-35 group compared with that of the AOM/DSS group (Fig.…”

“…We measured the colon length between the ileocecal junction and rectum. Each colon was cut open longitudinally, and the normal tissue of the proximal colon, dysplasia tissue of the middle colon and cancer tissue of the distal colon were distinguished and assessed using a stereoscopic microscope 33 . Sections of these normal, dysplasia, and cancer tissues were stored in liquid nitrogen for quantitative real-time RT-PCR, fixed in 10% buffered formalin and embedded in paraffin for histological examination.…”

Synergistic effects of hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis

“…Due to the absence of a precise etiology, there is no absolute cure for these diseases; hence, many patients don't respond quite positively to current treatment procedures and the disease relapses periodically, which can lead to GI cancer. 19 Pathogenesis of IBD isn't fully demystified today, however, risk factors may include a variety of environmental, immunologic, genetic, microbial, and psychological factors combined with unnatural autoimmune response to some stimuli, involvement of cells and proteins, with immune dysfunction, oxidative stress, and the inflammatory mediators playing a major role in IBD development. 20 Infiltration of white globules and macrophages into intestinal mucosa is a salient sign of IBD.…”