Animal Models of Colitis‐Associated Carcinogenesis

Kanneganti, Manasa; Mino‐Kenudson, Mari; Mizoguchi, Emiko

doi:10.1155/2011/342637

Cited by 92 publications

(80 citation statements)

References 216 publications

(230 reference statements)

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“…The early detection of premalignant and malignant lesions remains the best means of reducing the risk of mortality from colorectal cancer (2,3). The use of animal models allows the design of novel methods to screen for early signs of colon cancer (17,18). These models will expand our understanding of the mechanisms underlying tumor formation and may be useful to identify novel response indicators that are correlated with the early stages of tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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...

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Section: Discussionmentioning

confidence: 99%

“…Animal models of colitis-associated tumors for the study of cancer prevention and early detection have been reported (17,18). The oral administration of dextran sulfate sodium (DSS) to mice has been revealed to induce colonic inflammation that is clinically and histologically similar to UC (19).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…24,25 This protocol is based on the use of the mutagenic agent, AOM, which exerts colonotropic carcinogenicity. WT and Il10 −/− mice on 129/SvEv genetic background reared and housed in the same room were allowed to age to 10 weeks by which point the Il10 −/− mice develop spontaneous and progressive colitis.…”

Section: Aom/il10 −/− Model Of Cac and Experimental Groupsmentioning

confidence: 99%

275 The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

McFadden¹,

Larmonier²,

Midura-Kiela³

et al. 2014

Gastroenterology

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Background-Intestinal microbiota influences the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative and anti-proliferative properties.

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“…Patients with long-standing CU have a higher risk of developing colitis-associated cancer (CAC) approximately 8-10 years after the initial diagnosis when compared to the general population [5]. In addition to genomic instability that underlies the process of tumorigenesis, continuous infl ammation in the intestine seems to be a key factor in CAC development since chronic infl ammation is associated with an overexpression of proinfl ammatory cytokines, chemokines, growth factors as well as their receptors, and reactive oxygen species [6,7].…”

Section: Introductionmentioning

confidence: 99%

Use Of The Prebiotic Inulin In The Prevention Of Adverse Signs Of Acute Colitis

et al. 2015

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The aim of this study was to investigate the infl uence of prebiotic inulin diet intervention on the activity of β-glucuronidase and counts of coliforms and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8) and transcription nuclear factor kappa beta (NFkB) activities in the colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. Male Sprague-Dawley rats (8 per group) were randomly divided into three groups: Control, Acute colitis and Prebiotic. Colitis was induced using 5% DSS in drinking water for 7d. DSS application signifi cantly increased the activity of β-glucuronidase (p<0.001), increased counts of coliform bacteria and decreased lactobacilli count (p<0.05) in comparison to the control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFkB activities showed an increased expression in the acute colitis group. These results correspond to the average value of the disease activity index score (DAI) and revealed the maximum DAI score (6.5) in the acute colitis group. A decrease in the DAI score (4.13) was observed after application of the prebiotic inulin. Inulin diet intervention positively modifi ed the number of microorganims and decreased β-glucuronidase activity. Colon tissue activities of NFkB were signifi cantly suppressed (p<0.001). The synthesis of proinfl ammatory cytokines IL-6 (p<0.01) in the serum and in the colon tissue, as well as tissue in the prebiotic group were downregulated. These fi ndings indicate that the dietary intake of inulin suppressed the expression of the observed markers, which play an important role in the infl ammatory process, which predisposes to the use of inulin in the prevention or treatment of acute colitis in human and veterinary medicine.

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Animal Models of Colitis‐Associated Carcinogenesis

Cited by 92 publications

References 216 publications

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

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

275 The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

Use Of The Prebiotic Inulin In The Prevention Of Adverse Signs Of Acute Colitis

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