Lymphangioma involving the small bowel.
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Adenocarcinoma, followed by lymphosarcoma, are the most common feline intestinal neoplasms. Clinicopathological, survey radiographic, and ultrasonographic findings of five cats with intestinal adenocarcinoma are reported. An abdominal mass was palpable in all five cats, but the mass could be localized to bowel in only two cats. Radiographically an abdominal mass was detected in only one cat. Ultrasonographically there was a segmental intestinal mural mass in all five cats. The mass was characterized by circumferential bowel wall thickening with transmural loss of normal sonographic wall layers. In one cat, the circumferential symmetric hypoechoic bowel wall thickening was similar to that reported for segmental lymphoma. In the other four cats, the sonographic features of the thickened bowel wall were varied, being mixed echogenicity and asymmetric in 3 cats and mixed echogenicity and symmetric in one. The results of the present report suggest that sonographic observation of mixed echogenicity segmental intestinal wall thickening in the cat represents adenocarcinoma rather than lymphosarcoma, although other infiltrative diseases should be considered.
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We analyzed the expression profiles of intestinal adenomas from a new murine familial adenomatous polyposis model (Apc(delta14/+)) using suppression subtractive hybridization to identify novel diagnostic markers of colorectal carcinogenesis. We identified 18 candidate genes having increased expression levels in the adenoma. Subsequent Northern blotting, real-time reverse transcription-PCR, and in situ hybridization analysis confirmed their induction in beta-catenin-activated epithelial cells of murine adenomas. We showed that most of the genes also have altered expression levels in human colonic adenomas and carcinomas. We focused on the IFITM genes that encode IFN-inducible transmembrane proteins. Serial analyses of gene expression levels revealed high levels of expression in early and late intestinal neoplasm in both mice and humans. Using a conditional mouse model of Apc inactivation and a human colon carcinoma cell line, we showed that IFITM gene expression is rapidly induced after activation of the beta-catenin signaling. Using a large-scale analysis of human tumors, we showed that IFITM gene expression is significantly up-regulated specifically in colorectal tumors and thus may be a useful diagnostic tool in these tumors.
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We examined whether the n-3 polyunsaturated fatty acid ethyl ester enriched fish oil K85 (54.4% of eicosapentaenoic acid and 30.3% of docosahexaenoic acid as ethyl esters) could inhibit the intestinal tumorigenesis in Min mice, a murine model of familial adenomatous polyposis (FAP). Min mice that are heterozygous for a nonsense mutation in the Apc gene, develop spontaneously multiple intestinal neoplasms, primarily in the small intestine. K85 was dissolved in corn oil (vehicle) and mixed into the AIN-76A diet. The total oil content (K85 + corn oil) was 12% in all diets. The various experimental diets contained 0 (vehicle control), 0.4, 1.25 or 2.5% of K85. In the small intestine, the mean number of tumors/mouse was 105 +/- 18 (SEM) in control males and 70 +/- 11 in control females. Dietary K85 treatment reduced the number of small intestinal tumors: in males, the maximum reduction was 66% (P = 0.002) with 0.4% of K85; and in females, the maximum reduction was 48% (P = 0.043) with 2.5% of K85, but the inhibition was only slightly increased from 0.4% to 2.5% of K85. The mean tumor diameter was 1.33 +/- 0.08 mm in control males and 1.06 +/- 0.08 in control females, and the diameter ranged from <0.1 mm (monocryptal adenomas) to 4 mm. The small intestinal tumor diameter was reduced by K85 in a dose-dependent manner: in males, with a maximum reduction of 26% (r = -0.64, P = 0.004); and in females, with a maximum reduction of 38% (r = -0.61, P < 0.004). In the large intestine, the mean number of tumors/mouse was 1.0 +/- 0.5 in males and 0.8 +/- 0.2 in females. Although K85 treatment tended to reduce the number and diameter of the large intestinal tumors, these effects did not reach statistical significance. Aberrant crypt foci not elevated from the flat mucosa (ACF(Min)) occurring in the colon of Min mice were also scored. The mean number of ACF(Min)/colon (3.8 +/- 0.9) and the crypt multiplicity (1.49 +/- 0.28) in females were reduced by 73% (P = 0.03) and 60% (P = 0.048) with 2.5% of K85, respectively, whereas no significant effect could be observed in the males.
Three women had endometriosis that involved the rectosigmoid colon; their clinical presentation suggested primary colonic malignant neoplasm. Intestinal obstruction, weight loss, and, in two patients, rectal bleeding with radiologic evidence of a mass lesion that involved the rectosigmoid were present at initial evaluation. All patients eventually underwent colonic resection as definitive therapy. Endometriosis of the pelvic colon may mimic primary intestinal disease, mistakenly suggesting malignant neoplasm. Such symptoms in a young woman should prompt a search for endometriosis, which is a more likely diagnosis. Adequate therapy frequently requires surgical intervention.
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By virtue of its tissue-specific expression, carcinoembryonic antigen (CEA) is an important self, tumor-associated antigen, which is expressed by different human adenocarcinomas and also serves as a target for active-specific immunotherapy. Similar to humans, CEA expression in mice transgenic for the human CEA gene (CEA.Tg) occurs predominantly along the gastrointestinal tract. CEA.Tg mice were crossed with mice bearing a mutation in the Apc gene (MIN mice), and the CEA.Tg/MIN progeny developed multiple intestinal neoplasms, which overexpress CEA to levels that are reminiscent of those reported for tubulovillous intestinal adenomas from patients. CEA.Tg/MIN mice were vaccinated with an aggressive diversified prime/boost vaccine regimen: (a) a primary vaccine consisting of recombinant vaccinia virus-expressing CEA and a triad of costimulatory molecules (TRICOM): B7.1, ICAM-1, and LFA-3 (rV-CEA-TRICOM); and (b) a booster vaccine using CEA-TRICOM in a recombinant avipox (fowlpox) virus (rF-CEA-TRICOM). Granulocyte/macrophage colony-stimulating factor was administered as a biological adjuvant with all vaccinations, either as a recombinant protein (with rV-CEA-TRICOM) or as a recombinant avipox virus (with rF-CEA-TRICOM). That vaccine regimen generated strong CEA-specific host immune responses in CEA.Tg/MIN mice, which resulted in (a) a delayed onset of adult anemia and weight loss, (b) a significant reduction in the number of intestinal tumors, and (c) improved overall survival. No evidence of autoimmunity directed against normal tissues expressing CEA was observed in mice in which the CEA-based vaccine significantly reduced intestinal tumor load. The CEA.Tg/MIN mice present a clinically relevant model in which different CEA-based vaccine strategies can be tested on the spontaneous onset of intestinal tumorigenesis.
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