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PubMed1997

Suppression of intestinal polyp development by nimesulide, a selective cyclooxygenase-2 inhibitor, in Min mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) suppress colon carcinogenesis in man and experimental animals. However, conventional NSAIDs inhibit both cyclooxygenase (COX) isoforms, COX-1 and COX-2, and cause gastrointestinal side-effects. Nimesulide, a selective inhibitor of COX-2, is much less ulcerogenic. We, therefore, examined its influence on the development of intestinal polyps in Min mice. Female Min mice at 4 weeks old were given 400 ppm nimesulide in their diet for 11 weeks. This treatment resulted in a significant reduction of the numbers of both small and large intestinal polyps, the total being 52% of that in untreated control Min mice. The size of the polyps in the nimesulide-treated group was also significantly decreased. The results suggest that nimesulide is a good candidate as a chemopreventive agent for human colon cancer with low toxicity.

Animals↗
PubMed1997

Suppression of intestinal polyp development by low-fat and high-fiber diet in Apc(delta716) knockout mice.

Most epidemiological and animal studies show a positive correlation of the dietary intake of fat with the incidence of colon cancer, whereas an inverse correlation of the dietary intake of fiber. In rats fed a diet low in fat and high in wheat bran fiber and calcium, a significant decrease was reported in the number of azoxymethane-induced aberrant crypt foci compared with those fed a high-fat, low-fiber and low-calcium diet. Mutations in the human APC gene play a key role, not only in familial adenomatous polyposis, but also in many sporadic cancers of the entire digestive tract. We previously constructed a mouse strain Apc(delta716), carrying a truncation mutation at codon 716 of the Apc gene, the homolog of human APC (10). The heterozygous mice developed numerous intestinal polyps, and all microadenomas dissected from the earliest polyps had already lost the wild-type allele, indicating the loss of heterozygosity. Using these Apc(delta716) knockout mice, we have investigated the effect of a low-fat and high-fiber diet (LRD for 'low-risk' diet) on intestinal polyposis, and compared it with that of a high-fat and low-fiber diet (HRD for 'high-risk' diet). The mice were fed either diet for 7 weeks, and the number and size of intestinal polyps were scored. The LRD-fed mice had fewer polyps than the HRD-fed mice, by 36% in the small intestine and by 64% in the colon. As for the polyp size distribution, there was no significant difference between the HRD- and LRD-fed mice. These results indicate that LRD can suppress intestinal polyposis compared with HRD which does not, and suggest that its suppression is at the initiation of polyp formation. This is likely to be due to a decreased frequency of loss of heterozygosity, rather than a retarded growth of the polyp adenomas.

Animals↗
PubMed2002

[Intestinal polyp of the umbilical cord].

The morphology, pathogenesis, complications and differential diagnosis of an intestinal polyp of the umbilical cord are presented. The polyp were detected postnatal on the umbilical cord in an healthy male newborn. The presents of intestinal tissue upon the umbilical cord ist possible about the persistence from remnants of the ductus omphalomesentericus with prolapse and differentiation of the intestinal cells. The ductus omphalomesentericus is a tubular structure, a communication between the developing embryonic gut and the yolk sac, forming during the early embryonic life. Obliteration of the omphalomesenteric duct is usually complete by the 10(th) week of gestation. Various portions of the duct may persist, however, giving rise to polyps, fistulas or cysts of the umbilical cord with potentially dangerous clinical consequences. Other tumors of the umbilical cord are myxoma, angioma and teratoma are differential diagnosis.

Adult↗
PubMed1986

[Endoscopic removal of small intestinal polyps in total polyposis of the digestive tract].

In patients with proliferative and mixed forms of total polyposis of the digestive tract the intestinal polyps are mainly localized in the duodenum, with hamartomal polyposis--in the jejunum and ileus. The endoscopic polypectomy from the small intestine may be performed intraoperatively and during endoscopy under narcosis. 174 polyps with the diameter of 0.5-5 cm were removed in 27 patients. There were 3 complications (bleedings) after polypectomy.

Adolescent↗
PubMed1990

[Intestinal polyps in childhood].

From 1965 to 1987, 230 polypectomies were performed in patients between 8 month to 16 years old, 147 boys and 83 girls. The most frequent symptom was rectal bleeding and the most frequent location was the rectosigmoid (96%). The polyps measured from 0.8 to 2 cm., in only one case the polyp measured more than 5 cm. causing duodenal obstruction and it was associated with a gastric polyp. Solitary polyps represented 93.9% of all cases, Peutz-Jeghers syndrome 1.73 and juvenile polyposis 0.87%. In that period 3 cases of colonic carcinoma in children over 9 years old were diagnosed. The histology of 200 polyps were reviewed. In 21 cases the diagnosis was modified (10.5%). The juvenile polyp (J.P.) was the most frequent type (93%). The usual histopathological pattern was observed in 71.5% of the J.P., early lesions (26.3%) and hyperplastic changes (2.1%). Six cases were tubular adenoma and one tubulovillous. The multiple juvenile polyposis was found in girls (13 and 14 years old). None of the patients with Peutz-Jeghers syndrome had gonadal tumor. Endoscopic polypectomy in children is a safe and effective treatment for colorectal polyps. This study provides information on the clinicopathologic findings in argentinian children with intestinal polyps treated by polypectomy over a 22 year period. It emphasizes that juvenile polyps is the most frequent pattern however other lesions can be present in gastrointestinal tract and also associated with others tumors. Patients with polyps should be followed at regular intervals which can be modified according to the histologic type and family history.

Adenoma↗
PubMed2002

Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps.

Cyclooxygenase-2 (COX-2), the inducible COX isozyme, plays a key role in intestinal tumorigenesis. We have demonstrated recently that COX-2 protein is induced in the polyp stroma near the intestinal luminal surface in the Apc(Delta716) mouse, a model for human familial adenomatous polyposis, and stimulate tumor angiogenesis. However, the precise cell types that express COX-2 are still to be determined. By immunohistochemical analysis, here we show that the majority of COX-2-expressing cells in the intestinal polyps of Apc(Delta716) mice are fibroblasts and endothelial cells. Furthermore, the COX-2-expressing cells in human familial adenomatous polyposis polyps are also fibroblasts and endothelial cells. In contrast, bone marrow-derived cells such as macrophages and leukocytes express little COX-2 protein in the intestinal polyps. These results clearly indicate that fibroblasts and endothelial cells play important roles in polyp expansion by expressing COX-2, resulting in tumor angiogenesis.

Actins↗
PubMed1986

Metastatic spindle-cell renal carcinoma presenting as multiple intestinal polyps.

A 75-year-old woman presented with rapidly progressive intestinal and general symptoms including diarrhea, melena, weight loss, back pain, and lassitude. Endoscopy revealed multiple intestinal polyps which, microscopically, consisted of metastatic tumor deposits composed predominantly of spindle-shaped tumor cells. The primary tumor, a mixed spindle-cell and clear-cell carcinoma, was later identified in the kidney at autopsy. The patient had a cholecystectomy 13 years previously.

Aged↗
PubMed2000

Beef induces and rye bran prevents the formation of intestinal polyps in Apc(Min) mice: relation to beta-catenin and PKC isozymes.

Epidemiological studies suggest that high consumption of red meat and saturated fat and low consumption of fiber are associated with an increased risk of colon cancer. Therefore, we studied whether diets high in red meat or high in different grain fibers as well as inulin, polydisperse beta(2-->1) fructan, could affect the formation of intestinal polyps in Apc(Min) mice. Min mice were fed the following high-fat (40% of energy) diets for 5-6 weeks; a high-beef diet and a casein-based diet without added fiber or casein-based diet with 10% (w/w) oat, rye or wheat bran, or 2.5% (w/w) inulin. One group had a normal low-fat AIN93-G diet. The mice fed the rye-bran diet had the lowest number of polyps in the distal small intestine [15.4 +/- 8.7 (mean +/- SD)], and in the entire intestine (26.4 +/- 12.1). The rye-bran group differed significantly (P = 0. 001-0.004) from the beef group (36.6 +/- 9.4 and 52.8 +/- 13.2). In addition, the beef group differed significantly from the AIN93-G group (P = 0.009) and also from the wheat-bran group (21.0 +/- 6.1 and 35.0 +/- 8.2; P = 0.02) in the distal small intestine. The inulin group (32.9 +/- 14.3 and 49.3 +/- 16.3), on the other hand, was close to the beef group and it differed significantly from the rye-bran group in the distal small intestine. The number of animals bearing tumors in the colon + caecum was only 33% in the rye-bran group when compared with 89% in the beef and 100% in the inulin groups. The mice fed the rye-bran and beef diets had the lowest levels of cytosolic beta-catenin (0.60 +/- 0.42 and 0.67 +/- 0.26) and they differed significantly (P = 0.040 and 0.062) from the mice fed the oat-bran diet (1.46 +/- 0.43). No differences between groups in expression of protein kinase C (PKC) alpha, betaII, delta and zeta were found. The four PKC isozymes were positively correlated with cytosolic beta-catenin levels (r = 0.62-0.68; P < 0.0001).

Animals↗
PubMed2003

Exercise and intestinal polyp development in APCMin mice.

PURPOSE: Epidemiological evidence suggests that physical activity protects against colon cancer. We previously used a mouse predisposed to intestinal polyps (APCMin) to evaluate this association and found the suggestion of fewer polyps in exercised males but not females. The present study was designed to further explore the potential exercise x sex interaction on polyp development and to begin to look at potential mechanisms. METHODS: Six-week-old APCMin mice (N = 60 males; 60 females) were randomly assigned to one of two groups by sex: treadmill running at 20 m.min-1, 5% grade, 45 min.d-1, 5 d.wk-1 (EX) or nonrunning controls (CON) (N = 30 per group). EX mice ran in running wheels while in quarantine (weeks 0-3), followed by treadmill running weeks 3-8. Body weights were measured weekly. Urine was collected at 5 wk and fasting blood at 7.5 wk. Body composition was measured, serum was frozen, and polyp number and size were measured at sacrifice. RESULTS: EX resulted in lower body weights (P < 0.01) and reduced fat mass (P < 0.01). Fasting glucose was lower in EX (P < 0.01), and leptin was lower in EX (P = 0.05) compared with CON. EX did not affect serum insulin-like growth factor-1 or urinary corticosterone. Total polyp number and size were not statistically different between groups; however, there were fewer jejunal polyps in EX (3.6 +/- 0.7, mean +/- SE) versus CON males (5.2 +/- 0.8; P = 0.04) and an even larger difference when only the consistent runners were kept in the analysis (2.7 +/- 0.5 in EX; P = 0.01). CONCLUSION: Despite favorable changes in body composition, blood glucose, and leptin, 8 wk of running resulted in only minor changes related to polyp development in male but not female APCMin mice.

Animals↗
PubMedDate not supplied

Intestinal polyps in children and adolescents--a review of 103 cases.

Juvenile polyps are the most common tumors of the gastrointestinal tract in children and are the principal cause of hematochezia. A total of 103 children and adolescents with intestinal polyps have been treated in Veterans General Hospital-Taipei from March 1961 to March 1994. The diagnosis included 87 cases (84.5%) of juvenile polyps, 2 cases of isolated adenomatous polyp and 14 cases of inherited polyposis syndrome. Juvenile polyps most often occur in children between 2 to 10 years old, with a male-to-female ratio of 1.4:1. Rectal bleeding was the main symptom (97.7%). Of the 87 patients, 82.8% had isolated polyps and 83.3% of those were located in rectosigmoid colon. After extensive use of colonoscopy, the reported incidence of multiple polyps substantially increased, and more polyps were found proximal to the rectosigmoid colon. Most juvenile polyps were removed by colonoscopic polypectomy. The recurrent rate was 10.2%. One of the two cases of juvenile polyposis coli suffered from intussusception demanding partial colectomy. Recurrent polyps were found in the remaining colon and were removed by colonoscopic polypectomy. Seven patients of Peutz-Jeghers syndrome came from five families. At initial diagnosis, one case had no polyps and two presented with intussusception. A 19-year-old girl was found to have bilateral ovarian cysts. One of the three familial adenomatous polyposis had adenocarcinoma at initial evaluation. Two cases of Gardner's syndrome received sulindac treatment, and no evidence of malignancy was found after three years of follow-up.

Adenomatous Polyposis Coli↗
PubMed2002

No effects of Smad2 (madh2) null mutation on malignant progression of intestinal polyps in Apc(delta716) knockout mice.

The loss of heterozygosity (LOH) in human chromosome 18q21 is found at high frequencies in advanced pancreatic and colorectal cancers. Several candidate tumor suppressor genes, such as SMAD2, SMAD4, and DCC, are located in this region. The homologues of these genes in the mouse are also clustered on chromosome 18. Mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis, and we earlier constructed a mouse model for familial adenomatous polyposis, Apc(delta716). Although human APC is located on chromosome 5q, mouse Apc is on chromosome 18, 30 cM proximal to the Dcc-Smad4-Smad2 locus. Taking advantage of this fact, we constructed previously a cis-compound Apc(delta716) Smad4 mutant, the intestinal polyps of which progress to very invasive adenocarcinomas. To determine whether Smad2 mutations play similar roles in malignant progression, here we constructed compound mutant mice carrying Apc and Smad2 knockouts in the cis configuration. In contrast to the cis-compound Apc(delta716) Smad4 heterozygotes, the polyps in the cis-compound Apc(delta716) Smad2 heterozygotes showed no difference in the number, size, or histopathology from the polyps in the simple Apc(delta716) heterozygotes. These results suggest that, on human chromosome 18q21, the SMAD4 LOH plays a more significant role, and SMAD2 LOH is insufficient to cause malignant progression of colonic polyps.

Animals↗