Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Intestinal Polyposis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,351 records · Page 75Linked to original sources
PubMed2000

The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64.

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during a screen for polymorphic modifiers of intestinal tumorigenesis in ApcMin/+ mice. Here, we demonstrate that the Mom1AKR allele consists of two genetic components. These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines. A second region, distal to Pla2g2a, has also been identified using fine structure recombinants. Pla2g2aAKR transgenic mice demonstrate a modest resistance to tumorigenesis in the small intestine and a very robust resistance in the large intestine. Moreover, the tumor resistance in the colon of Pla2g2aAKR animals is dosage-dependent, a finding that is consistent with our observation that Pla2g2a is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier demonstrate a modest tumor resistance that is confined to the small intestine. Thus, the phenotypes of these two modifier loci are complementary, both in their quantitative and regional effects. The additive effects and tight linkage of these modifiers may have been necessary for the initial identification of the Mom1 region.

Adenomatous Polyposis Coli↗
PubMed1990

[The role of colonoscopy in screening for tumors of the large intestine].

In 1986-1988, 6434 patients underwent colonoscopy in general hospital: 2076 were at risk for large bowel cancer whereas in 4358 the procedure was used for prophylaxis. Benign polyps or polyposis were detected in a total of 1699 (26.4%) patients: 856 (41.2%) in the risk group and 843 (19.3%) in the prophylactic one. Malignancy was diagnosed in 248 (11.9%) and 41 (0.9%) patients, respectively. It was found that small and early tumors made up 22% of the total number of cancers in the prophylactic group and 16.9% in the high risk group only. Colonoscopic screening carried out under general hospital condition is psychologically and economically justified since it allows to form a risk group and diagnose early cancer whereas timely removal of polyps assures secondary prophylaxis of large bowel cancer.

Adult↗
PubMed2004

Apc10.1: an ApcMin/+ intestinal cell line with retention of heterozygosity.

APC10.1 is a new intestinal cell line derived from ApcMin/+ mice that retains both the heterozygous Apc genotype and a nonactivated Wnt signaling pathway and displays an early neoplastic phenotype. Although tumorigenic both in immunodepressed and in immunocompetent syngeneic mice, it requires a high cell dose and a long latency. Its epithelial/intestinal origin is shown, in a gene expression profile, by the expression of epithelial transcripts (such as cytokeratin and laminin isoforms) and of developmental regulatory genes (such as Tcf-4, Hnf3beta, p21, Ihh, Hes1) necessary for, or involved in, the maintenance of intestinal stem cells. The lack of activation of the Wnt cascade in APC10.1 cells is shown both by the expression profile of Wnt target genes and by the standard TCF reporter assay. APC10.1 cell line is a novel in vitro model that can contribute to a better understanding of the clinical evolution of familial adenomatous polyposis and to finding of new prophylactic and therapeutic approaches. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

Adenomatous Polyposis Coli↗
PubMed1980

Suppressor cells in healthy relatives of patients with hereditary colon cancer.

Patients with sporadic or hereditary colon cancer (cancer family syndrome) demonstrate in vitro defects of cellular immunity characterized by decreased lymphocyte responsiveness in mixed leukocyte culture, which can frequently be attributed to the influence of suppressor macrophages. Healthy relatives of affected patients with hereditary colon cancer can show the same defects of cellular immunity. Affected members with polyposis coli or healthy relatives do not show these defects, whereas individuals with Gardner's syndrome can. These defects of cellular immunity may be an important etiologic component of, or marker for, the cancer family syndrome. These defects could also serve to differentiate the colonic polyposis syndromes.

Colonic Neoplasms↗
PubMed1989

Juvenile polyposis: a case with early presentation and death attributable to adenocarcinoma of the pancreas.

A male child who first presented in the second year of life demonstrated all the recognized clinicopathological manifestations of juvenile polyposis with associated birth defects. Subsequent death at age 19 years from adenocarcinoma of the pancreas further broadens the recognized spectrum of possible sequelae in this disorder and is in keeping with current hypotheses of inherent cancer potential throughout the polyposis syndromes.

Adenocarcinoma↗
PubMed2002

A case of Cronkhite-Canada syndrome whose major complaint, taste disturbance, was improved by zinc therapy.

A patient whose major complaint was taste disturbance and who was diagnosed as having Cronkhite-Canada syndrome was prescribed zinc sulfate. Improvement in taste disturbance was noted after 3 weeks of treatment, followed by gradual improvement in skin and gastrointestinal symptoms. Cronkhite-Canada syndrome can be considered a zinc-deficiency disorder caused by gastrointestinal polyposis.

Aged↗
PubMed1991

[Colorectal diseases: diagnosis].

Colonoscopy is now the accepted diagnostic procedure for most colorectal diseases, although studies comparing sensitivity and specificity of double-contrast barium enema with total colonoscopy or combined procedures such as sigmoidoscopy and same-day double-contrast barium enema versus colonoscopy are still being performed. For diagnosis of diverticulitis and fistulas, however, barium enema is still the diagnostic procedure of first choice. Several studies have demonstrated a high sensitivity and specificity for ultrasonography in diagnosis of appendicitis. It seems that the number of unnecessary laparotomies in suspected appendicitis can be reduced by ultrasonography. In rectal carcinoma the therapeutic procedures are determined by the grade of local tumor infiltration and by tumor invasion of local lymph nodes. To predict the tumor stage, rectal endosonography has become the most reliable method. New genetical tests have been developed to diagnose presymptomatic stages in persons at risk of family adenomatous polyposis.

Colonic Diseases↗
PubMed1998

Ophthalmic and genetic screening in pedigrees with familial adenomatous polyposis.

PURPOSE: To study the possible association between ophthalmic findings, genetic status, and clinical course of the disease in Austrian pedigrees with familial adenomatous polyposis (FAP). METHODS: Thirty-nine members of 16 consecutive FAP families with 20 affected patients and 19 relatives with a 50% a priori risk to develop the disease were examined ophthalmologically. The intestinal status of all persons was established by colonoscopy. Direct or indirect molecular genetic analysis, or both, was possible in eight of the 16 FAP families. RESULTS: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was discovered in 15 (75%) of the 20 persons affected by familial adenomatous polyposis. Five (25%) of the patients with an established FAP were CHRPE-negative. Four of the 19 at-risk individuals were CHRPE-positive. According to DNA analysis, five of the 19 at-risk relatives had a high risk to develop a manifest disease. The ophthalmoscopic tests were in complete agreement with the molecular risk estimation. Furthermore, the combined results of endoscopy and ophthalmoscopy suggested a relationship between a positive CHRPE status and the severity of FAP. CONCLUSIONS: Ophthalmic examinations facilitate predictive diagnosis in FAP patients and first-degree relatives, permitting a noninvasive, highly reliable risk assessment. When present, CHRPE lesions are a reliable clinical marker for FAP in CHRPE-positive families. In CHRPE negative families, negative ophthalmic examinations are of no predictive value. The CHRPE status can add information about the location of the genetic mutation. The combination of an ophthalmic examination with DNA analysis and endoscopy improves the risk assessment of FAP carriers.

Adenomatous Polyposis Coli↗
PubMed2003

Dietary retinoic acid supplementation stimulates intestinal tumour formation and growth in multiple intestinal neoplasia (Min)/+ mice.

Chemopreventive activity by retinoic acid (RA) has been demonstrated previously in rat colon. The spontaneous tumourigenesis in the Min/+ mouse, which harbours a germline mutation in the tumour suppressor gene adenomatous polyposis coli (Apc), is characterized by inactivation of Apc, nuclear accumulation of beta-catenin and the enhanced expression of specific genes activated by T cell factor (TCF)/beta-catenin signalling. Recently it was reported that beta-catenin interacts with retinoic acid receptor in a retinoid-dependent manner, reducing beta-catenin/TCF regulated transcription. Our hypothesis was therefore that dietary supplementation with all-trans RA may inhibit the Apc-driven tumourigenesis in Min/+ mice. Surprisingly, in two different experiments the results showed that dietary RA significantly stimulated both the formation and growth of small intestinal tumours. In the first experiment Min/+ mice were exposed to 50 mg 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine/kg bodyweight at day 3-6 after birth and then treated with 50 mg/kg dietary RA in 1-3 weeks from the age of 2 weeks. In the second experiment the mice were not treated with carcinogen, and the diet was supplemented with 5 or 10 mg/kg RA from the age of 4 weeks until termination of the experiment at 11 weeks. Immunohistochemical studies revealed no differences in beta-catenin, cyclin D1 or proliferating cell nuclear antigen staining following RA treatment. There was no intestinal toxicity in mice fed 10 mg/kg RA, indicating that the increased tumourigenesis in Min/+ mice is a specific effect of all-trans RA.

Animals↗
PubMed1998

A resistant genetic background leading to incomplete penetrance of intestinal neoplasia and reduced loss of heterozygosity in ApcMin/+ mice.

Previous studies of Min/+ (multiple intestinal neoplasia) mice on a sensitive genetic background, C57BL/6 (B6), showed that adenomas have lost heterozygosity for the germ-line ApcMin mutation in the Apc (adenomatous polyposis coli) gene. We now report that on a strongly resistant genetic background, AKR/J (AKR), Min-induced adenoma multiplicity is reduced by about two orders of magnitude compared with that observed on the B6 background. Somatic treatment with a strong mutagen increases tumor number in AKR Min/+ mice in an age-dependent manner, similar to results previously reported for B6 Min/+ mice. Immunohistochemical analyses indicate that Apc expression is suppressed in all intestinal tumors from both untreated and treated AKR Min/+ mice. However, the mechanism of Apc inactivation in AKR Min/+ mice often differs from that observed for B6 Min/+ mice. Although loss of heterozygosity is observed in some tumors, a significant percentage of tumors showed neither loss of heterozygosity nor Apc truncation mutations. These results extend our understanding of the effects of genetic background on Min-induced tumorigenesis in several ways. First, the AKR strain carries modifiers of Min in addition to Mom1. This combination of AKR modifiers can almost completely suppress spontaneous intestinal tumorigenesis associated with the Min mutation. Second, even on such a highly resistant genetic background, tumor formation continues to involve an absence of Apc function. The means by which Apc function is inactivated is affected by genetic background. Possible scenarios are discussed.

Adenoma↗
PubMed2004

Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.

Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.

Adenomatous Polyposis Coli Protein↗
PubMed1998

Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal adenomas in APC gene 1309 knockout mice.

The use of nonsteroidal anti-inflammatory drugs has been suggested to have a chemopreventive effect against colon carcinoma, through the inhibition of cyclooxygenases 1 and 2, in patients with familial adenomatous polyposis and in animal models. Acarbose, an alpha-glycosidase inhibitor, may also be chemopreventive. In order to examine the effects of these drugs we employed APC gene knockout mice randomized into 3 groups, one for treatment with piroxicam (0.05% concentration in drinking water), one for acarbose (0.04% concentration in food) and another for the control. After 14 weeks of treatment, mice were killed for quantitation of gastric and intestinal adenomas. Tumor multiplicity in the whole gastrointestinal tract decreased from 33.89 +/- 13.07 tumors/mouse in the control group to 17.05 +/- 7 tumors/mouse in the piroxicam-treated group (P < 0.001). The decrease in the acarbose-treated group (29.68 +/- 12.86 tumors/mouse) was not significant (P < 0.05). The number of tumors > or = 3 mm in diameter was also quantified in all gastrointestinal segments. The number of such tumors in the piroxicam group was decreased to 0.56 +/- 1.2 tumors/mouse from the control value of 3.78 +/- 1.17 tumors/mouse (P < 0.001), while in the acarbose-treated group the number decreased to 2.36 +/- 1.7 tumors/mouse (P < 0.01). Thus, piroxicam decreases the size and number of gastrointestinal adenomas in APC 1309 knockout mice, while acarbose decreases only the size.

Acarbose↗
PubMed1977

Colorectal polyps and carcinoma in Southern Iran.

A study was made of the prevalence of colorectal polyps (excluding juvenile polyps, familial polyposis coli and villous adenomas) and the minimum frequency of colorectal carcinoma in Southern Iran. A total of 801 large intestines from necropsies performed on individuals 20 years or older was examined with or without magnifying lens for presence of polyps. Our prevalence rate was then compared with those reported on postmortem material from the USA, Australia, South Africa (Bantus), Colombia, and Hawaii (Japanese immigrants). Our surgical pathology files were reviewed for colorectal polyps over a 22-year period (1952-1973). Colorectal carcinomas diagnosed in the Department of Pathology were reviewed over 11 years (1963-1973) and the minimum frequency rates compared with corresponding age- and sex-specific incidence rates from Connecticut, USA. The data indicate 1) a very low prevalence rate for colorectal polyps as well as carcinoma in our region and 2) a rather striking predominance of right-sided colonic carcinoma.

Adenocarcinoma↗
PubMed1989

Heterogeneity in the response of familial polyposis epithelial cells and adenomas to increasing levels of calcium in vitro.

A biomarker of increased risk for colon cancer is abnormally high proliferation of colonic epithelial cells. The authors developed an in vitro assay that measures the ability of human colonic epithelial cells that are in progressive stages of abnormal development to respond to direct application of calcium as the chloride in tissue culture medium. Incorporation of 3H-thymidine and autoradiography in situ was employed to measure the number of proliferating cells cultured at 0.1 mM CaCl2, the optimum level for growth, and 2.2 to 5 mM, both levels achievable in the colonic lumen. Abnormal cell proliferation was reduced in biopsies from 13 of 14 patients without familial polyposis but at increased risk for colon cancer because of previous colonic neoplasms or familial association; in cells from three of four asymptomatic individuals in familial polyposis families at risk for that disease; and in cells of three of ten patients symptomatic with familial polyposis. Growth of tubular adenoma cells from two of seven familial polyposis patients was also inhibited by calcium. Growth inhibition was not observed in more advanced colon tumors including eight adenomas, either villotubular or villous, and five carcinomas. These findings indicate heterogeneity within the familial polyposis phenotype for the normal cellular response to growth inhibition by calcium, and a further loss of response to calcium as these cells progress toward malignancy.

Adenoma↗
PubMed1990

Investigations on the significance of the adenoma-carcinoma sequence in the small bowel.

In view of the rarity of small-bowel epithelial neoplasms as compared with the case for the large bowel, evidence for an adenoma-carcinoma sequence in the small bowel was studied based on a search for data in the medical literature for the years 1927 through 1986. Sufficiently defined data were found for comparison of 185 benign adenomas, 76 adenoma-with-carcinomas, and 1333 carcinomas in patients without familial polyposis disease and for 63, five, and 30, respectively, in patients with disease. For patients without polyposis, it was found that (1) 29.8% of all small-bowel adenomas (33.6% if those at Vater's ampulla are excluded) showed malignancy; (2) the mean and median ages were lower for benign adenoma than for adenoma-with-carcinoma and carcinoma, although the ratios by sex were the same; (3) there is a nearly identical spatial distribution of the three types of epithelial neoplasms within the small bowel; and (4) both the frequency of finding adenomatous residues existing in continuity with carcinoma and the life history of the adenoma-carcinoma sequence are similar in the small bowel as in the large. In comparing these results with those from patients with familial polyposis disease, it was particularly noted that (1) the only difference was that adenomas in familial polyposis occurred earlier and multiply, and (2) the spatial distributions of adenomas and carcinomas for both cases were closely similar. It is therefore postulated that the adenoma-carcinoma sequence is as significant in the small bowels as in the large. A hypothesis regarding the relationship of epithelial neoplasms in people with and without familial polyposis disease is suggested.

Adenoma↗
PubMed2006

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc(Min/+) mice: inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms.

The mouse model for familial adenomatous polyposis, Apc(Min/+) mouse, contains a truncating mutation in the Apc gene and spontaneously develops numerous adenomas in the small intestine but few in the large bowel. Our study investigated whether dextran sodium sulfate (DSS) treatment promotes the development of colonic neoplasms in Apc(Min/+) mice. Apc(Min/+) and Apc+/+ mice of both sexes were exposed to 2% dextran sodium sulfate in drinking water for 7 days, followed by no further treatment for 4 weeks. Immunohistochemistry for cyclooxygenase-2, inducible nitric oxide synthase, beta-catenin, p53, and nitrotyrosine, and mutations of beta-catenin and K-ras and loss of wild-type allele of the Apc gene in the colonic lesions were examined. Sequential observation of female Apc(Min/+) mice that received DSS was also performed up to week 5. At week 5, numerous colonic neoplasms developed in male and female Apc(Min/+) mice but did not develop in Apc+/+ mice. Adenocarcinomas developed in Apc(Min/+) mice that received DSS showed loss of heterozygosity of Apc and no mutations in the beta-catenin and K-ras genes. The treatment also significantly increased the number of small intestinal polyps. Sequential observation revealed increase in the incidences of colonic neoplasms and dysplastic crypts in female Apc(Min/+) mice given DSS. DSS treatment increased inflammation scores, associated with high intensity staining of beta-catenin, cyclooxygenase-2, inducible nitric oxide synthase and nitrotyrosine. Interestingly, strong nuclear staining of p53 was specifically observed in colonic lesions of Apc(Min/+) mice treated with DSS. Our results suggest a strong promotion effect of DSS in the intestinal carcinogenesis of Apc(Min/+) mice. The findings also suggest that strong oxidative/nitrosative stress caused by DSS-induced inflammation may contribute to the colonic neoplasms development.

Adenocarcinoma↗