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At least 1,243 records · Page 69Linked to original sources
PubMed1995

Hypergastrinemia in rats with azoxymethane-induced colon cancers.

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.

Animals↗
PubMed2005

Synchronous colon and gastric advanced carcinomas.

An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemigastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation.

Adult↗
PubMed1992

[Polyps of the colon and the rectum].

This is a retrospective study en 189 cases of colorectal polyps, from 1985-1989 including medical record review, pathologic diagnosis and surgical management. The main symptom was rectal bleeding. The follow up period and it's relation to colorectal cancer was evaluated, considering this entity as a premalignant lesion. 189 histopathology slides were reclassified according to the actual classification. Males were predominant (69%), with increasing incidence from the fifth decade (62% of the total); a 2% malignization rate was found.

Adolescent↗
PubMed2006

CT colonography: effect of colonic distension on polyp measurement accuracy and agreement-in vitro study.

RATIONAL AND OBJECTIVES: To investigate the effect of colonic distension on polyp measurement accuracy and reader agreement. MATERIALS AND METHODS: Institutional review board permission was obtained. A sealed colectomy specimen from a patient with familial adenomatous polyposis was scanned using a four-detector-row computed tomography (CT) after half and full air distension. A histopathologist measured the maximum dimension of all polyps in the opened specimen. Digital photographs and line drawings were used to individually match polyps visible in the CT datasets. Two observers (radiologist, technician) independently estimated the maximum polyp diameter using both two-dimensional (2D) and three-dimensional (3D) surface rendering. Full-distension measurements were repeated 1 week later. Accuracy was analyzed using paired t-test. Observer agreement was assessed using Bland Altman limits of agreement. RESULTS: Twenty-three polyps (4-15 mm) were identified. 2D measurements were significantly smaller than histologic size at both half distension (radiologist first): mean difference [md] -1.1 mm, md -1.7 mm, and full distension md -1.1 mm, md 1.4 mm (all P < .001). 3D measurements were not significantly different from true size other than after half distension for the technician (md -0.7 mm, P = .01). 95% Bland Altman limits for interobserver agreement were narrower after full distension, and better using 2D (half-distension span of agreement approximately 4.7 mm and 6 mm for 2D and 3D, respectively). 2D intraobserver span of agreement between half and full distension was approximately 3.8 mm and 3.2 mm for the radiologist and technician, respectively, compared with 6.2 mm and 5.5 mm using 3D. CONCLUSION: 3D polyp measurement is more accurate than 2D. However, in the presence of suboptimal distension, inter- and intraobserver agreement is superior using 2D.

Adenomatous Polyposis Coli↗
PubMed1997

Cryptic infection by whipworm mimicking a sessile polyp of the colon.

A case of trichocephaliasis in a 70-year-old male is described. The original diagnosis, based on radiological and endoscopic findings, was of a sessile polyp of the colon. Only when a fragment of the supposed polyp was removed at biopsy and examined histologically was it revealed as a single male specimen of whipworm.

Aged↗
PubMed1996

Multiple polyposis and adenocarcinoma arising in Barrett's esophagus.

Adenomatous polyps of the esophagus are rare in comparison with those of the lower gastrointestinal tract. Like adenomatous colon polyps, they have been associated with malignancy. We describe a case of early adenocarcinoma and multiple polyposis of the esophagus arising in a Barrett's epithelium, treated with surgical resection.

Adenocarcinoma↗
PubMed1976

Colonoscopic polypectomy: silent perforation.

The management of colon polyps has been completely revolutionized since the introduction of colonoscopic polypectomy. The reductions in patient time, cost, morbidity, and mortality are major advantages. Reported complications include primarily hemorrhage (1.7%) and frank clinical perforation (0.32%). This report describes a silent perforation after the removal of a broad based polyp through the colonscope.

Colon↗
PubMed1993

[Value of congenital hypertrophy of the retinal pigment epithelium as diagnostic marker in familial adenomatous polyposis].

Familial Adenomatous Polyposis (FAP) is a dominant autosomic disease characterized by the development of hundreds to thousands of colonic adenomatous polyps. Affected patients have a 100% risk of colon cancer development if they are not submitted to a prophylactic colectomy. Identification of carriers depends on the detection of colonic polyps, and endoscopic surveillance must be offered to all descendents, including healthy individuals. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) has been suggested to have a correlation with FAP trait, even before colonic polyp development. The objective of this study is to evaluate CHRPE as a diagnostic marker in FAP patients and descendents. CHRPE was studied in 26 members of 7 FAP families, using direct and indirect ophthalmoscopy, biomicroscopy and retinography. It was found in 62.5% of patients and in 10% of the descendents at risk. Two families did not show signs of CHRPE. Affected members in the remaining families, had positive examinations in 83.3% (two affected members were negative). These results suggest that CHRPE is an important diagnostic tool to identify FAP patients in those families which express the marker. To those descendents who have negative examinations, whether they belong to positive or negative CHRPE families, identification of FAP trait depends on endoscopic surveillance in order to detect colonic polyps.

Adenomatous Polyposis Coli↗
PubMed1976

Intraoperative fiberoptic colonoscopy--"the difficult polypectomy".

An alternative to transcolonic polypectomy, transabdominally directed, transanal colonoscopic polypectomy, for patients who require polyp removal but in whose cases standard colonoscopic approach has failed is presented. The early results are excellent, and the method also can be applied to other patients who have colonic polyps who undergo procedures such as hysterectomy and cholecystectomy.

Aged↗
PubMed1980

The Torre syndrome with gastrointestinal polyposis.

Multiple cutaneous sebaceous neoplasms with or without keratocanthomas are associated with internal low-grade malignant neoplasms, usually of the gastrointestinal (GI) tract (Torre syndrome). We describe a 75-year-old man with multiple sebaceous adenomas, sebaceous epithellomas, and keratoacanthomas in association with multiple colonic polyps. In one polypoid lesion, an adenocarcinoma was noted histologically. Although GI tract carcinoma is clearly established with the Torre syndrome, the occurrence of multiple GI polyps has not been recognized to our knowledge.

Adenocarcinoma↗
PubMed1995

Receptor tyrosine kinases expressed in metastatic colon cancer.

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the alpha and the beta forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the alpha-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease.

Amino Acid Sequence↗
PubMed1999

Inulin, oligofructose and intestinal function.

Inulin and oligofructose have attracted much attention recently as nonabsorbable carbohydrates with prebiotic properties. When inulin and oligofructose were added to a controlled diet, significant increases were noted in colonic bifidobacterial populations, and it has been proposed that these changes promote both colonic and systemic health through modification of the intestinal microflora. Inulin and oligofructose are rapidly and completely fermented by the colonic microflora with the production of acetate and other short-chain fatty acids. As with lactulose, they may also result in the growth of the fecal biomass, and in doing so, entrap ammonia for bacterial protein synthesis or conversion to the ammonium ion. As with dietary fiber and other nonabsorbable carbohydrates, there is also interest in inulin and oligofructose from the standpoint of inhibition of colonic carcinogenesis, blood cholesterol reduction, immune stimulation and enhanced vitamin synthesis. In these areas, the influence of their molecular weight is also an issue, with the longer chain length providing a more sustained fermentation pattern. More human studies are now required, including studies on the long-term effects of inulin and oligofructose consumption on colonic health, in particular on markers of cancer risk such as reduction in colonic polyp recurrence.

Animals↗
PubMed1999

Development of difluoromethylornithine (DFMO) as a chemoprevention agent.

D,L-alpha-difluoromethylornithine (DFMO) was synthesized over 20 years ago. It was hoped that this enzyme-activated, irreversible inhibitor of ornithine decarboxylase, the first enzyme in polyamine synthesis, would be effective as a chemotherapy for hyperproliferative diseases, including cancer and/or infectious processes. DFMO was generally found to exert cytostatic effects on mammalian cells and tissues, and its effectiveness as a therapeutic agent has been modest. DFMO was also found to cause treatment-limiting (but reversible) ototoxicity at high doses. This side effect, along with its minimal therapeutic activity, contributed to the loss of interest by many clinicians in further developing DFMO as a cancer therapeutic agent. However, DFMO was subsequently shown to inhibit carcinogen-induced cancer development in a number of rodent models, and interest in developing this compound as a preventive agent has increased. The rationale for the inhibition of ornithine decarboxylase as a cancer chemopreventive agent has been strengthened in recent years because this enzyme has been shown to be transactivated by the c-myc oncogene in certain cell/tissue types and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. Recent clinical cancer chemoprevention trials, using dose de-escalation designs, indicate that DFMO can be given over long periods of time at low doses that suppress polyamine contents in gastrointestinal and other epithelial tissues but cause no detectable hearing loss or other side effects. Current clinical chemoprevention trials are investigating the efficacy of DFMO to suppress surrogate end point biomarkers (e.g., colon polyp recurrence) of carcinogenesis in patient populations at elevated risk for the development of specific epithelial cancers, including colon, esophageal, breast, cutaneous, and prostate malignancies.

Animals↗
PubMed2005

CDX2-regulated expression of iron transport protein hephaestin in intestinal and colonic epithelium.

BACKGROUND & AIMS: The homeobox transcription factor CDX2 has a key role in intestinal development and differentiation. Mice heterozygous for Cdx2 inactivation develop colonic polyps with epithelial cells showing gastric or squamous differentiation. Loss of CDX2 expression is seen in some poorly differentiated colon carcinomas in humans. Conversely, ectopic CDX2 expression in the stomach of transgenic mice promotes intestinal metaplasia, and CDX2 expression often is seen in intestinal metaplasia in stomach and esophagus. To enhance knowledge of CDX2 function, we sought to define CDX2-regulated genes. METHODS: HT-29 and WiDr colorectal cancer (CRC) cells with low endogenous CDX2 expression were transduced with a CDX2 expression vector, and gene expression changes were assessed by microarrays. RESULTS: The gene for ceruloplasmin-related iron transport protein hephaestin (HEPH) was induced by CDX2 in HT-29 and WiDr. In other CRC lines and human and mice tissues, endogenous HEPH expression was linked to CDX2 expression. Activation of CDX2 rapidly induced HEPH expression, and RNA interference-mediated inhibition of CDX2 led to lower HEPH expression. Studies with HEPH reporter gene constructs and chromatin-immunoprecipitation approaches suggested that CDX2 directly regulates HEPH transcription. In CRC cells, CDX2 induction suppressed intracellular iron levels, consistent with the view that HEPH regulates iron export. CDX2 expression was modulated in response to changes in intracellular iron levels, implying a regulatory pathway in which increased iron levels lead to increased expression of CDX2 and HEPH and enhanced iron export. CONCLUSIONS: CDX2 has a key role in regulating HEPH expression and iron levels in intestinal cells.

Animals↗
PubMed1997

Expression of c-myc in human colonic tissue in response to beta-carotene supplementation.

Dietary supplementation with beta-carotene at 30 mg/day results in an increased serum trans-retinoic acid concentration in patients with a prior colonic polyp. In a number of human cell lines, trans-retinoic acid upregulates c-myc mRNA expression in colonic mucosa by reverse transcription polymerase chain reaction and correlated the results with serum concentrations of all-trans- (ATRA), 13-cis-(13-cRA), and total retinoic acid. Serum and colonic biopsy samples were obtained before and 90 days after administration of a placebo (n = 7) or 30 mg of beta-carotene (n = 5) daily. An increase in c-myc expression after supplementation was observed in 6 of 12 subjects, but 5 of these 6 subjects had decreased total serum retinoic acid concentration and 4 had decreased ATRA concentration. In addition, five of the six subjects with increased c-myc expression had received a placebo. Conversely, c-myc expression was increased in only two of five paired samples from subjects whose total serum retinoic acid concentration increased during the 90-day supplementation period. We conclude that c-myc expression is not correlated with ATRA, 13-cRA, or total retinoic acid concentration in vivo and that increased serum retinoic acid secondary to increased tissue beta-carotene is not sufficient to activate c-myc transcription.

Aged↗
PubMed1997

Colon cancer. Molecular biology of the APC protein.

The discovery of a tumor suppressor gene opens a new pathway to discovery of the fundamental mechanisms that underlie tumor initiation and progression. An inherited tumor suppressor gene is of special interest in that it defines a step in the tumorigenesis pathway that can be rate limiting in development of that tumor type. In the case of colon cancer, we were fortunate in identifying an inherited tumor suppressor gene, the APC gene, that plays a major etiologic role in both the inherited disease, familial adenomatous polyposis (FAP), and in sporadic colon polyps. Characterization of the molecular biology of that gene, and the underlying mechanisms that result in the development of colon tumors, could provide new approaches to both colon cancer diagnostics, therapeutics and chemopreventives. We have embarked, therefore, on a series of exploratory studies designed to provides clues to possible functional roles for the APC protein. We have found through immunocytochemistry that APC protein is distributed throughout the cell, in both the cytoplasm and nucleus. Furthermore, within the nucleus much of the APC protein seems associated with the nucleoli. The cytoplasmic label is distributed in a punctate pattern, with concentrations at the leading edge of migrating cells at the ends of microtubules. Furthermore, following an extraction of the cells that leaves behind primarily cytoskeletal and nuclear scaffold structures, we see strong APC staining of these structures. The yeast two-hybrid system has offered a number of potentially interacting partners for APC, including a new binding site for alpha-tubulin. These results, and others recent discoveries concerning APC, suggest a rather global role for APC protein, modulating cellular activity and signal transduction pathway from the cell periphery to the nucleus.

Adenomatous Polyposis Coli Protein↗
PubMed1979

Fibreoptic colonoscopy. Indications, results and complications.

Fibreoptic colonoscopy was commenced in the Edward Wilson Colon and Rectum Unit at Sydney Hospital in June, 1973. The experience of the first five years of its use is reported. Six hundred and twenty-six examinations have been performed in 568 patients. Fibreoptic colonoscopy has been of particular value in the diagnosis and treatment of colonic polyps. A total of 318 polyps were removed from 184 patients. Their distribution, size and histological features are recorded. Eight complications occurred in the 628 examinations (1.6%). There were six colonic perforations (1.2%) with one death, and two significant haemorrhages (0.4%). This incidence of complications is acceptably low, especially in view of the great benefits obtained by the patient from fibreoptic colonoscopy. The newer instruments, especially the medium length Olympus MB3 colonoscope, have greatly facilitated the examination and, combined with increasing experience, may significantly lower the incidence of complications in the future.

Adolescent↗