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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and experimental studies have shown that the carcinogenic process of colorectal mucosa is linked to the development of proliferative abnormalities which precede the occurrence of morphological abnormalities such as epithelial dysplasia. In humans, proliferative defects have been demonstrated in the normal rectal mucosa of population groups at risk for colon cancer. Several techniques are available to study cell kinetics in the gastrointestinal mucosa. Each explores different aspects of cell proliferation. We have attempted to evaluate the correlation between various techniques in the normal rectal mucosa of high-risk patients. We found a good correlation between bromodeoxyuridine (BrdU) labeling index and the mucosal activity of the enzyme ornithine decarboxylase, and between tritiated thymidine and the percentage of cells in the S phase of the proliferative cycle as determined by flow cytometry. However, these correlations concern only labeling indices, which can be influenced by physiological events, such as active inflammation or increased cell loss. It may not be the most reliable proliferative marker of cancer risk. Moreover, methods using cells isolated from homogenized tissue do not allow us to evaluate the pool of cells which are examined nor the distribution of proliferating cells within the tissue. For example, an inflamed mucosal specimen is highly infiltrated with inflammatory cells which can interfere with the measurement of epithelial cell proliferation. Nevertheless, the labeling index may be normal even in patients at high risk. For these reasons, we think that the most reliable methods are those using tissue culture, such as tritiated thymidine or BrdU uptake and proliferating cell nuclear antigen (PCNA) immunostaining.
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PMID:Methodological problems in the use of rectal cell proliferation as a biomarker of colorectal cancer risk. 782 6

Aberrant crypts are aggregates of single to multiple colonic crypts evidencing hallmarks of dysplasia and may be the earliest detectable pathological lesions for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In one, putative chemoprevention agents are tested for inhibitory effects when administered concomitantly with a carcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcinogen azoxymethane (AOM) and allowed to develop for 4 weeks, when an average of 90-100 aberrant crypt foci per colon were found in the methylene blue-stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi-crypt foci were observed. During this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and development. We found the non-steroidal anti-inflammatory drugs piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in suppressing aberrant crypt formation or the progression to foci of multiple aberrant crypts. Treatment with chemosuppressing agents 13-cis-retinoic acid (13-cRA) and 4-hydroxyphenretinamide (4-HPR), known differentiating agents, however, did suppress expansion of aberrant crypt foci, with 13-cRA being the much more potent agent.
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PMID:Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon. 782 66

Reports of cases of flat-type colorectal tumors are increasing in Japan, but almost nothing has been elucidated about the genetic abnormalities of these tumors. In this study, we have examined p53 mutations in six cases of colon cancer cell lines, 22 cases of flat-type colorectal tumors, and 27 cases of polypoid-type colorectal tumors using the polymerase chain reaction (PCR) and temperature-gradient gel electrophoresis (TGGE); the latter has recently been developed as a screening method for gene mutations. p53 mutations were observed in four colon cancer cell lines, six flat-type colorectal tumors, and three polypoid-type colorectal tumors, all of which were analyzed by direct sequencing. These mutations were observed only in adenomas with high-grade dysplasia and in colorectal cancers but not in adenomas with low-grade dysplasia. These observations suggest that p53 gene mutations are involved in flat-type as well as polypoid-type colorectal tumors at relatively later stages of carcinogenesis and that TGGE seems to be useful as one of the rapid screening methods.
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PMID:p53 mutations in flat- and polypoid-type colorectal tumors detected by temperature-gradient gel electrophoresis. 808 16

Juvenile Polyposis (JP) is a rare disease that may be found anywhere within the gastrointestinal tract, almost most cases so far reported have involved the colon. It is a precancerous condition, with the subsequently developing carcinomas so far also being found almost exclusively in the colon. A familial form is found in 20 to 50% of the cases. The present paper describes a family in whom three members of the second generation developed massive JP in the stomach requiring partial resection of the stomach or gastrectomy. Three members of the first generation died of carcinoma of the stomach and a forth of carcinoma of the colon. A male member of the second generation was treated at the age of 38 years for a carcinoma of the colon; 16 years later, he underwent resection of the stomach for juvenile polyposis and the histological work-up of the surgical specimen revealed in addition, areas of dysplasia and early carcinomas restricted to the mucosa.
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PMID:[Familial juvenile polyposis with predominant stomach involvement]. 823 87

Patients with extensive ulcerative colitis have a high risk of developing colon cancer. The etiology of mucosal dysplasia, a premalignant lesion that is used as a screening test in surveillance programs, is unknown. Previously, a case-control study [Lashner et al. (1989) Gastroenterology 97:255-259] suggested that folate supplementation was associated with a 62% reduction in the risk of developing dysplasia or cancer. The current case-control study was performed to obtain a better definition of this risk. All 67 patients with chronic ulcerative pancolitis having surveillance colonoscopy during a 1-year period were entered. There were 6 cases (4 with dysplasia and 2 with cancer) and 61 controls (no cancer or dysplasia). Red blood cell folate, reflecting intermediate-term stores, was a mean of 66.2 ng/ml lower in cases compared to controls. Serum folate, reflecting short-term stores, was not different between groups. Adjusting for confounding effects of age, sex, race, disease duration, and folate supplementation, the risk of dysplasia or cancer was significantly decreased by 18% for each 10 ng/ml increase in red blood cell folate (odds ratio 0.82, 95% confidence interval 0.68-0.99). Vitamins A, D, and E and carotene were lower in cases than in controls, but no water-soluble vitamin other than red blood cell folate was associated with an increased cancer risk. Depressed red blood cell folate is associated with an increased risk of dysplasia and cancer in patients with ulcerative colitis and may be a risk factor for neoplastic transformation.
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PMID:Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. 839 76

Photodynamic sensitizers are light-absorbing chemicals that cause photoreactions in biologic systems when exposed to light of the proper wave-length. Dihematoporphyrin ethers (DHE) are the active porphyrin derivatives most commonly used as a photosensitizer (Photofrin, QLT). DHE accumulates in tumor tissue and also fluoresces when light activated. A more reliable and less costly screening method for early detection and treatment of colon cancer is needed. The present study was designed to induce adenocarcinoma of the colon in rats with 1,2 dimethylhydrazine (DMH) and attempt to identify tumors early in their evolution by DHE fluorescence. Forty rats were injected with 20 mg/kg of DMH at weekly intervals until sacrifice. Photofrin (3 mg/kg) was injected through the tail vein in each prior to sacrifice. Eight colonic specimens contained invasive adenocarcinoma, seven of which fluoresced when exposed to a Woods lamp. Carcinoma in situ was identified in two specimens by fluorescence, and one fluorescent specimen contained dysplasia.
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PMID:Photo detection of carcinoma of the colon in a rat model: a pilot study. 847 97

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, inasmuch as it may allow tumors to escape immune surveillance. We have observed reduced expression of HLA antigens in sporadic colon cancer and adenomas from familial adenomatous polyposis patients. We now studied the expression of HLA class I antigens in patients with sporadic adenomas, which are precursors of colorectal cancer. Expression of HLA class I antigens was studied by immunohistochemistry in (a) sporadic colon adenomas, (b) histologically normal mucosa distant from the adenomas, (c) histologically normal colonic mucosa from patients with history of sporadic colon adenomas, and (d) colonic mucosa from normal subjects. HLA class I antigen expression was moderately reduced in 56% and severely reduced in 44% of the adenomas; this reduction was significant when compared to controls (P < 0.0001). The reduction of HLA class I expression in adenomas was related to the grade of dysplasia of the adenomas. HLA class I expression of normal appearing mucosa was decreased in 76% of patients with adenoma (P < 0.0001) and in 54% of patients with history of adenoma (P < 0.005) compared to normal controls. These changes were antigen specific, inasmuch as the expression of carcinoembryonic antigen, a surface antigen, was not affected. Our findings suggest that reduced HLA class I expression is an early event in the cell transformation process from normal to neoplastic state, preceding in many cases the onset of histological changes. HLA class I could be potentially used as a premalignant marker in the colon.
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PMID:Expression of HLA class I antigens in sporadic adenomas and histologically normal mucosa of the colon. 848 24

Adenomas of the colon and rectum are perhaps the most commonly encountered of human benign epithelial neoplasms. Evidence of their relationship to the development of colorectal carcinoma has mounted over the years. They represent a phase present for significant duration in many fated to develop colon cancer. Because of this, and because of the technical advances in endoscopy, a great deal of effort has been expended on identifying and removing these lesions. Subsequent care of the patient is heavily dependent on the pathologic analysis of these lesions. they must be properly classified; the presence of cancer must be carefully sought. If present, the character and location of the cancer arising in the polyp must be carefully described. Communication between clinician and pathologist if of paramount importance. Attention must be paid to the precise meaning of such terms as dysplasia, carcinoma, and invasion. The pathologist's report needs to detail parameters important in determining prognosis and further therapy.
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PMID:Polyps: the pathologist's perspective. 860 5

Aberrant crypt foci (ACF) are morphologically abnormal structures that can be identified in whole amounts of colonic tissue from rodents treated with colon carcinogens and from patients at risk for development of colon tumors. ACF are heterogeneous and exhibit properties, such as altered patterns of cell proliferation, the presence of dysplasia, and mutations in protooncogenes and tumor formation. In this study, we have investigated the presence of genomic instability in DNA isolated from human ACF from patients with colon cancer. Altered allele length detected by electrophoretic separation of PCR amplified oligo A or microsatellite loci was used to identify candidate samples which were then more rigorously investigated by sequence analysis for instability. Of 20 patients examined, two exhibited alterations at two loci, and this instability could be confirmed by sequence analysis. An additional seven of the 20 patients had evidence for instability at a single locus. Quantitative sequence analysis of the DNA from an ACF of one of these seven patients was consistent with alteration of allele length in this patient, but the alteration was not sufficiently different from normal to reach statistical significance. Thus, genomic instability, manifest as altered length of microsatellite and oligo A sequences, in present in some ACF, and therefore can be a very early event in the development of some human colon cancers.
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PMID:Evidence for genomic instability in human colonic aberrant crypt foci. 862 97

Patients with extensive ulcerative and Crohn's colitis represent a group at high risk for developing colorectal cancer. Two clear independent risk factors for developing colorectal cancer in patients with chronic colitis include duration and extent of disease. Cancers in chronic colitis do not develop from a colonoscopically recognizable adenomatous polyp similar to that in sporadic colon cancer, but instead arises from flat dysplastic epithelium that is typically not colonoscopically distinguishable from adjacent nondysplastic epithelium. All patients with extensive disease require active management of their increased cancer risk. Active management of cancer risk in chronic long-term colitis should not be presumed to be equivalent to colonoscopic surveillance. There is little data with which to reassure a patient regarding the efficacy of colonoscopic surveillance. A reasonable alternative to colonoscopic surveillance in patients with ulcerative colitis is the restorative proctocolectomy (ileoanal pull-through), which maintains continence and avoids a stoma and appliance. If colonoscopic surveillance is undertaken, a clear understanding of what the definition of a positive surveillance test, ie, when surgical action is taken, is pivotal to the success of the surveillance program. There are now ample data confirming that the finding of any unequivocal dysplasia (low- or high-grade) is associated with a high risk of coexistent or future colorectal cancer. Dysplasia confirmed by a second pathologist (preferably an experienced gastrointestinal pathologist) should prompt a recommendation for colectomy. Future cancer surveillance in chronic colitis will almost certainly involve some applied molecular genetic test.
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PMID:Inflammatory bowel disease. 870 63


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