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

Aberrant crypt foci (ACF) are putative precursor lesions of colon cancer, recently identified on the methylene blue-stained mucosal surface of human colon. No mutations in K-ras or p53 genes were found by non-radioactive single-strand conformation polymorphism analysis in 14 ACF collected from five patients. Using the more sensitive method of allele-specific polymerase chain reaction (PCR) for K-ras, 8 of 14 ACF were found to contain K-ras mutations, suggesting that mutated cells are present in minute clones in ACF. No dysplasia was observed in any of the ACF containing a mutated clone. The presence of K-ras mutations in ACF suggests that these lesions occur at a very early stage in human colorectal carcinogenesis.
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PMID:K-ras and p53 mutations in human colorectal aberrant crypt foci. 877 29

Aberrant crypt foci are putative preneoplastic lesions found in the colons of carcinogen-treated rodents and at an increased frequency in humans at increased risk for colon cancer. There is a strong association between aberrant crypt foci and colon cancer, including many shared phenotypic and genetic alterations. The aim of this study is to present further evidence of a relationship between aberrant crypt foci and colon cancer in humans. Multiple aberrant crypt foci from a single patient were identified in unembedded colonic mucosa. Histological sections of the aberrant crypt foci and adjacent mucosa were evaluated for dysplasia, proliferative activity, and pigment-laden macrophages that were characterized with histochemical techniques. The first patient with sporadic colon cancer identified with aberrant crypt foci with carcinoma in situ is described. It is interesting that this 99-year-old patient had multiple carcinomas in situ, pseudomelanosis coli, and two metachronous colon cancers. These data lend support to the hypothesis that aberrant crypt foci are precursors of some colon cancers.
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PMID:Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer. 878 May 84

The disaccharide tumor marker Gal-GalNAc visualized by galactose oxidase-Schiff sequence is commonly present in cancer cells and in rectal mucous of patients with colon cancer. The expression of this marker on tissue sections taken during experimental colon carcinogenesis shows excellent correlation with human precancerous lesions and even higher percentage of colon cancers express this marker, whereas, no expression is seen in the normal human large intestine. Multifocal expression of the marker is seen throughout the entire colon of patients with precancer and cancer; these include dysplasia, dilated and distorted crypts, regenerative dysplasia and hyperplastic crypts, as well as the morphologically normal crypts remote from cancer. Nearly identical pattern of Gal-GalNAc expression throughout the entire colon also appear during rat colon carcinogenesis induced by azoxymethane including non-expression by the normal and regenerative epithelia during wound healing following mechanical injury. Thus, Gal-GalNAc detected by the simple technique of galactose oxidase-Schiff sequence, is a biomarker that appears during the very early stages of progression of carcinogenesis. The expression pattern supports the field effect theory of carcinogenesis and also explains the basis for mass screening for cancer and precancerous conditions. Chemoprevention strategy using Gal-GalNAc as an intermediate marker detected by accurate and cost-effective rectal mucus test may have great potential.
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PMID:Gal-GalNAc: a biomarker of colon carcinogenesis. 883 67

Surrogate end-point biomarkers (SEBs) have become widely used in short-term cancer chemoprevention trials in place of cancer end points. This paper discusses criteria relevant to the selection and validation of SEBs for colon cancer risk and the use of SEBs in colon cancer chemoprevention trials. As with a number of other cancers, colon carcinogenesis is the result of a multistep process in which an increasing number of alterations, including specific gene mutations, occur as cells progress from normal to precancerous states of increasing size and dysplasia to cancer and finally to metastatic disease. Ideally, a SEB would show differential expression between the various phases of colon carcinogenesis (i.e., normal, premalignant, and malignant tissues) and be associated with risk of colon cancer. Some SEBs that do not meet these criteria may still be useful for demonstrating the effect of a particular agent. It is also necessary that a SEB be measured in tissues (or other sample material) accessible for multiple and sequential sampling and allow for development of appropriate quality control procedures. Some SEBs must have the potential for modulation by chemopreventive agents. Validation of SEBs for use in chemoprevention studies requires that a relationship between the marker and subsequent risk of cancer be established. Also, the assay reliability and accuracy for each SEB must be determined adequately in well-designed prospective studies.
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PMID:Surrogate end-point biomarkers as measures of colon cancer risk and their use in cancer chemoprevention trials. 899 96

Many studies have been conducted to assess the potential preneoplastic nature of colonic aberrant crypt foci (ACF), but still the biological significance of these foci and their relationship to colon neoplasia remains to be elucidated. In the present paper a battery of variables suggested to be indicative for colon cancer development has been studied in relation to ACF in rats. These include: (i) the degree of dysplasia; (ii) the type of mucus production; (iii) the cellular immunohistochemical expression and distribution of transforming growth factors alpha and beta and their respective receptors, epidermal growth factor receptor and transforming growth factor beta receptors I and II and phosphorylated cellular tyrosine. The parameters have been investigated in ACF selected from a previous study where the foci were induced under different circumstances, leading to disparities in the number as well as the crypt multiplicity obtained. The present study showed that for all parameters investigated, apart from sialomucin production, the different experimental conditions had no effect on the individual ACF, irrespective of the number and distribution of the different categories of ACF among the various diets. However, it was shown that the degree of dysplasia correlated strongly with crypt multiplicity and that all the investigated ACF lacked expression of transforming growth factor alpha and expressed a reduced amount of transforming growth factor beta compared with normal crypts. These observations may indicate that ACF are preneoplastic lesions and supports the suggestion that they may, at least in the rat, have the potential to gradually progress to tumors, but no single ACF showed particular characteristics indicating specific proneness to tumor development. The study could not confirm the presence of sialomucin-producing ACF as a valid marker for tumor development.
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PMID:Histomorphological and immunohistochemical characterization of colonic aberrant crypt foci in rats: relationship to growth factor expression. 906 43

Laparoscopic surgery is now widely accepted because of its many benefits. We have successfully performed laparoscopic curative resection in 72 patients with colon cancer or polyps. Of these patients, seven with cecal creeping tumor underwent laparoscopic local cecum excision (cecectomy). The creeping tumor is often found in the rectum and cecum. It is extremely difficult to remove endoscopically because of its shape and size. In addition, the recurrence rate after endoscopic mucosal resection is high. Therefore, laparoscopic cecectomy was thought to be a suitable procedure for such cases. This procedure was performed intracorporeally by using an ENDO-GIA and was less invasive than the extracorporeal procedure. These tumors, which showed local cancer limited to the mucosa or tubular adenoma with severe dysplasia in pathological findings, were resected completely. All patients tolerated liquids 1 day postoperatively and were discharged within 5 days. Our experience suggests that laparoscopic cecectomy has the potential to be useful for cecal creeping tumors.
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PMID:Laparoscopic local excision of the cecum for cecal creeping tumor. 910 46

Colorectal cancer is a significant clinical problem for patients with long-standing ulcerative colitis and Crohn's disease. Traditional risk factors include long disease duration and greater extent of colonic disease, but newer factors such as associated primary sclerosing cholangitis, folate deficiency, and family history of colon cancer may help to refine risk stratification. Molecular pathogenesis of colitis-associated colon cancer shares some of the same genetic abnormalities as sporadic colon cancer, but the timing of certain alterations suggests different carcinogenic pathways. Some molecular alterations show promise as complementary markers to dysplasia. Clinical studies of colonoscopic surveillance indicate that colon cancers can be detected early and that mortality may therefore be improved. A suggested surveillance strategy is proposed.
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PMID:Inflammatory bowel disease and cancer. 911 37

Aberrant crypt foci (ACF) have been identified in the methylene-blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty-four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5-10 min. The strips were measured, put on a glass slide and observed under a light microscope at x25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty-four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.
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PMID:Histology of aberrant crypt foci in the human colon. 914 80

Human carcinoembryonic antigen (CEA) is overexpressed in a wide variety of epithelial malignancies including colon cancer. CEA can function in vitro as a homotypic intercellular adhesion molecule and can block the terminal differentiation of rodent myoblasts, thus raising the possibility that deregulated expression of CEA might directly contribute to malignant progression. To address this question, the expression pattern and cell-surface levels of CEA were studied during malignant transformation of the colonic epithelium in sporadic and familial adenomatous polyposis-related neoplasms. The level of immunohistochemically detected CEA was higher in 30% to 62% of microadenomas and small adenomas from familial adenomatous polyposis patients compared with adjacent normal mucosa, and this proportion was positively correlated with lesion size and degree of dysplasia. Cytofluorometric analysis of highly purified single epithelial cell suspensions from freshly excised carcinomas versus adjacent normal tissue demonstrated up to a 20-fold increase of mean cell-surface CEA in a group of colon carcinomas representative of the overall majority of such tumors--from Dukes' stages A to D and ranging mainly from well to moderately differentiated, the degree of overproduction was inversely correlated with tumor differentiation and directly correlated with stage. A marked tendency toward nonpolarized versus apical cell-surface expression with progression was also noted. Nonspecific cross-reacting antigen (NCA), a CEA family member, is also a homotypic adhesion molecule and blocks terminal myogenic differentiation, whereas biliary glycoprotein is a CEA family adhesion molecule that does not. Cell-surface NCA showed even greater overexpression (up to 70-told) in dedifferentiated tumors, whereas total-cell biliary glycoprotein showed approximately 2-fold lower levels than was normal in more differentiated tumors and approximately 2-fold higher levels than in further progressed tumors. These results therefore support the suggestion that CEA and NCA can directly contribute to colon carcinogenesis by inhibiting colonocyte differentiation.
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PMID:Cell-surface levels of human carcinoembryonic antigen are inversely correlated with colonocyte differentiation in colon carcinogenesis. 916 89

Because patients with longstanding ulcerative colitis are at an increased risk for developing colorectal cancer, surveillance colonoscopy and colectomy for dysplasia or asymptomatic cancer is advised as a method of reducing cancer-related mortality. Generally, the use of dysplasia as a criterion for a positive test in cancer surveillance has performed poorly. The emerging field of colon cancer genetics has identified several important tumor markers that have the potential to improve sensitivity for the detection of early neoplasia. Specifically, p53 tumor suppressor gene mutations, aneuploidy, and mucin-associated sialosyl-Tn expression appear most promising for future use in surveillance programs.
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PMID:Cancer biology in ulcerative colitis and potential use in endoscopic surveillance. 917 46


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