Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive intestinal polypeptide (VIP) and substance P are found in neurons in the lamina propria and submucosa and muscularis propria of human small intestine and colon. VIP receptors coupled to adenylate cyclase are present on epithelial, smooth muscle, and mononuclear cells. This study analyzes the distribution of [125I]VIP binding and [125I]substance P in human colon and small intestine using autoradiographic techniques. [125I]VIP binding was present in high density in the mucosal layer of colon and small intestine. [125I]VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, [125I]substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, [125I]VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of [125I]VIP binding indicate that the highest density of VIP receptors was found in the small intestine and superficial colonic mucosa, whereas the density of substance P receptors was highest over the smooth muscle layers. These findings suggest a mismatch between immunochemical content of the peptide and autoradiographic density of the receptor.
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PMID:Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine. 247 37

We have evaluated the interaction of radiation and 1,2-dimethylhydrazine (DMH) with respect to colon carcinogenesis in the Fischer 344 rat and have demonstrated the utility of this model for future more detailed mechanistic studies. In initial experiments, single doses of abdomen-only radiation (9 Gy) or DMH (150 mg/kg) were employed alone or in combination. Radiation was administered 3.5 days prior to the DMH. At 8 months post-treatment, the incidence of DMH-induced colon tumors was doubled by prior radiation exposure. When the protocol was repeated employing a DMH dose of 135 mg/kg with a 6-month observation period, the incidence of tumors induced by DMH alone was reduced, but the combination of radiation plus DMH still resulted in an augmentation of tumor incidence. When the protocol of radiation plus DMH was repeated three times at monthly intervals, a 15-fold increase in tumor incidence (from 5 to 74%) was observed at 6 months post-treatment. This finding demonstrates an apparent synergy between the radiation and the chemical carcinogen. Throughout these studies, the appearance of carcinomas was associated with preexisting colonic lymphoid nodules. The reproducibility of tumor induction as well as range of tumor incidence generated by variations in this system may be adequately sensitive to examine the combination of much lower doses of radiation and/or chemical carcinogen. The relationship between existing lymphoid aggregates which alter local epithelial cell kinetics and which are associated with fenestrations in the basement membrane, and the development of colon cancer in congruent sites may assist in defining dose-response curves for combined agents as well as providing a system for evaluating the mechanisms underlying their interactions.
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PMID:Apparent synergism between radiation and the carcinogen 1,2-dimethylhydrazine in the induction of colonic tumors in rats. 292 75

Monoclonal antibody F30 was produced by the fusion of murine myeloma cell line P3-X63-Ag8-653 with spleen cells from a BALB/C mouse immunized with established human pancreatic cancer cell line (PK-1) and the reaction specificity was analyzed. The antigen recognized by monoclonal antibody F30 was different from HLA-associated antigen, beta 2-microglobulin, fetal bovine serum components, ferritin, AFP, or CEA. Monoclonal antibody F30 reacted with all of six pancreatic cancer cell lines established in our laboratory. Cross-reactivity was detected with a colon cancer cell line or an esophagus cancer cell line among various tumor cell lines tested. No reaction was detected with red blood cells, lymphocytes, or lymphoid and myeloid cell lines. By immunoperoxidase staining of frozen sections, the F30-defined antigen was detected not only on pancreatic cancer cell membrane but also on other adenocarcinomas. In addition, the monoclonal antibody F30 had a more wide-spread distribution on normal epithelial cells in the gastrointestinal organs, respiratory system, and urinary system. F30-defined antigen was composed of two protein components with molecular weight of 190 and 160 K. It was indicated that the antigen was an integral protein in the cell membrane since the antigen was not detected in the spent culture medium of antigen-positive cells.
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PMID:Human pancreatic cancer associated antigen detected by monoclonal antibody. 351 31

Spontaneous cell-mediated cytotoxicity (SCMC) and the marker of natural killer (NK) cells mediating SCMC of the human large intestine were studied. Lamina proprial lymphoid cells (LPL) were isolated by sequential dithiothreitol-EDTA-collagenase treatment of the gut specimen. SCMC was measured by the chromium release method. Target cells included P4788 in monolayer, a cell line derived from colon cancer, Chang cells in monolayer, and K562 in suspension. Target cells in monolayer including colon cancer cell line were chosen because they were thought to be more appropriate to assess SCMC for lymphoid cells in the solid organ. While lower compared to cytotoxicities (CT) by peripheral blood lymphoid cells (PBL), define CT were observed in LPL against all three targets. NK cells marker was studied both on LPL by an indirect fluorescent antibody method and on the gut tissue by indirect immunoperoxidase staining using anti HNK-1 monoclonal antibody which defines virtually all NK cells. HNK-1 positive (HNK-1 +) cells were identified in both methods. HNK-1 + cells were observed in the epithelium, lamina propria, and lymph follicle with or without germinal centers. These results clearly demonstrated the presence of SCMC and HNK-1 + cells in the human large bowel.
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PMID:Definite spontaneous cell-mediated cytotoxicity and HNK-1 cells in the human large intestine. 355 47

The histopathology of 304 patients registered in the Canadian Familial Polyposis Registry (CFPR) with a diagnosis of supposed adenomatous polyposis (AP) was reviewed. The diagnosis was changed in 17 (5.6 percent) of these patients. Group 1 consisted of nine patients who had adenocarcinomas plus multiple tubular adenomas (seven) or metaplastic polyps (two). Eight patients who had no colon cancer comprised Group 2. In these patients, the diagnosis was changed to lymphoid polyposis (2), metaplastic polyps (3), isolated adenomas (2), or juvenile polyposis (1). All 17 patients had had previous colonic resections. Following the change in diagnosis, this treatment was considered inappropriate in 11 patients. Treatment, prognosis, and follow-up of patients and affected family members depend on the type of polyposis syndrome diagnosed. Correct histologic assessment of polyps prior to initial surgery is essential.
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PMID:Surgery based on misdiagnosis of adenomatous polyposis. The Canadian Polyposis Registry experience. 362 61

p6e monoclonal antibody HNK-1 reacts exclusively with human granular lymphocytes that comprise 16 +/- 1.4% of blood mononuclear cells. In normal individuals, almost all natural killer (NK) and killer (K) cell function resides in this lymphocyte subset. The level of HNK-1+ granular lymphocytes, their stage of differentiation, and NK cell function were examined in 70 colon cancer patients and the results compared with data for 114 age-matched normal individuals. Median levels of granular lymphocytes were significantly depressed in colon cancer patients compared to controls (9% versus 16.5%, P less than 0.0001). Despite the depressed numbers of circulating HNK-1+ cells, NK cell function in the colon cancer patients was essentially the same as in normals (P = 0.78). The HNK-1+ lymphocyte level correlated exactly with NK cell function in about two thirds of normal individuals but only one third of colon cancer patients (P = 0.025). Three possible mechanisms for this dichotomy were examined. First, lymphoid cell subpopulations purified with a fluorescence-activated cell sorter (FACS) were examined for altered NK cell functional activity. HNK-1+ cells from the colon cancer patients exhibited significantly less NK functional activity compared to normals (796 versus 1046 lytic units, P = 0.04). Interestingly, the HNK-1- fraction (predominantly T lymphocytes) had increased NK cell functional activity in the colon cancer patients compared to normals (373 versus 218 lytic units, P = 0.0001). Purified monocytes did not contribute to NK cell functional activity. Second, the functional maturity of the HNK-1+ lymphocytes was correlated with NK activity. Two subsets of HNK-1+ cells were identified by surface membrane markers and purified with the FACS. The more mature HNK-1+ subset (i.e., HNK+Leu-4-M1+) exhibited almost ten times more NK cell functional activity than did the less mature cell fraction (i.e., HNK+Leu-4+M1-) cells in normal individuals (2230 versus 286 lytic units/10(7) cells). Further analysis demonstrated that the ratio of mature to immature HNK+ cells in normal individuals was 3:1, while it was decreased to a 1:1 ratio in colon cancer patients P = 0.005). Third, the influence of prostaglandin-mediated suppression on NK cell activity was examined. PGE2 did not appear to influence NK cell function, since NK cell function was unchanged in vitro in the presence of a prostaglandin synthesis inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heterogeneity of natural killer lymphocyte abnormalities in colon cancer patients. 658 46

The histogenesis of large intestinal carcinomas was studied by use of a low dose (2 mg/kg/wk) of azoxymethane [(AOM) CAS: 25843-45-2] administered im to inbred F344 rats. No evidence of benign polyp was seen, and the carcinomas in this model did arise directly from the flat mucosa. In marked contrast to the standard dose (8 mg/kg/wk) studies, low-dose AOM carcinogenesis yielded the following unusual features: a) There was a very high incidence of readily metastasizing mucinous adenocarcinomas that were extremely aggressive and easily transplantable; b) the carcinomas, microscopic and macroscopic, were localized predominantly in the proximal large intestine; c) foci of atypical early neoplastic (or so-called dysplastic) crypts as well as early carcinomas were frequently associated with the lymphoid aggregates in the intestinal wall; d) Paneth cells were commonly seen to be associated with these atypical crypts and/or early carcinomas associated with the lymphoid aggregates; and e) there was a virtual lack of the dilated, distorted, or hyperdistended crypts in noncarcinomatous epithelia. The significance of the lack of dilated, distorted, hyperdistended crypts and the similarity of this finding with the findings in the low incidence of colon cancer in the Japanese population are discussed.
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PMID:Large intestinal carcinogenesis. II. Histogenesis and unusual features of low-dose azoxymethane-induced carcinomas in F344 rats. 659 40

Alterations of the human MSH2 gene, a homologue of the bacterial MutS mismatch repair gene, co-segregate with the majority of hereditary non-polyposis colon cancer (HNPCC) cases. We have generated homozygous MSH2-/- mice. Surprisingly, these mice were found to be viable, produced offspring in a mendelian ratio and bred through at least two generations. Starting at two months of age homozygous-/- mice began, with high frequency, to develop lymphoid tumours that contained microsatellite instabilities. These data establish a direct link between MSH2 deficiency and the pathogenesis of cancer. These mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti-cancer agents.
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PMID:MSH2 deficient mice are viable and susceptible to lymphoid tumours. 755 Mar 17

The effects of specific dietary interventions on incidence of carcinogen-induced cancer and on cryptal cell proliferation in areas of the colon located either over aggregates of lymphoid nodules (ALN) or away from ALN was investigated. Groups of dimethylhydrazine (DMH) treated rats or non-DMH-treated rats were fed a basal AIN-76 diet less fiber of any type, or the basal fiber free diet supplemented with 10% pectin and with 5%, 10%, or 20% corn oil. The adenocarcinoma (AC) incidence was determined in regions of the colon, i.e. ascending, descending, descending over the ALN and descending away from the ALN. The results indicate that: (i) factors associated with ALN promote AC formation, (ii) dietary modifications (addition of pectin and of 20% corn oil to the diet) each cause significant site specific suppression of AC incidence, (iii) DMH-treatment rendered crypts non-responsive to the suppression of cryptal cell proliferation which occurred in the rats not treated with DMH (suggestive of a DMH-induced loss in the regulation of cell proliferation) and (iv) reduction of AC incidence was not always accompanied by reduction in crypt cell proliferation. Studies of intervention procedures designed to prevent colon cancer should take into account the colon site specific tumorigenic response to the preventive agent and should not rely on a single biomarker to predict the efficacy of the intervention.
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PMID:Site specific reduction of colon cancer incidence, without a concomitant reduction in cryptal cell proliferation, in 1,2-dimethylhydrazine treated rats by diets containing 10% pectin with 5% or 20% corn oil. 778 64

The presence of lymphoid aggregates within the muscularis propria or pericolic fibroadipose tissue apposing invasive colorectal carcinoma, termed the Crohn's-like lymphoid reaction, has been related to improved patient length of survival according to univariate statistical analysis. We tested the Crohn's-like lymphoid reaction as an indicator of prognosis in a multivariate statistical analysis of 344 resected right-sided colonic cancers. Improved 5-year survival in univariate analysis was associated with low tumor grade, regular tubule configuration, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of tumoral invasion of extramural veins, all levels of intramural and extramural invasion short of widespread local tumor permeation, conspicuous Crohn's-like lymphoid reaction, and absence of both nodal metastasis and nodal-independent tumor nodules in pericolic fat. By the Cox proportional hazard model using the stepwise method, depth of tumor invasion, lymph node metastasis, Crohn's-like lymphoid reaction, and metastatic tumor nodules in pericolic fat retained independent prognostic significance. Combining the four variables to formulate pathological prognostic categories yielded a highly favorable prognostic group-92% 5-year survival and 95% confidence limits (88% to 96%)--encompassing 53% of the study population. It included all Dukes' stage A carcinomas, 66% of Dukes' stage B adenocarcinomas, and 11% of Dukes' stage C cancers. Lymph node metastases coupled with intramural and extramural extent of tumor invasion are the cornerstones of colorectal cancer staging. Addition of other variables improves prognostication for the cecum and ascending colon. From this study the Crohn's-like lymphoid reaction and metastatic tumor nodules in pericolic fat emerge as significant independent indicators of prognosis for right-sided colon cancer. Complex correlations of both indicators with nonselected variables were observed.
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PMID:Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: results of multivariate analysis. 782 14


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