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

Reactive oxygen metabolites (ROM) have been postulated to contribute to the development of various carcinomas, including colon cancer. Indeed, the effects of ROM scavengers are being tested for chemoprevention of adenocarcinoma of the colon. However, there has been no evidence to indicate that high levels of ROM are indeed present in cancerous tissue. In this study, we used a chemiluminescence probe to estimate ROM levels in cancerous and neighboring noncancerous colonic tissues from seven patients with colon cancer. Cancerous tissues contained significantly (p less than 0.05) more luminol-enhanced chemiluminescence (4,808 +/- 2,282 counts/min/mg protein) than neighboring noncancerous tissues (2,175 +/- 1,111). The addition of an ROM scavenger, catalase (2, 4, and 8 micrograms/ml), to the tissue suspension inhibited chemiluminescence produced by both noncancerous (-74%, -85%, and -71%) and cancerous (-11%, -61%, and -53%) tissues. This study shows that colonic cancerous tissue contains high levels of ROM, which may play an important role in the pathogenesis of colon cancer.
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PMID:High levels of reactive oxygen metabolites in colon cancer tissue: analysis by chemiluminescence probe. 133 90

Ras regulates novel patterns of gene expression and the differentiation of various eukaryotic cell types. Stable transfection of Ha-ras into the human colon cancer line CaCo2 results in the morphologic differentiation to a small bowel phenotype. The purpose of our study was to determine whether the Ras regulatory pathway plays a role in the expression of the neurotensin gene (NT/N), a terminally differentiated endocrine product specifically localized in the gastrointestinal tract to the adult small bowel. We found that CaCo2-ras cells, but not parental CaCo2, express high levels of the human NT/N gene and, moreover, that this increase in gene expression is regulated at the level of transcription. Transfection experiments using NT/N-CAT mutation constructs identify the proximal 200 bp of NT/N flanking sequence as sufficient for maximal Ras-mediated NT/N reporter gene induction. Furthermore, a proximal AP-1/CRE motif is crucial for this Ras-mediated NT/N activation. Wild-type Ha-ras induces NT/N gene expression, albeit at lower levels than activated Ras; a dominant-negative Raf blocks this NT/N induction, suggesting that Raf lies down-stream of Ras in this pathway. In addition, postconfluent cultures of CaCo2 cells, which are differentiated to a small bowel phenotype, express the NT/N gene by 6 d after reaching confluency; this increase of NT/N expression is associated with concomitant increases of cellular p21ras protein. We conclude that Ras (both wild-type and activated) enhances expression of the NT/N gene in the gut-derived CaCo2 cell line, suggesting an important role for the Ras signaling pathway in NT/N gene transcription. Our results underscore the possibility that tissue-specific genes (such as NT/N) expressed in distinct subpopulations of the gut may be subject to Ras regulation. Finally, we speculate that the NT/N gene and the CaCo2 and CaCo2-ras cell systems will provide unique models to further define the cellular mechanisms leading to mammalian intestinal differentiation.
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PMID:The neurotensin gene is a downstream target for Ras activation. 776 22

A human colon cancer-derived cell line, KC-1, was established from the surgical specimen of mucinous adenocarcinoma of the colon. The cells grew as monolayers, showing formation of irregular aggregation of cells and pleomorphic nuclei. The doubling time in vitro was 56.6 hours. The cells produced CEA, CA19-9 and sialyl SSEA-1(SLX). Chromosome numbers were distributed between 79 and 83 with many structural abnormalities. A point mutation of the Ki-ras gene in codon 61 (CAA-->CAT) was found. The cells have been subcultured 13 times during these three years. This cell line can be useful for investigations of colon cancer.
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PMID:[Establishment of a human colon cancer-derived cell line (KC-1) which produces CEA, CA 19-9 and sialyl SSEA-1(SLX)]. 787 2

Loss of HLA antigen expression is considered to be one of the mechanisms whereby tumor cells escape immune surveillance. We recently observed reduced or lost expression of HLA antigens during human colon carcinogenesis. We studied the effect of bile acids (BAs), long implicated in the pathogenesis of colon cancer, on the expression of HLA class I antigens in human colon adenocarcinoma cells. Lithocholic acid (LCA) decreased by 42% the expression of HLA class I antigens on the surface of these cells. This dose-dependent reduction was specific for both the target genes and the chemical structure of LCA, and was not evident in cultured liver cells. None of the other BAs that were tested manifested this effect. LCA, and to a lesser extent deoxycholic acid (DCA), decreased steady-state HLA class I mRNA levels. LCA decreased the rate of transcription of HLA-B (64%) and HLA-C (87%) but not HLA-A; DCA had a similar but less pronounced effect. In transient gene expression (CAT assays) experiments, we evaluated the role of a 0.6-0.7 kb EcoRI/XbaI sequence from the 5' flanking region of HLA-A2, -B7 and -Cw7 genes in the regulation of class I gene expression by LCA. LCA down-regulated by 70% the expression of the reporter gene for all three genes. We interpret these results as indicating a differential regulation of the three HLA loci by LCA. Our findings, demonstrating a profound effect of LCA on HLA class I gene regulation, raise the possibility that such a mechanism may be operative in vivo.
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PMID:Lithocholic acid inhibits the expression of HLA class I genes in colon adenocarcinoma cells. Differential effect on HLA-A, -B and -C loci. 819 71

We studied the role of reactive oxygen intermediates (ROIs) in experimental liver metastasis induced in mice by the inoculation of COLON 26-M5 murine colon cancer cells, a highly metastatic variant of COLON 26 cells, and the effect of ROIs on the invasive capacity of the cells in an in vitro chemo-invasion assay model using reconstituted basement membrane matrigel. We also measured the release of ROIs from cells using electron spin resonance (ESR) spectrometry. Hydroxyl radicals (.OH) were constitutively released from the cells. This release was augmented by pre-treatment with phorbol 12-myristate 13-acetate (PMA). In experimental liver metastasis in CDF1 mice, the administration of recombinant human superoxide dismutase (r-hSOD) significantly increased the number of metastatic nodules, while administration of catalase significantly inhibited metastasis formation. In vitro pre-treatment of cells with PMA significantly increased the number of metastatic nodules. Invasive capacity of the cells was markedly augmented by pre-treatment with PMA. PMA-induced augmentation was significantly inhibited by the simultaneous addition of r-hSOD to the assay. Catalase had no significant effect. Our findings suggest that ROIs play an important role in tumor invasion and metastasis, and that hydrogen peroxide (H2O2) may contribute to the retention or extravasation of circulating tumor cells. Furthermore, the superoxide anion (O2-) released by tumor cells may play an important role in basement membrane degradation.
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PMID:Effect of reactive oxygen intermediates on the in vitro invasive capacity of tumor cells and liver metastasis in mice. 839 85

The promoter activity of the upstream region of the rat small intestinal lactase-phlorizin hydrolase gene has been analysed by transfection in the human colon cancer cell line Caco-2. A 0.9 kb mRNA, corresponding to the CAT reporter gene, was synthesized from the transcription start site of the LPH gene. The rate of expression, determined by semi-quantitative RT-PCR, was very low, and depended on the length of the promoter fragment in front of the reporter gene. By immunocytology, we found that the low level of expression resulted from the low number of cells (about 1%) in which CAT was produced. The endogenous lactase was present in 10-20% of the cells in culture, and evidence is provided that most cells that expressed CAT did not co-express the endogenous lactase. We conclude from this study that the rat small intestinal LPH gene promoter is active in the human Caco-2 colon cancer cells. Hence Caco-2 cells constitute an in vitro model to analyse the basic molecular mechanisms involved in the gene transcription of intestinal digestive enzymes. Yet, the mosaic expression of the endogenous lactase and of the reporter gene under the control of the rat LPH gene promoter, suggests that Caco-2 cells may present specific regulatory mechanisms of expression of small intestinal enzymes, possibly in relation to their tumourous origin.
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PMID:Activity of the rat lactase gene promoter in transfected human colon cancer cells. 857 90

We have previously shown that p53 disruption sensitizes certain cancer cell types to cisplatin (CDDP) (Fan et al., 1995). In the present study we investigated the role of the p53 downstream effector, p21CIP1/WAF1 (p21), in this sensitization. Studies were performed in human colon cancer HCT-116 cells and murine embryonic fibroblasts (MEF) with intact versus disrupted p21 genes. For comparison, HCT-116 cells lacking p53 function were also prepared through stable transfection with the human papillomavirus type-16 E6 gene. HCT-116/E6 cells were found to be more sensitive than control transfectants to CDDP and another DNA crosslinking agent, nitrogen mustard (HN2). HCT-116 cells with disrupted p21 genes also exhibited greater CDDP and HN2-sensitivity than parental HCT-116 cells. In contrast, the clonogenic survival of HCT-116 cells exposed to ionizing radiation, adriamycin, taxol or vincristine was not affected by p53 or p21 disruption. Sensitization of HCT-116/p21-/- cells to CDDP and HN2 was not limited to the HCT-116 cell background since MEF from p21 knockout mice were also more sensitive to these DNA crosslinking agents. Investigations into a possible cause of this enhanced sensitivity revealed that HCT-116 cells lacking p53 or p21 function exhibited a reduced ability to repair cisplatin-damaged CAT-reporter plasmids transfected into the cells. In addition, we found that HCT-116/p21-/- cells were much more susceptible to HN2-induced cell cycle delay than parental cells. Our results suggest that p21 disruption preferentially sensitizes at least some cell types to DNA crosslinking agents.
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PMID:Cells lacking CIP1/WAF1 genes exhibit preferential sensitivity to cisplatin and nitrogen mustard. 917 48

The urokinase-type plasminogen activator receptor (u-PAR) facilitates extracellular matrix degradation in part by accelerating plasmin formation at the cell surface. We previously reported that u-PAR expression is elevated in colon cancer cell lines characterized by their in vitro invasive capacity. Since, u-PAR expression is increased by a variety of growth factors, which signal through the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2), we determined if these mitogen-activated protein kinases (MAPKs) regulate u-PAR expression in two cultured colon cancer cell lines. An in-gel kinase assay showed that ERK1 activity was considerably higher in RKO cells, which display > or = 10(5) receptors/cell, than the GEO cells which have approximately 10(4) urokinase receptors per cell. The expression of either an ERK-inactivating phosphatase (CL100), or a kinase-defective ERK1, decreased the activity of a u-PAR promoter-driven CAT reporter in RKO cells. Immune complex kinase assays indicated that the constitutive ERK1 activity in RKO cells was largely a result of an activated MEK1. Further, treatment of RKO cells with a specific inhibitor (PD 098059) of MEK1 activation, which diminished ERK1 activity, reduced the amount of urokinase specifically bound to the cell surface and this was associated with reduced laminin degradation. The expression of a dominant negative c-Raf-1 also reduced u-PAR promoter activity suggesting that MEK1 activation involved an activator at, or upstream, of this serine-threonine kinase. Transfection of the u-PAR-deficient GEO cells with a constitutively activated MEK1 expression construct up-regulated u-PAR promoter activity. Similarly treatment of GEO cells with a phosphatase inhibitor (sodium vanadate) caused a dose-dependent increase in ERK1 activity which paralleled increased cell surface binding of urokinase. Taken together, these data suggest that elevated u-PAR expression, in at least a sub-population of colon cancer, is partly a consequence of a constitutively activated ERK-1-dependent signaling cascade.
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PMID:Elevated urokinase-type plasminogen activator receptor expression in a colon cancer cell line is due to a constitutively activated extracellular signal-regulated kinase-1-dependent signaling cascade. 919 Oct 56

Catalase (CAT) is an enzyme that is involved in antioxidant defense, cell growth, and is possibly associated with tumoral processes. In this paper, the results of experiments designed to determine the influence of metallic carcinogens such as nickel (Ni), lead (Pb), mercury (Hg), and cadmium (Cd), on CAT activity are reported. CAT activity was measured in erythrocytes from three groups: a group of colon cancer patients, a group of gastric cancer patients before clinical treatment, and a control group of healthy blood donors. Concentrations of this enzyme are significantly higher than controls in the colon cancer group, but lower in gastric neoplasia. By generating highly reactive oxygenated species, Ni, Pb, Hg, and Cd alter catalase activity. Solutions of Ni, Cd, and Pb at 0.2 mM concentrations inhibit CAT activity in colon cancer, but increase it in gastric neoplasia. Hg activates CAT in colon cancer, and causes a slightly increased activity in gastric cancer. No complete deactivation of the enzyme was observed.
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PMID:Catalase activity in erythrocytes from colon and gastric cancer patients. Influence of nickel, lead, mercury, and cadmium. 925 71

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3-fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)-epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.
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PMID:Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. 960 Mar 45


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