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

The human colon cancer cell lines HCT 116 (poorly differentiated) and GEO (well differentiated) express the mitogenic peptide transforming growth factor alpha (TGF-alpha). The secretion of TGF-alpha was enhanced by phorbol 12-myristate 13-acetate (PMA), indicating the possible role of protein kinase C (PKC) in the formation of mature TGF-alpha. Cells were metabolically labeled with 35S-cysteine and the formation of the mature 6 kDa TGF-alpha polypeptide from the 17 kDa pro-TGF-alpha precursor was determined. The conversion of pro-TGF-alpha was complete in 2-4 hr with the HCT 116 cells showing faster kinetics of TGF-alpha formation than GEO cells. HCT 116 cells secreted more TGF-alpha than GEO cells and the rate and extent of formation of TGF-alpha was enhanced by PMA in both cell lines. The expression of several PKC isozymes by HCT 116 and GEO cells was examined by immunoblotting. The expression of all isozymes examined was higher in HCT 116 cells compared with GEO cells. Calphostin C, an inhibitor of PKC, reduced the enzyme activity and significantly inhibited the PMA-induced secretion of TGF-alpha by both cell lines. Two agonists of PKC that act on specific PKC isozymes, thymeleatoxin and 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), stimulated the release of TGF-alpha into the medium to the same extent as PMA. Since dPPA has been reported to stimulate PKC-beta 1 specifically, our results suggest a potential role for PKC-beta in the processing of pro-TGF-alpha by these 2 human colon carcinoma cell lines.
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PMID:Pro-transforming growth factor-alpha processing in human colon carcinoma cells: role of protein kinase C. 763 77

Cell cultures can be used to study ion transport processes. X-ray microanalysis of cell cultures at the cellular level gives interesting information that can complement electrophysiological and tracer studies. In this paper, methods for culturing and preparing a variety of epithelial and secretory cells (fibroblasts, insulinoma cells, bovine mammary epithelial cells, colon cancer cells) for X-ray microanalysis are presented. Results show that sometimes cell cultures are not homogeneous with respect to ion content or reaction to physiological stimuli. In colon cancer cell cultures, a "high K" and a "low K" cell subpopulation was found; these subpopulations also differed with respect to other elements. As examples of biological applications, chloride efflux was studied in fibroblasts and colon cancer cells, and strontium uptake in insulinoma cells. Chloride efflux from colon cancer cells is stimulated by cyclic AMP and vaso-active intestinal peptide (VIP), and can be inhibited by pretreatment of the cells with phorbol myristate acetate, which downregulates the cAMP-regulated chloride efflux mechanism.
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PMID:X-ray microanalysis of epithelial and secretory cells in culture. 768 4

Using a retroviral vector system we have established derivatives of the E8 subclone of the human colon cancer cell line SW480 that stably overproduce a full-length rat cDNA encoding the beta 1 isoform of protein kinase C (PKC beta 1). In contrast to vectrol control cells, when treated with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), the overexpressing cell lines displayed a striking increase in doubling time, and a decrease in saturation density. Western blot analysis indicated that treatment with TPA was also associated with translocation and partial downregulation of the exogenous PKC beta 1 in the over-expressor cell lines. These results extend previous evidence that PKC beta 1 can inhibit the growth of the HT29 human colon cancer cell line. The HT29 cells have a normal c-k-ras oncogene but the SW480 cells used in the present study have an activating mutation in this oncogene. Thus PKC beta 1 can function as a suppressor in both types of colon cancer cells.
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PMID:Overexpression of protein kinase C beta 1 in the SW480 colon cancer cell line causes growth suppression. 776 74

Treatment of nontransformed rat intestinal crypt epithelial IEC-6 cells with tetradecanoyl phorbol acetate (TPA) + calcium ionophore (A23187) induces both the synthesis of prostacyclin and the expression of the TIS10/PGS-2 gene, a primary response gene encoding a second form of prostaglandin synthase (PGS). In addition to pharmacological induction by TPA + A23187, TIS10/PGS-2 message is also induced by the inflammatory cytokine interleukin 1-beta (IL-1 beta). Transforming growth factor beta 1 (TGF-beta), a potent cytokine known to modulate a variety of biological responses, does not by itself induce either prostanoid accumulation or TIS10/PGS-2 gene expression. TGF-beta does, however, augment both induced prostacyclin accumulation and the induced synthesis and accumulation of TIS10/PGS-2 protein and message in IEC-6 cells. TGF-beta concentrations in the range of 0.1-1.0 ng/ml (4.0-40 pM) maximally augment accumulation of TIS10/PGS-2 message. In contrast, dexamethasone attenuates prostacyclin production, TIS10/PGS-2 protein accumulation, and TIS10/PGS-2 message induction in IEC-6 cells. These results suggest that steroids and cytokines such as TGF-beta may (i) modulate intestinal epithelial cell growth and differentiation and (ii) influence gastrointestinal diseases such as gastric ulcers and colon cancer by modulating eicosanoid production.
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PMID:TGF-beta 1 augments expression of the TIS10/prostaglandin synthase-2 gene in intestinal epithelial cells. 778 83

The levels of a nonspecific steroidal esterase estimated as alpha naphthyl acetate esterase (ANAE) activity were measured in apparently normal (peritumoral) tissue of liver, colon and breast cancer patients, in malignant tumor tissue from the same patients and in normal colon tissue from healthy individuals who never had colon cancer. Cancer tissue from all three organs showed 35-79% reduced levels of ANAE activity when compared to peritumoral tissue of the same organ (p < 0.03). When ANAE activity of normal colon tissue from healthy individuals who never had colon cancer was compared with peritumoral colon tissue from colon cancer patients, which were combined with colonic biopsies from cancer-free patients previously operated on for colon cancer, a 50% reduced ANAE activity was observed in these tissues compared to the normal (p < 0.005). A highly significant reduction of enzyme activity was also found when malignant colon tissue from the cancer patients was compared to normal colon tissue from healthy individuals who never had colon cancer.
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PMID:Reduced nonspecific steroidal esterase activity in human malignant tumor tissue from liver, colon and breast when compared to peritumoral and normal tissue levels. 787 12

The purpose of this study was to investigate the effects of 2.45 GHz microwave (MW) radiation on dimethylhydrazine (DMH)-induced colon cancer in mice. The subjects were 115 Balb/c mice 4 weeks of age. The animals were divided into group A (control), group B (DMH), group C (DMH+MW), and group D [DMH + 12-O-tetradecanoylphorbol-13- acetate (TPA)]. Radiation (10 mW/cm2) was delivered dorsally with the E field parallel to the mouse's long body axis in an anechoic chamber. Radiations were administered 3 hr daily, 6 days per week, over a period of 5 months. The average SAR was estimated to be 10-12 W/kg. During the course of radiation treatments, DMH was injected once per week. The tumor promoter TPA was administered once per week for 10 weeks, from the third week on, after the initial treatment. The incidence of tumors did not significantly differ between the three test groups (groups B, C, and D; P > 0.25). However, the number of tumors, the size of the tumors, and the incidence of protuberant and infiltrative types in tumor-bearing animals were higher in group D compared to groups B and C (P < 0.05). No difference was found between groups B and C (P > 0.25). The study indicates that 2.45 GHz microwave radiation at 10 mW/cm2 power density did not promote DMH-induced colon cancers in young mice. The study also showed that TPA could accelerate colon tumor production if a tumor was initiated.
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PMID:Effects of 2.45-GHz microwave radiation and phorbol ester 12-O-tetradecanoylphorbol-13-acetate on dimethylhydrazine-induced colon cancer in mice. 788 Jan 66

This paper describes standard mortality and nested case-control analyses of colorectal cancer for a cohort of synthetic textiles workers in which a cluster of five cases was observed previously. The cohort consisted of 7,487 men and 2,724 women who had more than 1 year's experience at the plant and who were either working in 1947 or were newly employed between 1947 and 1977. The Standardized Mortality Ratio (SMR) for colorectal cancer for men was 0.69 (95% confidence interval (CI): 0.52-0.92; 50 deaths) and for women it was 1.02 (95% CI: 0.57-1.69; 15 deaths). Among men only there was a suggestion that risks increased according to the length of service at the plant. In the nested case-control study, incident cases as well as deceased cases were included. A variety of analyses were carried out according to duration of employment in the processing units. For men the risk of colon cancer increased with duration of employment in the polypropylene and cellulose triacetate extrusion unit (unadjusted odds ratio (OR) for > or = 5 years duration = 5.52; 95% CI: 1.12-27.26; 4 exposed cases). It was not possible, however, to provide an independent confirmation of this putative association because the case series included three of the original five cases. There was some evidence of increased risks in the cellulose acetate fiber manufacturing unit and in the dyeing and finishing unit, but the data were compatible with the null hypothesis of no effect. No associations were observed for employment in any of the other processing units.
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PMID:Retrospective cohort study of workers of a synthetic textiles plant in Quebec: II. Colorectal cancer mortality and incidence. 806 66

The effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the growth characteristics of the colon cancer cell line HT-29 M6 were studied. TPA induced the scattering of proliferative HT-29 M6 cells: in the presence of the phorbol ester, HT-29 M6 colonies scattered and the cells acquired a flatter aspect with diminished cell-cell contacts. This effect of TPA required a persistent activation of PK-C and was accompanied by a slight decrease (30%) in the growth rate. Modifications by TPA of two scattering associated properties of these cells were also detected: TPA decreased cell-to-cell aggregation and enhanced the cellular attachment to matrix substrata (collagen, laminin). The decrease in cell-to-cell adhesion was correlated with a loss of cellular E-cadherin as evidenced by immunofluorescence or immunoblotting with a specific monoclonal antibody. Cell scattering was dependent on the extracellular concentration of Ca2+; an increase from 1.6 to 10 mM in the concentration of this ion completely blocked the morphological effects of TPA as well as its action on cell aggregation. This high concentration of Ca2+ also prevented the down modulation of E-cadherin as determined by immunofluorescence. However, the TPA-induced increase in cell attachment to the matrix was not affected by high calcium. These findings support the importance of altered cell-cell adhesion in the process of scattering and provide a good system for the study of down modulation of E-cadherin, a protein involved in the control of cell growth, differentiation and invasion of epithelial cells.
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PMID:Phorbol ester-induced scattering of HT-29 human intestinal cancer cells is associated with down-modulation of E-cadherin. 828 58

One of the extension proteins on the carboxy terminus of ubiquitin was reported as the ribosomal protein S27a. We have cloned a gene which encodes this ubiquitin hybrid protein from a complementary DNA library of a human colon carcinoma cell line. Northern blot analysis of surgical specimens from colon cancer patients showed that these messenger RNA levels were higher in tumor tissue than in adjacent normal mucosa. Furthermore, to investigate the role of this novel ubiquitin hybrid gene in cellular growth control, the responsiveness of this gene to serum growth factors was examined. Within 30 min after serum or 12-O-tetradecanoylphorbol-13-acetate stimulation, its messenger RNA expression in rat fibroblast cells (Rat 1) was increased. Nuclear runoff transcription studies showed that the kinetics of induction of this gene is almost identical to that of protooncogene c-jun or c-fos, the known early growth response genes. Thus, this ubiquitin hybrid gene appears to be a novel early growth response gene overexpressed in human colon cancer and warrants further studies in the pathogenesis of colorectal carcinoma.
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PMID:Ubiquitin-ribosomal protein S27a gene overexpressed in human colorectal carcinoma is an early growth response gene. 838 74

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


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