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

Colon carcinoma cells are first found as microscopic foci within benign tumors or adenomas. The carcinoma must invade the adenoma which protrudes into the colon lumen before it can infiltrate the bowel wall. A quantitative model for this process has been developed in tissue culture in which human colon carcinoma cells destroy cocultivated adenoma colonies. 43 adenoma colonies were assayed by cocultivation with carcinoma cells. Constitutive secretion of the urokinase form of plasminogen activator by carcinoma cells apparently plays some role in adenoma destruction as inhibition of this protease by the competitive inhibitor benzamidine reversibly inhibited adenoma destruction (p less than 0.01). Elevation of plasminogen activator secretion by addition of the tumor promoter 12-tetradecanoylphorbol-13-acetate significantly enhanced the destruction of colonies cultured from tubular adenomas with only mild dysplasia (p less than 0.025) and from villous, villotubular and tubular adenomas with moderate to severe dysplasia (p less than 0.0005).
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PMID:Tumor-promoter-enhanced destruction of noninvasive human benign colon tumor cells by cocultivated carcinoma cells. 323 26

Cellular cytotoxicity of peripheral blood cells was studied in patients with Crohn's disease or ulcerative colitis and healthy controls. The spontaneous cytotoxicity or natural killer (NK) cell activity, evaluated against the erythroleukemia K-562 and the colon cancer CaCo-2 and HT-29 cell lines, of total mononuclear cells and enriched lymphocytes was depressed in Crohn's disease and ulcerative colitis patients compared to the controls. Phytohaemagglutinin (PHA) increased the cytotoxicity in the patients, to a similar maximal level as the stimulated controls. In contrast, the phorbol ester, phorbol-myristate-acetate (PMA), enhanced the cytotoxicity in patients and in controls, but in the patients not to the levels of the controls. No cytotoxicity was observed in the monocyte-enriched fraction both in patients and controls using the same assay system. A similar small but significant stimulation of monocyte cytotoxicity was obtained by PHA and PMA in patients and in controls. In conclusion, inflammatory bowel disease is associated with a depressed NK cell activity in peripheral blood which is not target specific. PHA but not PMA could restore the deficient NK cell activity. Monocytes seem not to be involved in the decreased NK cell activity in patients with inflammatory bowel disease.
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PMID:Natural, lectin- and phorbol ester-induced cellular cytotoxicity in Crohn's disease and ulcerative colitis. 324 86

12-O-Tetradecanoylphorbol-13-acetate (TPA), a highly active representative of the tumor-promoting phorbol esters, induces a rapid terminal differentiation of a human colon cancer cell line. Bryostatin 1, a macrocyclic lactone, completely counteracts this effect of TPA and promotes continued replication. The observed responses provide a system for identifying cellular processes which are involved in the induced terminal differentiation of human colon cancer cells.
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PMID:Bryostatin 1 antagonizes the terminal differentiating action of 12-O-tetradecanoylphorbol-13-acetate in a human colon cancer cell. 333 36

There is increasing evidence that the enzyme protein kinase C (PKC) mediates the action of phorbol ester tumor promoters and also the action of certain growth factors. The present studies indicate that the bile acids chenodeoxycholate and deoxycholate inhibit the Ca2+-phosphatidylserine (PS)-dependent activity of PKC in the presence of 1 mM Ca2+, whereas seven structurally related bile acids do not detectably inhibit the enzyme under these conditions. Chenodeoxycholate and deoxycholate appear to inhibit PKC by interactions with both Ca2+ and PS, since their inhibitory potencies are reduced at an elevated PS concentration and since both of these bile acids actually enhance PKC activity, approximately 2-fold, when assayed at an elevated Ca2+ concentration (2 mM). Seven related bile acids also caused an approximately 2-fold enhancement of PKC activity in the presence of 2 mM Ca2+. Chenodeoxycholate and deoxycholate also caused an approximately 1.3-fold enhancement of PKC activity in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) and PS, and the absence of added Ca2+. Thus, depending on the reaction conditions, specific bile acids can act directly to inhibit or enhance PKC activity. There is evidence that during colon cancer formation, both in rodents and in humans, bile acids may act as tumor promoters. Thus the mediation of tumor promotion by bile acids in vivo may involve direct activation of PKC by the bile acids themselves. The present results suggest that the relative extents of absorption of Ca2+ and bile acids by the colonic mucosa may alter the activity of PKC in the mucosa, and thus alter the growth properties of this tissue. The present studies also suggest that lipophilic anionic compounds may provide a new approach to developing therapeutic agents that act by modulating PKC.
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PMID:The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids. 380 3

A vitamin A (retinyl acetate)-deficient diet enhanced liver cancer in rats exposed to aflatoxin B1 (AFB1) and also caused a 29% incidence of colon cancer. The following factors were considered in attempts to define conditions under which vitamin-A-deprived rats were more susceptible to colon cancer induced by AFB1: liver morphology, enterohepatic recirculation, level of reduced glutathione (GSH) in liver, and differing capacities for conjugation of aflatoxin to GSH. Enzyme concentrations in liver, in intestinal and colon mucosa, and in intestinal and colon contents suggested that AFB1 may have different metabolites and that there may be differing susceptibilities of colon mucosa to carcinogenesis. Binding studies supported this hypothesis. Previous studies have shown that colon epithelium from vitamin-A-deficient rats binds more AFB1 than colon epithelium from normal, vitamin-A-supplemented animals. In the present study, vitamin A supplementation to the vitamin-A-deficient rats before oral administration of 3H-AFB1 significantly decreased the binding capacity at 12 and 15 hours after dosing with the carcinogen. These results suggest that the effect of vitamin A on the metabolism of the carcinogen, particularly on binding of AFB1 to cellular macromolecules, may be the mechanism by which vitamin A modifies aflatoxin's carcinogenic potential, influenced in part through enzymatic mechanisms.
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PMID:Vitamin A and aflatoxin: effect on liver and colon cancer. 641 17

Serum tissue polypeptide antigen (TPA) levels were measured in 33 patients with esophageal cancer, 39 with stomach cancer and 50 with colon cancer. At the same time five glycoproteins, namely immunosuppressive acidic glycoprotein (IAP), alpha 1-antichymotripsin (alpha 1-ACT), acid soluble glycoproteins (ASP), sialic acid and carcinoembryonic antigen (CEA), were measured for comparison. The mean TPA values were 59.0 +/- 15.4 U/l in 61 normal subjects, 103.6 +/- 104.2 U/l (positive rate, 24.2%) in esophageal cancer patients, 111.9 +/- 49.8 U/l (71.8%) in stomach cancer patients and 124.8 +/- 195.5 U/l (40%) in colon cancer patients. The serum TPA levels in patients with stomach cancer rose with an increased number of involved lymph nodes and with a higher degree of infiltrative growth and increased with the advancement of tumor growth postoperatively. Serum TPA levels correlated well with those of alpha 1-ACT, IAP and ASP in stomach cancer patients and with those of CEA, ASP and sialic acid in colon cancer, but not in esophageal cancer patients. It is suggested that the serum TPA might represent one of the reactant proteins and/or tumor-associated antigens that appear to be dependent upon the cancer status.
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PMID:[Clinical evaluation of tissue polypeptide antigen in patients with esophageal, stomach and colon cancer]. 648 66

The suitability of carcinogen-induced colon tumors in mice for chemotherapy investigations and the potential antitumoral activity of a new anthracycline, 4'-deoxydoxorubicin (4' deoDX ) were evaluated. The latter was compared with 5-fluorouracil (5-FU) and doxorubicin (DX) either alone or in combination. CF1 mice were given 10 weekly subcutaneous injections of methylazoxymethyl acetate (MAM) and killed between 16 and 39 weeks after delivery of the first carcinogen treatment. The number and size of macroscopic tumors was observed; only 6% of mice showed no tumor development (19 of 327). Statistically significant reduction of tumor size occurred at a tolerated dose of 5-FU given as six intravenous injections (46 mg/kg) (P less than 0.05). With 4' deoDX a significant decrease in tumor number was observed using four weekly injections of 2.7 mg/kg (P less than 0.05) or six weekly injections of 5 mg/kg (P less than 0.05). Given in combination, 4' deoDX (3.3 mg/kg) and 5-FU (23 mg/kg) demonstrated a statistically significant reduction of the tumor number as compared with the untreated controls (P less than 0.025). Moreover, this reduction was greater than the observed response with any dose levels of the single compound thus demonstrating a potentiation of activity. These results indicate that MAM-induced colonic tumors are an appropriate model for the assessment of chemotherapeutic drugs. Moreover, 4' deoDX showed antitumoral activity comparable with 5-FU indicating this new anthracycline may be a useful candidate either alone or combined with 5-FU for clinical trials against colon cancer.
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PMID:The antitumoral activity of 4'-deoxydoxorubicin compared to doxorubicin and 5-fluorouracil on methylazoxymethanol acetate-induced colon tumors in CF1 mice. 672 42

We have developed a method for the routine primary culture of human colonic epithelial cells. Cultured cells exhibited characteristic epithelial structures, including a brush border and junctional complexes. Flask-like goblet cells containing mucus were also seen within the epithelial monolayer. [3H]Thymidine labeling indices were used to distinguish between cultured cells from familial polyposis patients, other patients at high risk to develop colon cancer, and low-risk control subjects. 12-O-Tetradecanoylphorbol-13-acetate (TPA) at 10 ng/ml enhanced DNA synthesis an average of 8-fold when assayed by labeling index in colonic epithelial cells from five of six familial polyposis patients. No such stimulation by TPA was seen in cells from 13 high-risk patients without familial polyposis or in cells from five low-risk subjects. Hundreds of benign polyps can be found in the colons of familial polyposis patients. One such benign tubular adenoma exhibited the same enhancement of DNA synthesis by TPA as normal-appearing epithelial cells from a biopsy adjacent to that polyp. Mitogenic response to TPA had been seen earlier in cells from each of four tubular adenomas (Friedman, E. Cancer Res., 41: 4588-4599, 1981). Both familial polyposis epithelial cells and adenoma cells are considered preneoplastic, but they are not identical because their patterns of actin cytoskeletal organization differ. These results imply that familial polyposis epithelial cells are precursors of tubular adenoma cells, and their transition to the more advanced preneoplastic cells of this benign tumor is influenced by endogeneous tumor promoters.
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PMID:12-O-Tetradecanoylphorbol-13-acetate stimulation of DNA synthesis in cultured preneoplastic familial polyposis colonic epithelial cells but not in normal colonic epithelial cells. 674 21

Some lines of colon cancer cells are forced to undergo differentiation by 12-O-tetradecanoylphorbol-13-acetate (TPA). The increases in activities of both protein tyrosine phosphatase (PTP) and protein tyrosine kinase (PTK) have been reported to be associated with the TPA-induced differentiation of HL-60 leukemia cells. In the present study, a 2-fold increase in PTP activity was observed in SW620 human colon cancer cells after 30 min of TPA treatment; a maximal level (4- to 5-fold) was reached at 60 min and continued for more than 6 hr. In addition, two TPA-induced differentiated characteristics, morphological alteration and release of cellular surface proteoglycan, were effectively blocked by PTP inhibitors, such as sodium orthovanadate (50 microM), zinc chloride (100 microM), and iodoacetate (250 microM), but not by the protein serine/threonine phosphatase inhibitor okadaic acid (20 nM). On the other hand, although TPA induced a transient slight increase in PTK activity (1.4-fold) at 60 min, four PTK inhibitors (genistein, herbimycin A, tyrphostin-23 and quercetin) had different effects on the TPA-induced release of cell surface proteoglycan. Genistein (60 microM) potentiated this process, but in contrast, quercetin (45 microM) could partially inhibit the TPA effect. Taken together, these observations suggest that both PTP and PTK activities were increased in SW620 cells in response to TPA; however, the activation of PTP seems to be preferentially required for the TPA-induced differentiation of SW620 human colon cancer cells.
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PMID:Preferential requirement for protein tyrosine phosphatase activity in the 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of human colon cancer cells. 748 37

Short-chain fatty acids (SCFAs: acetate, propionate, n-butyrate) arising in the large bowel during bacterial fermentation of dietary fibre and starch have paradoxical effects on colonic epithelial proliferation. While the three major SCFAs stimulate proliferation of normal crypt cells, n-butyrate and, to a lesser degree, propionate inhibit growth of colon cancer cell lines. At the molecular level, n-butyrate causes histone acetylation, favours differentiation, induces apoptosis and regulates the expression of various oncogenes. To understand the complex effects of SCFAs on carcinogenesis, it is important to study the intermediate stages of the adenoma-carcinoma sequence where a "switch" from stimulation to suppression of cell proliferation must occur.
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PMID:Role of short-chain fatty acids in the prevention of colorectal cancer. 757 95


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