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)

Preliminary in vitro studies suggest that the combination of 5-fluorouracil (FUra) and 3'-azido-3'-deoxythymidine (AZT) is more cytotoxic than either agent alone. Therefore, a biochemical and therapeutic evaluation of this combination was initiated. Quantitation of the cytotoxicity of FUra plus AZT against the growth of HCT-8 cells in vitro revealed that 1 microM FUra (approximately 10% inhibitory concentration) increased the cytotoxicity of AZT and decreased its 50% inhibitory concentration by 60%. Similarly, incubating HCT-8 cells in 5 microM AZT (approximately 10% inhibitory concentration) decreased the 50% inhibitory concentration of FUra by over 50%. Biochemical analysis indicated that AZT did not affect FUra-induced inhibition of thymidylate synthase or [3H]-FUra incorporation into nucleic acids. In contrast, incubation in 5 microM FUra increased the incorporation of [3H]-AZT (5 microM) into the nucleic acid fraction of these cells by 52% (P less than 0.05). Therapeutic evaluation of this combination in athymic (nude) mice bearing HCT-8 xenographs revealed that, while weekly FUra (85 mg/kg) or AZT (600 mg/kg) exerts minimal antineoplastic activity (after 4 courses, treatment/control = 0.81 and 0.70, respectively), their combination, at the same doses, inhibited tumor growth by nearly 70% (P less than 0.01 versus FUra alone). FUra-related host toxicity was not increased by the addition of AZT. Higher doses of FUra alone were not more effective than FUra plus AZT. In vivo, AZT did not affect the incorporation of [3H]-FUra into the nucleic acid fraction of various murine tissues, including HCT-8 xenografts. FUra, however, increased [3H]-AZT incorporation into nucleic acids in a tissue-specific manner. In the presence of FUra, the incorporation of [3H]-AZT in spleen, liver, and gut increased 40, 21, and 4%, respectively, while in HCT-8 xenografts [3H]-AZT incorporation increased more than 2-fold. Analysis of the activities of selected enzymes involved in pyrimidine metabolism suggests that this tissue-specific effect may be related to the pyrimidine salvage capacity of these tissues. These findings are described in light of their potential impact on human colon cancer chemotherapy.
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PMID:5-Fluorouracil enhances azidothymidine cytotoxicity: in vitro, in vivo, and biochemical studies. 235 52

Fibers have been classified broadly as predominantly "soluble" or "insoluble," The soluble fibers have little effect on fecal bulk because they are largely fermented to short-chain fatty acids, so lowering colonic pH, and their influence on cancer risk is in relation to these variables. They are associated with increased fecal bile acid losses. Insoluble fibers are much less fermented and enhance fecal bulk without greatly increasing bile acid losses. Their effect in diluting carcinogens or bile acid promoters relates to their protective role in colon cancer. However, high-fiber foods not only contain combinations of different fiber types but also usually contain starch. Under various conditions, and possibly influenced by fiber, substantial amounts of starch (3-20% of dietary intake) may also enter the colon depending on the nature of the foods eaten. These carbohydrates will contribute to the effective fiber load. In considering the action of fiber in the human gut, fiber type, starch, and other components as well as the nature of foods making up the diet must be assessed. These factors are of importance both in interpreting epidemiological leads and in devising logical trials of fiber in terms of intervention.
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PMID:Starchy foods, type of fiber, and cancer risk. 281 49

Although natural killer cells are thought to play a major role in surveillance against tumor development, no systemic studies on natural killer cells and their activities have been reported in familial polyposis coli in which cancer always develops at an early age. Natural killer activities and natural killer cells were studied in 14 patients with familial polyposis coli. Peripheral blood lymphocytes from familial polyposis coli showed normal cytotoxicities against K562 cells, P4788 cells derived from colon cancer and Chang cells. The number of natural killer cells in peripheral blood lymphocytes identified by an immunofluorescence antibody method and that in gut tissue by immunoperoxidase staining using anti-HNK-1 monoclonal antibody were comparable to those seen in normal controls. These results led to the following conclusion: it seems unlikely that a deficiency or impairment of natural killer activity is one of backgrounds for the development and subsequent malignant change of adenomas in familial polyposis coli.
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PMID:NK activities and HNK-1+ cells in familial polyposis coli. 282 57

Analysis of total and individual fecal neutral steroids in different groups of intestinal pathology from 105 patients was performed to investigate a relationship between neutral steroid concentration and malignant potentiality of colon cells. The fecal concentration of total neutral steroids was significantly higher in patients with colon cancer (57.3 +/- 2.4 mmol/kg of wet feces) and patients with malignant degenerative polyps at Stage I or II (49.5 +/- 2.9) compared with controls (36.9 +/- 3.5) as well as patients with adenomatous polyps (22.4 +/- 2.0). Moreover, a significant correlation was found between total neutral steroid concentrations and coprostanol concentrations in patients with colon cancer (r = 0.928) and in patients with malignant polyps (r = 0.915). Coprostanol results only from the biohydrogenation of delta 5-3 beta-OH steroids by anerobic bacteria because the analysis of a malignant colon tumor in comparison with a healthy colon wall showed that cholesterol is the only steroid included in membrane cells, and that the incubation of Clostridium or Bacteroides with delta 5-3 beta-OH steroids, such as cholesterol (steroid of animal origin) or beta-sitosterol (steroid of plant origin) converts these steroids into coprostanol at a level of efficiency greater than 45%. The findings suggest that high levels of coprostanol reflecting a high growth of anerobic bacteria through the gut are related to the malignant potentiality of colon cells. The screening of neutral fecal steroids should provide a valuable parameter for predicting the malignancy of colon cells.
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PMID:Relationship between fecal neutral steroid concentrations and malignancy in colon cells. 311 79

Patients with colorectal cancer respond poorly to in vivo immunotherapy with lymphokine-activated killer (LAK) cells generated from peripheral blood mononuclear cells (PBMC). We postulated that gut-derived immune cells could be a more relevant source of LAK cells directed against colorectal cancer. Intestinal lamina propria mononuclear cells (LPMC) and colonic adenocarcinoma cells were isolated from operative specimens by combination of mechanical and enzymatic dissociation methods. LAK cells were generated by culturing PBMC and LPMC with recombinant interleukin 2 (IL2), with and without OKT3 monoclonal antibody, in short- (4 days) and long-term (21 days) cultures. Other cultured tumor cells, normal intestinal fibroblasts, and hapten-modified autologous LPMC were used as control targets. Cytotoxicity was measured by a 4-hr 51Cr release assay. Short-term cultured LAK cells exhibited a strong to moderate degree of killing against normal intestinal fibroblasts, hapten-modified self cells, and four different tumor cell lines. Instead, fresh colon cancer cells were resistant to cytotoxicity, regardless of their degree of histologic differentiation and the autologous or allogeneic nature of the LAK cells. Long-term culture with IL2 remarkably increased LAK cell activity against all tumor targets, but not against colonic adenocarcinoma cells. The results of this study, showing that freshly isolated colon cancer cells are intrinsically resistant in vitro to highly activated cytotoxic effector cells, may explain the poor clinical results observed in human trials with in vivo administration of IL2 or LAK cells.
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PMID:Lymphokine-activated killer (LAK) cells from human intestinal mucosa: cytotoxic activity against tumor cell lines and modified self but not autologous and allogeneic colon cancer cells. 336 87

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

Two hundred twenty-two patients with colon cancer, diagnosed in the past 5 years, were grouped by age into the sixth, seventh, and eighth decades. Examination showed an increased incidence of right-sided colon cancer by decade and a simultaneous fall in the incidence of rectosigmoid lesions. A trend toward a more favorable Dukes' pattern was evident with each rise in decade. We suggest that the shift in site of colon and rectal cancer toward the right is directly related to age and is a feature of the "aging gut."
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PMID:Rightward shift of colon cancer. A feature of the aging gut. 380 59

In recent years, salient advances have taken place in the knowledge of the interaction of diets containing high-fat and certain type of fibers and the production of bile acids potentially relevant in the etiology of colon cancer. Other studies also indicate that a high intake of certain dietary fibers, in spite of high dietary fat, not only leads to an increase in stool bulk, thus diluting carcinogens and promoters in the gut, but also modifies the metabolism of these putative substances. These studies thus suggest that both high intake of total fat and low intake of certain fibers may be necessary for the full expression of risk to colon cancer.
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PMID:Diet and excretion of bile acids. 626 64

Analysis of the etiologic factors and relevant mechanisms involved in carcinogenesis leads to a classification of agents involved in the carcinogenic process as genotoxic or epigenetic. Their mode of action is distinct, especially with regard to dose-response effects and reversibility. The genotoxic carcinogens for colon cancer are unknown, but mutagenic components found in fried beef and fish are under study. Epigenetic agents as promoting factors play a major role in the development of cancer of the colon. Specific nutritional elements associated with colon cancer risk are high fat diets, high cholesterol intake, and low fiber intake. The role of micronutrients as modulators and inhibitors needs to be explored. Through metabolic studies in diverse populations and in reliable animal models, it is now clear that dietary fat and cholesterol control the total flow of bile acids in lumen and a high-fat, high-cholesterol diet increases the total of bile acids in the gut. Bile acids but not neutral sterols have promoting effects and are related to colon cancer risk although bile acids by themselves do not act as complete carcinogens. The effect of dietary fiber such as cereal bran is to increase stool bulk which dilutes the concentration of bile acids. Reducing the concentration of bile acids either by lower dietary fat and cholesterol or by increasing dietary fiber may effectively lower the risk for colon cancer.
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PMID:Bile acids, but not neutral sterols, are tumor promoters in the colon in man and in rodents. 630 78

Specimens of mucosal tissue of the small and large bowel obtained either by a colonoscope or during surgical operations were investigated quantitatively for their bacterial flora. A detailed prescription of the methodology using an anaerobic chamber is given. Most of the mucosal specimens of the small intestine as well as all the specimens of the large intestine contained bacteria (about 10(4) germs/g). Predominantly, Bacteroides, gram-positive rods, and cocci were isolated. In contrast to the gut lumen flora anaerobic bacteria of the mucosal flora did not outnumber the aerobes. In patients with inflammatory bowel disease or with carcinoma of the colon the mucosal flora showed no demonstrable alterations even after undergoing a sulphonamide therapy.
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PMID:Some studies of the bacterial flora associated with the mucosa of the human gastrointestinal tract. 649 20


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