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

Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS). The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H(2)O(2) (75microM) and quercetin (25-100microM) treatment. Analytic detection of iron in cell cultures, treated with 250microM Fe-NTA for 15 min to 24h, showed that 48.02+/-5.14 to 68.31+/-2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000microM) induced DNA breaks and oxidised bases, which were enhanced by subsequent H(2)O(2) exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H(2)O(2) for 15 min, 37 degrees C did not change the effect of H(2)O(2) alone. The impact of Fe-NTA and H(2)O(2)-induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H(2)O(2)-control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor.
 ...
PMID:Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A. 1216 Sep

Both cooked red meat intake and chronic inflammation/infection are thought to play a role in the etiology of colon cancer. The heterocyclic amine 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ) is formed during cooking of red meat and may be involved in initiation of colon cancer. Reactive nitrogen oxygen species (RNOS), components of the inflammatory response, contribute to the deleterious effects attributed to inflammation on normal tissues. This study assessed the possible chemical transformation of IQ by RNOS. RNOS were generated by various conditions to react with (14)C-IQ, and samples were evaluated by HPLC. Myeloperoxidase (MPO)-catalyzed reaction was dependent upon both H(2)O(2) and NO(2)(-). This reaction produced an azo-IQ dimer and IQ dimer along with two nitrated IQ products identified by ESI/MS. 2-Nitro-IQ was not detected. Product formation was inhibited by 2 mM cyanide. Reduction in nitrated products observed with 100 mM chloride was not altered with 0.5 mM taurine. Nitrated products were also produced by other conditions, ONOO(-) and NO(2)(-) + HOCl, which generate nitrogen dioxide radical. In contrast, conditions which generate N(2)O(3), such as diethylamine NONOate, produced only small amounts of nitrated products with the major product identified by MS and NMR as N-nitroso-IQ. MPO activation of IQ to bind DNA was dependent upon both H(2)O(2) and NO(2)(-). RNOS generated by ONOO(-) and DEA NONOate also activated IQ DNA binding. The nitrated IQ products were not activated by MPO to bind DNA. In contrast, N-nitroso-IQ was activated to bind DNA by MPO +/- NO(2)(-). HOCl activated N-nitroso-IQ, but not IQ. RAW cells produced N-nitroso-IQ and increased amounts of NO(2)(-)/NO(3)(-), when incubated with 0.1 mM IQ and stimulated with lipopolysaccharide and interferon gamma. Results demonstrate chemical transformation and activation of IQ by RNOS and activation of its N-nitroso product by biological oxidants, events which may contribute to initiation of colon cancer.
 ...
PMID:Nitrosation and nitration of 2-amino-3-methylimidazo[4,5-f]quinoline by reactive nitrogen oxygen species. 1218 90

Mass transport and mixing of perfused scalar quantities in the NASA Rotating Wall Perfused Vessel bioreactor are studied using numerical models of the flow field and scalar concentration field. Operating conditions typical of both microgravity and ground-based cell cultures are studied to determine the expected vessel performance for both flight and ground-based control experiments. Results are presented for the transport of oxygen with cell densities and consumption rates typical of colon cancer cells cultured in the RWPV. The transport and mixing characteristics are first investigated with a step change in the perfusion inlet concentration by computing the time histories of the time to exceed 10% inlet concentration. The effects of a uniform cell utilization rate are then investigated with time histories of the outlet concentration, volume average concentration, and volume fraction starved. It is found that the operating conditions used in microgravity produce results that are quite different then those for ground-based conditions. Mixing times for microgravity conditions are significantly shorter than those for ground-based operation. Increasing the differential rotation rates (microgravity) increases the mixing and transport, while increasing the mean rotation rate (ground-based) suppresses both. Increasing perfusion rates enhances mass transport for both microgravity and ground-based cases, however, for the present range of operating conditions, above 5-10 cc/min there are diminishing returns as much of the inlet fluid is transported directly to the perfusion exit. The results show that exit concentration is not a good indicator of the concentration distributions in the vessel. In microgravity conditions, the NASA RWPV bioreactor with the viscous pump has been shown to provide an environment that is well mixed. Even when operated near the theoretical minimum perfusion rates, only a small fraction of the volume provides less than the required oxygen levels.
 ...
PMID:RWPV bioreactor mass transport: earth-based and in microgravity. 1232 55

The carcinogenic risk of aromatic amines in humans was first discovered when a physician related the occurrence of urinary bladder cancer to the occupation of his patients. They were employed in the dyestuff industry, chronically exposed to large amounts of intermediate arylamines. Laboratory investigations disclosed that rats and mice administered specific azo dyes arylamines or derivatives developed cancer, primarily in the liver. Also, at that time, a possible pesticide, 2-aminofluorene, was tested for chronic toxicity, revealing that it rapidly induced cancers in several organs of rodents. This led to investigations on the mode of action of this class of chemicals, including their metabolic conversion. Biochemical activation to more reactive N-hydroxy compounds was found to occur, mostly in the liver, through what is now known as the cytochrome p450 enzyme systems, and also through prostaglandin synthetases. There were species differences. Guinea pigs were resistant to carcinogenesis because of the low titer of the necessary activating enzymes. In target tissues, a second essential reaction was necessary, namely acylation or sulfate ester formation. The reactive compounds produced display attributes of genotoxicity in appropriate test systems. Interest in this class of compounds increased when of Sugimura and colleagues discovered the formation of mutagens at the surface of cooked meat or fish, that were identified as heterocyclic amines (HCAs). These compounds undergo the same type of activation reactions, as do other arylamines. Epidemiological data suggest that meat eaters may have a higher risk of breast and colon cancer. HCAs induced cancer in rats in these organs and also in the prostate and the pancreas. In addition, there is some evidence that they affect the vascular system. The formation of HCAs during cooking can be decreased by natural and synthetic antioxidants, by tryptophan or proline, or by removing the essential creatine through brief microwave cooking prior to frying or broiling. The amounts of HCAs in cooked foods are small, but other components in diet such as omega-6-polyunsaturated oils have powerful promoting effects in target organs of HCAs. On the other hand, the action of HCAs may be decreased by foods containing antioxidants, such as vegetables, soy, and tea. Some constituents in foods also induce phase II enzymes that detoxify reactive HCA metabolites. Additional mechanisms involved decreased growth of neoplasms by intake of protective foods. Possibly, the carcinogenic effect of HCAs is accompanied by the presence of reactive oxygen species (ROS), which are also inhibited by antioxidants. World-wide, there have been many contributors to knowledge in this field. Adequate information may permit now to adjust lifestyle and lower the risk of human disease stemming from this entire class of aryl and HCA.
 ...
PMID:Comments on the history and importance of aromatic and heterocyclic amines in public health. 1235 Nov 40

Results of this study indicate a radioprotective effect of peroxiredoxin-I. Peroxiredoxin-I is an antioxidant that scavenges hydroperoxides, whereas reactive oxygen species are the main mediators of ionizing radiation toxicity. We hypothesized that peroxiredoxin-I might be induced by cellular exposure to radiation and act to protect them against its cytotoxic effects. Western blot and Northern blot analyses were used to assess peroxiredoxin-I protein and mRNA expression. Rat C6 glioma cells were engineered to overexpress sense or antisense human peroxiredoxin-I using retroviral vectors. Clonogenic cell survival was used to assess radiosensitivities of the engineered cells. Ionizing radiation induced peroxiredoxin-I protein and mRNA expression in human HT29 colon cancer and rat C6 glioma cells in a dose- and time-dependent manner over a 24 hr period. To determine the effect of peroxiredoxin-I on radiation responses, C6 glioma cells were engineered to overexpress sense or antisense human peroxiredoxin-I. In clonogenic assays, cells overexpressing peroxiredoxin-I were more radioresistant. Cells transduced with antisense peroxiredoxin-I were marginally more sensitive to radiation toxicity. Irradiation can induce peroxiredoxin-I expression, and the increased peroxiredoxin-I may protect cells from further radiation damage. These results suggest that protection by peroxiredoxin-I may play an important role in the survival of glioma and colon cancer cells in patients undergoing radiation therapy.
 ...
PMID:Induction of radioprotective peroxiredoxin-I by ionizing irradiation. 1244 1

Vitamin E, part of the body's primary lipid-soluble defense against free radicals and reactive oxygen molecules, has been suggested to reduce the risk for some cancers. However, the role of vitamin E in the etiology and prevention of colon cancer, especially in the highest risk group, the aged, is not clear. Thus, this study was conducted to elucidate the effect of vitamin E supplementation on susceptibility to colon cancer by examining azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation, a surrogate biomarker of colon cancer. Young (3-4 mo) and old (19-20 mo) C57BL/6JNIA mice were fed either a control diet (30 mg dl-alpha-tocopheryl acetate/kg diet) or a vitamin E-supplemented diet (500 mg dl-alpha-tocopheryl acetate/kg diet) for 16 wk. After 6 wk of dietary supplementation, young and old mice were injected with saline or AOM weekly for 5 wk to receive the same total dose of AOM (2.2 mg) and killed 10 wk after the first AOM injection. Vitamin E supplementation had no effect on the number of AOM-induced ACF in young or old mice. In addition, vitamin E supplementation did not have an effect on splenocyte interferon-gamma, interluekin-6 and tumor necrosis factor-alpha levels, natural killer cell killing activity or colonic cell proliferation in young or old mice. Thus, alpha-tocopherol does not seem to affect the initiation and early promotion stages of AOM-induced colon carcinogenesis in young or old mice. Whether vitamin E supplementation might be effective in reducing AOM-induced colon tumors is unclear.
 ...
PMID:Vitamin E supplementation does not alter azoxymethane-induced colonic aberrant crypt foci formation in young or old mice. 1256 95

Reactive oxygen species (ROS) could be important causative agents of a number of human diseases, including cancer. Thus, antioxidants, which control the oxidative stress state, represent a major line of defense regulating overall health. Human plasma contains many different nonenzymatic antioxidants. Because of their number, it is difficult to measure each of these different antioxidants separately. In addition, the antioxidant status in human plasma is dynamic and may be affected by many factors. Thus, the relationship between nonenzymatic antioxidant capacity of plasma and levels of well-known markers of oxidative stress (oxidized proteins, lipid hydroperoxides, decreases in thiol groups) better reflects health status. The present study considers antioxidant capacity and oxidative stress in human plasma of patients with colon cancer or precancerous lesions, as well as before and after surgical removal of tumors and/or chemo/radiation therapy. Healthy blood donors were used as controls. Colon cancer patients demonstrated a significant decrease in nonproteic antioxidant status and in total thiol groups with respect to healthy controls, whereas oxidized proteins and lipid hydroperoxide levels were significantly increased. In patients with precancerous lesions, the only unmodified parameter was the thiol group level. After surgery, the levels of oxidized proteins, lipid hydroperoxides, and total thiol groups were restored to those seen in healthy subjects, whereas nonproteic antioxidant capacity remained unmodified from that determined before surgery. Conversely, chemo/radiation therapy increased both nonproteic antioxidant capacity and levels of oxidized proteins and lipid hydroperoxides and significantly decreased total thiol groups. These results further support the hypothesis that oxidative stress correlates to the risk of some forms of cancer, not only in the initial stages but also during progression.
 ...
PMID:Nonproteic antioxidant status in plasma of subjects with colon cancer. 1270 80

A 65-year-old male in malnutrition due to advanced colon cancer underwent resection of transverse colon tumor and the invaded abdominal muscles with necrosis and abscess. After epidural catheter insertion between Th 10-11 for 9 cm cephalad, anesthesia was induced with thiopental 200 mg and fentanyl 50 micrograms. Tracheal intubation was done with vecuronium 5 mg, and anesthesia was maintained with sevoflurane with nitrous oxide in oxygen and epidural block. During surgery, systolic blood pressure often went up to 130 to 140 mmHg and down to 50 to 60 mmHg. Dopamine 3-5 micrograms.kg-1.min-1 was administered but occasional ephedrine bolus injection was still necessary. The intestine, including the intact part, was edematous. After the surgery, when systolic blood pressure was stable at about 130 mmHg and his consciousness was clear with regular spontaneous respiration, the tracheal tube was removed. However, soon after the extubation, expiratory stridor and cyanosis of the bilateral hands and feet were observed. Hydrocortisone 200 mg and nicardipine 0.5 mg were administered and room temperature was raised. About 30 minutes later, stridor and cyanosis subsided. In the ward after surgery, only hoarseness was observed. The stridor might have been due to the laryngeal edema, which could be attributed to stimulation by tracheal tube in the patient with malnutrition. The hemodynamic instability during surgery and cyanosis after extubation might have come from changes of the vascular resistance by sepsis.
 ...
PMID:[A case report of the laryngeal edema and peripheral cyanosis after extubation of the tracheal tube]. 1367 88

Angiogenesis, the formation of new capillary blood vessels, is a fundamental process essential for reproduction and embryonic development. It is crucial to the healing of tissue injury because it provides essential oxygen and nutrients to the healing site. Angiogenesis is also required for cancer growth and progression since tumor growth requires an increased nutrient and oxygen supply. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs worldwide for treating pain, arthritis, cardiovascular diseases, and more recently for colon cancer prevention. However, NSAIDs produce gastrointestinal ulcers and delay ulcer healing. Recently NSAIDs have been demonstrated to inhibit angiogenesis, but the underlying mechanisms are only beginning to be elucidated. The inhibition of angiogenesis by NSAIDs is a causal factor in the delay of ulcer healing, and it is becoming clear that this is also likely to be one of the mechanisms by which NSAIDs can reduce or prevent cancer growth. Based on the experimental data and the literature, the mechanisms by which NSAIDs inhibit angiogenesis appear to be multifactorial and likely include local changes in angiogenic growth factor expression, alteration in key regulators and mediators of vascular endothelial growth factor (VEGF), increased endothelial cell apoptosis, inhibition of endothelial cell migration, recruitment of inflammatory cells and platelets, and/or thromboxane A2 mediated effects. Some of these mechanisms include: inhibition of mitogen-activated protein (Erk2) kinase activity; suppression of cell cycle proteins; inhibition of early growth response (Egr-1) gene activation; interference with hypoxia inducible factor 1 and VEGF gene activation; increased production of the angiogenesis inhibitor, endostatin; inhibition of endothelial cell proliferation, migration, and spreading; and induction of endothelial apoptosis.
 ...
PMID:Inhibition of angiogenesis by NSAIDs: molecular mechanisms and clinical implications. 1367 97

A 74-year-old male was operated for sigmoid colon cancer. Because of an agglutination of the patient's platelet, it was difficult to measure his platelet count under ethylene diamine tetra acetate (EDTA), heparin or citrate as anticoagulants with an automated cell counter. Even though there was a strong possibility of pseudothrombocytopenia, anesthetic management for the patient was safely conducted. His condition was stable throughout the perioperative course and no bleeding tendency was observed. Nitrous oxide, oxygen, sevoflurane, propofol and pancuronium were useful in this case.
 ...
PMID:[Anesthetic management of a patient with suspected pseudothrombocytopenia]. 1459 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>