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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relation of trihalomethanes (THM) to colorectal cancer was evaluated. A total of 395 colorectal cancer deaths among white women teachers in New York State was compared to an equal number of deaths of teachers from noncancerous causes. Cumulative chloroform (CHCl3) exposure was estimated by the application of a statistical model to operational records from the individual water treatment facilities that served the home and work addresses of each study subject during the 20 years prior to death. The odds of exposure to a surface source containing little or no THM was no greater for cases than for controls. The odds ratio = 1.07; the 90% confidence interval = 0.79-1.43; and the P = .68. The distribution of CHCl3 exposure was not significantly different between cases and controls (rated by Wilcoxon signed rank statistic = -0.52; P = .60). No effect of cumulative CHCl3 exposure on outcome was seen in a logistic analysis controlling for average source type, population density, marital status, age, and year of death (likelihood ratio test statistic = 0.047; P = .83).
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PMID:Trihalomethanes in drinking water and human colorectal cancer. 658 40

Cell poking, a new method for measuring mechanical properties of single cells was used to determine the elastic area compressibility modulus of osmotically swollen human erythrocytes. With this method we determined the force required to indent cells attached to a glass coverslip (Petersen, N.O., W. B. McConnaughey , and E. L. Elson , 1982, Proc. Natl. Acad. Sci. USA, 79:5327. Forces on the order of one millidyne and indentations on the order of one micron were detected. An analysis of these data in terms of a simplified mechanical model yielded the elastic area compressibility modulus. This analysis used a variational approach to minimize the isothermal elastic potential energy density function given by E. A. Evans and R. Skalak (Mechanics and Thermodynamics of Biomembranes, 1980, CRC Press, Boca Raton , FL). Measurements on swollen erythrocytes gave a range of values, depending in part on the osmotic conditions, of 17.9 +/- 8.2 to 34.8 +/- 12.0 mdyn /micron for the elastic area compressibility modulus at 25 degrees C. Fractional area expansion greater than 2.6 +/- 0.8% produced rapid cell lysis. These values were not corrected for the reversible movement of water across the cell membrane in response to hydrostatic pressure gradients. Our results agree reasonably with those obtained by Evans et al. (Evans, E.A., R. Waugh , and L. Melnick , 1976, Biophys. J., 16:585-595.) using micropipette aspiration under similar conditions.
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PMID:Cell poking. Determination of the elastic area compressibility modulus of the erythrocyte membrane. 672 61

One of the ways dietary fibers may protect against colorectal cancer is by adsorbing carcinogens and carrying them out of the digestive tract, thus lessening interaction of the carcinogens with the colonic tissue. We investigated this mechanism of action by testing in vitro the abilities of a range of carcinogens, including known animal colon carcinogens, to adsorb to alpha-cellulose, which we have used as a model insoluble dietary fiber. The carcinogens were N-nitroso-N-methylurea (NMU), benzo[a]pyrene (B[a]P) and a number of heterocyclic aromatic amines which have been found in heated foods. It was found that the ability of a carcinogen to adsorb to alpha-cellulose is strongly related to the hydrophobicity of the carcinogen measured as the calculated logarithm of the partition coefficient between 1-octanol and water (C log P). The hydrophilic carcinogen, NMU, (C log P = -0.204), adsorbed only poorly, whereas the very hydrophobic carcinogen, B[a]P, (C log P = 6.124), adsorbed strongly. Carcinogens with intermediate hydrophobicities showed intermediate abilities to adsorb.
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PMID:The adsorption of a range of dietary carcinogens by alpha-cellulose, a model insoluble dietary fiber. 750 98

CPT-11, a semisynthetic derivative of camptothecin, exhibited strong antitumor activity against lymphoma, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and cervical cancer. CPT-11 is a pro-drug that is converted to an active metabolite, SN-38, in vivo by enzymes such as carboxylesterase. We synthesized a water-soluble and non-pro-drug analog of camptothecin, DX-8951f. It showed both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. The anti-proliferative activity of DX-8951f, as indicated by the mean GI50 value, was about 6 and 28 times greater than that of SN-38 or SK&F 10486-A (Topotecan), respectively. These three derivatives of camptothecin showed similar patterns of differential response among 32 cell lines, that is, their spectra of in vitro cytotoxicity were almost the same. The antitumor activity of three doses of DX-8951f administered i.v. at 4-day intervals against human gastric adenocarcinoma SC-6 xenografts was greater than that of CPT-11 or SK&F 10486-A. Moreover, it overcame P-glycoprotein-mediated multi-drug resistance. These data suggest that DX-8951f has a high antitumor activity and is a potential therapeutic agent.
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PMID:A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo. 755 2

Because the environment of the human colon is so complex, factors which lead to the development of colorectal cancer are difficult to identify. The effects of 3 endogenous components that affect development of colorectal cancer--colonic bacteria, the mucus layer and bile acids--will be reviewed in this article. The major effects of the bacteria are deconjugation and reduction of bile acids, activation of mutagen precursors, fermentation and production of volatile fatty acids, formation of endogenous mutagens and physical adsorption of hydrophobic chemicals. The mucus layer covering the surface acts as a barrier, and its composition changes in premalignant and malignant colon tissue. Its secretion is elevated by certain plant cell wall components in the diet. Mucus has some hydrophobic properties, and its presence may alter the distribution of hydrophobic molecules. Bile acid concentration in faecal water, rather than the total bile acid concentration, determines the toxicity to epithelial cells and increased concentrations stimulate cell proliferation rates. There is evidence that elevated bile acids in the lumen can activate cellular protein kinase C, which stimulates cell proliferation. These effects are consistent with bile acids acting as tumour promoters.
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PMID:Roles of endogenous substances and bacteria in colorectal cancer. 769 1

Many dietary factors have been studied for their potential in the chemoprevention of human colorectal cancer. From an epidemiological standpoint, there have been many studies linking calcium intake to colon cancer risk. Significant reductions in risk have been shown for the consumption of milk, dietary calcium and dairy products in general. Additionally, there have been numerous studies of calcium and cell proliferation in experimental animals. Supplemental calcium in the diet or drinking water has been reported to decrease the colonic epithelial hyperproliferation induced by bile and fatty acids, enteric resection, a nutritional stress diet, and to suppress induction of the tumor-promotion enzyme ornithine decarboxylase. Calcium has also demonstrated an inhibitory effect on experimental colon carcinogenesis. Mechanisms of calcium inhibition are still speculative, but the "calcium soaps" hypothesis, fatty acid destabilization of cellular membranes, modulation of protein kinase C and K-ras mutations are under investigation. Additionally, numerous clinical studies of calcium modulation of human colonic hyperproliferation in high-risk groups as well as chemoprevention trials of calcium supplementation are currently ongoing. Although the question of whether dietary calcium can prevent human colorectal cancer remains to be answered, the data presently available appear promising.
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PMID:Role of calcium in colon cancer prevention: experimental and clinical studies. 769 3

Dietary fibre has a complex and highly variable composition. Although some dietary fibres may protect against colorectal cancer, it is unlikely that all are equally protective. Dietary fibre is principally composed of plant cell walls, but it also includes components obtained from cell walls (e.g. cellulose, pectin, and lignin), and non-starch polysaccharides (NSPs) from other sources (e.g. seaweeds and micro-organisms). The AOAC and Englyst methods are commonly used to determine the total amount of dietary fibre in foods. Most of the cell walls in food plants are from parenchyma cells, which are extensively degraded by bacteria in the colon. Cell types with walls containing the hydrophobic polymers lignin, suberin, or cutin also occur in food plants in small numbers, but they may be important in preventing colorectal cancer. Lignin, and possibly the other polymers, protect these walls from degradation. Epidemiological, human intervention, and animal studies can be used to try to identify the most protective dietary fibres. Epidemiological studies are difficult to interpret because usually only the total amount of dietary fibre eaten is reported. Intervention studies indicate that wheat bran dietary fibre may be protective. The results of animal carcinogenesis studies are variable, but sources of insoluble dietary fibres, including wheat bran, appear more protective than soluble dietary fibres, and some dietary fibres appear to enhance carcinogenesis. Possible mechanisms for protection by dietary fibres can be divided into two groups: those where the dietary fibre is acting directly, and those which result from the dietary fibre being degraded by colonic bacterial enzymes and the products fermented. Possible direct mechanisms include the binding of carcinogens to undegradable dietary fibres, and the absorption of water by undegradable dietary fibre resulting in increased faecal bulk and shortened transit times. Possible indirect mechanisms include the lowering of the colon pH by the short-chain fatty acids produced by bacterial fermentation, and the specific effects of butyrate. There are also a number of possible mechanisms by which some dietary fibres may enhance carcinogenesis. Use of better defined dietary fibres will increase our understanding of the role of dietary fibres in modulating colorectal cancer.
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PMID:Dietary fibre: its composition and role in protection against colorectal cancer. 769 4

Epidemiology and animal experiments indicate that dietary fibres protect against the development of colorectal cancer. However, insoluble dietary fibres appear to be more effective than soluble dietary fibres and one mechanism by which they may protect is by adsorbing dietary carcinogens. We found previously that the ability of a carcinogen to adsorb in vitro to alpha-cellulose (a model insoluble dietary fibre) was strongly related to the hydrophobicity of the carcinogen, measured as the calculated logarithm of the partition coefficient between 1-octanol and water (C log P). Furthermore, soluble dietary fibres (soluble-fibre polysaccharides), including gum arabic, reduced the adsorption of the hydrophobic carcinogen, DNP, to alpha-cellulose. In the present study we tested the ability of gum arabic to reduce the adsorption in vitro of the carcinogens BaP (C log P = 6.124), DNP (C log P = 4.384), and the heterocyclic amines, Trp-P-1 (C log P = 3.230) and MeIQx (C log P = 1.078). Gum arabic reduced the adsorption to alpha-cellulose of BaP and DNP, but not the adsorption of Trp-P-1 or MeIQx. Gum arabic also reduced the adsorption of BaP to an insoluble, dietary-fibre preparation from commercial cork which contains the hydrophobic component, suberin, but did not affect the adsorption of DNP, Trp-P-1 or MeIQx. It also did not affect the adsorption of DNP to an insoluble, dietary-fibre preparation from wheat straw, which contains the hydrophobic component, lignin. The results are discussed in terms of hydrophobic interactions between carcinogens and insoluble dietary fibres. In vivo, it is likely that soluble dietary fibres reduce the adsorption of only highly hydrophobic carcinogens to some insoluble dietary fibres.
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PMID:The effects of a soluble-fibre polysaccharide on the adsorption of carcinogens to insoluble dietary fibres. 772 95

The mechanical properties (diametral tensile strength, compressive strength, modulus of elasticity in compression, Knoop hardness, and Rockwell Superficial indentation and recovery) were measured for one light-cured composite (Herculite XRV) post-cured by five different conditions. The post-curing conditions were: boiling water, CRC-100, D.I.-500, Translux EC Light Box, and Triad 2000 with normal light curing as a control. Post-curing Herculite XRV significantly improved the diametral tensile strength (24-39%), Knoop hardness (8-22%) and Rockwell Superficial recovery (3-6%); decreased Rockwell Superficial indentation (0-19%) but did not affect the compressive strength significantly. Modulus of elasticity was not affected, except by the Translux EC Light Box, which increased the modulus by 33%. Post-curing Herculite XRV with the Triad 2000 and Translux EC Light Box produced the most improved properties. Water at 100 degrees C was the least effective of the post-curing methods.
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PMID:Effects of post-curing on mechanical properties of a composite. 788 Apr 65

The topoisomerase I inhibitor topotecan is a potent water-soluble camptothecin derivative with activity in a wide variety of preclinical models. Topotecan exhibits schedule dependency in vivo, with the greatest activity being observed on repeated dose schedules. On the basis of the initial clinical studies that showed a short plasma half-life, we attempted to prolong drug exposure by giving topotecan as a 24-h infusion weekly. In a phase I trial, we treated 32 patients at doses ranging from 1.0 to 2.0 mg/m2. The patient population had not been heavily pretreated with chemotherapy and was of good performance status. The incidence of neutropenia, which was dose-limiting, increased sharply with relatively small increments in dose. Doses greater than 1.5 mg/m2 were associated with nadirs that developed after one to three weekly treatments. A patient with metastatic colorectal cancer had a prolonged partial response. The plasma pharmacokinetics of topotecan (lactone and open forms) was characterized in 21 patients. Mean plasma steady-state drug levels were proportional to the dose and were within the range required to exert cytotoxicity in preclinical models. Plasma elimination curves were fit to a one-compartment model, in which the harmonic mean half-life of topotecan was 3.5 h. The ratio of the lactone to the total drug concentrations was constant throughout, which suggests that for this schedule the total drug concentration may be used as a measure of active lactone exposure. This conclusion is supported by the pharmacodynamic analysis, which revealed a positive correlation of both lactone and total drug steady-state concentrations with bone marrow toxicity. The further investigation of this and other infusional schedules in phase II trials will be conducted. The steady-state concentrations of total drug will be measured in several of these trials to establish its potential role in adaptive dosing using this schedule. Such a strategy is justified by the interpatient variability in toxicity and the steep dose-response curve observed in this study. Preliminary evidence of interpatient variability in the mRNA expression of topoisomerase I in the peripheral mononuclear cells and colon mucosa is presented. Trials are under way using biological endpoints for further selection of patients in whom the use of topoisomerase inhibitors may be therapeutically beneficial.
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PMID:Clinical, pharmacokinetic and biological studies of topotecan. 807 27


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