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

The incidence, distribution, size, and histopathology of small and large bowel tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats given 1% or 2% sodium butyrate dissolved in drinking water. Although previous in vitro reports on colon cancer cell lines have suggested that sodium butyrate might have a role to play as a chemotherapeutic "differentiating agent," the results of this in vivo study indicate that sodium butyrate treatment enhanced the development of colonic neoplasia and was associated with increased fecal butyric acid concentrations. In contrast, no changes were seen in the incidence of small bowel tumors, luminal butyric acid concentrations, mucosal morphology, or brush-border enzyme activities (i.e., sucrase, alkaline phosphatase). This study suggests that dietary butyrate has an important, possibly indirect, regulatory role in carcinogenesis associated with an experimental animal model of colonic neoplasia.
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PMID:Effects of differing concentrations of sodium butyrate on 1,2-dimethylhydrazine-induced rat intestinal neoplasia. 373 64

A novel, substituted 4-quinolinecarboxylic acid (NSC 339768) demonstrated antitumor activity against L1210 leukemia and B16 melanoma in the National Cancer Institute's Developmental Therapeutics Program. An extensive analogue synthesis program was initiated; over 200 derivatives were synthesized and tested for anticancer activity. One of these compounds, 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid sodium salt, NSC 368390 (DuP-785), was selected for further investigation because of its efficacy against a spectrum of human solid tumors and its water solubility. In initial studies with L1210 leukemia, the compound caused an increase in life span of greater than 80%. The activity was schedule dependent, and the compound was equally efficacious when administered i.p., i.v., s.c., or p.o. In tests against human tumors xenografted under the renal capsule of nude mice, NSC 368390 when injected i.p. in doses of 20-40 mg/kg daily for 9 days inhibited the growth of the MX-1 breast, LX-1 lung, BL/STX-1 stomach, and CX-1 colon carcinomas by greater than 90%. NSC 368390 also inhibited the growth of three distinct human colon carcinomas, the HCT-15, clone A, and DLD-2 tumors, growing s.c. in nude mice. An i.p. dose of 25 mg/kg given daily for 9 days inhibited the growth of the DLD-2 colon cancer by 98%. 1-beta-D-Arabinofuranosylcytosine and Adriamycin were ineffective, and fluorouracil was only moderately effective against these colon tumors. Because of its good activity against human colon tumors and other human carcinomas and its water solubility, NSC 368390 (DuP-785) is being developed as a Phase 1 anticancer agent.
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PMID:Activity of a novel 4-quinolinecarboxylic acid, NSC 368390 [6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarb oxylic acid sodium salt], against experimental tumors. 405 30

We have studied the thermotolerance (TTR) responses of three tumor cell populations obtained from a heterogeneous human colon cancer after exposure to 44 degrees C water bath hyperthermia given in a split dose regimen. The cell populations studied consist of the original tumor line (DLD-1) obtained from surgical biopsy, and two subcloned populations termed clones A and D. All tumor lines were treated with initial heat doses at 44 degrees C which reduced the initial survival level to about 30, 10, or 1%, after which cultures were returned to 37 degrees C. Complete survival curves were then determined for all three lines as a function of time after the initial treatment (0, 2, 4, 8, 12, 14, 20, and 24 h), and the magnitude and kinetics of thermotolerance development and its decay were determined. It was found that the DLD-1 line was more heat sensitive and exhibited a lesser degree of induced thermotolerance than did the A and D subpopulations, indicating intraclonal heterogeneity. Also, the rate of thermotolerance induction, the maximal thermotolerance reached (TTRmax), and the rate of thermotolerance decay were strongly dependent upon the survival level produced by the initial heat exposure. The importance of these findings to the treatment of heterogeneous cancers by heat is discussed.
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PMID:Similarity of thermotolerance characteristics in heterogeneous human colon tumor subpopulations after exposure to fractionated heat doses (44 degrees C). 408 Sep 71

Man-made organic chemicals have been found in drinking water for many years. Their numbers and varieties increase as our analytical capabilities improve. The identified chemicals comprise 10 to 20% of the total organic matter present. These are volatile or low molecular weight compounds which are easily identified. Many of them are carcinogenic or mutagenic. Chlorinated compounds have been found in untreated well water at levels up to 21,300 micrograms/L and are generally present at higher levels in chlorine-treated water than in untreated water. Aggregate risk studies for cancer are summarized. The most common sites are: bladder, stomach, colon, and rectum. Such studies cannot be linked to individual cases. However, they are useful for identifying exposed populations for epidemiologic studies. Five case-control studies were reviewed, and significant associations with water quality were found for: bladder cancer in two studies, colon cancer in three and rectal cancer in four. A large study by the National Cancer Institute found that there had been a change in the source of raw water for 50% of the persons in one area between the years 1955 and 1975. Such flaws in the data may preclude finding a causal relation between cancer and contaminants in drinking water. Large case-control and cohort studies are needed because of the low frequency of the marker diseases, bladder and rectal cancer. Cohort studies may be precluded by variations in the kinds of water contaminants. Definitive questions about these issues are posed for cooperative effort and resolution by water chemists, engineers, and epidemiologists.
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PMID:Chemical contamination of water supplies. 408 42

Established lines of human colon cancer cells from several sources (LS180, LS174T, HT29, SW480, SW1345) had water proton nuclear magnetic resonance (NMR) spin-lattice relaxation times (T1) of 460 +/- 45 msec to 982 +/- 9 msec and spin-spin relaxation times (T2) of 83 +/- 6 msec to 176 +/- 6 msec. Two clones derived from single cells of line LS174T were similar in T1 and T2 to the parent line. Differences among the cell lines were not totally a function of cellular hydration. Normal adult and fetal human primary colon cells were wetter and had higher T1 and T2 values than established cell lines. Relaxation times in this study substantiate variations seen for human colon tumors in earlier studies. Established cell lines maintained water relaxation times similar to tumor tissue values. Along with other morphological and biochemical criteria, the relaxation times suggest that these established human colon cancer cell lines may serve as a good experimental model for the study of human colon cancer.
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PMID:NMR relaxation times of water protons in human colon cancer cell lines and clones. 628 48

Because of potential significance of fecal mutagens (presumptive carcinogens) in the pathogenesis of colon cancer, feces from 99 healthy subjects from the New York metropolitan area were studied. The diet histories indicate that all participants were consuming a mixed-western diet which is high in total fat and low in fiber. Fecal samples that were incubated under anaerobic conditions at 37 degrees C for 96 h or frozen without incubation, were extracted with hexane: peroxide-free diethyl ether (1:1), partially purified on a silica Sep-pak cartridge and assayed for mutagenicity using the Salmonella typhimurium/mammalian microsome system. Aliquots of fecal samples incubated anaerobically showed a higher frequency of mutagenic activity (per cent samples showing activity) in strains TA98 and TA100 with and without microsomal (S9) activation. In addition, the mutagens requiring S9 activation, were more frequently inactivated when the fecal samples were frozen immediately after defecation and transported to the laboratory. Compared with hexane: ether, extraction of fecal samples with acetone increased the mutagenic activity mostly with TA98 with S9 activation. The HPLC fractionation of hexane: ether extract with methanol: water gradient using reverse phase C-18 column and UV detector at 254 nm indicated that the mutagenic activity (TA98 with S9 activation) is concentrated in several peaks. This is the first demonstration of HPLC profile of fecal samples that are active in TA98 with S9 activation. HPLC profile of fecal extracts and mutagenic activity of these extracts in strains TA98 and TA100 suggest the presence of several types of mutagens in the feces of healthy subjects consuming a high-fat, low-fiber mixed-western diet.
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PMID:Fecal mutagens from subjects consuming a mixed-western diet. 631 89

We have investigated the effect of age, a high-fat diet, sodium deoxycholate, and the ornithine analogue alpha-difluoromethylornithine on ornithine decarboxylase (ODC) activity in the rat colon. The relative levels of ODC activity were also determined in normal mucosa and tumor tissue from rat and human colon. The colonic ODC activity induced by intrarectal instillation of sodium deoxycholate in male Sprague-Dawley rats was highest in young animals, and it decreased with increasing age. A high level of dietary fat caused both an increased in basal colonic ODC activity and enhanced ODC induction by deoxycholate. alpha-Difluoromethylornithine given in drinking water inhibited, in a dose-dependent fashion, deoxycholate-induced ODC activity. The frequency of azoxymethane-induced intestinal tumors was also significantly reduced by alpha-difluoromethylornithine. Since colonic ODC activity is increased in carcinogenesis by known promoting agents and decreased by tumor inhibitors, this short-term assay may provide a useful system for identifying colon tumor promoters and inhibitors. The ODC activity in colon tumors of Sprague-Dawley rats was found to be significantly higher than in normal-appearing mucosa in the same animals. Similarly, ODC activity in human colon cancer was found to be higher than that of the normal-appearing mucosa in the same specimen. These results strengthen the utilization of the rat model for studies, the results of which may apply to the human situation.
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PMID:Ornithine decarboxylase activity in the rat and human colon. 643 May 47

The effects of cimetidine and indomethacin on the growth of dimethylhydrazine induced or transplanted intestinal tumours in the rat have been studied. Cimetidine is a histamine type 2 receptor antagonist and indomethacin is an inhibitor of prostaglandin synthesis. Two models of rat intestinal tumours were used: a colon carcinoma line transplantable in syngeneic animals and intestinal tumours induced by dimethylhydrazine treatment of Sprague-Dawley rats. Cimetidine and indomethacin were given in drinking water, alone or in combination. Cimetidine had no effect on the growth of transplanted colon cancer but significantly increased the incidence of chemically-induced tumours, with a tendency toward more invasive and metastatic tumours than in the control animals. Indomethacin did not significantly modify the incidence or other characteristics of the tumours in any of the models. This result is at variance with a protective effect of indomethacin on chemically-induced rat colon cancer previously reported by others.
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PMID:Effects of cimetidine and indomethacin on the growth of dimethylhydrazine-induced or transplanted intestinal cancers in the rat. 649 63

The non-steroid anti-inflammatory drug indomethacin, a prostaglandin synthesis inhibitor, may play a role to prevent the chemically induced colon cancer development in rats. CD-Fischer rats were given 3 intrarectal doses of 4 mg N-methyl-N-nitrosourea in week 1 as an initiation procedure to induce colon cancer. The experimental groups received a 0.001% water solution of indomethacin freely as drinking water at various times either during the initiation stage or the subsequent promotion stage. At autopsy in week 31, the treatment reduced the colon cancer development in the group of rats treated for week 1 (initiation stage), and for week 2-30 (early and late promotion stages) and for week 11-30 (late promotion stage), compared with untreated controls. However, removal of the treatment after effective treatment in promotion stage permitted the cancer development, and it suggests that the initiated cells are surviving during the treatment in promotion stage. It is concluded that indomethacin may inhibit methylnitrosourea-induced initiation and regulate promotion in colon carcinogenesis, presumably correlated with an inhibition of prostaglandin synthesis in the colon by indomethacin.
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PMID:Inhibition of initiation and promotion by N-methylnitrosourea-induced colon carcinogenesis in rats by non-steroid anti-inflammatory agent indomethacin. 661 52

To evaluate the influence of inhibitors of prostaglandin synthesis on the incidence of DMH-induced colon cancer, 90 male Sprague-Dawley rats were randomly assigned to: indomethacin 20 mg per liter drinking water, meclofenamate 50 mg per liter drinking water, or normal drinking water (control group). Dimethylhydrazine was given by weekly subcutaneous injections (20 mg/kg body weight) during the first 20 weeks. Thirty-two weeks after the start of treatment and carcinogen exposure, the animals were killed and examined for the number, size, location, and spread of intestinal tumors. Colon cancer incidence was significantly lower in animals receiving indomethacin (56 per cent) compared with the control group (88 per cent) and with the meclofenamate group (90 per cent) (P less than 0.005). The corresponding figures for tumors in the small intestine were 31, 46, and 35 per cent, respectively. The tumors in indomethacin-treated animals did not differ in number, size, location, or spread from tumors of the other groups, suggesting that indomethacin might influence the carcinogenic process itself, rather than the natural course of the established disease. We conclude that indomethacin significantly reduces the incidence of large-bowel cancer in this animal model and that this observation may have some potential for future chemopreventive studies in human high-risk groups (e.g. ulcerative colitis, familial polyposis).
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PMID:Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer. 673 60


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