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

Effects of dietary calcium on mammary carcinogenesis in rats were investigated because of evidence that calcium counteracts the promotion of colon cancer by dietary fat and because experimental diets for rats normally contain higher amounts of calcium and vitamin D than do human diets. Our earlier experiments indicated that yields of tumors induced in young, Sprague-Dawley rats by 7,12-dimethylbenz(a)-anthracene (DMBA) were higher when dietary calcium, phosphate, and vitamin D were decreased. Results of an experiment in which dietary amounts of calcium, phosphate, and vitamin D were varied independently suggested that phosphate and vitamin D have interactive effects with calcium. Another experiment in which dietary vitamin D alone was varied provided evidence that higher amounts inhibited tumorigenesis in the presence of low amounts of calcium and phosphate but the results with a high-calcium and -phosphate diet were inconclusive. The findings suggest that low amounts of dietary calcium and vitamin D and high amounts of phosphate increase susceptibility to DMBA-induced mammary neoplasia.
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PMID:Calcium and carcinogenesis of the mammary gland. 205 63

A search of the literature using National Library of Medicine databases and individual cancer journal articles yielded over 500 compounds with published chemopreventive activity in animals. From these, an initial 16 agents or agent combinations have been evaluated in the following animal tumor models: mouse skin papillomas/carcinomas induced by 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate; rat breast adenocarcinoma induced by N-methyl-N-nitrosourea or 7,12-dimethylbenz(a)anthracene; hamster lung carcinoma induced by N-methyl-N-nitrosourea or diethylnitrosamine; mouse bladder papillary carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine; and rat and mouse colon cancer induced by azoxymethane/methylazoxymethanol acetate. Some of the most interesting positive results observed include 4-hydroxyphenyl retinamide plus tamoxifen in breast cancer, piroxicam in colon cancer, dimethylfluoroornithine in breast and bladder cancer, oltipraz in lung cancer, dehydroepiandrosterone in colon cancer, and molybdate in bladder cancer. Eighteen human intervention trials in progress are described that involve the following agents: beta-carotene (eight trials). Retinol/retinoic acid (seven trials), vitamins C and E (three trials), 4-hydroxyphenyl retinamide (one trial), piroxicam (one trial), and calcium (one trial). By organ site these studies involve cancer of the lung (six studies), skin (five studies), colon (four studies), breast (one study), and uterine cervix (two studies).
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PMID:Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. 240 15

We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracene derivative, CL216,942. The object was to determine whether the system is useful for pinpointing the types of tumors in patients which should be studied in early phase II clinical trials. Tumors from 684 patients were placed in culture (27 different histologic tumor types). Two hundred seventy-three tumors both grew and formed enough colonies for drug sensitivity assays. In vitro antitumor activity was noted for CL216,942 against human breast cancer, ovarian cancer, renal cancer, squamous cell, small cell and large cell lung cancer, lymphoma, acute myelogenous leukemia, melanoma, adenocarcinoma of unknown origin, adrenal cancer, gastric cancer, pancreatic cancer, and head and neck cancer. The drug definitely showed no in vitro activity against colon cancer. These data indicate that CL216,942 has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of phase II clinical trials with the drug should allow an evaluation of the utility of the human cloning system for predicting clinical activity of a new compound.
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PMID:Activity of 9-10 anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone]dihydrochloride (CL216,942) in a human tumor cloning system. Leads for phase II trials in man. 730 32

Since phytic acid (inositol hexaphosphate, InsP6) and inositol (Ins) have been demonstrated to have anti-tumor and anti-cell proliferative action in several experimental models of carcinogenesis, in a pilot study we have examined their effect on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumor model. Starting a week prior to induction with DMBA, the drinking water of female Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15 mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (55-day-old) were given a single dose of DMBA (20 mg) in 1 ml of sesame oil by oral intubation. Four additional groups not receiving DMBA, but drinking tap water, InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were observed for the duration of the study to monitor for any putative toxicity following this long-term treatment. As opposed to the DMBA-only group, rats treated with InsP6 +/- Ins showed a 48% reduction in the number of tumors/tumor bearing animal (tumor multiplicity) and a 40% reduction in the number of tumors/rat. In contrast to 20% rats in DMBA-only group, only 0-8% animals in the treatment group had 5 or more tumors. Likewise, the tumor incidence was reduced by 19% in InsP6 +/- Ins as compared to control untreated animals. The tumors in the treated groups were also 16% smaller in size. Data from this pilot study suggest that in addition to being effective against colon cancer, InsP6 +/- Ins may be protective against mammary carcinoma as well; additional studies are however warranted.
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PMID:Inhibition of rat mammary carcinogenesis by inositol hexaphosphate (phytic acid). A pilot study. 829 26

A new class of antitumor agents, having structural analogy to amonafide, but differing by the addition of a fourth ring in the nucleus, was synthesized conveniently from anthracene. Compounds with a variety of substituents, containing a basic nitrogen atom and located on the imide nitrogen, were prepared. Thirteen of 19 new compounds had greater growth inhibitory potency than amonafide in a panel of cultured murine and human tumor cells using the sulforhodamine B and MTT dye assays. The most active agents were similarly more toxic than amonafide to normal neonatal rat myocytes in vitro, but they had better chemotherapeutic indexes. From these compounds, the one with a 2-(dimethylamino)ethyl side chain (named azonafide) was chosen for further study. It showed high potency against a panel of cultured human colon cancer cells and it was active against ip P388 leukemia and subcutaneous B16 melanoma in mice. Preliminary structure-activity correlations suggest that the basicity of the side-chain nitrogen and the length of side chain are important determinants of antitumor potency in vitro. Steric hindrance and rigidity of the side chains might be other determinants.
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PMID:2-substituted 1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. A new class of antitumor agent. 845 3

Curcumin and quercetin were evaluated in rats for their ability to modulate the carcinogenic activity of azoxymethane (AOM) in the colon and 7,12-dimethylbenz[a]anthracene (DMBA) in the mammary gland. In the AOM-induced colon cancer model, male Fischer 344 rats at 8 weeks of age started to receive either curcumin (8 and 16 g/kg) or quercetin (16.8 and 33.6 g/kg) in the diet and 1 week later, were administered AOM (30 mg/kg body wt.) by subcutaneous injection. The animals continued to receive the two agents in the diet until sacrificed 45 weeks later. Curcumin mediated a dose-dependent inhibition of the incidence and multiplicity of adenomas from 47% and 0.58 +/- 0.12 adenomas/rat in the AOM-treated control group to 19% and 0.22 +/- 0.08 and 0.06% and 0.08 +/- 0.06 adenomas/rat for the low and high dose groups, respectively. A low yield of adenocarcinomas (0.06 +/- 0.04 adenocarcinomas/rat) was induced by AOM which was not significantly altered by curcumin. Treatment with quercetin caused a dose-dependent increase in the yield of AOM-induced tumors in the colon from 0.06 +/- 0.04 adenocarcinoma/rat to 0.64 +/- 0.12 and 1.14 +/- 0.17 for the low and high dose groups, respectively. In the DMBA-induced mammary cancer model, curcumin or quercetin was administered at either 10 or 20 g/kg diet, beginning 7 days prior to DMBA and continually throughout the remainder of the experiment. Neither curcumin nor quercetin significantly altered the incidence of animals with tumors or the tumor multiplicity, while the high concentration of both agents significantly increased tumor latency. These results demonstrate different responses to these agents in the two models. While curcumin was highly effective as a chemopreventive agent in the colon model, it was only weakly effective in the mammary model. In contrast, quercetin which was also only weakly effective in the mammary model, caused a dose-dependent enhancement of tumors induced by AOM in the colon model.
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PMID:Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]anthracene-induced mammary cancer in rats. 868 47

Clarification of the mutational fingerprints of HCAs offers a promising approach in the investigation of the role of heterocyclic amines (HCAs) in human carcinogenesis. We analyzed mutations in the tumor related genes of tumors induced by HCAs, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which mainly yield DNA-adducts of C8-guanine. The G-->T transversion at codon 13-2nd position in Ha-ras was predominantly observed in mouse forestomach and rat Zymbal gland tumors induced by MeIQ. In contrast, various types of mutation were detected in the ras family genes of rat Zymbal gland tumors induced by IQ; the presence of a methyl group at position 4 of imidazo[4,5-f]quinoline gave rise to a remarkable difference in the mutational fingerprint. Apc mutations were detected in PhIP- and IQ-induced rat colon tumors, with incidences of 50% (4/8) and 15% (2/13), respectively. All five mutations detected in the four PhIP-induced tumors consisted of a guanine deletion from the 5'-GGGA-3' sequence, in contrast with T to C and C to T mutations in IQ-induced tumors. Four of these five mutations shared seven common nucleotides, -GTGGGAT- surrounding the guanine; indicating that PhIP leaves a characteristic mutational fingerprint in Apc. Colon tumors induced by PhIP were also found to have mutations in their microsatellite sequences, and similar results were detected in mammary gland tumors induced by PhIP, contrasting with no mutations in IQ-induced colon tumors and a very low frequency of mutations in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Although the mechanisms involved in the induction of microsatellite mutations are not known yet, microsatellite mutations which can also be detected in sporadic human tumors, including colon and breast tumors, were indicated to be a characteristic of PhIP. Mammary tumors induced by PhIP showed loss of heterozygocity (LOH) at the distal part of chromosome 10, which shows synteny with the distal part of human chromosome 17, where LOH frequently occurs in human breast cancer. In conclusion, each heterocyclic amine leave a mutational fingerprint which is specific to each compound. Since the tumor-related genes involved in PhIP-induced tumors have characteristics in common with those in human cancers, further detailed analysis will provide us with useful information on mutational fingerprints, and on the possible contribution of PhIP to human colon cancer.
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PMID:Genetic changes induced by heterocyclic amines. 920 52

Cancers of the colon and breast are two of the most prevalent cancers in developed countries. The present experiments were conducted to determine the influence of several dietary doses of grape seed proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis and azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a dual-organ tumor model. In addition, the effects of the grape seed proanthocyanidins on liver cytochrome P-450 1A and 2E1 and glutathione S-transferase activities and on colonic ornithine decarboxylase activity were examined to determine possible mechanisms of action. Feeding female rats diets containing 0.1-1.0% grape seed proanthocyanidins was associated with a significant 72-88% inhibition of AOM-induced aberrant crypt foci formation and a 20-56% inhibition of ornithine decarboxylase activity in the distal third of the colon. Feeding the grape proanthocyanidins resulted in no significant effect on the activity of liver cytochrome P-450 2E1. There was no effect of feeding these doses of proanthocyanidins on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis. This lack of action on mammary tumorigenesis in part may be due to lack of effect of dietary proanthocyanidins on the liver carcinogen-metabolizing enzymes cytochrome P-450 1A and glutathione S-transferase. These results indicate that grape polyphenolics warrant further evaluation as potential colon cancer chemopreventive agents.
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PMID:Effect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor model. 1175 89

Activity-guided fractionation of an ethyl acetate extract of the aerial parts of Tithonia diversifolia, using an antiproliferation bioassay performed with human colon cancer (Col2) cells, led to the isolation of three new sesquiterpenoids, 2alpha-hydroxytirotundin (1), tithofolinolide (2), and 3alpha-acetoxydiversifolol (3), along with eight known sesquiterpene lactones, 3beta-acetoxy-8beta-isobutyryloxyreynosin (4), tagitinin C (5), 1beta,2alpha-epoxytagitinin C (6), 4alpha,10alpha-dihydroxy-3-oxo-8beta-isobutyryloxyguaia-11(13)-en-12,6alpha-olide (7), 3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oic acid methyl ester, 17,20-dihydroxygeranylnerol, tagitinin A, and tirotundin. These isolates were evaluated for their potential as cancer chemopreventive agents, by measuring antiproliferative activity in Col2 cells and induction of cellular differentiation in human promyelocytic leukemia (HL-60) cells. Selected compounds were then investigated for their ability to inhibit 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in a mouse mammary organ culture assay. Among these isolates, 5 and 6 showed significant antiproliferative activity, 2, 4, and 7 induced HL-60 cellular differentiation, and 4 significantly inhibited (63.0% at 10 microg/mL) lesion formation in the mouse mammary organ culture assay. The chemical structures of 1-3 were elucidated by spectroscopic analysis. The absolute configurations of 1 and 2 were determined by Mosher ester methodology.
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PMID:Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity. 1197 95

There are relatively few reports on the cancer chemopreventive effects of lycopene or tomato carotenoids in animal models. The majority, but not all, of these studies indicate a protective effect. Inhibitory effects were reported in two studies using aberrant crypt foci, an intermediate lesion leading to colon cancer, as an end point and in two mammary tumor studies, one using the dimethylbenz(a)anthracene model, and the other the spontaneous mouse model. Inhibitory effects were also reported in mouse lung and rat hepatocarcinoma and bladder cancer models. However, a report from the author's laboratory found no effect in the N-nitrosomethylurea-induced mammary tumor model when crystalline lycopene or a lycopene-rich tomato carotenoid oleoresin was administered in the diet. Unfortunately, because of differences in routes of administration (gavage, intraperitoneal injection, intra-rectal instillation, drinking water, and diet supplementation), species and strain differences, form of lycopene (pure crystalline, beadlet, mixed carotenoid suspension), varying diets (grain-based, casein based) and dose ranges (0.5-500 ppm), no two studies are comparable. It is clear that the majority of ingested lycopene is excreted in the feces and that 1000-fold more lycopene is absorbed and stored in the liver than accumulates in other target organs. Nonetheless, physiologically significant (nanogram) levels of lycopene are assimilated by key organs such as breast, prostate, lung, and colon, and there is a rough dose-response relationship between lycopene intake and blood levels. Pure lycopene was absorbed less efficiently than the lycopene-rich tomato carotenoid oleoresin and blood levels of lycopene in rats fed a grain-based diet were consistently lower than those in rats fed lycopene in a casein-based diet. The latter suggests that the matrix in which lycopene is incorporated is an important determinant of lycopene uptake. A number of issues remain to be resolved before any definitive conclusions can be drawn concerning the anticancer effects of lycopene. These include the following: the optimal dose and form of lycopene, interactions among lycopene and other carotenoids and fat soluble vitamins such as vitamin E and D, the role of dietary fat in regulating lycopene uptake and disposition, organ and tissue specificity, and the problem of extrapolation from rodent models to human populations.
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PMID:A review of animal model studies of tomato carotenoids, lycopene, and cancer chemoprevention. 1242 27


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