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

The effect on colonic function of adding wheat fiber for 3 weeks to the metabolically-controlled diets of six healthy volunteers has been studied. Increasing dietary fiber intake from 17 to 45 g/day increased fecal weight from 79 +/- 6.6 g/day to 228 +/- 29.9 g/day and shortened mean transit time, measured by a continuous marker method, from 57.8 +/- 8.3 hr to 40.3 +/- 8.9 hr. The increase in fecal weight was largely due to water. Fiber caused a dilution of fecal marker and an increase in fecal fat, nitrogen, and calcium output. Fecal sodium, potassium, and chloride showed only small changes but volatile fatty acid output increased significantly without concentrations changing. Fecal bile acid output increased from 199 +/- 46 mg/day to 279 +/- 46 mg/day. These changes are discussed in light of current views of the role of dietary fiber in protecting against colon cancer.
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PMID:Changes in fecal composition and colonic function due to cereal fiber. 99 55

Epidemiological and animal studies suggest that faecal pH may be a risk factor for colorectal cancer with low faecal pH associated with a lower incidence of the disease. The aim of this study was to determine whether faecal pH (or dietary fibre) affects the short-term risk factors for colon cancer. Sixty-nine normal volunteers were randomized into three equal groups (A-C). They provided food records, faecal specimens and submitted to rectal biopsy for thymidine labelling studies before and after a 2-week intervention. Group A received a placebo of fruit juice. Group B, approximately 3.0 g d-1 sodium sulphate in juice. Group C, 30 g d-1 supplementary dietary fibre as wheat bran in bread. Age, sex, weight, height and intake of macronutrients and minerals were similar in the groups prior to intervention. Faecal pH was similar for the three groups before and was reduced in Group B after intervention (P = 0.001) with a relative reduction of 0.5 pH units. The labelling index for the three groups was similar prior to intervention; after, it was lowest in Group B with a relative reduction of 0.5% points, although this difference was not statistically significant. The results thus do not support the hypothesis that an acidification of faecal pH leads to a reduction in risk markers for colon cancer.
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PMID:The effect of lowering faecal pH on the rate of proliferation of the normal colonic mucosa. 134 Dec 34

Cytoplasmic alkalinization induced by activation of the Na+/H+ antiport plays an essential role in the initiation of cell proliferation. In the present study we examined the effects of amiloride, a specific and reversible inhibitor of Na+/H+ antiporter, on the growth of human colon cancer cells (HT-29). Amiloride (50-800 microM) inhibited the growth of HT-29 cells in a dose-dependent fashion. Forty-three percent inhibition of growth was found at an amiloride concentration of 400 microM after 4 days of treatment. The inhibitory effect of amiloride on growth of HT-29 cells was reversible since removal of amiloride by a media change after 48 h treatment lead to rapid regrowth to control levels. The reversibility of growth inhibition suggests that amiloride is not a non-specific cytotoxin for HT-29 cells. We examined the possible mechanisms for the inhibitory effects of amiloride. Amiloride (400 microM) completely abolished serum-stimulated ODC activity and inhibited difluoromethylornithine (DMFO)-stimulated putrescine uptake by 56%. We conclude that amiloride inhibits the in vitro growth of human colon cancer cells; since ODC-activity and polyamine transport were both inhibited, the inhibitory effects may be mediated in part by polyamine-dependent processes. Amiloride may be a useful agent in the treatment of colon cancer.
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PMID:Amiloride inhibits the growth of human colon cancer cells in vitro. 134 Dec 75

Several somatostatin analogs with recently synthesized acetylated N terminus were assayed in vivo for their effects on sodium pentobarbital-stimulated growth hormone (GH) levels in fed male rats and gastrin-releasing peptide (14-27)-stimulated gastrin levels in fasted male rats. The binding characteristics of these analogs to somatostatin receptors were also examined in various human tumors and normal tissues. The analog RC-101-I, injected at a dose of 0.1 micrograms/100 g body wt, significantly suppressed GH release (P less than 0.01) for at least 2 hr. Analog RC-160-II caused the longest inhibition of GH release, greater than that induced by nonacetylated parent analog RC-160, with GH levels showing significant suppression (P less than 0.01) for more than 3 hr. Analogs RC-160-II and RC-101-I and RC-160, injected at a dose of 1.0 micrograms/100 g body wt, significantly (P less than 0.01) suppressed gastrin-releasing peptide (14-27)-stimulated serum gastrin. Analog RC-101-I was active in this test at a dose of 0.1 micrograms/100 g body wt. RC-160-II showed significant binding to somatostatin-14 receptors in all investigated tissues (human colon, human colon cancer, breast cancer, human pancreas and pancreatic cancer, human prostate and prostate cancer, and rat cerebral cortex), but there were marked variations in binding affinities among various normal and cancerous tissues. The highest affinity was found in membranes of colon cancer (Ka = 18.4 nM-1) and breast cancer (Ka = 12.46 nM-1). The binding affinity of RC-160-II to somatostatin receptors in membranes of the breast cancer was similar to that of RC-160. RC-101-I showed higher binding affinity to somatostatin-14 receptors than RC-160 in human breast, pancreatic, and prostate cancer. With the exception of breast cancer tissue, the binding affinity of RC-101-I was significantly lower than that of RC-160-II in membranes of all investigated tissues. It can be concluded that acetylated somatostatin analogs RC-101-I and RC-160-II possess prolonged and enhanced biological activities in suppressing serum GH and gastrin in rats. Significant variations in binding affinities for these analogs in different tissues and various tumors suggest that differences may exist between somatostatin receptors in normal versus malignant tissues. This raises the possibility that some of these analogs could be used more selectively in the treatment of various neoplasms.
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PMID:Biological activity and receptor binding characteristics to various human tumors of acetylated somatostatin analogs. 134 89

The HT-29 human adenocarcinoma cell line has been used extensively in the study of colonic cell differentiation and colon cancer. We report here that substitution of glucose with trehalose (alpha-D-glucopyranosyl-alpha-D-glucopyranoside) depresses growth and promotes mucin-producing, goblet-like maturation of HT-29. An initial characterization of this process was made by analyzing several cDNA clones whose RNA templates were differentially expressed at elevated levels in cells grown in trehalose-containing medium. Seven of the 9 clones examined corresponded to 6 mitochondrial genes whose expression levels, relative to those from glucose-grown cells, ranged from approximately 3-fold for 16S rRNA to 8-23-fold for NADH dehydrogenase subunit 4. On the other hand, levels of mitochondrial DNA copy, measured by using NADH dehydrogenase subunit 4 cDNA as probe, were shown to be unaffected by trehalose treatment. Elevation of cellular NADH dehydrogenase subunit 4 RNA in HT-29 cultures grown in medium containing different components (sodium butyrate, galactose, no-sugar, glucose, cellobiose) generally correlated with depressed growth levels and specifically with increased numbers of mucin-producing cells present. Like butyrate, the sugar, trehalose, is an effective inducer of HT-29 differentiation, and may prove useful as a dietary therapeutic, and as a probe for elucidating mitochondrial involvement in colonic cell differentiation and transformation.
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PMID:Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation. 137 97

Aberrant crypts are putative preneoplastic lesions that have been proposed as intermediate biomarkers for colon cancer. The goals of these studies were to determine (i) if the colon cancer chemopreventive agent, sodium phytate, when started 1 week after a single dose of carcinogen, has any effect on the development of aberrant crypt foci (ACF) in treated rats; and (ii) if ACF at an early time period under these conditions correlate with the later formation of tumors in similarly treated animals. The number of ACF with four or more crypts was greater (P = 0.02, Mann-Whitney test) in rats with tumors compared with rats without tumors killed at 36 weeks after the injection of azoxymethane (AOM); the total number of ACF was not significantly different in these two groups. The incidence of tumors in F344 rats treated with AOM without phytate was 83% (10/12) compared to 25% (3/12) in rats treated with AOM plus phytate (P = 0.0045, two-tail Fisher's exact test). The finding of more (P = 0.005, Mann-Whitney test) ACF with four or more crypts in rats without phytate than in rats with phytate at 12 weeks after the injection of AOM is consistent with the hypothesis that the development of larger ACF (with four or more crypts) is predictive of the tumor incidence. These results validate the use of this parameter, i.e. ACF with four or more crypts, as an intermediate biomarker for tumor incidence in this system.
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PMID:Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate. 139 32

Six ruthenium derivatives were evaluated in vitro in two human colon cancer cell lines (SW707 and SW948) utilizing the microculture tetrazolium test (MTT) and cell counting with a Coulter Counter. The ruthenium compound sodium-(tetrachloroimidazoledimethylsulfoxideruthenate)- bisdimethylsulfoxide (Na(RuDMSOimCl4)) showed the best efficacy in inhibiting cell proliferation of both colon cancer cell lines followed by the other DMSO ruthenium compound sodium-(tetrachloroindazoledimethylsulfoxideruthenate) - bisdimethylsulfoxide (Na(RuDMSOIndCl4)), as demonstrated by IC50 values (80 and 90 micrograms/ml in SW707 and SW948 cell lines for Na(RuDMSOImCl4); 155 and 165 micrograms/ml in SW707 and SW948 cell lines for Na(RuDMSOIndCl4), respectively). Out of the ruthenium derivatives without DMSO, transindazolium - [tetrachlorobis(1H - indazole)ruthenate (III,N2)] (HInd[RuInd2Cl4(N2)]), was as active as its DMSO-containing congener whereas trans-imidazolium- [tetrachlorobisimidazoleruthenate)(III)], (HIm(RuIm2Cl4)) was less active, as shown by the IC50 values: (HIm (RuIm2Cl4) = 250 and 260 micrograms/ml in cell lines SW707 and SW948; HInd[RuInd2Cl4(N2)] = 110 and greater than 200 micrograms/ml in cell lines SW707 and SW948, respectively). The other ruthenium derivatives containing pyrazole and triazole as ligands (trans - pyrazolium (tetrachlorobispyrazoleruthenate) (III), PzH(RuPz2Cl4) and triazolium(tetrachlorobistriazoleruthenate) (III), TrH(RuTr2Cl4)) were active only at high concentrations that cannot be regarded as realistic in vivo, as shown by the respective IC50 values: (PzH(RuPz2Cl4) = 1056 and 750 micrograms/ml in cell lines SW707 and SW948; TrH(RuTr2Cl4) = 350 and 300 micrograms/ml in cell lines SW707 and SW948). The promising activity of ruthenium compounds with DMSO, indazole and imidazole as ligands should be evaluated in vivo for elucidating their possible role in the treatment of colorectal cancer.
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PMID:Antitumor activity of some ruthenium derivatives in human colon cancer cell lines in vitro. 141 38

Bile salts and acids have been implicated in the etiology of colon cancer, possibly through their ability to cause DNA damage. Taurine-conjugated and nonconjugated forms of three bile salts and one bile acid were tested for DNA repair-inducing potential and for cellular toxicity in a recently developed Escherichia coli chromotest system. The taurine-conjugated forms of sodium deoxycholate and lithocholic acid had reduced ability to induce DNA repair. Also the taurine-conjugated form of lithocholic acid had a reduced lethal effect. These observations suggest that the biotransformation step, whereby bacteria in the intestine remove the taurine added to bile salts in the liver, may be significant in the etiology of colon cancer.
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PMID:Bile salt/acid induction of DNA damage in bacterial cells: effect of taurine conjugation. 143 52

Single and multiple colonic crypts exhibiting dysplasia that are detectable in situ by staining of rat colon with methylene blue are called aberrant crypts (AC) and may serve as an intermediate marker for colon cancer. In a characterization study, we have established the kinetics of AC growth and development over a period of 20 d following injection of rats with the carcinogen azoxymethane (AOM). AC are not present at 5 d post-injection, but are a constant feature at 10 d and thereafter. Multiple AC, presumably clonal, begin to evolve at 10 d and are consistent by 20 d, forming incipient microadenomata. We have examined 20 candidate chemopreventive agents for inhibition of AC. All agents were given in AIN-76 diet, at two dose levels, with injections of AOM. AC were measured after 5 weeks of growth. Among the most active AC-inhibiting agents were BHA, DFMO, quercetin, diallyl sulfide, 18 beta-glycyrrhetinic acid, and ascorbyl palmitate. In a post-initiation study, the differentiating agent sodium butyrate was ineffective, but piroxicam was highly effective in modulating AC growth. Further, piroxicam inhibited AC development at all stages of growth from single to polycryptal clusters of AC. The AC assay shows marked sensitivity and specificity for screening agents for chemoprevention of colon cancer.
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PMID:Growth kinetics and chemoprevention of aberrant crypts in the rat colon. 146 5

The human alkaline phosphatases constitute a multigene family with at least four members. Placental-like alkaline phosphatase (PLAP) is of particular interest because it is frequently present in tumors, where it serves as a marker of malignant transformation. Moreover, its expression is highly inducible by differentiating agents such as sodium butyrate. In the present study we have examined the PLAP gene promoter in order to better understand the mechanisms involved in its expression and induction. The PLAP promoters from four colon cancer cell lines with widely varied butyrate-inducible alkaline phosphatase activity were thermally amplified and sequenced. The overall sequence similarity of this region was found to be 99% between cell lines; thus, sequence variation of the promoter does not appear to account for the differential expression of this marker. We therefore analyzed the activity of the LS174T cell PLAP promoter using transient transfection experiments. Here, the 5'-flanking region of the gene was found to have positive regulatory elements in nucleotides -1 to -170 and -363 to -512 (relative to the start of transcription). A negative control element was also found to be present in the region between nucleotides -170 and -363. Mobility shift electrophoresis indicated that a nuclear factor bound to the promoter between bases -182 and -341. Furthermore, the activity of the PLAP promoter was found to be inducible by sodium butyrate. In contrast, the closely related placental alkaline phosphatase gene promoter exhibited almost no response to this agent. These results confirm that the activity of the PLAP promoter is stimulated by sodium butyrate and delineate regions that control this induction process.
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PMID:Transcriptional regulation of the human placental-like alkaline phosphatase gene and mechanisms involved in its induction by sodium butyrate. 159 96


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