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)

Elimination of both alleles of the gene that encodes the cyclin kinase inhibitor p21(WAF1/cip1) increases the frequency and size of intestinal tumors in Apc1638+/- mice that inherit a mutant allele of the Apc gene, and intermediate effects are seen if a single p21 allele is inactivated. The increased tumor formation is associated with altered cell maturation in the intestinal mucosa of the p21-deficient mice--increased cell proliferation, and decreased apoptosis, and goblet cell differentiation--that is also a function of p21 gene dosage. Moreover, a Western-style diet that mimics principal risk factors for colon cancer (high fat and phosphate, low calcium and vitamin D) accelerates tumor formation in Apc1638+/- mice, and the loss of a single or both p21 alleles is additive with the tumor-promoting effects of this diet, resulting in more and larger tumors, and a highly significant decrease in survival time. Thus, p21 normally suppresses Apc-initiated tumor formation and is haplo-insufficient in this regard. This is consistent with recent reports that Apc initiates tumor formation by up-regulating c-myc expression through altered beta-catenin-Tcf signaling and that c-myc then up-regulates cdk4, whose activity is inhibited by p21. Decreased expression of p21 is also a marker of poor prognosis in patients, and the data presented suggest that dietary alterations in patients undergoing treatment for colon cancer might be highly effective in improving outcome.
 ...
PMID:Targeted inactivation of the p21(WAF1/cip1) gene enhances Apc-initiated tumor formation and the tumor-promoting activity of a Western-style high-risk diet by altering cell maturation in the intestinal mucosal. 1121 50

High intake of red meat is associated with increased colon cancer risk. We have shown earlier that this may be due to the high haem content of red meat, because dietary haem increased cytolytic activity of faecal water and colonic epithelial proliferation. Dietary calcium inhibits diet-induced epithelial hyperproliferation. Furthermore, it has been shown that supplemental calcium inhibited the recurrence of colorectal adenomas. Therefore, we studied whether dietary calcium phosphate can exert its protective effects by inhibiting the deleterious effects of haem. In vitro, calcium phosphate precipitated haem and inhibited the haem-induced cytotoxicity. Subsequently, rats were fed diets, differing in haem (0 or 1.3 micromol/g) and calcium phosphate content only (20 or 180 micromol/g). Faeces were collected for biochemical analyses. Cytolytic activity of faecal water was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. In rats fed low calcium diets, dietary haem increased cytolytic activity of faecal water (98 +/- 1 versus 1 +/- 1%, P < 0.001) and the concentration of cations in faeces (964 +/- 31 versus 254 +/- 20 micromol/g), when compared with controls. This indicates that dietary haem increased colonic mucosal exposure to luminal irritants. Colonic epithelial proliferation was increased compared with controls (70 +/- 4 versus 48 +/- 8 d.p.m./microg DNA, P < 0.001). This was accompanied by metabolism of the ingested haem and solubilization of haem compounds in the faecal water. A high calcium diet largely prevented this metabolism and solubilization. It also inhibited the haem-induced cytolytic activity of faecal water and increase in faecal cation concentration. In accordance, the haem-induced colonic epithelial hyperproliferation was prevented. We therefore suggest that dietary calcium phosphate acts as a chemopreventive agent in colon carcinogenesis by inhibiting the cytolytic and hyperproliferative effects of dietary haem.
 ...
PMID:Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium. 1157 5

The purpose of this study was to examine whether L-type amino acid transporter 1 (LAT1), one of the amino acid transporters, is related closely to tumor size in liver metastasis. Rat colon cancer cells (RCN-9) were injected into the capsule of the spleen of 12 male rats (inbred F344/DuCrj). Conversely, four rats received only phosphate-buffered saline (control group 1), and four rats underwent only laparotomy (control group 2). In each rat, the metastatic tumors, areas surrounding tumor nodules, or the livers of the control groups were immunostained with the antibodies to LAT1 C peptide antigen. In control groups 1 and 2, normal hepatocytes did not indicate a staining of LAT1. A total of 90 metastatic nodules were found in 12 livers with metastasis. Of the 90 metastatic nodules, 43 nodules indicated a positive staining of LAT1. Conversely, the remaining 47 metastatic nodules had a negative staining of LAT1. The average size in metastatic nodules in the group with positive staining of LAT1 was 1.6 +/- 0.4 mm2, which was significantly higher than that of the group with negative staining of LAT1 (0.6 +/- 0.2 mm2; P = .0007). The ratio of the average area of the metastatic nodule against the average largest section of the left lobe of the lateral segment (RML, %) was measured. The RML in the group with positive staining of LAT1 was 1.2 +/- 0.3%, whereas the RML in the group with negative staining of LAT1 was 0.4 +/- 0.1%. A significant difference was noted between the two groups (P = .0004). We concluded that LAT1 plays an important role in tumor cell growth of liver metastatic tumors.
 ...
PMID:Expression of L-type amino acid transporter 1 in a rat model of liver metastasis: positive correlation with tumor size. 1171 50

Colon cancer is the third leading class of cancer causing increased mortality in developed countries. A polyp is one type of lesion observed in a majority of colon cancer patients. Here, we report a microscopic Fourier transform infrared (FTIR) study of normal, adenomatous polyp and malignant cells from biopsies of 24 patients. The goal of our study was to differentiate an adenomatous polyp from a malignant cell using FTIR microspectroscopy and artificial neural network (ANN) analysis. FTIR spectra and biological markers such as phosphate, RNA/DNA derived from spectra, were useful in identifying normal cells from abnormal ones that consisted of adenomatous polyp and malignant cells. However, the biological markers failed to differentiate between adenomatous polyp and malignant cases. By employing a combination of wavelet features and an ANN based classifier, we were able to classify the different cells as normal, adenomatous polyp and cancerous in a given tissue sample. The percentage of success of classification was 89%, 81%, and 83% for normal, adenomatous polyp, and malignant cells, respectively. A comparison of the method proposed with the pathological method is also discussed.
 ...
PMID:Diagnostic potential of Fourier-transform infrared microspectroscopy and advanced computational methods in colon cancer patients. 1196 11

Lithocholic acid (LA) conjugates interact with M3 receptors, the muscarinic receptor subtype that modulates colon cancer cell proliferation. This observation prompted us to examine the action of bile acids on two human colon cancer cell lines: H508, which expresses M3 receptors, and SNU-C4, which does not. Cellular proliferation was determined using a colorimetric assay. Interaction with muscarinic receptors was determined by measuring inhibition of muscarinic radioligand binding and changes in cellular inositol phosphate (IP) formation. Lithocholyltaurine (LCT) caused a dose-dependent increase in H508 cell proliferation that was not observed in SNU-C4 cells. After a 6-day incubation with 300 microM LCT, H508 cell proliferation increased by 200% compared to control. Moreover, in H508 cells, LCT caused a dose-dependent inhibition of radioligand binding and an increase in IP formation. LCT did not alter the rate of apoptosis in H508 or SNU-C4 cells. These data indicate that, at concentrations achievable in the gut, LA derivatives interact with M3 muscarinic receptors on H508 human colon cancer cells, thereby causing an increase in IP formation and cell proliferation. This suggests a mechanism whereby alterations in intestinal bile acids may affect the growth of colon cancer cells.
 ...
PMID:Functional interaction of lithocholic acid conjugates with M3 muscarinic receptors on a human colon cancer cell line. 1237 13

Growth-inhibitory effects on DS19 mouse erythroleukemia cells were seen in the micromolar concentration range with allicin and S-allylmercaptocysteine and in the millimolar range with allyl butyrate, allyl phenyl sulfone, and S-allyl cysteine. Increased acetylation of histones was induced by incubation of cells with the allyl compounds at concentrations similar to those that resulted in the inhibition of cell proliferation. The induction of histone acetylation by S-allylmercaptocysteine was also observed in Caco-2 human colon cancer cells and T47D human breast cancer cells. In contrast to the effect on histone acetylation, there was a decrease in the incorporation of phosphate into histones when DS19 cells were incubated with 25 microM S-allylmercaptocysteine. Histone deacetylase activity was inhibited by allyl butyrate, but there was little or no effect with the allyl sulfur compounds examined in this study. A similar degree of downregulation of histone deacetylase and histone acetyltransferase was observed when DS19 cells were incubated with S-allylmercaptocysteine or allyl isothiocyanate. The induction of histone acetylation by S-allylmercaptocysteine was not blocked by a proteasome inhibitor. The mechanism by which S-allylmercaptocysteine induces histone acetylation remains to be characterized. It may be related in part to metabolism to allyl mercaptan, which is a more effective inhibitor of histone deacetylase.
 ...
PMID:Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine. 1246 40

Platelet derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) catalyzes the phosphorolysis of thymidine (TdR) to thymine and deoxyribose-1-phosphate (dR-1-P) and has a pro-angiogenic effect for which dR-1-P may be responsible. Using a purine nucleoside phosphorylase based assay it was found that TdR incubation did not increase dR-1-P accumulation in colon cancer cell line Colo320 and its PD-ECGF/TP transfected variant Colo320TP1. The assay was linear up to 25,000pmol dR-1-P with complete recovery of dR-1-P from cellular extracts. There was a huge discrepancy between thymine production and the measured dR-1-P level, 0.05% of the expected value for dR-1-P was found, indicating that there was a rapid disappearance of dR-1-P. However, in cellular extracts, TdR incubation increased dR-1-P, measurable by trapping, which was inhibited by a thymidine phosphorylase inhibitor. dR-1-P directly added to cellular extracts disappeared within 5-10min. In conclusion, large amounts of dR-1-P are produced by Colo320TP1 cells, which rapidly disappear thus not resulting in a net accumulation of dR-1-P in these cells.
 ...
PMID:Rapid disappearance of deoxyribose-1-phosphate in platelet derived endothelial cell growth factor/thymidine phosphorylase overexpressing cells. 1256 33

Cancer development results from the interaction between genetic factors, the environment, and dietary factors have been identified as modulators of carcinogenesis process. The formation of DNA adducts is recognized as the initial step in chemical carcinogenesis. Accordingly, blocking DNA adducts formation would be the first line of defense against cancer caused by carcinogens. Glutathione-S-transferases inactivate chemical carcinogens into less toxic or inactive metabolite through reduction of DNA adducts formation. There are many different types of glutathione S-transferase isozymes. For example, GST delta serves as a marker for hepatotoxicity in rodent system, and also plays an important role in carcinogen detoxification. Therefore, inhibition of GST activity might potentiate the deleterious effects of many environmental toxicants and carcinogens. In addition, approximately half of the population lacks GST Mu expression. Epidemiological evidence showed that persons possessing this genotype are predisposed to a number of cancers including breast, prostate, liver and colon cancers. In addition, individual risk of cancer depends on the frequency of mutational events in target oncogenes and tumor suppressor genes which could lead to loss of chromosomal materials and tumor progression. The most frequent genetic alteration in a variety of human malignant tumors is the mutation of the coding sequence of the p53 tumor suppressor gene. O(6)-alkylguanine in DNA leads to very high rates of G:C deltaA:T transitions in p53 gene. These alterations will modulate the expression of p53 gene and consequently change DNA repair, cell division, and cell death by apoptosis. Also, changes in the expression of BcI-2 gene results in extended viability of cells by over-riding programmed cell death (apoptosis) induced under various conditions. The prolonged life-span increases the risk of acquiring genetic changes resulting in malignant transformation. In addition, a huge variety of food ingredients have been shown to affect cell proliferation rates. They, therefore, may either reduce or increase the risk of cancer development and progression. For example, it has been found that a high intake of dietary fat accelerates the development of breast cancer in animal models. Certain diets have been suggested to act as tumor promoters also in other types of cancer such as colon cancer, where high intake of fat and phosphate have been linked to colonic hyper-proliferation and colon cancer development. Different factors such as oncogenes, aromatic amines, alkylating agents, and diet have a significant role in cancer induction. Determination of glutathione S-transferase isozymes in plasma or serum could be used as a biomarker for cancer in different organs and could give an early detection.
 ...
PMID:Cancer and phase II drug-metabolizing enzymes. 1257 Jul 45

Epidemiological studies have reported an inverse association between vitamin B(6) intake and colon cancer risk. Our recent study has been conducted to examine the effect of dietary vitamin B(6) on colon tumorigenesis in mice. Mice were fed diets containing 1, 7, 14 or 36 mg/kg pyridoxine for 22 weeks, and given a weekly injection of azoxymethane (AOM) for the initial 10 weeks. Compared with the 1 mg/kg pyridoxine diet, 7, 14 and 35 mg/kg pyridoxine diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. Supplemental vitamin B(6) lowered the levels of colonic 8-hydroxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE, oxidative stress markers) and inducible nitric oxide (NO) synthase protein. In an ex vivo serum-free matrix culture model using rat aortic ring, supplemental pyridoxine and pyridoxal 5'-phosphate (PLP) had antiangiogenic effect. The results suggest that dietary vitamin B(6) suppresses colon tumorigenesis by reducing cell proliferation, oxidative stress, NO production and angiogenesis.
 ...
PMID:Antitumor effect of vitamin B6 and its mechanisms. 1268 21

Although exposure to ultraviolet light is often viewed as pathogenic owing to its role in the genesis of skin cancer and skin aging, there is growing epidemiological evidence that such exposure may decrease risk for a number of more serious cancers, may have a favorable impact on blood pressure and vascular health, and may help to prevent certain autoimmune disorders - in addition to its well-known influence on bone density. Most likely, these health benefits are reflective of improved vitamin D status. Increased synthesis or intake of vitamin D can be expected to down-regulate parathyroid hormone (PTH), and to increase autocrine synthesis of its active metabolite calcitriol in certain tissues; these effects, in turn, may impact cancer risk, vascular health, immune regulation, and bone density through a variety of mechanisms. Presumably, a truly adequate supplemental intake of vitamin D - manyfold higher than the grossly inadequate current RDA - could replicate the benefits of optimal UV exposure, without however damaging the skin. Diets moderately low in bioavailable phosphate - like many vegan diets - might be expected to have a complementary impact on disease risks, inasmuch as serum phosphate suppresses renal calcitriol synthesis while up-regulating that of PTH. A proviso is that the impact of dietary phosphorus on bone health is more equivocal than that of vitamin D. Increased intakes of calcium, on the other hand, down-regulate the production of both PTH and calcitriol - the latter effect may explain why the impact of dietary calcium on cancer risk (excepting colon cancer), hypertension, and autoimmunity is not clearly positive. An overview suggests that a vegan diet supplemented with high-dose vitamin D should increase both systemic and autocrine calcitriol production while suppressing PTH secretion, and thus should represent a highly effective way to achieve the wide-ranging health protection conferred by optimal UV exposure.
 ...
PMID:A moderately low phosphate intake may provide health benefits analogous to those conferred by UV light - a further advantage of vegan diets. 1459 85


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