Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulphasalazine (salicyl-azo-sulphapiridine, SAS) is a drug commonly used in the treatment of non-specific inflammatory bowel diseases, such as ulcerative colitis and Crohn disease. Chronic inflammatory states of the colon can lead to neoplastic changes of the intestinal mucosa. There are some suggestions in the literature that the intestinal bacterial azo-reductases are involved in biotransformation of SAS into 5-aminosalicylic acid (5-ASA) and sulphapyridine (SP). For this reason, it seemed worth of investigating whether transformation of SAS could be performed by the colon epithelial cells themselves. No enzymatic systems presumably exist in Caco-2, which could be responsible for SAS metabolism, because after 72 h-incubation of cell cultures with 1 mM SAS, its metabolites i.e., 5-ASA and SP were not detected in cells, neither in culture media. SAS metabolism, therefore, seems to depend on the presence of intestinal bacterial enzymatic systems. It was confirmed that 5-ASA is converted by Caco-2 cells to N-acetyl-5-aminosalicylic acid (Ac-5-ASA), which migrates to the culture medium. The other metabolite of SAS i.e., SP, was not transformed in the human colon cancer cells at all.
Acta Pol Pharm 2004 Dec
PMID:Evaluation of biotransformation of sulphasalazine in the colon epithelial Caco-2 cells. 1590 23

Activities of two principal cytosolic forms of human aldehyde dehydrogenase, ALDH1A1 and ALDH3AI in colon tumor homogenates and surrounding tissue fragments were measured, using isozymeselective, fluorimetric assays. The assays are based on two fluorogenic substrates, 6-methoxy-2-naphthaldehyde and 7-methoxy-l-naphthaldehyde, and are independent of NADH determinations. The results show high variability of ALDH levels in colon tumors, with several samples below sensitivity level (< 0.01 units per gram protein), while the highest activities of both ALDH1A1 and ALDH3A1 in tumor tissue were close to 0.5 U/g. Correlation coefficients between tumor and colon tissue activities were found to be below 0.5 for both ALDH activities examined, but the average activities were similar. and close to 0.1 U/g. thus similar to that found in the thyroid fragments. It is concluded that ALDH probably cannot be directly responsible for oxazaphosphorine resistance in colon cancer.
Acta Pol Pharm
PMID:Activities of cytosolic aldehyde dehydrogenase isozymes in colon cancer: determination using selective, fluorimetric assays. 1658 81

The aim of this study was to analyze the molecular mechanism of inositol hexaphosphate (InsP(6)) action through which it may inhibit proliferation of colon cancer cells and cell cycle progression. A kinetic study of p53 and p21(WAF1) mRNA increase was performed on human colon cancer HT-29 cells after treatment with 1, 5 and 10 mM InsP(6) for 6, 12, 24 and 48 h. Real-time-QPCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. The transcription of beta-actin and GAPDH genes was assessed in parallel to select the control gene with least variability. The 2(-Delta Delta Ct) method was used to analyze the relative changes in gene transcription. InsP(6) stimulated p53 and p21(WAF1) expression at the mRNA level, with the highest increase in p21(WAF1) mRNA occurring at 24 h, i.e., following the highest increase in p53 mRNA observed at 12 h. Based on these studies it may be concluded that the ability of InsP(6) to arrest the cell cycle may be mediated by the transcriptional up-regulation of the p53-responsive p21(WAF1) gene.
Acta Biochim Pol 2006
PMID:Quantitative analysis of the level of p53 and p21(WAF1) mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate. 1673 61

The role of gastrins and their receptors in the pathogenesis of colon cancer has been discussed for many years but it still remains unresolved. Although fluorouracil (FU) remains to be reference chemotherapy for colon cancer, its efficacy is unsatisfactory. Recently, we have shown a synergistic effect of proglumide (a non-selective blocker of cholecystokinin-gastrin receptors) applied together with FU, on the proliferation and apoptosis of transplantable Colon 38 cancer cells in vivo. The aim of this study was to examine direct effects of proglumide (10(-5)-10(-10) M) applied either alone or together with FU (0.25, 2.5 and 25 microg/ml) on the proliferation of murine Colon 38 cancer cells in vitro. Cell proliferation was assessed by the modified colorimetric Mosmann method. Proglumide inhibited the proliferation of Colon 38 cells at the concentrations of 10(-6), 10(-8) and 10(-10) M. FU inhibited the proliferation of cancer cells in all studied concentrations, exerting the most profound antiproliferative effect at the concentrations of 2.5 and 25 microg/ml. Thus, the former concentration was chosen to study its interactions with proglumide. Proglumide applied together with FU exerted a synergistic effect on the inhibition of proliferation of Colon 38 cells at 10(-8), 10(-9), 10(-10) M concentrations. The most profound inhibitory effect was observed in the group incubated with FU and 10(-10) M of proglumide. The obtained results indicate a possibility of new therapeutic options for colon cancer, but further studies are needed to elucidate, if the synergistic effect of FU and proglumide occurs also in the colon cancer in humans.
Endokrynol Pol
PMID:The combined effects of proglumide and fluorouracil on the growth of murine Colon 38 cancer cells in vitro. 1682 Dec 14

The extent of lymph node metastasis is a major determinant for the staging and the prognosis of most human malignancies. Although the clinical significance of lymph node involvement is well documented, molecular mechanisms that promote tumor spread into the lymphatic or blood vascular systems and widespread dissemination are not well understood. Although there is a large body of evidence that newly visualized lymphatics facilitate formation of metastases, it remains unclear whether these are "new" or simply pre-existing dilated vessels. High level of permeability of tumor blood capillaries brings about high tissue fluid and lymph formation. The physical forces but not the putative cancer-produced VEGF C may be responsible for more lymphatics seen around cancer than in normal tissue. The main question to be answered is: are there morphologic and functional differences between newly formed and pre-existing intra- or peri-tumoral lymphatics? In our experience specimens of gastric and colon cancer revealed presence of peri-tumoral but not intra-tumoral lymphatics. Tumor tissue contained numerous tissue fluid "lakes" communicating with lymphatics. We speculate that increased production of lymph in the tumor tissue caused by high blood capillary permeability brings about dilatation of the interstitial space and peri-tumoral lymphatics. Excessive lymph flow may drag tumor cells. This article is reviews current literature on the role of angiogenesis and lymphangiogenesis in cancer metastasis with respect to own research.
Pol Merkur Lekarski 2007 May
PMID:[The role of immune system in colon metastasis. Lymphangiogenesis or lymphedema in cancer tissue]. 1767 95

One of the most promising strategies in colon cancer therapy is the sensitization of cancer cells to natural proapoptotic cytokines, such as death ligands and interferons, which are able to eliminate abnormal cells. The investigation of mechanisms determining the immune escape of cancer cells revealed the presence of antiapoptotic proteins, such as cFLIP, which inhibit cell death signal transduction. Numerous studies showed that the use of different metabolic inhibitors, such as cycloheximide (CHX), reduces the cFLIP protein level, thus restoring the susceptibility to TNF-alpha-induced apoptosis. However, high non-specific toxicity of CHX excludes the clinical use of this substance. The current efforts are focused on identification of bioactive compounds which could safely support immunotherapy. The review presents in vitro and in vivo evidence that butyrate (Bt), fatty acid produced in colon during fermentation process and parthenolide (PN), sesquiterpene lactone isolated from Tanacetum parthenium specifically affect different cancer cells. Among described various molecular mechanisms of Bt and PN action, one reduces the level of antiapoptotic proteins. This paper clearly demonstrates that bioactive compounds, especially combined with immune cytokines could be seriously considered as an alternative for routine colon anti-cancer therapy.
Pol J Vet Sci 2007
PMID:Antiapoptotic proteins as targets for bioactive compounds. 1788 39

The poor efficacy of reference chemotherapy (fluorouracil -FU) in colon cancer has resulted in a constant search for agents which could augment the action of FU. Epidemiological data, such as the decreased risk of colorectal cancer among menopausal women receiving hormonal replacement therapy, indicate the role of oestrogen in the pathogenesis of this disease. The differences between normal and neoplastic colon cells in the expression of oestrogen receptor beta (ERbeta) could confirm this association. However, the direct influence of oestrogen or tamoxifen (SERM, selective oestrogen receptor modulator) on colon cancer growth has rarely been studied. The aim of the present study was to examine the direct effects of various concentrations of oestradiol and tamoxifen (10(-4) to 10(-12) M), applied alone or together with FU, on the growth of murine Colon 38 cancer in vitro as assessed by three colorimetric methods: Mosmann's method, incorporation of BrdU into cell nuclei and the TUNEL method. At high concentrations oestradiol and tamoxifen decreased the cancer growth in a dose- and time-dependent manner (the Mosmann and BrdU methods) and at some concentrations augmented the cytotoxic action of FU (Mosmann's method). Tamoxifen exerted a very early and potent inhibitory effect, inducing even total cancer growth inhibition at the concentration of 10(-4) M (the Mosmann and BrdU methods). All the substances studied at different concentrations and at different incubation time points increased the apoptosis of tumour cells (the TUNEL method). The results indicate that oestradiol and tamoxifen inhibit Colon 38 cancer growth and increase the cytotoxic effect of FU, which confirms the role of sex steroids in colon carcinogenesis and even suggests new therapeutic schemes.
Endokrynol Pol
PMID:Oestradiol and tamoxifen inhibit murine Colon 38 cancer growth and increase the cytotoxic effect of fluorouracil. 1805 39

Inositol hexaphosphate (IP6, phytic acid) is a naturally occurring carbohydrate abundantly present in high-fiber diets and it is also contained in almost all mammalian cells. It plays an important role in signal transduction, cell proliferation and differentiation. Some natural substances have been shown to elicit an impact on the expression of TNF-alpha and its receptors in cancer cells. TNF-alpha represents cytokine very often deregulated at the level of both gene expression and signal transmission through TNF-alpha receptors (TNFRI and TNFRII). The aim of the present study was to analyze the IP6 influence on the transcription of genes coding for TNF-alpha and its receptors in human colon cancer cells line Caco-2 Real-time QRT-PCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. Three concentrations (1, 2.5 and 5 mM) of IP6 were used for Caco-2 cells stimulation for 1, 6, 12 and 24 h. The results showed that IP6 modulated the expression of the listed genes at transcription level in a dose and time dependent manner. The enhanced TNFRI and decreased TNF-alpha and TNFRII transcription in Caco-2 cells stimulated for 12 h with IP6 seems to be the presumptive evidence for anti-inflammatory and antitumor activity of IP6.
Acta Pol Pharm
PMID:The influence of phytic acid on TNF-alpha and its receptors genes' expression in colon cancer Caco-2 cells. 1853 77

Over the last years phytic acid, a hexaphosphorylated inositol (IP6) has attracted particular attention due to its anti-cancer activity, however, the molecular mechanisms of its action have not been elucidated, as yet. The aim of this study was to evaluate the influence of phytic acid on the expression of genes encoding p65 and p50 subunits of NF-kappaB and of its inhibitor IkappaBalpha in human colorectal cancer cell line Caco-2. A kinetic study of p65 and p50 subunits and IkappaBalpha mRNAs expression was performed on Caco-2 cells after treatment with 1, 2.5 and 5 mM IP6 for 1, 6, 12 and 24 h. Quantification of the genes expression was carried out using real time QRT-PCR technique. Treatment of cells with 5 mM IP6 resulted in a strong increase in IkappaBalpha expression at 6 h, 12 h and 24 h. The level of p65 transcript after 1 h was lower in the cells exposed to 1, 2.5, and 5 mM IP6 than in the control cells. The increase in transcriptional activity of p65 gene in response to 5 mM IP6 after 6 h and 12 h was observed. Cells treated for 24 h with 2.5 mM and 5 mM IP6 showed a significant decrease in expression of p65 gene. There were no quantitative changes in the p50 gene expression in the cells treated with IP6 compared to the control cells. High positive correlation between the expression of IkappaBalpha and p65 was detected. The results of this study suggest that IP6 primarily influences p65 and IkappaBalpha genes expression in colon cancer cells. Changes in transcriptional activities of IkappaBalpha and p65 depend on IP6 concentration and time of its action.
Acta Pol Pharm
PMID:Evaluation of the expression of transcriptional factor NF-kappaB induced by phytic acid in colon cancer cells. 1917 51

Colorectal cancer, one of the most challenging malignancies, still has a limited number of recognized prognostic and predictive markers indicating appropriate treatment. MACC1 (metastasis-associated in colon cancer-1), a novel regulator of tumor growth and metastasis has recently been identified as an important prognostic factor of metastatic disease in colorectal cancer. The mechanism of MACC1 activity remains undetermined. Here we apply a combination of fold recognition and homology modeling algorithms to draft MACC1 function. The applied methods revealed that the MACC1 protein consists of four domains: ZU5, SH3, and two C-terminal death domains (DD). Previously a similar domain architecture (ZU5-DD) was observed in other proteins, involved mainly in signal transduction and apoptosis regulation. Based on the specific aspects of the closest homologues' biology functional hypotheses on MACC1 are proposed. A broad range of bioinformatic analyzes indicates that MACC1, besides its involvement in signal transduction from the MET receptor, links MET signaling and apoptosis.
Acta Biochim Pol 2009
PMID:Unexpected domain composition of MACC1 links MET signaling and apoptosis. 1949 89


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