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

For investigations involving monoclonal antibodies (mAbs) against cellular antigens cell binding assays are routinely used to determine the immunoreactive fraction after radiolabeling. In general, surface antigens are targets for radioimmunodetection, but recent studies indicate that intracellular determinants may also prove useful for this purpose. Thus, there is a need to adapt the regular cell binding assay for use with antibodies directed against cytoplasmic antigens. Here we describe a fixation method which permits such mAbs to bind to cell surfaces as well as to intracellular determinants. Moreover, the procedure may be used for antigens that are sensitive to the commonly used aldehyde fixatives. The method is illustrated with two human IgM mAbs 16.88 and 28A32, which recognize cytoplasmic antigens. Human colon cancer cells in suspension were fixed with either acetone or glutaraldehyde. Intracellular antigens appeared to be best exposed for antibody binding after fixation with acetone as determined by immunofluorescent staining and flow cytometry. An antibody directed against the cell surface antigen HLA class I showed similar binding with both live cells and acetone-fixed cells. Double-inverse plots of the binding of radiolabeled 16.88 or 28A32 antibody with acetone-fixed cells gave reliable immunoreactive fraction values. Acetone-fixed cells stored at 4 degrees C could be used for immunoreactivity assays for at least 6 months without loss of performance.
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PMID:Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies directed against intracellular antigens. 140 43

To establish patterns of mucin staining in the colon, a differential staining method was developed separating acid mucins into sialomucins and sulfomucins, and their distribution was studied along the colon of 9 normal subjects, 6 patients with ulcerative colitis in remission and 9 with colon cancer. Serial mucosal biopsies from the cecum to the rectum, were taken at colonoscopy and stained with aldehyde-fuchsin and alcian blue. The mean score of staining intensity in normals for sialomucins was higher than for sulfomucins, 1.85 +/- 0.05 versus 0.60 +/- 0.08 (p < 0.05). A significantly lower staining score for sulfomucins was found in the descending colon and in the cecum when compared with the rectum. Ninety-seven percent of the slides were positive for sialomucins, but only 50% for sulfomucins (p < 0.05). The mean (+/- SE) staining intensity for sialomucins in the ulcerative colitis and cancer group was 1.60 +/- 0.08 and 1.60 +/- 0.05 (p = 0.002 and p < 0.05 when compared with the controls, respectively). A difference in the percentage of biopsies positive for sulfomucins, in controls and proctosigmoiditis groups, was also observed: 50.0 and 33.3%, respectively (p = 0.013). No significant change was demonstrated in the mean sulfomucin staining score comparing normal and colon cancer patients. Our results may be used as a baseline for further research on mucin staining patterns in colorectal inflammatory and neoplastic diseases.
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PMID:Histochemical characterization of mucosal mucin in serial biopsies along the human colon. 878 99

Alcohol ingested orally is transported to the colon by blood circulation, and after the distribution phase, intracolonic ethanol levels are equal to those in the blood. Recent studies in our laboratory suggest that in the large bowel ethanol is oxidized by a bacteriocolonic pathway. In this pathway intracolonic ethanol is at first oxidized by bacterial alcohol dehydrogenase to acetaldehyde. Then acetaldehyde is oxidized either by colonic mucosal or bacterial aldehyde dehydrogenase to acetate. Part of intracolonic acetaldehyde may also be absorbed to portal vein and be metabolized in the liver. The bacteriocolonic pathway offers a new explanation for the disappearance of a part of ethanol calories. Due to the low aldehyde dehydrogenase activity of colonic mucosa, acetaldehyde accumulates in the colon. Accordingly during ethanol oxidation highest acetaldehyde levels of the body are found in the colon and not in the liver. High intracolonic acetaldehyde may contribute to the pathogenesis of alcohol-induced diarrhoea. Because acetaldehyde is a carcinogen in experimental animals, it may also contribute to the increased risk of colon polyps and colon cancer, which have been found to be associated with heavy alcohol consumption. Intracolonic acetaldehyde may also be an important determinant of the blood acetaldehyde level and a possible hepatotoxin. In addition to acetaldehyde, gut-derived endotoxin is another potential candidate in the pathogenesis of alcohol-related liver injury. Experimental alcoholic liver injury has recently been prevented by antibiotics, and this effect was related to the prevention of endotoxin-induced activation of Kupffer's cells.
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PMID:Bacteriocolonic pathway for ethanol oxidation: characteristics and implications. 881 Nov 62

Thermally oxidized animal fat (beef tallow) was assessed for colon cancer-promoting and -initiating activity in F-344 rats and CF-1 mice with the use of the aberrant crypt focus (ACF) assay. In two promotion studies, extensively oxidized beef tallow (110 degrees C for 144-168 h, peroxide value approx 200 meq/kg, with > 80% loss of allylic and olefinic protons) had relatively little effect on the growth of ACF in F-344 rats. The multiplication constant for treatment/control of ACF size in aberrant crypts per ACF at 100 days was 1.07 (95% confidence interval = 1.01-1.14) and 0.98 (95% confidence interval = 0.91-1.06). ACF size was not affected by less extensively oxidized beef tallow or by a 10-fold reduction of dietary alpha-tocopherol during the growth of the ACF. In initiation studies, extensively oxidized beef tallow administered by gavage increased the number of animals with ACF and the number of ACF per colon (11 of 23 and 5 of 29 animals with ACF; 1.09 +/- 0.29 and 0.21 +/- 0.09 ACF/colon, respectively). Less severely oxidized beef tallow was without effect. Further studies with CF-1 mice confirmed that extensively oxidized beef tallow increased numbers of animals with ACF and average ACF per colon. The unsaturated aldehyde acrolein was without effect in the ACF assay. These data suggest that highly thermolyzed beef tallow contains an uncharacterized initiator or leads to conditions in which spontaneously initiated ACF are increased.
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PMID:Thermally oxidized dietary fat and colon carcinogenesis in rodents. 950 16

Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer; however, these data are confounded by numerous cosegregating variables. Previous experimental reports with the rodent carcinogen model have also yielded discordant results. To clarify the alcohol-colon cancer relationship, we used the MIN (multiple intestinal neoplasia) mouse, a genetic model of intestinal tumorigenesis. Twenty-four MIN mice were randomized to ethanol supplementation in the drinking water (15% alternating with 20% on a daily basis) or control. Mice were sacrificed after 10 weeks, and the intestinal tumors were scored under magnification. Tissue sections were assessed for apoptosis and cell proliferation rates, along with the presence of the malondialdehyde-acetaldehyde (MAA) adduct, a mutagenic adduct associated with ethanol consumption. Ethanol supplementation resulted in a significant increase in tumor number (135 +/- 35%; P = 0.027 versus control). The induction of tumorigenesis by ethanol was most dramatic in the distal small bowel (167 +/- 56%; P = 0.01). In the uninvolved intestinal mucosa, there was no difference in proliferative or apoptotic indices. Cytoplasmic and nuclear MAA adducts were detected in both ethanol-treated and control mice. We demonstrated that ethanol ingestion increased intestinal tumorigenesis in the MIN mouse model. Furthermore, whereas mechanisms remain incompletely elucidated, our data implicate formation of MAA adducts. This report provides further support that ethanol consumption is a risk factor for colorectal cancer.
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PMID:Ethanol promotes intestinal tumorigenesis in the MIN mouse. Multiple intestinal neoplasia. 1243 35

A synthesis of four Annonaceous acetogenins, asiminocin, asimicin, asimin, and bullanin, by a modular approach from seven fundamental subunits, A-G, is described. The approach employs a central core aldehyde segment, C, to which are appended an aliphatic terminus, A or B, a spacer subunit, D or E, and a butenolide terminus, F or G. Coupling of the A, B, D, and E segments to the core aldehyde unit is effected by highly diastereoselective additions of enantiopure allylic indium or tin reagents. The butenolide termini are attached to the ACD, BCE, or BCD intermediates by means of a Sonogashira coupling. The design of the core, spacer, and termini subunits is such that any of the C30, C10, or C4 natural acetogenins or stereoisomers thereof could be prepared. IC50 values for the four aforementioned acetogenins against H-116 human colon cancer cells were found to be in the 10(-3) to 10(-4) microM range. The IC90 activities were ca. 10(-3) microM for asimicin and asimin but only 0.1-1 microM for bullanin and asiminocin.
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PMID:A modular synthesis of annonaceous acetogenins. 1260 90

Bis-cyclic butenolides, 5-arylated 2(5H)-furanones 6a - c, 7a, b and the 3(2H)-pyridazones 9a - d were prepared by using the aldehyde form of muco halogen acids in electrophilic substitution reactions and in an aldol-like condensation reaction. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture studies on MAC 13 and MAC 16 murine colon cancer cell lines. The butyl furanone 3 displayed the highest cytotoxicity of 3 microM, as one selected example of a series of dichlorinated pseudoesters. The 5-arylated 2(5H)-furanones 6 and 7 did not show a structure-activity relationship (SAR) depending on the substitution pattern of the aromatic system. An IC50 (concentration inhibiting growth by 50%) was found within a range of 30-50 and 40-50 microM for the MAC 13 and MAC 16 cell lines, respectively. The pyridazine series 9 showed a maximum in-vitro activity for the p-methoxydrivative 9b, having an IC50 of 17 in MAC 13 and 11 microM in MAC 16 cell lines. Selected examples of each series and further novel 2(5H)-furanones such as the hydrazone 5 and the hydantoin 8 have been screened in-vivo in mice and the data are presented. For the pyridazines 9a - d, the in-vitro cytotoxicity correlated with an in-vivo inhibition of tumour growth. The ring expansion of the 5-membered 2(5H)-furanone ring system such as 6a into the 6-membered 3(2H)-pyridazone 9b led to an agent with improved antineoplastic properties. On the resistant MAC 16 cell line the pyridazone 9b displayed 52% tumour inhibition in mice at a dose of 50 mg kg(-1) compared with 27% for the 5-FU standard.
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PMID:Synthesis and evaluation of 5-arylated 2(5H)-furanones and 2-arylated pyridazin-3(2H)-ones as anti-cancer agents. 1460 69

Inhibition of prostaglandin E(2) (PGE(2)) and cyclooxygenase (COX)-2 by nonsteroidal anti-inflammatory drugs reduces the progression of colon cancer. Inhibition of aldose reductase (AR; EC. 1.1.1.21.) by sorbinil or by antisense ablation prevented fibroblast growth factor-induced and platelet-derived growth factor-induced up-regulation of PGE(2) synthesis in human colon cancer cells, Caco-2. AR besides reducing aldo-sugars efficiently reduces toxic lipid aldehydes and their conjugates with glutathione. Inhibition of AR prevented growth factor-induced COX-2 activity, protein, and mRNA and significantly decreased activation of nuclear factor-kappaB and protein kinase C (PKC) and phosphorylation of PKC-beta2 as well as progression of Caco-2 cell growth but had no effect on COX-1 activity. Cell cycle analysis suggests that inhibition of AR prevents growth factor-induced proliferation of Caco-2 cells at S phase. Treatment of Caco-2 cells with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal (HNE) or its glutathione-conjugate [glutathionyl-HNE (GS-HNE)] or AR-catalyzed product of GS-HNE, glutathionyl-1,4-dihydroxynonane (GS-DHN), resulted in increased COX-2 expression and PGE(2) production. Inhibition of AR prevented HNE- or GS-HNE-induced but not GS-DHN-induced up-regulation of COX-2 and PGE(2). More importantly, in vivo studies showed that administration of AR-small interfering RNA (siRNA), but not control siRNA, to nude mice bearing SW480 human colon adenocarcinoma cells completely arrested tumor progression. Collectively, these observations suggest that AR is an obligatory mediator of growth factor-induced up-regulation of COX-2, PGE(2), and growth of Caco-2 cells, indicating that inhibition of AR may be a novel therapeutic approach in preventing the progression of colon cancer.
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PMID:Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and prostaglandin E2 production in human colon cancer cells. 1701 29

The effects of polyunsaturated fatty acids (PUFAs) obtained from the diet on colorectal cancer have been widely explored. However, controversial results have been obtained about the role played by the lipid peroxidation products of PUFAs, such as 4-hydroxy-nonenal (HNE), in the control of colon cancer growth. This aldehyde, indeed, showed both procarcinogenic and protective effects. In an attempt to verify the action of HNE, we studied the effects of a low dose of HNE (1 microM), similar to those "physiologically" found in normal cells and plasma, on telomerase activity, a key parameter of malignant transformation. Caco-2 cells were exposed to HNE and, paralleling cell growth inhibition, we observed the down-regulation of telomerase activity and hTERT expression. Similar effects have also been observed in HT-29 cells, in which HNE inhibited cell proliferation, telomerase activity and hTERT expression, suggesting that the inhibition of telomerase activity could be a general mechanism involved in the antiproliferative effect exerted by this aldehyde. Finally, we elucidated the mechanism of hTERT inhibition by HNE. A reduction of GSH content preceded the decrease of telomerase activity, but this only partially explained the telomerase activity inhibition. The major mechanism of HNE action seems to be the modulation of expression and activity of transcription factors belonging to the Myc/Mad/Max network. Since the presence of PUFAs in the diet exposes epithelial colon cells to HNE, this aldehyde could contribute to cell growth control through the inhibitory action on telomerase activity and hTERT expression, suggesting a protective effect on colon mucosa.
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PMID:4-hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity. 1973 43

A series of DAG-lactones with polar 3-alkylidene substituents have been investigated as PKC-alpha ligands and antitumor agents. Extensive analysis of structure-activity relationships for the 3-alkylidene chain revealed that polar groups such as ether, hydroxyl, aldehyde, ester, acyloxy, and amido were tolerated with similar binding affinities and reduced lipophilicities compared to the corresponding unsubstituted alkylidene chain. Among the derivatives, compounds 5, 6 and 8 with an ether type of side chain showed high binding affinities in range of K(i)= 3-5 nM and excellent antitumor profiles, particularly against the colo205 colon cancer and the K562 leukemia cell lines.
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PMID:Polar 3-alkylidene-5-pivaloyloxymethyl-5'-hydroxymethyl-gamma-lactones as protein kinase C ligands and antitumor agents. 2004 44


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