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

The synthesis and secretion of mucin-like high-molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco-2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H-glucosamine labelling and chromatography on Sepharose CL-4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high-molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N-glycanase), alkaline-borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl-alpha-GalNAc, and by CsCl-density-gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco-2 cells, the spontaneous post-confluent enterocytic differentiation with increased brush-border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GalNAc transferase and beta 1,3-galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin-like glycoproteins can be synthesized by cell lines derived from non-mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.
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PMID:Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro. 172 5

Several different strategies to improve the in vitro cytocidal effect of 5-fluorouracil/leucovorin (5FU/LV), including modulation of dosage and schedule and combination with other cytotoxic agents or biochemical modulators, were examined in the COLO 320DM and Ht-29 cell lines by means of the Bactec system. Modest enhancement of 5FU activity by coadministration of LV was observed in both human colon cancer cell lines. Neither increased concentrations of LV nor prolonged drug exposure or preincubation with LV were found to enhance significantly the growth inhibitory activity of combined 5FU/LV. The only parameter that was found to affect the killing potential of the combination was the concentration of 5-FU, suggesting that lower doses of the antimetabolite would be more effective (COLO 320DM: P less than 0.003; Ht-29 P less than 0.02). The addition of either cisplatin, hyaluronidase or dipyridamole to 5-FU/LV yielded synergistic growth inhibition in 3/6, 2/6 and 2/6 human colon cancer cell lines, respectively. Strictly additive effects were noted for the combination with BCNU as well as concurrent exposure of the cells to 42 degrees C hyperthermia. Whether or not certain combined 5FU/LV drug regimens will result in an improved therapeutic index, however, remains to be determined in properly designed clinical trials.
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PMID:A study of various strategies to enhance the cytotoxic activity of 5-fluorouracil/leucovorin in human colorectal cancer cell lines. 262 28

Colon cancer cells in culture synthesize and secrete mucin glycoproteins, which carry a number of cancer-associated antigens. However, the structures and mechanisms of biosynthetic processing are not well understood. Mucins synthesized and secreted by LS174T human colon cancer cells were compared to those in LS174T xenografts in athymic mice. Mucins radiolabeled with glucosamine or sulfate were purified by gel filtration and cesium chloride density gradient centrifugation. The mucins were of high molecular weight and were resistant to chondroitinase ABC, hyaluronidase and HNO2 treatment. They were, however, susceptible to pronase digestion and mild alkaline treatment. Using radiochemical precursors, the cellular mucin was shown to contain fucose, galactose, N-acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid, and sulfate. Oligosaccharides released by beta-elimination had N-acetylgalactosaminitol as the reduced amino sugar and also unreduced galactosamine, indicating that there is N-acetyl-galactosamine O-glycosidically attached to protein core and also peripheral N-acetyl-galactosamine not directly linked to protein. DEAE-cellulose chromatography of mucins showed two major peaks with both intracellular and secreted mucins, but xenograft mucins also had more acidic components. Sulfate-labeled mucins were shifted to less acidic peaks by neuraminidase digestion, which indicates that the same mucin molecules are both sialylated and sulfated. We conclude that the intracellular mucins of cultured colon cancer cells, those secreted into the medium, and those in nude mouse xenografts are chemically similar, but differ in sialic acid and sulfate content. This experimental model system, LS174T cells maintained in culture and as nude mouse xenografts, may be useful for further biosynthetic and structural studies of colon cancer mucin.
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PMID:Comparison of metabolically labeled mucins of LS174T human colon cancer cells in tissue culture and xenograft. 273 49

The human colon cancer cell line Caco-2 cultured in vitro displayed morphological differentiation which was shown to be a growth-related event. We have investigated this phenomenon further in relation to the cell surface glycosaminoglycans produced by growing (5-day, i.e., prior to differentiation) and confluent (9-day, i.e., after morphological and functional differentiation) cultures. Neosynthesized [35S]glycosaminoglycans were purified on DEAE-cellulose; at confluency, they were bound more strongly to the column than the corresponding fractions from the growing cells. Analysis of Kav values of heparan sulfate and chondroitin sulfates from growing and confluent cells indicated an increase in chain length of both glycosaminoglycans in morphologically differentiated cells. Heparan sulfate was the main 35S-labeled glycosaminoglycan of the cell surface of both 5-day and 9-day cultures. Paper chromatography of the unsaturated disaccharides obtained by chondroitinase digestion showed that chondroitin sulfate chains were primarily 6-sulfated in the 2 studied extracts. Heparan sulfate chains were isolated as chondroitinase-resistant material and treated with nitrous acid. Analysis of N- and O-sulfate group-related radioactivity showed an increase in the amount of 35S-label in the form of N-sulfate groups and an increase in the O-35S-sulfation pattern in heparan sulfate from morphologically differentiated cells. Thus, the structural features of both chondroitin sulfates and heparan sulfate were significantly different when the growing cells became morphologically differentiated.
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PMID:Biosynthesis of glycosaminoglycans in the human colonic tumor cell line Caco-2: structural changes occurring with the morphological differentiation of the cells. 340 19

Sulfated macromolecules synthesized in tumor and mucosa tissues derived from colorectal cancer patients were labeled with [35S]sulfate and separated into two fractions on DEAE-Sephacel: the slightly acidic peak (peak I) was eluted with 0.2 M NaCl and the highly acidic peak (peak II) was eluted with 0.5 M NaCl. A total of 40 specimens, which included primary colon cancer, liver metastases, and normal mucosa obtained at surgery (16 patients), were examined regarding the amount of peak I and peak II. The amount of peak I significantly decreased in the order of normal mucosa greater than primary tumors greater than metastases, while the amount of peak II did not significantly change among the tissues. Peak I was mostly resistant to chondroitinase ABC and nitrous acid treatment under acidic conditions, whereas combined chondroitinase-sensitive materials and nitrous acid-sensitive materials were greater than 80% of the radioactivity in peak II. The major radioactive component of peak I migrated at a position corresponding to Mr greater than 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and became Mr less than 40,000 after alkaline borohydride treatment. The major component of peak I was likely to be a sulfated glycoprotein containing sulfate groups on alkaline labile carbohydrate chains. Peak II consisted of a mixture of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans. Differential incorporation of [35S]sulfate into peak I among normal mucosa, primary colon carcinoma, and colon carcinoma metastasis was observed. Therefore, decreased peak I production may be a biochemical change associated with colorectal cancer progression and metastasis.
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PMID:Differential production of high molecular weight sulfated glycoproteins in normal colonic mucosa, primary colon carcinoma, and metastases. 356

Changes in colonic faecal microflora, enzymes of colonic energy metabolism, of cell proliferation and lipid profile in the serum and colon were studied in 48 mice exposed to cycas and fed a Nigeria-type diet. The animals were divided into three diet classes of 16 mice per class, and each class of animals was fed ad libitum either a normal diet, a high-carbohydrate high-fibre (HCF) diet or a high-protein high-fat (HPF) diet. Each diet class was subdivided into two equal groups of 8 animals each. One group was fed a diet type (acted as the diet control) without cycas, and the other group was fed the corresponding diet with cycas. The study period lasted for 3 weeks. The colonic faecal materials were acidified in the HCF-fed mice compared with the other diet-fed mice. Faecal beta-glucuronidase activity was significantly (p < 0.05) increased in the cycas-fed mice compared with the diet controls. Feeding mice with the HPF diet significantly (p < 0.05) increased beta-glucuronidase and mucinase activities. Colonic phosphofructokinase, glucose 6-phosphate dehydrogenase, lactate dehydrogenase and hyaluronidase activities were also significantly (p < 0.05) elevated in the cycas-treated mice. Feeding mice with the HPF diet also significantly (p < 0.05) increased these enzyme activities. Mice fed with the HCF diet significantly (p < 0.05) lowered serum total cholesterol, triglyceride and colonic total lipid. Colonic phosphatidylethanolamine and phosphatidylcholine were significantly (p < 0.05) increased in the HPF-fed mice. This study shows that the HCF diet alters the colonic faecal environment, colonic energy metabolism and hyaluronidase activity in ways which suggest its protective ability against the development of colon cancer in mice.
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PMID:Early biochemical events in mice exposed to cycas and fed a Nigerian-like diet. 787 55

Early alterations in cellular energy metabolism, reductive biosynthesis and enzymes related to cell proliferation were studied in 40 Wistar albino rats exposed to an acute level of deoxycholate (DOC), and fed different diets. The animals were divided into four equal groups and fed ad libitum either a normal diet (ND), a high-carbohydrate high-fibre (HCF) diet, or a high-protein high-fat (HPF) diet. Three times weekly intrarectal injection of 40 mg/0.2 ml DOC was given to three groups of the rats for 9 weeks. The specific activities of phosphofructokinase, pyruvate kinase, lactate dehydrogenase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were all significantly (p < 0.05) increased in the DOC-treated animals compared with the physiological saline-treated control. Reductive biosynthetic enzyme activities (malic enzyme, isocitrate dehydrogenase-NADP(+)-dependent, and ATP-citrate lyase) were reduced in the DOC-treated animals compared with the control. Feeding rats with the HCF diet significantly (p < 0.05) lowered the specific activities of the enzymes of glycolysis, of the pentose phosphate pathway (oxidative) and hyaluronidase and proteinase compared with those of the HPF-fed rats. These results show an altered enzymic profile in rats fed an HCF and an HPF diet compared with rats fed the ND and suggests a protective role of the HCF diet against the development of colon cancer.
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PMID:Early changes in energy metabolism in rats exposed to an acute level of deoxycholate and fed a Nigerian-like diet. 797 71

Decorin, a small proteoglycan containing a dermatan sulfate (DS) chain, is expressed abnormally in human colon cancer stroma. The aim of this study was to determine neoplastic changes in DS chains from human colon cancer and normal colonic mucosa. Proteoglycans were extracted from human colon cancer and normal colonic mucosa and successively digested with enzymes. The glycosaminoglycan obtained was fluoro-labeled with 2-aminopyridine at reducing terminals and fractionated by HPLC. Fluoro-labeled DS chains were collected and digested with bovine testicular hyaluronidase, followed by HPLC. The repeating disaccharide connected to the linkage region [glucuronosyl-galactosyl-galactosyl-xylosyl(2-aminopyridine)] of pyridylaminated DS chains from both types of tissue was glucuronosyl-N-acetylgalactosamine. The other glucuronic acid of the pyridylaminated DS chain was located 12 saccharides from the reducing terminal in colon cancer, and 18 saccharides from the reducing terminal in normal colon. The saccharide sequence of DS chains from human colon cancer is altered from that in normal colon.
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PMID:Neoplastic changes in saccharide sequence of dermatan sulfate chains derived from human colon cancer. 1185 49

Extracts of Aesculus hippocastanum (horse chestnut) seed have been used in the treatment of chronic venous insufficiency, edema, and hemorrhoids. Most of the beneficial effects of horse chestnut are attributed to its principal component beta-escin or aescin. Recent studies suggest that beta-escin may possess anti-inflammatory, anti-hyaluronidase, and anti-histamine properties. We have evaluated the chemopreventive efficacy of dietary beta-escin on azoxymethane-induced colonic aberrant crypt foci (ACF). In addition, we analyzed the cell growth inhibitory effects and the induction of apoptosis in HT-29 human colon cancer cell line. To evaluate the inhibitory properties of beta-escin on colonic ACF, 7-week-old male F344 rats were fed experimental diets containing 0%, 0.025%, or 0.05% beta-escin. After 1 week, the rats received s.c. injections of azoxymethane (15 mg/kg body weight, once weekly for 2 weeks) or an equal volume of normal saline (vehicle). Rats were continued on respective experimental diets and sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated histopathologically for ACF. Administration of dietary 0.025% and 0.05% beta-escin significantly suppressed total colonic ACF formation up to approximately 40% (P < 0.001) and approximately 50% (P < 0.0001), respectively, when compared with control diet group. Importantly, rats fed beta-escin showed dose-dependent inhibition (approximately 49% to 65%, P < 0.0001) of foci containing four or more aberrant crypts. To understand the growth inhibitory effects, HT-29 human colon carcinoma cell lines were treated with various concentrations of beta-escin and analyzed by flow cytometry for apoptosis and cell cycle progression. Beta-escin treatment in HT-29 cells induced growth arrest at the G1-S phase, which was associated with the induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), and this correlated with reduced phosphorylation of retinoblastoma protein. Results also indicate that beta-escin inhibited growth of colon cancer cells with either wild-type or mutant p53. This novel feature of beta-escin, a triterpene saponin, may be a useful candidate agent for colon cancer chemoprevention and treatment.
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PMID:Beta-escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21(waf1/cip1) in colon cancer cells. 1681 4

To treat cancer cells overexpressing P-glycoprotein (P-gp), we propose a new concept using a nanodrug. The nanodrug was prepared from polyethyleneimine (PEI)/all-trans retinoic acid (ATRA) conjugates (PRA) and covered with hyaluronic acid (HA) to control the cytotoxicity of PRA (yielding PRA-H). The size distribution of PRA-H was narrow, with an average particle size of approximately 143 nm. Its superior stability in phosphate-buffered saline (PBS) was verified by monitoring changes in particle size and zeta potential for 24 h, which were negligible. In contrast, PEI-H (not conjugated with ATRA) exhibited a significant change in particle size and zeta potential. Although PRA was highly cytotoxic against HCT-8 and SNU-484 cancer cells, both of which overexpress P-gp, the cytotoxicity was significantly reduced by shielding with HA. The cytotoxicity of PRA-H was recovered by treatment with hyaluronidase (HAase), which degrades HA and is present in tumors at high concentrations. These results were confirmed by optical microscopy, fluorescence-activated cell sorting (FACs) analysis, and confocal microscopy. The cytotoxic mechanism of PRA was revealed as a type of necrotic lysis by FACs analysis with propidium iodide (PI) staining. Furthermore, PRA increased HCT-8 cell (colon cancer) permeability to doxorubicin (DOX). Therefore, we concluded that PRA-H is a promising new candidate for the treatment of cells with multidrug resistance (MDR) induced by overexpression of P-gp and cancer stem cells.
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PMID:Polycationic nanodrug covered with hyaluronic acid for treatment of P-glycoprotein overexpressing cancer cells. 2068 38


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