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)

Immunoperoxidase staining for Regan isoenzyme of alkaline phosphatase was performed on cryostat sections of five human tumor tisssues. With a direct immunoperoxidase staining for the localization of Regan isoenzyme at the light and electron microscope levels, sections previously fixed with 0.05 M phosphate-buffered 4% paraformaldehyde were reacted with rabbit antisera to human placenta alkaline phosphatase conjugated to horseradish peroxidase. Comparison of conventional histochemistry and immunohistochemistry for Regan isoenzyme indicated that strong specific immunoperoxidase staining appeared on the cell membrane surface, and a diffuse one, in the cytoplasm of lung and colon cancer tissue cells showing L-phenylalanine-sensitive alkaline phosphatase. No immunoperoxidase reaction was obtained in tumor cells showing sensitivity to L-homoarginine or lacking aklaline phosphatase activity.
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PMID:Direct immunoperoxidase staining for Regan isoenzyme of alkaline phosphatase in human tumor tissues. 18 52

Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.
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PMID:Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors. 167 42

Conjugates of the chemotactic peptide fMet-Leu-Phe (fMLP) to IgG retain chemotactic and antigen recognition function in vitro and enhance intra-tumour macrophage numbers in a guinea pig model. We report a study approved by the ethics committee on the acute toxicity of fMLP conjugates in ten consenting cancer patients with metastasizing melanoma and colon cancer. They were given increasing single doses (1-2500 micrograms) IgG-fMLP made with the anti-melanoma monoclonal antibody (mAb) 9.2.27. Clinical examinations and blood cell counts, urinalysis, electrolytes, and liver and kidney function tests before and after the infusion and weekly thereafter revealed no relevant toxicities. One patient had a herpes zooster exacerbation on day 1, which was judged to be coincidental. Peak post-infusion conjugate serum concentrations fell to unmeasurable levels within a few days. In no case was a human humoral anti-(mouse Ig) immune response detected.
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PMID:Acute and subacute toxicity of chemotactic conjugates between monoclonal antibody and fMet-Leu-Phe in humans: a phase I clinical trial. 200 48

A new enzyme which hydrolyzes anilide substrates of p-guanidino-L-phenylalanine in preference to those of arginine was found in the ascitic plasma from Ehrlich ascites tumor-bearing mice. The activity of this enzyme on N alpha-benzyloxycarbonyl-p-guanidino-L-phenylalanine p-nitroanilide was strongly inhibited by diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride but not by sulfhydryl-reactive reagents and metal chelating agents. Peptide substrates containing p-guanidino-L-phenylalanine were hydrolyzed by this enzyme much faster than those containing arginine. These results suggest that this enzyme is a different type of serine protease from trypsin and thrombin. This enzyme was also found in the human gastric and colon cancer cells and their surrounding ascitic plasmas.
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PMID:A new serine protease which preferentially recognizes p-guanidino-L-phenylalanyl residue in ascitic plasma from Ehrlich ascites tumor-bearing mice. 389 Aug 49

Treatment of the human rectal cancer cell line HRT-18 with sodium butyrate caused a reversible elevation of alkaline phosphatase activity which was inhibited by cycloheximide and actinomycin D. The alkaline phosphatase in untreated cells was heat stable at neutral pH and inhibited by phenylalanine but not by homoarginine, and 80% of the enzyme activity was precipitated by antibody against human term-placental enzyme. Following butyrate treatment, the enzyme became more sensitive to all the inhibitors tested and more heat stable, compared to the enzyme in control cells. In addition, the butyrate-induced enzyme could be completely precipitated by anti-placental alkaline phosphatase antibody. The electrophoretic pattern of the butyrate-induced enzyme was different from that of control cells. Control HRT-18 cells contained a butyrate-insensitive heat-labile alkaline phosphatase component with an electrophoretic mobility similar to the enzyme from human colon cancer tissues. The alkaline phosphatase from four human colon cancer tissues was of the early placental form, while the enzyme from human normal mucosa was of the intestinal type.
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PMID:Effect of sodium butyrate on alkaline phosphatase in HRT-18, a human rectal cancer cell line. 712 94

Metastatic rat colon cancer cells but not normal rat hepatocytes showed activity of cathepsin B on their plasma membranes. Activity was visualized in living cells with a new fluorogenic substrate, [Z-Arg]2-cresyl violet, and confocal microscopy. When these cancer cells were injected into the portal vein of rats, the animals developed tumors in the liver in a heterogeneous fashion. Three- to four-fold more tumors were found in the small caudate lobe than in the other three large lobes of the liver. Oral treatment with a selective water-soluble inhibitor of extracellular cathepsin B, Mu-Phe-homoPhe-fluoromethylketone, resulted in 60% reduction of the number of tumors and 80% reduction of the volume of tumors in the three large lobes whereas tumor development was not affected in the small caudate lobe. This study supports the conclusions that (a) extracellular cathepsin B plays a crucial but complex role in liver colonisation by rat colon carcinoma cells in vivo, (b) its selective inhibition suppresses tumor growth heterogeneously in the liver and (c) the caudate lobe of the liver is a relatively large risk factor for tumor development.
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PMID:Heterogeneous suppression of experimentally induced colon cancer metastasis in rat liver lobes by inhibition of extracellular cathepsin B. 951 97

Flavonoids are found in many food items of plant origin. Intake of flavonoids has been linked to the prevention of human diseases including cancer. However, little is known about the intestinal absorption of flavonoids in the cellular level. This study was designed to study the absorption of dietary flavonoids using cultured human intestinal epithelial cell monolayer as a model system and 14C-flavone as a model compound. 14C-flavone at 10 microM was found to move across the cell monolayer rapidly both from the luminal to basolateral direction and from the basolateral to luminal direction. The rate of transport from the luminal to basolateral direction was 5 times of the rate for phenylalanine, an aromatic amino acid. Flavone also accumulated substantially in the cells. Replacing sodium in the transport buffer with potassium did not affect the transport but reducing the incubation temperature significantly decreased the initial rate of transport. The presence of protein in the transport buffer reduced the initial rate of transport to half. Other flavonoids and hydrophobic chemicals at 100 microM had no effects on the transport. Together with the evidence from microscopic observation (Cancer Letts. 110: 41-48, 1996), this study supports that rapid diffusional transport may be the main route for flavonoid absorption. The ability of intestinal cells to accumulate flavone is consistent with the role of flavonoids in colon cancer prevention.
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PMID:Transepithelial transport and accumulation of flavone in human intestinal Caco-2 cells. 987 22

IL-1beta stimulation of cultured epithelial cells induces the degradation of IkappaBalpha and the consequent nuclear translocation of NF-lambdaB, a critical proinflammatory transcription factor in the mucosal host immune response. The role of reactive oxygen intermediates, serine protease activity, and tyrosine kinase activity in the activation of NF-kappaB is weakly conserved across various cell lineages and has not been defined in human enterocytes, a major target of oxidant stress in sepsis, thermal injury, and hemorrhagic shock. We report here that in Caco-2BBe cells, a transformed human colon cancer cell line with features of small intestinal epithelial cells in culture, exposure to oxidant stress (hydrogen peroxide 1-10 mM) did not induce NF-kappaB activation. Similarly, scavenging of free radicals and oxidants by pyrrolidine dithiocarbamate and dimethyl sulfoxide did not block IL-1beta-induced IkappaBalpha degradation and NF-kappaB activation. Genistein, a nonspecific tyrosine kinase inhibitor, also had no effect on IL-1beta-mediated effects on NF-kappaB. Serine protease inhibition by tosyl-lysine-chloromethylketone and tosyl-phenylalanine-chloromethylketone inhibited IkappaBalpha degradation and NF-kappaB activation stimulated by IL-1beta. Our data highlight the strong divergence between epithelial and mononuclear cells in the signal transduction pathways relating IL-1beta stimulation and NF-kappaB nuclear translocation.
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PMID:IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling. 1063 62

A new bifunctional chelating agent MAGIPG was synthesized in good yield using Boc-p-nitro-phenylalanine as the starting material. 99mTc-labeled-MAGIPG-D612 conjugates reactive with human colon cancer were prepared in 3% to 15% yield with a radiochemical purity of 63% to 97%. 186Re-labeled MAGIPG-D612 conjugates were prepared with a 7% to 30% yield and a radiochemical purity of 82% to 98%. The biodistribution results demonstrate that these radioimmuno-conjugates selectively localized in LS174T human colon cancer xenografts.
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PMID:Synthesis and biodistribution of peptide based 99mTc/186Re-MAGIPG-D612 monoclonal antibody in nude mice bearing colon cancer xenografts. 1085 48

Goblet cell depletion occurs in various forms of colitis, but its mechanism is unknown. We have investigated two linked hypotheses: (i) that bacterial peptides, such as formyl-methionyl-leucyl-phenylalanine (fMLP), interact with epithelial cells inducing the release of chemokines, including interleukin-8 (IL-8), which in turn leads to the recruitment of neutrophils which release mucin secretagogues; (ii) that fMLP acts directly on epithelial cells to cause mucus secretion. Studies were performed to measure the effects of fMLP on the synthesis and secretion of IL-8 and mucus by the goblet cell differentiated colon cancer cell lines HT29-MTX (methotrexate-conditioned HT29 colonic adenocarcinoma cell line) and LS174T, and to assess the effects of neutrophil-derived secretagogues on goblet cell secretion in these cell lines. fMLP (0.1 microM) increased the secretion of IL-8 by 105% (P<0.0001) in HT29-MTX cells and by 401% (P<0.0001) in LS174T cells. fMLP also increased the synthesis and secretion of mucins by these cell lines, with maximal effects of 65% above control values for synthesis (P<0.01) and 73% for secretion (P<0.01). A dose-related increase (up to 67%; P<0.01) in mucin secretion was demonstrated in HT29-MTX cells in response to incubation with supernatant from activated neutrophils. This effect was largely (83%; P<0.02) inhibited by ICI 200,355, a specific inhibitor of neutrophil elastase. In conclusion, the bacterial peptide fMLP and neutrophil elastase are both potent mucus secretagogues for colon epithelial cells. fMLP also elicits release of the potent neutrophil chemoattractant IL-8 from colon epithelial cells. These findings support the hypothesis that the mucosal inflammation and mucus depletion seen in ulcerative colitis could result from interaction between bacterial peptides and the mucosa.
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PMID:Interaction between bacterial peptides, neutrophils and goblet cells: a possible mechanism for neutrophil recruitment and goblet cell depletion in colitis. 1156 77


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