Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sucrase-isomaltase (SI), trehalase (T) and lactase-beta-glucosidase (LG) activities were assessed histochemically in samples of colorectal adenomas (11 tubular, 12 tubulovillous, 10 villous) and 30 adenocarcinomas obtained by biopsy during colonoscopy or from specimens removed by surgical intervention. Small samples of tumor tissue, tissue of the transitional zone and of macroscopically normal mucosa were quenched in heptan cooled in an acetone-dry ice mixture. Cryostat sections, transferred to non-precooled slides and in some cases to semipermeable membranes, were dried and subjected to the histochemical reactions for SI, T and LG. Sucrose, 2-naphthyl, 6-Br-2-naphthyl, and 5-Br-4-Cl-3-indoxyl alpha-D-glucosides, trehalose, and 5-Br-4-Cl-3-indoxyl-beta-D-fucoside were used as substrates. Sections of jejunal biopsies with normal activities of brush border glycosidases were used as controls. From samples of 5 adenomas, 5 adenocarcinomas and collected rests of jejunal biopsies with a normal finding 10% (w/vol) homogenates in 2% Triton X-100 were prepared. Homogenates were frozen and thawed 3 times and their supernatants subjected to isoelectric focusing on polyacrylamide gel plates. Zymograms were developed with the same methods as for the detection of alpha-glucosidases in sections. In no colorectal tumor LG was present. SI was found in 70% adenocarcinomas, 50% villous, 25% tubulovillous and 19% tubular adenomas when the method with sucrose, glucose oxidase-peroxidase and 3,3'-diaminobenzidine was used. Hardly discernible traces of activity were found in tumors with azo-coupling reactions applied at pH 5, 6 and 6.5. No reaction was detected with the indigogenic method applied at pH above 6.0. However, jejunal biopsies displayed very strong reactions confined to the brush border of enterocytes under the same conditions. A strongly positive reaction was seen in 7 of 12 tumors investigated recently when the indigogenic reaction was applied at pH below 6.0 (particularly at pH 5.0). In this case the deposition of indigo was due to membrane and lysosomal alpha-glucosidases of the tumor cells and lysosomal alpha-glucosidase of macrophages and leukocytes. These findings were corroborated by zymograms. T was detected in the same tumors as SI; its activity was lower, however. SI activity in colorectal tumors is a useful, but not general marker of these tumors.
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PMID:Sucrase-isomaltase and other brush border glycosidases in colorectal tumors. 886 57

Axonal changes which develop around hematogenous metastases of the human brain were studied by immunohistochemistry using a monoclonal antibody to beta-amyloid precursor protein (beta APP) and the ABC method combined with glucose-glucose oxidase technique and nickel enhancement. The metastases were obtained from 18 autopsy cases with pulmonary carcinomas and 6 control cases without clinical history or gross pathology of brain diseases. beta APP immunoreactive material was present in distended axons around all the investigated metastases. Such immunoreactive axons were located close to the invading tumor cells. No immunoreactivity was seen in 5 of the 6 controls. Our investigation indicates that axonal transport is disturbed around metastases, made visible by the accumulation of beta APP immunoreactive material. The axonal dysfunction may well influence the clinical symptoms in cases with brain metastases.
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PMID:Beta-amyloid precursor protein accumulates in axons around hematogenous metastases of the human brain: immunohistochemical observations. 892

Natural killer-enhancing factor (NKEF) was identified and cloned on the basis of its ability to increase NK cytotoxicity. Two genes, NKEF-A and -B, encode NKEF proteins and sequence analysis presented suggests that each belongs to a highly conserved family of antioxidants. To examine the antioxidant potential of NKEF, we transfected the coding region of NKEF-B cDNA into the human endothelial cell line ECV304. The stable transfectant, B/1, was found to overexpress NKEF-B gene transcript and protein. We subjected B/1 to oxidative stress by either culturing them with glucose oxidase (GO), which continuously generates hydrogen peroxide, or by direct addition of hydrogen peroxide. We found that B/1 cells were more resistant than control cell lines. Resistance to hydrogen peroxide was originally thought to be mediated mainly by catalase and the glutathione cycle. Therefore, we used inhibitors to block the two pathways and found that B/1 cells were more resistant to oxidative stress than control cells when we used inhibitors to preblock either pathway. We also examined the cellular inflammatory responses to oxidized low-density lipoprotein (LDL) and bacterial lipopolysaccharide (LPS) by measuring monocyte adhesion to endothelial cells in vitro and found that B/1 cells were resistant to such responses. Lastly, we found that B/1 cells were more resistant to a novel chemotherapeutic agent CT-2584, which appears to kill tumor cells by stimulating production of reactive oxygen intermediates in mitochondria. These results demonstrate that the NKEF-B is an antioxidant that protects cells from oxidative stress, chemotherapy agents, and inflammation-induced monocyte adhesion. Furthermore, its expression may mediate cellular responses to proinflammatory molecules.
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PMID:Endogenous natural killer enhancing factor-B increases cellular resistance to oxidative stresses. 898 Oct 42

Hemin (ferriprotoporphyrin IX), the oxidized prosthetic group of hemoglobin, is a potential source of prooxidant iron in heavily vascularized tumors. We have evaluated hemin's effects on photodynamic inactivation of bovine artery endothelial cells, using a partially purified oligomeric fraction of hematoporphyrin derivative (HPD-A) as the sensitizing agent. Confluent cells in 5% serum/RPMI medium showed a progressive loss of thiazolyl blue (MTT)-detectable viability when irradiated with broadband visible light in the presence of HPD-A. Cells pretreated with desferrioxamine (DFO) were substantially less sensitive to photokilling, implying that non-heme iron plays a role in cytotoxic activity. Hemin (10-20 microM) had remarkably different effects on photokilling, depending on the time interval between adding it to cells and exposing them to photodynamic action. For example, cells were more sensitive when photostressed immediately after 1 h hemin treatment and washing but much more resistant when photostressed 23 h later. Similar responses were observed when cells were challenged with glucose oxidase. Immunoblot analysis following hemin treatment revealed a progressive induction of the heavy (H) subunit of ferritin that paralleled the development of hyperresistance. After incubation with saturating levels of the synthetic iron donor [55Fe]ferric-8-hydroxyquinoline, hemin-stimulated cells contained about four times more immunoprecipitable ferritin 55Fe than controls. This is consistent with the notion that sequestration of toxic iron as a result of induction of H-chain-enriched ferritin is a key factor in hyperresistance. Inflammatory injury in tumor vasculatures could expose endothelial and neoplastic cells to chronic hemoglobin-derived iron. Consequent upregulation of ferritin could impact negatively on the efficacy of photodynamic therapy and other oxidant-based cancer therapies.
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PMID:Delayed hyperresistance of endothelial cells to photodynamic inactivation after contact with hemin. 972 13

In this study, the antioxidant, cytotoxic, and antitumorigenic activities of a fractionated, ethanol extract derived from Rhus verniciflua Stokes (RVS), a plant indigenous to Korea, China, and Japan, were determined. Physicochemical analysis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that the active component of a Sephadex G-150-fractionated RVS extract (PII fraction) was a copper-containing glycoprotein, possibly a plant laccase. Antioxidant activity of the fractionated RVS extract, observed in both aqueous and lipid in vitro oxidation reactions using 1,1-diphenyl 2-picrylhydrazyl (DPPH) radical, site-specific Fenton-reaction deoxyribose, and a model lipid emulsion test system, indicated an affinity for protection against hydroxyl and peroxyl radicals. Cultured mouse brain neurons were protected against glucose oxidase-induced hydroxyl radical in the presence of the fractionated RVS extract (e.g., 58% protection at 4.9 microM and 95% protection with 22.7 microM RVS). RVS was further shown to protect against in vitro Fenton-reaction-induced single- and double-strand scission in supercoiled plasmid DNA. Further testing for bioactivity of the fractionated RVS extract was based on the affinity to inhibit cell proliferation in cultured HeLa and CT-26 tumor cells. The presence of RVS resulted in 70% cell death after 24 h of incubation in both cell lines at a minimum concentration of 2.48 microM RVS. Data demonstrate multiple bioactive chemopreventative properties of a Sephadex G-150-fractionated extract derived from RVS.
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PMID:Antitumorigenic and cytotoxic properties of an ethanol extract derived from Rhus verniciflua Stokes (RVS). 1169 93

Earlier studies using GM10115 cells analyzed the capability of different DNA-damaging agents to induce genomic instability and found that acute oxidative stress was relatively inefficient at eliciting a persistent destabilization of chromosomes. To determine whether this situation would change under chronic exposure conditions, the human-hamster hybrid line GM10115 was cultured under conditions of oxidative stress. Chronic treatments consisted of 1-hour incubations using a range of hydrogen peroxide (25-200 microM) or glucose oxidase (GO; 5-50 mU/ml) concentrations that were administered once daily over 10 to 30 consecutive days. The toxicity of chronic treatments was modest (- one log kill) and consistent with the low yield of first division aberrations (<5%). However, analysis of over 180 clones and 36,000 metaphases indicated that chronic oxidative stress led to a high incidence of chromosomal instability. Treatment of cells with 100 and 200 microM hydrogen peroxide or 50 mU/ml GO was found to elicit chromosomal instability in 11%, 22%, and 19% of the clones analyzed, respectively. In contrast, control clones isolated after mock treatment did not show signs of chromosomal destabilization. These data suggest that chronic oxidative stress constitutes a biochemical mechanism capable of disrupting the genomic integrity of cells.
Neoplasia
PMID:Induction of chromosomal instability by chronic oxidative stress. 1451 5

The bioflavonoid quercetin is a dietary anticancer chemical that is capable of inducing apoptosis in tumor cells. Although the activity of quercetin is believed to be due to its antioxidative properties, it has recently been suggested that quercetin also has prooxidant activities, which might effect cytotoxicity directly. In this study, we used mouse thymocytes to investigate whether quercetin behaved as a protector against oxidative stress or as a cytotoxic agent. Quercetin treatment did not induce oxidative damage, but protected mouse thymocytes from glucose oxidase (GO)-mediated apoptosis in a dose-dependent manner. Furthermore, electrophoretic mobility shift assays revealed that quercetin (50 microM) treatment suppressed the GO-mediated DNA binding activity of redox state-sensitive transcription factors, such as NF-kappaB, AP-1, and p53. This result suggests that quercetin has antioxidative effects on thymocytes. More interestingly, quercetin treatment alone (50 microM) increased the DNA-binding activity of AP-1, which consisted of heterodimer of c-Jun and Fra-2. Finally, the antioxidant activity of quercetin was confirmed using a cell-free system of radical generation. Our findings suggest that quercetin protects mouse thymocytes from oxidative stress-mediated apoptosis and modulates the intracellular redox state through its antioxidant activity.
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PMID:The antioxidant, rather than prooxidant, activities of quercetin on normal cells: quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis. 1464 60

Despite biotechnological and clinical applications very few monoclonal antibodies (MAbs) directed to the enzyme glucose oxidase, have been produced so far because of the heavy side effects of the immunization schedule for conventional MAb preparation. In contrast, the phage display method allows for the selection of monoclonal human antibody fragments against any antigens, including toxic proteins. Furthermore, cDNA sequences encoding selected antibody fragments are readily identified, facilitating various molecular targeting approaches. In order to obtain such human fragments recognizing glucose oxidase, we used the large synthetic ETH-2 library based on the principle of protein design. Phage displaying glucose oxidase reactive scFvs were obtained after three rounds of selection on glucose oxidase-coated immunotubes and subsequent amplification in TG1 E. coli cells. Eventually, one high reactive scFv clone was selected and further examined. The anti-glucose oxidase scFv C10 was found suitable for Western blot; Biacore analysis showed that the binding affinity of the glucose oxidase-reactive scFv is almost equal that of MAbs prepared with conventional hybridoma technology. Finally, the cDNA sequence of this human scFv may be exploited to generate bispecific antibodies to target in the tumor environment-specific toxic enzymatic reaction.
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PMID:Isolation and characterization of the human monoclonal antibodies C10 in single-chain fragment variable (scFv) format to glucose oxidase from Aspergillus niger. 1568 66

The research began with an investigation of tannins from traditional medicinal plants and resulted in isolation and structure determination of hundreds of ellagitannins and dehydroellagitannins, as well as their oligomers and oxidized derivatives with various structures specific to each plant species. These polyphenols have been classified according to the stage of oxidative structural transformation and oligomerization, into types I-IV and I+ to IV+, etc. Parallels were found between their oxidative transformations and plant evolution. They were also classified by the linkage units between the monomers, into DOG, GOD, GOG and DOGOD types (D=Diphenoyl, G=Galloyl, O=Oxygen), etc. Besides their fundamental activities, e.g., reduction and anti-peroxidation properties, remarkable biological and pharmacological activities of various potencies have also been found, including, amongst others, inhibition of lipid-peroxidation, mutagenicity of carcinogens and tumor promotion, host-mediated antitumor effects specific to particular tannin structures, antiviral activity and potentiation of antibacterial activity.
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PMID:Systematics and health effects of chemically distinct tannins in medicinal plants. 1598 79

Glucose oxidase (GOD) is an oxidoreductase catalyzing the reaction of glucose and oxygen to peroxide and gluconolacton (EC 1.1.3.4.). GOD is a widely used enzyme in biotechnology. Therefore the production of monoclonal antibodies and antibody fragments to GOD are of interest in bioanalytics and even tumor therapy. We describe here the generation of a panel of monoclonal antibodies to native and heat inactivated GOD. One of the hybridomas, E13BC8, was used for cloning of a single chain antibody (scFv). This scFv was expressed in Escherichia coli XL1-blue with the help of the vector system pOPE101. The scFv was isolated from the periplasmic fraction and detected by western blotting. It reacts specifically with soluble active GOD but does not recognize denatured GOD adsorbed to the solid phase. The same binding properties were also found for the monoclonal antibody E13BC8.
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PMID:Cloning and characterization of a single chain antibody to glucose oxidase from a murine hybridoma. 1804 81


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