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

Catechin components of green tea have been shown to possess anticarcinogenic properties possible related to their antioxidant activity. In the present study, a catechin containing green tea extract (GTE) was examined for its effect on three previously defined properties of liver tumor promoters, induction of cytolethality, inhibition of gap junctional intercellular communication, and induction of cell proliferation. Hepatocytes from male B6C3F1 mice were isolated and placed in primary culture. The effects of GTE of oxygen free radical-induced cytolethality was examined by coincubating GTE with the oxygen radical generating compounds paraquat, glucose oxidase (GO), and xanthine oxidase (XO). GTE prevented the induction of hepatocyte cytolethality by GO, XO, and paraquat in a dose-responsive manner. Similarly, GTE prevented the inhibition of gap junctional-mediated intercellular communication (measured by lucifer yellow dye coupling) by phenobarbital, lindane, and paraquat in a dose-dependent manner. The effect of GTE on hepatocyte DNA synthesis was examined in male mice containing preneoplastic liver lesions induced by diethylnitrosamine. GTE significantly decreased the labeling index in hepatic preneoplastic foci from animals treated with phenobarbital for 7 days. These studies suggest that the previous reported anticarcinogenic activity of green tea may be related to its effect on the tumor promotion stage of the cancer process.
 ...
PMID:Chemopreventive effects of green tea components on hepatic carcinogenesis. 140 92

A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of "modern" leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies+complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types--monkey kidney epithelial cells and rat beating heart cells. Monolayers of 51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic "cocktails" comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn(2+)+glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.
 ...
PMID:Synergism among oxidants, proteinases, phospholipases, microbial hemolysins, cationic proteins, and cytokines. 142 26

Incubation of whole bovine lens with 10(-7) M 12-O-tetradecanoylphorbol-13-acetate (TPA) led to the lens opacity within 24 h. The hydrogen peroxide (H2O2) concentration in the whole lens was elevated 4 fold after treatment with either 10(-7) M TPA or 2.5 mM glucose/20 microM glucose oxidase. The lens opacification and H2O2 elevation were TPA dose-dependent. Preincubation of the lens with anti-tumor promoting agents EGCG (epigallocatechin gallate) or Sarp A (sarcophytol A) stopped the TPA-mediated opacification process and suppressed H2O2 elevation.
 ...
PMID:Lens opacification and H2O2 elevation induced by a tumor promoter. 159 6

Activated neutrophils cause extensive DNA damage in neighboring nonphagocytic cells. To determine whether compounds in the extracellular milieu participate in the DNA damage process, murine neutrophils were cocultivated with target tumor cells in media of varying composition. Using the alkaline elution assay, it was found that the level of strand breaks induced was significantly higher (2.8-fold) in complex cell culture media than in minimal phosphate-buffered saline. Addition of amino acids in general and of histidine in particular increased the level of damage nearly to that observed in complete media (2.7- and 2.1-fold, respectively). The histidine stimulation was concentration-dependent and reached a maximum at 100-400 microM. The mechanism whereby this occurred is not proven but probably derived from chelation of metals and participation in a site-specific Fenton reaction. Addition of the cell-impermeable chelator EDTA dramatically inhibited induction of strand breaks by neutrophils in complete media and prevented the enhancement of damage induced by histidine in phosphate-buffered saline. None of the effects on neutrophil-induced damage could be attributed to modulation of the oxidative burst activity of the cells (O2- and H2O2 production). Histidine also enhanced induction of strand breaks by reagent H2O2. However, EDTA had no effect or actually increased the level of damage induced by both a bolus of H2O2 and a flux of H2O2 generated by glucose oxidase. The cell-permeable chelator o-phenanthroline inhibited both neutrophil- and H2O2-induced damage. The results indicate that secondary reactions involving extracellular amino acids and metals contribute significantly to neutrophil-induced DNA damage to neighboring cells. Moreover, the data show that the mechanism whereby neutrophils induce this damage cannot be attributed solely to secretion of H2O2.
 ...
PMID:DNA damage induced by phorbol ester-stimulated neutrophils is augmented by extracellular cofactors. Role of histidine and metals. 215 7

It may be difficult to differentiate the possible causes of hyperglycemia in the cat. The following investigation was on transient hyperglycemia in 320 cats. The frequency and degree of stress-hyperglycemia and its relation to different types of primary diseases was proven. Animals with overt diabetes mellitus or pancreatic diseases were not included in this study. Plasma glucose was analyzed with the o-Toluidine- or with the glucose oxidase-method. Plasma immune-reactive insulin (IRI) was estimated by RIA. A glucose concentration of greater than or equal to 140 mg/dl (7.77 mmol/l) in the fasted animal was defined as hyperglycemia. The results of the retrospective investigation show in cats transient hyperglycemia occurs more often (3.2%) than permanent hyperglycemia (0.57%). Contrary to overt diabetes mellitus there is no sex- or age-related predisposition. Glucose values above 300 mg/dl (16.65 mmol/l) with maximal values up to 620 mg/dl (34.42 mmol/l) were estimated in 12% of the animals. In 12 from 19 hyperglycemic animals the basal IRI values were between 4 and 14 microU/ml, 11 animals had a lowered I/G ratio. In the following order of frequency the primary diseases found in combination with transient hyperglycemia were: dys- and stranguria, viral and bacterial infections, gastrointestinal diseases, neoplasia, renal insufficiency, cardiopathies etc. With improvement of the underlying disturbance the stress-related hyperglycemia normalized without insulin therapy within a few days. In conclusion, it is necessary to initially identify basic diseases that may trigger the onset of stress-hyperglycemia in the cat. Neither the extent of the glucose level nor a single plasma-insulin-value are valid indicators of confirming the diagnosis of diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Stress hyperglycemia in cats]. 219 50

With an in vitro culture technique combined with light microscopy, immunocytochemistry and molecular probing, we previously detected occult tumor cells in histologically-normal human bone marrow harvested for autologous transplantation. In this study, we mixed known numbers of malignant lymphoid (Raji and CEM) or breast cancer (MCF-7) cells with normal human bone marrow cells to determine the levels at which tumor cells can be detected before and after culture. Cytocentrifuge preparations were made before culture and after 2 or more weeks of culture and examined by light microscopy. We detected contaminating lymphoma cells at a level of more than 5% before culture, and at a level of 0.01% after culture for 2 or more weeks in 2% human lymphocyte conditioned medium. Before culture, we detected MCF-7 cells at a level of 0.001% using glucose oxidase immunocytochemical staining techniques; these cells were detected at a level of 0.00001% after culture. Since, of necessity, these calibrations rations were performed using cell lines, it is likely that these results overestimate the absolute sensitivity of these methods for detection of tumor cells in patient samples. We found the glucose oxidase immunocytochemical method more specific for detecting occult tumor cells in bone marrow than the immunoperoxidase staining method because of the absence of non-specific staining arising from endogenous peroxidase in bone marrow cells which makes the interpretation of the latter difficult. We conclude that culture techniques can increase the sensitivity of detection of occult tumor cells in human bone marrow about 100-fold.
 ...
PMID:Levels of detection of tumor cells in human bone marrow with or without prior culture. 225 57

The liver tumor promoters, phenobarbital (20-500 micrograms/ml), lindane (1,2,3,4,5,6-hexachlorocyclohexane, gamma-isomer; 0.1-5.0 micrograms/ml), and DDT (1,1-bis[4-chlorophenyl]-2,2,2-trichloroethane; 0.5-10.0 micrograms/ml), and the hydrogen peroxide-generating enzyme, glucose oxidase (0.01-0.10 units/ml) inhibited gap junctional intercellular communication between B6C3F1 mouse hepatocytes in primary culture. Addition of the antioxidants, superoxide dismutase (100 units/ml), DPPD (N,N'-diphenyl-1,4-phenylenediamine; 25 microM), and vitamin E (DL-alpha-tocopherol acetate; 100 microM), to tumor promoter-treated cultures prevented the inhibition of hepatocyte intercellular communication. DPPD and vitamin E, prevented the inhibition of hepatocyte intercellular communication by glucose oxidase. Superoxide dismutase had no effect on the inhibition of intercellular communication caused by glucose oxidase. These results suggest that activated oxygen species are produced during liver tumor promoter treatment of cultured mouse hepatocytes and are responsible for the inhibition of mouse hepatocyte intercellular communication by the promoters.
 ...
PMID:Antioxidant prevention of tumor promoter induced inhibition of mouse hepatocyte intercellular communication. 243 62

An antioxidant fraction of Chinese green tea (green tea antioxidant; GTA), containing several catechins, has been previously shown to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In the present study, GTA was shown to have antioxidative activity toward hydrogen peroxide (H2O2) and the superoxide radical (O2-). GTA also prevented oxygen radical and H2O2-induced cytotoxicity and inhibition of intercellular communication in cultured B6C3F1 mouse hepatocytes and human keratinocytes (NHEK cells). GTA (0.05-50 micrograms/ml) prevented the killing of hepatocytes (measured by lactate dehydrogenase release) by paraquat (1-10 mM) and glucose oxidase (0.8-40 micrograms/ml) in a concentration-dependent fashion. GTA (50 micrograms/ml) also prevented the inhibition of hepatocyte intercellular communication by paraquat (5 mM), glucose oxidase (0.8 micrograms/ml), and phenobarbital (500 micrograms/ml). In addition, GTA (50 micrograms/ml) prevented the inhibition of intercellular communication in human keratinocytes by TPA (100 ng/ml). Cytotoxicity and inhibition of intercellular communication, two possible mechanisms by which tumor promoters may produce their promoting effects were therefore prevented by GTA. The inhibition of these two effects of pro-oxidant compounds may suggest a mechanism by which GTA inhibits tumor promotion in vivo.
 ...
PMID:Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. 247 May 25

Recent evidence supports the concept that Adriamycin cytotoxicity may be mediated by drug semiquinone free radical and oxyradical generation. We tested this hypothesis further by exposing drug-sensitive (WT) and 500-fold Adriamycin-resistant MCF-7 human breast tumor cells (ADRR) to exogenous superoxide- and hydrogen peroxide-generating systems and subsequently monitored cell proliferation as a measure of cytotoxicity. The ADRR tumor cells tolerated a 4-fold greater exposure than sensitive cells to superoxide generated by the xanthine/xanthine oxidase system. Likewise, exposure to hydrogen peroxide produced by the action of glucose oxidase on glucose revealed a 4-fold diminished susceptibility of the drug-resistant cells to this reduced form of oxygen. Similar results were obtained by the direct application of hydrogen peroxide to cells. For both cell lines, cytotoxicity was dependent upon the magnitude and the duration of reactive oxygen exposure. When WT and ADRR cells were cultured under hyperoxia (95% O2:5% CO2), in order to stimulate the intracellular production of oxyradicals, proliferation was inhibited to a greater extent in the drug-sensitive cell line. Additionally, hyperoxia potentiated the cytotoxicity of Adriamycin to both sensitive and drug-resistant cells, but the effect depended upon the concentration of the drug. Under hyperoxic conditions, Adriamycin caused oxygen radical-dependent cytotoxicity to the WT tumor cells at clinically relevant drug concentrations as low as 2 to 3 nM. With ADRR tumor cells, hyperoxia increased the cytotoxicity of Adriamycin at concentrations above 5 microM. Paradoxically, both the WT and the ADRR tumor cells were equally susceptible to the cytotoxic effects of gamma irradiation. It is known that the Adriamycin-resistant MCF-7 cells greatly overexpress glutathione peroxidase and glutathione transferase activities; however, other biochemical defenses against reactive drug intermediates and oxygen radicals have been reported to be similar in the two cell lines. We have reexamined those observations in this report. The resistance of ADRR breast tumor cells to Adriamycin appears to be associated with a developed tolerance to superoxide, most likely because of a twofold increase in superoxide dismutase activity, and a decreased susceptibility to hydrogen peroxide, most likely because of 12-fold augmented selenium-dependent glutathione peroxidase activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Differential oxygen radical susceptibility of adriamycin-sensitive and -resistant MCF-7 human breast tumor cells. 253 95

The effectiveness of an antibody-enzyme immunotoxin (eIT) was investigated on human T cells. This enzyme immunotoxin contained glucose oxidase (GO) and lactoperoxidase (LPO) chemically coupled to the pan-leukocyte-specific mouse monoclonal antibody (MoAb) 097 (097-GO and 097-LPO). Human peripheral blood mononuclear cells or tumor cells were suspended in a mixture of 097-GO and 097-LPO for 30 min, and then for 2 h with glucose and NaI. The effectiveness of this eIT system was indicated by the almost complete reduction of T cell viability, as estimated by a phytohemagglutinin induced proliferation assay (99.4% +/- 0.31 depletion, mean +/- SEM of 15 experiments). The specificity of the cytotoxicity reaction was indicated by the lack of cytotoxicity of control irrelevant MoAb conjugates to T cells (1.9% +/- 4.17 of T cell depletion, eight experiments). The growth of human bone marrow myeloid progenitors (CFU-GM) was not affected by the conjugates even by increasing 100-fold the optimal cytotoxic dose. T cells were susceptible to the conjugates in the presence of up to 90% of erythrocytes. This eIT system may thus represent a new alternative immunospecific procedure for allograft and/or autograft purging, and appears to effectively replace complement-mediated methods of T cell depletion.
 ...
PMID:An immunotoxin system intended for bone marrow purging composed of glucose oxidase and lactoperoxidase coupled to monoclonal antibody 097. 279 Mar 30


1 2 3 4 5 6 7 8 9 10 Next >>