Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-lived non-dividing CD5(+) B cells. Nitric oxide (NO) is an important regulator of apoptosis, and the viability of cultured B-CLL cells may be dependent on the autocrine production of nitric oxide by inducible nitric oxide synthase (NOS2). We performed this study to determine whether cytokine factors that prevent spontaneous in vitroapoptosis of B-CLL cells induce B-CLL cell NOS2 enzyme activity. B-CLL cells expressed NOS enzyme activity and NOS2 protein and mRNA. IL-4 and IFN-gamma increased B-CLL cell NOS2 enzyme activity and protein expression during in vitro culture. IFN-gamma, but not IL-4, increased NOS2 mRNA expression in cultured B-CLL cells suggesting that IL-4-mediated changes of NOS2 protein expression occurred at the post-transcriptional level. We were unable to detect increased concentrations of nitrite or nitrate (NO(x)) as surrogate markers of NO production in B-CLL cell cultures treated with IL-4 or IFN-gamma. IL-4 and IFN-gamma diminished NOS inhibitor-induced B-CLL cell death. In summary, we found that B-CLL cells expressed NOS2 and that IL-4 and IFN-gamma increased B-CLL NOS2 expression. Cytokine-mediated expression of NOS2 by B-CLL cells may promote their survival, and therapeutic strategies that target NOS2 or quench NO may be beneficial in patients with B-CLL.
Leukemia 2003 Feb
PMID:IL-4 and interferon gamma regulate expression of inducible nitric oxide synthase in chronic lymphocytic leukemia cells. 1259 45

Four new isomeric azine-bridged complexes ([(cis-Pt(NH(3))(2)Cl)(2)(mu-pzn)]Cl(2) (1a) (pzn = pyrazine) and its corresponding nitrate salt (1b), [(cis-Pt(NH(3))(2)Cl)(2)(mu-pmn)]Cl(2) (2) (pmn = pyrimidine), and [(cis-Pt(NH(3))(2)Cl)(2)(mu-pdn)](NO(3))(2) (3) (pdn = pyridazine) have been newly synthesized as potential anticancer compounds. These complexes have been characterized by (1)H and (195)Pt NMR spectroscopy, and also the X-ray crystal structure of 1b has been determined. The reactions of 1a, 2, and 3 with guanosine-5'-monophosphate (GMP) have been monitored and kinetically investigated in D(2)O solutions at 310 K using (1)H NMR spectroscopy. Both 1a and 2 react with 2 equiv of GMP to form 1:2 complexes. The reactions involve a stepwise direct substitution of chloride ligands by GMP, with similar reaction rates for both complexes. On the other hand, the reaction of 3 with GMP results in the cleavage of one of the Pt-N(pyridazine) bonds to form an N7,O6-platinated polymer. The reaction products have been separated and have been characterized by (1)H and (195)Pt NMR spectroscopy. A cytotoxicity assay of the azine-bridged complexes (1a, 1b, 2, and 3) has been performed on human tumor cell lines and two L1210 murine leukemia cell lines (one sensitive to and one resistant to cisplatin). In general, the complexes show lower cytotoxicity than cisplatin for the human tumor cell lines except for the IGROV cell line. Their cytotoxicity for the mouse cell lines is comparable to or higher than that of cisplatin. Furthermore, these complexes appeared to largely or partly overcome the cross-resistance to cisplatin. Implications of these findings are discussed in the context of a structure-activity relationship for this class of compounds.
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PMID:New isomeric azine-bridged dinuclear platinum(II) complexes circumvent cross-resistance to cisplatin. 1264 31

Leachates are wastewater generated principally from landfills and solid waste disposal sites. Leachates emanating from municipal wastes are a major source of surface and groundwater pollution worldwide. Globally, leachates have been implicated in low yield of farm produce, developmental anomalies, low birth weights, leukemia incidence, and other cancers in communities around the site. They have also been implicated in hazards to the environment, loss of biodiversity, and contamination of water sources. At Aba-Eku in Nigeria, leachates are being discharged into the Omi Stream without treatment. A study was conducted on a method of leachate treatment that passes the leachate through constructed wetlands using Ipomoea aquatica (Forsk), a locally available plant found close to the landfill site. The aim of the study was to evolve a sustainable and cost-effective method of treatment whose effluents can be discharged into the Omi Stream with no or minimal impact. The study was descriptive and analytical in design. Samples were collected and analyzed with standard methods for pH, suspended solids (SS), biochemical oxygen demand (BOD), chemical oxygen demand (COD), ammonia, nitrate, and trace metals. Raw leachates were turbid and amber in color and contained suspended solids (197.5 mg/L), ammonia (610.9 mg/L), lead (1.64 mg/L), iron (198.10 mg/L), and manganese (23.20 mg/L). When the leachates were passed through the constructed wetland with eight hours' detention time, effluents showed significant reductions in suspended solids (81.01 percent), BOD (86.03 percent), and ammonia (97.77 percent). The study shows that a constructed wetland is a feasible tool for the treatment of leachates before their disposal into the environment in Nigeria and can help safeguard environmental quality.
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PMID:Application of constructed wetlands to the treatment of leachates from a municipal solid waste landfill in Ibadan, Nigeria. 1599 86

PT-ACRAMTU {[PtCl(en)(ACRAMTU)](NO3)2, 2; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, 1, en = ethane-1,2-diamine} is the prototype of a series of DNA-targeted adenine-affinic dual intercalating/platinating agents. Several novel 4,9-disubstituted acridines and the corresponding platinum-acridine conjugates were synthesized. The newly introduced 4-carboxamide side chains contain H-bond donor/acceptor functions designed to promote groove- and sequence-specific platinum binding. In HL-60 (leukemia) and H460 (lung) cancer cells, IC50 values in the micromolar to millimolar range were observed. Several of the intercalators show enhanced cytotoxicity compared to prototype 1, but conjugate 2 appears to be the most potent hybrid agent. Enzymatic digestion assays in conjunction with liquid chromatography-electrospray mass spectrometry analysis indicate that the new conjugates produce PT-ACRAMTU-type DNA damage. Platinum-modified 2'-deoxyguanosine, dG, and several dinucleotide fragments, d(NpN)*, were detected. One of the conjugates showed significantly higher levels of binding to A-containing sites than conjugate 2 (35 +/- 3% vs 24 +/- 3%). Possible structure-activity relationships are discussed.
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PMID:Synthesis, biological activity, and DNA-damage profile of platinum-threading intercalator conjugates designed to target adenine. 1672 38

Methotrexate (MTX), a structural analogue of folic acid, is widely used as a chemotherapeutic agent for leukemia and other malignancies. One of the major toxic effects of MTX is intestinal injury and enterocolitis .The mechanism of gastrointestinal toxicity of methotrexate has not been investigated completely. Therefore cancer chemotherapy has to be accompanied by symptomatic therapy such as antibiotics and anti-diarrheal drugs. It is important to investigate the mechanism by which methotrexate induces intestinal damage in order to perform cancer chemotherapy effectively by preventing the side effects. This study aimed at investigating whether nitrosative stress plays a role in methotrexate induced small intestinal damage using a rat model. Adult male rats were administered methotrexate at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the final dose of methotrexate. Vehicle treated rats served as control. The intestinal tissue was used for light microscopic studies and markers of nitrosative stress including tissue nitrite level and nitrotyrosine. Myeloperoxidase (MPO) activity, a marker of neutrophil infiltration was also measured in intestinal homogenates. The villi were damaged at 12 h and the damage progressed and became severe at 24 h after the final dose of MTX. Biochemically, tissue nitrate was elevated fivefold at 12 h and fourfold at 24 h after the final dose of MTX as compared with control. Nitrotyrosine, measured immunohistochemically was detected in all the parts of the small intestine. Duodenum stained the most for nitrotyrosine, followed by ileum and then jejunum. The staining for nitrotyrosine was more intense at 24 h as compared with 12 h after the final dose of methotrexate. There was marked neutrophil infiltration as evidenced by increase in MPO activity in the small intestines. In conclusion, the results of the present study reveal that nitrosative stress may play a critical role in methotrexate induced small intestinal damage. Intervention studies using nitric oxide synthase inhibitors is being carried out in order to confirm the role of nitrosative stress in methotrexate induced small intestinal damage.
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PMID:Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat. 1825 14

The aim of this study was to establish and optimize two-dimensional electrophoresis method for human bone marrow leukemia cells in order to obtain the profiles with high resolution and reproducibility. The total protein was extracted and separated by isoelectric focusing (IEF) and SDS polyacrylamide gel electrophoresis (SDS-PAGE). The gels were stained with silver nitrate or Coomassie brilliant blue, and then scanned and analyzed with PDQuest 7.4 analysis software. The effects of different protein preparation methods and electrophoresis conditions on the profiles were compared. The results indicated that by optimizing preparation of protein sample and electrophoresis protocols, clear profiles with 780 +/- 73 well separated protein spots on an average were obtained and the match rate was 82 +/- 5% between reproducible gels from leukemia cells of different sub-type. It is concluded that the two-dimensional electrophoresis method of proteome from human bone marrow leukemia cells is established successfully and is suitable for the further comparative proteomic research between leukemia of different types.
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PMID:[Establishment and optimization of two-dimensional gel electrophoresis technique of proteome from bone marrow leukemia cells]. 1854 16

The purpose of this study was to test the hypothesis that warfarin may enhance free radical production and oxidative damage on cancer cells. We examined the possible concentration-dependent effect of warfarin on cytotoxicity with respect to oxidative stress on leukemia cell lines (K562 and HL-60) and normal human peripheral blood mononuclear cells (PBMC). Gamma radiation was used as a positive control agent for oxidative stress. At all concentrations of warfarin (5-200 muM), 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)- and bis-N-methylacridinium nitrate (lucigenin)-amplified chemiluminescence responses and lipid peroxidation and protein oxidation were stable after 72 h incubation at 37 degrees C. However, The 2',7'-dichlorofluorescein diacetate (DCFH-DA) oxidation was increased when cells were incubated with high concentrations (50-200 muM) of warfarin. In these concentration ranges, warfarin reduced cell growth in a dose-dependent manner, producing apoptosis. Our results also revealed that at concentrations above 5 muM, warfarin had a potentiating effect on radiation-mediated growth inhibition and apoptosis. Furthermore, marked effects were observed on leukemic cells compared with PBMC. We report here that the increase of DCFH oxidation might be due to the increase in the release of cytochrome C caused by warfarin, as cytosolic cytochrome C content was significantly elevated in the warfarin-treated cells compared with control cells, and because cotreatment with antioxidants N- acetylcysteine or 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) was unable to prevent cytochrome C release and DCFH oxidation induced by the drug. Taken together, these results suggest that high warfarin concentrations may be toxic to leukemic cells in vitro through apoptosis, although at the pharmacological concentrations (<50 muM), warfarin has no prooxidant or cytotoxic effect on PBMC, K562, and HL-60 cells. In addition, when the treatment of leukemic cells with warfarin at concentrations above 5 muM is combined with radiation, we observed an increase in radiation-induced cytotoxicity. The mechanism by which warfarin potentiates this cytotoxicity is unclear, but it may not be directly due to toxic damage induced by warfarin-generated free radicals.
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PMID:Toxic-dose warfarin-induced apoptosis and its enhancement by gamma ionizing radiation in leukemia K562 and HL-60 cells is not mediated by induction of oxidative stress. 1856 37

The ionizing radiation dose-response relationships for internally deposited radionuclides are examined using data from humans involving Ra and laboratory animal studies involving alpha-emitters Ra, Ra, Ra, Th, Pu, Pu, and Am and beta-emitters Y, Sr, Y, and Ce. Intake routes included ingestion, inhalation, and injection. The lifetime effects are best described by three-dimensional average-dose-rate/time/response surfaces that compete with other causes of death during an individual's lifetime. Using maximum likelihood survival regression methods, the characteristic logarithmic slope for cancer induction was found to be about negative one-third for alpha-emitters or about negative two-thirds for beta-emitters. At the higher average dose-rates the principal deleterious effects were those associated with radiation-induced injury while at intermediate average dose-rates radiation-induced cancer predominates. The relative biological effectiveness for cancer induction of high linear energy transfer alpha radiation with respect to low linear energy transfer beta radiation is a strong function of dose-rate. As average dose-rate decreases, the effectiveness of the beta irradiation drops off more rapidly than that of the alpha irradiation. The cumulative dose yielding a specific level of induced cancer risk is less at lower dose-rates than at higher dose-rates showing an apparent inverse dose-rate effect (up to a factor of about 10 for high linear energy transfer alpha radiation and a factor of about 2 for low linear energy transfer beta radiation). The cumulative radiation dose is neither an accurate nor an appropriate measure of cancer risk associated with protracted ionizing radiation exposure. Cancer risk associated with protracted ionizing radiation exposure is a non-linear function of lifetime average dose-rate to the affected tissues. At low average dose-rates the long latency time required for radiation-induced cancer may exceed the natural lifespan. This long latency results in a lifespan virtual threshold (cancer risk p < 0.001) for each internally deposited radionuclide. For young adult beagles, bone sarcoma induction from alpha-emitting radionuclides was unlikely for cumulative doses below about 1 Gy (20 Sv) delivered specifically to the sensitive tissues at bone surfaces in a manner associated with radionuclide relative potency from highest for Th, Pu, and Pu to lowest for Ra. Bone sarcoma induction from ingested Sr was unlikely for cumulative beta radiation doses below about 20 Gy (20 Sv), but beta irradiation of tissues adjacent to bone also induced leukemia and soft tissue carcinomas above 10 Gy (10 Sv). Inhaled radionuclides tended to be most potent in producing lung carcinoma when the radiation dose was most uniformly distributed in the lung. In young adult beagles lung carcinoma from inhaled alpha-emitting Pu in the dispersible nitrate form was unlikely for cumulative doses below about 0.5 Gy (10 Sv) and below higher cumulative doses for other forms of Pu and Pu depending on relative potency. Lung carcinoma from inhaled beta-emitting Y in relatively insoluble fused aluminosilicate particles was unlikely for cumulative doses below about 5 Gy (5 Sv) and below higher doses for inhaled particles with Y, Ce, or Sr in order of decreasing potency.
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PMID:Concerning the health effects of internally deposited radionuclides. 2014 92

Reactions between 4'-phenyl-terpyridine (L) and several Zn(II) salts (sulfate, nitrate, chloride or acetate) led to the formation of the complexes [Zn(2)(mu-O(2)SO(2))(2)L(2)(CH(3)OH)(2)] (1), [Zn(NO(3))L(H(2)O)]NO(3) (2), [Zn(Cl)(2)L] (3) and [Zn(CH(3)COO)(2)L] (4) which were characterized by IR, (1)H NMR and fluorescence spectroscopies, elemental analysis and single crystal X-ray diffraction. In the dinuclear molecule of 1 the Zn atom is hexacoordinated, with a N(3)O(3) coordination environment and forms an octagonal ZnOSOZnOSO metallacycle. In the remaining structures, the metal atom is envisaged as possessing highly distorted N(3)X(2) (X = O or Cl) square pyramid coordination geometries. The structure of 3 presents two different packing patterns which lead to distinct pi-pi stackings. In both structures 2 and 4, strong intermolecular hydrogen bonds were identified. The complexes exhibit promising in vitro tumor-inhibiting activities, which are higher than that of cisplatin, against the following human tumor cell lines: promyelocyticfina leukaemia (HL-60), hepatocellular carcinoma (Bel-7402), gastric carcinoma (BGC-823) and nasopharyngeal carcinoma (KB).
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PMID:Synthesis, characterization, solid-state photo-luminescence and anti-tumor activity of zinc(II) 4'-phenyl-terpyridine compounds. 2040 91

Prostaglandin D(2) (PGD(2)) is known to have antipruritic activity by suppressing histamine release. However, agents that can topically induce PGD(2) for itch relief are not well established. The antimycotic sertaconazole nitrate (STZ) has been shown to exhibit anti-itch properties; however, the mechanism for this activity has not been elucidated. STZ mitigated degranulation of RBL-2H3 (rat basophilic leukemia) mast cells induced by compound 48/80, a pruritogenic agent known to promote the release of histamine, and augmented PGD(2) production in mast cells and macrophages. Addition of exogenous PGD(2) abrogated compound 48/80-induced degranulation by acting through the prostanoid D receptor 1 (DP1). STZ induced p38 mitogen-activated protein kinase (MAPK) phosphorylation in mast cells and a pharmacological inhibitor of p38 MAPK, SB203580, resulted in the attenuation of PGD(2) levels. Finally, in a murine model of pruritus, the scratching behavior induced by compound 48/80 was mitigated by topical application of STZ. This effect was reversed by the addition of the cyclooxygenase inhibitor, ibuprofen, or a DP1 receptor antagonist (MK0524). Collectively, these results suggest that STZ mediates its anti-itch effects by boosting the antipruritic agent, PGD(2), by the activation of the p38-MAPK pathway. This is the first report to demonstrate a promising approach to topically induce PGD(2) for improving pruritus.
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PMID:Induction of prostaglandin D2 through the p38 MAPK pathway is responsible for the antipruritic activity of sertaconazole nitrate. 2050 47


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