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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an interactive relationship between leukaemia and oxidative stress. Leukaemic cells produce larger amounts of reactive oxygen species (ROS) than non-leukaemic cells as they are under a continual state of oxidative siege. So, this study was performed on 20 patients with chronic leukaemia from the Oncology Centre, Mansoura University. We measured leucocytic H(2)O(2) concentrations and lipid peroxidation as serum malondialdehyde (MDA) concentration, serum total antioxidant activity, plasma ascorbic acid and dehydroascorbic acid concentrations, blood reduced glutathione concentration, haemolysate G6PD activity, blood catalase activity, serum superoxide dismutase (SOD) activity and serum anti-dsDNA concentration. We found that chronic leukaemia patients showed a significant increase (P < 0.05) in leucocytic H(2)O(2), serum MDA concentration and total antioxidant activity either before or after treatment as compared with control group. Also, there was a significant increase in the other parameters (glutathione, catalase and SOD) either before or after treatment, but we found a significant decrease in ascorbic acid concentration and G6PD activity. There was a significant increase in anti-dsDNA concentration either before or after treatment. It can be concluded that leukaemic patients produce larger amounts of ROS than non-leukaemic patients. Also, the increase in antioxidant activity in leukaemic patients is not high enough to counteract the harmful effects of free radicals. This scenario becomes worse after administration of chemotherapy.
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PMID:Measurements of oxidative stress status and antioxidant activity in chronic leukaemia patients. 1733 45

Lipid rafts are involved in many cell biology events, yet the molecular mechanisms on how rafts are formed are poorly understood. In this study we probed the possible requirement of reactive oxygen species (ROS) for T-cell receptor (TCR)-induced lipid raft formation. Microscopy and biochemical analyses illustrated that blockage of ROS production, by superoxide dismutase-mimic MnTBAP, significantly reduced partitioning of LAT, phospho-LAT, and PLC-gamma in lipid rafts. Another antioxidant N-acetylcysteine (NAC) displayed a similar suppressive effect on the entry of phospho-LAT into raft microdomains. The involvement of ROS in TCR-mediated raft assembly was observed in T-cell hybridomas, T leukemia cells, and normal T cells. Removal of ROS was accompanied by an attenuated activation of LAT and PKCtheta, with reduced production of IL-2. Consistently, treating T cells with the ROS-producer tert-butyl hydrogen peroxide (TBHP) greatly enhanced membrane raft formation, distribution of phospho-LAT into lipid rafts, and increased IL-2 production. Our results indicate for the first time that ROS contribute to TCR-induced membrane raft formation.
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PMID:Reactive oxygen species promote raft formation in T lymphocytes. 1734 21

All methods used for quantitation of superoxide have limitations when it comes to differentiating between extracellular and intracellular sites of superoxide production. In the present study, we monitored dihydroethidium (DHE)-derived fluorescence at 570 nm, which indicates hydroxyethidium derived from reaction with superoxide produced by human leukemia cells (HL-60) and microvascular endothelial cells (HMEC-1). Phorbol-12-myristate 13-acetate (PMA; 100 ng/ml) caused an increase in fluorescence and lucigenin chemiluminescence in HL-60, which was abolished by superoxide dismutase (SOD; 600 U/ml) indicating that DHE detects extracellular superoxide. Furthermore, both HL-60 cells and HMEC-1 generated a fluorescence signal in the presence of DHE under resting conditions, which was unaffected by SOD, but abolished by polyethylene glycosylated-SOD (PEG-SOD) (100 U/ml) and MnTmPyP (25 microM), indicating that DHE also detects superoxide produced intracellularly. In HMEC-1, silencing of either Nox2 or Nox4 components of NADPH oxidase with small interference RNA (siRNA) resulted in a significant reduction in superoxide detected by both DHE fluorescence (Nox2 siRNA; 71 +/- 6% and Nox4 siRNA 83 +/- 7% of control) and lucigenin chemiluminescence (Nox2; 54 +/- 6% and Nox4 74 +/- 4% of control). In conclusion, DHE-derived fluorescence at 570 nm is a convenient method for detection of intracellular and extracellular superoxide produced by phagocytic and vascular NADPH oxidase.
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PMID:Analysis of dihydroethidium fluorescence for the detection of intracellular and extracellular superoxide produced by NADPH oxidase. 1751 43

Down syndrome (DS) is characterized by increased mortality rates, both during early and later stages of life, and age-specific mortality risk remains higher in adults with DS compared with the overall population of people with mental retardation and with typically developing populations. Causes of increased mortality rates early in life are primarily due to the increased incidence of congenital heart disease and leukemia, while causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer's disease (AD) and an apparent tendency toward premature aging. In this article, we describe the increase in lifespan for people with DS that has occurred over the past 100 years, as well as advances in the understanding of the occurrence of AD in adults with DS. Aspects of the neurobiology of AD, including the role of amyloid, oxidative stress, Cu/ZN dismutase (SOD-1), as well as advances in neuroimaging are presented. The function of risk factors in the observed heterogeneity in the expression of AD dementia in adults with DS, as well as the need for sensitive and specific biomarkers of the clinical and pathological progressing of AD in adults with DS is considered.
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PMID:Alzheimer's disease in Down syndrome: neurobiology and risk. 1791 85

In the last decade, arsenic trioxide (As2O3) has been used very successfully to treat acute promyelocytic leukaemia (APL). Much less is known about the effectiveness of As2O3 in other neoplastic disorders. In this paper, we report that after 18 h in vitro treatment with 4 microM As2O3, 75+/-18% of B cell chronic lymphocytic leukaemia (B-CLL) cells (n=52) underwent apoptosis. It is important to note that B-CLL cells harboring a deletion of chromosome 17p13, which predisposes to fludarabine resistance and has been identified as an important negative predictor of clinical outcome, were more susceptible to As2O3 toxicity than cells lacking this aberration. Furthermore, unfavourable risk profiles such as unmutated IgVH status, high CD38 expression and prior treatment were associated with significantly higher sensitivity of B-CLL cells to As2O3. As2O3 also preferentially killed B-CLL cells compared to B cells from healthy age-matched controls. Molecular analysis revealed that basal superoxide dismutase activity was positively correlated with the pro-apoptotic activity of As2O3 pointing to a role of reactive oxygen species in cell death induction. The high activity of As2O3 in B-CLL cells from high-risk patients makes it a promising drug for high-risk and/or fludarabine-refractory B-CLL patients.
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PMID:Arsenic trioxide induces apoptosis preferentially in B-CLL cells of patients with unfavourable prognostic factors including del17p13. 1829 55

The aim of the work was the investigation of pharmacological activity of unique dihydroflavonol glycoside, micranthoside, extracted from the leaves Eupatorium micranthum Less. introduced into Georgia. Mature human T-cell leukemia cell lines (Jurkat) were analyzed in the study under the modeled oxidative stress. For modelling of oxidative stress 30% hydrogen peroxide (H(2)O(2)) (Sigma) (100 microM) was added to Jurkat cell incubation suspension with subsequent incubation for 24, 48 h. Under the effect of H(2)O(2) there was significant elevation of superoxide and peroxyl radical levels, as well as free NO levels, and reduced antioxidant enzyme SOD activity. It was shown that dihydroflavonol glycoside, micranthoside, extragated from Eupatorium micranthum Less., has marked antioxidant properties, it inhibits hyperproduction of reactive oxygen species, and protects cells against oxidative damage, stimulates cell proliferation and inhibits necrosis in cell line.
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PMID:[Pharmacological activity of dihydroflavonol glycoside isolated from the plant Eupatorium micranthum Less]. 1848 95

Tannic acid (TA), a glucoside of gallic acid polymer, has been shown to possess anti-bacterial, anti-enzymatic, anti-tumor and astringent properties. However, the anti-cancer activity of TA in leukemia is still obscure. In this study, we showed TA-induced apoptotic death in acute myeloid leukemia (AML) HL-60 cells via dose- and time-dependent manner as well as increase of sub-G1 fraction, chromosome condensation, and DNA fragmentation. Further analysis demonstrated the involvement of activation of caspase cascade, cleavage of poly (ADP-ribose) polymerase (PARP), disruption of mitochondrial membrane potential, and release of Cytochrome C, in TA-induced apoptosis. These effects were probably associated with the increase of intracellular superoxide in mitochondrial signaling pathway which attributed to the down-regulation of superoxide dismutase (SOD). Notably, a low dose of TA is sufficient to aggravate arsenic trioxide (As(2)O(3))-induced cytotoxicity in HL-60 cells. Altogether, this study suggested the effects of TA to induce apoptosis in HL-60 and therapeutic potential in AML by being an adjunct to As(2)O(3).
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PMID:Tannic acid-induced apoptosis and -enhanced sensitivity to arsenic trioxide in human leukemia HL-60 cells. 1879 May 33

Human promonocytic cell line U937 cells can be induced to differentiate into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA treatment induced the expression of the monocytic differentiation markers CD11b and CD36, with concomitant morphological changes. Moreover, TPA enhanced reactive oxygen species (ROS) generation in these cells, and phagocytic ability was also stimulated during differentiation. The antioxidant agent N-acetyl-L-cysteine inhibited the TPA-induced differentiation of U937 cells. TPA treatment decreased the expression level of catalase, which catalyzes the decomposition of hydrogen peroxide (H(2)O(2)) to H(2)O and O(2). In contrast, TPA increased the level of manganese superoxide dismutase, which catalyzes the dismutation of superoxide into H(2)O(2) and O(2) without affecting the levels of copper-zinc superoxide dismutase or glutathione peroxidase 1, which removes H(2)O(2) using glutathione as substrate. Treatment of U937 cells with catalase inhibited the enhancement of ROS generation induced by TPA, and blocked the TPA-induced differentiation of U937 cells. Human promyelocytic cell line HL60 cells were also induced to differentiate into macrophages by TPA. However, HP100-1 cells, its variant cell line overexpressing catalase, were resistant to TPA-induced differentiation. Our results suggest that catalase inhibits monocytic differentiation by TPA; the decrease in catalase level and the accumulation of H(2)O(2) are significant events for monocyte/macrophage differentiation by TPA.
Leukemia 2009 Apr
PMID:Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen peroxide as a second messenger. 1909 50

Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid with anti- and pro-oxidant activity present in various natural sources. Kaempferol has been shown to posses anticancer properties through the induction of the apoptotic program. Here we report that treatment of the chronic myelogenous leukemia cell line K562 and promyelocitic human leukemia U937 with 50 microM kaempferol resulted in an increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD). Kaempferol treatment induced apoptosis by decreasing the expression of Bcl-2 and increasing the expressions of Bax. There were also induction of mitochondrial release of cytochrome c into cytosol and significant activation of caspase-3, and -9 with PARP cleavage. Kaempferol treatment increased the expression and the mitochondria localization of the NAD-dependent deacetylase SIRT3. K562 cells stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3 silencing did not increase the resistance of K562 cells to kaempferol. Inhibition of PI3K and de-phosphorylation of Akt at Ser473 and Thr308 was also observed after treating both K562 and U937 cells with kaempferol. In conclusion our study shows that the oxidative stress induced by kaempferol in K562 and U937 cell lines causes the inactivation of Akt and the activation of the mitochondrial phase of the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl-2, release of cytochrome c, caspase-3 activation, and cell death.
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PMID:Kaempferol induces apoptosis in two different cell lines via Akt inactivation, Bax and SIRT3 activation, and mitochondrial dysfunction. 1916 Apr 23

It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10(7) promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red-ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [(3)H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT(2A) receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.
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PMID:Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia. 1926 4


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