Inflammation, Oxidative Stress and Cobalt Deficiency in Acute Childhood Leukemia

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Moses O Akiibinu ◽  
Bashiru S Oseni ◽  
Adekunle A Adesiyan ◽  
Susanah O Akiibinu ◽  
John I Anetor
Keyword(s):  
Oxidative Stress ◽  
Childhood Leukemia ◽  
Cobalt Deficiency

scholarly journals Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Claudia Consales ◽  
Caterina Merla ◽  
Carmela Marino ◽  
Barbara Benassi
Keyword(s):  
Oxidative Stress ◽  
Electromagnetic Fields ◽  
Childhood Leukemia ◽  
Low Frequency ◽  
Epidemiological Studies ◽  
Data Uncertainty ◽  
International Agency ◽  
Neuroprotective Effects ◽  
Great Debate ◽  
Increased Risk

Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system.

Investigating Drug Resistance In Leukemia Initiating Cell Populations.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1570-1570
Author(s):  
Paraskevi Diamanti ◽  
Charlotte Victoria Cox ◽  
Allison Blair
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Childhood Leukemia ◽  
Conflicts Of Interest ◽  
Annexin V ◽  
Cell Populations ◽  
Childhood All ◽  
Nsg Mice ◽  
Cd34 Cells

Abstract Abstract 1570 Outcomes for childhood leukemia have improved significantly in recent years with remission rates of over 98% and reported cure rates of 80% for standard risk cases. However, 20% of patients relapse due to failure to eradicate the disease. Further improvement in outcomes will require a better understanding of the biology of this malignancy and the mechanisms of drug resistance. Evidence that several leukemia subpopulations can initiate and maintain this disease in xenograft models and that some of these subpopulations are resistant to current therapeutic agents suggests that relapse may arise from these cells. Parthenolide (PTL), a sesquiterpene lactone compound, has been shown to cause apoptosis in malignant cells by inducing oxidative stress and by inhibiting NF-κB mediated cell survival. In this investigation we have assessed the effects of PTL on leukemia subpopulations in a cohort of childhood ALL cases from mixed prognostic subgroups. Cells from 15 B-ALL cases were stained with antibodies against CD34 and CD19, while CD34 and CD7 were used for 7 T-ALL cases. Cells were then sorted based on expression or lack of expression of the antibody combinations. Unsorted cells and the 4 sorted subpopulations from each type of leukemia were treated with 7.5 and 10 μM PTL for 18–24 hours. The effect of PTL on viability was studied by flow cytometry using Annexin V and Propidium iodide. In B-ALL cases, the CD34+/CD19- population was the least affected with 89.1±6.9% cells surviving PTL treatment. This was significantly higher than the unsorted cells and the other sorted populations (<53%; P<0.01). Most of the T-ALL cases (6/7) were classed as high risk by MRD analyses at day 28. Despite this, unsorted T-ALL cells were more responsive to PTL with only 29.7±12.8% surviving treatment. The CD34+/CD7- population was the least affected (59.9±13.3% viable cells). The functional capacity of the PTL treated unsorted cells and sorted populations was also assessed in vivo. NOD/SCID IL2Rγ null (NSG) mice were inoculated with untreated or PTL treated cells and the levels of engraftment after 10 weeks were compared. The results to date indicate that PTL treatment prevented engraftment of unsorted ALL cells. Mean engraftment levels of 65±20% CD45+ (range 29–99%) were observed using untreated cells while there was no detectable human cell engraftment with the PTL treated cells. This suggests PTL is more effective on unsorted ALL cells than the data from the short term apoptosis assays indicated. Engraftment was achieved using CD34- cells from 3 cases (73±29%, range 40–96%). However, no engraftment was observed when CD34- cells were treated with PTL. In contrast, the levels of engraftment observed with PTL treated CD34+/CD19- B-ALL cells were similar to or greater than those observed with the untreated counterparts (95±8% and 64±9% CD45+ respectively, P≤0.07). The levels of engraftment observed with CD34+/CD7- T-ALL cells were reduced with PTL treatment from 67±21% to 12±9% CD45+ (P≤0.03) but not eliminated. Subsequently, we investigated the mechanisms for this apparent resistance to PTL in the primitive cell populations. PTL has been associated with induction of oxidative stress, activation of p53 and inhibition of NF-κB in AML and CLL. We used confocal microscopy to investigate whether NF-κB is constitutively expressed in ALL cases and to evaluate the effect of PTL on the phosphorylation of NF-κB. Three B-ALL and 3 T-ALL cases, where the unsorted populations had been affected by PTL while the respective CD34+/CD19- and CD34+/CD7- populations were more resistant, were investigated. Cells were stained with anti-phospho-p65 polyclonal antibody and Alexa fluor 488. NF-κB was constitutively activated in all cases. There was evidence of decreased phosphorylation in unsorted PTL treated cells indicating inhibition of NF-κB. However, in the phenotypically primitive cells there was no difference in the phosphorylation levels compared to untreated cells or phosphorylation was increased. This suggests NF-κB was not inhibited, which could explain the observed resistance of these leukemia populations to PTL. These data demonstrate that some leukemia initiating cell populations in childhood B-ALL and T-ALL are resistant to PTL. A more thorough understanding of these leukemia initiating cell populations and their mechanisms of resistance will be required for the development of more effective therapies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals F2-Isoprostanes

2013 ◽  
Vol 16 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Marilyn J. Hockenberry ◽  
Olga A. Taylor ◽  
Patricia M. Gundy ◽  
Adam K. Ross ◽  
Alice Pasvogel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
The United States ◽  
Cns Injury ◽  
Childhood All ◽  
The Central Nervous System ◽  
The Mean ◽  
Oxidative Stress Indicators

Acute lymphoblastic leukemia (ALL) is the most prevalent and curable cancer among children and adolescents less than 15 years of age in the United States. Essential for cure of childhood ALL is prophylactic treatment of the central nervous system (CNS), with methotrexate (MTX) being the most widely used drug in this treatment. While CNS treatment has contributed to long-term disease-free survival, resulting declines in academic abilities have been reported. There is growing evidence that CNS treatment with MTX increases oxidative stress, a potential mechanism of CNS injury. This article reports changes in oxidative stress, measured by the biomarker F2-isoprostane (F2-IsoP), in the cerebrospinal fluid (CSF) in 47 children with ALL during the first 18 months of treatment. The number of CSF samples ranged from 5 to 14 during postinduction and from 1 to 9 during continuation. Total doses of intrathecal MTX during postinduction were significantly correlated with the mean and highest concentrations of F2-IsoP during postinduction and the mean concentration of F2-IsoP during continuation. F2-IsoP concentrations during postinduction and continuation were higher in children who received more than six doses of intrathecal MTX. New therapies for a highly curable disease such as childhood leukemia have the potential to be individualized in the future, requiring reliable molecular and biochemical markers, such as oxidative stress indicators. Innovative use of biomarkers has the potential to increase our understanding of treatment-related toxicities and associated symptoms and to inform future therapeutic approaches for optimizing cure and quality of life among children with leukemia.

scholarly journals The Influence of Oxidative Stress on Symptom Occurrence, Severity, and Distress During Childhood Leukemia Treatment

2014 ◽  
Vol 41 (4) ◽  
pp. E238-E247 ◽  
Author(s):  
Marilyn J. Hockenberry ◽  
Olga A. Taylor ◽  
Alice Pasvogel ◽  
Cheryl Rodgers ◽  
Kathy McCarthy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Childhood Leukemia ◽  
Leukemia Treatment

scholarly journals Assessment of the Role of Oxidative Stress and Circulating Biochemical markers in Childhood Leukemia

2019 ◽  
Vol 1294 ◽  
pp. 062089
Author(s):  
Nour Shakir Rezaieg ◽  
Mohammed H. Musleh
Keyword(s):  
Oxidative Stress ◽  
Biochemical Markers ◽  
Childhood Leukemia

Lycopene alleviates sulfamethoxazole-induced hepatotoxicity in grass carp (Ctenopharyngodon idellus) via suppression of oxidative stress, inflammation and apoptosis

2020 ◽  
Vol 11 (10) ◽  
pp. 8547-8559
Author(s):  
Hongjing Zhao ◽  
Yu Wang ◽  
Mengyao Mu ◽  
Menghao Guo ◽  
Hongxian Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Secondary Metabolites ◽  
Human Health ◽  
Grass Carp ◽  
Aquatic Environment ◽  
Ctenopharyngodon Idellus

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

Pancreatic stones shockwave lithotripsy induces oxidative stress. A study of lipoperoxidation products in pure pancreatic juice

2001 ◽  
Vol 120 (5) ◽  
pp. A217-A217
Author(s):  
C SPADA ◽  
S SANTINI ◽  
F FOSCHIA ◽  
M PANDOLFI ◽  
V PERRI ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Juice ◽  
Shockwave Lithotripsy ◽  
Pure Pancreatic Juice ◽  
Pancreatic Stones

Dilinoleoylphosphatidylcholine (DLPC) protects against alcohol-induced oxidative stress in rats

2001 ◽  
Vol 120 (5) ◽  
pp. A116-A116
Author(s):  
S ALEYNIK ◽  
M ALEYNIK ◽  
C LIEBER
Keyword(s):  
Oxidative Stress
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